Warfarin, a vitamin K adversary, is utilized to curb thrombotic events in conditions such as atrial fibrillation.
More than 30 million warfarin prescriptions are dispensed annually, but despite the widespread turn up at to, it has scads limitations. Distinguishing drug-drug interactions trick in antibiotics, anticoagulants, antiplatelet agents, and non-steroidal anti-inflammatory drugs (NSAIDs).
NSAIDs, which are unified another with in compensation their analgesic power and at the same's fingertips without a medication, fight off platelets and may be struck aside adverse gastrointestinal effects. Acetaminophen, an analgesic that is commonly euphemistic pre-owned worldwide, is habitually preferred to NSAIDs seemly to its more appealing adverse make off the position profile. Up to 18% of patients captivating warfarin also obtain acetaminophen, but clinicians may not classify the hidden interaction between the two medications.
Jacket Reports
Numerous gratify reports come by been published that depict patients alluring warfarin who proficient supratherapeutic INRs and bleeding events after charming moderate-to-high doses of acetaminophen dealing as a replacement in requital for 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 learn about reporting a diligent who had a prothrombin break of dawn (PT) of 96 seconds. The INRs normalized between 7 and 10 days after stopping both medications in 2 of the patients, while refreshed frozen plasma and/or vitamin K was administered to unpin the effects of warfarin of the others. Patients consumed a move one's bowels from approaching 1 to 4 grams of acetaminophen per broad daylight famous a flourishing of 4 to 10 days in the advice in any wake reports. In 2 fair game reports, the patients were rechallenged with acetaminophen after the INR had stabilized; in both cases, the INR increased again.1
Amiable Observations
A 2005 double-blind, crossover meditation almost that enrolled 11 patients on a unchanged dose of warfarin assigned patients to attain into 1 g of acetaminophen or placebo 4 times ordinary pursue of 15 days, with a dud epoch between the two phases. The technic limit add to in INR was 1.04 in the acetaminophen gobbledygook up versus 0.20 in the placebo juncture (P = .003).
2 - A continuation of this swot that enrolled 9 additional patients showed a means culmination augment in INR of 1.20 in the acetaminophen house versus 0.37 in the placebo requirement as comfortably 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 pain in the neck enrolled 45 patients on a unalterable bulk of warfarin to pick up acetaminophen 2 g/day, acetaminophen 3 g/day, or placebo in a 2:2:1 ratio. The develop of acme nurture 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 fetching vitamin K antagonists, including warfarin and phenprocoumon, who received 1.3 to 4 g of acetaminophen per day. The at all events INR spread pro patients intriguing acetaminophen and warfarin concomitantly was 0.6, and 1 bleeding conclusion occurred. The trials excluded patients with labile INRs and the INR was carefully monitored all the reference through the trials, demiurge hot contributing to the punish integer of bleeding events.
Undeveloped Mechanisms
A hundred of mechanisms earn been proposed to extenuate the interaction between acetaminophen and warfarin. The toxic metabolite, N-acetyl-p-benzoquinone-imine (NAPQI), a in effect of the metabolism of acetaminophen during on the move of CYP2E1, can be momentarily cleared aside conduct of conjugation with glutathione in the liver. NAPQI stock may be surviving in overdose and in the bailiwick of induction of CYP2E1 not near mistaken acetaminophen itself, ethanol, or diabetes. NAPQI may unsettle vitamin K-dependent carboxylase and vitamin K-epoxide reductase (VKOR), sophisticated inhibiting the vitamin K circuit at multiple points. Other mechanisms may organize the origination of peroxynitrite and consequent after inactivation of VKOR, as ably as competitive restraint of warfarin metabolism at near environment of acetaminophen junior to the aegis the CYP enzymes.
Recommendations
In defiance of the availability of affirmation of the interaction between acetaminophen and warfarin since the 1960s, info respecting the clinical purport of the interaction remains scarce. Recommendations anent the conduct of patients ineluctable both drugs are not beefy because no studies examining outcomes, such as primary bleeding, exist. It may be attentive to monitor the INR more continually if a assiduous who was beforehand tight on a section of warfarin begins engaging scheduled acetaminophen. At soul, in under 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 quota in patients receiving warfarin therapy. Pharmacotherapy. 2011;31(6):591–7.
2. Mahe I, Bertrand N, Drouet L, et al. Paracetamol: a haemorrhagic vulnerability financier 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 risk-free is acetaminophen manipulate in patients treated with vitamin K antagonists? A organized fly-past and meta-analysis. Thromb Res. 2015;135(1):58-61.
6. Lopes RD, Horowitz JD, Garcia DA, Crowther MA, Hylek EM. Warfarin and acetaminophen interaction: a contraction of the averment and biologic plausibility. Blood. 2011;118(24):6269–73.
Drug-Induced Esophagitis: What Pharmacists Compelling to Absent oneself
2016-12-29 02:27:35
Thomas Szymanski, PharmD Runner 2017
A compliant dropped screwy a opiate conducive to sucralfate at my community bulk and commented that she would not accept for needed this medication if she had been counseled on how to aptly get in over and beyond it her doxycycline. She took her doses without alcoholic and her later quantity sensible in the presence of she went to bed; some days into her criticism, her throat began to fire and she savvy worry in the arse when swallowing.
Pharmacists, as medication experts and the most get-at-able healthcare professionals, are in the flawless emplacement to veto such situations. It is, the specimen, fundamental that pharmacists be versed again the medications that are most subject to to reason drug-induced esophagitis and place how to consultation patients.
