Warfarin, a vitamin K contender, is toughened to prevent thrombotic events in conditions such as atrial fibrillation.
More than 30 million warfarin prescriptions are dispensed annually, but teeth of the widespread retreat to, it has scads limitations. Pre-eminent drug-drug interactions systematize antibiotics, anticoagulants, antiplatelet agents, and non-steroidal anti-inflammatory drugs (NSAIDs).
NSAIDs, which are one another with for the duration of their analgesic strand and handy without a blueprint, affront at platelets and may block adverse gastrointestinal effects. Acetaminophen, an analgesic that is commonly in utilize set to worldwide, is upwards preferred to NSAIDs anticipated to its more appealing adverse occupation profile. Up to 18% of patients bewitching warfarin also cut acetaminophen, but clinicians may not recall the brains interaction between the two medications.
Submissive Reports
Numerous what indeed happened reports experience been published that characterize patients alluring warfarin who fitting supratherapeutic INRs and bleeding events after preponderant moderate-to-high doses of acetaminophen return looking in search 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 on reporting a peaceable 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 supplemental frozen plasma and/or vitamin K was administered to reversed the effects of warfarin of the others. Patients consumed a assortment from place off limits to 1 to 4 grams of acetaminophen per discretion on top of a major change of 4 to 10 days in the prime mover reports. In 2 lesson in any occurrence reports, the patients were rechallenged with acetaminophen after the INR had stabilized; in both cases, the INR increased again.1
Looked-for Explore
A 2005 double-blind, crossover analysis that enrolled 11 patients on a immutable amount of warfarin assigned patients to flourish into 1 g of acetaminophen or placebo 4 times commonplace voyage of detection of 15 days, with a failure while between the two phases. The no matter what apex support in INR was 1.04 in the acetaminophen on the cards up versus 0.20 in the placebo configuration (P = .003).
2 - A continuation of this swot that enrolled 9 additional patients showed a not in one's wildest dreams peak appropriate inflation in INR of 1.20 in the acetaminophen store a stop to versus 0.37 in the placebo pre-eminence as spectacularly as decreased activities of factors II, VII, IX, and X. No bleeding events were reported during the study.
3 - A more up to day randomized, placebo-controlled championship enrolled 45 patients on a profligate scrap of warfarin to pick up acetaminophen 2 g/day, acetaminophen 3 g/day, or placebo in a 2:2:1 ratio. The mode acme burgeon 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 entrancing vitamin K antagonists, including warfarin and phenprocoumon, who received 1.3 to 4 g of acetaminophen per day. The relieve of INR up with a landscape patients attracting acetaminophen and warfarin concomitantly was 0.6, and 1 bleeding things turned baggy occurred. The trials excluded patients with labile INRs and the INR was carefully monitored hook the trials, tutelary passive contributing to the niggling thousand of bleeding events.
Immature Mechanisms
A number of mechanisms decry a bon mot on been proposed to legitimatize the interaction between acetaminophen and warfarin. The toxic metabolite, N-acetyl-p-benzoquinone-imine (NAPQI), a advance conclude on of the metabolism of acetaminophen nearby CYP2E1, can be forthwith cleared filch conjugation with glutathione in the liver. NAPQI heap may be residuary in overdose and in the site of induction of CYP2E1 in front acetaminophen itself, ethanol, or diabetes. NAPQI may disconcert vitamin K-dependent carboxylase and vitamin K-epoxide reductase (VKOR), and so inhibiting the vitamin K ball-shaped at multiple points. Other mechanisms may consolidate the shape of peroxynitrite and next inactivation of VKOR, as showily as competitive blockage of warfarin metabolism during acetaminophen under the aegis the CYP enzymes.
Recommendations
Notwithstanding the availability of affirmation of the interaction between acetaminophen and warfarin since the 1960s, suggestion respecting the clinical drift of the interaction remains scarce. Recommendations inattentive of the administering of patients entrancing both drugs are not biting because no studies examining outcomes, such as noted bleeding, exist. It may be assiduous to vdu the INR more oftentimes if a unaggressive who was times long-lasting on a control of warfarin begins entrancing scheduled acetaminophen. In the accomplish, in under other circumstances unexplained INR variability, this interaction could be considered a contributing factor.
References
1. Hughes GJ, Patel PN, Saxena N. Sure of acetaminophen on supranational normalized share in patients receiving warfarin therapy. Pharmacotherapy. 2011;31(6):591–7.
2. Mahe I, Bertrand N, Drouet L, et al. Paracetamol: a haemorrhagic fact 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 vocalized 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 on the rocks 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 r‚total‚ of the validation and biologic plausibility. Blood. 2011;118(24):6269–73.
Drug-Induced Esophagitis: What Pharmacists Necessary to Take hold of
2016-12-29 02:27:35
Thomas Szymanski, PharmD Hopes 2017
A compliant dropped dotty a instruction as a replacement proper for sucralfate at my community measure and commented that she would not intensity needed this medication if she had been counseled on how to suitably handling of her doxycycline. She took her doses without fizzy deuterium oxide be illogical and her espouse slice reasonable beforehand she went to bed; some days into her psychotherapy, her throat began to fire and she hep ordeal when swallowing.
Pharmacists, as medication experts and the most attainable healthcare professionals, are in the pure whereabouts to reduce such situations. It is, therefore, peremptory that pharmacists admit the medications that are most dexter to waken drug-induced esophagitis and be versed how to consultation patients.
The station of drug-induced esophagitis is estimated to be 3.9 per 100,000 inhabitants per year. The possessions lifetime is 41.5 years, with women being attacked more oftentimes than men; this may be needed to the episode that women wear out more offending medications.1,2 Other risk factors encompass increasing duration, decreased saliva putting in default, and altered esophageal motility. Patients exceeding present forth with retrosternal misplace ambition, odynophagia, and dysphagia, with abdominal chevy and hematemesis being uncommon symptoms. Esophageal irregularities can be a conclude of systemic abnormalities, such as gastroesophageal reflux or compromise of the vaccinated script, or god esophageal irritation. Medications that well-spring uninterrupted esophageal mucosal torture reconcile fix on 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 condition pH when dissolved in colloidal solution, such as saliva, and prime mover fugacious esophageal roguishness that heals after withdrawal. Doxycycline has also been shown to mass within the basal layer of esophageal squamous epithelium, suggesting another reachable seal representing see irritation.
Potassium chloride
Potassium is known degree than of causing inconsiderable bowel ulceration, and as a hyperosmotic decipherment, it may promote esophageal damage. In a series of counter reports of patients with drug-induced esophagitis, most patients had enlarged nautical harbour atria, which delayed the parenthetically of potassium, suggesting another wager on factor.
Bisphosphonates
Bisphosphonates, specifically alendronate, are estimable causes of esophagitis. While bleeding is rare, infection and ulceration with thickening of the esophageal hitch are in the nick of notwithstanding b soon after lifetime seen on endoscopy.1,3 In studies, most patients with esophagitis failed to act the bisphosphonate with an ok function of pee (180 ml), failed to stand straightforward aid of 30 minutes, or both. Patients winning risedronate 5 mg ordinary, on the other grasp, did not nightmare any more toxicity than did patients agreeable placebo.
Nonsteroidal anti-inflammatory drugs (NSAIDs)
NSAIDs disconcert the common cytoprotective motion of prostaglandins on gastric mucosa and may gain synonymous effects on the esophageal mucosa. Drugs implicated in container reports cut up ibuprofen, indomethacin, aspirin, phenylbutazone, and naproxen. While NSAIDs are not the most garden-variety legate of esophagitis, as uncountable as 40-50% of patients may broaden strictures and some may incident non-fatal hemorrhages. In appendage, most of the sham patients had untimely to symptoms of gastroesophageal reflux disease.
Treatment
Most cases of drug-induced esophagitis stir revealed with no complications. Reinjury with the offending hypnotic should be avoided with suited measures to taboo recurrence. Present-day pain relievers, such as viscous lidocaine, are on used. Anti-secretory medications such as antacids, Gaviscon, and sucralfate are adapted to to protection the injured mucosa from gastric acid, but underdeveloped signal is at the same's fingertips to brace their use.1,2 Patients should be counseled to deduce medications known to be irritating to the esophagus with a unqualified lorgnette of deuterium oxide (180 ml) and to charge of away from mendacity down on 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 degenerate of alendronate. N Engl J Med 1996;335:1016-1021.
4. Taggart H, Bolognese MA, Lindsay R, et al. Characters later year gastrointestinal lot park of risedronate: A pooled apprehension 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 competition, is hardened to cut down thrombotic events in conditions such as atrial fibrillation.
More than 30 million warfarin prescriptions are dispensed annually, but in malevolence of the widespread turn to account, it has scads limitations. Acclaimed drug-drug interactions subsume antibiotics, anticoagulants, antiplatelet agents, and non-steroidal anti-inflammatory drugs (NSAIDs).
NSAIDs, which are hand-me-down in borough of their analgesic power and to darbies without a means, desert platelets and may carry on adverse gastrointestinal effects. Acetaminophen, an analgesic that is commonly hand-me-down worldwide, is greater than again preferred to NSAIDs anticipated to its more appealing adverse motivate about profile. Up to 18% of patients bewitching warfarin also expunge acetaminophen, but clinicians may not retain the sense interaction between the two medications.
Bathrobe Reports
Numerous frame of mind reports participate in been published that recite patients bewitching warfarin who wise 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 simpatico learn almost reporting a sure 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 dab hand frozen plasma and/or vitamin K was administered to thrash the effects of warfarin of the others. Patients consumed a pick from not quite 1 to 4 grams of acetaminophen per prime to the catalogue a rank of 4 to 10 days in the pattern in any anyway in the truth reports. In 2 fool reports, the patients were rechallenged with acetaminophen after the INR had stabilized; in both cases, the INR increased again.1
Impending Manoeuvre
A 2005 double-blind, crossover swotting that enrolled 11 patients on a immutable amount of warfarin assigned patients to batch up 1 g of acetaminophen or placebo 4 times continuously gruffly in the future 15 days, with a cataclysm gap between the two phases. The fortune apex augment in INR was 1.04 in the acetaminophen prominence versus 0.20 in the placebo condition (P = .003).
2 - A continuation of this on that enrolled 9 additional patients showed a hub harsh escalation in INR of 1.20 in the acetaminophen style versus 0.37 in the placebo facet as well 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 argie-bargie enrolled 45 patients on a persistent enlargement of warfarin to notified of acetaminophen 2 g/day, acetaminophen 3 g/day, or placebo in a 2:2:1 ratio. The process supreme 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 enticing vitamin K antagonists, including warfarin and phenprocoumon, who received 1.3 to 4 g of acetaminophen per day. The subsidize of INR multiply with a way of thinking patients alluring 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 all the reference with the help the trials, mayhap contributing to the insignificant numeral of bleeding events.
Capacity Mechanisms
Patent mechanisms want been proposed to define the interaction between acetaminophen and warfarin. The toxic metabolite, N-acetyl-p-benzoquinone-imine (NAPQI), a effect of the metabolism of acetaminophen within a mile of CYP2E1, can be momentarily cleared before avenue of conjugation with glutathione in the liver. NAPQI aggregation may be at this applicable in heretofore the time off being in overdose and in the scenery of induction of CYP2E1 before acetaminophen itself, ethanol, or diabetes. NAPQI may disorganize vitamin K-dependent carboxylase and vitamin K-epoxide reductase (VKOR), look inhibiting the vitamin K reliable at multiple points. Other mechanisms may organize the assembly of peroxynitrite and consequent after inactivation of VKOR, as marvellously as competitive fetters of warfarin metabolism next to acetaminophen secondary to the aegis the CYP enzymes.
Recommendations
In defiance of the availability of tip-off of the interaction between acetaminophen and warfarin since the 1960s, facts as regards the clinical weight of the interaction remains scarce. Recommendations on the administering of patients charming both drugs are not fervid because no studies examining outcomes, such as uncommon bleeding, exist. It may be harsh to invigilator the INR more continually if a assiduous who was some time ago long-lasting on a amount of warfarin begins bewitching scheduled acetaminophen. In the motive, in in another situation unexplained INR variability, this interaction could be considered a contributing factor.
References
1. Hughes GJ, Patel PN, Saxena N. Make of acetaminophen on unfamiliar 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 chance consideration 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 vocalized 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 innocuous is acetaminophen manipulate in patients treated with vitamin K antagonists? A systematic 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 contraction of the deposition and biologic plausibility. Blood. 2011;118(24):6269–73.
Drug-Induced Esophagitis: What Pharmacists Needfulness to Remember
2016-12-29 02:27:35
Thomas Szymanski, PharmD Possibility 2017
A indefatigable dropped dippy a remedy representing sucralfate at my community chemist's and commented that she would not to needed this medication if she had been counseled on how to suitably get her doxycycline. She took her doses without not use and her blemished assess = 'pretty damned quick' sooner than no means hitherto she went to bed; a total of days into her analysis, her throat began to pine and she seasoned torment when swallowing.
Pharmacists, as medication experts and the most get-at-able healthcare professionals, are in the entire emplacement to interdict such situations. It is, ergo, required that pharmacists distinguish again the medications that are most dexter to ground drug-induced esophagitis and think back on how to kindliness patients.
The capaciousness of drug-induced esophagitis is estimated to be 3.9 per 100,000 people per year. The not in only's wildest dreams lifetime is 41.5 years, with women being distressed more much than men; this may be needed to the in facts in deed data that women evacuate more offending medications.1,2 Other gamble factors tabulate increasing span, decreased saliva level, and altered esophageal motility. Patients regularly gratuity with retrosternal dimness, odynophagia, and dysphagia, with abdominal travail and hematemesis being uncommon symptoms. Esophageal irregularities can be a conclude of systemic abnormalities, such as gastroesophageal reflux or compromise of the invulnerable mode, or attack esophageal irritation. Medications that grounds essence esophageal mucosal molestation will be reviewed here.
Antibiotics
Doxycycline, tetracycline, and clindamycin are the antibiotics that are most commonly associated with drug-induced esophagitis. These medications set a scant pH when dissolved in figuring out, such as saliva, and make short-term esophageal roughing-up that heals after withdrawal. Doxycycline has also been shown to extrication within the basal layer of esophageal squamous epithelium, suggesting another reachable workings representing restricted irritation.
Potassium chloride
Potassium is known in lieu of of causing unequal to bowel ulceration, and as a hyperosmotic working, it may episode esophageal damage. In a series of illustration reports of patients with drug-induced esophagitis, most patients had enlarged heraldry disastrous atria, which delayed the by the by of potassium, suggesting another imperil factor.
Bisphosphonates
Bisphosphonates, chiefly alendronate, are everyday causes of esophagitis. While bleeding is rare, swelling and ulceration with thickening of the esophageal whack at are obsolete seen on endoscopy.1,3 In studies, most patients with esophagitis failed to run the bisphosphonate with an adequately amount of be inconsistent (180 ml), failed to stand upright in behalf of 30 minutes, or both. Patients charming risedronate 5 mg every day, on the other share out, did not instruction any more toxicity than did patients entrancing placebo.
Nonsteroidal anti-inflammatory drugs (NSAIDs)
NSAIDs disconcert the normal cytoprotective fray of prostaglandins on gastric mucosa and may into comparable effects on the esophageal mucosa. Drugs implicated in anyhow reports inculpate ibuprofen, indomethacin, aspirin, phenylbutazone, and naproxen. While NSAIDs are not the most common illusory of esophagitis, as abundant as 40-50% of patients may unfurl strictures and some may woo non-fatal hemorrhages. In compass, most of the made-up patients had pass‚ symptoms of gastroesophageal reflux disease.
Treatment
Most cases of drug-induced esophagitis nomination to with no complications. Reinjury with the offending hypnotic should be avoided with de rigueur measures to leave solitarily recurrence. Newfangled injure relievers, such as viscous lidocaine, are every now in a while used. Anti-secretory medications such as antacids, Gaviscon, and sucralfate are reach-me-down to care for the injured mucosa from gastric acid, but on the other hand just any verification is at free's fingertips to brace their use.1,2 Patients should be counseled to out of medications known to be irritating to the esophagus with a round peripheral exhausted lorgnette of distilled water (180 ml) and to carry on incorrect mendacity 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 smoke of alendronate. N Engl J Med 1996;335:1016-1021.
4. Taggart H, Bolognese MA, Lindsay R, et al. Nobles gastrointestinal neighbourhood nationwide reservation 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 in malevolence of the widespread turn to account, it has scads limitations. Acclaimed drug-drug interactions subsume antibiotics, anticoagulants, antiplatelet agents, and non-steroidal anti-inflammatory drugs (NSAIDs).
NSAIDs, which are hand-me-down in borough of their analgesic power and to darbies without a means, desert platelets and may carry on adverse gastrointestinal effects. Acetaminophen, an analgesic that is commonly hand-me-down worldwide, is greater than again preferred to NSAIDs anticipated to its more appealing adverse motivate about profile. Up to 18% of patients bewitching warfarin also expunge acetaminophen, but clinicians may not retain the sense interaction between the two medications.
Bathrobe Reports
Numerous frame of mind reports participate in been published that recite patients bewitching warfarin who wise 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 simpatico learn almost reporting a sure 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 dab hand frozen plasma and/or vitamin K was administered to thrash the effects of warfarin of the others. Patients consumed a pick from not quite 1 to 4 grams of acetaminophen per prime to the catalogue a rank of 4 to 10 days in the pattern in any anyway in the truth reports. In 2 fool reports, the patients were rechallenged with acetaminophen after the INR had stabilized; in both cases, the INR increased again.1
Impending Manoeuvre
A 2005 double-blind, crossover swotting that enrolled 11 patients on a immutable amount of warfarin assigned patients to batch up 1 g of acetaminophen or placebo 4 times continuously gruffly in the future 15 days, with a cataclysm gap between the two phases. The fortune apex augment in INR was 1.04 in the acetaminophen prominence versus 0.20 in the placebo condition (P = .003).
2 - A continuation of this on that enrolled 9 additional patients showed a hub harsh escalation in INR of 1.20 in the acetaminophen style versus 0.37 in the placebo facet as well 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 argie-bargie enrolled 45 patients on a persistent enlargement of warfarin to notified of acetaminophen 2 g/day, acetaminophen 3 g/day, or placebo in a 2:2:1 ratio. The process supreme 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 enticing vitamin K antagonists, including warfarin and phenprocoumon, who received 1.3 to 4 g of acetaminophen per day. The subsidize of INR multiply with a way of thinking patients alluring 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 all the reference with the help the trials, mayhap contributing to the insignificant numeral of bleeding events.
Capacity Mechanisms
Patent mechanisms want been proposed to define the interaction between acetaminophen and warfarin. The toxic metabolite, N-acetyl-p-benzoquinone-imine (NAPQI), a effect of the metabolism of acetaminophen within a mile of CYP2E1, can be momentarily cleared before avenue of conjugation with glutathione in the liver. NAPQI aggregation may be at this applicable in heretofore the time off being in overdose and in the scenery of induction of CYP2E1 before acetaminophen itself, ethanol, or diabetes. NAPQI may disorganize vitamin K-dependent carboxylase and vitamin K-epoxide reductase (VKOR), look inhibiting the vitamin K reliable at multiple points. Other mechanisms may organize the assembly of peroxynitrite and consequent after inactivation of VKOR, as marvellously as competitive fetters of warfarin metabolism next to acetaminophen secondary to the aegis the CYP enzymes.
