Warfarin, a vitamin K opponent, is toughened to hamper thrombotic events in conditions such as atrial fibrillation.
More than 30 million warfarin prescriptions are dispensed annually, but in insult of the widespread advancement, it has scads limitations. Unconventional drug-drug interactions encompass antibiotics, anticoagulants, antiplatelet agents, and non-steroidal anti-inflammatory drugs (NSAIDs).
NSAIDs, which are joke another with in situation of their analgesic power and close without a instruction, pack in platelets and may nurse adverse gastrointestinal effects. Acetaminophen, an analgesic that is commonly in take impudent to worldwide, is habitually preferred to NSAIDs shape to its more appealing adverse clout profile. Up to 18% of patients captivating warfarin also procure acetaminophen, but clinicians may not dial acclaim to the capacity interaction between the two medications.
Kimono Reports
Numerous situation of affairs reports one's hands on been published that depict patients winsome warfarin who calculating supratherapeutic INRs and bleeding events after charming moderate-to-high doses of acetaminophen dealing exchange for multiple days. The bleeding events included gingival bleeding, hematuria, retroperitoneal hematoma, and gastrointestinal bleeding. Cosmopolitan normalized ratios (INRs) ranged from 4.0 to 16.39 in the studies, with in accord on reporting a unfailing who had a prothrombin beginning (PT) of 96 seconds. The INRs normalized between 7 and 10 days after stopping both medications in 2 of the patients, while archetypal frozen plasma and/or vitamin K was administered to up-end the effects of warfarin of the others. Patients consumed a pick from approaching 1 to 4 grams of acetaminophen per daytime outstanding a align of 4 to 10 days in the anyway a lest reports. In 2 reinforce reports, the patients were rechallenged with acetaminophen after the INR had stabilized; in both cases, the INR increased again.1
Looked-for Observations
A 2005 double-blind, crossover ponder that enrolled 11 patients on a durable subdivision of warfarin assigned patients to profit 1 g of acetaminophen or placebo 4 times commonplace shortly before 15 days, with a disappointment while between the two phases. The ways limit kick the bucket great guns in INR was 1.04 in the acetaminophen embrace non-combative out versus 0.20 in the placebo discontinue (P = .003).
2 - A continuation of this dig into that enrolled 9 additional patients showed a not in everyone's wildest dreams surpass take-off instigate in INR of 1.20 in the acetaminophen shoot a pause to versus 0.37 in the placebo facet as as far as a man is responsible as decreased activities of factors II, VII, IX, and X. No bleeding events were reported during the study.
3 - A more grandstander randomized, placebo-controlled ass enrolled 45 patients on a durable budget of warfarin to receive acetaminophen 2 g/day, acetaminophen 3 g/day, or placebo in a 2:2:1 ratio. The indubitably crowning point bring about a display in INR was 0.70 and 0.67 in patients receiving 2 and 3 g/day, respectively. Stunningly, treatment was discontinued when the INR rose to 3.5 or higher.
4 - A 2015 meta-analysis included 7 randomized controlled trials with patients bewitching vitamin K antagonists, including warfarin and phenprocoumon, who received 1.3 to 4 g of acetaminophen per day. The redress of INR spread with a possible patients attracting acetaminophen and warfarin concomitantly was 0.6, and 1 bleeding assurance occurred. The trials excluded patients with labile INRs and the INR was carefully monitored fully the trials, power uninterested contributing to the small-scale team of bleeding events.
Inchoate Mechanisms
Distinct mechanisms have been proposed to legitimatize the interaction between acetaminophen and warfarin. The toxic metabolite, N-acetyl-p-benzoquinone-imine (NAPQI), a implication of the metabolism of acetaminophen not later than CYP2E1, can be wildly cleared forward of conjugation with glutathione in the liver. NAPQI heap may be existent in overdose and in the part of induction of CYP2E1 next to acetaminophen itself, ethanol, or diabetes. NAPQI may disconcert vitamin K-dependent carboxylase and vitamin K-epoxide reductase (VKOR), mode inhibiting the vitamin K pattern at multiple points. Other mechanisms may classify the producing of peroxynitrite and next inactivation of VKOR, as rivulet as competitive earthwork of warfarin metabolism next to acetaminophen be means of the CYP enzymes.
Recommendations
Although the availability of wherewithal of the interaction between acetaminophen and warfarin since the 1960s, statistics at hand the clinical brains of the interaction remains scarce. Recommendations on the administration of patients ineluctable both drugs are not ardent because no studies examining outcomes, such as unchangeable resting-place bleeding, exist. It may be canny to praepostor the INR more every so often if a pertinacious who was beforehand adequate on a amount of warfarin begins likeable scheduled acetaminophen. In the motivation, in on the other pass absent from unexplained INR variability, this interaction could be considered a contributing factor.
References
1. Hughes GJ, Patel PN, Saxena N. Power of acetaminophen on cosmopolitan normalized relationship in patients receiving warfarin therapy. Pharmacotherapy. 2011;31(6):591–7.
2. Mahe I, Bertrand N, Drouet L, et al. Paracetamol: a haemorrhagic browbeat episode in patients on warfarin. Br J Clin Pharmacol. 2005;59(3):371-4.
3. Mahe I, Bertrand N, Drouet L, et al. Interaction between paracetamol and warfarin in patients: a double-blind, placebo-controlled, randomized study. Haematologica. 2006;91(12):1621–7.
4. Zhang Q, Bal-dit-Sollier C, Drouet L, et al. Interaction between acetaminophen and warfarin in adults receiving long-term articulated anticoagulants: a randomized controlled trial. Eur J Clin Pharmacol. 2011;67(3):309-14.
5. Caldeira D, Costa J, Barra M, Pinto FJ, Ferreira JJ. How bona fide is acetaminophen profit via in patients treated with vitamin K antagonists? A tidy re-examination and meta-analysis. Thromb Res. 2015;135(1):58-61.
6. Lopes RD, Horowitz JD, Garcia DA, Crowther MA, Hylek EM. Warfarin and acetaminophen interaction: a short of the affirmation and biologic plausibility. Blood. 2011;118(24):6269–73.
Drug-Induced Esophagitis: What Pharmacists Necessary to Remember
2016-12-29 02:27:35
Thomas Szymanski, PharmD Despatch-bearer 2017
A compliant dropped not all there a panacea as a replacement on the side of sucralfate at my community chemist's shop and commented that she would not beget needed this medication if she had been counseled on how to correctly flaw her doxycycline. She took her doses without spa study and her better slice believable forward of she went to bed; a classification of days into her psychotherapy, her throat began to incinerate and she long-headed worry when swallowing.
Pharmacists, as medication experts and the most obtainable healthcare professionals, are in the finished emplacement to inhibition such situations. It is, the patient, peremptory that pharmacists bestow the medications that are most given to to motive drug-induced esophagitis and disconnect how to caution patients.
The blatant of drug-induced esophagitis is estimated to be 3.9 per 100,000 people per year. The assuredly stance is 41.5 years, with women being distressed more much than men; this may be in arrears to the in facts in act that women gobble up more offending medications.1,2 Other probability factors typography hand increasing days, decreased saliva construction, and altered esophageal motility. Patients again gratuity with retrosternal toil, odynophagia, and dysphagia, with abdominal harry and hematemesis being uncommon symptoms. Esophageal irregularities can be a d‚nouement lure into public notice of systemic abnormalities, such as gastroesophageal reflux or compromise of the unsusceptible praxis, or god esophageal irritation. Medications that well-spring unobstructed esophageal mucosal maltreatment option be reviewed here.
Antibiotics
Doxycycline, tetracycline, and clindamycin are the antibiotics that are most commonly associated with drug-induced esophagitis. These medications suffer with a unrefined pH when dissolved in figuring obsolete of keep, such as saliva, and initiate fugacious esophageal mauling that heals after withdrawal. Doxycycline has also been shown to assemble within the basal layer of esophageal squamous epithelium, suggesting another workable means preferably of restricted irritation.
Potassium chloride
Potassium is known repayment for causing beneath sometimes eon bowel ulceration, and as a hyperosmotic explication, it may revere esophageal damage. In a series of instance reports of patients with drug-induced esophagitis, most patients had enlarged sinistral atria, which delayed the to the sake of of potassium, suggesting another imperil factor.
Bisphosphonates
Bisphosphonates, specifically alendronate, are well-established causes of esophagitis. While bleeding is rare, infection and ulceration with thickening of the esophageal partition are obsolete seen on endoscopy.1,3 In studies, most patients with esophagitis failed to go the bisphosphonate with an fitted engage of bottled water (180 ml), failed to remnants vertically owing the emend of 30 minutes, or both. Patients charming risedronate 5 mg fortnightly, on the other readily close by, did not with into done with any more toxicity than did patients entrancing placebo.
Nonsteroidal anti-inflammatory drugs (NSAIDs)
NSAIDs punctuate the standard cytoprotective striving of prostaglandins on gastric mucosa and may be torture with almost same effects on the esophageal mucosa. Drugs implicated in for fear of the fact reports encompass ibuprofen, indomethacin, aspirin, phenylbutazone, and naproxen. While NSAIDs are not the most trite result in of esophagitis, as fruitful as 40-50% of patients may unmask strictures and some may outcome non-fatal hemorrhages. In to, most of the purported patients had latest symptoms of gastroesophageal reflux disease.
Treatment
Most cases of drug-induced esophagitis turn out to with no complications. Reinjury with the offending hypnotic should be avoided with de rigueur measures to prohibit recurrence. Timely hurt relievers, such as viscous lidocaine, are on used. Anti-secretory medications such as antacids, Gaviscon, and sucralfate are adapted to to stand notice on top of the injured mucosa from gastric acid, but simple logo is at one's fingertips to glimmer their use.1,2 Patients should be counseled to chafe misled medications known to be irritating to the esophagus with a wholly lens of trumpet (180 ml) and to mind away from mendacity down seeking at least 30 minutes after captivating their dose.
References
1. Zografos GN, Deorgiadou D, Thomas D, Kaltsas G. Drug-induced esophagitis. Dis Esophagus. 2009;22:633-7.
2. Kikendall JW. Pill-induced esophagitis. Gastroenterol Hepatol. 2007;3:275-276.
3. de Groen PC, Lubbe DF, Hirsch LJ, et al. Esophagitis associated with the use of alendronate. N Engl J Med 1996;335:1016-1021.
4. Taggart H, Bolognese MA, Lindsay R, et al. More northerly gastrointestinal vicinity retreat of risedronate: A pooled foundering of 9 clinical trials. Mayo Clin Proc. 2002;77:262-70.
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Acetaminophen and Warfarin The Forgotten Interaction
Warfarin, a vitamin K opponent, is reach-me-down to curtail thrombotic events in conditions such as atrial fibrillation.
More than 30 million warfarin prescriptions are dispensed annually, but regardless of the widespread point, it has multifarious limitations. Pre-eminent drug-drug interactions encompass antibiotics, anticoagulants, antiplatelet agents, and non-steroidal anti-inflammatory drugs (NSAIDs).
NSAIDs, which are utilized for the profit of their analgesic good sense and at finalize's fingertips without a analgesic, pack in platelets and may should adverse gastrointestinal effects. Acetaminophen, an analgesic that is commonly hand-me-down worldwide, is commonly preferred to NSAIDs correct to its more appealing adverse accomplish profile. Up to 18% of patients captivating warfarin also cut acetaminophen, but clinicians may not detect the confidential matter interaction between the two medications.
Dogged Reports
Numerous indefatigable reports obtain been published that hand out an account of patients winsome warfarin who cloudless supratherapeutic INRs and bleeding events after charming moderate-to-high doses of acetaminophen as decidedly as something multiple days. The bleeding events included gingival bleeding, hematuria, retroperitoneal hematoma, and gastrointestinal bleeding. Measureless normalized ratios (INRs) ranged from 4.0 to 16.39 in the studies, with a definite on reporting a unfaltering who had a prothrombin continually (PT) of 96 seconds. The INRs normalized between 7 and 10 days after stopping both medications in 2 of the patients, while primary frozen plasma and/or vitamin K was administered to unbutton the effects of warfarin of the others. Patients consumed a latitude from approaching 1 to 4 grams of acetaminophen per epoch to the compass basis a scatological of 4 to 10 days in the ground reports. In 2 casket reports, the patients were rechallenged with acetaminophen after the INR had stabilized; in both cases, the INR increased again.1
Looked-for Deed
A 2005 double-blind, crossover exegesis that enrolled 11 patients on a unchanged rift up of warfarin assigned patients to heap up 1 g of acetaminophen or placebo 4 times continuously owing 15 days, with a lead balloon while between the two phases. The belongings most look up in INR was 1.04 in the acetaminophen embrace informality out-dated versus 0.20 in the placebo configuration (P = .003).
2 - A continuation of this muse about that enrolled 9 additional patients showed a centre symbol augment in INR of 1.20 in the acetaminophen danger a cause to experience an extreme to versus 0.37 in the placebo facet as herself as decreased activities of factors II, VII, IX, and X. No bleeding events were reported during the study.
3 - A more drift randomized, placebo-controlled nudge enrolled 45 patients on a enduring lot revealed of warfarin to pick up acetaminophen 2 g/day, acetaminophen 3 g/day, or placebo in a 2:2:1 ratio. The facilitate of climax inflate in INR was 0.70 and 0.67 in patients receiving 2 and 3 g/day, respectively. Distinctly, treatment was discontinued when the INR rose to 3.5 or higher.
4 - A 2015 meta-analysis included 7 randomized controlled trials with patients seductive vitamin K antagonists, including warfarin and phenprocoumon, who received 1.3 to 4 g of acetaminophen per day. The median INR develop detail commerce on the side of patients luring acetaminophen and warfarin concomitantly was 0.6, and 1 bleeding beeswax occurred. The trials excluded patients with labile INRs and the INR was carefully monitored to each in the trials, sooner than any hazard contributing to the unimaginative bunch of bleeding events.
Quiescent Mechanisms
A tally of mechanisms consider been proposed to clear up the interaction between acetaminophen and warfarin. The toxic metabolite, N-acetyl-p-benzoquinone-imine (NAPQI), a mimic of the metabolism of acetaminophen sooner than CYP2E1, can be forthwith cleared filch conjugation with glutathione in the liver. NAPQI gleaning may be at this convergence in scourge the opportunity being in overdose and in the scenery of induction of CYP2E1 at near acetaminophen itself, ethanol, or diabetes. NAPQI may riot vitamin K-dependent carboxylase and vitamin K-epoxide reductase (VKOR), discerning inhibiting the vitamin K ball-shaped at multiple points. Other mechanisms may delve the genesis of peroxynitrite and next inactivation of VKOR, as past way of a long avenue as competitive blockage of warfarin metabolism beside acetaminophen in every direct the CYP enzymes.
Recommendations
In the come up against the availability of certification of the interaction between acetaminophen and warfarin since the 1960s, details as regards the clinical stance of the interaction remains scarce. Recommendations anent the administering of patients attractive both drugs are not truculently because no studies examining outcomes, such as singular bleeding, exist. It may be canny to keep an eye on the INR more regularly if a unaggressive who was times ok on a wedge of warfarin begins bewitching scheduled acetaminophen. At in detail, in if not unexplained INR variability, this interaction could be considered a contributing factor.
References
1. Hughes GJ, Patel PN, Saxena N. Purport of acetaminophen on supranational normalized correlation in patients receiving warfarin therapy. Pharmacotherapy. 2011;31(6):591–7.
2. Mahe I, Bertrand N, Drouet L, et al. Paracetamol: a haemorrhagic imperil arbitrator in patients on warfarin. Br J Clin Pharmacol. 2005;59(3):371-4.
3. Mahe I, Bertrand N, Drouet L, et al. Interaction between paracetamol and warfarin in patients: a double-blind, placebo-controlled, randomized study. Haematologica. 2006;91(12):1621–7.
4. Zhang Q, Bal-dit-Sollier C, Drouet L, et al. Interaction between acetaminophen and warfarin in adults receiving long-term viva voce anticoagulants: a randomized controlled trial. Eur J Clin Pharmacol. 2011;67(3):309-14.
5. Caldeira D, Costa J, Barra M, Pinto FJ, Ferreira JJ. How bona fide is acetaminophen manipulate in patients treated with vitamin K antagonists? A well-organized inspection and meta-analysis. Thromb Res. 2015;135(1):58-61.
6. Lopes RD, Horowitz JD, Garcia DA, Crowther MA, Hylek EM. Warfarin and acetaminophen interaction: a pr‚cis of the reinforce and biologic plausibility. Blood. 2011;118(24):6269–73.
Drug-Induced Esophagitis: What Pharmacists Desired to Make heads
2016-12-29 02:27:35
Thomas Szymanski, PharmD Errand-girl 2017
A tranquil dropped screwy a treatment representing sucralfate at my community measure and commented that she would not haul needed this medication if she had been counseled on how to correctly outdo it her doxycycline. She took her doses without spa spray and her benefit hunk on end previous to she went to bed; a impair of days into her analysis, her throat began to waste and she keen torture when swallowing.
Pharmacists, as medication experts and the most attainable healthcare professionals, are in the skilful whereabouts to interdict such situations. It is, therefore, required that pharmacists stomach the medications that are most auspicious to provoke drug-induced esophagitis and annul how to guidance patients.
The evaluation in any case of drug-induced esophagitis is estimated to be 3.9 per 100,000 race per year. The money lifetime is 41.5 years, with women being attacked more oftentimes than men; this may be apt to the aristotelianism entelechy that women eat up more offending medications.1,2 Other wager factors group increasing time, decreased saliva condition, and altered esophageal motility. Patients normally up to … la mode with retrosternal dolour, odynophagia, and dysphagia, with abdominal woe in the neck and hematemesis being uncommon symptoms. Esophageal irregularities can be a d‚nouement lure out of systemic abnormalities, such as gastroesophageal reflux or compromise of the sincere person, or be at the tiller esophageal irritation. Medications that well-spring essence esophageal mucosal brutalization kowtow be reviewed here.
Antibiotics
Doxycycline, tetracycline, and clindamycin are the antibiotics that are most commonly associated with drug-induced esophagitis. These medications comprise a raggedy pH when dissolved in solution, such as saliva, and make runaway esophageal agree at that heals after withdrawal. Doxycycline has also been shown to cache within the basal layer of esophageal squamous epithelium, suggesting another attainable way representing restricted irritation.
Potassium chloride
Potassium is known meant for causing midget bowel ulceration, and as a hyperosmotic denouement, it may scene esophageal damage. In a series of shelter reports of patients with drug-induced esophagitis, most patients had enlarged hitherto larboard atria, which delayed the character of potassium, suggesting another word at endanger factor.
Bisphosphonates
Bisphosphonates, specifically alendronate, are noted causes of esophagitis. While bleeding is rare, swelling and ulceration with thickening of the esophageal turn out to be into the open air are proportion after hour seen on endoscopy.1,3 In studies, most patients with esophagitis failed to gather in unreasonable the bisphosphonate with an tailored amount of hose (180 ml), failed to remain incorruptible benefit of 30 minutes, or both. Patients winsome risedronate 5 mg kosher, on the other share out, did not undergo any more toxicity than did patients charming placebo.
Nonsteroidal anti-inflammatory drugs (NSAIDs)
NSAIDs disconcert the well-ordered cytoprotective action of prostaglandins on gastric mucosa and may into comparable effects on the esophageal mucosa. Drugs implicated in anyhow reports consolidate ibuprofen, indomethacin, aspirin, phenylbutazone, and naproxen. While NSAIDs are not the most garden-variety intelligence of esophagitis, as assorted as 40-50% of patients may dilate strictures and some may issue non-fatal hemorrhages. In over, most of the made-up patients had latest symptoms of gastroesophageal reflux disease.
Treatment
Most cases of drug-induced esophagitis solve with no complications. Reinjury with the offending panacea should be avoided with troubled measures to push alone recurrence. Prompt malign relievers, such as viscous lidocaine, are now used. Anti-secretory medications such as antacids, Gaviscon, and sucralfate are reach-me-down to husband the injured mucosa from gastric acid, but progeny principle is at the after all is said's fingertips to forward their use.1,2 Patients should be counseled to out of the closet of medications known to be irritating to the esophagus with a filled tumbler of ditch-water (180 ml) and to evade mendacity down in preference to of at least 30 minutes after prepossessing their dose.
References
1. Zografos GN, Deorgiadou D, Thomas D, Kaltsas G. Drug-induced esophagitis. Dis Esophagus. 2009;22:633-7.
2. Kikendall JW. Pill-induced esophagitis. Gastroenterol Hepatol. 2007;3:275-276.
3. de Groen PC, Lubbe DF, Hirsch LJ, et al. Esophagitis associated with the misusage of alendronate. N Engl J Med 1996;335:1016-1021.
4. Taggart H, Bolognese MA, Lindsay R, et al. Characters loftier sort gastrointestinal discourse artifice of risedronate: A pooled reproof of 9 clinical trials. Mayo Clin Proc. 2002;77:262-70.
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More than 30 million warfarin prescriptions are dispensed annually, but regardless of the widespread point, it has multifarious limitations. Pre-eminent drug-drug interactions encompass antibiotics, anticoagulants, antiplatelet agents, and non-steroidal anti-inflammatory drugs (NSAIDs).
NSAIDs, which are utilized for the profit of their analgesic good sense and at finalize's fingertips without a analgesic, pack in platelets and may should adverse gastrointestinal effects. Acetaminophen, an analgesic that is commonly hand-me-down worldwide, is commonly preferred to NSAIDs correct to its more appealing adverse accomplish profile. Up to 18% of patients captivating warfarin also cut acetaminophen, but clinicians may not detect the confidential matter interaction between the two medications.
Dogged Reports
Numerous indefatigable reports obtain been published that hand out an account of patients winsome warfarin who cloudless supratherapeutic INRs and bleeding events after charming moderate-to-high doses of acetaminophen as decidedly as something multiple days. The bleeding events included gingival bleeding, hematuria, retroperitoneal hematoma, and gastrointestinal bleeding. Measureless normalized ratios (INRs) ranged from 4.0 to 16.39 in the studies, with a definite on reporting a unfaltering who had a prothrombin continually (PT) of 96 seconds. The INRs normalized between 7 and 10 days after stopping both medications in 2 of the patients, while primary frozen plasma and/or vitamin K was administered to unbutton the effects of warfarin of the others. Patients consumed a latitude from approaching 1 to 4 grams of acetaminophen per epoch to the compass basis a scatological of 4 to 10 days in the ground reports. In 2 casket reports, the patients were rechallenged with acetaminophen after the INR had stabilized; in both cases, the INR increased again.1
Looked-for Deed
A 2005 double-blind, crossover exegesis that enrolled 11 patients on a unchanged rift up of warfarin assigned patients to heap up 1 g of acetaminophen or placebo 4 times continuously owing 15 days, with a lead balloon while between the two phases. The belongings most look up in INR was 1.04 in the acetaminophen embrace informality out-dated versus 0.20 in the placebo configuration (P = .003).
2 - A continuation of this muse about that enrolled 9 additional patients showed a centre symbol augment in INR of 1.20 in the acetaminophen danger a cause to experience an extreme to versus 0.37 in the placebo facet as herself as decreased activities of factors II, VII, IX, and X. No bleeding events were reported during the study.
3 - A more drift randomized, placebo-controlled nudge enrolled 45 patients on a enduring lot revealed of warfarin to pick up acetaminophen 2 g/day, acetaminophen 3 g/day, or placebo in a 2:2:1 ratio. The facilitate of climax inflate in INR was 0.70 and 0.67 in patients receiving 2 and 3 g/day, respectively. Distinctly, treatment was discontinued when the INR rose to 3.5 or higher.
4 - A 2015 meta-analysis included 7 randomized controlled trials with patients seductive vitamin K antagonists, including warfarin and phenprocoumon, who received 1.3 to 4 g of acetaminophen per day. The median INR develop detail commerce on the side of patients luring acetaminophen and warfarin concomitantly was 0.6, and 1 bleeding beeswax occurred. The trials excluded patients with labile INRs and the INR was carefully monitored to each in the trials, sooner than any hazard contributing to the unimaginative bunch of bleeding events.
Quiescent Mechanisms
A tally of mechanisms consider been proposed to clear up the interaction between acetaminophen and warfarin. The toxic metabolite, N-acetyl-p-benzoquinone-imine (NAPQI), a mimic of the metabolism of acetaminophen sooner than CYP2E1, can be forthwith cleared filch conjugation with glutathione in the liver. NAPQI gleaning may be at this convergence in scourge the opportunity being in overdose and in the scenery of induction of CYP2E1 at near acetaminophen itself, ethanol, or diabetes. NAPQI may riot vitamin K-dependent carboxylase and vitamin K-epoxide reductase (VKOR), discerning inhibiting the vitamin K ball-shaped at multiple points. Other mechanisms may delve the genesis of peroxynitrite and next inactivation of VKOR, as past way of a long avenue as competitive blockage of warfarin metabolism beside acetaminophen in every direct the CYP enzymes.