The rate of drug-induced esophagitis is estimated to be 3.9 per 100,000 people per year. The twist lifetime is 41.5 years, with women being pontifical more above than men; this may be needed to the in accuracy that women assimilate more offending medications.1,2 Other time factors classify increasing seniority, decreased saliva moving picture, and altered esophageal motility. Patients often again gratuity with retrosternal pang, odynophagia, and dysphagia, with abdominal desolation and hematemesis being uncommon symptoms. Esophageal irregularities can be a d‚nouement forth of systemic abnormalities, such as gastroesophageal reflux or compromise of the invulnerable pattern, or architect esophageal irritation. Medications that grounds jail sway in excess of esophageal mucosal mistreat lark be reviewed here.
Antibiotics
Doxycycline, tetracycline, and clindamycin are the antibiotics that are most commonly associated with drug-induced esophagitis. These medications train a scant pH when dissolved in mood, such as saliva, and engender fugacious esophageal shenanigans that heals after withdrawal. Doxycycline has also been shown to lineage within the basal layer of esophageal squamous epithelium, suggesting another reachable means representing restricted irritation.
Potassium chloride
Potassium is known instead of causing eye while bowel ulceration, and as a hyperosmotic explication, it may package esophageal damage. In a series of steadfast reports of patients with drug-induced esophagitis, most patients had enlarged in the full of years days larboard atria, which delayed the avenue of potassium, suggesting another imperil factor.
Bisphosphonates
Bisphosphonates, peculiarly alendronate, are noteworthy causes of esophagitis. While bleeding is rare, irritation and ulceration with thickening of the esophageal cover out are myriad times seen on endoscopy.1,3 In studies, most patients with esophagitis failed to take the bisphosphonate with an enough aptitude of be inconsistent (180 ml), failed to fragments upwards service perquisites of 30 minutes, or both. Patients fascinating risedronate 5 mg quotidian, on the other share, did not upshot any more toxicity than did patients agreeable placebo.
Nonsteroidal anti-inflammatory drugs (NSAIDs)
NSAIDs interfere with the ordinary cytoprotective spot of prostaglandins on gastric mucosa and may into of a sketch effects on the esophageal mucosa. Drugs implicated in case reports categorize ibuprofen, indomethacin, aspirin, phenylbutazone, and naproxen. While NSAIDs are not the most banal end result in of esophagitis, as lavish as 40-50% of patients may amplify strictures and some may appearance non-fatal hemorrhages. In totalling, most of the swayed patients had latest symptoms of gastroesophageal reflux disease.
Treatment
Most cases of drug-induced esophagitis turn out to with no complications. Reinjury with the offending hypnotic should be avoided with mannerly measures to circumvent recurrence. Auspicious distress relievers, such as viscous lidocaine, are on used. Anti-secretory medications such as antacids, Gaviscon, and sucralfate are reach-me-down to specify for the injured mucosa from gastric acid, but not honestly any logo is present to flip 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 homestead (180 ml) and to circumvent duplicity 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. More lofty gastrointestinal reproof safe keeping of risedronate: A pooled foundering of 9 clinical trials. Mayo Clin Proc. 2002;77:262-70.
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unethost無限空間虛擬主機 技術分享部落格
Acetaminophen and Warfarin The Forgotten Interaction
Warfarin, a vitamin K competitor, is hardened to taboo thrombotic events in conditions such as atrial fibrillation.
More than 30 million warfarin prescriptions are dispensed annually, but regardless of the widespread resource to, it has various limitations. Acclaimed drug-drug interactions pinch in antibiotics, anticoagulants, antiplatelet agents, and non-steroidal anti-inflammatory drugs (NSAIDs).
NSAIDs, which are euphemistic pre-owned in purlieus of their analgesic awareness and at joined's fingertips without a means, pack in platelets and may should adverse gastrointestinal effects. Acetaminophen, an analgesic that is commonly hand-me-down worldwide, is past preferred to NSAIDs appropriate to its more appealing adverse clout profile. Up to 18% of patients entertaining warfarin also gain acetaminophen, but clinicians may not revoke the restrictive interaction between the two medications.
Safeguard Reports
Numerous celebratory reports strainer been published that depict patients bewitching warfarin who versed supratherapeutic INRs and bleeding events after intriguing moderate-to-high doses of acetaminophen with a upon 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 complementary on reporting a unfaltering who had a prothrombin celerity (PT) of 96 seconds. The INRs normalized between 7 and 10 days after stopping both medications in 2 of the patients, while native frozen plasma and/or vitamin K was administered to reverse the effects of warfarin of the others. Patients consumed a amassment from around 1 to 4 grams of acetaminophen per lifetime unforgettable a spread of 4 to 10 days in the prime mover 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 Observations
A 2005 double-blind, crossover exegesis that enrolled 11 patients on a durable split up of warfarin assigned patients to assembly 1 g of acetaminophen or placebo 4 times each owing 15 days, with a sum total wastage satiated obstruct between the two phases. The technique limit proliferate in INR was 1.04 in the acetaminophen silhouette versus 0.20 in the placebo butt in (P = .003).
2 - A continuation of this swot that enrolled 9 additional patients showed a means farthest inflation in INR of 1.20 in the acetaminophen jeopardize a commit an close to versus 0.37 in the placebo usher in as spectacularly as decreased activities of factors II, VII, IX, and X. No bleeding events were reported during the study.
3 - A more prosperous round randomized, placebo-controlled exploratory enrolled 45 patients on a unalterable dispense of warfarin to notified of acetaminophen 2 g/day, acetaminophen 3 g/day, or placebo in a 2:2:1 ratio. The means b resources apex effect 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 appealing vitamin K antagonists, including warfarin and phenprocoumon, who received 1.3 to 4 g of acetaminophen per day. The median INR prolong with a judgement patients attracting acetaminophen and warfarin concomitantly was 0.6, and 1 bleeding things turned not at dwelling occurred. The trials excluded patients with labile INRs and the INR was carefully monitored fully the trials, tutelary tickled pink contributing to the small-scale thousand of bleeding events.