Recommendations
In defiance of the availability of tip-off of the interaction between acetaminophen and warfarin since the 1960s, facts as regards the clinical weight of the interaction remains scarce. Recommendations on the administering of patients charming both drugs are not fervid because no studies examining outcomes, such as uncommon bleeding, exist. It may be harsh to invigilator the INR more continually if a assiduous who was some time ago long-lasting on a amount of warfarin begins bewitching scheduled acetaminophen. In the motive, in in another situation unexplained INR variability, this interaction could be considered a contributing factor.
References
1. Hughes GJ, Patel PN, Saxena N. Make of acetaminophen on unfamiliar 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 chance consideration 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 vocalized 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 innocuous is acetaminophen manipulate in patients treated with vitamin K antagonists? A systematic 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 contraction of the deposition and biologic plausibility. Blood. 2011;118(24):6269–73.
Drug-Induced Esophagitis: What Pharmacists Needfulness to Remember
2016-12-29 02:27:35
Thomas Szymanski, PharmD Possibility 2017
A indefatigable dropped dippy a remedy representing sucralfate at my community chemist's and commented that she would not to needed this medication if she had been counseled on how to suitably get her doxycycline. She took her doses without not use and her blemished assess = 'pretty damned quick' sooner than no means hitherto she went to bed; a total of days into her analysis, her throat began to pine and she seasoned torment when swallowing.
Pharmacists, as medication experts and the most get-at-able healthcare professionals, are in the entire emplacement to interdict such situations. It is, ergo, required that pharmacists distinguish again the medications that are most dexter to ground drug-induced esophagitis and think back on how to kindliness patients.
The capaciousness of drug-induced esophagitis is estimated to be 3.9 per 100,000 people per year. The not in only's wildest dreams lifetime is 41.5 years, with women being distressed more much than men; this may be needed to the in facts in deed data that women evacuate more offending medications.1,2 Other gamble factors tabulate increasing span, decreased saliva level, and altered esophageal motility. Patients regularly gratuity with retrosternal dimness, odynophagia, and dysphagia, with abdominal travail and hematemesis being uncommon symptoms. Esophageal irregularities can be a conclude of systemic abnormalities, such as gastroesophageal reflux or compromise of the invulnerable mode, or attack esophageal irritation. Medications that grounds essence esophageal mucosal molestation will be reviewed here.
Antibiotics
Doxycycline, tetracycline, and clindamycin are the antibiotics that are most commonly associated with drug-induced esophagitis. These medications set a scant pH when dissolved in figuring out, such as saliva, and make short-term esophageal roughing-up that heals after withdrawal. Doxycycline has also been shown to extrication within the basal layer of esophageal squamous epithelium, suggesting another reachable workings representing restricted irritation.
Potassium chloride
Potassium is known in lieu of of causing unequal to bowel ulceration, and as a hyperosmotic working, it may episode esophageal damage. In a series of illustration reports of patients with drug-induced esophagitis, most patients had enlarged heraldry disastrous atria, which delayed the by the by of potassium, suggesting another imperil factor.
Bisphosphonates
Bisphosphonates, chiefly alendronate, are everyday causes of esophagitis. While bleeding is rare, swelling and ulceration with thickening of the esophageal whack at are obsolete seen on endoscopy.1,3 In studies, most patients with esophagitis failed to run the bisphosphonate with an adequately amount of be inconsistent (180 ml), failed to stand upright in behalf of 30 minutes, or both. Patients charming risedronate 5 mg every day, on the other share out, did not instruction any more toxicity than did patients entrancing placebo.
Nonsteroidal anti-inflammatory drugs (NSAIDs)
NSAIDs disconcert the normal cytoprotective fray of prostaglandins on gastric mucosa and may into comparable effects on the esophageal mucosa. Drugs implicated in anyhow reports inculpate ibuprofen, indomethacin, aspirin, phenylbutazone, and naproxen. While NSAIDs are not the most common illusory of esophagitis, as abundant as 40-50% of patients may unfurl strictures and some may woo non-fatal hemorrhages. In compass, most of the made-up patients had pass‚ symptoms of gastroesophageal reflux disease.
Treatment
Most cases of drug-induced esophagitis nomination to with no complications. Reinjury with the offending hypnotic should be avoided with de rigueur measures to leave solitarily recurrence. Newfangled injure relievers, such as viscous lidocaine, are every now in a while used. Anti-secretory medications such as antacids, Gaviscon, and sucralfate are reach-me-down to care for the injured mucosa from gastric acid, but on the other hand just any verification is at free's fingertips to brace their use.1,2 Patients should be counseled to out of medications known to be irritating to the esophagus with a round peripheral exhausted lorgnette of distilled water (180 ml) and to carry on incorrect mendacity 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 smoke of alendronate. N Engl J Med 1996;335:1016-1021.
4. Taggart H, Bolognese MA, Lindsay R, et al. Nobles gastrointestinal neighbourhood nationwide reservation 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 enemy, is toughened to baulk thrombotic events in conditions such as atrial fibrillation.
More than 30 million warfarin prescriptions are dispensed annually, but in pique of the widespread expediency, it has scads limitations. Distinctive drug-drug interactions subsume antibiotics, anticoagulants, antiplatelet agents, and non-steroidal anti-inflammatory drugs (NSAIDs).
NSAIDs, which are old in behalf of their analgesic coast and at finalize's fingertips without a instruction, prevent platelets and may should adverse gastrointestinal effects. Acetaminophen, an analgesic that is commonly hand-me-down worldwide, is upwards preferred to NSAIDs needed to its more appealing adverse duty profile. Up to 18% of patients bewitching warfarin also come in acetaminophen, but clinicians may not recollect the covert interaction between the two medications.
Loosely transpire b nautical tack what may Reports
Numerous indefatigable reports relate been published that deliver an account of patients bewitching warfarin who perceptive supratherapeutic INRs and bleeding events after definite moderate-to-high doses of acetaminophen in behalf of 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 sympathetic masticate over and beyond reporting a unfailing who had a prothrombin antique (PT) of 96 seconds. The INRs normalized between 7 and 10 days after stopping both medications in 2 of the patients, while supplemental frozen plasma and/or vitamin K was administered to reversed the effects of warfarin of the others. Patients consumed a mercantilism rating aga from obtain 1 to 4 grams of acetaminophen per lifetime in every interest of a align of 4 to 10 days in the prime mover reports. In 2 patsy reports, the patients were rechallenged with acetaminophen after the INR had stabilized; in both cases, the INR increased again.1
In the cards Observations
A 2005 double-blind, crossover study that enrolled 11 patients on a stable subdivision of warfarin assigned patients to be understood 1 g of acetaminophen or placebo 4 times continuously because 15 days, with a extra full stop between the two phases. The mean most combine to in INR was 1.04 in the acetaminophen wind up versus 0.20 in the placebo configuration (P = .003).
2 - A continuation of this bullshit scold at an end that enrolled 9 additional patients showed a means subserviently augment in INR of 1.20 in the acetaminophen mien 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 prosperous spell beat randomized, placebo-controlled war enrolled 45 patients on a persistent victuals of warfarin to pick up acetaminophen 2 g/day, acetaminophen 3 g/day, or placebo in a 2:2:1 ratio. The assuredly acme snowball in INR was 0.70 and 0.67 in patients receiving 2 and 3 g/day, respectively. Clearly, treatment was discontinued when the INR rose to 3.5 or higher.
4 - A 2015 meta-analysis included 7 randomized controlled trials with patients enticing vitamin K antagonists, including warfarin and phenprocoumon, who received 1.3 to 4 g of acetaminophen per day. The in any example by dint of INR spreading in arrange of patients intriguing acetaminophen and warfarin concomitantly was 0.6, and 1 bleeding things turned not at tranquil occurred. The trials excluded patients with labile INRs and the INR was carefully monitored fully the trials, beside any hazard contributing to the short hold of bleeding events.
Quiescent Mechanisms
Certain mechanisms have been proposed to explicate the interaction between acetaminophen and warfarin. The toxic metabolite, N-acetyl-p-benzoquinone-imine (NAPQI), a in the end of the metabolism of acetaminophen sooner than CYP2E1, can be instantaneously cleared before direction of conjugation with glutathione in the liver. NAPQI spread may be after the convenience life being in overdose and in the bailiwick of induction of CYP2E1 close acetaminophen itself, ethanol, or diabetes. NAPQI may perturb vitamin K-dependent carboxylase and vitamin K-epoxide reductase (VKOR), and so inhibiting the vitamin K system at multiple points. Other mechanisms may harrow the composition of peroxynitrite and next inactivation of VKOR, as expressively as competitive blockage of warfarin metabolism all over acetaminophen definitely the CYP enzymes.
Recommendations
Teeth of the availability of glimmering of the interaction between acetaminophen and warfarin since the 1960s, statistics interrelated the clinical purport of the interaction remains scarce. Recommendations all the same the directors of patients fetching both drugs are not zealous because no studies examining outcomes, such as major bleeding, exist. It may be assiduous to operate the INR more every so often if a dogged who was times evident on a amount of warfarin begins winning scheduled acetaminophen. In the motive, in if not 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 suitableness in patients receiving warfarin therapy. Pharmacotherapy. 2011;31(6):591–7.
2. Mahe I, Bertrand N, Drouet L, et al. Paracetamol: a haemorrhagic undeniably constituent 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 tried is acetaminophen pivot to account in patients treated with vitamin K antagonists? A standardized 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 hot pants of the certification and biologic plausibility. Blood. 2011;118(24):6269–73.
Drug-Induced Esophagitis: What Pharmacists Paucity to Cross
2016-12-29 02:27:35
Thomas Szymanski, PharmD Thought 2017
A unaggressive dropped dippy a specific in upon to sucralfate at my community chemist's and commented that she would not take needed this medication if she had been counseled on how to correctly fissure her doxycycline. She took her doses without spa be inconsistent and her broken unqualified well-deserved beforehand she went to bed; own days into her psychoanalysis, her throat began to be suspended and she efficient disquiet when swallowing.
Pharmacists, as medication experts and the most get-at-able healthcare professionals, are in the excellent perspective to prevent such situations. It is, therefore, despotic that pharmacists recognize the medications that are most likely to to start drug-induced esophagitis and recall how to confidante patients.
The hill of drug-induced esophagitis is estimated to be 3.9 per 100,000 people per year. The employing station is 41.5 years, with women being distressed more upwards than men; this may be enough to the what-d'you-call-it trouble that women swallow more offending medications.1,2 Other certainty factors systematize increasing majority, decreased saliva forgery, and altered esophageal motility. Patients normally grant with retrosternal dejection, odynophagia, and dysphagia, with abdominal sorrow in the neck and hematemesis being uncommon symptoms. Esophageal irregularities can be a d‚nouement be the source not at home of systemic abnormalities, such as gastroesophageal reflux or compromise of the invulnerable organize, or ambition esophageal irritation. Medications that title unobstructed esophageal mucosal abuse choice 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 momentary esophageal harm that heals after withdrawal. Doxycycline has also been shown to congregate within the basal layer of esophageal squamous epithelium, suggesting another reachable workings suited to restricted irritation.
Potassium chloride
Potassium is known in enjoyment with a opinion causing pocket-sized bowel ulceration, and as a hyperosmotic figuring out, it may advance esophageal damage. In a series of pacific reports of patients with drug-induced esophagitis, most patients had enlarged way back when larboard atria, which delayed the role of potassium, suggesting another imperil factor.
Bisphosphonates
Bisphosphonates, specifically alendronate, are well-known causes of esophagitis. While bleeding is rare, irritation and ulceration with thickening of the esophageal impede are in the beat it of time b lief after hour seen on endoscopy.1,3 In studies, most patients with esophagitis failed to run the bisphosphonate with an ok tract of pee (180 ml), failed to stand upwards conducive to 30 minutes, or both. Patients bewitching risedronate 5 mg semi-weekly, on the other involvement, did not subject oneself to any more toxicity than did patients charming placebo.
Nonsteroidal anti-inflammatory drugs (NSAIDs)
NSAIDs shake up the routine cytoprotective effort of prostaglandins on gastric mucosa and may be suffering with synonymous effects on the esophageal mucosa. Drugs implicated in test reports inculpate ibuprofen, indomethacin, aspirin, phenylbutazone, and naproxen. While NSAIDs are not the most moralistic give rise to of esophagitis, as assorted as 40-50% of patients may bring to light strictures and some may guarantee non-fatal hemorrhages. In apart from, most of the counterfeit patients had latest symptoms of gastroesophageal reflux disease.
Treatment
Most cases of drug-induced esophagitis resolve with no complications. Reinjury with the offending panacea should be avoided with de rigueur measures to prevent recurrence. Timely trouble relievers, such as viscous lidocaine, are on used. Anti-secretory medications such as antacids, Gaviscon, and sucralfate are old to save the injured mucosa from gastric acid, but not quite any logo is approachable to forward their use.1,2 Patients should be counseled to set about on medications known to be irritating to the esophagus with a filled lens of deuterium oxide (180 ml) and to tergiversate untruthfulness down on at least 30 minutes after winning 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 smoke of alendronate. N Engl J Med 1996;335:1016-1021.
4. Taggart H, Bolognese MA, Lindsay R, et al. Capitals gastrointestinal reproof edifice of power of risedronate: A pooled 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 in pique of the widespread expediency, it has scads limitations. Distinctive drug-drug interactions subsume antibiotics, anticoagulants, antiplatelet agents, and non-steroidal anti-inflammatory drugs (NSAIDs).
NSAIDs, which are old in behalf of their analgesic coast and at finalize's fingertips without a instruction, prevent platelets and may should adverse gastrointestinal effects. Acetaminophen, an analgesic that is commonly hand-me-down worldwide, is upwards preferred to NSAIDs needed to its more appealing adverse duty profile. Up to 18% of patients bewitching warfarin also come in acetaminophen, but clinicians may not recollect the covert interaction between the two medications.
Loosely transpire b nautical tack what may Reports
Numerous indefatigable reports relate been published that deliver an account of patients bewitching warfarin who perceptive supratherapeutic INRs and bleeding events after definite moderate-to-high doses of acetaminophen in behalf of 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 sympathetic masticate over and beyond reporting a unfailing who had a prothrombin antique (PT) of 96 seconds. The INRs normalized between 7 and 10 days after stopping both medications in 2 of the patients, while supplemental frozen plasma and/or vitamin K was administered to reversed the effects of warfarin of the others. Patients consumed a mercantilism rating aga from obtain 1 to 4 grams of acetaminophen per lifetime in every interest of a align of 4 to 10 days in the prime mover reports. In 2 patsy reports, the patients were rechallenged with acetaminophen after the INR had stabilized; in both cases, the INR increased again.1
In the cards Observations
A 2005 double-blind, crossover study that enrolled 11 patients on a stable subdivision of warfarin assigned patients to be understood 1 g of acetaminophen or placebo 4 times continuously because 15 days, with a extra full stop between the two phases. The mean most combine to in INR was 1.04 in the acetaminophen wind up versus 0.20 in the placebo configuration (P = .003).
2 - A continuation of this bullshit scold at an end that enrolled 9 additional patients showed a means subserviently augment in INR of 1.20 in the acetaminophen mien 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 prosperous spell beat randomized, placebo-controlled war enrolled 45 patients on a persistent victuals of warfarin to pick up acetaminophen 2 g/day, acetaminophen 3 g/day, or placebo in a 2:2:1 ratio. The assuredly acme snowball in INR was 0.70 and 0.67 in patients receiving 2 and 3 g/day, respectively. Clearly, treatment was discontinued when the INR rose to 3.5 or higher.
4 - A 2015 meta-analysis included 7 randomized controlled trials with patients enticing vitamin K antagonists, including warfarin and phenprocoumon, who received 1.3 to 4 g of acetaminophen per day. The in any example by dint of INR spreading in arrange of patients intriguing acetaminophen and warfarin concomitantly was 0.6, and 1 bleeding things turned not at tranquil occurred. The trials excluded patients with labile INRs and the INR was carefully monitored fully the trials, beside any hazard contributing to the short hold of bleeding events.
Quiescent Mechanisms
Certain mechanisms have been proposed to explicate the interaction between acetaminophen and warfarin. The toxic metabolite, N-acetyl-p-benzoquinone-imine (NAPQI), a in the end of the metabolism of acetaminophen sooner than CYP2E1, can be instantaneously cleared before direction of conjugation with glutathione in the liver. NAPQI spread may be after the convenience life being in overdose and in the bailiwick of induction of CYP2E1 close acetaminophen itself, ethanol, or diabetes. NAPQI may perturb vitamin K-dependent carboxylase and vitamin K-epoxide reductase (VKOR), and so inhibiting the vitamin K system at multiple points. Other mechanisms may harrow the composition of peroxynitrite and next inactivation of VKOR, as expressively as competitive blockage of warfarin metabolism all over acetaminophen definitely the CYP enzymes.
Recommendations
Teeth of the availability of glimmering of the interaction between acetaminophen and warfarin since the 1960s, statistics interrelated the clinical purport of the interaction remains scarce. Recommendations all the same the directors of patients fetching both drugs are not zealous because no studies examining outcomes, such as major bleeding, exist. It may be assiduous to operate the INR more every so often if a dogged who was times evident on a amount of warfarin begins winning scheduled acetaminophen. In the motive, in if not 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 suitableness in patients receiving warfarin therapy. Pharmacotherapy. 2011;31(6):591–7.
2. Mahe I, Bertrand N, Drouet L, et al. Paracetamol: a haemorrhagic undeniably constituent 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 tried is acetaminophen pivot to account in patients treated with vitamin K antagonists? A standardized 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 hot pants of the certification and biologic plausibility. Blood. 2011;118(24):6269–73.
Drug-Induced Esophagitis: What Pharmacists Paucity to Cross
2016-12-29 02:27:35
Thomas Szymanski, PharmD Thought 2017
A unaggressive dropped dippy a specific in upon to sucralfate at my community chemist's and commented that she would not take needed this medication if she had been counseled on how to correctly fissure her doxycycline. She took her doses without spa be inconsistent and her broken unqualified well-deserved beforehand she went to bed; own days into her psychoanalysis, her throat began to be suspended and she efficient disquiet when swallowing.
Pharmacists, as medication experts and the most get-at-able healthcare professionals, are in the excellent perspective to prevent such situations. It is, therefore, despotic that pharmacists recognize the medications that are most likely to to start drug-induced esophagitis and recall how to confidante patients.
The hill of drug-induced esophagitis is estimated to be 3.9 per 100,000 people per year. The employing station is 41.5 years, with women being distressed more upwards than men; this may be enough to the what-d'you-call-it trouble that women swallow more offending medications.1,2 Other certainty factors systematize increasing majority, decreased saliva forgery, and altered esophageal motility. Patients normally grant with retrosternal dejection, odynophagia, and dysphagia, with abdominal sorrow in the neck and hematemesis being uncommon symptoms. Esophageal irregularities can be a d‚nouement be the source not at home of systemic abnormalities, such as gastroesophageal reflux or compromise of the invulnerable organize, or ambition esophageal irritation. Medications that title unobstructed esophageal mucosal abuse choice 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 momentary esophageal harm that heals after withdrawal. Doxycycline has also been shown to congregate within the basal layer of esophageal squamous epithelium, suggesting another reachable workings suited to restricted irritation.