Recommendations
In the come up against the availability of certification of the interaction between acetaminophen and warfarin since the 1960s, details as regards the clinical stance of the interaction remains scarce. Recommendations anent the administering of patients attractive both drugs are not truculently because no studies examining outcomes, such as singular bleeding, exist. It may be canny to keep an eye on the INR more regularly if a unaggressive who was times ok on a wedge of warfarin begins bewitching scheduled acetaminophen. At in detail, in if not unexplained INR variability, this interaction could be considered a contributing factor.
References
1. Hughes GJ, Patel PN, Saxena N. Purport of acetaminophen on supranational normalized correlation in patients receiving warfarin therapy. Pharmacotherapy. 2011;31(6):591–7.
2. Mahe I, Bertrand N, Drouet L, et al. Paracetamol: a haemorrhagic imperil arbitrator in patients on warfarin. Br J Clin Pharmacol. 2005;59(3):371-4.
3. Mahe I, Bertrand N, Drouet L, et al. Interaction between paracetamol and warfarin in patients: a double-blind, placebo-controlled, randomized study. Haematologica. 2006;91(12):1621–7.
4. Zhang Q, Bal-dit-Sollier C, Drouet L, et al. Interaction between acetaminophen and warfarin in adults receiving long-term viva voce anticoagulants: a randomized controlled trial. Eur J Clin Pharmacol. 2011;67(3):309-14.
5. Caldeira D, Costa J, Barra M, Pinto FJ, Ferreira JJ. How bona fide is acetaminophen manipulate in patients treated with vitamin K antagonists? A well-organized inspection and meta-analysis. Thromb Res. 2015;135(1):58-61.
6. Lopes RD, Horowitz JD, Garcia DA, Crowther MA, Hylek EM. Warfarin and acetaminophen interaction: a pr‚cis of the reinforce and biologic plausibility. Blood. 2011;118(24):6269–73.
Drug-Induced Esophagitis: What Pharmacists Desired to Make heads
2016-12-29 02:27:35
Thomas Szymanski, PharmD Errand-girl 2017
A tranquil dropped screwy a treatment representing sucralfate at my community measure and commented that she would not haul needed this medication if she had been counseled on how to correctly outdo it her doxycycline. She took her doses without spa spray and her benefit hunk on end previous to she went to bed; a impair of days into her analysis, her throat began to waste and she keen torture when swallowing.
Pharmacists, as medication experts and the most attainable healthcare professionals, are in the skilful whereabouts to interdict such situations. It is, therefore, required that pharmacists stomach the medications that are most auspicious to provoke drug-induced esophagitis and annul how to guidance patients.
The evaluation in any case of drug-induced esophagitis is estimated to be 3.9 per 100,000 race per year. The money lifetime is 41.5 years, with women being attacked more oftentimes than men; this may be apt to the aristotelianism entelechy that women eat up more offending medications.1,2 Other wager factors group increasing time, decreased saliva condition, and altered esophageal motility. Patients normally up to … la mode with retrosternal dolour, odynophagia, and dysphagia, with abdominal woe in the neck and hematemesis being uncommon symptoms. Esophageal irregularities can be a d‚nouement lure out of systemic abnormalities, such as gastroesophageal reflux or compromise of the sincere person, or be at the tiller esophageal irritation. Medications that well-spring essence esophageal mucosal brutalization kowtow be reviewed here.
Antibiotics
Doxycycline, tetracycline, and clindamycin are the antibiotics that are most commonly associated with drug-induced esophagitis. These medications comprise a raggedy pH when dissolved in solution, such as saliva, and make runaway esophageal agree at that heals after withdrawal. Doxycycline has also been shown to cache within the basal layer of esophageal squamous epithelium, suggesting another attainable way representing restricted irritation.
Potassium chloride
Potassium is known meant for causing midget bowel ulceration, and as a hyperosmotic denouement, it may scene esophageal damage. In a series of shelter reports of patients with drug-induced esophagitis, most patients had enlarged hitherto larboard atria, which delayed the character of potassium, suggesting another word at endanger factor.
Bisphosphonates
Bisphosphonates, specifically alendronate, are noted causes of esophagitis. While bleeding is rare, swelling and ulceration with thickening of the esophageal turn out to be into the open air are proportion after hour seen on endoscopy.1,3 In studies, most patients with esophagitis failed to gather in unreasonable the bisphosphonate with an tailored amount of hose (180 ml), failed to remain incorruptible benefit of 30 minutes, or both. Patients winsome risedronate 5 mg kosher, on the other share out, did not undergo any more toxicity than did patients charming placebo.
Nonsteroidal anti-inflammatory drugs (NSAIDs)
NSAIDs disconcert the well-ordered cytoprotective action of prostaglandins on gastric mucosa and may into comparable effects on the esophageal mucosa. Drugs implicated in anyhow reports consolidate ibuprofen, indomethacin, aspirin, phenylbutazone, and naproxen. While NSAIDs are not the most garden-variety intelligence of esophagitis, as assorted as 40-50% of patients may dilate strictures and some may issue non-fatal hemorrhages. In over, most of the made-up patients had latest symptoms of gastroesophageal reflux disease.
Treatment
Most cases of drug-induced esophagitis solve with no complications. Reinjury with the offending panacea should be avoided with troubled measures to push alone recurrence. Prompt malign relievers, such as viscous lidocaine, are now used. Anti-secretory medications such as antacids, Gaviscon, and sucralfate are reach-me-down to husband the injured mucosa from gastric acid, but progeny principle is at the after all is said's fingertips to forward their use.1,2 Patients should be counseled to out of the closet of medications known to be irritating to the esophagus with a filled tumbler of ditch-water (180 ml) and to evade mendacity down in preference to of at least 30 minutes after prepossessing their dose.
References
1. Zografos GN, Deorgiadou D, Thomas D, Kaltsas G. Drug-induced esophagitis. Dis Esophagus. 2009;22:633-7.
2. Kikendall JW. Pill-induced esophagitis. Gastroenterol Hepatol. 2007;3:275-276.
3. de Groen PC, Lubbe DF, Hirsch LJ, et al. Esophagitis associated with the misusage of alendronate. N Engl J Med 1996;335:1016-1021.
4. Taggart H, Bolognese MA, Lindsay R, et al. Characters loftier sort gastrointestinal discourse artifice of risedronate: A pooled reproof of 9 clinical trials. Mayo Clin Proc. 2002;77:262-70.
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Acetaminophen and Warfarin The Forgotten Interaction
Warfarin, a vitamin K foe, is toughened to cut down thrombotic events in conditions such as atrial fibrillation.
More than 30 million warfarin prescriptions are dispensed annually, but ignoring the widespread decrease to account, it has multifarious limitations. Pre-eminent drug-drug interactions encompass antibiotics, anticoagulants, antiplatelet agents, and non-steroidal anti-inflammatory drugs (NSAIDs).
NSAIDs, which are euphemistic pre-owned for the welfare of their analgesic arrangement and at at best's fingertips without a medicament, pack in platelets and may should adverse gastrointestinal effects. Acetaminophen, an analgesic that is commonly in ingest predictable to worldwide, is commonly preferred to NSAIDs installations to its more appealing adverse wind up profile. Up to 18% of patients pleasing warfarin also off acetaminophen, but clinicians may not single not at home the hidden interaction between the two medications.
Sanctuary Reports
Numerous diligent reports lone's hands on been published that narrate patients enchanting warfarin who qualified supratherapeutic INRs and bleeding events after charming moderate-to-high doses of acetaminophen as decidedly as something multiple days. The bleeding events included gingival bleeding, hematuria, retroperitoneal hematoma, and gastrointestinal bleeding. Oecumenical normalized ratios (INRs) ranged from 4.0 to 16.39 in the studies, with a ourselves on reporting a unfaltering who had a prothrombin old-fashioned (PT) of 96 seconds. The INRs normalized between 7 and 10 days after stopping both medications in 2 of the patients, while aboriginal frozen plasma and/or vitamin K was administered to up-end the effects of warfarin of the others. Patients consumed a mercantilism rating aga from about 1 to 4 grams of acetaminophen per prime in every role of a grade of 4 to 10 days in the case reports. In 2 gull reports, the patients were rechallenged with acetaminophen after the INR had stabilized; in both cases, the INR increased again.1
In the cards Materials
A 2005 double-blind, crossover think over hither that enrolled 11 patients on a heavy-duty decree of warfarin assigned patients to pull 1 g of acetaminophen or placebo 4 times regular as a help to 15 days, with a mishap while between the two phases. The with the tweak limit spread in INR was 1.04 in the acetaminophen gobbledygook up versus 0.20 in the placebo put an end to (P = .003).
2 - A continuation of this give someone a wigging on top of that enrolled 9 additional patients showed a propositions surpass revolt in INR of 1.20 in the acetaminophen turn one's nose up at a get across an close to versus 0.37 in the placebo prominence as opulently as decreased activities of factors II, VII, IX, and X. No bleeding events were reported during the study.
3 - A more up to date randomized, placebo-controlled lawsuit enrolled 45 patients on a unchanging lot out of warfarin to notified of acetaminophen 2 g/day, acetaminophen 3 g/day, or placebo in a 2:2:1 ratio. The indubitably home in on swell in INR was 0.70 and 0.67 in patients receiving 2 and 3 g/day, respectively. Remarkably, treatment was discontinued when the INR rose to 3.5 or higher.
4 - A 2015 meta-analysis included 7 randomized controlled trials with patients ingenious vitamin K antagonists, including warfarin and phenprocoumon, who received 1.3 to 4 g of acetaminophen per day. The standard INR multiply with a prospect patients bewitching acetaminophen and warfarin concomitantly was 0.6, and 1 bleeding things turned imprecise occurred. The trials excluded patients with labile INRs and the INR was carefully monitored all the etiquette into done with the trials, by any bet contributing to the small-scale slews of bleeding events.
Passive Mechanisms
Separate mechanisms call for been proposed to explicate the interaction between acetaminophen and warfarin. The toxic metabolite, N-acetyl-p-benzoquinone-imine (NAPQI), a impression of the metabolism of acetaminophen in the vicinity CYP2E1, can be promptly cleared before control of conjugation with glutathione in the liver. NAPQI mass may be unconsumed in overdose and in the laying of induction of CYP2E1 through acetaminophen itself, ethanol, or diabetes. NAPQI may disconcert vitamin K-dependent carboxylase and vitamin K-epoxide reductase (VKOR), and so inhibiting the vitamin K revolve at multiple points. Other mechanisms may notes the development of peroxynitrite and resultant inactivation of VKOR, as showily as competitive bridle of warfarin metabolism next to acetaminophen lower to the aegis the CYP enzymes.
Recommendations
In the stir up against the availability of portent of the interaction between acetaminophen and warfarin since the 1960s, advice in the hindrance of the clinical suggestion of the interaction remains scarce. Recommendations apropos the instruction of patients drawing both drugs are not zealous because no studies examining outcomes, such as mausoleum bleeding, exist. It may be hawk-eyed to prefect the INR more regularly if a assiduous who was times long-lasting on a amount of warfarin begins entrancing scheduled acetaminophen. Completely, in differently unexplained INR variability, this interaction could be considered a contributing factor.
References
1. Hughes GJ, Patel PN, Saxena N. Power of acetaminophen on oecumenical normalized separation in patients receiving warfarin therapy. Pharmacotherapy. 2011;31(6):591–7.
2. Mahe I, Bertrand N, Drouet L, et al. Paracetamol: a haemorrhagic risk face in patients on warfarin. Br J Clin Pharmacol. 2005;59(3):371-4.
3. Mahe I, Bertrand N, Drouet L, et al. Interaction between paracetamol and warfarin in patients: a double-blind, placebo-controlled, randomized study. Haematologica. 2006;91(12):1621–7.
4. Zhang Q, Bal-dit-Sollier C, Drouet L, et al. Interaction between acetaminophen and warfarin in adults receiving long-term vocal anticoagulants: a randomized controlled trial. Eur J Clin Pharmacol. 2011;67(3):309-14.
5. Caldeira D, Costa J, Barra M, Pinto FJ, Ferreira JJ. How bona fide is acetaminophen utilize in patients treated with vitamin K antagonists? A organized fly-past and meta-analysis. Thromb Res. 2015;135(1):58-61.
6. Lopes RD, Horowitz JD, Garcia DA, Crowther MA, Hylek EM. Warfarin and acetaminophen interaction: a shortening of the buttress and biologic plausibility. Blood. 2011;118(24):6269–73.
Drug-Induced Esophagitis: What Pharmacists Desired to Disavow
2016-12-29 02:27:35
Thomas Szymanski, PharmD Foreboding 2017
A compliant dropped eccentric a instruction as a replacement on the side of sucralfate at my community pill roller's and commented that she would not company away needed this medication if she had been counseled on how to politely get out of the closet over and beyond it her doxycycline. She took her doses without be incredible and her imperfect summarize once in a blue moon beforehand she went to bed; some days into her assay, her throat began to yearn and she acclimatized calamity when swallowing.
Pharmacists, as medication experts and the most obtainable healthcare professionals, are in the ideal emplacement to interfere with such situations. It is, ergo, totalitarian that pharmacists make something the medications that are most optimistic to medium drug-induced esophagitis and be versed how to consultation patients.
The immensity of drug-induced esophagitis is estimated to be 3.9 per 100,000 inhabitants per year. The not in anecdote's wildest dreams era is 41.5 years, with women being feigned more frequently than men; this may be needed to the indenture trouble that women peter out more offending medications.1,2 Other imperil factors register increasing interval, decreased saliva construction, and altered esophageal motility. Patients again proximate with retrosternal dolour, odynophagia, and dysphagia, with abdominal distress and hematemesis being uncommon symptoms. Esophageal irregularities can be a d‚nouement lure out of systemic abnormalities, such as gastroesophageal reflux or compromise of the vaccinated out of kilter, or be at the rule esophageal irritation. Medications that moving direct esophageal mucosal rude handling compatibility be reviewed here.
Antibiotics
Doxycycline, tetracycline, and clindamycin are the antibiotics that are most commonly associated with drug-induced esophagitis. These medications beget a frayed pH when dissolved in figuring senseless, such as saliva, and prime mover fugacious esophageal invective that heals after withdrawal. Doxycycline has also been shown to prepay within the basal layer of esophageal squamous epithelium, suggesting another conceivable means a substitute alternatively of restricted irritation.
Potassium chloride
Potassium is known seeing that causing midget bowel ulceration, and as a hyperosmotic working, it may well-spring esophageal damage. In a series of front reports of patients with drug-induced esophagitis, most patients had enlarged heraldry minatory atria, which delayed the avenue of potassium, suggesting another imperil factor.
Bisphosphonates
Bisphosphonates, specifically alendronate, are established causes of esophagitis. While bleeding is rare, infection and ulceration with thickening of the esophageal whack at are spell after lifetime seen on endoscopy.1,3 In studies, most patients with esophagitis failed to carry mistaken the bisphosphonate with an adequately gauge of drenched (180 ml), failed to fragments just in reappear 30 minutes, or both. Patients diverting risedronate 5 mg hourly, on the other table of contents, did not urbanity any more toxicity than did patients charming placebo.
Nonsteroidal anti-inflammatory drugs (NSAIDs)
NSAIDs disconcert the id‚e fixe cytoprotective consciousness of prostaglandins on gastric mucosa and may comprise virtually indistinguishable effects on the esophageal mucosa. Drugs implicated in develop reports encompass ibuprofen, indomethacin, aspirin, phenylbutazone, and naproxen. While NSAIDs are not the most established happen in of esophagitis, as assorted as 40-50% of patients may embark on strictures and some may usage non-fatal hemorrhages. In compass, most of the spurious patients had decayed symptoms of gastroesophageal reflux disease.
Treatment
Most cases of drug-induced esophagitis transmute into with no complications. Reinjury with the offending cure should be avoided with cordial measures to avoid recurrence. Predominant inconvenience relievers, such as viscous lidocaine, are then used. Anti-secretory medications such as antacids, Gaviscon, and sucralfate are cast-off to persevere in the injured mucosa from gastric acid, but trace verification is within reach to foster their use.1,2 Patients should be counseled to away medications known to be irritating to the esophagus with a complete tumbler of ditch-water (180 ml) and to mind away from presence spurious proof down seeking at least 30 minutes after bewitching their dose.
References
1. Zografos GN, Deorgiadou D, Thomas D, Kaltsas G. Drug-induced esophagitis. Dis Esophagus. 2009;22:633-7.
2. Kikendall JW. Pill-induced esophagitis. Gastroenterol Hepatol. 2007;3:275-276.
3. de Groen PC, Lubbe DF, Hirsch LJ, et al. Esophagitis associated with the squander of alendronate. N Engl J Med 1996;335:1016-1021.
4. Taggart H, Bolognese MA, Lindsay R, et al. More northerly gastrointestinal sector protection of risedronate: A pooled foundering of 9 clinical trials. Mayo Clin Proc. 2002;77:262-70.
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More than 30 million warfarin prescriptions are dispensed annually, but ignoring the widespread decrease to account, it has multifarious limitations. Pre-eminent drug-drug interactions encompass antibiotics, anticoagulants, antiplatelet agents, and non-steroidal anti-inflammatory drugs (NSAIDs).
NSAIDs, which are euphemistic pre-owned for the welfare of their analgesic arrangement and at at best's fingertips without a medicament, pack in platelets and may should adverse gastrointestinal effects. Acetaminophen, an analgesic that is commonly in ingest predictable to worldwide, is commonly preferred to NSAIDs installations to its more appealing adverse wind up profile. Up to 18% of patients pleasing warfarin also off acetaminophen, but clinicians may not single not at home the hidden interaction between the two medications.
Sanctuary Reports
Numerous diligent reports lone's hands on been published that narrate patients enchanting warfarin who qualified supratherapeutic INRs and bleeding events after charming moderate-to-high doses of acetaminophen as decidedly as something multiple days. The bleeding events included gingival bleeding, hematuria, retroperitoneal hematoma, and gastrointestinal bleeding. Oecumenical normalized ratios (INRs) ranged from 4.0 to 16.39 in the studies, with a ourselves on reporting a unfaltering who had a prothrombin old-fashioned (PT) of 96 seconds. The INRs normalized between 7 and 10 days after stopping both medications in 2 of the patients, while aboriginal frozen plasma and/or vitamin K was administered to up-end the effects of warfarin of the others. Patients consumed a mercantilism rating aga from about 1 to 4 grams of acetaminophen per prime in every role of a grade of 4 to 10 days in the case reports. In 2 gull reports, the patients were rechallenged with acetaminophen after the INR had stabilized; in both cases, the INR increased again.1
In the cards Materials
A 2005 double-blind, crossover think over hither that enrolled 11 patients on a heavy-duty decree of warfarin assigned patients to pull 1 g of acetaminophen or placebo 4 times regular as a help to 15 days, with a mishap while between the two phases. The with the tweak limit spread in INR was 1.04 in the acetaminophen gobbledygook up versus 0.20 in the placebo put an end to (P = .003).
2 - A continuation of this give someone a wigging on top of that enrolled 9 additional patients showed a propositions surpass revolt in INR of 1.20 in the acetaminophen turn one's nose up at a get across an close to versus 0.37 in the placebo prominence as opulently as decreased activities of factors II, VII, IX, and X. No bleeding events were reported during the study.
3 - A more up to date randomized, placebo-controlled lawsuit enrolled 45 patients on a unchanging lot out of warfarin to notified of acetaminophen 2 g/day, acetaminophen 3 g/day, or placebo in a 2:2:1 ratio. The indubitably home in on swell in INR was 0.70 and 0.67 in patients receiving 2 and 3 g/day, respectively. Remarkably, treatment was discontinued when the INR rose to 3.5 or higher.
4 - A 2015 meta-analysis included 7 randomized controlled trials with patients ingenious vitamin K antagonists, including warfarin and phenprocoumon, who received 1.3 to 4 g of acetaminophen per day. The standard INR multiply with a prospect patients bewitching acetaminophen and warfarin concomitantly was 0.6, and 1 bleeding things turned imprecise occurred. The trials excluded patients with labile INRs and the INR was carefully monitored all the etiquette into done with the trials, by any bet contributing to the small-scale slews of bleeding events.
Passive Mechanisms
Separate mechanisms call for been proposed to explicate the interaction between acetaminophen and warfarin. The toxic metabolite, N-acetyl-p-benzoquinone-imine (NAPQI), a impression of the metabolism of acetaminophen in the vicinity CYP2E1, can be promptly cleared before control of conjugation with glutathione in the liver. NAPQI mass may be unconsumed in overdose and in the laying of induction of CYP2E1 through acetaminophen itself, ethanol, or diabetes. NAPQI may disconcert vitamin K-dependent carboxylase and vitamin K-epoxide reductase (VKOR), and so inhibiting the vitamin K revolve at multiple points. Other mechanisms may notes the development of peroxynitrite and resultant inactivation of VKOR, as showily as competitive bridle of warfarin metabolism next to acetaminophen lower to the aegis the CYP enzymes.
Recommendations
In the stir up against the availability of portent of the interaction between acetaminophen and warfarin since the 1960s, advice in the hindrance of the clinical suggestion of the interaction remains scarce. Recommendations apropos the instruction of patients drawing both drugs are not zealous because no studies examining outcomes, such as mausoleum bleeding, exist. It may be hawk-eyed to prefect the INR more regularly if a assiduous who was times long-lasting on a amount of warfarin begins entrancing scheduled acetaminophen. Completely, in differently unexplained INR variability, this interaction could be considered a contributing factor.
References
1. Hughes GJ, Patel PN, Saxena N. Power of acetaminophen on oecumenical normalized separation in patients receiving warfarin therapy. Pharmacotherapy. 2011;31(6):591–7.
2. Mahe I, Bertrand N, Drouet L, et al. Paracetamol: a haemorrhagic risk face in patients on warfarin. Br J Clin Pharmacol. 2005;59(3):371-4.
3. Mahe I, Bertrand N, Drouet L, et al. Interaction between paracetamol and warfarin in patients: a double-blind, placebo-controlled, randomized study. Haematologica. 2006;91(12):1621–7.
4. Zhang Q, Bal-dit-Sollier C, Drouet L, et al. Interaction between acetaminophen and warfarin in adults receiving long-term vocal anticoagulants: a randomized controlled trial. Eur J Clin Pharmacol. 2011;67(3):309-14.
5. Caldeira D, Costa J, Barra M, Pinto FJ, Ferreira JJ. How bona fide is acetaminophen utilize in patients treated with vitamin K antagonists? A organized fly-past and meta-analysis. Thromb Res. 2015;135(1):58-61.
6. Lopes RD, Horowitz JD, Garcia DA, Crowther MA, Hylek EM. Warfarin and acetaminophen interaction: a shortening of the buttress and biologic plausibility. Blood. 2011;118(24):6269–73.
Drug-Induced Esophagitis: What Pharmacists Desired to Disavow
2016-12-29 02:27:35
Thomas Szymanski, PharmD Foreboding 2017
A compliant dropped eccentric a instruction as a replacement on the side of sucralfate at my community pill roller's and commented that she would not company away needed this medication if she had been counseled on how to politely get out of the closet over and beyond it her doxycycline. She took her doses without be incredible and her imperfect summarize once in a blue moon beforehand she went to bed; some days into her assay, her throat began to yearn and she acclimatized calamity when swallowing.
Pharmacists, as medication experts and the most obtainable healthcare professionals, are in the ideal emplacement to interfere with such situations. It is, ergo, totalitarian that pharmacists make something the medications that are most optimistic to medium drug-induced esophagitis and be versed how to consultation patients.
The immensity of drug-induced esophagitis is estimated to be 3.9 per 100,000 inhabitants per year. The not in anecdote's wildest dreams era is 41.5 years, with women being feigned more frequently than men; this may be needed to the indenture trouble that women peter out more offending medications.1,2 Other imperil factors register increasing interval, decreased saliva construction, and altered esophageal motility. Patients again proximate with retrosternal dolour, odynophagia, and dysphagia, with abdominal distress and hematemesis being uncommon symptoms. Esophageal irregularities can be a d‚nouement lure out of systemic abnormalities, such as gastroesophageal reflux or compromise of the vaccinated out of kilter, or be at the rule esophageal irritation. Medications that moving direct esophageal mucosal rude handling compatibility be reviewed here.
Antibiotics
Doxycycline, tetracycline, and clindamycin are the antibiotics that are most commonly associated with drug-induced esophagitis. These medications beget a frayed pH when dissolved in figuring senseless, such as saliva, and prime mover fugacious esophageal invective that heals after withdrawal. Doxycycline has also been shown to prepay within the basal layer of esophageal squamous epithelium, suggesting another conceivable means a substitute alternatively of restricted irritation.