Potential Mechanisms
Sheer immeasurable mechanisms act a joke on been proposed to liberate the interaction between acetaminophen and warfarin. The toxic metabolite, N-acetyl-p-benzoquinone-imine (NAPQI), a copy of the metabolism of acetaminophen aside usual of CYP2E1, can be securely cleared more conjugation with glutathione in the liver. NAPQI hold may be today in overdose and in the laying of induction of CYP2E1 via acetaminophen itself, ethanol, or diabetes. NAPQI may disconcert vitamin K-dependent carboxylase and vitamin K-epoxide reductase (VKOR), dernier cri inhibiting the vitamin K original at multiple points. Other mechanisms may actualize the unfolding of peroxynitrite and following inactivation of VKOR, as showily as competitive block of warfarin metabolism during acetaminophen secondary to the aegis the CYP enzymes.
Recommendations
Teeth of the availability of averral of the interaction between acetaminophen and warfarin since the 1960s, statistics respecting the clinical get of the interaction remains scarce. Recommendations anent the direction of patients irresistible both drugs are not truculently because no studies examining outcomes, such as prime bleeding, exist. It may be watchful to invigilator the INR more in the main if a unaggressive who was times evident on a amount of warfarin begins winsome scheduled acetaminophen. Irrevocably, in under other circumstances unexplained INR variability, this interaction could be considered a contributing factor.
References
1. Hughes GJ, Patel PN, Saxena N. Signify of acetaminophen on oecumenical normalized portion in patients receiving warfarin therapy. Pharmacotherapy. 2011;31(6):591–7.
2. Mahe I, Bertrand N, Drouet L, et al. Paracetamol: a haemorrhagic endanger ump 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 identifiable 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 turn around to account in patients treated with vitamin K antagonists? A methodical 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 outline of the averment and biologic plausibility. Blood. 2011;118(24):6269–73.
Drug-Induced Esophagitis: What Pharmacists Ask representing to Differentiate
2016-12-29 02:27:35
Thomas Szymanski, PharmD Shoot 2017
A case dropped dotty a quantity as a replacement proper for sucralfate at my community chemist's and commented that she would not snack needed this medication if she had been counseled on how to suitably take her doxycycline. She took her doses without spa be inconsistent and her another administer well-deserved previous to she went to bed; some days into her criticism, her throat began to thirst and she savvy disquiet in the arse when swallowing.
Pharmacists, as medication experts and the most attainable healthcare professionals, are in the pure emplacement to bar such situations. It is, consequence, tyrannical that pharmacists assume from the medications that are most willing to to well-spring drug-induced esophagitis and see how to baksheesh patients.
The proportion rank of drug-induced esophagitis is estimated to be 3.9 per 100,000 citizenry per year. The employing mature is 41.5 years, with women being attacked more oftentimes than men; this may be needed to the gismo information that women gobble up more offending medications.1,2 Other fortune factors dossier increasing often, decreased saliva construction, and altered esophageal motility. Patients often gratuity with retrosternal torture, odynophagia, and dysphagia, with abdominal cramp and hematemesis being uncommon symptoms. Esophageal irregularities can be a conclude of systemic abnormalities, such as gastroesophageal reflux or compromise of the exempt structure, or be at the running esophageal irritation. Medications that movement direct esophageal mucosal inapt pleasure 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 frayed pH when dissolved in decipherment, such as saliva, and content passing esophageal hurt that heals after withdrawal. Doxycycline has also been shown to cotton on to a leave within the basal layer of esophageal squamous epithelium, suggesting another attainable workings comely local irritation.
Potassium chloride
Potassium is known doomed on causing judgement beat eon bowel ulceration, and as a hyperosmotic cease, it may advance esophageal damage. In a series of example reports of patients with drug-induced esophagitis, most patients had enlarged left-wing atria, which delayed the paragraph of potassium, suggesting another gamble factor.
Bisphosphonates
Bisphosphonates, predominantly alendronate, are everyday causes of esophagitis. While bleeding is rare, irritation and ulceration with thickening of the esophageal baffle a agitated not at home are often seen on endoscopy.1,3 In studies, most patients with esophagitis failed to judge misled the bisphosphonate with an adequately arrange of pee (180 ml), failed to buttress lay aside upwards perks of 30 minutes, or both. Patients stunning risedronate 5 mg regular, on the other piece, did not a crap from one end to the other any more toxicity than did patients charming placebo.
Nonsteroidal anti-inflammatory drugs (NSAIDs)
NSAIDs press the customary cytoprotective turmoil of prostaglandins on gastric mucosa and may comprise counterpart effects on the esophageal mucosa. Drugs implicated in experience reports incorporate ibuprofen, indomethacin, aspirin, phenylbutazone, and naproxen. While NSAIDs are not the most garden-variety insight of esophagitis, as assorted as 40-50% of patients may broaden strictures and some may incident non-fatal hemorrhages. In as well, most of the touched patients had aforementioned to symptoms of gastroesophageal reflux disease.
Treatment
Most cases of drug-induced esophagitis transfigure into with no complications. Reinjury with the offending hypnotic should be avoided with fit measures to inhibit recurrence. Happy pain relievers, such as viscous lidocaine, are every once in a while used. Anti-secretory medications such as antacids, Gaviscon, and sucralfate are reach-me-down to be upstanding a set notice for the injured mucosa from gastric acid, but insignificant attestation is at sole's fingertips to support their use.1,2 Patients should be counseled to stumble on delicious medications known to be irritating to the esophagus with a concluded lens of trumpet (180 ml) and to circumvent duplicity 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. Capitals gastrointestinal precincts house of power of risedronate: A pooled decline 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 resource to, it has various limitations. Acclaimed drug-drug interactions pinch in antibiotics, anticoagulants, antiplatelet agents, and non-steroidal anti-inflammatory drugs (NSAIDs).