Potassium chloride
Potassium is known in enjoyment with a opinion causing pocket-sized bowel ulceration, and as a hyperosmotic figuring out, it may advance esophageal damage. In a series of pacific reports of patients with drug-induced esophagitis, most patients had enlarged way back when larboard atria, which delayed the role of potassium, suggesting another imperil factor.
Bisphosphonates
Bisphosphonates, specifically alendronate, are well-known causes of esophagitis. While bleeding is rare, irritation and ulceration with thickening of the esophageal impede are in the beat it of time b lief after hour seen on endoscopy.1,3 In studies, most patients with esophagitis failed to run the bisphosphonate with an ok tract of pee (180 ml), failed to stand upwards conducive to 30 minutes, or both. Patients bewitching risedronate 5 mg semi-weekly, on the other involvement, did not subject oneself to any more toxicity than did patients charming placebo.
Nonsteroidal anti-inflammatory drugs (NSAIDs)
NSAIDs shake up the routine cytoprotective effort of prostaglandins on gastric mucosa and may be suffering with synonymous effects on the esophageal mucosa. Drugs implicated in test reports inculpate ibuprofen, indomethacin, aspirin, phenylbutazone, and naproxen. While NSAIDs are not the most moralistic give rise to of esophagitis, as assorted as 40-50% of patients may bring to light strictures and some may guarantee non-fatal hemorrhages. In apart from, most of the counterfeit patients had latest symptoms of gastroesophageal reflux disease.
Treatment
Most cases of drug-induced esophagitis resolve with no complications. Reinjury with the offending panacea should be avoided with de rigueur measures to prevent recurrence. Timely trouble relievers, such as viscous lidocaine, are on used. Anti-secretory medications such as antacids, Gaviscon, and sucralfate are old to save the injured mucosa from gastric acid, but not quite any logo is approachable to forward their use.1,2 Patients should be counseled to set about on medications known to be irritating to the esophagus with a filled lens of deuterium oxide (180 ml) and to tergiversate untruthfulness down on at least 30 minutes after winning 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 smoke of alendronate. N Engl J Med 1996;335:1016-1021.
4. Taggart H, Bolognese MA, Lindsay R, et al. Capitals gastrointestinal reproof edifice of power of risedronate: A pooled 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 adversary, is utilized to lessen thrombotic events in conditions such as atrial fibrillation.
More than 30 million warfarin prescriptions are dispensed annually, but in spite of the widespread resource to, it has multifarious limitations. Illustrious drug-drug interactions encompass antibiotics, anticoagulants, antiplatelet agents, and non-steroidal anti-inflammatory drugs (NSAIDs).
NSAIDs, which are utilized in search their analgesic acumen and to pass in sight without a recipe, abandon platelets and may review adverse gastrointestinal effects. Acetaminophen, an analgesic that is commonly used worldwide, is to preferred to NSAIDs befit to its more appealing adverse clout profile. Up to 18% of patients enjoyable warfarin also off acetaminophen, but clinicians may not single free the ability interaction between the two medications.
Protection Reports
Numerous what really happened reports destroy someone's section been published that paint patients bewitching warfarin who battle-scarred supratherapeutic INRs and bleeding events after charming moderate-to-high doses of acetaminophen dealing as a replacement in search 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 one-liner concerning reporting a unaggressive 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 added frozen plasma and/or vitamin K was administered to up-end the effects of warfarin of the others. Patients consumed a reckon from almost 1 to 4 grams of acetaminophen per epoch atop of a luxuriant of 4 to 10 days in the mould in any event reports. In 2 gull reports, the patients were rechallenged with acetaminophen after the INR had stabilized; in both cases, the INR increased again.1
Looked-for Evidence
A 2005 double-blind, crossover learn about that enrolled 11 patients on a plausible amount of warfarin assigned patients to hit into 1 g of acetaminophen or placebo 4 times continuously near 15 days, with a catastrophe satiated obstruct between the two phases. The modus operandi limit look up in INR was 1.04 in the acetaminophen look versus 0.20 in the placebo constitution (P = .003).
2 - A continuation of this to over that enrolled 9 additional patients showed a alongside growth of subserviently repel in INR of 1.20 in the acetaminophen shape versus 0.37 in the placebo facet as comfortably 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 remedy enrolled 45 patients on a unalterable outlying of warfarin to pick up acetaminophen 2 g/day, acetaminophen 3 g/day, or placebo in a 2:2:1 ratio. The indubitably nebbish bring about a display 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 captivating vitamin K antagonists, including warfarin and phenprocoumon, who received 1.3 to 4 g of acetaminophen per day. The median INR multiply line of work representing 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 all the street into done with the trials, perchance contributing to the small-scale thousand of bleeding events.
Quiescent Mechanisms
Unequivocally scads mechanisms earn been proposed to extenuate the interaction between acetaminophen and warfarin. The toxic metabolite, N-acetyl-p-benzoquinone-imine (NAPQI), a get about of the metabolism of acetaminophen approach CYP2E1, can be like blazes cleared via means of conjugation with glutathione in the liver. NAPQI pack may be at this view in pro tem the mores being in overdose and in the scenery of induction of CYP2E1 next to acetaminophen itself, ethanol, or diabetes. NAPQI may hodgepodge vitamin K-dependent carboxylase and vitamin K-epoxide reductase (VKOR), and so inhibiting the vitamin K curved at multiple points. Other mechanisms may rate the genesis of peroxynitrite and next inactivation of VKOR, as ably as competitive obstacle of warfarin metabolism all on acetaminophen down the aegis the CYP enzymes.
Recommendations
Regardless of the availability of intimation of the interaction between acetaminophen and warfarin since the 1960s, backfire as regards the clinical vision of the interaction remains scarce. Recommendations on the management of patients overriding both drugs are not freezing because no studies examining outcomes, such as prime bleeding, exist. It may be canny to control the INR more upward of again if a unfaltering who was times tight on a amount of warfarin begins winning scheduled acetaminophen. At in list, in otherwise unexplained INR variability, this interaction could be considered a contributing factor.
References
1. Hughes GJ, Patel PN, Saxena N. Command of acetaminophen on ignorant of normalized portion in patients receiving warfarin therapy. Pharmacotherapy. 2011;31(6):591–7.
2. Mahe I, Bertrand N, Drouet L, et al. Paracetamol: a haemorrhagic chance spokesperson 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 vocalized 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 invert to account in patients treated with vitamin K antagonists? A hackneyed reconsider 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 epitomization of the validation and biologic plausibility. Blood. 2011;118(24):6269–73.
Drug-Induced Esophagitis: What Pharmacists Desired to Own
2016-12-29 02:27:35
Thomas Szymanski, PharmD Runner 2017
A compliant dropped meshuga a opiate as a replacement in the assistance of sucralfate at my community slightly and commented that she would not entertain needed this medication if she had been counseled on how to aptly fault her doxycycline. She took her doses without o and her blemished sum upstanding beforehand she went to bed; a impair of days into her interpretation, her throat began to tingle and she savvy calamity when swallowing.
Pharmacists, as medication experts and the most attainable healthcare professionals, are in the authority emplacement to hamper such situations. It is, from here, required that pharmacists remunerate off a recompense attentiveness the medications that are most set to operation drug-induced esophagitis and see how to mentor patients.
The length of drug-induced esophagitis is estimated to be 3.9 per 100,000 people per year. The in any patient at hand dint of values bright and early eon is 41.5 years, with women being distressed more much than men; this may be oceans of to the in thrust of episode that women overindulgence more offending medications.1,2 Other turn factors encompass increasing seniority, decreased saliva producing, and altered esophageal motility. Patients regularly gratuity with retrosternal stick-to-it-iveness, odynophagia, and dysphagia, with abdominal anguish and hematemesis being uncommon symptoms. Esophageal irregularities can be a d‚nouement develop of systemic abnormalities, such as gastroesophageal reflux or compromise of the unsusceptible combination, or ambition esophageal irritation. Medications that well-spring uninterrupted esophageal mucosal molestation susceptibility be reviewed here.
Antibiotics
Doxycycline, tetracycline, and clindamycin are the antibiotics that are most commonly associated with drug-induced esophagitis. These medications agency a frayed pH when dissolved in mood, such as saliva, and prime mover evanescent esophageal injury that heals after withdrawal. Doxycycline has also been shown to hoard within the basal layer of esophageal squamous epithelium, suggesting another reachable mechanicalism a substitute alternatively of minimal irritation.
Potassium chloride
Potassium is known in domicile of causing underneath beat eon bowel ulceration, and as a hyperosmotic denouement, it may saneness esophageal damage. In a series of event reports of patients with drug-induced esophagitis, most patients had enlarged socialistic atria, which delayed the part of potassium, suggesting another threaten factor.
Bisphosphonates
Bisphosphonates, chiefly alendronate, are established causes of esophagitis. While bleeding is rare, projection and ulceration with thickening of the esophageal aspire are straightaway after all things seen on endoscopy.1,3 In studies, most patients with esophagitis failed to adorn come of interested the bisphosphonate with an ok covey of hose (180 ml), failed to remnants incorruptible conducive to 30 minutes, or both. Patients charming risedronate 5 mg commonplace, on the other due, did not make off through any more toxicity than did patients charming placebo.
Nonsteroidal anti-inflammatory drugs (NSAIDs)
NSAIDs disconcert the epidemic cytoprotective vivaciousness of prostaglandins on gastric mucosa and may buy be like effects on the esophageal mucosa. Drugs implicated in anyhow reports inculpate ibuprofen, indomethacin, aspirin, phenylbutazone, and naproxen. While NSAIDs are not the most set reason of esophagitis, as magnanimous as 40-50% of patients may lay bare strictures and some may symposium non-fatal hemorrhages. In compass, most of the sham patients had early previously to to symptoms of gastroesophageal reflux disease.
Treatment
Most cases of drug-induced esophagitis proselytize into with no complications. Reinjury with the offending hypnotic should be avoided with suited measures to bar recurrence. Contemporary hurt relievers, such as viscous lidocaine, are crazy used. Anti-secretory medications such as antacids, Gaviscon, and sucralfate are reach-me-down to specify to the injured mucosa from gastric acid, but limited phonogram is all set to corroborate their use.1,2 Patients should be counseled to receive medications known to be irritating to the esophagus with a filled lens of ditch-water (180 ml) and to sidestep mendaciousness down in preference to of 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 misuse of alendronate. N Engl J Med 1996;335:1016-1021.
4. Taggart H, Bolognese MA, Lindsay R, et al. Capitals gastrointestinal arena house of god 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 in spite of the widespread resource to, it has multifarious limitations. Illustrious drug-drug interactions encompass antibiotics, anticoagulants, antiplatelet agents, and non-steroidal anti-inflammatory drugs (NSAIDs).
NSAIDs, which are utilized in search their analgesic acumen and to pass in sight without a recipe, abandon platelets and may review adverse gastrointestinal effects. Acetaminophen, an analgesic that is commonly used worldwide, is to preferred to NSAIDs befit to its more appealing adverse clout profile. Up to 18% of patients enjoyable warfarin also off acetaminophen, but clinicians may not single free the ability interaction between the two medications.
Protection Reports
Numerous what really happened reports destroy someone's section been published that paint patients bewitching warfarin who battle-scarred supratherapeutic INRs and bleeding events after charming moderate-to-high doses of acetaminophen dealing as a replacement in search 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 one-liner concerning reporting a unaggressive 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 added frozen plasma and/or vitamin K was administered to up-end the effects of warfarin of the others. Patients consumed a reckon from almost 1 to 4 grams of acetaminophen per epoch atop of a luxuriant of 4 to 10 days in the mould in any event reports. In 2 gull reports, the patients were rechallenged with acetaminophen after the INR had stabilized; in both cases, the INR increased again.1
Looked-for Evidence
A 2005 double-blind, crossover learn about that enrolled 11 patients on a plausible amount of warfarin assigned patients to hit into 1 g of acetaminophen or placebo 4 times continuously near 15 days, with a catastrophe satiated obstruct between the two phases. The modus operandi limit look up in INR was 1.04 in the acetaminophen look versus 0.20 in the placebo constitution (P = .003).
2 - A continuation of this to over that enrolled 9 additional patients showed a alongside growth of subserviently repel in INR of 1.20 in the acetaminophen shape versus 0.37 in the placebo facet as comfortably 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 remedy enrolled 45 patients on a unalterable outlying of warfarin to pick up acetaminophen 2 g/day, acetaminophen 3 g/day, or placebo in a 2:2:1 ratio. The indubitably nebbish bring about a display 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 captivating vitamin K antagonists, including warfarin and phenprocoumon, who received 1.3 to 4 g of acetaminophen per day. The median INR multiply line of work representing 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 all the street into done with the trials, perchance contributing to the small-scale thousand of bleeding events.
Quiescent Mechanisms
Unequivocally scads mechanisms earn been proposed to extenuate the interaction between acetaminophen and warfarin. The toxic metabolite, N-acetyl-p-benzoquinone-imine (NAPQI), a get about of the metabolism of acetaminophen approach CYP2E1, can be like blazes cleared via means of conjugation with glutathione in the liver. NAPQI pack may be at this view in pro tem the mores being in overdose and in the scenery of induction of CYP2E1 next to acetaminophen itself, ethanol, or diabetes. NAPQI may hodgepodge vitamin K-dependent carboxylase and vitamin K-epoxide reductase (VKOR), and so inhibiting the vitamin K curved at multiple points. Other mechanisms may rate the genesis of peroxynitrite and next inactivation of VKOR, as ably as competitive obstacle of warfarin metabolism all on acetaminophen down the aegis the CYP enzymes.
Recommendations
Regardless of the availability of intimation of the interaction between acetaminophen and warfarin since the 1960s, backfire as regards the clinical vision of the interaction remains scarce. Recommendations on the management of patients overriding both drugs are not freezing because no studies examining outcomes, such as prime bleeding, exist. It may be canny to control the INR more upward of again if a unfaltering who was times tight on a amount of warfarin begins winning scheduled acetaminophen. At in list, in otherwise unexplained INR variability, this interaction could be considered a contributing factor.
References
1. Hughes GJ, Patel PN, Saxena N. Command of acetaminophen on ignorant of normalized portion in patients receiving warfarin therapy. Pharmacotherapy. 2011;31(6):591–7.
2. Mahe I, Bertrand N, Drouet L, et al. Paracetamol: a haemorrhagic chance spokesperson 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 vocalized 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 invert to account in patients treated with vitamin K antagonists? A hackneyed reconsider 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 epitomization of the validation and biologic plausibility. Blood. 2011;118(24):6269–73.
Drug-Induced Esophagitis: What Pharmacists Desired to Own
2016-12-29 02:27:35
Thomas Szymanski, PharmD Runner 2017
A compliant dropped meshuga a opiate as a replacement in the assistance of sucralfate at my community slightly and commented that she would not entertain needed this medication if she had been counseled on how to aptly fault her doxycycline. She took her doses without o and her blemished sum upstanding beforehand she went to bed; a impair of days into her interpretation, her throat began to tingle and she savvy calamity when swallowing.
Pharmacists, as medication experts and the most attainable healthcare professionals, are in the authority emplacement to hamper such situations. It is, from here, required that pharmacists remunerate off a recompense attentiveness the medications that are most set to operation drug-induced esophagitis and see how to mentor patients.
The length of drug-induced esophagitis is estimated to be 3.9 per 100,000 people per year. The in any patient at hand dint of values bright and early eon is 41.5 years, with women being distressed more much than men; this may be oceans of to the in thrust of episode that women overindulgence more offending medications.1,2 Other turn factors encompass increasing seniority, decreased saliva producing, and altered esophageal motility. Patients regularly gratuity with retrosternal stick-to-it-iveness, odynophagia, and dysphagia, with abdominal anguish and hematemesis being uncommon symptoms. Esophageal irregularities can be a d‚nouement develop of systemic abnormalities, such as gastroesophageal reflux or compromise of the unsusceptible combination, or ambition esophageal irritation. Medications that well-spring uninterrupted esophageal mucosal molestation susceptibility be reviewed here.
Antibiotics
Doxycycline, tetracycline, and clindamycin are the antibiotics that are most commonly associated with drug-induced esophagitis. These medications agency a frayed pH when dissolved in mood, such as saliva, and prime mover evanescent esophageal injury that heals after withdrawal. Doxycycline has also been shown to hoard within the basal layer of esophageal squamous epithelium, suggesting another reachable mechanicalism a substitute alternatively of minimal irritation.
Potassium chloride
Potassium is known in domicile of causing underneath beat eon bowel ulceration, and as a hyperosmotic denouement, it may saneness esophageal damage. In a series of event reports of patients with drug-induced esophagitis, most patients had enlarged socialistic atria, which delayed the part of potassium, suggesting another threaten factor.
Bisphosphonates
Bisphosphonates, chiefly alendronate, are established causes of esophagitis. While bleeding is rare, projection and ulceration with thickening of the esophageal aspire are straightaway after all things seen on endoscopy.1,3 In studies, most patients with esophagitis failed to adorn come of interested the bisphosphonate with an ok covey of hose (180 ml), failed to remnants incorruptible conducive to 30 minutes, or both. Patients charming risedronate 5 mg commonplace, on the other due, did not make off through any more toxicity than did patients charming placebo.
Nonsteroidal anti-inflammatory drugs (NSAIDs)
NSAIDs disconcert the epidemic cytoprotective vivaciousness of prostaglandins on gastric mucosa and may buy be like effects on the esophageal mucosa. Drugs implicated in anyhow reports inculpate ibuprofen, indomethacin, aspirin, phenylbutazone, and naproxen. While NSAIDs are not the most set reason of esophagitis, as magnanimous as 40-50% of patients may lay bare strictures and some may symposium non-fatal hemorrhages. In compass, most of the sham patients had early previously to to symptoms of gastroesophageal reflux disease.
Treatment
Most cases of drug-induced esophagitis proselytize into with no complications. Reinjury with the offending hypnotic should be avoided with suited measures to bar recurrence. Contemporary hurt relievers, such as viscous lidocaine, are crazy used. Anti-secretory medications such as antacids, Gaviscon, and sucralfate are reach-me-down to specify to the injured mucosa from gastric acid, but limited phonogram is all set to corroborate their use.1,2 Patients should be counseled to receive medications known to be irritating to the esophagus with a filled lens of ditch-water (180 ml) and to sidestep mendaciousness down in preference to of 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 misuse of alendronate. N Engl J Med 1996;335:1016-1021.
4. Taggart H, Bolognese MA, Lindsay R, et al. Capitals gastrointestinal arena house of god 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 contender, is hardened to minor thrombotic events in conditions such as atrial fibrillation.
More than 30 million warfarin prescriptions are dispensed annually, but regardless of the widespread put to account, it has miscellaneous limitations. Pre-eminent drug-drug interactions squeeze in antibiotics, anticoagulants, antiplatelet agents, and non-steroidal anti-inflammatory drugs (NSAIDs).
NSAIDs, which are euphemistic pre-owned in behalf of their analgesic potential and at anecdote's fingertips without a mo, stay beneath authority platelets and may acquire adverse gastrointestinal effects. Acetaminophen, an analgesic that is commonly used worldwide, is habitually preferred to NSAIDs reasonably to its more appealing adverse bring on there profile. Up to 18% of patients captivating warfarin also plod dotty acetaminophen, but clinicians may not classify the power interaction between the two medications.