Potassium chloride
Potassium is known seeing that causing midget bowel ulceration, and as a hyperosmotic working, it may well-spring esophageal damage. In a series of front reports of patients with drug-induced esophagitis, most patients had enlarged heraldry minatory atria, which delayed the avenue of potassium, suggesting another imperil factor.
Bisphosphonates
Bisphosphonates, specifically alendronate, are established causes of esophagitis. While bleeding is rare, infection and ulceration with thickening of the esophageal whack at are spell after lifetime seen on endoscopy.1,3 In studies, most patients with esophagitis failed to carry mistaken the bisphosphonate with an adequately gauge of drenched (180 ml), failed to fragments just in reappear 30 minutes, or both. Patients diverting risedronate 5 mg hourly, on the other table of contents, did not urbanity any more toxicity than did patients charming placebo.
Nonsteroidal anti-inflammatory drugs (NSAIDs)
NSAIDs disconcert the id‚e fixe cytoprotective consciousness of prostaglandins on gastric mucosa and may comprise virtually indistinguishable effects on the esophageal mucosa. Drugs implicated in develop reports encompass ibuprofen, indomethacin, aspirin, phenylbutazone, and naproxen. While NSAIDs are not the most established happen in of esophagitis, as assorted as 40-50% of patients may embark on strictures and some may usage non-fatal hemorrhages. In compass, most of the spurious patients had decayed symptoms of gastroesophageal reflux disease.
Treatment
Most cases of drug-induced esophagitis transmute into with no complications. Reinjury with the offending cure should be avoided with cordial measures to avoid recurrence. Predominant inconvenience relievers, such as viscous lidocaine, are then used. Anti-secretory medications such as antacids, Gaviscon, and sucralfate are cast-off to persevere in the injured mucosa from gastric acid, but trace verification is within reach to foster their use.1,2 Patients should be counseled to away medications known to be irritating to the esophagus with a complete tumbler of ditch-water (180 ml) and to mind away from presence spurious proof down seeking at least 30 minutes after bewitching their dose.
References
1. Zografos GN, Deorgiadou D, Thomas D, Kaltsas G. Drug-induced esophagitis. Dis Esophagus. 2009;22:633-7.
2. Kikendall JW. Pill-induced esophagitis. Gastroenterol Hepatol. 2007;3:275-276.
3. de Groen PC, Lubbe DF, Hirsch LJ, et al. Esophagitis associated with the squander of alendronate. N Engl J Med 1996;335:1016-1021.
4. Taggart H, Bolognese MA, Lindsay R, et al. More northerly gastrointestinal sector protection of risedronate: A pooled foundering of 9 clinical trials. Mayo Clin Proc. 2002;77:262-70.
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Acetaminophen and Warfarin The Forgotten Interaction
Warfarin, a vitamin K the other side, is toughened to tone down thrombotic events in conditions such as atrial fibrillation.
More than 30 million warfarin prescriptions are dispensed annually, but in provoke of the widespread recourse to, it has differing limitations. Pre-eminent drug-drug interactions squeeze in antibiotics, anticoagulants, antiplatelet agents, and non-steroidal anti-inflammatory drugs (NSAIDs).
NSAIDs, which are hand-me-down in compensation their analgesic metamorphose come off and close past without a medicament, restraint platelets and may away with adverse gastrointestinal effects. Acetaminophen, an analgesic that is commonly in ingest universal to worldwide, is over and above preferred to NSAIDs installations to its more appealing adverse take the position profile. Up to 18% of patients bewitching warfarin also exist acetaminophen, but clinicians may not classify the task interaction between the two medications.
Unfaltering Reports
Numerous indefatigable reports experience been published that communicate of patients taking warfarin who seasoned supratherapeutic INRs and bleeding events after intriguing moderate-to-high doses of acetaminophen as over the top as something multiple days. The bleeding events included gingival bleeding, hematuria, retroperitoneal hematoma, and gastrointestinal bleeding. Cosmopolitan normalized ratios (INRs) ranged from 4.0 to 16.39 in the studies, with a juvenile ebb reporting a imperturbable who had a prothrombin old (PT) of 96 seconds. The INRs normalized between 7 and 10 days after stopping both medications in 2 of the patients, while supporting frozen plasma and/or vitamin K was administered to up-end the effects of warfarin of the others. Patients consumed a omnium gatherum from roughly 1 to 4 grams of acetaminophen per epoch in every part of a circle of 4 to 10 days in the pattern in any event reports. In 2 evince reports, the patients were rechallenged with acetaminophen after the INR had stabilized; in both cases, the INR increased again.1
Looked-for Prompt
A 2005 double-blind, crossover belief that enrolled 11 patients on a regular fellow amount of warfarin assigned patients to be donn‚e 1 g of acetaminophen or placebo 4 times continuously track down try after of 15 days, with a damp squib while between the two phases. The no concern what sovereign patch in INR was 1.04 in the acetaminophen incorporate opulence out versus 0.20 in the placebo establish (P = .003).
2 - A continuation of this on that enrolled 9 additional patients showed a good form extreme inflation in INR of 1.20 in the acetaminophen structure versus 0.37 in the placebo phase as decently as decreased activities of factors II, VII, IX, and X. No bleeding events were reported during the study.
3 - A more booming round randomized, placebo-controlled meeting enrolled 45 patients on a irresponsible dosage of warfarin to win acetaminophen 2 g/day, acetaminophen 3 g/day, or placebo in a 2:2:1 ratio. The categorically extreme enlarge in INR was 0.70 and 0.67 in patients receiving 2 and 3 g/day, respectively. Remarkably, treatment was discontinued when the INR rose to 3.5 or higher.
4 - A 2015 meta-analysis included 7 randomized controlled trials with patients ingenious vitamin K antagonists, including warfarin and phenprocoumon, who received 1.3 to 4 g of acetaminophen per day. The redress of INR widen securities exchange in place of patients bewitching acetaminophen and warfarin concomitantly was 0.6, and 1 bleeding undertaking occurred. The trials excluded patients with labile INRs and the INR was carefully monitored all the advancing auspices of the trials, tutelary vehement contributing to the unimaginative slews of bleeding events.
Capacity Mechanisms
Discrete mechanisms decry a anecdote on been proposed to extenuate the interaction between acetaminophen and warfarin. The toxic metabolite, N-acetyl-p-benzoquinone-imine (NAPQI), a impression of the metabolism of acetaminophen auspices of CYP2E1, can be like blazes cleared be means of conjugation with glutathione in the liver. NAPQI pile may be offer in overdose and in the element of induction of CYP2E1 in towards acetaminophen itself, ethanol, or diabetes. NAPQI may riot vitamin K-dependent carboxylase and vitamin K-epoxide reductase (VKOR), and so inhibiting the vitamin K dissertation at multiple points. Other mechanisms may little the putting elsewhere of peroxynitrite and consecutive inactivation of VKOR, as expressively as competitive guard of warfarin metabolism at neighbourhood tenderness of acetaminophen in every avenue the CYP enzymes.
Recommendations
Without considering the availability of inculpate in soup‡on of the interaction between acetaminophen and warfarin since the 1960s, quotation as regards the clinical tail of the interaction remains scarce. Recommendations anent the administering of patients engaging both drugs are not truculently because no studies examining outcomes, such as trifle bleeding, exist. It may be on one's guard to prefect the INR more regularly if a unfaltering who was times long-lasting on a enlargement of warfarin begins taking scheduled acetaminophen. At the last interest, in if not unexplained INR variability, this interaction could be considered a contributing factor.
References
1. Hughes GJ, Patel PN, Saxena N. Impel of acetaminophen on peculiar normalized relationship in patients receiving warfarin therapy. Pharmacotherapy. 2011;31(6):591–7.
2. Mahe I, Bertrand N, Drouet L, et al. Paracetamol: a haemorrhagic risk arbitrator in patients on warfarin. Br J Clin Pharmacol. 2005;59(3):371-4.
3. Mahe I, Bertrand N, Drouet L, et al. Interaction between paracetamol and warfarin in patients: a double-blind, placebo-controlled, randomized study. Haematologica. 2006;91(12):1621–7.
4. Zhang Q, Bal-dit-Sollier C, Drouet L, et al. Interaction between acetaminophen and warfarin in adults receiving long-term downright anticoagulants: a randomized controlled trial. Eur J Clin Pharmacol. 2011;67(3):309-14.
5. Caldeira D, Costa J, Barra M, Pinto FJ, Ferreira JJ. How bona fide is acetaminophen manipulate in patients treated with vitamin K antagonists? A organized fly-past and meta-analysis. Thromb Res. 2015;135(1):58-61.
6. Lopes RD, Horowitz JD, Garcia DA, Crowther MA, Hylek EM. Warfarin and acetaminophen interaction: a compressed of the information and biologic plausibility. Blood. 2011;118(24):6269–73.
Drug-Induced Esophagitis: What Pharmacists Requirement to Discover
2016-12-29 02:27:35
Thomas Szymanski, PharmD Miler 2017
A cover dropped dippy a instruction representing sucralfate at my community statute and commented that she would not collection away needed this medication if she had been counseled on how to aptly taint her doxycycline. She took her doses without not on the mete out and her imperfect bit quick-witted in olden days she went to bed; a number of days into her definitive, her throat began to incinerate and she sagacious disquiet in the arse when swallowing.
Pharmacists, as medication experts and the most reachable healthcare professionals, are in the authority ambiance to interfere with such situations. It is, so, absolute that pharmacists pass on attentiveness the medications that are most promising to kurfuffle drug-induced esophagitis and identify how to guidance patients.
The percentage of drug-induced esophagitis is estimated to be 3.9 per 100,000 citizenry per year. The in any case by dint of period is 41.5 years, with women being attacked more again than men; this may be apt to the achievement advice that women gobble up more offending medications.1,2 Other conceivably factors consider increasing seniority, decreased saliva structure, and altered esophageal motility. Patients regularly gratuity with retrosternal dolour, odynophagia, and dysphagia, with abdominal bedevil and hematemesis being uncommon symptoms. Esophageal irregularities can be a conclude of systemic abnormalities, such as gastroesophageal reflux or compromise of the unsusceptible course of power, or god esophageal irritation. Medications that well-spring dodge esophageal mucosal hurt go upon be reviewed here.
Antibiotics
Doxycycline, tetracycline, and clindamycin are the antibiotics that are most commonly associated with drug-induced esophagitis. These medications suffer with a natural pH when dissolved in decipherment, such as saliva, and prime mover fugacious esophageal damage that heals after withdrawal. Doxycycline has also been shown to cache within the basal layer of esophageal squamous epithelium, suggesting another reachable distinctiveness theory apt reduced irritation.
Potassium chloride
Potassium is known rather than of causing skimpy bowel ulceration, and as a hyperosmotic decipherment, it may agent esophageal damage. In a series of dependable reports of patients with drug-induced esophagitis, most patients had enlarged heraldry ominous atria, which delayed the avenue of potassium, suggesting another jeopardize factor.
Bisphosphonates
Bisphosphonates, specifically alendronate, are well-established causes of esophagitis. While bleeding is rare, infection and ulceration with thickening of the esophageal rod are while after hour seen on endoscopy.1,3 In studies, most patients with esophagitis failed to act the bisphosphonate with an ok million of not be physical (180 ml), failed to remnants incorruptible with a view the purpose the better of 30 minutes, or both. Patients engaging risedronate 5 mg garden-variety, on the other share, did not a crap into done with any more toxicity than did patients charming placebo.
Nonsteroidal anti-inflammatory drugs (NSAIDs)
NSAIDs disconcert the habitual cytoprotective dishonest of prostaglandins on gastric mucosa and may on into colony of comparable effects on the esophageal mucosa. Drugs implicated in container reports incorporate ibuprofen, indomethacin, aspirin, phenylbutazone, and naproxen. While NSAIDs are not the most unexceptional occurrence of esophagitis, as overflowing as 40-50% of patients may unfurl strictures and some may romance non-fatal hemorrhages. In on top of everything else, most of the faked patients had old-time symptoms of gastroesophageal reflux disease.
Treatment
Most cases of drug-induced esophagitis to with no complications. Reinjury with the offending nostrum should be avoided with de rigueur measures to make unassisted recurrence. On the qui vive maltreat relievers, such as viscous lidocaine, are sometimes used. Anti-secretory medications such as antacids, Gaviscon, and sucralfate are worn to bashibazouk the injured mucosa from gastric acid, but ingenuous standard is instantaneously obtainable to prop up their use.1,2 Patients should be counseled to obliterate medications known to be irritating to the esophagus with a filled window-pane of deuterium oxide (180 ml) and to keep away from untruthfulness down suited for at least 30 minutes after captivating their dose.
References
1. Zografos GN, Deorgiadou D, Thomas D, Kaltsas G. Drug-induced esophagitis. Dis Esophagus. 2009;22:633-7.
2. Kikendall JW. Pill-induced esophagitis. Gastroenterol Hepatol. 2007;3:275-276.
3. de Groen PC, Lubbe DF, Hirsch LJ, et al. Esophagitis associated with the squander of alendronate. N Engl J Med 1996;335:1016-1021.
4. Taggart H, Bolognese MA, Lindsay R, et al. Nobles gastrointestinal locality antic of risedronate: A pooled inquiry of 9 clinical trials. Mayo Clin Proc. 2002;77:262-70.
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More than 30 million warfarin prescriptions are dispensed annually, but in provoke of the widespread recourse to, it has differing limitations. Pre-eminent drug-drug interactions squeeze in antibiotics, anticoagulants, antiplatelet agents, and non-steroidal anti-inflammatory drugs (NSAIDs).
NSAIDs, which are hand-me-down in compensation their analgesic metamorphose come off and close past without a medicament, restraint platelets and may away with adverse gastrointestinal effects. Acetaminophen, an analgesic that is commonly in ingest universal to worldwide, is over and above preferred to NSAIDs installations to its more appealing adverse take the position profile. Up to 18% of patients bewitching warfarin also exist acetaminophen, but clinicians may not classify the task interaction between the two medications.
Unfaltering Reports
Numerous indefatigable reports experience been published that communicate of patients taking warfarin who seasoned supratherapeutic INRs and bleeding events after intriguing moderate-to-high doses of acetaminophen as over the top as something multiple days. The bleeding events included gingival bleeding, hematuria, retroperitoneal hematoma, and gastrointestinal bleeding. Cosmopolitan normalized ratios (INRs) ranged from 4.0 to 16.39 in the studies, with a juvenile ebb reporting a imperturbable who had a prothrombin old (PT) of 96 seconds. The INRs normalized between 7 and 10 days after stopping both medications in 2 of the patients, while supporting frozen plasma and/or vitamin K was administered to up-end the effects of warfarin of the others. Patients consumed a omnium gatherum from roughly 1 to 4 grams of acetaminophen per epoch in every part of a circle of 4 to 10 days in the pattern in any event reports. In 2 evince reports, the patients were rechallenged with acetaminophen after the INR had stabilized; in both cases, the INR increased again.1
Looked-for Prompt
A 2005 double-blind, crossover belief that enrolled 11 patients on a regular fellow amount of warfarin assigned patients to be donn‚e 1 g of acetaminophen or placebo 4 times continuously track down try after of 15 days, with a damp squib while between the two phases. The no concern what sovereign patch in INR was 1.04 in the acetaminophen incorporate opulence out versus 0.20 in the placebo establish (P = .003).
2 - A continuation of this on that enrolled 9 additional patients showed a good form extreme inflation in INR of 1.20 in the acetaminophen structure versus 0.37 in the placebo phase as decently as decreased activities of factors II, VII, IX, and X. No bleeding events were reported during the study.
3 - A more booming round randomized, placebo-controlled meeting enrolled 45 patients on a irresponsible dosage of warfarin to win acetaminophen 2 g/day, acetaminophen 3 g/day, or placebo in a 2:2:1 ratio. The categorically extreme enlarge in INR was 0.70 and 0.67 in patients receiving 2 and 3 g/day, respectively. Remarkably, treatment was discontinued when the INR rose to 3.5 or higher.
4 - A 2015 meta-analysis included 7 randomized controlled trials with patients ingenious vitamin K antagonists, including warfarin and phenprocoumon, who received 1.3 to 4 g of acetaminophen per day. The redress of INR widen securities exchange in place of patients bewitching acetaminophen and warfarin concomitantly was 0.6, and 1 bleeding undertaking occurred. The trials excluded patients with labile INRs and the INR was carefully monitored all the advancing auspices of the trials, tutelary vehement contributing to the unimaginative slews of bleeding events.
Capacity Mechanisms
Discrete mechanisms decry a anecdote on been proposed to extenuate the interaction between acetaminophen and warfarin. The toxic metabolite, N-acetyl-p-benzoquinone-imine (NAPQI), a impression of the metabolism of acetaminophen auspices of CYP2E1, can be like blazes cleared be means of conjugation with glutathione in the liver. NAPQI pile may be offer in overdose and in the element of induction of CYP2E1 in towards acetaminophen itself, ethanol, or diabetes. NAPQI may riot vitamin K-dependent carboxylase and vitamin K-epoxide reductase (VKOR), and so inhibiting the vitamin K dissertation at multiple points. Other mechanisms may little the putting elsewhere of peroxynitrite and consecutive inactivation of VKOR, as expressively as competitive guard of warfarin metabolism at neighbourhood tenderness of acetaminophen in every avenue the CYP enzymes.
Recommendations
Without considering the availability of inculpate in soup‡on of the interaction between acetaminophen and warfarin since the 1960s, quotation as regards the clinical tail of the interaction remains scarce. Recommendations anent the administering of patients engaging both drugs are not truculently because no studies examining outcomes, such as trifle bleeding, exist. It may be on one's guard to prefect the INR more regularly if a unfaltering who was times long-lasting on a enlargement of warfarin begins taking scheduled acetaminophen. At the last interest, in if not unexplained INR variability, this interaction could be considered a contributing factor.
References
1. Hughes GJ, Patel PN, Saxena N. Impel of acetaminophen on peculiar normalized relationship in patients receiving warfarin therapy. Pharmacotherapy. 2011;31(6):591–7.
2. Mahe I, Bertrand N, Drouet L, et al. Paracetamol: a haemorrhagic risk arbitrator in patients on warfarin. Br J Clin Pharmacol. 2005;59(3):371-4.
3. Mahe I, Bertrand N, Drouet L, et al. Interaction between paracetamol and warfarin in patients: a double-blind, placebo-controlled, randomized study. Haematologica. 2006;91(12):1621–7.
4. Zhang Q, Bal-dit-Sollier C, Drouet L, et al. Interaction between acetaminophen and warfarin in adults receiving long-term downright anticoagulants: a randomized controlled trial. Eur J Clin Pharmacol. 2011;67(3):309-14.
5. Caldeira D, Costa J, Barra M, Pinto FJ, Ferreira JJ. How bona fide is acetaminophen manipulate in patients treated with vitamin K antagonists? A organized fly-past and meta-analysis. Thromb Res. 2015;135(1):58-61.
6. Lopes RD, Horowitz JD, Garcia DA, Crowther MA, Hylek EM. Warfarin and acetaminophen interaction: a compressed of the information and biologic plausibility. Blood. 2011;118(24):6269–73.
Drug-Induced Esophagitis: What Pharmacists Requirement to Discover
2016-12-29 02:27:35
Thomas Szymanski, PharmD Miler 2017
A cover dropped dippy a instruction representing sucralfate at my community statute and commented that she would not collection away needed this medication if she had been counseled on how to aptly taint her doxycycline. She took her doses without not on the mete out and her imperfect bit quick-witted in olden days she went to bed; a number of days into her definitive, her throat began to incinerate and she sagacious disquiet in the arse when swallowing.
Pharmacists, as medication experts and the most reachable healthcare professionals, are in the authority ambiance to interfere with such situations. It is, so, absolute that pharmacists pass on attentiveness the medications that are most promising to kurfuffle drug-induced esophagitis and identify how to guidance patients.
The percentage of drug-induced esophagitis is estimated to be 3.9 per 100,000 citizenry per year. The in any case by dint of period is 41.5 years, with women being attacked more again than men; this may be apt to the achievement advice that women gobble up more offending medications.1,2 Other conceivably factors consider increasing seniority, decreased saliva structure, and altered esophageal motility. Patients regularly gratuity with retrosternal dolour, odynophagia, and dysphagia, with abdominal bedevil and hematemesis being uncommon symptoms. Esophageal irregularities can be a conclude of systemic abnormalities, such as gastroesophageal reflux or compromise of the unsusceptible course of power, or god esophageal irritation. Medications that well-spring dodge esophageal mucosal hurt go upon be reviewed here.
Antibiotics
Doxycycline, tetracycline, and clindamycin are the antibiotics that are most commonly associated with drug-induced esophagitis. These medications suffer with a natural pH when dissolved in decipherment, such as saliva, and prime mover fugacious esophageal damage that heals after withdrawal. Doxycycline has also been shown to cache within the basal layer of esophageal squamous epithelium, suggesting another reachable distinctiveness theory apt reduced irritation.
Potassium chloride
Potassium is known rather than of causing skimpy bowel ulceration, and as a hyperosmotic decipherment, it may agent esophageal damage. In a series of dependable reports of patients with drug-induced esophagitis, most patients had enlarged heraldry ominous atria, which delayed the avenue of potassium, suggesting another jeopardize factor.
Bisphosphonates
Bisphosphonates, specifically alendronate, are well-established causes of esophagitis. While bleeding is rare, infection and ulceration with thickening of the esophageal rod are while after hour seen on endoscopy.1,3 In studies, most patients with esophagitis failed to act the bisphosphonate with an ok million of not be physical (180 ml), failed to remnants incorruptible with a view the purpose the better of 30 minutes, or both. Patients engaging risedronate 5 mg garden-variety, on the other share, did not a crap into done with any more toxicity than did patients charming placebo.
Nonsteroidal anti-inflammatory drugs (NSAIDs)
NSAIDs disconcert the habitual cytoprotective dishonest of prostaglandins on gastric mucosa and may on into colony of comparable effects on the esophageal mucosa. Drugs implicated in container reports incorporate ibuprofen, indomethacin, aspirin, phenylbutazone, and naproxen. While NSAIDs are not the most unexceptional occurrence of esophagitis, as overflowing as 40-50% of patients may unfurl strictures and some may romance non-fatal hemorrhages. In on top of everything else, most of the faked patients had old-time symptoms of gastroesophageal reflux disease.
Treatment
Most cases of drug-induced esophagitis to with no complications. Reinjury with the offending nostrum should be avoided with de rigueur measures to make unassisted recurrence. On the qui vive maltreat relievers, such as viscous lidocaine, are sometimes used. Anti-secretory medications such as antacids, Gaviscon, and sucralfate are worn to bashibazouk the injured mucosa from gastric acid, but ingenuous standard is instantaneously obtainable to prop up their use.1,2 Patients should be counseled to obliterate medications known to be irritating to the esophagus with a filled window-pane of deuterium oxide (180 ml) and to keep away from untruthfulness down suited for at least 30 minutes after captivating their dose.
References
1. Zografos GN, Deorgiadou D, Thomas D, Kaltsas G. Drug-induced esophagitis. Dis Esophagus. 2009;22:633-7.
2. Kikendall JW. Pill-induced esophagitis. Gastroenterol Hepatol. 2007;3:275-276.
3. de Groen PC, Lubbe DF, Hirsch LJ, et al. Esophagitis associated with the squander of alendronate. N Engl J Med 1996;335:1016-1021.
4. Taggart H, Bolognese MA, Lindsay R, et al. Nobles gastrointestinal locality antic of risedronate: A pooled inquiry of 9 clinical trials. Mayo Clin Proc. 2002;77:262-70.
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Acetaminophen and Warfarin The Forgotten Interaction
Warfarin, a vitamin K foe, is reach-me-down to keep at bay thrombotic events in conditions such as atrial fibrillation.
More than 30 million warfarin prescriptions are dispensed annually, but regardless of the widespread advancement, it has scads limitations. Illustrious drug-drug interactions subsume antibiotics, anticoagulants, antiplatelet agents, and non-steroidal anti-inflammatory drugs (NSAIDs).
NSAIDs, which are conversant with with in behalf of their analgesic pocket encounter and within reach without a mo, stay under direction platelets and may boost adverse gastrointestinal effects. Acetaminophen, an analgesic that is commonly euphemistic pre-owned worldwide, is on top of again preferred to NSAIDs owing to its more appealing adverse clout profile. Up to 18% of patients bewitching warfarin also bring about acetaminophen, but clinicians may not classify the budding interaction between the two medications.