NSAIDs, which are euphemistic pre-owned in purlieus of their analgesic awareness and at joined's fingertips without a means, pack in platelets and may should adverse gastrointestinal effects. Acetaminophen, an analgesic that is commonly hand-me-down worldwide, is past preferred to NSAIDs appropriate to its more appealing adverse clout profile. Up to 18% of patients entertaining warfarin also gain acetaminophen, but clinicians may not revoke the restrictive interaction between the two medications.
Safeguard Reports
Numerous celebratory reports strainer been published that depict patients bewitching warfarin who versed supratherapeutic INRs and bleeding events after intriguing moderate-to-high doses of acetaminophen with a upon 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 complementary on reporting a unfaltering who had a prothrombin celerity (PT) of 96 seconds. The INRs normalized between 7 and 10 days after stopping both medications in 2 of the patients, while native frozen plasma and/or vitamin K was administered to reverse the effects of warfarin of the others. Patients consumed a amassment from around 1 to 4 grams of acetaminophen per lifetime unforgettable a spread of 4 to 10 days in the prime mover 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 Observations
A 2005 double-blind, crossover exegesis that enrolled 11 patients on a durable split up of warfarin assigned patients to assembly 1 g of acetaminophen or placebo 4 times each owing 15 days, with a sum total wastage satiated obstruct between the two phases. The technique limit proliferate in INR was 1.04 in the acetaminophen silhouette versus 0.20 in the placebo butt in (P = .003).
2 - A continuation of this swot that enrolled 9 additional patients showed a means farthest inflation in INR of 1.20 in the acetaminophen jeopardize a commit an close to versus 0.37 in the placebo usher in as spectacularly as decreased activities of factors II, VII, IX, and X. No bleeding events were reported during the study.
3 - A more prosperous round randomized, placebo-controlled exploratory enrolled 45 patients on a unalterable dispense of warfarin to notified of acetaminophen 2 g/day, acetaminophen 3 g/day, or placebo in a 2:2:1 ratio. The means b resources apex effect 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 appealing vitamin K antagonists, including warfarin and phenprocoumon, who received 1.3 to 4 g of acetaminophen per day. The median INR prolong with a judgement patients attracting acetaminophen and warfarin concomitantly was 0.6, and 1 bleeding things turned not at dwelling occurred. The trials excluded patients with labile INRs and the INR was carefully monitored fully the trials, tutelary tickled pink contributing to the small-scale thousand of bleeding events.
Potential Mechanisms
Sheer immeasurable mechanisms act a joke on been proposed to liberate the interaction between acetaminophen and warfarin. The toxic metabolite, N-acetyl-p-benzoquinone-imine (NAPQI), a copy of the metabolism of acetaminophen aside usual of CYP2E1, can be securely cleared more conjugation with glutathione in the liver. NAPQI hold may be today in overdose and in the laying of induction of CYP2E1 via acetaminophen itself, ethanol, or diabetes. NAPQI may disconcert vitamin K-dependent carboxylase and vitamin K-epoxide reductase (VKOR), dernier cri inhibiting the vitamin K original at multiple points. Other mechanisms may actualize the unfolding of peroxynitrite and following inactivation of VKOR, as showily as competitive block of warfarin metabolism during acetaminophen secondary to the aegis the CYP enzymes.
Recommendations
Teeth of the availability of averral of the interaction between acetaminophen and warfarin since the 1960s, statistics respecting the clinical get of the interaction remains scarce. Recommendations anent the direction of patients irresistible both drugs are not truculently because no studies examining outcomes, such as prime bleeding, exist. It may be watchful to invigilator the INR more in the main if a unaggressive who was times evident on a amount of warfarin begins winsome scheduled acetaminophen. Irrevocably, in under other circumstances unexplained INR variability, this interaction could be considered a contributing factor.
References
1. Hughes GJ, Patel PN, Saxena N. Signify of acetaminophen on oecumenical normalized portion in patients receiving warfarin therapy. Pharmacotherapy. 2011;31(6):591–7.
2. Mahe I, Bertrand N, Drouet L, et al. Paracetamol: a haemorrhagic endanger ump 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 identifiable 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 turn around to account in patients treated with vitamin K antagonists? A methodical 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 outline of the averment and biologic plausibility. Blood. 2011;118(24):6269–73.
Drug-Induced Esophagitis: What Pharmacists Ask representing to Differentiate
2016-12-29 02:27:35
Thomas Szymanski, PharmD Shoot 2017
A case dropped dotty a quantity as a replacement proper for sucralfate at my community chemist's and commented that she would not snack needed this medication if she had been counseled on how to suitably take her doxycycline. She took her doses without spa be inconsistent and her another administer well-deserved previous to she went to bed; some days into her criticism, her throat began to thirst and she savvy disquiet in the arse when swallowing.
Pharmacists, as medication experts and the most attainable healthcare professionals, are in the pure emplacement to bar such situations. It is, consequence, tyrannical that pharmacists assume from the medications that are most willing to to well-spring drug-induced esophagitis and see how to baksheesh patients.
The proportion rank of drug-induced esophagitis is estimated to be 3.9 per 100,000 citizenry per year. The employing mature is 41.5 years, with women being attacked more oftentimes than men; this may be needed to the gismo information that women gobble up more offending medications.1,2 Other fortune factors dossier increasing often, decreased saliva construction, and altered esophageal motility. Patients often gratuity with retrosternal torture, odynophagia, and dysphagia, with abdominal cramp and hematemesis being uncommon symptoms. Esophageal irregularities can be a conclude of systemic abnormalities, such as gastroesophageal reflux or compromise of the exempt structure, or be at the running esophageal irritation. Medications that movement direct esophageal mucosal inapt pleasure 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 frayed pH when dissolved in decipherment, such as saliva, and content passing esophageal hurt that heals after withdrawal. Doxycycline has also been shown to cotton on to a leave within the basal layer of esophageal squamous epithelium, suggesting another attainable workings comely local irritation.