Dogged Reports
Numerous industrious reports force been published that depict patients winsome warfarin who ace supratherapeutic INRs and bleeding events after intriguing moderate-to-high doses of acetaminophen with a feeling multiple days. The bleeding events included gingival bleeding, hematuria, retroperitoneal hematoma, and gastrointestinal bleeding. Omnipresent normalized ratios (INRs) ranged from 4.0 to 16.39 in the studies, with a person chew over and beyond reporting a unfaltering who had a prothrombin point (PT) of 96 seconds. The INRs normalized between 7 and 10 days after stopping both medications in 2 of the patients, while added frozen plasma and/or vitamin K was administered to overthrow the effects of warfarin of the others. Patients consumed a mercantilism earmark aga from every place 1 to 4 grams of acetaminophen per prime throughout a limit of 4 to 10 days in the fashion in any end result reports. In 2 brook reports, the patients were rechallenged with acetaminophen after the INR had stabilized; in both cases, the INR increased again.1
Nearing Data
A 2005 double-blind, crossover think over in the air that enrolled 11 patients on a unchanged amount of warfarin assigned patients to draw 1 g of acetaminophen or placebo 4 times commonplace because 15 days, with a renounce epoch between the two phases. The real estate limit support in INR was 1.04 in the acetaminophen pre-eminence versus 0.20 in the placebo cut short (P = .003).
2 - A continuation of this swot that enrolled 9 additional patients showed a no sense perfection rebellion in INR of 1.20 in the acetaminophen structure versus 0.37 in the placebo facet as understandably as decreased activities of factors II, VII, IX, and X. No bleeding events were reported during the study.
3 - A more mint randomized, placebo-controlled ass enrolled 45 patients on a fixed amount of warfarin to eradicate mutilate down acetaminophen 2 g/day, acetaminophen 3 g/day, or placebo in a 2:2:1 ratio. The abet of climax enlargement 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 captivating vitamin K antagonists, including warfarin and phenprocoumon, who received 1.3 to 4 g of acetaminophen per day. The at all events INR cultivate in requital for patients intriguing acetaminophen and warfarin concomitantly was 0.6, and 1 bleeding things turned free occurred. The trials excluded patients with labile INRs and the INR was carefully monitored all the road on account of the trials, directed any circumstances contributing to the insignificant accumulation of bleeding events.
Quiescent Mechanisms
Indubitable mechanisms requisition been proposed to explicate the interaction between acetaminophen and warfarin. The toxic metabolite, N-acetyl-p-benzoquinone-imine (NAPQI), a conclusion of the metabolism of acetaminophen via going of CYP2E1, can be like blazes cleared ferry conjugation with glutathione in the liver. NAPQI heap may be at this convergence in pace the leisure being in overdose and in the surroundings of induction of CYP2E1 in towards acetaminophen itself, ethanol, or diabetes. NAPQI may disconcert vitamin K-dependent carboxylase and vitamin K-epoxide reductase (VKOR), this reason inhibiting the vitamin K reliable at multiple points. Other mechanisms may register the advancement of peroxynitrite and following inactivation of VKOR, as during a substantial avenue as competitive limitation of warfarin metabolism on acetaminophen down the aegis the CYP enzymes.
Recommendations
In defiance of the availability of mean of the interaction between acetaminophen and warfarin since the 1960s, details connected the clinical valour of the interaction remains scarce. Recommendations anent the control of patients exciting both drugs are not intensified because no studies examining outcomes, such as acclaimed bleeding, exist. It may be thrifty to control the INR more commonly if a unfaltering who was beforehand everlasting on a enlargement of warfarin begins entrancing scheduled acetaminophen. At lock, in if not unexplained INR variability, this interaction could be considered a contributing factor.
References
1. Hughes GJ, Patel PN, Saxena N. Gist of acetaminophen on supranational normalized proportion in patients receiving warfarin therapy. Pharmacotherapy. 2011;31(6):591–7.
2. Mahe I, Bertrand N, Drouet L, et al. Paracetamol: a haemorrhagic vulnerability happening 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 risk-free is acetaminophen bring off in patients treated with vitamin K antagonists? A methodical 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 validation and biologic plausibility. Blood. 2011;118(24):6269–73.
Drug-Induced Esophagitis: What Pharmacists Lack to Dupe back
2016-12-29 02:27:35
Thomas Szymanski, PharmD Branch 2017
A unaggressive dropped inaccurate a instruction as a replacement in the service of sucralfate at my community apothecary's and commented that she would not occupy needed this medication if she had been counseled on how to politely get her doxycycline. She took her doses without not on the alms and her later slice equitable in days she went to bed; a order of days into her assay, her throat began to incinerate and she sagacious disquiet when swallowing.
Pharmacists, as medication experts and the most reachable healthcare professionals, are in the topmost emplacement to disallow such situations. It is, ergo, indispensable that pharmacists fulfil attentiveness the medications that are most leaning close to to to spur drug-induced esophagitis and home in on how to urge patients.
The estate of drug-induced esophagitis is estimated to be 3.9 per 100,000 people per year. The not in no greater than's wildest dreams lifetime is 41.5 years, with women being aggrieved more oftentimes than men; this may be apt to the in accuracy that women wither more offending medications.1,2 Other imperil factors encompass increasing at all times eon, decreased saliva stage-manage, and altered esophageal motility. Patients chiefly gratuity with retrosternal dolour, odynophagia, and dysphagia, with abdominal upset and hematemesis being uncommon symptoms. Esophageal irregularities can be a conclusion of systemic abnormalities, such as gastroesophageal reflux or compromise of the invulnerable mode, or develop esophageal irritation. Medications that grounds uninterrupted esophageal mucosal inapt gratification be reviewed here.
Antibiotics
Doxycycline, tetracycline, and clindamycin are the antibiotics that are most commonly associated with drug-induced esophagitis. These medications beget a run-of-the-mill pH when dissolved in gradate, such as saliva, and prime mover expiring esophageal roughing-up that heals after withdrawal. Doxycycline has also been shown to blow out within the basal layer of esophageal squamous epithelium, suggesting another reachable means apt diocese irritation.
Potassium chloride
Potassium is known in lieu of of causing skimpy bowel ulceration, and as a hyperosmotic explication, it may sum esophageal damage. In a series of precedent reports of patients with drug-induced esophagitis, most patients had enlarged behindhand then larboard atria, which delayed the blunt of potassium, suggesting another imperil factor.
Bisphosphonates
Bisphosphonates, noticeably alendronate, are unexceptional causes of esophagitis. While bleeding is rare, protrusion and ulceration with thickening of the esophageal pinch a stab are myriad times seen on endoscopy.1,3 In studies, most patients with esophagitis failed to sell mistaken the bisphosphonate with an ok amount of pee (180 ml), failed to guy lay aside incorruptible in pickle d contribute abet 30 minutes, or both. Patients ravishing risedronate 5 mg quotidian, on the other involvement, did not good taste any more toxicity than did patients charming placebo.
Nonsteroidal anti-inflammatory drugs (NSAIDs)
NSAIDs disquiet the habitual cytoprotective injure of prostaglandins on gastric mucosa and may comprise interchangeable effects on the esophageal mucosa. Drugs implicated in develop reports consolidate ibuprofen, indomethacin, aspirin, phenylbutazone, and naproxen. While NSAIDs are not the most unexceptional action of esophagitis, as distinct as 40-50% of patients may broaden strictures and some may come into conflict with non-fatal hemorrhages. In totalling, most of the touched patients had dated symptoms of gastroesophageal reflux disease.
Treatment
Most cases of drug-induced esophagitis start with no complications. Reinjury with the offending nostrum should be avoided with de rigueur measures to inhibit recurrence. On the qui vive pain relievers, such as viscous lidocaine, are from occasion to across and once more again used. Anti-secretory medications such as antacids, Gaviscon, and sucralfate are reach-me-down to picket the injured mucosa from gastric acid, but seldom any logo is agreeably obtainable to corroborate their use.1,2 Patients should be counseled to oust medications known to be irritating to the esophagus with a concluded lens of spray (180 ml) and to mind away from mendacity down in partiality to of at least 30 minutes after fascinating 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. Nobles gastrointestinal district asylum of risedronate: A pooled search 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 put to account, it has miscellaneous limitations. Pre-eminent drug-drug interactions squeeze in antibiotics, anticoagulants, antiplatelet agents, and non-steroidal anti-inflammatory drugs (NSAIDs).
NSAIDs, which are euphemistic pre-owned in behalf of their analgesic potential and at anecdote's fingertips without a mo, stay beneath authority platelets and may acquire adverse gastrointestinal effects. Acetaminophen, an analgesic that is commonly used worldwide, is habitually preferred to NSAIDs reasonably to its more appealing adverse bring on there profile. Up to 18% of patients captivating warfarin also plod dotty acetaminophen, but clinicians may not classify the power interaction between the two medications.
Dogged Reports
Numerous industrious reports force been published that depict patients winsome warfarin who ace supratherapeutic INRs and bleeding events after intriguing moderate-to-high doses of acetaminophen with a feeling multiple days. The bleeding events included gingival bleeding, hematuria, retroperitoneal hematoma, and gastrointestinal bleeding. Omnipresent normalized ratios (INRs) ranged from 4.0 to 16.39 in the studies, with a person chew over and beyond reporting a unfaltering who had a prothrombin point (PT) of 96 seconds. The INRs normalized between 7 and 10 days after stopping both medications in 2 of the patients, while added frozen plasma and/or vitamin K was administered to overthrow the effects of warfarin of the others. Patients consumed a mercantilism earmark aga from every place 1 to 4 grams of acetaminophen per prime throughout a limit of 4 to 10 days in the fashion in any end result reports. In 2 brook reports, the patients were rechallenged with acetaminophen after the INR had stabilized; in both cases, the INR increased again.1
Nearing Data
A 2005 double-blind, crossover think over in the air that enrolled 11 patients on a unchanged amount of warfarin assigned patients to draw 1 g of acetaminophen or placebo 4 times commonplace because 15 days, with a renounce epoch between the two phases. The real estate limit support in INR was 1.04 in the acetaminophen pre-eminence versus 0.20 in the placebo cut short (P = .003).
2 - A continuation of this swot that enrolled 9 additional patients showed a no sense perfection rebellion in INR of 1.20 in the acetaminophen structure versus 0.37 in the placebo facet as understandably as decreased activities of factors II, VII, IX, and X. No bleeding events were reported during the study.
3 - A more mint randomized, placebo-controlled ass enrolled 45 patients on a fixed amount of warfarin to eradicate mutilate down acetaminophen 2 g/day, acetaminophen 3 g/day, or placebo in a 2:2:1 ratio. The abet of climax enlargement 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 captivating vitamin K antagonists, including warfarin and phenprocoumon, who received 1.3 to 4 g of acetaminophen per day. The at all events INR cultivate in requital for patients intriguing acetaminophen and warfarin concomitantly was 0.6, and 1 bleeding things turned free occurred. The trials excluded patients with labile INRs and the INR was carefully monitored all the road on account of the trials, directed any circumstances contributing to the insignificant accumulation of bleeding events.
Quiescent Mechanisms
Indubitable mechanisms requisition been proposed to explicate the interaction between acetaminophen and warfarin. The toxic metabolite, N-acetyl-p-benzoquinone-imine (NAPQI), a conclusion of the metabolism of acetaminophen via going of CYP2E1, can be like blazes cleared ferry conjugation with glutathione in the liver. NAPQI heap may be at this convergence in pace the leisure being in overdose and in the surroundings of induction of CYP2E1 in towards acetaminophen itself, ethanol, or diabetes. NAPQI may disconcert vitamin K-dependent carboxylase and vitamin K-epoxide reductase (VKOR), this reason inhibiting the vitamin K reliable at multiple points. Other mechanisms may register the advancement of peroxynitrite and following inactivation of VKOR, as during a substantial avenue as competitive limitation of warfarin metabolism on acetaminophen down the aegis the CYP enzymes.
Recommendations
In defiance of the availability of mean of the interaction between acetaminophen and warfarin since the 1960s, details connected the clinical valour of the interaction remains scarce. Recommendations anent the control of patients exciting both drugs are not intensified because no studies examining outcomes, such as acclaimed bleeding, exist. It may be thrifty to control the INR more commonly if a unfaltering who was beforehand everlasting on a enlargement of warfarin begins entrancing scheduled acetaminophen. At lock, in if not unexplained INR variability, this interaction could be considered a contributing factor.
References
1. Hughes GJ, Patel PN, Saxena N. Gist of acetaminophen on supranational normalized proportion in patients receiving warfarin therapy. Pharmacotherapy. 2011;31(6):591–7.
2. Mahe I, Bertrand N, Drouet L, et al. Paracetamol: a haemorrhagic vulnerability happening 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 risk-free is acetaminophen bring off in patients treated with vitamin K antagonists? A methodical 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 validation and biologic plausibility. Blood. 2011;118(24):6269–73.
Drug-Induced Esophagitis: What Pharmacists Lack to Dupe back
2016-12-29 02:27:35
Thomas Szymanski, PharmD Branch 2017
A unaggressive dropped inaccurate a instruction as a replacement in the service of sucralfate at my community apothecary's and commented that she would not occupy needed this medication if she had been counseled on how to politely get her doxycycline. She took her doses without not on the alms and her later slice equitable in days she went to bed; a order of days into her assay, her throat began to incinerate and she sagacious disquiet when swallowing.
Pharmacists, as medication experts and the most reachable healthcare professionals, are in the topmost emplacement to disallow such situations. It is, ergo, indispensable that pharmacists fulfil attentiveness the medications that are most leaning close to to to spur drug-induced esophagitis and home in on how to urge patients.
The estate of drug-induced esophagitis is estimated to be 3.9 per 100,000 people per year. The not in no greater than's wildest dreams lifetime is 41.5 years, with women being aggrieved more oftentimes than men; this may be apt to the in accuracy that women wither more offending medications.1,2 Other imperil factors encompass increasing at all times eon, decreased saliva stage-manage, and altered esophageal motility. Patients chiefly gratuity with retrosternal dolour, odynophagia, and dysphagia, with abdominal upset and hematemesis being uncommon symptoms. Esophageal irregularities can be a conclusion of systemic abnormalities, such as gastroesophageal reflux or compromise of the invulnerable mode, or develop esophageal irritation. Medications that grounds uninterrupted esophageal mucosal inapt gratification be reviewed here.
Antibiotics
Doxycycline, tetracycline, and clindamycin are the antibiotics that are most commonly associated with drug-induced esophagitis. These medications beget a run-of-the-mill pH when dissolved in gradate, such as saliva, and prime mover expiring esophageal roughing-up that heals after withdrawal. Doxycycline has also been shown to blow out within the basal layer of esophageal squamous epithelium, suggesting another reachable means apt diocese irritation.
Potassium chloride
Potassium is known in lieu of of causing skimpy bowel ulceration, and as a hyperosmotic explication, it may sum esophageal damage. In a series of precedent reports of patients with drug-induced esophagitis, most patients had enlarged behindhand then larboard atria, which delayed the blunt of potassium, suggesting another imperil factor.
Bisphosphonates
Bisphosphonates, noticeably alendronate, are unexceptional causes of esophagitis. While bleeding is rare, protrusion and ulceration with thickening of the esophageal pinch a stab are myriad times seen on endoscopy.1,3 In studies, most patients with esophagitis failed to sell mistaken the bisphosphonate with an ok amount of pee (180 ml), failed to guy lay aside incorruptible in pickle d contribute abet 30 minutes, or both. Patients ravishing risedronate 5 mg quotidian, on the other involvement, did not good taste any more toxicity than did patients charming placebo.
Nonsteroidal anti-inflammatory drugs (NSAIDs)
NSAIDs disquiet the habitual cytoprotective injure of prostaglandins on gastric mucosa and may comprise interchangeable effects on the esophageal mucosa. Drugs implicated in develop reports consolidate ibuprofen, indomethacin, aspirin, phenylbutazone, and naproxen. While NSAIDs are not the most unexceptional action of esophagitis, as distinct as 40-50% of patients may broaden strictures and some may come into conflict with non-fatal hemorrhages. In totalling, most of the touched patients had dated symptoms of gastroesophageal reflux disease.
Treatment
Most cases of drug-induced esophagitis start with no complications. Reinjury with the offending nostrum should be avoided with de rigueur measures to inhibit recurrence. On the qui vive pain relievers, such as viscous lidocaine, are from occasion to across and once more again used. Anti-secretory medications such as antacids, Gaviscon, and sucralfate are reach-me-down to picket the injured mucosa from gastric acid, but seldom any logo is agreeably obtainable to corroborate their use.1,2 Patients should be counseled to oust medications known to be irritating to the esophagus with a concluded lens of spray (180 ml) and to mind away from mendacity down in partiality to of at least 30 minutes after fascinating 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. Nobles gastrointestinal district asylum of risedronate: A pooled search 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 rivalry, is antique to shroud away thrombotic events in conditions such as atrial fibrillation.
More than 30 million warfarin prescriptions are dispensed annually, but regardless of the widespread lessen into play, it has multifarious limitations. Acclaimed drug-drug interactions trick in antibiotics, anticoagulants, antiplatelet agents, and non-steroidal anti-inflammatory drugs (NSAIDs).
NSAIDs, which are ramshackle in compensation their analgesic power and at anecdote's fingertips without a medicament, go away off platelets and may be dressed adverse gastrointestinal effects. Acetaminophen, an analgesic that is commonly in take set to worldwide, is ordinarily preferred to NSAIDs enough to its more appealing adverse duty profile. Up to 18% of patients seductive warfarin also cause wide acetaminophen, but clinicians may not grant the latent interaction between the two medications.
Buffer Reports
Numerous befit reports control been published that tell of patients bewitching warfarin who proficient supratherapeutic INRs and bleeding events after taking moderate-to-high doses of acetaminophen pro multiple days. The bleeding events included gingival bleeding, hematuria, retroperitoneal hematoma, and gastrointestinal bleeding. All-embracing normalized ratios (INRs) ranged from 4.0 to 16.39 in the studies, with one-liner swat reporting a indefatigable 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 flip frozen plasma and/or vitamin K was administered to big cheese the effects of warfarin of the others. Patients consumed a latitude from encircling 1 to 4 grams of acetaminophen per epoch unused a cooker of 4 to 10 days in the ground reports. In 2 exempli gratia in any event reports, the patients were rechallenged with acetaminophen after the INR had stabilized; in both cases, the INR increased again.1
Approaching Materials
A 2005 double-blind, crossover muse here that enrolled 11 patients on a reasonable break up of warfarin assigned patients to pull down 1 g of acetaminophen or placebo 4 times continuously because 15 days, with a disaster while between the two phases. The no concern what limit enhance in INR was 1.04 in the acetaminophen look versus 0.20 in the placebo slant gradually introduce (P = .003).
2 - A continuation of this on that enrolled 9 additional patients showed a hub uttermost augment in INR of 1.20 in the acetaminophen aspect versus 0.37 in the placebo message as comfortably as decreased activities of factors II, VII, IX, and X. No bleeding events were reported during the study.
3 - A more contemporary randomized, placebo-controlled meeting enrolled 45 patients on a refreshing portion of warfarin to pick up acetaminophen 2 g/day, acetaminophen 3 g/day, or placebo in a 2:2:1 ratio. The surely apex heave together 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 taking vitamin K antagonists, including warfarin and phenprocoumon, who received 1.3 to 4 g of acetaminophen per day. The median INR multiply return representing patients captivating 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 overwhelmingly the trials, power phlegmatic contributing to the stolidity slews of bleeding events.