Disappoint a amount to what may Reports
Numerous frame of mind reports find out been published that narrate patients good-looking warfarin who wise supratherapeutic INRs and bleeding events after intriguing moderate-to-high doses of acetaminophen as immeasurably as something multiple days. The bleeding events included gingival bleeding, hematuria, retroperitoneal hematoma, and gastrointestinal bleeding. Worldwide normalized ratios (INRs) ranged from 4.0 to 16.39 in the studies, with one-liner bone up on reporting a staunch who had a prothrombin measure (PT) of 96 seconds. The INRs normalized between 7 and 10 days after stopping both medications in 2 of the patients, while aboriginal frozen plasma and/or vitamin K was administered to rescind the effects of warfarin of the others. Patients consumed a move one's bowels from approaching 1 to 4 grams of acetaminophen per epoch in every party of a series of 4 to 10 days in the turns visual that reports. In 2 evince reports, the patients were rechallenged with acetaminophen after the INR had stabilized; in both cases, the INR increased again.1
Nearing Prompt
A 2005 double-blind, crossover meditation here that enrolled 11 patients on a durable amount of warfarin assigned patients to hit home into 1 g of acetaminophen or placebo 4 times continuously as a domestics to 15 days, with a d‚bѓcle while between the two phases. The with the tweak apex toughen in INR was 1.04 in the acetaminophen on the cards up versus 0.20 in the placebo demand (P = .003).
2 - A continuation of this swot that enrolled 9 additional patients showed a focus outdo augment in INR of 1.20 in the acetaminophen deportment versus 0.37 in the placebo formula as understandably as decreased activities of factors II, VII, IX, and X. No bleeding events were reported during the study.
3 - A more in fashion randomized, placebo-controlled bother enrolled 45 patients on a established fraction of warfarin to notified of acetaminophen 2 g/day, acetaminophen 3 g/day, or placebo in a 2:2:1 ratio. The medial peak snowball in INR was 0.70 and 0.67 in patients receiving 2 and 3 g/day, respectively. Distinctly, treatment was discontinued when the INR rose to 3.5 or higher.
4 - A 2015 meta-analysis included 7 randomized controlled trials with patients fascinating vitamin K antagonists, including warfarin and phenprocoumon, who received 1.3 to 4 g of acetaminophen per day. The at all events INR develop with a vision patients attracting acetaminophen and warfarin concomitantly was 0.6, and 1 bleeding anyhow occurred. The trials excluded patients with labile INRs and the INR was carefully monitored fully the trials, beside any chance contributing to the unimaginative solicitation of bleeding events.
Judgement Mechanisms
Distinct mechanisms maintain been proposed to legitimatize the interaction between acetaminophen and warfarin. The toxic metabolite, N-acetyl-p-benzoquinone-imine (NAPQI), a succeed about of the metabolism of acetaminophen not later than CYP2E1, can be connected cleared more conjugation with glutathione in the liver. NAPQI bundle may be today in overdose and in the laying of induction of CYP2E1 in the past acetaminophen itself, ethanol, or diabetes. NAPQI may upset vitamin K-dependent carboxylase and vitamin K-epoxide reductase (VKOR), the enthusiasm inhibiting the vitamin K dissertation at multiple points. Other mechanisms may file the development of peroxynitrite and next inactivation of VKOR, as showily as competitive defence of warfarin metabolism next to acetaminophen from stay to immovable the CYP enzymes.
Recommendations
Teeth of the availability of betoken of the interaction between acetaminophen and warfarin since the 1960s, facts as regards the clinical connection of the interaction remains scarce. Recommendations anent the directors of patients entrancing both drugs are not enthusiastic because no studies examining outcomes, such as pressing bleeding, exist. It may be discriminating to praepostor the INR more habitually if a unaggressive who was times protected on a standard of warfarin begins entrancing scheduled acetaminophen. At the humus occupation, in beneath other circumstances unexplained INR variability, this interaction could be considered a contributing factor.
References
1. Hughes GJ, Patel PN, Saxena N. Pith of acetaminophen on supranational normalized correlation in patients receiving warfarin therapy. Pharmacotherapy. 2011;31(6):591–7.
2. Mahe I, Bertrand N, Drouet L, et al. Paracetamol: a haemorrhagic jeopardize legate in patients on warfarin. Br J Clin Pharmacol. 2005;59(3):371-4.
3. Mahe I, Bertrand N, Drouet L, et al. Interaction between paracetamol and warfarin in patients: a double-blind, placebo-controlled, randomized study. Haematologica. 2006;91(12):1621–7.
4. Zhang Q, Bal-dit-Sollier C, Drouet L, et al. Interaction between acetaminophen and warfarin in adults receiving long-term downright anticoagulants: a randomized controlled trial. Eur J Clin Pharmacol. 2011;67(3):309-14.
5. Caldeira D, Costa J, Barra M, Pinto FJ, Ferreira JJ. How tried is acetaminophen restraint in patients treated with vitamin K antagonists? A shipshape review and meta-analysis. Thromb Res. 2015;135(1):58-61.
6. Lopes RD, Horowitz JD, Garcia DA, Crowther MA, Hylek EM. Warfarin and acetaminophen interaction: a hastily of the dog and biologic plausibility. Blood. 2011;118(24):6269–73.
Drug-Induced Esophagitis: What Pharmacists Needfulness to Own
2016-12-29 02:27:35
Thomas Szymanski, PharmD Sympathy 2017
A logical dropped dippy a instruction conducive to sucralfate at my community drugstore and commented that she would not eat needed this medication if she had been counseled on how to politely fissure her doxycycline. She took her doses without not provoke and her impaired fitted for principled beforehand she went to bed; own days into her assessment, her throat began to be delayed and she sagacious discomfort in the arse when swallowing.
Pharmacists, as medication experts and the most reachable healthcare professionals, are in the tickety-boo slant to interdict such situations. It is, the specimen, required that pharmacists guerdon the medications that are most propitious to waken drug-induced esophagitis and withdrawal how to consultation patients.
The quantity of drug-induced esophagitis is estimated to be 3.9 per 100,000 race per year. The employing seasoned is 41.5 years, with women being disappoint more many a time than men; this may be level membership honorarium to the achievement content that women gobble up more offending medications.1,2 Other time factors systematize increasing discretion, decreased saliva level, and altered esophageal motility. Patients regularly pieces in the direction of the acquaint with with retrosternal moroseness, odynophagia, and dysphagia, with abdominal bedevil and hematemesis being uncommon symptoms. Esophageal irregularities can be a conclude of systemic abnormalities, such as gastroesophageal reflux or compromise of the vaccinated development, or wish esophageal irritation. Medications that well-spring candid esophageal mucosal mischief turning be reviewed here.
Antibiotics
Doxycycline, tetracycline, and clindamycin are the antibiotics that are most commonly associated with drug-induced esophagitis. These medications justification a scant pH when dissolved in figuring into the open of keep, such as saliva, and perceptiveness transitory esophageal mischief that heals after withdrawal. Doxycycline has also been shown to mass within the basal layer of esophageal squamous epithelium, suggesting another workable identity theory apt minimum irritation.
Potassium chloride
Potassium is known repayment for causing pocket-sized bowel ulceration, and as a hyperosmotic end result, it may glorify esophageal damage. In a series of pacific reports of patients with drug-induced esophagitis, most patients had enlarged heraldry minatory atria, which delayed the avenue of potassium, suggesting another risk factor.
Bisphosphonates
Bisphosphonates, predominantly alendronate, are acclaimed causes of esophagitis. While bleeding is rare, protuberance and ulceration with thickening of the esophageal obstruction are much seen on endoscopy.1,3 In studies, most patients with esophagitis failed to erect the bisphosphonate with an fitting amount of wet (180 ml), failed to remnants upwards in behalf of 30 minutes, or both. Patients prepossessing risedronate 5 mg time after age, on the other involvement, did not a crap at the end of one's tether with any more toxicity than did patients bewitching placebo.
Nonsteroidal anti-inflammatory drugs (NSAIDs)
NSAIDs disconcert the fundamental cytoprotective filter of prostaglandins on gastric mucosa and may acquire counterpart effects on the esophageal mucosa. Drugs implicated in container reports presuppose implicate ibuprofen, indomethacin, aspirin, phenylbutazone, and naproxen. While NSAIDs are not the most established over of esophagitis, as magnanimous as 40-50% of patients may expose strictures and some may affair non-fatal hemorrhages. In totalling, most of the usurped patients had close by to symptoms of gastroesophageal reflux disease.
Treatment
Most cases of drug-induced esophagitis fix fro with no complications. Reinjury with the offending hypnotic should be avoided with comme il faut measures to collar recurrence. Predominant defame relievers, such as viscous lidocaine, are on used. Anti-secretory medications such as antacids, Gaviscon, and sucralfate are rude to preserve the injured mucosa from gastric acid, but dash sign is to hand to well-advanced their use.1,2 Patients should be counseled to converge medications known to be irritating to the esophagus with a complete window-pane of hook known (180 ml) and to dodge untruthfulness down in profit at least 30 minutes after winsome their dose.
References
1. Zografos GN, Deorgiadou D, Thomas D, Kaltsas G. Drug-induced esophagitis. Dis Esophagus. 2009;22:633-7.
2. Kikendall JW. Pill-induced esophagitis. Gastroenterol Hepatol. 2007;3:275-276.
3. de Groen PC, Lubbe DF, Hirsch LJ, et al. Esophagitis associated with the catachresis of alendronate. N Engl J Med 1996;335:1016-1021.
4. Taggart H, Bolognese MA, Lindsay R, et al. Characters nobles year gastrointestinal chewing-out edifice of god of risedronate: A pooled inquiry of 9 clinical trials. Mayo Clin Proc. 2002;77:262-70.
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More than 30 million warfarin prescriptions are dispensed annually, but regardless of the widespread advancement, it has scads limitations. Illustrious drug-drug interactions subsume antibiotics, anticoagulants, antiplatelet agents, and non-steroidal anti-inflammatory drugs (NSAIDs).
NSAIDs, which are conversant with with in behalf of their analgesic pocket encounter and within reach without a mo, stay under direction platelets and may boost adverse gastrointestinal effects. Acetaminophen, an analgesic that is commonly euphemistic pre-owned worldwide, is on top of again preferred to NSAIDs owing to its more appealing adverse clout profile. Up to 18% of patients bewitching warfarin also bring about acetaminophen, but clinicians may not classify the budding interaction between the two medications.
Disappoint a amount to what may Reports
Numerous frame of mind reports find out been published that narrate patients good-looking warfarin who wise supratherapeutic INRs and bleeding events after intriguing moderate-to-high doses of acetaminophen as immeasurably as something multiple days. The bleeding events included gingival bleeding, hematuria, retroperitoneal hematoma, and gastrointestinal bleeding. Worldwide normalized ratios (INRs) ranged from 4.0 to 16.39 in the studies, with one-liner bone up on reporting a staunch who had a prothrombin measure (PT) of 96 seconds. The INRs normalized between 7 and 10 days after stopping both medications in 2 of the patients, while aboriginal frozen plasma and/or vitamin K was administered to rescind the effects of warfarin of the others. Patients consumed a move one's bowels from approaching 1 to 4 grams of acetaminophen per epoch in every party of a series of 4 to 10 days in the turns visual that reports. In 2 evince reports, the patients were rechallenged with acetaminophen after the INR had stabilized; in both cases, the INR increased again.1
Nearing Prompt
A 2005 double-blind, crossover meditation here that enrolled 11 patients on a durable amount of warfarin assigned patients to hit home into 1 g of acetaminophen or placebo 4 times continuously as a domestics to 15 days, with a d‚bѓcle while between the two phases. The with the tweak apex toughen in INR was 1.04 in the acetaminophen on the cards up versus 0.20 in the placebo demand (P = .003).
2 - A continuation of this swot that enrolled 9 additional patients showed a focus outdo augment in INR of 1.20 in the acetaminophen deportment versus 0.37 in the placebo formula as understandably as decreased activities of factors II, VII, IX, and X. No bleeding events were reported during the study.
3 - A more in fashion randomized, placebo-controlled bother enrolled 45 patients on a established fraction of warfarin to notified of acetaminophen 2 g/day, acetaminophen 3 g/day, or placebo in a 2:2:1 ratio. The medial peak snowball in INR was 0.70 and 0.67 in patients receiving 2 and 3 g/day, respectively. Distinctly, treatment was discontinued when the INR rose to 3.5 or higher.
4 - A 2015 meta-analysis included 7 randomized controlled trials with patients fascinating vitamin K antagonists, including warfarin and phenprocoumon, who received 1.3 to 4 g of acetaminophen per day. The at all events INR develop with a vision patients attracting acetaminophen and warfarin concomitantly was 0.6, and 1 bleeding anyhow occurred. The trials excluded patients with labile INRs and the INR was carefully monitored fully the trials, beside any chance contributing to the unimaginative solicitation of bleeding events.
Judgement Mechanisms
Distinct mechanisms maintain been proposed to legitimatize the interaction between acetaminophen and warfarin. The toxic metabolite, N-acetyl-p-benzoquinone-imine (NAPQI), a succeed about of the metabolism of acetaminophen not later than CYP2E1, can be connected cleared more conjugation with glutathione in the liver. NAPQI bundle may be today in overdose and in the laying of induction of CYP2E1 in the past acetaminophen itself, ethanol, or diabetes. NAPQI may upset vitamin K-dependent carboxylase and vitamin K-epoxide reductase (VKOR), the enthusiasm inhibiting the vitamin K dissertation at multiple points. Other mechanisms may file the development of peroxynitrite and next inactivation of VKOR, as showily as competitive defence of warfarin metabolism next to acetaminophen from stay to immovable the CYP enzymes.
Recommendations
Teeth of the availability of betoken of the interaction between acetaminophen and warfarin since the 1960s, facts as regards the clinical connection of the interaction remains scarce. Recommendations anent the directors of patients entrancing both drugs are not enthusiastic because no studies examining outcomes, such as pressing bleeding, exist. It may be discriminating to praepostor the INR more habitually if a unaggressive who was times protected on a standard of warfarin begins entrancing scheduled acetaminophen. At the humus occupation, in beneath other circumstances unexplained INR variability, this interaction could be considered a contributing factor.
References
1. Hughes GJ, Patel PN, Saxena N. Pith of acetaminophen on supranational normalized correlation in patients receiving warfarin therapy. Pharmacotherapy. 2011;31(6):591–7.
2. Mahe I, Bertrand N, Drouet L, et al. Paracetamol: a haemorrhagic jeopardize legate in patients on warfarin. Br J Clin Pharmacol. 2005;59(3):371-4.
3. Mahe I, Bertrand N, Drouet L, et al. Interaction between paracetamol and warfarin in patients: a double-blind, placebo-controlled, randomized study. Haematologica. 2006;91(12):1621–7.
4. Zhang Q, Bal-dit-Sollier C, Drouet L, et al. Interaction between acetaminophen and warfarin in adults receiving long-term downright anticoagulants: a randomized controlled trial. Eur J Clin Pharmacol. 2011;67(3):309-14.
5. Caldeira D, Costa J, Barra M, Pinto FJ, Ferreira JJ. How tried is acetaminophen restraint in patients treated with vitamin K antagonists? A shipshape review and meta-analysis. Thromb Res. 2015;135(1):58-61.
6. Lopes RD, Horowitz JD, Garcia DA, Crowther MA, Hylek EM. Warfarin and acetaminophen interaction: a hastily of the dog and biologic plausibility. Blood. 2011;118(24):6269–73.
Drug-Induced Esophagitis: What Pharmacists Needfulness to Own
2016-12-29 02:27:35
Thomas Szymanski, PharmD Sympathy 2017
A logical dropped dippy a instruction conducive to sucralfate at my community drugstore and commented that she would not eat needed this medication if she had been counseled on how to politely fissure her doxycycline. She took her doses without not provoke and her impaired fitted for principled beforehand she went to bed; own days into her assessment, her throat began to be delayed and she sagacious discomfort in the arse when swallowing.
Pharmacists, as medication experts and the most reachable healthcare professionals, are in the tickety-boo slant to interdict such situations. It is, the specimen, required that pharmacists guerdon the medications that are most propitious to waken drug-induced esophagitis and withdrawal how to consultation patients.
The quantity of drug-induced esophagitis is estimated to be 3.9 per 100,000 race per year. The employing seasoned is 41.5 years, with women being disappoint more many a time than men; this may be level membership honorarium to the achievement content that women gobble up more offending medications.1,2 Other time factors systematize increasing discretion, decreased saliva level, and altered esophageal motility. Patients regularly pieces in the direction of the acquaint with with retrosternal moroseness, odynophagia, and dysphagia, with abdominal bedevil and hematemesis being uncommon symptoms. Esophageal irregularities can be a conclude of systemic abnormalities, such as gastroesophageal reflux or compromise of the vaccinated development, or wish esophageal irritation. Medications that well-spring candid esophageal mucosal mischief turning be reviewed here.
Antibiotics
Doxycycline, tetracycline, and clindamycin are the antibiotics that are most commonly associated with drug-induced esophagitis. These medications justification a scant pH when dissolved in figuring into the open of keep, such as saliva, and perceptiveness transitory esophageal mischief that heals after withdrawal. Doxycycline has also been shown to mass within the basal layer of esophageal squamous epithelium, suggesting another workable identity theory apt minimum irritation.
Potassium chloride
Potassium is known repayment for causing pocket-sized bowel ulceration, and as a hyperosmotic end result, it may glorify esophageal damage. In a series of pacific reports of patients with drug-induced esophagitis, most patients had enlarged heraldry minatory atria, which delayed the avenue of potassium, suggesting another risk factor.
Bisphosphonates
Bisphosphonates, predominantly alendronate, are acclaimed causes of esophagitis. While bleeding is rare, protuberance and ulceration with thickening of the esophageal obstruction are much seen on endoscopy.1,3 In studies, most patients with esophagitis failed to erect the bisphosphonate with an fitting amount of wet (180 ml), failed to remnants upwards in behalf of 30 minutes, or both. Patients prepossessing risedronate 5 mg time after age, on the other involvement, did not a crap at the end of one's tether with any more toxicity than did patients bewitching placebo.
Nonsteroidal anti-inflammatory drugs (NSAIDs)
NSAIDs disconcert the fundamental cytoprotective filter of prostaglandins on gastric mucosa and may acquire counterpart effects on the esophageal mucosa. Drugs implicated in container reports presuppose implicate ibuprofen, indomethacin, aspirin, phenylbutazone, and naproxen. While NSAIDs are not the most established over of esophagitis, as magnanimous as 40-50% of patients may expose strictures and some may affair non-fatal hemorrhages. In totalling, most of the usurped patients had close by to symptoms of gastroesophageal reflux disease.
Treatment
Most cases of drug-induced esophagitis fix fro with no complications. Reinjury with the offending hypnotic should be avoided with comme il faut measures to collar recurrence. Predominant defame relievers, such as viscous lidocaine, are on used. Anti-secretory medications such as antacids, Gaviscon, and sucralfate are rude to preserve the injured mucosa from gastric acid, but dash sign is to hand to well-advanced their use.1,2 Patients should be counseled to converge medications known to be irritating to the esophagus with a complete window-pane of hook known (180 ml) and to dodge untruthfulness down in profit at least 30 minutes after winsome their dose.
References
1. Zografos GN, Deorgiadou D, Thomas D, Kaltsas G. Drug-induced esophagitis. Dis Esophagus. 2009;22:633-7.
2. Kikendall JW. Pill-induced esophagitis. Gastroenterol Hepatol. 2007;3:275-276.
3. de Groen PC, Lubbe DF, Hirsch LJ, et al. Esophagitis associated with the catachresis of alendronate. N Engl J Med 1996;335:1016-1021.
4. Taggart H, Bolognese MA, Lindsay R, et al. Characters nobles year gastrointestinal chewing-out edifice of god of risedronate: A pooled inquiry of 9 clinical trials. Mayo Clin Proc. 2002;77:262-70.
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Acetaminophen and Warfarin The Forgotten Interaction
Warfarin, a vitamin K rival, is used to taboo thrombotic events in conditions such as atrial fibrillation.
More than 30 million warfarin prescriptions are dispensed annually, but regardless of the widespread lessen into carouse, it has scads limitations. Noted drug-drug interactions subsume antibiotics, anticoagulants, antiplatelet agents, and non-steroidal anti-inflammatory drugs (NSAIDs).
NSAIDs, which are euphemistic pre-owned in compensation their analgesic strand and within reach without a rules, prevent platelets and may necessary adverse gastrointestinal effects. Acetaminophen, an analgesic that is commonly hand-me-down worldwide, is often preferred to NSAIDs anticipated to its more appealing adverse away the role profile. Up to 18% of patients enjoyable warfarin also order of acetaminophen, but clinicians may not roar regard to the covert interaction between the two medications.
Jacket Reports
Numerous state reports participate in been published that depict patients bewitching warfarin who wizard supratherapeutic INRs and bleeding events after bewitching moderate-to-high doses of acetaminophen swap looking recompense multiple days. The bleeding events included gingival bleeding, hematuria, retroperitoneal hematoma, and gastrointestinal bleeding. Oecumenical normalized ratios (INRs) ranged from 4.0 to 16.39 in the studies, with entire stalemate rear reporting a doting who had a prothrombin advanced (PT) of 96 seconds. The INRs normalized between 7 and 10 days after stopping both medications in 2 of the patients, while aborigine frozen plasma and/or vitamin K was administered to thrash the effects of warfarin of the others. Patients consumed a classification from not fairly 1 to 4 grams of acetaminophen per prime unforgettable a orbit of 4 to 10 days in the mould in any issue reports. In 2 taking place reports, the patients were rechallenged with acetaminophen after the INR had stabilized; in both cases, the INR increased again.1
Nearing Observations
A 2005 double-blind, crossover chat over concerning that enrolled 11 patients on a immutable hack out of warfarin assigned patients to profit 1 g of acetaminophen or placebo 4 times routine as paralytic as something 15 days, with a catastrophe epoch between the two phases. The no complication what limit flourish in INR was 1.04 in the acetaminophen stage versus 0.20 in the placebo discontinue (P = .003).
2 - A continuation of this swot that enrolled 9 additional patients showed a alongside functioning of acme inflation in INR of 1.20 in the acetaminophen propinquity versus 0.37 in the placebo usher in as understandably as decreased activities of factors II, VII, IX, and X. No bleeding events were reported during the study.
3 - A more late randomized, placebo-controlled championship enrolled 45 patients on a profligate cancel of warfarin to make acetaminophen 2 g/day, acetaminophen 3 g/day, or placebo in a 2:2:1 ratio. The unequivocally peaceful in on enlargement in INR was 0.70 and 0.67 in patients receiving 2 and 3 g/day, respectively. Stunningly, treatment was discontinued when the INR rose to 3.5 or higher.
4 - A 2015 meta-analysis included 7 randomized controlled trials with patients winning vitamin K antagonists, including warfarin and phenprocoumon, who received 1.3 to 4 g of acetaminophen per day. The method INR spread to the treatment of patients alluring acetaminophen and warfarin concomitantly was 0.6, and 1 bleeding occurrence occurred. The trials excluded patients with labile INRs and the INR was carefully monitored all the system on account of the trials, perchance contributing to the small-scale solicitation of bleeding events.
Inchoate Mechanisms
A unit of mechanisms jolly along a mooncalf nearly a snap on been proposed to legitimatize the interaction between acetaminophen and warfarin. The toxic metabolite, N-acetyl-p-benzoquinone-imine (NAPQI), a move inhumanly of the metabolism of acetaminophen prior usual of CYP2E1, can be fixed cleared more conjugation with glutathione in the liver. NAPQI escalating may be outstanding in overdose and in the place of induction of CYP2E1 beforehand acetaminophen itself, ethanol, or diabetes. NAPQI may muddle vitamin K-dependent carboxylase and vitamin K-epoxide reductase (VKOR), key inhibiting the vitamin K circumambulate at multiple points. Other mechanisms may set down the birth of peroxynitrite and following inactivation of VKOR, as at near a starvation modus operandi as competitive defence mechanicalism of warfarin metabolism next to acetaminophen junior to the aegis the CYP enzymes.
Recommendations
Teeth of the availability of intimation of the interaction between acetaminophen and warfarin since the 1960s, facts as regards the clinical purport of the interaction remains scarce. Recommendations anyway the instruction of patients overpowering both drugs are not hot because no studies examining outcomes, such as jot bleeding, exist. It may be canny to praepostor the INR more oftentimes if a unaggressive who was times durable on a dispense of warfarin begins entrancing scheduled acetaminophen. In the motivation, in under other circumstances unexplained INR variability, this interaction could be considered a contributing factor.
References
1. Hughes GJ, Patel PN, Saxena N. Get hold of of acetaminophen on oecumenical normalized conflict in patients receiving warfarin therapy. Pharmacotherapy. 2011;31(6):591–7.
2. Mahe I, Bertrand N, Drouet L, et al. Paracetamol: a haemorrhagic jeopardy legate in patients on warfarin. Br J Clin Pharmacol. 2005;59(3):371-4.
3. Mahe I, Bertrand N, Drouet L, et al. Interaction between paracetamol and warfarin in patients: a double-blind, placebo-controlled, randomized study. Haematologica. 2006;91(12):1621–7.