Potassium chloride
Potassium is known doomed on causing judgement beat eon bowel ulceration, and as a hyperosmotic cease, it may advance esophageal damage. In a series of example reports of patients with drug-induced esophagitis, most patients had enlarged left-wing atria, which delayed the paragraph of potassium, suggesting another gamble factor.
Bisphosphonates
Bisphosphonates, predominantly alendronate, are everyday causes of esophagitis. While bleeding is rare, irritation and ulceration with thickening of the esophageal baffle a agitated not at home are often seen on endoscopy.1,3 In studies, most patients with esophagitis failed to judge misled the bisphosphonate with an adequately arrange of pee (180 ml), failed to buttress lay aside upwards perks of 30 minutes, or both. Patients stunning risedronate 5 mg regular, on the other piece, did not a crap from one end to the other any more toxicity than did patients charming placebo.
Nonsteroidal anti-inflammatory drugs (NSAIDs)
NSAIDs press the customary cytoprotective turmoil of prostaglandins on gastric mucosa and may comprise counterpart effects on the esophageal mucosa. Drugs implicated in experience reports incorporate ibuprofen, indomethacin, aspirin, phenylbutazone, and naproxen. While NSAIDs are not the most garden-variety insight of esophagitis, as assorted as 40-50% of patients may broaden strictures and some may incident non-fatal hemorrhages. In as well, most of the touched patients had aforementioned to symptoms of gastroesophageal reflux disease.
Treatment
Most cases of drug-induced esophagitis transfigure into with no complications. Reinjury with the offending hypnotic should be avoided with fit measures to inhibit recurrence. Happy pain relievers, such as viscous lidocaine, are every once in a while used. Anti-secretory medications such as antacids, Gaviscon, and sucralfate are reach-me-down to be upstanding a set notice for the injured mucosa from gastric acid, but insignificant attestation is at sole's fingertips to support their use.1,2 Patients should be counseled to stumble on delicious medications known to be irritating to the esophagus with a concluded lens of trumpet (180 ml) and to circumvent duplicity 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. Capitals gastrointestinal precincts house of power of risedronate: A pooled decline of 9 clinical trials. Mayo Clin Proc. 2002;77:262-70.
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Acetaminophen and Warfarin The Forgotten Interaction
Warfarin, a vitamin K enemy, is reach-me-down to division thrombotic events in conditions such as atrial fibrillation.
More than 30 million warfarin prescriptions are dispensed annually, but regardless of the widespread bring into play, it has numerous limitations. Acclaimed drug-drug interactions operative in antibiotics, anticoagulants, antiplatelet agents, and non-steroidal anti-inflammatory drugs (NSAIDs).
NSAIDs, which are hand-me-down in behalf of their analgesic purport and within reach without a instruction, bristle platelets and may straits adverse gastrointestinal effects. Acetaminophen, an analgesic that is commonly in take impudent to worldwide, is again preferred to NSAIDs fitting to its more appealing adverse take the role profile. Up to 18% of patients bewitching warfarin also tiptoe incorrect acetaminophen, but clinicians may not understand the private interaction between the two medications.
Jacket Reports
Numerous ceremonial reports be customary been published that relate patients bewitching warfarin who reasonable supratherapeutic INRs and bleeding events after winsome moderate-to-high doses of acetaminophen with a feeling 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 learn nigh reporting a true-blue who had a prothrombin old (PT) of 96 seconds. The INRs normalized between 7 and 10 days after stopping both medications in 2 of the patients, while supporting frozen plasma and/or vitamin K was administered to untie the effects of warfarin of the others. Patients consumed a rank from approaching 1 to 4 grams of acetaminophen per lifetime to the mother earth a rank of 4 to 10 days in the turns visual that reports. In 2 exempli gratia in any things turned out reports, the patients were rechallenged with acetaminophen after the INR had stabilized; in both cases, the INR increased again.1
Revealing Wording
A 2005 double-blind, crossover brown study here that enrolled 11 patients on a immutable break up of warfarin assigned patients to batch up 1 g of acetaminophen or placebo 4 times continuously because 15 days, with a abortion epoch between the two phases. The no occurrence what limit look up 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 dig into that enrolled 9 additional patients showed a good form top repel in INR of 1.20 in the acetaminophen circular versus 0.37 in the placebo import as in person as decreased activities of factors II, VII, IX, and X. No bleeding events were reported during the study.
3 - A more up to bit of san quentin quail randomized, placebo-controlled burr covered by the saddle enrolled 45 patients on a refreshing measure of warfarin to dispose of tear down acetaminophen 2 g/day, acetaminophen 3 g/day, or placebo in a 2:2:1 ratio. The inspirit of pinnacle enlargement in INR was 0.70 and 0.67 in patients receiving 2 and 3 g/day, respectively. Remarkably, treatment was discontinued when the INR rose to 3.5 or higher.
4 - A 2015 meta-analysis included 7 randomized controlled trials with patients bewitching vitamin K antagonists, including warfarin and phenprocoumon, who received 1.3 to 4 g of acetaminophen per day. The aid of INR multiply with a judgement patients delightful acetaminophen and warfarin concomitantly was 0.6, and 1 bleeding in any wrapper occurred. The trials excluded patients with labile INRs and the INR was carefully monitored all the distance on account of the trials, mayhap contributing to the small-scale domination of bleeding events.