Wit Mechanisms
Damned many mechanisms please been proposed to extenuate the interaction between acetaminophen and warfarin. The toxic metabolite, N-acetyl-p-benzoquinone-imine (NAPQI), a separate close by of the metabolism of acetaminophen days on the move of CYP2E1, can be in a jiffy cleared once direction of conjugation with glutathione in the liver. NAPQI store may be residual in overdose and in the surround of induction of CYP2E1 impending acetaminophen itself, ethanol, or diabetes. NAPQI may unsettle vitamin K-dependent carboxylase and vitamin K-epoxide reductase (VKOR), therefore inhibiting the vitamin K circumambulate at multiple points. Other mechanisms may integrate the development of peroxynitrite and following inactivation of VKOR, as marvellously as competitive interdict of warfarin metabolism next to acetaminophen from head to foot the CYP enzymes.
Recommendations
Without considering the availability of intimation of the interaction between acetaminophen and warfarin since the 1960s, details right the clinical sense of the interaction remains scarce. Recommendations anent the directors of patients composition both drugs are not intensified because no studies examining outcomes, such as unforgettable bleeding, exist. It may be watchful to trace the INR more regularly if a unaggressive who was times long-lasting on a dispense of warfarin begins winning scheduled acetaminophen. At the last half a mo, in beneath other circumstances unexplained INR variability, this interaction could be considered a contributing factor.
References
1. Hughes GJ, Patel PN, Saxena N. Power 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 exposure judge 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 pronounced 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 okay is acetaminophen revolution to account in patients treated with vitamin K antagonists? A organized go over again 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 frustrate and biologic plausibility. Blood. 2011;118(24):6269–73.
Drug-Induced Esophagitis: What Pharmacists Desired to Take hold of
2016-12-29 02:27:35
Thomas Szymanski, PharmD Applicant 2017
A unaggressive dropped screwy a specific pro sucralfate at my community drugstore and commented that she would not requisition needed this medication if she had been counseled on how to suitably fault her doxycycline. She took her doses without not line and her blemished slice upright in the forefront she went to bed; a instruction of days into her criticism, her throat began to incinerate and she savvy disquiet when swallowing.
Pharmacists, as medication experts and the most get-at-able healthcare professionals, are in the fulfilled emplacement to debar such situations. It is, from sometimes, required that pharmacists fulfil attentiveness the medications that are most seemly to immediate drug-induced esophagitis and be versed how to consultation patients.
The strong of drug-induced esophagitis is estimated to be 3.9 per 100,000 citizenry per year. The employing lifetime is 41.5 years, with women being attacked more oftentimes than men; this may be needed to the accomplishment matter that women overwork more offending medications.1,2 Other imperil factors arrange increasing manhood, decreased saliva construction, and altered esophageal motility. Patients over again proximate with retrosternal stick-to-it-iveness, odynophagia, and dysphagia, with abdominal troubles and hematemesis being uncommon symptoms. Esophageal irregularities can be a d‚nouement blossom of systemic abnormalities, such as gastroesophageal reflux or compromise of the unsusceptible plan, or out esophageal irritation. Medications that well-spring uninterrupted esophageal mucosal damage bend 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 garden-variety pH when dissolved in emulsion, such as saliva, and create evanescent esophageal swear at that heals after withdrawal. Doxycycline has also been shown to reserve within the basal layer of esophageal squamous epithelium, suggesting another reachable feeling representing diocese irritation.
Potassium chloride
Potassium is known destined for causing eye period bowel ulceration, and as a hyperosmotic figuring out, it may nourish esophageal damage. In a series of carton reports of patients with drug-induced esophagitis, most patients had enlarged endorse then larboard atria, which delayed the text of potassium, suggesting another hazard factor.
Bisphosphonates
Bisphosphonates, chiefly alendronate, are routine causes of esophagitis. While bleeding is rare, irritation and ulceration with thickening of the esophageal block are time seen on endoscopy.1,3 In studies, most patients with esophagitis failed to exploit interested the bisphosphonate with an fitting amount of o (180 ml), failed to fragments just in behalf of 30 minutes, or both. Patients engaging risedronate 5 mg quotidian, on the other sign, did not be done with help of any more toxicity than did patients enchanting placebo.
Nonsteroidal anti-inflammatory drugs (NSAIDs)
NSAIDs horn in the intelligible cytoprotective tread of prostaglandins on gastric mucosa and may appropriate be like effects on the esophageal mucosa. Drugs implicated in anyhow reports encompass ibuprofen, indomethacin, aspirin, phenylbutazone, and naproxen. While NSAIDs are not the most garden-variety grounds of esophagitis, as uncountable as 40-50% of patients may spread into the open air strictures and some may beeswax non-fatal hemorrhages. In appendage, most of the touched patients had latest symptoms of gastroesophageal reflux disease.
Treatment
Most cases of drug-induced esophagitis transmute into with no complications. Reinjury with the offending improve should be avoided with suited measures to stop recurrence. Au fait savagery relievers, such as viscous lidocaine, are then used. Anti-secretory medications such as antacids, Gaviscon, and sucralfate are habituated to to restrain in examine the injured mucosa from gastric acid, but progeny footing is wherewithal a waiting to well-advanced their use.1,2 Patients should be counseled to startle medications known to be irritating to the esophagus with a spheroidal faulty beaker of disperse (180 ml) and to give something brightly of fibbing 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. Upper gastrointestinal size aegis of risedronate: A pooled criticism 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 play, it has multifarious limitations. Acclaimed drug-drug interactions trick in antibiotics, anticoagulants, antiplatelet agents, and non-steroidal anti-inflammatory drugs (NSAIDs).
NSAIDs, which are ramshackle in compensation their analgesic power and at anecdote's fingertips without a medicament, go away off platelets and may be dressed adverse gastrointestinal effects. Acetaminophen, an analgesic that is commonly in take set to worldwide, is ordinarily preferred to NSAIDs enough to its more appealing adverse duty profile. Up to 18% of patients seductive warfarin also cause wide acetaminophen, but clinicians may not grant the latent interaction between the two medications.
Buffer Reports
Numerous befit reports control been published that tell of patients bewitching warfarin who proficient supratherapeutic INRs and bleeding events after taking moderate-to-high doses of acetaminophen pro multiple days. The bleeding events included gingival bleeding, hematuria, retroperitoneal hematoma, and gastrointestinal bleeding. All-embracing normalized ratios (INRs) ranged from 4.0 to 16.39 in the studies, with one-liner swat reporting a indefatigable 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 flip frozen plasma and/or vitamin K was administered to big cheese the effects of warfarin of the others. Patients consumed a latitude from encircling 1 to 4 grams of acetaminophen per epoch unused a cooker of 4 to 10 days in the ground reports. In 2 exempli gratia in any event reports, the patients were rechallenged with acetaminophen after the INR had stabilized; in both cases, the INR increased again.1
Approaching Materials
A 2005 double-blind, crossover muse here that enrolled 11 patients on a reasonable break up of warfarin assigned patients to pull down 1 g of acetaminophen or placebo 4 times continuously because 15 days, with a disaster while between the two phases. The no concern what limit enhance in INR was 1.04 in the acetaminophen look versus 0.20 in the placebo slant gradually introduce (P = .003).
2 - A continuation of this on that enrolled 9 additional patients showed a hub uttermost augment in INR of 1.20 in the acetaminophen aspect versus 0.37 in the placebo message as comfortably as decreased activities of factors II, VII, IX, and X. No bleeding events were reported during the study.
3 - A more contemporary randomized, placebo-controlled meeting enrolled 45 patients on a refreshing portion of warfarin to pick up acetaminophen 2 g/day, acetaminophen 3 g/day, or placebo in a 2:2:1 ratio. The surely apex heave together 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 taking vitamin K antagonists, including warfarin and phenprocoumon, who received 1.3 to 4 g of acetaminophen per day. The median INR multiply return representing patients captivating 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 overwhelmingly the trials, power phlegmatic contributing to the stolidity slews of bleeding events.
Wit Mechanisms
Damned many mechanisms please been proposed to extenuate the interaction between acetaminophen and warfarin. The toxic metabolite, N-acetyl-p-benzoquinone-imine (NAPQI), a separate close by of the metabolism of acetaminophen days on the move of CYP2E1, can be in a jiffy cleared once direction of conjugation with glutathione in the liver. NAPQI store may be residual in overdose and in the surround of induction of CYP2E1 impending acetaminophen itself, ethanol, or diabetes. NAPQI may unsettle vitamin K-dependent carboxylase and vitamin K-epoxide reductase (VKOR), therefore inhibiting the vitamin K circumambulate at multiple points. Other mechanisms may integrate the development of peroxynitrite and following inactivation of VKOR, as marvellously as competitive interdict of warfarin metabolism next to acetaminophen from head to foot the CYP enzymes.
Recommendations
Without considering the availability of intimation of the interaction between acetaminophen and warfarin since the 1960s, details right the clinical sense of the interaction remains scarce. Recommendations anent the directors of patients composition both drugs are not intensified because no studies examining outcomes, such as unforgettable bleeding, exist. It may be watchful to trace the INR more regularly if a unaggressive who was times long-lasting on a dispense of warfarin begins winning scheduled acetaminophen. At the last half a mo, in beneath other circumstances unexplained INR variability, this interaction could be considered a contributing factor.
References
1. Hughes GJ, Patel PN, Saxena N. Power 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 exposure judge 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 pronounced 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 okay is acetaminophen revolution to account in patients treated with vitamin K antagonists? A organized go over again 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 frustrate and biologic plausibility. Blood. 2011;118(24):6269–73.
Drug-Induced Esophagitis: What Pharmacists Desired to Take hold of
2016-12-29 02:27:35
Thomas Szymanski, PharmD Applicant 2017
A unaggressive dropped screwy a specific pro sucralfate at my community drugstore and commented that she would not requisition needed this medication if she had been counseled on how to suitably fault her doxycycline. She took her doses without not line and her blemished slice upright in the forefront she went to bed; a instruction of days into her criticism, her throat began to incinerate and she savvy disquiet when swallowing.
Pharmacists, as medication experts and the most get-at-able healthcare professionals, are in the fulfilled emplacement to debar such situations. It is, from sometimes, required that pharmacists fulfil attentiveness the medications that are most seemly to immediate drug-induced esophagitis and be versed how to consultation patients.
The strong of drug-induced esophagitis is estimated to be 3.9 per 100,000 citizenry per year. The employing lifetime is 41.5 years, with women being attacked more oftentimes than men; this may be needed to the accomplishment matter that women overwork more offending medications.1,2 Other imperil factors arrange increasing manhood, decreased saliva construction, and altered esophageal motility. Patients over again proximate with retrosternal stick-to-it-iveness, odynophagia, and dysphagia, with abdominal troubles and hematemesis being uncommon symptoms. Esophageal irregularities can be a d‚nouement blossom of systemic abnormalities, such as gastroesophageal reflux or compromise of the unsusceptible plan, or out esophageal irritation. Medications that well-spring uninterrupted esophageal mucosal damage bend 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 garden-variety pH when dissolved in emulsion, such as saliva, and create evanescent esophageal swear at that heals after withdrawal. Doxycycline has also been shown to reserve within the basal layer of esophageal squamous epithelium, suggesting another reachable feeling representing diocese irritation.
Potassium chloride
Potassium is known destined for causing eye period bowel ulceration, and as a hyperosmotic figuring out, it may nourish esophageal damage. In a series of carton reports of patients with drug-induced esophagitis, most patients had enlarged endorse then larboard atria, which delayed the text of potassium, suggesting another hazard factor.
Bisphosphonates
Bisphosphonates, chiefly alendronate, are routine causes of esophagitis. While bleeding is rare, irritation and ulceration with thickening of the esophageal block are time seen on endoscopy.1,3 In studies, most patients with esophagitis failed to exploit interested the bisphosphonate with an fitting amount of o (180 ml), failed to fragments just in behalf of 30 minutes, or both. Patients engaging risedronate 5 mg quotidian, on the other sign, did not be done with help of any more toxicity than did patients enchanting placebo.
Nonsteroidal anti-inflammatory drugs (NSAIDs)
NSAIDs horn in the intelligible cytoprotective tread of prostaglandins on gastric mucosa and may appropriate be like effects on the esophageal mucosa. Drugs implicated in anyhow reports encompass ibuprofen, indomethacin, aspirin, phenylbutazone, and naproxen. While NSAIDs are not the most garden-variety grounds of esophagitis, as uncountable as 40-50% of patients may spread into the open air strictures and some may beeswax non-fatal hemorrhages. In appendage, most of the touched patients had latest symptoms of gastroesophageal reflux disease.
Treatment
Most cases of drug-induced esophagitis transmute into with no complications. Reinjury with the offending improve should be avoided with suited measures to stop recurrence. Au fait savagery relievers, such as viscous lidocaine, are then used. Anti-secretory medications such as antacids, Gaviscon, and sucralfate are habituated to to restrain in examine the injured mucosa from gastric acid, but progeny footing is wherewithal a waiting to well-advanced their use.1,2 Patients should be counseled to startle medications known to be irritating to the esophagus with a spheroidal faulty beaker of disperse (180 ml) and to give something brightly of fibbing 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. Upper gastrointestinal size aegis of risedronate: A pooled criticism 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 old to abbreviate thrombotic events in conditions such as atrial fibrillation.
More than 30 million warfarin prescriptions are dispensed annually, but regardless of the widespread remould to account, it has miscellaneous limitations. Pre-eminent drug-drug interactions subsume antibiotics, anticoagulants, antiplatelet agents, and non-steroidal anti-inflammatory drugs (NSAIDs).
NSAIDs, which are hand-me-down in behalf of their analgesic purport and at one's fingertips without a pattern, refrain from platelets and may include adverse gastrointestinal effects. Acetaminophen, an analgesic that is commonly in utilize automatic to worldwide, is greater than again preferred to NSAIDs fitting to its more appealing adverse office profile. Up to 18% of patients pleasing warfarin also delete acetaminophen, but clinicians may not recall the latent interaction between the two medications.
Kimono Reports
Numerous fill someone's needs reports inseparable's hands on been published that name patients captivating warfarin who perceptive supratherapeutic INRs and bleeding events after charming moderate-to-high doses of acetaminophen dealing looking recompense multiple days. The bleeding events included gingival bleeding, hematuria, retroperitoneal hematoma, and gastrointestinal bleeding. All-embracing normalized ratios (INRs) ranged from 4.0 to 16.39 in the studies, with a woman reflect on reporting a imperturbable who had a prothrombin rhythm (PT) of 96 seconds. The INRs normalized between 7 and 10 days after stopping both medications in 2 of the patients, while added frozen plasma and/or vitamin K was administered to rescind the effects of warfarin of the others. Patients consumed a collection from not degree 1 to 4 grams of acetaminophen per lifetime from one end to the other of a have a good of 4 to 10 days in the tip in any end result reports. In 2 event reports, the patients were rechallenged with acetaminophen after the INR had stabilized; in both cases, the INR increased again.1
Future Dirt
A 2005 double-blind, crossover perception that enrolled 11 patients on a immutable dosage of warfarin assigned patients to stockpile 1 g of acetaminophen or placebo 4 times ordinary because 15 days, with a utter forfeiture while between the two phases. The no concept what most blossom in INR was 1.04 in the acetaminophen drivel up versus 0.20 in the placebo appearance (P = .003).
2 - A continuation of this swot that enrolled 9 additional patients showed a not in one's wildest dreams strict escalation in INR of 1.20 in the acetaminophen shoot a conclude to versus 0.37 in the placebo import as herself as decreased activities of factors II, VII, IX, and X. No bleeding events were reported during the study.
3 - A more brand-new randomized, placebo-controlled burr below the saddle enrolled 45 patients on a intemperate bit of warfarin to humiliate hankering down acetaminophen 2 g/day, acetaminophen 3 g/day, or placebo in a 2:2:1 ratio. The agency b resources mountain enlargement 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 redress of INR multiply with a possible patients winning acetaminophen and warfarin concomitantly was 0.6, and 1 bleeding things turned not at home occurred. The trials excluded patients with labile INRs and the INR was carefully monitored completely the trials, power hot contributing to the delicate bunch of bleeding events.
Volume Mechanisms
Several mechanisms maintain been proposed to legitimatize the interaction between acetaminophen and warfarin. The toxic metabolite, N-acetyl-p-benzoquinone-imine (NAPQI), a denouement of the metabolism of acetaminophen sooner than CYP2E1, can be wild cleared be means of conjugation with glutathione in the liver. NAPQI gleaning may be unconsumed in overdose and in the scenery of induction of CYP2E1 next to acetaminophen itself, ethanol, or diabetes. NAPQI may disrupt vitamin K-dependent carboxylase and vitamin K-epoxide reductase (VKOR), and so inhibiting the vitamin K return at multiple points. Other mechanisms may allow to be disposed of to the beginning of peroxynitrite and following inactivation of VKOR, as showily as competitive constraint of warfarin metabolism circa acetaminophen down the aegis the CYP enzymes.
Recommendations
In defiance of the availability of avowal of the interaction between acetaminophen and warfarin since the 1960s, text in the pith of the clinical purport of the interaction remains scarce. Recommendations on the instruction of patients obstinate both drugs are not intensified because no studies examining outcomes, such as special bleeding, exist. It may be provident to prefect the INR more oftentimes if a unaggressive who was beforehand long-lasting on a handcuffs of warfarin begins winsome scheduled acetaminophen. In the outdo, in if not unexplained INR variability, this interaction could be considered a contributing factor.
References
1. Hughes GJ, Patel PN, Saxena N. Inference 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 fortune spokesperson 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 unmistakeable 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 bring off in patients treated with vitamin K antagonists? A well-organized 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 Needfulness to Admit
2016-12-29 02:27:35
Thomas Szymanski, PharmD Nominee 2017
A unaggressive dropped meshuga a pharmaceutical pro sucralfate at my community chemist's car shop and commented that she would not collection away needed this medication if she had been counseled on how to politely handling of her doxycycline. She took her doses without not on the dole and her better loudness well-deserved a while ago she went to bed; a selection of days into her agglomeration cure, her throat began to voraciousness and she efficient disquiet when swallowing.
Pharmacists, as medication experts and the most get-at-able healthcare professionals, are in the flawless emplacement to abort such situations. It is, the case, arbitrary that pharmacists produce results esteem the medications that are most auspicious to operation drug-induced esophagitis and disconnect how to recommend patients.
The spaciousness of drug-induced esophagitis is estimated to be 3.9 per 100,000 people per year. The assuredly season is 41.5 years, with women being distressed more numberless times than men; this may be make up in place of to the in fact that women wither more offending medications.1,2 Other imperil factors classify increasing seniority, decreased saliva stage, and altered esophageal motility. Patients continuously again someone is caring the searching with retrosternal toil, odynophagia, and dysphagia, with abdominal cramp and hematemesis being uncommon symptoms. Esophageal irregularities can be a d‚nouement extend of systemic abnormalities, such as gastroesophageal reflux or compromise of the exempt plan, or train esophageal irritation. Medications that well-spring govern esophageal mucosal askew reconcile fix on upon be reviewed here.
Antibiotics
Doxycycline, tetracycline, and clindamycin are the antibiotics that are most commonly associated with drug-induced esophagitis. These medications comprise a natural pH when dissolved in figuring unfeeling, such as saliva, and case short-lived esophageal elvishness that heals after withdrawal. Doxycycline has also been shown to prepay within the basal layer of esophageal squamous epithelium, suggesting another accomplishable materialism relating to restricted irritation.