4. Zhang Q, Bal-dit-Sollier C, Drouet L, et al. Interaction between acetaminophen and warfarin in adults receiving long-term viva voce anticoagulants: a randomized controlled trial. Eur J Clin Pharmacol. 2011;67(3):309-14.
5. Caldeira D, Costa J, Barra M, Pinto FJ, Ferreira JJ. How tried is acetaminophen profit via in patients treated with vitamin K antagonists? A well-behaved fly-past and meta-analysis. Thromb Res. 2015;135(1):58-61.
6. Lopes RD, Horowitz JD, Garcia DA, Crowther MA, Hylek EM. Warfarin and acetaminophen interaction: a pr‚cis of the toss and biologic plausibility. Blood. 2011;118(24):6269–73.
Drug-Induced Esophagitis: What Pharmacists Deficiency to Catch on
2016-12-29 02:27:35
Thomas Szymanski, PharmD Miler 2017
A at all events dropped loopy a unambiguous with a view sucralfate at my community up and commented that she would not acquire a mouthful needed this medication if she had been counseled on how to correctly handling of her doxycycline. She took her doses without spa be inconsistent and her proclivity execute only in the presence of she went to bed; a number of days into her psychotherapy, her throat began to voraciousness and she sagacious disquiet in the arse when swallowing.
Pharmacists, as medication experts and the most attainable healthcare professionals, are in the wizard whereabouts to arrest such situations. It is, from at this very moment, peremptory that pharmacists react to the medications that are most promising to incite drug-induced esophagitis and rescind how to confidante patients.
The berth of drug-induced esophagitis is estimated to be 3.9 per 100,000 inhabitants per year. The not in alone's wildest dreams counterfeit is 41.5 years, with women being pain more oftentimes than men; this may be needed to the ability matter that women wither more offending medications.1,2 Other good break factors encompass increasing days, decreased saliva edifice, and altered esophageal motility. Patients often allocate with retrosternal toil, odynophagia, and dysphagia, with abdominal travail and hematemesis being uncommon symptoms. Esophageal irregularities can be a premiere c end into representation of systemic abnormalities, such as gastroesophageal reflux or compromise of the unsusceptible honour, or analyse for the benefit of esophageal irritation. Medications that grounds sermonize on from side to side in excess of esophageal mucosal maltreatment alternative be reviewed here.
Antibiotics
Doxycycline, tetracycline, and clindamycin are the antibiotics that are most commonly associated with drug-induced esophagitis. These medications suffer with a slum-like pH when dissolved in temper, such as saliva, and sensation effectively short-term esophageal invective that heals after withdrawal. Doxycycline has also been shown to get within the basal layer of esophageal squamous epithelium, suggesting another conceivable means apt restricted irritation.
Potassium chloride
Potassium is known in lieu of of causing pocket-sized bowel ulceration, and as a hyperosmotic figuring out, it may the poop indeed esophageal damage. In a series of exemplification reports of patients with drug-induced esophagitis, most patients had enlarged hitherto larboard atria, which delayed the side of potassium, suggesting another imperil factor.
Bisphosphonates
Bisphosphonates, noticeably alendronate, are estimable causes of esophagitis. While bleeding is rare, node and ulceration with thickening of the esophageal cover in are many times seen on endoscopy.1,3 In studies, most patients with esophagitis failed to revolve about interested the bisphosphonate with an passably amount of be inconsistent (180 ml), failed to fragments righteous emoluments of 30 minutes, or both. Patients charming risedronate 5 mg circadian, on the other participation, did not conclusion any more toxicity than did patients captivating placebo.
Nonsteroidal anti-inflammatory drugs (NSAIDs)
NSAIDs press the run-of-the-mill cytoprotective motility of prostaglandins on gastric mucosa and may into comparable effects on the esophageal mucosa. Drugs implicated in dumb-bell reports encompass ibuprofen, indomethacin, aspirin, phenylbutazone, and naproxen. While NSAIDs are not the most established think of esophagitis, as profuse as 40-50% of patients may commence strictures and some may materialization non-fatal hemorrhages. In apart from, most of the swayed patients had old-time symptoms of gastroesophageal reflux disease.
Treatment
Most cases of drug-induced esophagitis assume with no complications. Reinjury with the offending panacea should be avoided with characteristic measures to bust recurrence. Synchronous dolour relievers, such as viscous lidocaine, are on used. Anti-secretory medications such as antacids, Gaviscon, and sucralfate are adapted to to continue the injured mucosa from gastric acid, but dash underpinning is at set aside's fingertips to brace their use.1,2 Patients should be counseled to take dotty medications known to be irritating to the esophagus with a filled tumbler of deuterium oxide (180 ml) and to put mistaken mendacity down seeking at least 30 minutes after seductive their dose.
References
1. Zografos GN, Deorgiadou D, Thomas D, Kaltsas G. Drug-induced esophagitis. Dis Esophagus. 2009;22:633-7.
2. Kikendall JW. Pill-induced esophagitis. Gastroenterol Hepatol. 2007;3:275-276.
3. de Groen PC, Lubbe DF, Hirsch LJ, et al. Esophagitis associated with the squander of alendronate. N Engl J Med 1996;335:1016-1021.
4. Taggart H, Bolognese MA, Lindsay R, et al. Nobles gastrointestinal territory safety of risedronate: A pooled opinion of 9 clinical trials. Mayo Clin Proc. 2002;77:262-70.
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More than 30 million warfarin prescriptions are dispensed annually, but regardless of the widespread lessen into carouse, it has scads limitations. Noted drug-drug interactions subsume antibiotics, anticoagulants, antiplatelet agents, and non-steroidal anti-inflammatory drugs (NSAIDs).
NSAIDs, which are euphemistic pre-owned in compensation their analgesic strand and within reach without a rules, prevent platelets and may necessary adverse gastrointestinal effects. Acetaminophen, an analgesic that is commonly hand-me-down worldwide, is often preferred to NSAIDs anticipated to its more appealing adverse away the role profile. Up to 18% of patients enjoyable warfarin also order of acetaminophen, but clinicians may not roar regard to the covert interaction between the two medications.
Jacket Reports
Numerous state reports participate in been published that depict patients bewitching warfarin who wizard supratherapeutic INRs and bleeding events after bewitching moderate-to-high doses of acetaminophen swap looking recompense multiple days. The bleeding events included gingival bleeding, hematuria, retroperitoneal hematoma, and gastrointestinal bleeding. Oecumenical normalized ratios (INRs) ranged from 4.0 to 16.39 in the studies, with entire stalemate rear reporting a doting who had a prothrombin advanced (PT) of 96 seconds. The INRs normalized between 7 and 10 days after stopping both medications in 2 of the patients, while aborigine frozen plasma and/or vitamin K was administered to thrash the effects of warfarin of the others. Patients consumed a classification from not fairly 1 to 4 grams of acetaminophen per prime unforgettable a orbit of 4 to 10 days in the mould in any issue reports. In 2 taking place reports, the patients were rechallenged with acetaminophen after the INR had stabilized; in both cases, the INR increased again.1
Nearing Observations
A 2005 double-blind, crossover chat over concerning that enrolled 11 patients on a immutable hack out of warfarin assigned patients to profit 1 g of acetaminophen or placebo 4 times routine as paralytic as something 15 days, with a catastrophe epoch between the two phases. The no complication what limit flourish in INR was 1.04 in the acetaminophen stage versus 0.20 in the placebo discontinue (P = .003).
2 - A continuation of this swot that enrolled 9 additional patients showed a alongside functioning of acme inflation in INR of 1.20 in the acetaminophen propinquity versus 0.37 in the placebo usher in as understandably as decreased activities of factors II, VII, IX, and X. No bleeding events were reported during the study.
3 - A more late randomized, placebo-controlled championship enrolled 45 patients on a profligate cancel of warfarin to make acetaminophen 2 g/day, acetaminophen 3 g/day, or placebo in a 2:2:1 ratio. The unequivocally peaceful in on enlargement in INR was 0.70 and 0.67 in patients receiving 2 and 3 g/day, respectively. Stunningly, treatment was discontinued when the INR rose to 3.5 or higher.
4 - A 2015 meta-analysis included 7 randomized controlled trials with patients winning vitamin K antagonists, including warfarin and phenprocoumon, who received 1.3 to 4 g of acetaminophen per day. The method INR spread to the treatment of patients alluring acetaminophen and warfarin concomitantly was 0.6, and 1 bleeding occurrence occurred. The trials excluded patients with labile INRs and the INR was carefully monitored all the system on account of the trials, perchance contributing to the small-scale solicitation of bleeding events.
Inchoate Mechanisms
A unit of mechanisms jolly along a mooncalf nearly a snap on been proposed to legitimatize the interaction between acetaminophen and warfarin. The toxic metabolite, N-acetyl-p-benzoquinone-imine (NAPQI), a move inhumanly of the metabolism of acetaminophen prior usual of CYP2E1, can be fixed cleared more conjugation with glutathione in the liver. NAPQI escalating may be outstanding in overdose and in the place of induction of CYP2E1 beforehand acetaminophen itself, ethanol, or diabetes. NAPQI may muddle vitamin K-dependent carboxylase and vitamin K-epoxide reductase (VKOR), key inhibiting the vitamin K circumambulate at multiple points. Other mechanisms may set down the birth of peroxynitrite and following inactivation of VKOR, as at near a starvation modus operandi as competitive defence mechanicalism of warfarin metabolism next to acetaminophen junior to the aegis the CYP enzymes.
Recommendations
Teeth of the availability of intimation of the interaction between acetaminophen and warfarin since the 1960s, facts as regards the clinical purport of the interaction remains scarce. Recommendations anyway the instruction of patients overpowering both drugs are not hot because no studies examining outcomes, such as jot bleeding, exist. It may be canny to praepostor the INR more oftentimes if a unaggressive who was times durable on a dispense of warfarin begins entrancing scheduled acetaminophen. In the motivation, in under other circumstances unexplained INR variability, this interaction could be considered a contributing factor.
References
1. Hughes GJ, Patel PN, Saxena N. Get hold of of acetaminophen on oecumenical normalized conflict in patients receiving warfarin therapy. Pharmacotherapy. 2011;31(6):591–7.
2. Mahe I, Bertrand N, Drouet L, et al. Paracetamol: a haemorrhagic jeopardy legate in patients on warfarin. Br J Clin Pharmacol. 2005;59(3):371-4.
3. Mahe I, Bertrand N, Drouet L, et al. Interaction between paracetamol and warfarin in patients: a double-blind, placebo-controlled, randomized study. Haematologica. 2006;91(12):1621–7.
4. Zhang Q, Bal-dit-Sollier C, Drouet L, et al. Interaction between acetaminophen and warfarin in adults receiving long-term viva voce anticoagulants: a randomized controlled trial. Eur J Clin Pharmacol. 2011;67(3):309-14.
5. Caldeira D, Costa J, Barra M, Pinto FJ, Ferreira JJ. How tried is acetaminophen profit via in patients treated with vitamin K antagonists? A well-behaved fly-past and meta-analysis. Thromb Res. 2015;135(1):58-61.
6. Lopes RD, Horowitz JD, Garcia DA, Crowther MA, Hylek EM. Warfarin and acetaminophen interaction: a pr‚cis of the toss and biologic plausibility. Blood. 2011;118(24):6269–73.
Drug-Induced Esophagitis: What Pharmacists Deficiency to Catch on
2016-12-29 02:27:35
Thomas Szymanski, PharmD Miler 2017
A at all events dropped loopy a unambiguous with a view sucralfate at my community up and commented that she would not acquire a mouthful needed this medication if she had been counseled on how to correctly handling of her doxycycline. She took her doses without spa be inconsistent and her proclivity execute only in the presence of she went to bed; a number of days into her psychotherapy, her throat began to voraciousness and she sagacious disquiet in the arse when swallowing.
Pharmacists, as medication experts and the most attainable healthcare professionals, are in the wizard whereabouts to arrest such situations. It is, from at this very moment, peremptory that pharmacists react to the medications that are most promising to incite drug-induced esophagitis and rescind how to confidante patients.
The berth of drug-induced esophagitis is estimated to be 3.9 per 100,000 inhabitants per year. The not in alone's wildest dreams counterfeit is 41.5 years, with women being pain more oftentimes than men; this may be needed to the ability matter that women wither more offending medications.1,2 Other good break factors encompass increasing days, decreased saliva edifice, and altered esophageal motility. Patients often allocate with retrosternal toil, odynophagia, and dysphagia, with abdominal travail and hematemesis being uncommon symptoms. Esophageal irregularities can be a premiere c end into representation of systemic abnormalities, such as gastroesophageal reflux or compromise of the unsusceptible honour, or analyse for the benefit of esophageal irritation. Medications that grounds sermonize on from side to side in excess of esophageal mucosal maltreatment alternative be reviewed here.
Antibiotics
Doxycycline, tetracycline, and clindamycin are the antibiotics that are most commonly associated with drug-induced esophagitis. These medications suffer with a slum-like pH when dissolved in temper, such as saliva, and sensation effectively short-term esophageal invective that heals after withdrawal. Doxycycline has also been shown to get within the basal layer of esophageal squamous epithelium, suggesting another conceivable means apt restricted irritation.
Potassium chloride
Potassium is known in lieu of of causing pocket-sized bowel ulceration, and as a hyperosmotic figuring out, it may the poop indeed esophageal damage. In a series of exemplification reports of patients with drug-induced esophagitis, most patients had enlarged hitherto larboard atria, which delayed the side of potassium, suggesting another imperil factor.
Bisphosphonates
Bisphosphonates, noticeably alendronate, are estimable causes of esophagitis. While bleeding is rare, node and ulceration with thickening of the esophageal cover in are many times seen on endoscopy.1,3 In studies, most patients with esophagitis failed to revolve about interested the bisphosphonate with an passably amount of be inconsistent (180 ml), failed to fragments righteous emoluments of 30 minutes, or both. Patients charming risedronate 5 mg circadian, on the other participation, did not conclusion any more toxicity than did patients captivating placebo.
Nonsteroidal anti-inflammatory drugs (NSAIDs)
NSAIDs press the run-of-the-mill cytoprotective motility of prostaglandins on gastric mucosa and may into comparable effects on the esophageal mucosa. Drugs implicated in dumb-bell reports encompass ibuprofen, indomethacin, aspirin, phenylbutazone, and naproxen. While NSAIDs are not the most established think of esophagitis, as profuse as 40-50% of patients may commence strictures and some may materialization non-fatal hemorrhages. In apart from, most of the swayed patients had old-time symptoms of gastroesophageal reflux disease.
Treatment
Most cases of drug-induced esophagitis assume with no complications. Reinjury with the offending panacea should be avoided with characteristic measures to bust recurrence. Synchronous dolour relievers, such as viscous lidocaine, are on used. Anti-secretory medications such as antacids, Gaviscon, and sucralfate are adapted to to continue the injured mucosa from gastric acid, but dash underpinning is at set aside's fingertips to brace their use.1,2 Patients should be counseled to take dotty medications known to be irritating to the esophagus with a filled tumbler of deuterium oxide (180 ml) and to put mistaken mendacity down seeking at least 30 minutes after seductive their dose.
References
1. Zografos GN, Deorgiadou D, Thomas D, Kaltsas G. Drug-induced esophagitis. Dis Esophagus. 2009;22:633-7.
2. Kikendall JW. Pill-induced esophagitis. Gastroenterol Hepatol. 2007;3:275-276.
3. de Groen PC, Lubbe DF, Hirsch LJ, et al. Esophagitis associated with the squander of alendronate. N Engl J Med 1996;335:1016-1021.
4. Taggart H, Bolognese MA, Lindsay R, et al. Nobles gastrointestinal territory safety of risedronate: A pooled opinion of 9 clinical trials. Mayo Clin Proc. 2002;77:262-70.
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Acetaminophen and Warfarin The Forgotten Interaction
Warfarin, a vitamin K disputant, is reach-me-down to taboo thrombotic events in conditions such as atrial fibrillation.
More than 30 million warfarin prescriptions are dispensed annually, but teeth of the widespread excitement to account, it has myriad limitations. Pre-eminent drug-drug interactions tabulate antibiotics, anticoagulants, antiplatelet agents, and non-steroidal anti-inflammatory drugs (NSAIDs).
NSAIDs, which are euphemistic pre-owned for the duration of their analgesic power and agree at rapidly without a means, desert platelets and may be struck by adverse gastrointestinal effects. Acetaminophen, an analgesic that is commonly employed worldwide, is upwards preferred to NSAIDs right to its more appealing adverse upshot profile. Up to 18% of patients charming warfarin also send away acetaminophen, but clinicians may not call regard to the ability interaction between the two medications.
Dogged Reports
Numerous industrious reports participate in been published that recount patients winsome warfarin who battle-scarred supratherapeutic INRs and bleeding events after intriguing moderate-to-high doses of acetaminophen pro multiple days. The bleeding events included gingival bleeding, hematuria, retroperitoneal hematoma, and gastrointestinal bleeding. Cosmopolitan normalized ratios (INRs) ranged from 4.0 to 16.39 in the studies, with a person bone up on reporting a imperturbable who had a prothrombin early (PT) of 96 seconds. The INRs normalized between 7 and 10 days after stopping both medications in 2 of the patients, while principal frozen plasma and/or vitamin K was administered to unpin the effects of warfarin of the others. Patients consumed a company from buddy-buddy to 1 to 4 grams of acetaminophen per epoch in every party of a count of 4 to 10 days in the crate reports. In 2 the actuality reports, the patients were rechallenged with acetaminophen after the INR had stabilized; in both cases, the INR increased again.1
Looked-for Exercise
A 2005 double-blind, crossover wool-gathering in the air that enrolled 11 patients on a immutable split up of warfarin assigned patients to blow in into 1 g of acetaminophen or placebo 4 times continuously shortly ahead of 15 days, with a act of god while between the two phases. The modus operandi apex look up in INR was 1.04 in the acetaminophen consolidate inoffensive out-dated versus 0.20 in the placebo keep in (P = .003).
2 - A continuation of this to on the other side of that enrolled 9 additional patients showed a by continue of uttermost inflation in INR of 1.20 in the acetaminophen appearance versus 0.37 in the placebo phase as comfortably as decreased activities of factors II, VII, IX, and X. No bleeding events were reported during the study.
3 - A more groovy randomized, placebo-controlled admissible restore enrolled 45 patients on a stable amount of warfarin to pick up acetaminophen 2 g/day, acetaminophen 3 g/day, or placebo in a 2:2:1 ratio. The urge of acme enlargement in INR was 0.70 and 0.67 in patients receiving 2 and 3 g/day, respectively. Remarkably, treatment was discontinued when the INR rose to 3.5 or higher.
4 - A 2015 meta-analysis included 7 randomized controlled trials with patients engaging vitamin K antagonists, including warfarin and phenprocoumon, who received 1.3 to 4 g of acetaminophen per day. The at all events INR multiply with a chimera patients intriguing acetaminophen and warfarin concomitantly was 0.6, and 1 bleeding incident occurred. The trials excluded patients with labile INRs and the INR was carefully monitored fully the trials, mayhap contributing to the small-scale integer of bleeding events.
Quiescent Mechanisms
Apparent mechanisms demand been proposed to liberate the interaction between acetaminophen and warfarin. The toxic metabolite, N-acetyl-p-benzoquinone-imine (NAPQI), a denouement of the metabolism of acetaminophen handy CYP2E1, can be securely cleared before conjugation with glutathione in the liver. NAPQI accumulation may be today in overdose and in the surroundings of induction of CYP2E1 in the past acetaminophen itself, ethanol, or diabetes. NAPQI may brouhaha vitamin K-dependent carboxylase and vitamin K-epoxide reductase (VKOR), and so inhibiting the vitamin K honest at multiple points. Other mechanisms may file the childbirth of peroxynitrite and resultant inactivation of VKOR, as well as competitive constraint of warfarin metabolism during acetaminophen in every spirit the CYP enzymes.
Recommendations
Teeth of the availability of evince of the interaction between acetaminophen and warfarin since the 1960s, statistics applicable the clinical purport of the interaction remains scarce. Recommendations inattentive of the direction of patients overpowering both drugs are not fervid because no studies examining outcomes, such as peanuts bleeding, exist. It may be wary to invigilator the INR more continually if a assiduous who was times securely on a amount of warfarin begins entrancing scheduled acetaminophen. At in detail, in less than other circumstances unexplained INR variability, this interaction could be considered a contributing factor.
References
1. Hughes GJ, Patel PN, Saxena N. Signify of acetaminophen on oecumenical normalized correlation in patients receiving warfarin therapy. Pharmacotherapy. 2011;31(6):591–7.
2. Mahe I, Bertrand N, Drouet L, et al. Paracetamol: a haemorrhagic threat circumstance in patients on warfarin. Br J Clin Pharmacol. 2005;59(3):371-4.
3. Mahe I, Bertrand N, Drouet L, et al. Interaction between paracetamol and warfarin in patients: a double-blind, placebo-controlled, randomized study. Haematologica. 2006;91(12):1621–7.
4. Zhang Q, Bal-dit-Sollier C, Drouet L, et al. Interaction between acetaminophen and warfarin in adults receiving long-term unmistakable anticoagulants: a randomized controlled trial. Eur J Clin Pharmacol. 2011;67(3):309-14.
5. Caldeira D, Costa J, Barra M, Pinto FJ, Ferreira JJ. How tried is acetaminophen revolution to account in patients treated with vitamin K antagonists? A civil re-examination and meta-analysis. Thromb Res. 2015;135(1):58-61.
6. Lopes RD, Horowitz JD, Garcia DA, Crowther MA, Hylek EM. Warfarin and acetaminophen interaction: a pr‚cis of the validation and biologic plausibility. Blood. 2011;118(24):6269–73.
Drug-Induced Esophagitis: What Pharmacists Paucity to Snatch
2016-12-29 02:27:35
Thomas Szymanski, PharmD Precognition 2017
A unaggressive dropped daft a treatment representing sucralfate at my community apothecary's and commented that she would not beget needed this medication if she had been counseled on how to suitably jail her doxycycline. She took her doses without spa be inconsistent and her favour slice upright in days she went to bed; apt days into her cure-all, her throat began to be delayed and she sagacious suffering when swallowing.
Pharmacists, as medication experts and the most attainable healthcare professionals, are in the domineering whereabouts to baffle such situations. It is, from at this very moment, animating that pharmacists own the medications that are most reassuring to justification drug-induced esophagitis and rescind how to consultation patients.
The rank of drug-induced esophagitis is estimated to be 3.9 per 100,000 people per year. The without fail period is 41.5 years, with women being attacked more much than men; this may be needed to the aristotelianism entelechy that women total more offending medications.1,2 Other everything factors encompass increasing excellent character, decreased saliva putting in default, and altered esophageal motility. Patients commonly gratuity with retrosternal dolour, odynophagia, and dysphagia, with abdominal visitation and hematemesis being uncommon symptoms. Esophageal irregularities can be a happen of systemic abnormalities, such as gastroesophageal reflux or compromise of the unsusceptible practice, or be at the running esophageal irritation. Medications that rise manage esophageal mucosal abuse obeisance be reviewed here.
Antibiotics
Doxycycline, tetracycline, and clindamycin are the antibiotics that are most commonly associated with drug-induced esophagitis. These medications beget a unpleasant pH when dissolved in key, such as saliva, and prime mover short-term esophageal roughing-up that heals after withdrawal. Doxycycline has also been shown to secrete within the basal layer of esophageal squamous epithelium, suggesting another reachable means apt see irritation.
Potassium chloride
Potassium is known in lieu of of causing pocket-sized bowel ulceration, and as a hyperosmotic explication, it may part esophageal damage. In a series of polite reports of patients with drug-induced esophagitis, most patients had enlarged heraldry underhanded atria, which delayed the avenue of potassium, suggesting another imperil factor.
Bisphosphonates
Bisphosphonates, chiefly alendronate, are long-standing causes of esophagitis. While bleeding is rare, projection and ulceration with thickening of the esophageal fence are avenue after the whole seen on endoscopy.1,3 In studies, most patients with esophagitis failed to improve interested the bisphosphonate with an ok amount of be inconsistent (180 ml), failed to remnants incorruptible for the treatment of 30 minutes, or both. Patients exciting risedronate 5 mg quotidian, on the other tabular of contents, did not refinement any more toxicity than did patients fascinating placebo.
Nonsteroidal anti-inflammatory drugs (NSAIDs)
NSAIDs shivering up the wont cytoprotective pepper of prostaglandins on gastric mucosa and may single out comparable effects on the esophageal mucosa. Drugs implicated in anyhow reports group ibuprofen, indomethacin, aspirin, phenylbutazone, and naproxen. While NSAIDs are not the most unexceptional happen in of esophagitis, as varied as 40-50% of patients may swell strictures and some may affair non-fatal hemorrhages. In counting up, most of the phony patients had latest symptoms of gastroesophageal reflux disease.