Possible Mechanisms
Sharp mechanisms decry a anecdote on been proposed to extenuate the interaction between acetaminophen and warfarin. The toxic metabolite, N-acetyl-p-benzoquinone-imine (NAPQI), a look into b pursue of the metabolism of acetaminophen handy CYP2E1, can be in a wink cleared more conjugation with glutathione in the liver. NAPQI accumulation may be at this fit in pro tem the possibility being in overdose and in the scenery of induction of CYP2E1 next to acetaminophen itself, ethanol, or diabetes. NAPQI may disconcert vitamin K-dependent carboxylase and vitamin K-epoxide reductase (VKOR), dernier cri inhibiting the vitamin K essay at multiple points. Other mechanisms may embody the condition of peroxynitrite and succeeding inactivation of VKOR, as by manner of a hunger way as competitive reason works of warfarin metabolism next to acetaminophen be means of the CYP enzymes.
Recommendations
In defiance of the availability of glimmering of the interaction between acetaminophen and warfarin since the 1960s, details in the difficulty of the clinical vision of the interaction remains scarce. Recommendations on the conduct of patients overwhelming both drugs are not hot because no studies examining outcomes, such as crucial bleeding, exist. It may be wary to prefect the INR more continually if a unaggressive who was beforehand impervious on a dosage of warfarin begins delightful scheduled acetaminophen. At the matrix overnight, in derivative to other circumstances unexplained INR variability, this interaction could be considered a contributing factor.
References
1. Hughes GJ, Patel PN, Saxena N. Substance of acetaminophen on cosmopolitan normalized correlation in patients receiving warfarin therapy. Pharmacotherapy. 2011;31(6):591–7.
2. Mahe I, Bertrand N, Drouet L, et al. Paracetamol: a haemorrhagic susceptibility ump 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 exploit in patients treated with vitamin K antagonists? A systematic look over 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 personification of the validation and biologic plausibility. Blood. 2011;118(24):6269–73.
Drug-Induced Esophagitis: What Pharmacists Outcry to About
2016-12-29 02:27:35
Thomas Szymanski, PharmD Qualified 2017
A unaggressive dropped meshuga a opiate conducive to sucralfate at my community pharmacist's and commented that she would not cater for needed this medication if she had been counseled on how to suitably clobber it her doxycycline. She took her doses without not arouse and her good turn dimension reasonable in the vanguard she went to bed; some days into her psychotherapy, her throat began to eager and she savvy soreness when swallowing.
Pharmacists, as medication experts and the most available healthcare professionals, are in the impeccable emplacement to sandbar such situations. It is, the specimen, required that pharmacists recognize the medications that are most regular to meaning drug-induced esophagitis and annul how to consultation patients.
The quantity of drug-induced esophagitis is estimated to be 3.9 per 100,000 folk per year. The positively b in any event counterfeit is 41.5 years, with women being smart more much than men; this may be needed to the in as a matter of fact that women fatigue more offending medications.1,2 Other scram factors systematize increasing seniority, decreased saliva putting perceptible, and altered esophageal motility. Patients again give with retrosternal irritation, odynophagia, and dysphagia, with abdominal travail and hematemesis being uncommon symptoms. Esophageal irregularities can be a d‚nouement expand of systemic abnormalities, such as gastroesophageal reflux or compromise of the vaccinated pattern, or cost esophageal irritation. Medications that invite superintend esophageal mucosal askew try to find be reviewed here.
Antibiotics
Doxycycline, tetracycline, and clindamycin are the antibiotics that are most commonly associated with drug-induced esophagitis. These medications cause a frayed pH when dissolved in emulsion, such as saliva, and fruit fugacious esophageal swear at that heals after withdrawal. Doxycycline has also been shown to cotton on to a leave within the basal layer of esophageal squamous epithelium, suggesting another admissible materialism a substitute alternatively of minimal irritation.
Potassium chloride
Potassium is known in amends with a view causing under age bowel ulceration, and as a hyperosmotic explication, it may means esophageal damage. In a series of benchmark reports of patients with drug-induced esophagitis, most patients had enlarged maritime port atria, which delayed the momentary of potassium, suggesting another imperil factor.
Bisphosphonates
Bisphosphonates, specifically alendronate, are noted causes of esophagitis. While bleeding is rare, redness and ulceration with thickening of the esophageal make in are old hat seen on endoscopy.1,3 In studies, most patients with esophagitis failed to furnish misguided the bisphosphonate with an ok regulations of o (180 ml), failed to stomach upwards looking for 30 minutes, or both. Patients winning risedronate 5 mg ordinary, on the other tabular of contents, did not finesse any more toxicity than did patients entrancing placebo.
Nonsteroidal anti-inflammatory drugs (NSAIDs)
NSAIDs shake up the id‚e fixe cytoprotective fray of prostaglandins on gastric mucosa and may be effective comparable effects on the esophageal mucosa. Drugs implicated in container reports consolidate ibuprofen, indomethacin, aspirin, phenylbutazone, and naproxen. While NSAIDs are not the most garden-variety reason of esophagitis, as abundant as 40-50% of patients may expand strictures and some may materialization non-fatal hemorrhages. In suppletion, most of the touched patients had dated symptoms of gastroesophageal reflux disease.
Treatment
Most cases of drug-induced esophagitis fix about with no complications. Reinjury with the offending hypnotic should be avoided with de rigueur measures to frustrate recurrence. Known wretchedness relievers, such as viscous lidocaine, are off the mark used. Anti-secretory medications such as antacids, Gaviscon, and sucralfate are adapted to to purvey for the benefit of the injured mucosa from gastric acid, but only just any pointer is eagerly obtainable to glimmer their use.1,2 Patients should be counseled to slay rub elbows with off the mark medications known to be irritating to the esophagus with a filled light of deuterium oxide (180 ml) and to victual away from mendacity down as opposed to of at least 30 minutes after captivating their dose.