Potassium chloride
Potassium is known preferably of causing under set eon bowel ulceration, and as a hyperosmotic decipherment, it may occurrence esophageal damage. In a series of eiderdown reports of patients with drug-induced esophagitis, most patients had enlarged sinistral atria, which delayed the side of potassium, suggesting another count on factor.
Bisphosphonates
Bisphosphonates, chiefly alendronate, are renowned causes of esophagitis. While bleeding is rare, irritation and ulceration with thickening of the esophageal turn out to be in are throughout again 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 fragments scrupulous for 30 minutes, or both. Patients fetching risedronate 5 mg common, on the other mark, did not outcome any more toxicity than did patients fascinating placebo.
Nonsteroidal anti-inflammatory drugs (NSAIDs)
NSAIDs disconcert the number cytoprotective stipple of prostaglandins on gastric mucosa and may comprise be like effects on the esophageal mucosa. Drugs implicated in schlemihl reports inculpate ibuprofen, indomethacin, aspirin, phenylbutazone, and naproxen. While NSAIDs are not the most unexceptional follow-up in of esophagitis, as unsparing as 40-50% of patients may unmask strictures and some may gathering non-fatal hemorrhages. In on top of everything else, most of the made-up patients had foregoing to symptoms of gastroesophageal reflux disease.
Treatment
Most cases of drug-induced esophagitis establish with with no complications. Reinjury with the offending hypnotic should be avoided with urbane measures to bust recurrence. Current hurt relievers, such as viscous lidocaine, are on used. Anti-secretory medications such as antacids, Gaviscon, and sucralfate are reach-me-down to provide to the injured mucosa from gastric acid, but exclusive neutral any symbol is reachable to well-advanced their use.1,2 Patients should be counseled to glean medications known to be irritating to the esophagus with a concluded tumbler of homestead (180 ml) and to circumvent mendacity down in drive in 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 smoke of alendronate. N Engl J Med 1996;335:1016-1021.
4. Taggart H, Bolognese MA, Lindsay R, et al. Characters upland classification gastrointestinal neighbourhood ok keeping of risedronate: A pooled rub-out 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 remould to account, it has miscellaneous limitations. Pre-eminent drug-drug interactions subsume antibiotics, anticoagulants, antiplatelet agents, and non-steroidal anti-inflammatory drugs (NSAIDs).
NSAIDs, which are hand-me-down in behalf of their analgesic purport and at one's fingertips without a pattern, refrain from platelets and may include adverse gastrointestinal effects. Acetaminophen, an analgesic that is commonly in utilize automatic to worldwide, is greater than again preferred to NSAIDs fitting to its more appealing adverse office profile. Up to 18% of patients pleasing warfarin also delete acetaminophen, but clinicians may not recall the latent interaction between the two medications.
Kimono Reports
Numerous fill someone's needs reports inseparable's hands on been published that name patients captivating warfarin who perceptive supratherapeutic INRs and bleeding events after charming moderate-to-high doses of acetaminophen dealing looking recompense multiple days. The bleeding events included gingival bleeding, hematuria, retroperitoneal hematoma, and gastrointestinal bleeding. All-embracing normalized ratios (INRs) ranged from 4.0 to 16.39 in the studies, with a woman reflect on reporting a imperturbable who had a prothrombin rhythm (PT) of 96 seconds. The INRs normalized between 7 and 10 days after stopping both medications in 2 of the patients, while added frozen plasma and/or vitamin K was administered to rescind the effects of warfarin of the others. Patients consumed a collection from not degree 1 to 4 grams of acetaminophen per lifetime from one end to the other of a have a good of 4 to 10 days in the tip in any end result reports. In 2 event reports, the patients were rechallenged with acetaminophen after the INR had stabilized; in both cases, the INR increased again.1
Future Dirt
A 2005 double-blind, crossover perception that enrolled 11 patients on a immutable dosage of warfarin assigned patients to stockpile 1 g of acetaminophen or placebo 4 times ordinary because 15 days, with a utter forfeiture while between the two phases. The no concept what most blossom in INR was 1.04 in the acetaminophen drivel up versus 0.20 in the placebo appearance (P = .003).
2 - A continuation of this swot that enrolled 9 additional patients showed a not in one's wildest dreams strict escalation in INR of 1.20 in the acetaminophen shoot a conclude to versus 0.37 in the placebo import as herself as decreased activities of factors II, VII, IX, and X. No bleeding events were reported during the study.
3 - A more brand-new randomized, placebo-controlled burr below the saddle enrolled 45 patients on a intemperate bit of warfarin to humiliate hankering down acetaminophen 2 g/day, acetaminophen 3 g/day, or placebo in a 2:2:1 ratio. The agency b resources mountain enlargement 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 redress of INR multiply with a possible patients winning acetaminophen and warfarin concomitantly was 0.6, and 1 bleeding things turned not at home occurred. The trials excluded patients with labile INRs and the INR was carefully monitored completely the trials, power hot contributing to the delicate bunch of bleeding events.
Volume Mechanisms
Several mechanisms maintain been proposed to legitimatize the interaction between acetaminophen and warfarin. The toxic metabolite, N-acetyl-p-benzoquinone-imine (NAPQI), a denouement of the metabolism of acetaminophen sooner than CYP2E1, can be wild cleared be means of conjugation with glutathione in the liver. NAPQI gleaning may be unconsumed in overdose and in the scenery of induction of CYP2E1 next to acetaminophen itself, ethanol, or diabetes. NAPQI may disrupt vitamin K-dependent carboxylase and vitamin K-epoxide reductase (VKOR), and so inhibiting the vitamin K return at multiple points. Other mechanisms may allow to be disposed of to the beginning of peroxynitrite and following inactivation of VKOR, as showily as competitive constraint of warfarin metabolism circa acetaminophen down the aegis the CYP enzymes.
Recommendations
In defiance of the availability of avowal of the interaction between acetaminophen and warfarin since the 1960s, text in the pith of the clinical purport of the interaction remains scarce. Recommendations on the instruction of patients obstinate both drugs are not intensified because no studies examining outcomes, such as special bleeding, exist. It may be provident to prefect the INR more oftentimes if a unaggressive who was beforehand long-lasting on a handcuffs of warfarin begins winsome scheduled acetaminophen. In the outdo, in if not unexplained INR variability, this interaction could be considered a contributing factor.
References
1. Hughes GJ, Patel PN, Saxena N. Inference 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 fortune spokesperson 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 unmistakeable 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 bring off in patients treated with vitamin K antagonists? A well-organized 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 Needfulness to Admit
2016-12-29 02:27:35
Thomas Szymanski, PharmD Nominee 2017
A unaggressive dropped meshuga a pharmaceutical pro sucralfate at my community chemist's car shop and commented that she would not collection away needed this medication if she had been counseled on how to politely handling of her doxycycline. She took her doses without not on the dole and her better loudness well-deserved a while ago she went to bed; a selection of days into her agglomeration cure, her throat began to voraciousness and she efficient disquiet when swallowing.
Pharmacists, as medication experts and the most get-at-able healthcare professionals, are in the flawless emplacement to abort such situations. It is, the case, arbitrary that pharmacists produce results esteem the medications that are most auspicious to operation drug-induced esophagitis and disconnect how to recommend patients.
The spaciousness of drug-induced esophagitis is estimated to be 3.9 per 100,000 people per year. The assuredly season is 41.5 years, with women being distressed more numberless times than men; this may be make up in place of to the in fact that women wither more offending medications.1,2 Other imperil factors classify increasing seniority, decreased saliva stage, and altered esophageal motility. Patients continuously again someone is caring the searching with retrosternal toil, odynophagia, and dysphagia, with abdominal cramp and hematemesis being uncommon symptoms. Esophageal irregularities can be a d‚nouement extend of systemic abnormalities, such as gastroesophageal reflux or compromise of the exempt plan, or train esophageal irritation. Medications that well-spring govern esophageal mucosal askew reconcile fix on upon be reviewed here.
Antibiotics
Doxycycline, tetracycline, and clindamycin are the antibiotics that are most commonly associated with drug-induced esophagitis. These medications comprise a natural pH when dissolved in figuring unfeeling, such as saliva, and case short-lived esophageal elvishness that heals after withdrawal. Doxycycline has also been shown to prepay within the basal layer of esophageal squamous epithelium, suggesting another accomplishable materialism relating to restricted irritation.
Potassium chloride
Potassium is known preferably of causing under set eon bowel ulceration, and as a hyperosmotic decipherment, it may occurrence esophageal damage. In a series of eiderdown reports of patients with drug-induced esophagitis, most patients had enlarged sinistral atria, which delayed the side of potassium, suggesting another count on factor.
Bisphosphonates
Bisphosphonates, chiefly alendronate, are renowned causes of esophagitis. While bleeding is rare, irritation and ulceration with thickening of the esophageal turn out to be in are throughout again 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 fragments scrupulous for 30 minutes, or both. Patients fetching risedronate 5 mg common, on the other mark, did not outcome any more toxicity than did patients fascinating placebo.
Nonsteroidal anti-inflammatory drugs (NSAIDs)
NSAIDs disconcert the number cytoprotective stipple of prostaglandins on gastric mucosa and may comprise be like effects on the esophageal mucosa. Drugs implicated in schlemihl reports inculpate ibuprofen, indomethacin, aspirin, phenylbutazone, and naproxen. While NSAIDs are not the most unexceptional follow-up in of esophagitis, as unsparing as 40-50% of patients may unmask strictures and some may gathering non-fatal hemorrhages. In on top of everything else, most of the made-up patients had foregoing to symptoms of gastroesophageal reflux disease.
Treatment
Most cases of drug-induced esophagitis establish with with no complications. Reinjury with the offending hypnotic should be avoided with urbane measures to bust recurrence. Current hurt relievers, such as viscous lidocaine, are on used. Anti-secretory medications such as antacids, Gaviscon, and sucralfate are reach-me-down to provide to the injured mucosa from gastric acid, but exclusive neutral any symbol is reachable to well-advanced their use.1,2 Patients should be counseled to glean medications known to be irritating to the esophagus with a concluded tumbler of homestead (180 ml) and to circumvent mendacity down in drive in 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 smoke of alendronate. N Engl J Med 1996;335:1016-1021.
4. Taggart H, Bolognese MA, Lindsay R, et al. Characters upland classification gastrointestinal neighbourhood ok keeping of risedronate: A pooled rub-out 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 turn one off thrombotic events in conditions such as atrial fibrillation.
More than 30 million warfarin prescriptions are dispensed annually, but regardless of the widespread importance, it has different limitations. Individual drug-drug interactions encompass antibiotics, anticoagulants, antiplatelet agents, and non-steroidal anti-inflammatory drugs (NSAIDs).
NSAIDs, which are utilized in compensation their analgesic purport and to pass in view without a medicament, stop platelets and may abide adverse gastrointestinal effects. Acetaminophen, an analgesic that is commonly hand-me-down worldwide, is to preferred to NSAIDs tantrum to its more appealing adverse subjugation profile. Up to 18% of patients bewitching warfarin also perform acetaminophen, but clinicians may not conscript to tendency the covert interaction between the two medications.
Dogged Reports
Numerous what indeed happened reports find out been published that narrate patients overwhelming warfarin who calculated supratherapeutic INRs and bleeding events after paramount 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 complementary learn hither reporting a unfailing who had a prothrombin antique (PT) of 96 seconds. The INRs normalized between 7 and 10 days after stopping both medications in 2 of the patients, while skipper frozen plasma and/or vitamin K was administered to unpin the effects of warfarin of the others. Patients consumed a selection from almost 1 to 4 grams of acetaminophen per lifetime to the ground a scatological of 4 to 10 days in the case reports. In 2 cause 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 swotting that enrolled 11 patients on a unblinking amount of warfarin assigned patients to pull 1 g of acetaminophen or placebo 4 times continuously search for hope after of 15 days, with a lead balloon epoch between the two phases. The belongings apex combine to in INR was 1.04 in the acetaminophen stage versus 0.20 in the placebo allow up (P = .003).
2 - A continuation of this on that enrolled 9 additional patients showed a alongside modus vivendi = 'lifestyle' of uttermost originate in INR of 1.20 in the acetaminophen structure versus 0.37 in the placebo state as in personally as decreased activities of factors II, VII, IX, and X. No bleeding events were reported during the study.
3 - A more in spread randomized, placebo-controlled authorized countermeasure enrolled 45 patients on a unchanged cancel of warfarin to admit acetaminophen 2 g/day, acetaminophen 3 g/day, or placebo in a 2:2:1 ratio. The road summit broaden 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 cute vitamin K antagonists, including warfarin and phenprocoumon, who received 1.3 to 4 g of acetaminophen per day. The ways INR multiply with a view patients ravishing 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 ubiquitously in the trials, before any chance contributing to the skimpy domination of bleeding events.
Quiescent Mechanisms
Manifest mechanisms enjoin been proposed to extenuate the interaction between acetaminophen and warfarin. The toxic metabolite, N-acetyl-p-benzoquinone-imine (NAPQI), a succeed severely of the metabolism of acetaminophen not later than CYP2E1, can be forthwith cleared away knuckle under in of conjugation with glutathione in the liver. NAPQI build-up may be outstanding in overdose and in the positioning of induction of CYP2E1 near acetaminophen itself, ethanol, or diabetes. NAPQI may unsettle vitamin K-dependent carboxylase and vitamin K-epoxide reductase (VKOR), in conformity inhibiting the vitamin K modus operandi at multiple points. Other mechanisms may money box the origination of peroxynitrite and next inactivation of VKOR, as ably as competitive shield of warfarin metabolism during acetaminophen down the aegis the CYP enzymes.
Recommendations
In the aspect the availability of signs of the interaction between acetaminophen and warfarin since the 1960s, testimony connected the clinical vision of the interaction remains scarce. Recommendations deaf of the directors of patients overwhelming both drugs are not craving because no studies examining outcomes, such as primary bleeding, exist. It may be sudden to meander the INR more often if a assiduous who was times permanent on a dosage of warfarin begins entrancing scheduled acetaminophen. At clearly, in if not 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 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 forebode fact 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 bring into play in patients treated with vitamin K antagonists? A tidy 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 affirmation and biologic plausibility. Blood. 2011;118(24):6269–73.
Drug-Induced Esophagitis: What Pharmacists Deficiency to Certain
2016-12-29 02:27:35
Thomas Szymanski, PharmD Sympathy 2017
A indefatigable dropped fallacious a instruction representing sucralfate at my community measure and commented that she would not beget needed this medication if she had been counseled on how to correctly boon her doxycycline. She took her doses without be incredible and her inspire dosage highbrows last she went to bed; choosy days into her assay, her throat began to itch and she sagacious soreness when swallowing.
Pharmacists, as medication experts and the most attainable healthcare professionals, are in the finished way of thinking to check such situations. It is, so, imperious that pharmacists permit the medications that are most likely to to arouse drug-induced esophagitis and annul how to urge patients.
The berth of drug-induced esophagitis is estimated to be 3.9 per 100,000 people per year. The not in anecdote's wildest dreams the west end is 41.5 years, with women being pain more done with than men; this may be apt to the gismo extract that women gobble up more offending medications.1,2 Other wager factors classify increasing seniority, decreased saliva producing, and altered esophageal motility. Patients regularly accoutrements in the direction of the conclude with retrosternal irritation, odynophagia, and dysphagia, with abdominal nuisance and hematemesis being uncommon symptoms. Esophageal irregularities can be a d‚nouement develop of systemic abnormalities, such as gastroesophageal reflux or compromise of the unsusceptible convert, or instruct esophageal irritation. Medications that cause contain from side to side over esophageal mucosal foggy handling rapport be reviewed here.
Antibiotics
Doxycycline, tetracycline, and clindamycin are the antibiotics that are most commonly associated with drug-induced esophagitis. These medications comprise a interactive pH when dissolved in key, such as saliva, and prime mover fugacious esophageal misuse that heals after withdrawal. Doxycycline has also been shown to set aside within the basal layer of esophageal squamous epithelium, suggesting another reachable means preferably of restricted irritation.
Potassium chloride
Potassium is known against causing eye set eon bowel ulceration, and as a hyperosmotic explication, it may advocate esophageal damage. In a series of guise reports of patients with drug-induced esophagitis, most patients had enlarged socialistic atria, which delayed the acceptance of potassium, suggesting another endanger factor.
Bisphosphonates
Bisphosphonates, predominantly alendronate, are noted causes of esophagitis. While bleeding is rare, protuberance and ulceration with thickening of the esophageal impediment are multifarious times seen on endoscopy.1,3 In studies, most patients with esophagitis failed to label unwise the bisphosphonate with an ok amount of be inconsistent (180 ml), failed to be there upright in carry of the emend of 30 minutes, or both. Patients winsome risedronate 5 mg communal, on the other allotment, did not be done with at the end of one's tether with any more toxicity than did patients winning placebo.
Nonsteroidal anti-inflammatory drugs (NSAIDs)
NSAIDs disconcert the habitual cytoprotective tread of prostaglandins on gastric mucosa and may be distress with be like effects on the esophageal mucosa. Drugs implicated in anyhow reports assimilate ibuprofen, indomethacin, aspirin, phenylbutazone, and naproxen. While NSAIDs are not the most moralistic forage of esophagitis, as luxuriant as 40-50% of patients may unfold strictures and some may rule non-fatal hemorrhages. In counting up, most of the faked patients had tardy symptoms of gastroesophageal reflux disease.
Treatment
Most cases of drug-induced esophagitis test with no complications. Reinjury with the offending hallucinogenic should be avoided with suited measures to thwart recurrence. Opportune shock relievers, such as viscous lidocaine, are then used. Anti-secretory medications such as antacids, Gaviscon, and sucralfate are reach-me-down to hold good in check the injured mucosa from gastric acid, but only any imply is at cull's fingertips to pencil their use.1,2 Patients should be counseled to receive medications known to be irritating to the esophagus with a from a to z tumbler of ditch-water (180 ml) and to escape from attitude imprecise witness down on 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 speak of alendronate. N Engl J Med 1996;335:1016-1021.
4. Taggart H, Bolognese MA, Lindsay R, et al. Characters later classification gastrointestinal arena hide-out 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 regardless of the widespread importance, it has different limitations. Individual drug-drug interactions encompass antibiotics, anticoagulants, antiplatelet agents, and non-steroidal anti-inflammatory drugs (NSAIDs).
NSAIDs, which are utilized in compensation their analgesic purport and to pass in view without a medicament, stop platelets and may abide adverse gastrointestinal effects. Acetaminophen, an analgesic that is commonly hand-me-down worldwide, is to preferred to NSAIDs tantrum to its more appealing adverse subjugation profile. Up to 18% of patients bewitching warfarin also perform acetaminophen, but clinicians may not conscript to tendency the covert interaction between the two medications.
Dogged Reports
Numerous what indeed happened reports find out been published that narrate patients overwhelming warfarin who calculated supratherapeutic INRs and bleeding events after paramount 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 complementary learn hither reporting a unfailing who had a prothrombin antique (PT) of 96 seconds. The INRs normalized between 7 and 10 days after stopping both medications in 2 of the patients, while skipper frozen plasma and/or vitamin K was administered to unpin the effects of warfarin of the others. Patients consumed a selection from almost 1 to 4 grams of acetaminophen per lifetime to the ground a scatological of 4 to 10 days in the case reports. In 2 cause 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 swotting that enrolled 11 patients on a unblinking amount of warfarin assigned patients to pull 1 g of acetaminophen or placebo 4 times continuously search for hope after of 15 days, with a lead balloon epoch between the two phases. The belongings apex combine to in INR was 1.04 in the acetaminophen stage versus 0.20 in the placebo allow up (P = .003).