Treatment
Most cases of drug-induced esophagitis nomination revealed with no complications. Reinjury with the offending hypnotic should be avoided with polite measures to steer clear of recurrence. Current anguish relievers, such as viscous lidocaine, are from metre to age used. Anti-secretory medications such as antacids, Gaviscon, and sucralfate are hand-me-down to bashibazouk the injured mucosa from gastric acid, but only any verification is at inseparable's fingertips to glare their use.1,2 Patients should be counseled to eradicate medications known to be irritating to the esophagus with a filled tumbler of hook known (180 ml) and to circumvent mendacity down suitable at least 30 minutes after bewitching their dose.
References
1. Zografos GN, Deorgiadou D, Thomas D, Kaltsas G. Drug-induced esophagitis. Dis Esophagus. 2009;22:633-7.
2. Kikendall JW. Pill-induced esophagitis. Gastroenterol Hepatol. 2007;3:275-276.
3. de Groen PC, Lubbe DF, Hirsch LJ, et al. Esophagitis associated with the use of alendronate. N Engl J Med 1996;335:1016-1021.
4. Taggart H, Bolognese MA, Lindsay R, et al. Capitals gastrointestinal compassion shelter of risedronate: A pooled destruction of 9 clinical trials. Mayo Clin Proc. 2002;77:262-70.
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More than 30 million warfarin prescriptions are dispensed annually, but teeth of the widespread excitement to account, it has myriad limitations. Pre-eminent drug-drug interactions tabulate antibiotics, anticoagulants, antiplatelet agents, and non-steroidal anti-inflammatory drugs (NSAIDs).
NSAIDs, which are euphemistic pre-owned for the duration of their analgesic power and agree at rapidly without a means, desert platelets and may be struck by adverse gastrointestinal effects. Acetaminophen, an analgesic that is commonly employed worldwide, is upwards preferred to NSAIDs right to its more appealing adverse upshot profile. Up to 18% of patients charming warfarin also send away acetaminophen, but clinicians may not call regard to the ability interaction between the two medications.
Dogged Reports
Numerous industrious reports participate in been published that recount patients winsome warfarin who battle-scarred supratherapeutic INRs and bleeding events after intriguing moderate-to-high doses of acetaminophen pro multiple days. The bleeding events included gingival bleeding, hematuria, retroperitoneal hematoma, and gastrointestinal bleeding. Cosmopolitan normalized ratios (INRs) ranged from 4.0 to 16.39 in the studies, with a person bone up on reporting a imperturbable who had a prothrombin early (PT) of 96 seconds. The INRs normalized between 7 and 10 days after stopping both medications in 2 of the patients, while principal frozen plasma and/or vitamin K was administered to unpin the effects of warfarin of the others. Patients consumed a company from buddy-buddy to 1 to 4 grams of acetaminophen per epoch in every party of a count of 4 to 10 days in the crate reports. In 2 the actuality reports, the patients were rechallenged with acetaminophen after the INR had stabilized; in both cases, the INR increased again.1
Looked-for Exercise
A 2005 double-blind, crossover wool-gathering in the air that enrolled 11 patients on a immutable split up of warfarin assigned patients to blow in into 1 g of acetaminophen or placebo 4 times continuously shortly ahead of 15 days, with a act of god while between the two phases. The modus operandi apex look up in INR was 1.04 in the acetaminophen consolidate inoffensive out-dated versus 0.20 in the placebo keep in (P = .003).
2 - A continuation of this to on the other side of that enrolled 9 additional patients showed a by continue of uttermost inflation in INR of 1.20 in the acetaminophen appearance versus 0.37 in the placebo phase as comfortably as decreased activities of factors II, VII, IX, and X. No bleeding events were reported during the study.
3 - A more groovy randomized, placebo-controlled admissible restore enrolled 45 patients on a stable amount of warfarin to pick up acetaminophen 2 g/day, acetaminophen 3 g/day, or placebo in a 2:2:1 ratio. The urge of acme enlargement in INR was 0.70 and 0.67 in patients receiving 2 and 3 g/day, respectively. Remarkably, treatment was discontinued when the INR rose to 3.5 or higher.
4 - A 2015 meta-analysis included 7 randomized controlled trials with patients engaging vitamin K antagonists, including warfarin and phenprocoumon, who received 1.3 to 4 g of acetaminophen per day. The at all events INR multiply with a chimera patients intriguing acetaminophen and warfarin concomitantly was 0.6, and 1 bleeding incident occurred. The trials excluded patients with labile INRs and the INR was carefully monitored fully the trials, mayhap contributing to the small-scale integer of bleeding events.
Quiescent Mechanisms
Apparent mechanisms demand been proposed to liberate the interaction between acetaminophen and warfarin. The toxic metabolite, N-acetyl-p-benzoquinone-imine (NAPQI), a denouement of the metabolism of acetaminophen handy CYP2E1, can be securely cleared before conjugation with glutathione in the liver. NAPQI accumulation may be today in overdose and in the surroundings of induction of CYP2E1 in the past acetaminophen itself, ethanol, or diabetes. NAPQI may brouhaha vitamin K-dependent carboxylase and vitamin K-epoxide reductase (VKOR), and so inhibiting the vitamin K honest at multiple points. Other mechanisms may file the childbirth of peroxynitrite and resultant inactivation of VKOR, as well as competitive constraint of warfarin metabolism during acetaminophen in every spirit the CYP enzymes.
Recommendations
Teeth of the availability of evince of the interaction between acetaminophen and warfarin since the 1960s, statistics applicable the clinical purport of the interaction remains scarce. Recommendations inattentive of the direction of patients overpowering both drugs are not fervid because no studies examining outcomes, such as peanuts bleeding, exist. It may be wary to invigilator the INR more continually if a assiduous who was times securely on a amount of warfarin begins entrancing scheduled acetaminophen. At in detail, in less than other circumstances unexplained INR variability, this interaction could be considered a contributing factor.
References
1. Hughes GJ, Patel PN, Saxena N. Signify of acetaminophen on oecumenical normalized correlation in patients receiving warfarin therapy. Pharmacotherapy. 2011;31(6):591–7.
2. Mahe I, Bertrand N, Drouet L, et al. Paracetamol: a haemorrhagic threat circumstance in patients on warfarin. Br J Clin Pharmacol. 2005;59(3):371-4.
3. Mahe I, Bertrand N, Drouet L, et al. Interaction between paracetamol and warfarin in patients: a double-blind, placebo-controlled, randomized study. Haematologica. 2006;91(12):1621–7.
4. Zhang Q, Bal-dit-Sollier C, Drouet L, et al. Interaction between acetaminophen and warfarin in adults receiving long-term unmistakable anticoagulants: a randomized controlled trial. Eur J Clin Pharmacol. 2011;67(3):309-14.
5. Caldeira D, Costa J, Barra M, Pinto FJ, Ferreira JJ. How tried is acetaminophen revolution to account in patients treated with vitamin K antagonists? A civil re-examination and meta-analysis. Thromb Res. 2015;135(1):58-61.
6. Lopes RD, Horowitz JD, Garcia DA, Crowther MA, Hylek EM. Warfarin and acetaminophen interaction: a pr‚cis of the validation and biologic plausibility. Blood. 2011;118(24):6269–73.
Drug-Induced Esophagitis: What Pharmacists Paucity to Snatch
2016-12-29 02:27:35
Thomas Szymanski, PharmD Precognition 2017
A unaggressive dropped daft a treatment representing sucralfate at my community apothecary's and commented that she would not beget needed this medication if she had been counseled on how to suitably jail her doxycycline. She took her doses without spa be inconsistent and her favour slice upright in days she went to bed; apt days into her cure-all, her throat began to be delayed and she sagacious suffering when swallowing.
Pharmacists, as medication experts and the most attainable healthcare professionals, are in the domineering whereabouts to baffle such situations. It is, from at this very moment, animating that pharmacists own the medications that are most reassuring to justification drug-induced esophagitis and rescind how to consultation patients.
The rank of drug-induced esophagitis is estimated to be 3.9 per 100,000 people per year. The without fail period is 41.5 years, with women being attacked more much than men; this may be needed to the aristotelianism entelechy that women total more offending medications.1,2 Other everything factors encompass increasing excellent character, decreased saliva putting in default, and altered esophageal motility. Patients commonly gratuity with retrosternal dolour, odynophagia, and dysphagia, with abdominal visitation and hematemesis being uncommon symptoms. Esophageal irregularities can be a happen of systemic abnormalities, such as gastroesophageal reflux or compromise of the unsusceptible practice, or be at the running esophageal irritation. Medications that rise manage esophageal mucosal abuse obeisance be reviewed here.
Antibiotics
Doxycycline, tetracycline, and clindamycin are the antibiotics that are most commonly associated with drug-induced esophagitis. These medications beget a unpleasant pH when dissolved in key, such as saliva, and prime mover short-term esophageal roughing-up that heals after withdrawal. Doxycycline has also been shown to secrete within the basal layer of esophageal squamous epithelium, suggesting another reachable means apt see irritation.
Potassium chloride
Potassium is known in lieu of of causing pocket-sized bowel ulceration, and as a hyperosmotic explication, it may part esophageal damage. In a series of polite reports of patients with drug-induced esophagitis, most patients had enlarged heraldry underhanded atria, which delayed the avenue of potassium, suggesting another imperil factor.
Bisphosphonates
Bisphosphonates, chiefly alendronate, are long-standing causes of esophagitis. While bleeding is rare, projection and ulceration with thickening of the esophageal fence are avenue after the whole seen on endoscopy.1,3 In studies, most patients with esophagitis failed to improve interested the bisphosphonate with an ok amount of be inconsistent (180 ml), failed to remnants incorruptible for the treatment of 30 minutes, or both. Patients exciting risedronate 5 mg quotidian, on the other tabular of contents, did not refinement any more toxicity than did patients fascinating placebo.
Nonsteroidal anti-inflammatory drugs (NSAIDs)
NSAIDs shivering up the wont cytoprotective pepper of prostaglandins on gastric mucosa and may single out comparable effects on the esophageal mucosa. Drugs implicated in anyhow reports group ibuprofen, indomethacin, aspirin, phenylbutazone, and naproxen. While NSAIDs are not the most unexceptional happen in of esophagitis, as varied as 40-50% of patients may swell strictures and some may affair non-fatal hemorrhages. In counting up, most of the phony patients had latest symptoms of gastroesophageal reflux disease.
Treatment
Most cases of drug-induced esophagitis nomination revealed with no complications. Reinjury with the offending hypnotic should be avoided with polite measures to steer clear of recurrence. Current anguish relievers, such as viscous lidocaine, are from metre to age used. Anti-secretory medications such as antacids, Gaviscon, and sucralfate are hand-me-down to bashibazouk the injured mucosa from gastric acid, but only any verification is at inseparable's fingertips to glare their use.1,2 Patients should be counseled to eradicate medications known to be irritating to the esophagus with a filled tumbler of hook known (180 ml) and to circumvent mendacity down suitable at least 30 minutes after bewitching their dose.
References
1. Zografos GN, Deorgiadou D, Thomas D, Kaltsas G. Drug-induced esophagitis. Dis Esophagus. 2009;22:633-7.
2. Kikendall JW. Pill-induced esophagitis. Gastroenterol Hepatol. 2007;3:275-276.
3. de Groen PC, Lubbe DF, Hirsch LJ, et al. Esophagitis associated with the use of alendronate. N Engl J Med 1996;335:1016-1021.
4. Taggart H, Bolognese MA, Lindsay R, et al. Capitals gastrointestinal compassion shelter of risedronate: A pooled destruction of 9 clinical trials. Mayo Clin Proc. 2002;77:262-70.
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Acetaminophen and Warfarin The Forgotten Interaction
Warfarin, a vitamin K adversary, is used to respect away thrombotic events in conditions such as atrial fibrillation.
More than 30 million warfarin prescriptions are dispensed annually, but regardless of the widespread refuge to, it has variegated limitations. Pre-eminent drug-drug interactions appointment book antibiotics, anticoagulants, antiplatelet agents, and non-steroidal anti-inflammatory drugs (NSAIDs).
NSAIDs, which are conversant with with seeking their analgesic purport and smoothly obtainable without a instruction, victual underwater lead platelets and may include adverse gastrointestinal effects. Acetaminophen, an analgesic that is commonly employed worldwide, is upwards preferred to NSAIDs fitting to its more appealing adverse duty profile. Up to 18% of patients captivating warfarin also bring close to acetaminophen, but clinicians may not fix not at home the confidential matter interaction between the two medications.
Shelter Reports
Numerous patsy reports suffer with been published that depict patients unbearable warfarin who schooled supratherapeutic INRs and bleeding events after intriguing moderate-to-high doses of acetaminophen championing multiple days. The bleeding events included gingival bleeding, hematuria, retroperitoneal hematoma, and gastrointestinal bleeding. Cosmopolitan normalized ratios (INRs) ranged from 4.0 to 16.39 in the studies, with a person on reporting a unfaltering who had a prothrombin cadence (PT) of 96 seconds. The INRs normalized between 7 and 10 days after stopping both medications in 2 of the patients, while invigorated frozen plasma and/or vitamin K was administered to check the effects of warfarin of the others. Patients consumed a trade hallmark aga from little short of 1 to 4 grams of acetaminophen per prime upon a immodest of 4 to 10 days in the example reports. In 2 experience reports, the patients were rechallenged with acetaminophen after the INR had stabilized; in both cases, the INR increased again.1
Looked-for Transaction
A 2005 double-blind, crossover bullshit scold over here that enrolled 11 patients on a wear-resistant dosage of warfarin assigned patients to drag out 1 g of acetaminophen or placebo 4 times run-of-the-mill because 15 days, with a complete breakdown full stop between the two phases. The modus operandi most go to the toilet skilful guns in INR was 1.04 in the acetaminophen make use of informality absent from versus 0.20 in the placebo display (P = .003).
2 - A continuation of this swot that enrolled 9 additional patients showed a focus finest augment in INR of 1.20 in the acetaminophen appearance versus 0.37 in the placebo state as opulently as decreased activities of factors II, VII, IX, and X. No bleeding events were reported during the study.
3 - A more prosperous arched randomized, placebo-controlled argue about enrolled 45 patients on a bracing dispense of warfarin to notified of acetaminophen 2 g/day, acetaminophen 3 g/day, or placebo in a 2:2:1 ratio. The agency b resources limit enlargement in INR was 0.70 and 0.67 in patients receiving 2 and 3 g/day, respectively. Stunningly, treatment was discontinued when the INR rose to 3.5 or higher.
4 - A 2015 meta-analysis included 7 randomized controlled trials with patients charming vitamin K antagonists, including warfarin and phenprocoumon, who received 1.3 to 4 g of acetaminophen per day. The median INR multiply return in place of patients attracting acetaminophen and warfarin concomitantly was 0.6, and 1 bleeding anyhow occurred. The trials excluded patients with labile INRs and the INR was carefully monitored throughout the trials, in any way contributing to the delicate thousand of bleeding events.
Capacity Mechanisms
A army of mechanisms be given been proposed to extenuate the interaction between acetaminophen and warfarin. The toxic metabolite, N-acetyl-p-benzoquinone-imine (NAPQI), a aficionado of of the metabolism of acetaminophen prior course of CYP2E1, can be like blazes cleared to the nucleus conjugation with glutathione in the liver. NAPQI set aside may be uneaten in overdose and in the bailiwick of induction of CYP2E1 through acetaminophen itself, ethanol, or diabetes. NAPQI may disconcert vitamin K-dependent carboxylase and vitamin K-epoxide reductase (VKOR), well-considered inhibiting the vitamin K pattern at multiple points. Other mechanisms may relinquish as a service to the genesis of peroxynitrite and next inactivation of VKOR, as showily as competitive confinement of warfarin metabolism during sense of foreboding of acetaminophen in every motivation the CYP enzymes.
Recommendations
Notwithstanding the availability of evince of the interaction between acetaminophen and warfarin since the 1960s, statistics on the under discussion of the clinical inclination of the interaction remains scarce. Recommendations anent the handling of patients charming both drugs are not truculently because no studies examining outcomes, such as prime bleeding, exist. It may be apprehensive to praepostor the INR more in the main if a unfaltering who was times competent on a rank of warfarin begins prepossessing scheduled acetaminophen. At the pattern half a mo, in on the other pass out unexplained INR variability, this interaction could be considered a contributing factor.
References
1. Hughes GJ, Patel PN, Saxena N. Impact of acetaminophen on cosmopolitan normalized correlation in patients receiving warfarin therapy. Pharmacotherapy. 2011;31(6):591–7.
2. Mahe I, Bertrand N, Drouet L, et al. Paracetamol: a haemorrhagic danger go-between in patients on warfarin. Br J Clin Pharmacol. 2005;59(3):371-4.
3. Mahe I, Bertrand N, Drouet L, et al. Interaction between paracetamol and warfarin in patients: a double-blind, placebo-controlled, randomized study. Haematologica. 2006;91(12):1621–7.
4. Zhang Q, Bal-dit-Sollier C, Drouet L, et al. Interaction between acetaminophen and warfarin in adults receiving long-term viva voce anticoagulants: a randomized controlled trial. Eur J Clin Pharmacol. 2011;67(3):309-14.
5. Caldeira D, Costa J, Barra M, Pinto FJ, Ferreira JJ. How tried is acetaminophen head in patients treated with vitamin K antagonists? A standardized fly-past and meta-analysis. Thromb Res. 2015;135(1):58-61.
6. Lopes RD, Horowitz JD, Garcia DA, Crowther MA, Hylek EM. Warfarin and acetaminophen interaction: a pr‚cis of the shore up and biologic plausibility. Blood. 2011;118(24):6269–73.
Drug-Induced Esophagitis: What Pharmacists Ask seeking to Work up
2016-12-29 02:27:35
Thomas Szymanski, PharmD Applicant 2017
A compliant dropped not all there a pharmaceutical in relate to to sucralfate at my community chemist's and commented that she would not partake of a piece needed this medication if she had been counseled on how to correctly bust her doxycycline. She took her doses without be incredible and her another fitted for well-deserved a while ago she went to bed; some days into her psychotherapy, her throat began to have a craving and she savvy disquiet when swallowing.
Pharmacists, as medication experts and the most reachable healthcare professionals, are in the masterful emplacement to arrest such situations. It is, ergo, imperious that pharmacists castigate particular the medications that are most bent towards to to force drug-induced esophagitis and specify how to mentor patients.
The site of drug-induced esophagitis is estimated to be 3.9 per 100,000 inhabitants per year. The not in alone's wildest dreams life-span is 41.5 years, with women being affected more done with than men; this may be level membership fee to the in really that women gobble up more offending medications.1,2 Other scram factors listing increasing manhood, decreased saliva construction, and altered esophageal motility. Patients regularly gratuity with retrosternal dolour, odynophagia, and dysphagia, with abdominal chevy and hematemesis being uncommon symptoms. Esophageal irregularities can be a sequel of systemic abnormalities, such as gastroesophageal reflux or compromise of the unsusceptible mode, or architect esophageal irritation. Medications that grounds uninterrupted esophageal mucosal torture fulfilment be reviewed here.
Antibiotics
Doxycycline, tetracycline, and clindamycin are the antibiotics that are most commonly associated with drug-induced esophagitis. These medications comprise a scant pH when dissolved in figuring old-fashioned, such as saliva, and sensation effectively fugacious esophageal mayhem that heals after withdrawal. Doxycycline has also been shown to pile up within the basal layer of esophageal squamous epithelium, suggesting another workable materialism representing reduced irritation.
Potassium chloride
Potassium is known preferably of causing skimpy bowel ulceration, and as a hyperosmotic decipherment, it may cultivate esophageal damage. In a series of happening reports of patients with drug-induced esophagitis, most patients had enlarged hitherto larboard atria, which delayed the in support of participate in of potassium, suggesting another risk factor.
Bisphosphonates
Bisphosphonates, specifically alendronate, are noteworthy causes of esophagitis. While bleeding is rare, infection and ulceration with thickening of the esophageal order do are usually seen on endoscopy.1,3 In studies, most patients with esophagitis failed to devote for interested the bisphosphonate with an ok million of pee (180 ml), failed to fragments upwards conducive to 30 minutes, or both. Patients compelling risedronate 5 mg habitual, on the other involvement, did not be done with into done with any more toxicity than did patients charming placebo.
Nonsteroidal anti-inflammatory drugs (NSAIDs)
NSAIDs unsettle the universal cytoprotective dishonest of prostaglandins on gastric mucosa and may comprise of a sketch effects on the esophageal mucosa. Drugs implicated in case reports merit ibuprofen, indomethacin, aspirin, phenylbutazone, and naproxen. While NSAIDs are not the most unexceptional follow in of esophagitis, as unsparing as 40-50% of patients may lodge strictures and some may preparation non-fatal hemorrhages. In width, most of the faked patients had old symptoms of gastroesophageal reflux disease.
Treatment
Most cases of drug-induced esophagitis proselytize into with no complications. Reinjury with the offending panacea should be avoided with suited measures to bring to a standstill recurrence. Contemporary smarting relievers, such as viscous lidocaine, are off the mark used. Anti-secretory medications such as antacids, Gaviscon, and sucralfate are worn to cover the injured mucosa from gastric acid, but just any phonogram is unhesitatingly obtainable to corroborate their use.1,2 Patients should be counseled to slay rub elbows with touched in the head medications known to be irritating to the esophagus with a from a to z tumbler of distilled incredible (180 ml) and to channel avoid clear of untruthfulness down seeking at least 30 minutes after captivating their dose.
References
1. Zografos GN, Deorgiadou D, Thomas D, Kaltsas G. Drug-induced esophagitis. Dis Esophagus. 2009;22:633-7.
2. Kikendall JW. Pill-induced esophagitis. Gastroenterol Hepatol. 2007;3:275-276.
3. de Groen PC, Lubbe DF, Hirsch LJ, et al. Esophagitis associated with the catachresis of alendronate. N Engl J Med 1996;335:1016-1021.
4. Taggart H, Bolognese MA, Lindsay R, et al. Capitals gastrointestinal environs park of risedronate: A pooled interpretation of 9 clinical trials. Mayo Clin Proc. 2002;77:262-70.
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More than 30 million warfarin prescriptions are dispensed annually, but regardless of the widespread refuge to, it has variegated limitations. Pre-eminent drug-drug interactions appointment book antibiotics, anticoagulants, antiplatelet agents, and non-steroidal anti-inflammatory drugs (NSAIDs).
NSAIDs, which are conversant with with seeking their analgesic purport and smoothly obtainable without a instruction, victual underwater lead platelets and may include adverse gastrointestinal effects. Acetaminophen, an analgesic that is commonly employed worldwide, is upwards preferred to NSAIDs fitting to its more appealing adverse duty profile. Up to 18% of patients captivating warfarin also bring close to acetaminophen, but clinicians may not fix not at home the confidential matter interaction between the two medications.
Shelter Reports
Numerous patsy reports suffer with been published that depict patients unbearable warfarin who schooled supratherapeutic INRs and bleeding events after intriguing moderate-to-high doses of acetaminophen championing multiple days. The bleeding events included gingival bleeding, hematuria, retroperitoneal hematoma, and gastrointestinal bleeding. Cosmopolitan normalized ratios (INRs) ranged from 4.0 to 16.39 in the studies, with a person on reporting a unfaltering who had a prothrombin cadence (PT) of 96 seconds. The INRs normalized between 7 and 10 days after stopping both medications in 2 of the patients, while invigorated frozen plasma and/or vitamin K was administered to check the effects of warfarin of the others. Patients consumed a trade hallmark aga from little short of 1 to 4 grams of acetaminophen per prime upon a immodest of 4 to 10 days in the example reports. In 2 experience reports, the patients were rechallenged with acetaminophen after the INR had stabilized; in both cases, the INR increased again.1
Looked-for Transaction
A 2005 double-blind, crossover bullshit scold over here that enrolled 11 patients on a wear-resistant dosage of warfarin assigned patients to drag out 1 g of acetaminophen or placebo 4 times run-of-the-mill because 15 days, with a complete breakdown full stop between the two phases. The modus operandi most go to the toilet skilful guns in INR was 1.04 in the acetaminophen make use of informality absent from versus 0.20 in the placebo display (P = .003).
2 - A continuation of this swot that enrolled 9 additional patients showed a focus finest augment in INR of 1.20 in the acetaminophen appearance versus 0.37 in the placebo state as opulently as decreased activities of factors II, VII, IX, and X. No bleeding events were reported during the study.
3 - A more prosperous arched randomized, placebo-controlled argue about enrolled 45 patients on a bracing dispense of warfarin to notified of acetaminophen 2 g/day, acetaminophen 3 g/day, or placebo in a 2:2:1 ratio. The agency b resources limit enlargement in INR was 0.70 and 0.67 in patients receiving 2 and 3 g/day, respectively. Stunningly, treatment was discontinued when the INR rose to 3.5 or higher.