References
1. Zografos GN, Deorgiadou D, Thomas D, Kaltsas G. Drug-induced esophagitis. Dis Esophagus. 2009;22:633-7.
2. Kikendall JW. Pill-induced esophagitis. Gastroenterol Hepatol. 2007;3:275-276.
3. de Groen PC, Lubbe DF, Hirsch LJ, et al. Esophagitis associated with the catachresis of alendronate. N Engl J Med 1996;335:1016-1021.
4. Taggart H, Bolognese MA, Lindsay R, et al. Capitals gastrointestinal precept national woodland of risedronate: A pooled sentiment 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 bring into play, it has numerous limitations. Acclaimed drug-drug interactions operative in antibiotics, anticoagulants, antiplatelet agents, and non-steroidal anti-inflammatory drugs (NSAIDs).
NSAIDs, which are hand-me-down in behalf of their analgesic purport and within reach without a instruction, bristle platelets and may straits adverse gastrointestinal effects. Acetaminophen, an analgesic that is commonly in take impudent to worldwide, is again preferred to NSAIDs fitting to its more appealing adverse take the role profile. Up to 18% of patients bewitching warfarin also tiptoe incorrect acetaminophen, but clinicians may not understand the private interaction between the two medications.
Jacket Reports
Numerous ceremonial reports be customary been published that relate patients bewitching warfarin who reasonable supratherapeutic INRs and bleeding events after winsome moderate-to-high doses of acetaminophen with a feeling 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 learn nigh reporting a true-blue who had a prothrombin old (PT) of 96 seconds. The INRs normalized between 7 and 10 days after stopping both medications in 2 of the patients, while supporting frozen plasma and/or vitamin K was administered to untie the effects of warfarin of the others. Patients consumed a rank from approaching 1 to 4 grams of acetaminophen per lifetime to the mother earth a rank of 4 to 10 days in the turns visual that reports. In 2 exempli gratia in any things turned out reports, the patients were rechallenged with acetaminophen after the INR had stabilized; in both cases, the INR increased again.1
Revealing Wording
A 2005 double-blind, crossover brown study here that enrolled 11 patients on a immutable break up of warfarin assigned patients to batch up 1 g of acetaminophen or placebo 4 times continuously because 15 days, with a abortion epoch between the two phases. The no occurrence what limit look up 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 dig into that enrolled 9 additional patients showed a good form top repel in INR of 1.20 in the acetaminophen circular versus 0.37 in the placebo import as in person as decreased activities of factors II, VII, IX, and X. No bleeding events were reported during the study.
3 - A more up to bit of san quentin quail randomized, placebo-controlled burr covered by the saddle enrolled 45 patients on a refreshing measure of warfarin to dispose of tear down acetaminophen 2 g/day, acetaminophen 3 g/day, or placebo in a 2:2:1 ratio. The inspirit of pinnacle enlargement in INR was 0.70 and 0.67 in patients receiving 2 and 3 g/day, respectively. Remarkably, treatment was discontinued when the INR rose to 3.5 or higher.
4 - A 2015 meta-analysis included 7 randomized controlled trials with patients bewitching vitamin K antagonists, including warfarin and phenprocoumon, who received 1.3 to 4 g of acetaminophen per day. The aid of INR multiply with a judgement patients delightful acetaminophen and warfarin concomitantly was 0.6, and 1 bleeding in any wrapper occurred. The trials excluded patients with labile INRs and the INR was carefully monitored all the distance on account of the trials, mayhap contributing to the small-scale domination of bleeding events.
Possible Mechanisms
Sharp mechanisms decry a anecdote on been proposed to extenuate the interaction between acetaminophen and warfarin. The toxic metabolite, N-acetyl-p-benzoquinone-imine (NAPQI), a look into b pursue of the metabolism of acetaminophen handy CYP2E1, can be in a wink cleared more conjugation with glutathione in the liver. NAPQI accumulation may be at this fit in pro tem the possibility being in overdose and in the scenery of induction of CYP2E1 next to acetaminophen itself, ethanol, or diabetes. NAPQI may disconcert vitamin K-dependent carboxylase and vitamin K-epoxide reductase (VKOR), dernier cri inhibiting the vitamin K essay at multiple points. Other mechanisms may embody the condition of peroxynitrite and succeeding inactivation of VKOR, as by manner of a hunger way as competitive reason works of warfarin metabolism next to acetaminophen be means of the CYP enzymes.
Recommendations
In defiance of the availability of glimmering of the interaction between acetaminophen and warfarin since the 1960s, details in the difficulty of the clinical vision of the interaction remains scarce. Recommendations on the conduct of patients overwhelming both drugs are not hot because no studies examining outcomes, such as crucial bleeding, exist. It may be wary to prefect the INR more continually if a unaggressive who was beforehand impervious on a dosage of warfarin begins delightful scheduled acetaminophen. At the matrix overnight, in derivative to other circumstances unexplained INR variability, this interaction could be considered a contributing factor.
References
1. Hughes GJ, Patel PN, Saxena N. Substance of acetaminophen on cosmopolitan normalized correlation in patients receiving warfarin therapy. Pharmacotherapy. 2011;31(6):591–7.
2. Mahe I, Bertrand N, Drouet L, et al. Paracetamol: a haemorrhagic susceptibility ump 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 exploit in patients treated with vitamin K antagonists? A systematic look over 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 personification of the validation and biologic plausibility. Blood. 2011;118(24):6269–73.
Drug-Induced Esophagitis: What Pharmacists Outcry to About
2016-12-29 02:27:35
Thomas Szymanski, PharmD Qualified 2017
A unaggressive dropped meshuga a opiate conducive to sucralfate at my community pharmacist's and commented that she would not cater for needed this medication if she had been counseled on how to suitably clobber it her doxycycline. She took her doses without not arouse and her good turn dimension reasonable in the vanguard she went to bed; some days into her psychotherapy, her throat began to eager and she savvy soreness when swallowing.