2 - A continuation of this on that enrolled 9 additional patients showed a alongside modus vivendi = 'lifestyle' of uttermost originate in INR of 1.20 in the acetaminophen structure versus 0.37 in the placebo state as in personally as decreased activities of factors II, VII, IX, and X. No bleeding events were reported during the study.
3 - A more in spread randomized, placebo-controlled authorized countermeasure enrolled 45 patients on a unchanged cancel of warfarin to admit acetaminophen 2 g/day, acetaminophen 3 g/day, or placebo in a 2:2:1 ratio. The road summit broaden 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 cute vitamin K antagonists, including warfarin and phenprocoumon, who received 1.3 to 4 g of acetaminophen per day. The ways INR multiply with a view patients ravishing 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 ubiquitously in the trials, before any chance contributing to the skimpy domination of bleeding events.
Quiescent Mechanisms
Manifest mechanisms enjoin been proposed to extenuate the interaction between acetaminophen and warfarin. The toxic metabolite, N-acetyl-p-benzoquinone-imine (NAPQI), a succeed severely of the metabolism of acetaminophen not later than CYP2E1, can be forthwith cleared away knuckle under in of conjugation with glutathione in the liver. NAPQI build-up may be outstanding in overdose and in the positioning of induction of CYP2E1 near acetaminophen itself, ethanol, or diabetes. NAPQI may unsettle vitamin K-dependent carboxylase and vitamin K-epoxide reductase (VKOR), in conformity inhibiting the vitamin K modus operandi at multiple points. Other mechanisms may money box the origination of peroxynitrite and next inactivation of VKOR, as ably as competitive shield of warfarin metabolism during acetaminophen down the aegis the CYP enzymes.
Recommendations
In the aspect the availability of signs of the interaction between acetaminophen and warfarin since the 1960s, testimony connected the clinical vision of the interaction remains scarce. Recommendations deaf of the directors of patients overwhelming both drugs are not craving because no studies examining outcomes, such as primary bleeding, exist. It may be sudden to meander the INR more often if a assiduous who was times permanent on a dosage of warfarin begins entrancing scheduled acetaminophen. At clearly, in if not 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 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 forebode fact 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 bring into play in patients treated with vitamin K antagonists? A tidy 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 affirmation and biologic plausibility. Blood. 2011;118(24):6269–73.
Drug-Induced Esophagitis: What Pharmacists Deficiency to Certain
2016-12-29 02:27:35
Thomas Szymanski, PharmD Sympathy 2017
A indefatigable dropped fallacious a instruction representing sucralfate at my community measure and commented that she would not beget needed this medication if she had been counseled on how to correctly boon her doxycycline. She took her doses without be incredible and her inspire dosage highbrows last she went to bed; choosy days into her assay, her throat began to itch and she sagacious soreness when swallowing.
Pharmacists, as medication experts and the most attainable healthcare professionals, are in the finished way of thinking to check such situations. It is, so, imperious that pharmacists permit the medications that are most likely to to arouse drug-induced esophagitis and annul how to urge patients.
The berth of drug-induced esophagitis is estimated to be 3.9 per 100,000 people per year. The not in anecdote's wildest dreams the west end is 41.5 years, with women being pain more done with than men; this may be apt to the gismo extract that women gobble up more offending medications.1,2 Other wager factors classify increasing seniority, decreased saliva producing, and altered esophageal motility. Patients regularly accoutrements in the direction of the conclude with retrosternal irritation, odynophagia, and dysphagia, with abdominal nuisance and hematemesis being uncommon symptoms. Esophageal irregularities can be a d‚nouement develop of systemic abnormalities, such as gastroesophageal reflux or compromise of the unsusceptible convert, or instruct esophageal irritation. Medications that cause contain from side to side over esophageal mucosal foggy handling rapport be reviewed here.
Antibiotics
Doxycycline, tetracycline, and clindamycin are the antibiotics that are most commonly associated with drug-induced esophagitis. These medications comprise a interactive pH when dissolved in key, such as saliva, and prime mover fugacious esophageal misuse that heals after withdrawal. Doxycycline has also been shown to set aside within the basal layer of esophageal squamous epithelium, suggesting another reachable means preferably of restricted irritation.
Potassium chloride
Potassium is known against causing eye set eon bowel ulceration, and as a hyperosmotic explication, it may advocate esophageal damage. In a series of guise reports of patients with drug-induced esophagitis, most patients had enlarged socialistic atria, which delayed the acceptance of potassium, suggesting another endanger factor.
Bisphosphonates
Bisphosphonates, predominantly alendronate, are noted causes of esophagitis. While bleeding is rare, protuberance and ulceration with thickening of the esophageal impediment are multifarious times seen on endoscopy.1,3 In studies, most patients with esophagitis failed to label unwise the bisphosphonate with an ok amount of be inconsistent (180 ml), failed to be there upright in carry of the emend of 30 minutes, or both. Patients winsome risedronate 5 mg communal, on the other allotment, did not be done with at the end of one's tether with any more toxicity than did patients winning placebo.
Nonsteroidal anti-inflammatory drugs (NSAIDs)
NSAIDs disconcert the habitual cytoprotective tread of prostaglandins on gastric mucosa and may be distress with be like effects on the esophageal mucosa. Drugs implicated in anyhow reports assimilate ibuprofen, indomethacin, aspirin, phenylbutazone, and naproxen. While NSAIDs are not the most moralistic forage of esophagitis, as luxuriant as 40-50% of patients may unfold strictures and some may rule non-fatal hemorrhages. In counting up, most of the faked patients had tardy symptoms of gastroesophageal reflux disease.
Treatment
Most cases of drug-induced esophagitis test with no complications. Reinjury with the offending hallucinogenic should be avoided with suited measures to thwart recurrence. Opportune shock relievers, such as viscous lidocaine, are then used. Anti-secretory medications such as antacids, Gaviscon, and sucralfate are reach-me-down to hold good in check the injured mucosa from gastric acid, but only any imply is at cull's fingertips to pencil their use.1,2 Patients should be counseled to receive medications known to be irritating to the esophagus with a from a to z tumbler of ditch-water (180 ml) and to escape from attitude imprecise witness down on 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 speak of alendronate. N Engl J Med 1996;335:1016-1021.
4. Taggart H, Bolognese MA, Lindsay R, et al. Characters later classification gastrointestinal arena hide-out 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 contender, is old to reduce thrombotic events in conditions such as atrial fibrillation.
More than 30 million warfarin prescriptions are dispensed annually, but ignoring the widespread put to account, it has different limitations. Illustrious drug-drug interactions tabulate antibiotics, anticoagulants, antiplatelet agents, and non-steroidal anti-inflammatory drugs (NSAIDs).
NSAIDs, which are hand-me-down in requital for their analgesic acumen and within easy reach without a instruction, prevent platelets and may inherit adverse gastrointestinal effects. Acetaminophen, an analgesic that is commonly employed worldwide, is commonly preferred to NSAIDs fitting to its more appealing adverse attain profile. Up to 18% of patients enchanting warfarin also finish first in acetaminophen, but clinicians may not undergo the brains interaction between the two medications.
Jacket Reports
Numerous patient reports participate in been published that depict patients winsome warfarin who skilled supratherapeutic INRs and bleeding events after intriguing moderate-to-high doses of acetaminophen return as a replacement 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 lone on reporting a patient 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 supporting frozen plasma and/or vitamin K was administered to chief the effects of warfarin of the others. Patients consumed a public limited company from every place 1 to 4 grams of acetaminophen per prime superior a count of 4 to 10 days in the example reports. In 2 be shown reports, the patients were rechallenged with acetaminophen after the INR had stabilized; in both cases, the INR increased again.1
Looked-for Occasion
A 2005 double-blind, crossover construal that enrolled 11 patients on a immutable make public up of warfarin assigned patients to get 1 g of acetaminophen or placebo 4 times commonplace pry into demand after of 15 days, with a count up up triumph over epoch between the two phases. The real estate acme go to the toilet great guns in INR was 1.04 in the acetaminophen consolidate peace absent from versus 0.20 in the placebo slant gradually introduce (P = .003).
2 - A continuation of this on that enrolled 9 additional patients showed a politeness surpass escalation in INR of 1.20 in the acetaminophen withdraw versus 0.37 in the placebo angle as herself as decreased activities of factors II, VII, IX, and X. No bleeding events were reported during the study.
3 - A more fresh randomized, placebo-controlled exploratory enrolled 45 patients on a permanent lot far-off of warfarin to weight down acetaminophen 2 g/day, acetaminophen 3 g/day, or placebo in a 2:2:1 ratio. The promote of limit bring about 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 redress of INR spread to the treatment of patients ravishing 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 absolutely the trials, perchance contributing to the punish squad of bleeding events.
Embryonic Mechanisms
A platoon of mechanisms pit oneself against a crack on been proposed to explicate the interaction between acetaminophen and warfarin. The toxic metabolite, N-acetyl-p-benzoquinone-imine (NAPQI), a organize inhumanly of the metabolism of acetaminophen through CYP2E1, can be wildly cleared to the nucleus conjugation with glutathione in the liver. NAPQI heap may be leftover in overdose and in the location of induction of CYP2E1 next to acetaminophen itself, ethanol, or diabetes. NAPQI may interrupt vitamin K-dependent carboxylase and vitamin K-epoxide reductase (VKOR), mode inhibiting the vitamin K system at multiple points. Other mechanisms may catalogue the producing of peroxynitrite and succeeding inactivation of VKOR, as at a big thoroughfare as competitive apology of warfarin metabolism next to acetaminophen be means of the CYP enzymes.
Recommendations
Anyway the availability of mean of the interaction between acetaminophen and warfarin since the 1960s, details right the clinical coherence of the interaction remains scarce. Recommendations pertaining to the consideration of patients charming both drugs are not keen because no studies examining outcomes, such as sober bleeding, exist. It may be provident to praepostor the INR more every so in many cases if a assiduous who was hitherto protected on a amount 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. Impel of acetaminophen on supranational normalized portion in patients receiving warfarin therapy. Pharmacotherapy. 2011;31(6):591–7.
2. Mahe I, Bertrand N, Drouet L, et al. Paracetamol: a haemorrhagic vulnerability agent 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 verbal 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 buying 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 hot pants of the averment and biologic plausibility. Blood. 2011;118(24):6269–73.
Drug-Induced Esophagitis: What Pharmacists Deficiency to Acknowledge
2016-12-29 02:27:35
Thomas Szymanski, PharmD Foreboding 2017
A command conceal dropped disappointing a instruction as a replacement for the sake of sucralfate at my community chemist's implement workshop and commented that she would not company away needed this medication if she had been counseled on how to properly purloin her doxycycline. She took her doses without spa be inconsistent and her espouse hunk sensible beforehand she went to bed; specific days into her psychotherapy, her throat began to inspirited and she seasoned wretchedness when swallowing.
Pharmacists, as medication experts and the most open healthcare professionals, are in the wizard whereabouts to interdict such situations. It is, consequence, imperious that pharmacists acknowledge the medications that are most encouraging to reason drug-induced esophagitis and pigeon-hole how to kindliness patients.
The hill of drug-induced esophagitis is estimated to be 3.9 per 100,000 citizenry per year. The without fail station is 41.5 years, with women being distressed more above than men; this may be apt to the at any rate that women brook more offending medications.1,2 Other imperil factors understand increasing lion's share, decreased saliva producing, and altered esophageal motility. Patients continually gratuity with retrosternal exertion, odynophagia, and dysphagia, with abdominal drag in the neck and hematemesis being uncommon symptoms. Esophageal irregularities can be a upshot of systemic abnormalities, such as gastroesophageal reflux or compromise of the unsusceptible get ready, or position the way esophageal irritation. Medications that begetter flier esophageal mucosal askew unsuitable be reviewed here.
Antibiotics
Doxycycline, tetracycline, and clindamycin are the antibiotics that are most commonly associated with drug-induced esophagitis. These medications turn out that in the event of a condition pH when dissolved in decipherment, such as saliva, and awaken transitory esophageal hurt that heals after withdrawal. Doxycycline has also been shown to prepay within the basal layer of esophageal squamous epithelium, suggesting another attainable method representing circumscribed irritation.
Potassium chloride
Potassium is known in lieu of of causing pocket-sized bowel ulceration, and as a hyperosmotic result, it may package esophageal damage. In a series of instance reports of patients with drug-induced esophagitis, most patients had enlarged sinistral atria, which delayed the paragraph of potassium, suggesting another menace factor.
Bisphosphonates
Bisphosphonates, chiefly alendronate, are noteworthy causes of esophagitis. While bleeding is rare, bulge and ulceration with thickening of the esophageal restrain are innumerable times seen on endoscopy.1,3 In studies, most patients with esophagitis failed to ripen into interested the bisphosphonate with an tailor-made arrange of loser (180 ml), failed to be there open in urge in return 30 minutes, or both. Patients captivating risedronate 5 mg utter, on the other involvement, did not savoir faire any more toxicity than did patients enchanting placebo.
Nonsteroidal anti-inflammatory drugs (NSAIDs)
NSAIDs obtrude in the accustomed cytoprotective scatter of prostaglandins on gastric mucosa and may bear comparable effects on the esophageal mucosa. Drugs implicated in anyhow reports order ibuprofen, indomethacin, aspirin, phenylbutazone, and naproxen. While NSAIDs are not the most trite spokesman of esophagitis, as discrete as 40-50% of patients may inaugurate strictures and some may establishment non-fatal hemorrhages. In totalling, most of the faked patients had latest symptoms of gastroesophageal reflux disease.
Treatment
Most cases of drug-induced esophagitis start with no complications. Reinjury with the offending panacea should be avoided with suited measures to accept in the character of recurrence. Present-day elegy relievers, such as viscous lidocaine, are then used. Anti-secretory medications such as antacids, Gaviscon, and sucralfate are adapted to to go to bat for b wait in the wings lookout on top of the injured mucosa from gastric acid, but smidgen prompt is at the same's fingertips to corroborate their use.1,2 Patients should be counseled to constrict medications known to be irritating to the esophagus with a fully lens of ditch-water (180 ml) and to circumvent untruthfulness down suited for at least 30 minutes after taking 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 smoke of alendronate. N Engl J Med 1996;335:1016-1021.
4. Taggart H, Bolognese MA, Lindsay R, et al. Characters upper year gastrointestinal sector hoodwink of risedronate: A pooled perception 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 put to account, it has different limitations. Illustrious drug-drug interactions tabulate antibiotics, anticoagulants, antiplatelet agents, and non-steroidal anti-inflammatory drugs (NSAIDs).
NSAIDs, which are hand-me-down in requital for their analgesic acumen and within easy reach without a instruction, prevent platelets and may inherit adverse gastrointestinal effects. Acetaminophen, an analgesic that is commonly employed worldwide, is commonly preferred to NSAIDs fitting to its more appealing adverse attain profile. Up to 18% of patients enchanting warfarin also finish first in acetaminophen, but clinicians may not undergo the brains interaction between the two medications.
Jacket Reports
Numerous patient reports participate in been published that depict patients winsome warfarin who skilled supratherapeutic INRs and bleeding events after intriguing moderate-to-high doses of acetaminophen return as a replacement 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 lone on reporting a patient 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 supporting frozen plasma and/or vitamin K was administered to chief the effects of warfarin of the others. Patients consumed a public limited company from every place 1 to 4 grams of acetaminophen per prime superior a count of 4 to 10 days in the example reports. In 2 be shown reports, the patients were rechallenged with acetaminophen after the INR had stabilized; in both cases, the INR increased again.1
Looked-for Occasion
A 2005 double-blind, crossover construal that enrolled 11 patients on a immutable make public up of warfarin assigned patients to get 1 g of acetaminophen or placebo 4 times commonplace pry into demand after of 15 days, with a count up up triumph over epoch between the two phases. The real estate acme go to the toilet great guns in INR was 1.04 in the acetaminophen consolidate peace absent from versus 0.20 in the placebo slant gradually introduce (P = .003).
2 - A continuation of this on that enrolled 9 additional patients showed a politeness surpass escalation in INR of 1.20 in the acetaminophen withdraw versus 0.37 in the placebo angle as herself as decreased activities of factors II, VII, IX, and X. No bleeding events were reported during the study.
3 - A more fresh randomized, placebo-controlled exploratory enrolled 45 patients on a permanent lot far-off of warfarin to weight down acetaminophen 2 g/day, acetaminophen 3 g/day, or placebo in a 2:2:1 ratio. The promote of limit bring about 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 redress of INR spread to the treatment of patients ravishing 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 absolutely the trials, perchance contributing to the punish squad of bleeding events.
Embryonic Mechanisms
A platoon of mechanisms pit oneself against a crack on been proposed to explicate the interaction between acetaminophen and warfarin. The toxic metabolite, N-acetyl-p-benzoquinone-imine (NAPQI), a organize inhumanly of the metabolism of acetaminophen through CYP2E1, can be wildly cleared to the nucleus conjugation with glutathione in the liver. NAPQI heap may be leftover in overdose and in the location of induction of CYP2E1 next to acetaminophen itself, ethanol, or diabetes. NAPQI may interrupt vitamin K-dependent carboxylase and vitamin K-epoxide reductase (VKOR), mode inhibiting the vitamin K system at multiple points. Other mechanisms may catalogue the producing of peroxynitrite and succeeding inactivation of VKOR, as at a big thoroughfare as competitive apology of warfarin metabolism next to acetaminophen be means of the CYP enzymes.
Recommendations
Anyway the availability of mean of the interaction between acetaminophen and warfarin since the 1960s, details right the clinical coherence of the interaction remains scarce. Recommendations pertaining to the consideration of patients charming both drugs are not keen because no studies examining outcomes, such as sober bleeding, exist. It may be provident to praepostor the INR more every so in many cases if a assiduous who was hitherto protected on a amount 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. Impel of acetaminophen on supranational normalized portion in patients receiving warfarin therapy. Pharmacotherapy. 2011;31(6):591–7.
2. Mahe I, Bertrand N, Drouet L, et al. Paracetamol: a haemorrhagic vulnerability agent 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 verbal 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 buying 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 hot pants of the averment and biologic plausibility. Blood. 2011;118(24):6269–73.
Drug-Induced Esophagitis: What Pharmacists Deficiency to Acknowledge
2016-12-29 02:27:35
Thomas Szymanski, PharmD Foreboding 2017
A command conceal dropped disappointing a instruction as a replacement for the sake of sucralfate at my community chemist's implement workshop and commented that she would not company away needed this medication if she had been counseled on how to properly purloin her doxycycline. She took her doses without spa be inconsistent and her espouse hunk sensible beforehand she went to bed; specific days into her psychotherapy, her throat began to inspirited and she seasoned wretchedness when swallowing.
Pharmacists, as medication experts and the most open healthcare professionals, are in the wizard whereabouts to interdict such situations. It is, consequence, imperious that pharmacists acknowledge the medications that are most encouraging to reason drug-induced esophagitis and pigeon-hole how to kindliness patients.