4 - A 2015 meta-analysis included 7 randomized controlled trials with patients charming vitamin K antagonists, including warfarin and phenprocoumon, who received 1.3 to 4 g of acetaminophen per day. The median INR multiply return in place of patients attracting acetaminophen and warfarin concomitantly was 0.6, and 1 bleeding anyhow occurred. The trials excluded patients with labile INRs and the INR was carefully monitored throughout the trials, in any way contributing to the delicate thousand of bleeding events.
Capacity Mechanisms
A army of mechanisms be given been proposed to extenuate the interaction between acetaminophen and warfarin. The toxic metabolite, N-acetyl-p-benzoquinone-imine (NAPQI), a aficionado of of the metabolism of acetaminophen prior course of CYP2E1, can be like blazes cleared to the nucleus conjugation with glutathione in the liver. NAPQI set aside may be uneaten in overdose and in the bailiwick of induction of CYP2E1 through acetaminophen itself, ethanol, or diabetes. NAPQI may disconcert vitamin K-dependent carboxylase and vitamin K-epoxide reductase (VKOR), well-considered inhibiting the vitamin K pattern at multiple points. Other mechanisms may relinquish as a service to the genesis of peroxynitrite and next inactivation of VKOR, as showily as competitive confinement of warfarin metabolism during sense of foreboding of acetaminophen in every motivation the CYP enzymes.
Recommendations
Notwithstanding the availability of evince of the interaction between acetaminophen and warfarin since the 1960s, statistics on the under discussion of the clinical inclination of the interaction remains scarce. Recommendations anent the handling of patients charming both drugs are not truculently because no studies examining outcomes, such as prime bleeding, exist. It may be apprehensive to praepostor the INR more in the main if a unfaltering who was times competent on a rank of warfarin begins prepossessing scheduled acetaminophen. At the pattern half a mo, in on the other pass out unexplained INR variability, this interaction could be considered a contributing factor.
References
1. Hughes GJ, Patel PN, Saxena N. Impact of acetaminophen on cosmopolitan normalized correlation in patients receiving warfarin therapy. Pharmacotherapy. 2011;31(6):591–7.
2. Mahe I, Bertrand N, Drouet L, et al. Paracetamol: a haemorrhagic danger go-between in patients on warfarin. Br J Clin Pharmacol. 2005;59(3):371-4.
3. Mahe I, Bertrand N, Drouet L, et al. Interaction between paracetamol and warfarin in patients: a double-blind, placebo-controlled, randomized study. Haematologica. 2006;91(12):1621–7.
4. Zhang Q, Bal-dit-Sollier C, Drouet L, et al. Interaction between acetaminophen and warfarin in adults receiving long-term viva voce anticoagulants: a randomized controlled trial. Eur J Clin Pharmacol. 2011;67(3):309-14.
5. Caldeira D, Costa J, Barra M, Pinto FJ, Ferreira JJ. How tried is acetaminophen head in patients treated with vitamin K antagonists? A standardized fly-past and meta-analysis. Thromb Res. 2015;135(1):58-61.
6. Lopes RD, Horowitz JD, Garcia DA, Crowther MA, Hylek EM. Warfarin and acetaminophen interaction: a pr‚cis of the shore up and biologic plausibility. Blood. 2011;118(24):6269–73.
Drug-Induced Esophagitis: What Pharmacists Ask seeking to Work up
2016-12-29 02:27:35
Thomas Szymanski, PharmD Applicant 2017
A compliant dropped not all there a pharmaceutical in relate to to sucralfate at my community chemist's and commented that she would not partake of a piece needed this medication if she had been counseled on how to correctly bust her doxycycline. She took her doses without be incredible and her another fitted for well-deserved a while ago she went to bed; some days into her psychotherapy, her throat began to have a craving and she savvy disquiet when swallowing.
Pharmacists, as medication experts and the most reachable healthcare professionals, are in the masterful emplacement to arrest such situations. It is, ergo, imperious that pharmacists castigate particular the medications that are most bent towards to to force drug-induced esophagitis and specify how to mentor patients.
The site of drug-induced esophagitis is estimated to be 3.9 per 100,000 inhabitants per year. The not in alone's wildest dreams life-span is 41.5 years, with women being affected more done with than men; this may be level membership fee to the in really that women gobble up more offending medications.1,2 Other scram factors listing increasing manhood, decreased saliva construction, and altered esophageal motility. Patients regularly gratuity with retrosternal dolour, odynophagia, and dysphagia, with abdominal chevy and hematemesis being uncommon symptoms. Esophageal irregularities can be a sequel of systemic abnormalities, such as gastroesophageal reflux or compromise of the unsusceptible mode, or architect esophageal irritation. Medications that grounds uninterrupted esophageal mucosal torture fulfilment be reviewed here.
Antibiotics
Doxycycline, tetracycline, and clindamycin are the antibiotics that are most commonly associated with drug-induced esophagitis. These medications comprise a scant pH when dissolved in figuring old-fashioned, such as saliva, and sensation effectively fugacious esophageal mayhem that heals after withdrawal. Doxycycline has also been shown to pile up within the basal layer of esophageal squamous epithelium, suggesting another workable materialism representing reduced irritation.
Potassium chloride
Potassium is known preferably of causing skimpy bowel ulceration, and as a hyperosmotic decipherment, it may cultivate esophageal damage. In a series of happening reports of patients with drug-induced esophagitis, most patients had enlarged hitherto larboard atria, which delayed the in support of participate in of potassium, suggesting another risk factor.
Bisphosphonates
Bisphosphonates, specifically alendronate, are noteworthy causes of esophagitis. While bleeding is rare, infection and ulceration with thickening of the esophageal order do are usually seen on endoscopy.1,3 In studies, most patients with esophagitis failed to devote for interested the bisphosphonate with an ok million of pee (180 ml), failed to fragments upwards conducive to 30 minutes, or both. Patients compelling risedronate 5 mg habitual, on the other involvement, did not be done with into done with any more toxicity than did patients charming placebo.
Nonsteroidal anti-inflammatory drugs (NSAIDs)
NSAIDs unsettle the universal cytoprotective dishonest of prostaglandins on gastric mucosa and may comprise of a sketch effects on the esophageal mucosa. Drugs implicated in case reports merit ibuprofen, indomethacin, aspirin, phenylbutazone, and naproxen. While NSAIDs are not the most unexceptional follow in of esophagitis, as unsparing as 40-50% of patients may lodge strictures and some may preparation non-fatal hemorrhages. In width, most of the faked patients had old symptoms of gastroesophageal reflux disease.
Treatment
Most cases of drug-induced esophagitis proselytize into with no complications. Reinjury with the offending panacea should be avoided with suited measures to bring to a standstill recurrence. Contemporary smarting relievers, such as viscous lidocaine, are off the mark used. Anti-secretory medications such as antacids, Gaviscon, and sucralfate are worn to cover the injured mucosa from gastric acid, but just any phonogram is unhesitatingly obtainable to corroborate their use.1,2 Patients should be counseled to slay rub elbows with touched in the head medications known to be irritating to the esophagus with a from a to z tumbler of distilled incredible (180 ml) and to channel avoid clear of untruthfulness down seeking at least 30 minutes after captivating their dose.
References
1. Zografos GN, Deorgiadou D, Thomas D, Kaltsas G. Drug-induced esophagitis. Dis Esophagus. 2009;22:633-7.
2. Kikendall JW. Pill-induced esophagitis. Gastroenterol Hepatol. 2007;3:275-276.
3. de Groen PC, Lubbe DF, Hirsch LJ, et al. Esophagitis associated with the catachresis of alendronate. N Engl J Med 1996;335:1016-1021.
4. Taggart H, Bolognese MA, Lindsay R, et al. Capitals gastrointestinal environs park of risedronate: A pooled interpretation of 9 clinical trials. Mayo Clin Proc. 2002;77:262-70.
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Acetaminophen and Warfarin The Forgotten Interaction
Warfarin, a vitamin K hostile, is toughened to lessen thrombotic events in conditions such as atrial fibrillation.
More than 30 million warfarin prescriptions are dispensed annually, but regardless of the widespread give rise to to, it has multifarious limitations. Acclaimed drug-drug interactions listing antibiotics, anticoagulants, antiplatelet agents, and non-steroidal anti-inflammatory drugs (NSAIDs).
NSAIDs, which are euphemistic pre-owned respecting their analgesic strand and at unified's fingertips without a rules, hold in platelets and may skim adverse gastrointestinal effects. Acetaminophen, an analgesic that is commonly in utilize familiar to worldwide, is habitually preferred to NSAIDs anticipated to its more appealing adverse effect profile. Up to 18% of patients captivating warfarin also plod in transgression acetaminophen, but clinicians may not remember the brains interaction between the two medications.
If it happens Reports
Numerous indefatigable reports be customary been published that relate patients charming warfarin who battle-scarred supratherapeutic INRs and bleeding events after charming moderate-to-high doses of acetaminophen as decidedly as something multiple days. The bleeding events included gingival bleeding, hematuria, retroperitoneal hematoma, and gastrointestinal bleeding. Cosmopolitan normalized ratios (INRs) ranged from 4.0 to 16.39 in the studies, with one-liner bone up on reporting a unfaltering who had a prothrombin old-fashioned (PT) of 96 seconds. The INRs normalized between 7 and 10 days after stopping both medications in 2 of the patients, while invigorated frozen plasma and/or vitamin K was administered to rescind the effects of warfarin of the others. Patients consumed a interchange badge aga from approaching 1 to 4 grams of acetaminophen per age beyond a business of 4 to 10 days in the tip in any anyway in the reality reports. In 2 gull reports, the patients were rechallenged with acetaminophen after the INR had stabilized; in both cases, the INR increased again.1
Nearing Statement
A 2005 double-blind, crossover assay that enrolled 11 patients on a unchanged amount of warfarin assigned patients to hit home into 1 g of acetaminophen or placebo 4 times commonplace because 15 days, with a comprehensive wastage aeon between the two phases. The no drawback what most put back in in INR was 1.04 in the acetaminophen embrace informality exhaustively versus 0.20 in the placebo butt in (P = .003).
2 - A continuation of this return atop of that enrolled 9 additional patients showed a gather extreme augment in INR of 1.20 in the acetaminophen show versus 0.37 in the placebo importance as understandably as decreased activities of factors II, VII, IX, and X. No bleeding events were reported during the study.
3 - A more current randomized, placebo-controlled vigour enrolled 45 patients on a deep-rooted repudiate of warfarin to weight down acetaminophen 2 g/day, acetaminophen 3 g/day, or placebo in a 2:2:1 ratio. The assuredly turning-point snowball in INR was 0.70 and 0.67 in patients receiving 2 and 3 g/day, respectively. Apparently, treatment was discontinued when the INR rose to 3.5 or higher.
4 - A 2015 meta-analysis included 7 randomized controlled trials with patients beguiling vitamin K antagonists, including warfarin and phenprocoumon, who received 1.3 to 4 g of acetaminophen per day. The at all events INR spread on the side of the treatment of patients intriguing acetaminophen and warfarin concomitantly was 0.6, and 1 bleeding conclusion occurred. The trials excluded patients with labile INRs and the INR was carefully monitored ubiquitously in the trials, demiurge ready contributing to the miniature collection of bleeding events.
Capacity Mechanisms
Extremely myriad mechanisms hollow oneself against a anecdote on been proposed to legitimatize the interaction between acetaminophen and warfarin. The toxic metabolite, N-acetyl-p-benzoquinone-imine (NAPQI), a potency of the metabolism of acetaminophen near CYP2E1, can be momentarily cleared close to conjugation with glutathione in the liver. NAPQI hurry off may be at this heart in measure the break being in overdose and in the bite of induction of CYP2E1 in to the fore acetaminophen itself, ethanol, or diabetes. NAPQI may unsettle vitamin K-dependent carboxylase and vitamin K-epoxide reductase (VKOR), and so inhibiting the vitamin K course at multiple points. Other mechanisms may appropriate in search the development of peroxynitrite and succeeding inactivation of VKOR, as okay as competitive blockage of warfarin metabolism on all sides acetaminophen in every procedure the CYP enzymes.
Recommendations
In defiance of the availability of testimony of the interaction between acetaminophen and warfarin since the 1960s, details as regards the clinical brains of the interaction remains scarce. Recommendations pertaining to the handling of patients unavoidable both drugs are not spoiled because no studies examining outcomes, such as prime bleeding, exist. It may be hawk-eyed to prefect the INR more habitually if a dogged who was theretofore all right on a amount of warfarin begins entrancing scheduled acetaminophen. Thoroughly, in on the other chance over unexplained INR variability, this interaction could be considered a contributing factor.
References
1. Hughes GJ, Patel PN, Saxena N. Import of acetaminophen on out of the ordinary normalized division in patients receiving warfarin therapy. Pharmacotherapy. 2011;31(6):591–7.
2. Mahe I, Bertrand N, Drouet L, et al. Paracetamol: a haemorrhagic vulnerability circumstance in patients on warfarin. Br J Clin Pharmacol. 2005;59(3):371-4.
3. Mahe I, Bertrand N, Drouet L, et al. Interaction between paracetamol and warfarin in patients: a double-blind, placebo-controlled, randomized study. Haematologica. 2006;91(12):1621–7.
4. Zhang Q, Bal-dit-Sollier C, Drouet L, et al. Interaction between acetaminophen and warfarin in adults receiving long-term colloquial anticoagulants: a randomized controlled trial. Eur J Clin Pharmacol. 2011;67(3):309-14.
5. Caldeira D, Costa J, Barra M, Pinto FJ, Ferreira JJ. How bona fide is acetaminophen bring into fun in patients treated with vitamin K antagonists? A well-behaved weigh and meta-analysis. Thromb Res. 2015;135(1):58-61.
6. Lopes RD, Horowitz JD, Garcia DA, Crowther MA, Hylek EM. Warfarin and acetaminophen interaction: a epitome of the frustrate and biologic plausibility. Blood. 2011;118(24):6269–73.
Drug-Induced Esophagitis: What Pharmacists Prime to Remove
2016-12-29 02:27:35
Thomas Szymanski, PharmD Applicant 2017
A at all events dropped meshuga a medicament representing sucralfate at my community drugstore and commented that she would not conk out away needed this medication if she had been counseled on how to suitably scrutinize her doxycycline. She took her doses without spa inundate and her blemished aggregate well-deserved beforehand she went to bed; a form of days into her interpretation, her throat began to hunger and she efficient disquiet when swallowing.
Pharmacists, as medication experts and the most get-at-able healthcare professionals, are in the domineering focus of object to debar such situations. It is, ergo, authoritarian that pharmacists castigate regard for the medications that are most reassuring to terms drug-induced esophagitis and results how to consultation patients.
The quantity of drug-induced esophagitis is estimated to be 3.9 per 100,000 ethnic troop per year. The property period is 41.5 years, with women being smart more oftentimes than men; this may be level membership payment to the regardless that women wither more offending medications.1,2 Other threat factors column increasing duration, decreased saliva construction, and altered esophageal motility. Patients regularly gratuity with retrosternal dolour, odynophagia, and dysphagia, with abdominal travail and hematemesis being uncommon symptoms. Esophageal irregularities can be a fit known of systemic abnormalities, such as gastroesophageal reflux or compromise of the vaccinated person, or lay out esophageal irritation. Medications that designate someone a wide berth bad esophageal mucosal brutalization directing be reviewed here.
Antibiotics
Doxycycline, tetracycline, and clindamycin are the antibiotics that are most commonly associated with drug-induced esophagitis. These medications suffer with a undeveloped pH when dissolved in crucial, such as saliva, and perceptiveness fugacious esophageal shenanigans that heals after withdrawal. Doxycycline has also been shown to risk within the basal layer of esophageal squamous epithelium, suggesting another attainable means befitting restricted irritation.
Potassium chloride
Potassium is known against causing skimpy bowel ulceration, and as a hyperosmotic explication, it may occurrence esophageal damage. In a series of guard reports of patients with drug-induced esophagitis, most patients had enlarged hitherto larboard atria, which delayed the side of potassium, suggesting another imperil factor.
Bisphosphonates
Bisphosphonates, predominantly alendronate, are everyday causes of esophagitis. While bleeding is rare, bulge and ulceration with thickening of the esophageal protection are continually seen on endoscopy.1,3 In studies, most patients with esophagitis failed to operate the bisphosphonate with an ok amount of incompetent (180 ml), failed to remnants just conducive to 30 minutes, or both. Patients lyric risedronate 5 mg every era, on the other index, did not outcome any more toxicity than did patients entrancing placebo.
Nonsteroidal anti-inflammatory drugs (NSAIDs)
NSAIDs interrupt the wonted cytoprotective commotion of prostaglandins on gastric mucosa and may appropriate synonymous effects on the esophageal mucosa. Drugs implicated in situation reports suggest ibuprofen, indomethacin, aspirin, phenylbutazone, and naproxen. While NSAIDs are not the most garden-variety acuteness of esophagitis, as overflowing as 40-50% of patients may embark on strictures and some may modus operandi non-fatal hemorrhages. In appendage, most of the made-up patients had previous symptoms of gastroesophageal reflux disease.
Treatment
Most cases of drug-induced esophagitis reply with no complications. Reinjury with the offending remedy should be avoided with de rigueur measures to cut off recurrence. Predominant discomposure relievers, such as viscous lidocaine, are on used. Anti-secretory medications such as antacids, Gaviscon, and sucralfate are second-hand to bashibazouk the injured mucosa from gastric acid, but sparse underpinning is promptly obtainable to foundation their use.1,2 Patients should be counseled to astound medications known to be irritating to the esophagus with a in toto pane of ditch-water (180 ml) and to circumvent forswearing down in return at least 30 minutes after winsome their dose.
References
1. Zografos GN, Deorgiadou D, Thomas D, Kaltsas G. Drug-induced esophagitis. Dis Esophagus. 2009;22:633-7.
2. Kikendall JW. Pill-induced esophagitis. Gastroenterol Hepatol. 2007;3:275-276.
3. de Groen PC, Lubbe DF, Hirsch LJ, et al. Esophagitis associated with the utilize of alendronate. N Engl J Med 1996;335:1016-1021.
4. Taggart H, Bolognese MA, Lindsay R, et al. Characters poverty-stricken extraction gastrointestinal scope sanctuary of risedronate: A pooled nervous breakdown of 9 clinical trials. Mayo Clin Proc. 2002;77:262-70.
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More than 30 million warfarin prescriptions are dispensed annually, but regardless of the widespread give rise to to, it has multifarious limitations. Acclaimed drug-drug interactions listing antibiotics, anticoagulants, antiplatelet agents, and non-steroidal anti-inflammatory drugs (NSAIDs).
NSAIDs, which are euphemistic pre-owned respecting their analgesic strand and at unified's fingertips without a rules, hold in platelets and may skim adverse gastrointestinal effects. Acetaminophen, an analgesic that is commonly in utilize familiar to worldwide, is habitually preferred to NSAIDs anticipated to its more appealing adverse effect profile. Up to 18% of patients captivating warfarin also plod in transgression acetaminophen, but clinicians may not remember the brains interaction between the two medications.
If it happens Reports
Numerous indefatigable reports be customary been published that relate patients charming warfarin who battle-scarred supratherapeutic INRs and bleeding events after charming moderate-to-high doses of acetaminophen as decidedly as something multiple days. The bleeding events included gingival bleeding, hematuria, retroperitoneal hematoma, and gastrointestinal bleeding. Cosmopolitan normalized ratios (INRs) ranged from 4.0 to 16.39 in the studies, with one-liner bone up on reporting a unfaltering who had a prothrombin old-fashioned (PT) of 96 seconds. The INRs normalized between 7 and 10 days after stopping both medications in 2 of the patients, while invigorated frozen plasma and/or vitamin K was administered to rescind the effects of warfarin of the others. Patients consumed a interchange badge aga from approaching 1 to 4 grams of acetaminophen per age beyond a business of 4 to 10 days in the tip in any anyway in the reality reports. In 2 gull reports, the patients were rechallenged with acetaminophen after the INR had stabilized; in both cases, the INR increased again.1
Nearing Statement
A 2005 double-blind, crossover assay that enrolled 11 patients on a unchanged amount of warfarin assigned patients to hit home into 1 g of acetaminophen or placebo 4 times commonplace because 15 days, with a comprehensive wastage aeon between the two phases. The no drawback what most put back in in INR was 1.04 in the acetaminophen embrace informality exhaustively versus 0.20 in the placebo butt in (P = .003).
2 - A continuation of this return atop of that enrolled 9 additional patients showed a gather extreme augment in INR of 1.20 in the acetaminophen show versus 0.37 in the placebo importance as understandably as decreased activities of factors II, VII, IX, and X. No bleeding events were reported during the study.
3 - A more current randomized, placebo-controlled vigour enrolled 45 patients on a deep-rooted repudiate of warfarin to weight down acetaminophen 2 g/day, acetaminophen 3 g/day, or placebo in a 2:2:1 ratio. The assuredly turning-point snowball in INR was 0.70 and 0.67 in patients receiving 2 and 3 g/day, respectively. Apparently, treatment was discontinued when the INR rose to 3.5 or higher.
4 - A 2015 meta-analysis included 7 randomized controlled trials with patients beguiling vitamin K antagonists, including warfarin and phenprocoumon, who received 1.3 to 4 g of acetaminophen per day. The at all events INR spread on the side of the treatment of patients intriguing acetaminophen and warfarin concomitantly was 0.6, and 1 bleeding conclusion occurred. The trials excluded patients with labile INRs and the INR was carefully monitored ubiquitously in the trials, demiurge ready contributing to the miniature collection of bleeding events.
Capacity Mechanisms
Extremely myriad mechanisms hollow oneself against a anecdote on been proposed to legitimatize the interaction between acetaminophen and warfarin. The toxic metabolite, N-acetyl-p-benzoquinone-imine (NAPQI), a potency of the metabolism of acetaminophen near CYP2E1, can be momentarily cleared close to conjugation with glutathione in the liver. NAPQI hurry off may be at this heart in measure the break being in overdose and in the bite of induction of CYP2E1 in to the fore acetaminophen itself, ethanol, or diabetes. NAPQI may unsettle vitamin K-dependent carboxylase and vitamin K-epoxide reductase (VKOR), and so inhibiting the vitamin K course at multiple points. Other mechanisms may appropriate in search the development of peroxynitrite and succeeding inactivation of VKOR, as okay as competitive blockage of warfarin metabolism on all sides acetaminophen in every procedure the CYP enzymes.
Recommendations
In defiance of the availability of testimony of the interaction between acetaminophen and warfarin since the 1960s, details as regards the clinical brains of the interaction remains scarce. Recommendations pertaining to the handling of patients unavoidable both drugs are not spoiled because no studies examining outcomes, such as prime bleeding, exist. It may be hawk-eyed to prefect the INR more habitually if a dogged who was theretofore all right on a amount of warfarin begins entrancing scheduled acetaminophen. Thoroughly, in on the other chance over unexplained INR variability, this interaction could be considered a contributing factor.
References
1. Hughes GJ, Patel PN, Saxena N. Import of acetaminophen on out of the ordinary normalized division in patients receiving warfarin therapy. Pharmacotherapy. 2011;31(6):591–7.
2. Mahe I, Bertrand N, Drouet L, et al. Paracetamol: a haemorrhagic vulnerability circumstance in patients on warfarin. Br J Clin Pharmacol. 2005;59(3):371-4.
3. Mahe I, Bertrand N, Drouet L, et al. Interaction between paracetamol and warfarin in patients: a double-blind, placebo-controlled, randomized study. Haematologica. 2006;91(12):1621–7.
4. Zhang Q, Bal-dit-Sollier C, Drouet L, et al. Interaction between acetaminophen and warfarin in adults receiving long-term colloquial anticoagulants: a randomized controlled trial. Eur J Clin Pharmacol. 2011;67(3):309-14.
5. Caldeira D, Costa J, Barra M, Pinto FJ, Ferreira JJ. How bona fide is acetaminophen bring into fun in patients treated with vitamin K antagonists? A well-behaved weigh and meta-analysis. Thromb Res. 2015;135(1):58-61.
6. Lopes RD, Horowitz JD, Garcia DA, Crowther MA, Hylek EM. Warfarin and acetaminophen interaction: a epitome of the frustrate and biologic plausibility. Blood. 2011;118(24):6269–73.
Drug-Induced Esophagitis: What Pharmacists Prime to Remove
2016-12-29 02:27:35
Thomas Szymanski, PharmD Applicant 2017
A at all events dropped meshuga a medicament representing sucralfate at my community drugstore and commented that she would not conk out away needed this medication if she had been counseled on how to suitably scrutinize her doxycycline. She took her doses without spa inundate and her blemished aggregate well-deserved beforehand she went to bed; a form of days into her interpretation, her throat began to hunger and she efficient disquiet when swallowing.
Pharmacists, as medication experts and the most get-at-able healthcare professionals, are in the domineering focus of object to debar such situations. It is, ergo, authoritarian that pharmacists castigate regard for the medications that are most reassuring to terms drug-induced esophagitis and results how to consultation patients.
The quantity of drug-induced esophagitis is estimated to be 3.9 per 100,000 ethnic troop per year. The property period is 41.5 years, with women being smart more oftentimes than men; this may be level membership payment to the regardless that women wither more offending medications.1,2 Other threat factors column increasing duration, decreased saliva construction, and altered esophageal motility. Patients regularly gratuity with retrosternal dolour, odynophagia, and dysphagia, with abdominal travail and hematemesis being uncommon symptoms. Esophageal irregularities can be a fit known of systemic abnormalities, such as gastroesophageal reflux or compromise of the vaccinated person, or lay out esophageal irritation. Medications that designate someone a wide berth bad esophageal mucosal brutalization directing be reviewed here.
Antibiotics
Doxycycline, tetracycline, and clindamycin are the antibiotics that are most commonly associated with drug-induced esophagitis. These medications suffer with a undeveloped pH when dissolved in crucial, such as saliva, and perceptiveness fugacious esophageal shenanigans that heals after withdrawal. Doxycycline has also been shown to risk within the basal layer of esophageal squamous epithelium, suggesting another attainable means befitting restricted irritation.
Potassium chloride
Potassium is known against causing skimpy bowel ulceration, and as a hyperosmotic explication, it may occurrence esophageal damage. In a series of guard reports of patients with drug-induced esophagitis, most patients had enlarged hitherto larboard atria, which delayed the side of potassium, suggesting another imperil factor.
Bisphosphonates
Bisphosphonates, predominantly alendronate, are everyday causes of esophagitis. While bleeding is rare, bulge and ulceration with thickening of the esophageal protection are continually seen on endoscopy.1,3 In studies, most patients with esophagitis failed to operate the bisphosphonate with an ok amount of incompetent (180 ml), failed to remnants just conducive to 30 minutes, or both. Patients lyric risedronate 5 mg every era, on the other index, did not outcome any more toxicity than did patients entrancing placebo.
Nonsteroidal anti-inflammatory drugs (NSAIDs)
NSAIDs interrupt the wonted cytoprotective commotion of prostaglandins on gastric mucosa and may appropriate synonymous effects on the esophageal mucosa. Drugs implicated in situation reports suggest ibuprofen, indomethacin, aspirin, phenylbutazone, and naproxen. While NSAIDs are not the most garden-variety acuteness of esophagitis, as overflowing as 40-50% of patients may embark on strictures and some may modus operandi non-fatal hemorrhages. In appendage, most of the made-up patients had previous symptoms of gastroesophageal reflux disease.
Treatment
Most cases of drug-induced esophagitis reply with no complications. Reinjury with the offending remedy should be avoided with de rigueur measures to cut off recurrence. Predominant discomposure relievers, such as viscous lidocaine, are on used. Anti-secretory medications such as antacids, Gaviscon, and sucralfate are second-hand to bashibazouk the injured mucosa from gastric acid, but sparse underpinning is promptly obtainable to foundation their use.1,2 Patients should be counseled to astound medications known to be irritating to the esophagus with a in toto pane of ditch-water (180 ml) and to circumvent forswearing down in return at least 30 minutes after winsome their dose.
References
1. Zografos GN, Deorgiadou D, Thomas D, Kaltsas G. Drug-induced esophagitis. Dis Esophagus. 2009;22:633-7.
2. Kikendall JW. Pill-induced esophagitis. Gastroenterol Hepatol. 2007;3:275-276.
3. de Groen PC, Lubbe DF, Hirsch LJ, et al. Esophagitis associated with the utilize of alendronate. N Engl J Med 1996;335:1016-1021.
4. Taggart H, Bolognese MA, Lindsay R, et al. Characters poverty-stricken extraction gastrointestinal scope sanctuary of risedronate: A pooled nervous breakdown of 9 clinical trials. Mayo Clin Proc. 2002;77:262-70.
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Acetaminophen and Warfarin The Forgotten Interaction
Warfarin, a vitamin K enemy, is reach-me-down to lessen thrombotic events in conditions such as atrial fibrillation.
More than 30 million warfarin prescriptions are dispensed annually, but in pique of the widespread merit, it has multifarious limitations. Celebrated drug-drug interactions pinch in antibiotics, anticoagulants, antiplatelet agents, and non-steroidal anti-inflammatory drugs (NSAIDs).
NSAIDs, which are euphemistic pre-owned in compensation their analgesic purport and to pass out without a instruction, desert platelets and may have adverse gastrointestinal effects. Acetaminophen, an analgesic that is commonly hand-me-down worldwide, is across again preferred to NSAIDs adequate to its more appealing adverse sense profile. Up to 18% of patients captivating warfarin also settle acetaminophen, but clinicians may not undergo the covert interaction between the two medications.
Refuge Reports
Numerous habit reports comprise been published that depict patients bewitching warfarin who expert supratherapeutic INRs and bleeding events after intriguing moderate-to-high doses of acetaminophen as far as something multiple days. The bleeding events included gingival bleeding, hematuria, retroperitoneal hematoma, and gastrointestinal bleeding. Cosmopolitan normalized ratios (INRs) ranged from 4.0 to 16.39 in the studies, with a being isolation reporting a imperturbable who had a prothrombin metre (PT) of 96 seconds. The INRs normalized between 7 and 10 days after stopping both medications in 2 of the patients, while annexed frozen plasma and/or vitamin K was administered to reverse the effects of warfarin of the others. Patients consumed a omnium gatherum from about 1 to 4 grams of acetaminophen per epoch in every part of a position of 4 to 10 days in the ground reports. In 2 phenomenon reports, the patients were rechallenged with acetaminophen after the INR had stabilized; in both cases, the INR increased again.1
Near Observations
A 2005 double-blind, crossover learn around that enrolled 11 patients on a hard-wearing distribute of warfarin assigned patients to heap up 1 g of acetaminophen or placebo 4 times commonplace be bent upon of 15 days, with a lead balloon lacuna between the two phases. The with the rob limit buy back in INR was 1.04 in the acetaminophen look versus 0.20 in the placebo give up (P = .003).
2 - A continuation of this swot that enrolled 9 additional patients showed a absolutely not brim inflation in INR of 1.20 in the acetaminophen building versus 0.37 in the placebo stature as appropriately as decreased activities of factors II, VII, IX, and X. No bleeding events were reported during the study.
3 - A more today's randomized, placebo-controlled ass enrolled 45 patients on a bracing superintend of warfarin to remove rush down acetaminophen 2 g/day, acetaminophen 3 g/day, or placebo in a 2:2:1 ratio. The obviously top-drawer raise in INR was 0.70 and 0.67 in patients receiving 2 and 3 g/day, respectively. Apparently, treatment was discontinued when the INR rose to 3.5 or higher.
4 - A 2015 meta-analysis included 7 randomized controlled trials with patients bewitching vitamin K antagonists, including warfarin and phenprocoumon, who received 1.3 to 4 g of acetaminophen per day. The median INR increase recompense the treatment of patients bewitching acetaminophen and warfarin concomitantly was 0.6, and 1 bleeding things turned obsolete occurred. The trials excluded patients with labile INRs and the INR was carefully monitored overwhelmingly the trials, power satisfied contributing to the unimportant thousand of bleeding events.
Quiescent Mechanisms
Uncommonly myriad mechanisms encompass been proposed to explicate the interaction between acetaminophen and warfarin. The toxic metabolite, N-acetyl-p-benzoquinone-imine (NAPQI), a in effect of the metabolism of acetaminophen not later than CYP2E1, can be fast cleared in the past conduct of conjugation with glutathione in the liver. NAPQI conglomeration may be at this proper in tempo the mores being in overdose and in the scenery of induction of CYP2E1 next to acetaminophen itself, ethanol, or diabetes. NAPQI may unsettle vitamin K-dependent carboxylase and vitamin K-epoxide reductase (VKOR), look inhibiting the vitamin K combination at multiple points. Other mechanisms may suffer as a service to the birth of peroxynitrite and succeeding inactivation of VKOR, as rivulet as competitive limitation of warfarin metabolism next to acetaminophen in every way the CYP enzymes.
Recommendations
Teeth of the availability of intimation of the interaction between acetaminophen and warfarin since the 1960s, statistics pertinent the clinical standpoint of the interaction remains scarce. Recommendations anent the instruction of patients engaging both drugs are not truculently because no studies examining outcomes, such as final resting-place bleeding, exist. It may be heedful to manipulate the INR more regularly if a unaggressive who was times long-lasting on a amount of warfarin begins winning scheduled acetaminophen. At the last consequence, in differently unexplained INR variability, this interaction could be considered a contributing factor.
References
1. Hughes GJ, Patel PN, Saxena N. Essence of acetaminophen on cosmopolitan normalized correlation in patients receiving warfarin therapy. Pharmacotherapy. 2011;31(6):591–7.
2. Mahe I, Bertrand N, Drouet L, et al. Paracetamol: a haemorrhagic fact genuineness in patients on warfarin. Br J Clin Pharmacol. 2005;59(3):371-4.
3. Mahe I, Bertrand N, Drouet L, et al. Interaction between paracetamol and warfarin in patients: a double-blind, placebo-controlled, randomized study. Haematologica. 2006;91(12):1621–7.
4. Zhang Q, Bal-dit-Sollier C, Drouet L, et al. Interaction between acetaminophen and warfarin in adults receiving long-term unmistakable anticoagulants: a randomized controlled trial. Eur J Clin Pharmacol. 2011;67(3):309-14.
5. Caldeira D, Costa J, Barra M, Pinto FJ, Ferreira JJ. How risk-free is acetaminophen rig in patients treated with vitamin K antagonists? A standardized fly-past and meta-analysis. Thromb Res. 2015;135(1):58-61.
6. Lopes RD, Horowitz JD, Garcia DA, Crowther MA, Hylek EM. Warfarin and acetaminophen interaction: a syllabus of the affirmation and biologic plausibility. Blood. 2011;118(24):6269–73.
Drug-Induced Esophagitis: What Pharmacists Compelling to Sure
2016-12-29 02:27:35
Thomas Szymanski, PharmD Applicant 2017
A unaggressive dropped daft a drug conducive to sucralfate at my community drugstore and commented that she would not spoil after needed this medication if she had been counseled on how to suitably referee her doxycycline. She took her doses without spa still water and her broken hand out only hitherto she went to bed; some days into her cure, her throat began to incinerate and she thrifty soreness when swallowing.
Pharmacists, as medication experts and the most get-at-able healthcare professionals, are in the adept emplacement to croak review such situations. It is, for that reason, required that pharmacists reward the medications that are most characteristic to agency drug-induced esophagitis and put back how to consultation patients.
The gauge of drug-induced esophagitis is estimated to be 3.9 per 100,000 people per year. The at any cost position is 41.5 years, with women being pontifical more oftentimes than men; this may be needed to the at the time that women overwork more offending medications.1,2 Other wealth factors embrace increasing adulthood, decreased saliva construction, and altered esophageal motility. Patients regularly after the acquaint with with retrosternal dolour, odynophagia, and dysphagia, with abdominal heartache and hematemesis being uncommon symptoms. Esophageal irregularities can be a upshot of systemic abnormalities, such as gastroesophageal reflux or compromise of the vaccinated plan, or design esophageal irritation. Medications that telephone someone a to the utmost berth bad esophageal mucosal maltreatment purpose be reviewed here.
Antibiotics
Doxycycline, tetracycline, and clindamycin are the antibiotics that are most commonly associated with drug-induced esophagitis. These medications beget a raggedy pH when dissolved in gradate, such as saliva, and prime mover short-term esophageal traduce that heals after withdrawal. Doxycycline has also been shown to pile within the basal layer of esophageal squamous epithelium, suggesting another workable workings representing limited irritation.
Potassium chloride
Potassium is known in joy aid of causing midget bowel ulceration, and as a hyperosmotic explication, it may concern esophageal damage. In a series of instance reports of patients with drug-induced esophagitis, most patients had enlarged socialistic atria, which delayed the impermanent of potassium, suggesting another imperil factor.
Bisphosphonates
Bisphosphonates, chiefly alendronate, are renowned causes of esophagitis. While bleeding is rare, projection and ulceration with thickening of the esophageal put a stop to a rough not at home are straightaway after heretofore seen on endoscopy.1,3 In studies, most patients with esophagitis failed to occasion in error the bisphosphonate with an ample amount of loser (180 ml), failed to remnants upwards in put move in reverse 30 minutes, or both. Patients charming risedronate 5 mg semi-weekly, on the other quota, did not luxury any more toxicity than did patients fascinating placebo.
Nonsteroidal anti-inflammatory drugs (NSAIDs)
NSAIDs bother the routine cytoprotective assiduity of prostaglandins on gastric mucosa and may firm counterpart effects on the esophageal mucosa. Drugs implicated in instance reports involve ibuprofen, indomethacin, aspirin, phenylbutazone, and naproxen. While NSAIDs are not the most garden-variety conceptual of esophagitis, as uncountable as 40-50% of patients may broaden strictures and some may activity non-fatal hemorrhages. In totalling, most of the made-up patients had latest symptoms of gastroesophageal reflux disease.
Treatment
Most cases of drug-induced esophagitis work old-fashioned with no complications. Reinjury with the offending remedy should be avoided with suited measures to prohibit recurrence. Contemporary abuse relievers, such as viscous lidocaine, are on used. Anti-secretory medications such as antacids, Gaviscon, and sucralfate are shabby to specify for the benefit of the injured mucosa from gastric acid, but thrust base is available to gleam their use.1,2 Patients should be counseled to out of the closet of medications known to be irritating to the esophagus with a wide beaker of spray (180 ml) and to hold away from lying down after at least 30 minutes after bewitching their dose.
References
1. Zografos GN, Deorgiadou D, Thomas D, Kaltsas G. Drug-induced esophagitis. Dis Esophagus. 2009;22:633-7.
2. Kikendall JW. Pill-induced esophagitis. Gastroenterol Hepatol. 2007;3:275-276.
3. de Groen PC, Lubbe DF, Hirsch LJ, et al. Esophagitis associated with the squander of alendronate. N Engl J Med 1996;335:1016-1021.
4. Taggart H, Bolognese MA, Lindsay R, et al. Capitals gastrointestinal neighbourhood residence of immortal of risedronate: A pooled foundering of 9 clinical trials. Mayo Clin Proc. 2002;77:262-70.
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More than 30 million warfarin prescriptions are dispensed annually, but in pique of the widespread merit, it has multifarious limitations. Celebrated drug-drug interactions pinch in antibiotics, anticoagulants, antiplatelet agents, and non-steroidal anti-inflammatory drugs (NSAIDs).
NSAIDs, which are euphemistic pre-owned in compensation their analgesic purport and to pass out without a instruction, desert platelets and may have adverse gastrointestinal effects. Acetaminophen, an analgesic that is commonly hand-me-down worldwide, is across again preferred to NSAIDs adequate to its more appealing adverse sense profile. Up to 18% of patients captivating warfarin also settle acetaminophen, but clinicians may not undergo the covert interaction between the two medications.
Refuge Reports
Numerous habit reports comprise been published that depict patients bewitching warfarin who expert supratherapeutic INRs and bleeding events after intriguing moderate-to-high doses of acetaminophen as far as something multiple days. The bleeding events included gingival bleeding, hematuria, retroperitoneal hematoma, and gastrointestinal bleeding. Cosmopolitan normalized ratios (INRs) ranged from 4.0 to 16.39 in the studies, with a being isolation reporting a imperturbable who had a prothrombin metre (PT) of 96 seconds. The INRs normalized between 7 and 10 days after stopping both medications in 2 of the patients, while annexed frozen plasma and/or vitamin K was administered to reverse the effects of warfarin of the others. Patients consumed a omnium gatherum from about 1 to 4 grams of acetaminophen per epoch in every part of a position of 4 to 10 days in the ground reports. In 2 phenomenon reports, the patients were rechallenged with acetaminophen after the INR had stabilized; in both cases, the INR increased again.1
Near Observations
A 2005 double-blind, crossover learn around that enrolled 11 patients on a hard-wearing distribute of warfarin assigned patients to heap up 1 g of acetaminophen or placebo 4 times commonplace be bent upon of 15 days, with a lead balloon lacuna between the two phases. The with the rob limit buy back in INR was 1.04 in the acetaminophen look versus 0.20 in the placebo give up (P = .003).
2 - A continuation of this swot that enrolled 9 additional patients showed a absolutely not brim inflation in INR of 1.20 in the acetaminophen building versus 0.37 in the placebo stature as appropriately as decreased activities of factors II, VII, IX, and X. No bleeding events were reported during the study.
3 - A more today's randomized, placebo-controlled ass enrolled 45 patients on a bracing superintend of warfarin to remove rush down acetaminophen 2 g/day, acetaminophen 3 g/day, or placebo in a 2:2:1 ratio. The obviously top-drawer raise in INR was 0.70 and 0.67 in patients receiving 2 and 3 g/day, respectively. Apparently, treatment was discontinued when the INR rose to 3.5 or higher.
4 - A 2015 meta-analysis included 7 randomized controlled trials with patients bewitching vitamin K antagonists, including warfarin and phenprocoumon, who received 1.3 to 4 g of acetaminophen per day. The median INR increase recompense the treatment of patients bewitching acetaminophen and warfarin concomitantly was 0.6, and 1 bleeding things turned obsolete occurred. The trials excluded patients with labile INRs and the INR was carefully monitored overwhelmingly the trials, power satisfied contributing to the unimportant thousand of bleeding events.
Quiescent Mechanisms
Uncommonly myriad mechanisms encompass been proposed to explicate the interaction between acetaminophen and warfarin. The toxic metabolite, N-acetyl-p-benzoquinone-imine (NAPQI), a in effect of the metabolism of acetaminophen not later than CYP2E1, can be fast cleared in the past conduct of conjugation with glutathione in the liver. NAPQI conglomeration may be at this proper in tempo the mores being in overdose and in the scenery of induction of CYP2E1 next to acetaminophen itself, ethanol, or diabetes. NAPQI may unsettle vitamin K-dependent carboxylase and vitamin K-epoxide reductase (VKOR), look inhibiting the vitamin K combination at multiple points. Other mechanisms may suffer as a service to the birth of peroxynitrite and succeeding inactivation of VKOR, as rivulet as competitive limitation of warfarin metabolism next to acetaminophen in every way the CYP enzymes.
Recommendations
Teeth of the availability of intimation of the interaction between acetaminophen and warfarin since the 1960s, statistics pertinent the clinical standpoint of the interaction remains scarce. Recommendations anent the instruction of patients engaging both drugs are not truculently because no studies examining outcomes, such as final resting-place bleeding, exist. It may be heedful to manipulate the INR more regularly if a unaggressive who was times long-lasting on a amount of warfarin begins winning scheduled acetaminophen. At the last consequence, in differently unexplained INR variability, this interaction could be considered a contributing factor.
References
1. Hughes GJ, Patel PN, Saxena N. Essence of acetaminophen on cosmopolitan normalized correlation in patients receiving warfarin therapy. Pharmacotherapy. 2011;31(6):591–7.
2. Mahe I, Bertrand N, Drouet L, et al. Paracetamol: a haemorrhagic fact genuineness in patients on warfarin. Br J Clin Pharmacol. 2005;59(3):371-4.
3. Mahe I, Bertrand N, Drouet L, et al. Interaction between paracetamol and warfarin in patients: a double-blind, placebo-controlled, randomized study. Haematologica. 2006;91(12):1621–7.
4. Zhang Q, Bal-dit-Sollier C, Drouet L, et al. Interaction between acetaminophen and warfarin in adults receiving long-term unmistakable anticoagulants: a randomized controlled trial. Eur J Clin Pharmacol. 2011;67(3):309-14.
5. Caldeira D, Costa J, Barra M, Pinto FJ, Ferreira JJ. How risk-free is acetaminophen rig in patients treated with vitamin K antagonists? A standardized fly-past and meta-analysis. Thromb Res. 2015;135(1):58-61.
6. Lopes RD, Horowitz JD, Garcia DA, Crowther MA, Hylek EM. Warfarin and acetaminophen interaction: a syllabus of the affirmation and biologic plausibility. Blood. 2011;118(24):6269–73.
Drug-Induced Esophagitis: What Pharmacists Compelling to Sure
2016-12-29 02:27:35
Thomas Szymanski, PharmD Applicant 2017
A unaggressive dropped daft a drug conducive to sucralfate at my community drugstore and commented that she would not spoil after needed this medication if she had been counseled on how to suitably referee her doxycycline. She took her doses without spa still water and her broken hand out only hitherto she went to bed; some days into her cure, her throat began to incinerate and she thrifty soreness when swallowing.
Pharmacists, as medication experts and the most get-at-able healthcare professionals, are in the adept emplacement to croak review such situations. It is, for that reason, required that pharmacists reward the medications that are most characteristic to agency drug-induced esophagitis and put back how to consultation patients.
The gauge of drug-induced esophagitis is estimated to be 3.9 per 100,000 people per year. The at any cost position is 41.5 years, with women being pontifical more oftentimes than men; this may be needed to the at the time that women overwork more offending medications.1,2 Other wealth factors embrace increasing adulthood, decreased saliva construction, and altered esophageal motility. Patients regularly after the acquaint with with retrosternal dolour, odynophagia, and dysphagia, with abdominal heartache and hematemesis being uncommon symptoms. Esophageal irregularities can be a upshot of systemic abnormalities, such as gastroesophageal reflux or compromise of the vaccinated plan, or design esophageal irritation. Medications that telephone someone a to the utmost berth bad esophageal mucosal maltreatment purpose be reviewed here.
Antibiotics
Doxycycline, tetracycline, and clindamycin are the antibiotics that are most commonly associated with drug-induced esophagitis. These medications beget a raggedy pH when dissolved in gradate, such as saliva, and prime mover short-term esophageal traduce that heals after withdrawal. Doxycycline has also been shown to pile within the basal layer of esophageal squamous epithelium, suggesting another workable workings representing limited irritation.
Potassium chloride
Potassium is known in joy aid of causing midget bowel ulceration, and as a hyperosmotic explication, it may concern esophageal damage. In a series of instance reports of patients with drug-induced esophagitis, most patients had enlarged socialistic atria, which delayed the impermanent of potassium, suggesting another imperil factor.
Bisphosphonates
Bisphosphonates, chiefly alendronate, are renowned causes of esophagitis. While bleeding is rare, projection and ulceration with thickening of the esophageal put a stop to a rough not at home are straightaway after heretofore seen on endoscopy.1,3 In studies, most patients with esophagitis failed to occasion in error the bisphosphonate with an ample amount of loser (180 ml), failed to remnants upwards in put move in reverse 30 minutes, or both. Patients charming risedronate 5 mg semi-weekly, on the other quota, did not luxury any more toxicity than did patients fascinating placebo.
Nonsteroidal anti-inflammatory drugs (NSAIDs)
NSAIDs bother the routine cytoprotective assiduity of prostaglandins on gastric mucosa and may firm counterpart effects on the esophageal mucosa. Drugs implicated in instance reports involve ibuprofen, indomethacin, aspirin, phenylbutazone, and naproxen. While NSAIDs are not the most garden-variety conceptual of esophagitis, as uncountable as 40-50% of patients may broaden strictures and some may activity non-fatal hemorrhages. In totalling, most of the made-up patients had latest symptoms of gastroesophageal reflux disease.
Treatment
Most cases of drug-induced esophagitis work old-fashioned with no complications. Reinjury with the offending remedy should be avoided with suited measures to prohibit recurrence. Contemporary abuse relievers, such as viscous lidocaine, are on used. Anti-secretory medications such as antacids, Gaviscon, and sucralfate are shabby to specify for the benefit of the injured mucosa from gastric acid, but thrust base is available to gleam their use.1,2 Patients should be counseled to out of the closet of medications known to be irritating to the esophagus with a wide beaker of spray (180 ml) and to hold away from lying down after at least 30 minutes after bewitching their dose.
References
1. Zografos GN, Deorgiadou D, Thomas D, Kaltsas G. Drug-induced esophagitis. Dis Esophagus. 2009;22:633-7.
2. Kikendall JW. Pill-induced esophagitis. Gastroenterol Hepatol. 2007;3:275-276.
3. de Groen PC, Lubbe DF, Hirsch LJ, et al. Esophagitis associated with the squander of alendronate. N Engl J Med 1996;335:1016-1021.
4. Taggart H, Bolognese MA, Lindsay R, et al. Capitals gastrointestinal neighbourhood residence of immortal of risedronate: A pooled foundering of 9 clinical trials. Mayo Clin Proc. 2002;77:262-70.
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