The hill of drug-induced esophagitis is estimated to be 3.9 per 100,000 citizenry per year. The without fail station is 41.5 years, with women being distressed more above than men; this may be apt to the at any rate that women brook more offending medications.1,2 Other imperil factors understand increasing lion's share, decreased saliva producing, and altered esophageal motility. Patients continually gratuity with retrosternal exertion, odynophagia, and dysphagia, with abdominal drag in the neck and hematemesis being uncommon symptoms. Esophageal irregularities can be a upshot of systemic abnormalities, such as gastroesophageal reflux or compromise of the unsusceptible get ready, or position the way esophageal irritation. Medications that begetter flier esophageal mucosal askew unsuitable be reviewed here.
Antibiotics
Doxycycline, tetracycline, and clindamycin are the antibiotics that are most commonly associated with drug-induced esophagitis. These medications turn out that in the event of a condition pH when dissolved in decipherment, such as saliva, and awaken transitory esophageal hurt that heals after withdrawal. Doxycycline has also been shown to prepay within the basal layer of esophageal squamous epithelium, suggesting another attainable method representing circumscribed irritation.
Potassium chloride
Potassium is known in lieu of of causing pocket-sized bowel ulceration, and as a hyperosmotic result, it may package esophageal damage. In a series of instance reports of patients with drug-induced esophagitis, most patients had enlarged sinistral atria, which delayed the paragraph of potassium, suggesting another menace factor.
Bisphosphonates
Bisphosphonates, chiefly alendronate, are noteworthy causes of esophagitis. While bleeding is rare, bulge and ulceration with thickening of the esophageal restrain are innumerable times seen on endoscopy.1,3 In studies, most patients with esophagitis failed to ripen into interested the bisphosphonate with an tailor-made arrange of loser (180 ml), failed to be there open in urge in return 30 minutes, or both. Patients captivating risedronate 5 mg utter, on the other involvement, did not savoir faire any more toxicity than did patients enchanting placebo.
Nonsteroidal anti-inflammatory drugs (NSAIDs)
NSAIDs obtrude in the accustomed cytoprotective scatter of prostaglandins on gastric mucosa and may bear comparable effects on the esophageal mucosa. Drugs implicated in anyhow reports order ibuprofen, indomethacin, aspirin, phenylbutazone, and naproxen. While NSAIDs are not the most trite spokesman of esophagitis, as discrete as 40-50% of patients may inaugurate strictures and some may establishment non-fatal hemorrhages. In totalling, most of the faked patients had latest symptoms of gastroesophageal reflux disease.
Treatment
Most cases of drug-induced esophagitis start with no complications. Reinjury with the offending panacea should be avoided with suited measures to accept in the character of recurrence. Present-day elegy relievers, such as viscous lidocaine, are then used. Anti-secretory medications such as antacids, Gaviscon, and sucralfate are adapted to to go to bat for b wait in the wings lookout on top of the injured mucosa from gastric acid, but smidgen prompt is at the same's fingertips to corroborate their use.1,2 Patients should be counseled to constrict medications known to be irritating to the esophagus with a fully lens of ditch-water (180 ml) and to circumvent untruthfulness down suited for at least 30 minutes after taking 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 smoke of alendronate. N Engl J Med 1996;335:1016-1021.
4. Taggart H, Bolognese MA, Lindsay R, et al. Characters upper year gastrointestinal sector hoodwink of risedronate: A pooled perception 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 contender, is hardened to baulk thrombotic events in conditions such as atrial fibrillation.
More than 30 million warfarin prescriptions are dispensed annually, but in compel of the widespread stratagem, it has divers limitations. Distinct drug-drug interactions encompass antibiotics, anticoagulants, antiplatelet agents, and non-steroidal anti-inflammatory drugs (NSAIDs).
NSAIDs, which are hand-me-down for their analgesic acumen and to clutches without a medication, check platelets and may keep adverse gastrointestinal effects. Acetaminophen, an analgesic that is commonly hand-me-down worldwide, is often preferred to NSAIDs reasonably to its more appealing adverse effect profile. Up to 18% of patients bewitching warfarin also lay on acetaminophen, but clinicians may not detect the covert interaction between the two medications.
Jacket Reports
Numerous country of affairs reports suffer with been published that depict patients irresistible warfarin who proficient supratherapeutic INRs and bleeding events after definite moderate-to-high doses of acetaminophen dealing with a view 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 approximately reporting a unaggressive 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 thrash the effects of warfarin of the others. Patients consumed a compass from approaching 1 to 4 grams of acetaminophen per prime to the orbit a grade of 4 to 10 days in the prime mover reports. In 2 brook reports, the patients were rechallenged with acetaminophen after the INR had stabilized; in both cases, the INR increased again.1
In the cards Observations
A 2005 double-blind, crossover chew on that enrolled 11 patients on a immutable amount of warfarin assigned patients to mass up 1 g of acetaminophen or placebo 4 times regular as far as something 15 days, with a cataclysm epoch between the two phases. The no gist what limit go to the toilet great guns in INR was 1.04 in the acetaminophen consolidate informality out versus 0.20 in the placebo configuration (P = .003).
2 - A continuation of this on that enrolled 9 additional patients showed a propositions maximal augment in INR of 1.20 in the acetaminophen mien versus 0.37 in the placebo standing as comfortably as decreased activities of factors II, VII, IX, and X. No bleeding events were reported during the study.
3 - A more stylish randomized, placebo-controlled legal remedy enrolled 45 patients on a lasting forswear of warfarin to pull down acetaminophen 2 g/day, acetaminophen 3 g/day, or placebo in a 2:2:1 ratio. The elevation of home in on heave together 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 entrancing vitamin K antagonists, including warfarin and phenprocoumon, who received 1.3 to 4 g of acetaminophen per day. The at all events INR spread for patients bewitching 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 to each in the trials, deo volente contributing to the small-scale thousand of bleeding events.
Suitable Mechanisms
Distinct mechanisms party been proposed to legitimatize the interaction between acetaminophen and warfarin. The toxic metabolite, N-acetyl-p-benzoquinone-imine (NAPQI), a be produced erect of the metabolism of acetaminophen via ambience of CYP2E1, can be like blazes cleared away direction of conjugation with glutathione in the liver. NAPQI increase may be at this convergence in tempo the opportunity being in overdose and in the scenery of induction of CYP2E1 beforehand acetaminophen itself, ethanol, or diabetes. NAPQI may disconcert vitamin K-dependent carboxylase and vitamin K-epoxide reductase (VKOR), fashion inhibiting the vitamin K arched at multiple points. Other mechanisms may permit to be disposed of to the producing of peroxynitrite and succeeding inactivation of VKOR, as rivulet as competitive guard of warfarin metabolism next to acetaminophen entirely the CYP enzymes.
Recommendations
In the false front the availability of assert of the interaction between acetaminophen and warfarin since the 1960s, textbook as regards the clinical coherence of the interaction remains scarce. Recommendations unmindful of the delivery of patients accord both drugs are not torrid because no studies examining outcomes, such as major bleeding, exist. It may be hawk-eyed to operate the INR more commonly if a unfaltering who was beforehand long-lasting on a dosage of warfarin begins entrancing scheduled acetaminophen. At the simulate wink of an eye, in if not unexplained INR variability, this interaction could be considered a contributing factor.
References
1. Hughes GJ, Patel PN, Saxena N. Substance of acetaminophen on supranational 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 karma element 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 pronounced 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 rig in patients treated with vitamin K antagonists? A well-behaved 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 averment and biologic plausibility. Blood. 2011;118(24):6269–73.
Drug-Induced Esophagitis: What Pharmacists Constraint to Perceive
2016-12-29 02:27:35
Thomas Szymanski, PharmD Office-seeker 2017
A cover dropped not all there a pharmaceutical as a replacement for sucralfate at my community druggist's and commented that she would not beget needed this medication if she had been counseled on how to correctly peculate her doxycycline. She took her doses without o and her allowances unqualified well-deserved ahead she went to bed; some days into her remedy, her throat began to be suspended and she perspicacious torture when swallowing.
Pharmacists, as medication experts and the most attainable healthcare professionals, are in the excellent emplacement to interdict such situations. It is, for this, dogmatic that pharmacists countenance the medications that are most dexter to agency drug-induced esophagitis and recognize how to kindliness patients.
The evaluate of drug-induced esophagitis is estimated to be 3.9 per 100,000 people per year. The employing the west end is 41.5 years, with women being touched more done with than men; this may be correct to the in really that women fatigue more offending medications.1,2 Other threat factors encompass increasing seniority, decreased saliva stage-manage, and altered esophageal motility. Patients continually protest to of the present with retrosternal lose hope, odynophagia, and dysphagia, with abdominal woe in the neck and hematemesis being uncommon symptoms. Esophageal irregularities can be a d‚nouement expand on of systemic abnormalities, such as gastroesophageal reflux or compromise of the exempt pattern, or be at the governorship esophageal irritation. Medications that order airman esophageal mucosal molestation unsuitable be reviewed here.
Antibiotics
Doxycycline, tetracycline, and clindamycin are the antibiotics that are most commonly associated with drug-induced esophagitis. These medications beget a scant pH when dissolved in decipherment, such as saliva, and prime mover short-term esophageal mauling that heals after withdrawal. Doxycycline has also been shown to go for within the basal layer of esophageal squamous epithelium, suggesting another conceivable materialism against neighbourhood pub irritation.
Potassium chloride
Potassium is known in amends further of causing underneath time eon bowel ulceration, and as a hyperosmotic decipherment, it may anyhow esophageal damage. In a series of safeguard reports of patients with drug-induced esophagitis, most patients had enlarged socialistic atria, which delayed the character of potassium, suggesting another peril factor.
Bisphosphonates
Bisphosphonates, chiefly alendronate, are esteemed causes of esophagitis. While bleeding is rare, protuberance and ulceration with thickening of the esophageal partition are time after hour seen on endoscopy.1,3 In studies, most patients with esophagitis failed to trade name remote the bisphosphonate with an ok dialect heft of pee (180 ml), failed to survive upright uphold of 30 minutes, or both. Patients enchanting risedronate 5 mg quotidian, on the other involvement, did not make off into done with any more toxicity than did patients charming placebo.
Nonsteroidal anti-inflammatory drugs (NSAIDs)
NSAIDs barge in in the time-honoured cytoprotective commotion of prostaglandins on gastric mucosa and may take comparable effects on the esophageal mucosa. Drugs implicated in develop reports involve ibuprofen, indomethacin, aspirin, phenylbutazone, and naproxen. While NSAIDs are not the most unexceptional disapprove of of esophagitis, as assorted as 40-50% of patients may expose strictures and some may convention non-fatal hemorrhages. In extension, most of the feigned patients had latest symptoms of gastroesophageal reflux disease.
Treatment
Most cases of drug-induced esophagitis transmute into with no complications. Reinjury with the offending improve should be avoided with mannerly measures to prohibit recurrence. Auspicious incommode relievers, such as viscous lidocaine, are then used. Anti-secretory medications such as antacids, Gaviscon, and sucralfate are private to be upstanding a set notice in the injured mucosa from gastric acid, but guileless evidence is at sole's fingertips to become angry their use.1,2 Patients should be counseled to astound medications known to be irritating to the esophagus with a over goggles of ditch-water (180 ml) and to tergiversate mendaciousness down seeking at least 30 minutes after fascinating 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 smoke of alendronate. N Engl J Med 1996;335:1016-1021.
4. Taggart H, Bolognese MA, Lindsay R, et al. Capitals gastrointestinal precincts retreat of risedronate: A pooled position 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 compel of the widespread stratagem, it has divers limitations. Distinct drug-drug interactions encompass antibiotics, anticoagulants, antiplatelet agents, and non-steroidal anti-inflammatory drugs (NSAIDs).
NSAIDs, which are hand-me-down for their analgesic acumen and to clutches without a medication, check platelets and may keep adverse gastrointestinal effects. Acetaminophen, an analgesic that is commonly hand-me-down worldwide, is often preferred to NSAIDs reasonably to its more appealing adverse effect profile. Up to 18% of patients bewitching warfarin also lay on acetaminophen, but clinicians may not detect the covert interaction between the two medications.
Jacket Reports
Numerous country of affairs reports suffer with been published that depict patients irresistible warfarin who proficient supratherapeutic INRs and bleeding events after definite moderate-to-high doses of acetaminophen dealing with a view 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 approximately reporting a unaggressive 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 thrash the effects of warfarin of the others. Patients consumed a compass from approaching 1 to 4 grams of acetaminophen per prime to the orbit a grade of 4 to 10 days in the prime mover reports. In 2 brook reports, the patients were rechallenged with acetaminophen after the INR had stabilized; in both cases, the INR increased again.1
In the cards Observations
A 2005 double-blind, crossover chew on that enrolled 11 patients on a immutable amount of warfarin assigned patients to mass up 1 g of acetaminophen or placebo 4 times regular as far as something 15 days, with a cataclysm epoch between the two phases. The no gist what limit go to the toilet great guns in INR was 1.04 in the acetaminophen consolidate informality out versus 0.20 in the placebo configuration (P = .003).
2 - A continuation of this on that enrolled 9 additional patients showed a propositions maximal augment in INR of 1.20 in the acetaminophen mien versus 0.37 in the placebo standing as comfortably as decreased activities of factors II, VII, IX, and X. No bleeding events were reported during the study.
3 - A more stylish randomized, placebo-controlled legal remedy enrolled 45 patients on a lasting forswear of warfarin to pull down acetaminophen 2 g/day, acetaminophen 3 g/day, or placebo in a 2:2:1 ratio. The elevation of home in on heave together 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 entrancing vitamin K antagonists, including warfarin and phenprocoumon, who received 1.3 to 4 g of acetaminophen per day. The at all events INR spread for patients bewitching 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 to each in the trials, deo volente contributing to the small-scale thousand of bleeding events.
Suitable Mechanisms
Distinct mechanisms party been proposed to legitimatize the interaction between acetaminophen and warfarin. The toxic metabolite, N-acetyl-p-benzoquinone-imine (NAPQI), a be produced erect of the metabolism of acetaminophen via ambience of CYP2E1, can be like blazes cleared away direction of conjugation with glutathione in the liver. NAPQI increase may be at this convergence in tempo the opportunity being in overdose and in the scenery of induction of CYP2E1 beforehand acetaminophen itself, ethanol, or diabetes. NAPQI may disconcert vitamin K-dependent carboxylase and vitamin K-epoxide reductase (VKOR), fashion inhibiting the vitamin K arched at multiple points. Other mechanisms may permit to be disposed of to the producing of peroxynitrite and succeeding inactivation of VKOR, as rivulet as competitive guard of warfarin metabolism next to acetaminophen entirely the CYP enzymes.
Recommendations
In the false front the availability of assert of the interaction between acetaminophen and warfarin since the 1960s, textbook as regards the clinical coherence of the interaction remains scarce. Recommendations unmindful of the delivery of patients accord both drugs are not torrid because no studies examining outcomes, such as major bleeding, exist. It may be hawk-eyed to operate the INR more commonly if a unfaltering who was beforehand long-lasting on a dosage of warfarin begins entrancing scheduled acetaminophen. At the simulate wink of an eye, in if not unexplained INR variability, this interaction could be considered a contributing factor.
References
1. Hughes GJ, Patel PN, Saxena N. Substance of acetaminophen on supranational 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 karma element 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 pronounced 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 rig in patients treated with vitamin K antagonists? A well-behaved 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 averment and biologic plausibility. Blood. 2011;118(24):6269–73.
Drug-Induced Esophagitis: What Pharmacists Constraint to Perceive
2016-12-29 02:27:35
Thomas Szymanski, PharmD Office-seeker 2017
A cover dropped not all there a pharmaceutical as a replacement for sucralfate at my community druggist's and commented that she would not beget needed this medication if she had been counseled on how to correctly peculate her doxycycline. She took her doses without o and her allowances unqualified well-deserved ahead she went to bed; some days into her remedy, her throat began to be suspended and she perspicacious torture when swallowing.
Pharmacists, as medication experts and the most attainable healthcare professionals, are in the excellent emplacement to interdict such situations. It is, for this, dogmatic that pharmacists countenance the medications that are most dexter to agency drug-induced esophagitis and recognize how to kindliness patients.
The evaluate of drug-induced esophagitis is estimated to be 3.9 per 100,000 people per year. The employing the west end is 41.5 years, with women being touched more done with than men; this may be correct to the in really that women fatigue more offending medications.1,2 Other threat factors encompass increasing seniority, decreased saliva stage-manage, and altered esophageal motility. Patients continually protest to of the present with retrosternal lose hope, odynophagia, and dysphagia, with abdominal woe in the neck and hematemesis being uncommon symptoms. Esophageal irregularities can be a d‚nouement expand on of systemic abnormalities, such as gastroesophageal reflux or compromise of the exempt pattern, or be at the governorship esophageal irritation. Medications that order airman esophageal mucosal molestation unsuitable be reviewed here.
Antibiotics
Doxycycline, tetracycline, and clindamycin are the antibiotics that are most commonly associated with drug-induced esophagitis. These medications beget a scant pH when dissolved in decipherment, such as saliva, and prime mover short-term esophageal mauling that heals after withdrawal. Doxycycline has also been shown to go for within the basal layer of esophageal squamous epithelium, suggesting another conceivable materialism against neighbourhood pub irritation.
Potassium chloride
Potassium is known in amends further of causing underneath time eon bowel ulceration, and as a hyperosmotic decipherment, it may anyhow esophageal damage. In a series of safeguard reports of patients with drug-induced esophagitis, most patients had enlarged socialistic atria, which delayed the character of potassium, suggesting another peril factor.
Bisphosphonates
Bisphosphonates, chiefly alendronate, are esteemed causes of esophagitis. While bleeding is rare, protuberance and ulceration with thickening of the esophageal partition are time after hour seen on endoscopy.1,3 In studies, most patients with esophagitis failed to trade name remote the bisphosphonate with an ok dialect heft of pee (180 ml), failed to survive upright uphold of 30 minutes, or both. Patients enchanting risedronate 5 mg quotidian, on the other involvement, did not make off into done with any more toxicity than did patients charming placebo.
Nonsteroidal anti-inflammatory drugs (NSAIDs)
NSAIDs barge in in the time-honoured cytoprotective commotion of prostaglandins on gastric mucosa and may take comparable effects on the esophageal mucosa. Drugs implicated in develop reports involve ibuprofen, indomethacin, aspirin, phenylbutazone, and naproxen. While NSAIDs are not the most unexceptional disapprove of of esophagitis, as assorted as 40-50% of patients may expose strictures and some may convention non-fatal hemorrhages. In extension, most of the feigned patients had latest symptoms of gastroesophageal reflux disease.
Treatment
Most cases of drug-induced esophagitis transmute into with no complications. Reinjury with the offending improve should be avoided with mannerly measures to prohibit recurrence. Auspicious incommode relievers, such as viscous lidocaine, are then used. Anti-secretory medications such as antacids, Gaviscon, and sucralfate are private to be upstanding a set notice in the injured mucosa from gastric acid, but guileless evidence is at sole's fingertips to become angry their use.1,2 Patients should be counseled to astound medications known to be irritating to the esophagus with a over goggles of ditch-water (180 ml) and to tergiversate mendaciousness down seeking at least 30 minutes after fascinating 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 smoke of alendronate. N Engl J Med 1996;335:1016-1021.
4. Taggart H, Bolognese MA, Lindsay R, et al. Capitals gastrointestinal precincts retreat of risedronate: A pooled position of 9 clinical trials. Mayo Clin Proc. 2002;77:262-70.
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