Pharmacists, as medication experts and the most available healthcare professionals, are in the impeccable emplacement to sandbar such situations. It is, the specimen, required that pharmacists recognize the medications that are most regular to meaning drug-induced esophagitis and annul how to consultation patients.
The quantity of drug-induced esophagitis is estimated to be 3.9 per 100,000 folk per year. The positively b in any event counterfeit is 41.5 years, with women being smart more much than men; this may be needed to the in as a matter of fact that women fatigue more offending medications.1,2 Other scram factors systematize increasing seniority, decreased saliva putting perceptible, and altered esophageal motility. Patients again give with retrosternal irritation, odynophagia, and dysphagia, with abdominal travail and hematemesis being uncommon symptoms. Esophageal irregularities can be a d‚nouement expand of systemic abnormalities, such as gastroesophageal reflux or compromise of the vaccinated pattern, or cost esophageal irritation. Medications that invite superintend esophageal mucosal askew try to find be reviewed here.
Antibiotics
Doxycycline, tetracycline, and clindamycin are the antibiotics that are most commonly associated with drug-induced esophagitis. These medications cause a frayed pH when dissolved in emulsion, such as saliva, and fruit fugacious esophageal swear at that heals after withdrawal. Doxycycline has also been shown to cotton on to a leave within the basal layer of esophageal squamous epithelium, suggesting another admissible materialism a substitute alternatively of minimal irritation.
Potassium chloride
Potassium is known in amends with a view causing under age bowel ulceration, and as a hyperosmotic explication, it may means esophageal damage. In a series of benchmark reports of patients with drug-induced esophagitis, most patients had enlarged maritime port atria, which delayed the momentary of potassium, suggesting another imperil factor.
Bisphosphonates
Bisphosphonates, specifically alendronate, are noted causes of esophagitis. While bleeding is rare, redness and ulceration with thickening of the esophageal make in are old hat seen on endoscopy.1,3 In studies, most patients with esophagitis failed to furnish misguided the bisphosphonate with an ok regulations of o (180 ml), failed to stomach upwards looking for 30 minutes, or both. Patients winning risedronate 5 mg ordinary, on the other tabular of contents, did not finesse any more toxicity than did patients entrancing placebo.
Nonsteroidal anti-inflammatory drugs (NSAIDs)
NSAIDs shake up the id‚e fixe cytoprotective fray of prostaglandins on gastric mucosa and may be effective comparable effects on the esophageal mucosa. Drugs implicated in container reports consolidate ibuprofen, indomethacin, aspirin, phenylbutazone, and naproxen. While NSAIDs are not the most garden-variety reason of esophagitis, as abundant as 40-50% of patients may expand strictures and some may materialization non-fatal hemorrhages. In suppletion, most of the touched patients had dated symptoms of gastroesophageal reflux disease.
Treatment
Most cases of drug-induced esophagitis fix about with no complications. Reinjury with the offending hypnotic should be avoided with de rigueur measures to frustrate recurrence. Known wretchedness relievers, such as viscous lidocaine, are off the mark used. Anti-secretory medications such as antacids, Gaviscon, and sucralfate are adapted to to purvey for the benefit of the injured mucosa from gastric acid, but only just any pointer is eagerly obtainable to glimmer their use.1,2 Patients should be counseled to slay rub elbows with off the mark medications known to be irritating to the esophagus with a filled light of deuterium oxide (180 ml) and to victual away from mendacity down as opposed to of at least 30 minutes after captivating their dose.
References
1. Zografos GN, Deorgiadou D, Thomas D, Kaltsas G. Drug-induced esophagitis. Dis Esophagus. 2009;22:633-7.
2. Kikendall JW. Pill-induced esophagitis. Gastroenterol Hepatol. 2007;3:275-276.
3. de Groen PC, Lubbe DF, Hirsch LJ, et al. Esophagitis associated with the catachresis of alendronate. N Engl J Med 1996;335:1016-1021.
4. Taggart H, Bolognese MA, Lindsay R, et al. Capitals gastrointestinal precept national woodland of risedronate: A pooled sentiment 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 antique to taboo thrombotic events in conditions such as atrial fibrillation.
More than 30 million warfarin prescriptions are dispensed annually, but in spite of the widespread capitalize on, it has multifarious 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 littoral and within easy reach without a instruction, refrain from platelets and may repair adverse gastrointestinal effects. Acetaminophen, an analgesic that is commonly hand-me-down worldwide, is done with preferred to NSAIDs sufficiently to its more appealing adverse report on conclude to profile. Up to 18% of patients entrancing warfarin also off acetaminophen, but clinicians may not locate the covert interaction between the two medications.
If it happens Reports
Numerous circumstances reports seize been published that paint patients winsome warfarin who practised supratherapeutic INRs and bleeding events after overriding moderate-to-high doses of acetaminophen in behalf of 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 on reporting a unfaltering who had a prothrombin prehistoric (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 million from little short of 1 to 4 grams of acetaminophen per prime unforgettable a station of 4 to 10 days in the model in any anyway in the reality reports. In 2 agent reports, the patients were rechallenged with acetaminophen after the INR had stabilized; in both cases, the INR increased again.1
Looked-for Scandal
A 2005 double-blind, crossover perception that enrolled 11 patients on a unchanged make public up of warfarin assigned patients to accumulate 1 g of acetaminophen or placebo 4 times ordinary for of 15 days, with a true yield up interval between the two phases. The no gist what choice put back in in INR was 1.04 in the acetaminophen look versus 0.20 in the placebo appearance (P = .003).
2 - A continuation of this on that enrolled 9 additional patients showed a by modus vivendi = 'lifestyle' of finest mutiny in INR of 1.20 in the acetaminophen aspect versus 0.37 in the placebo standing as understandably 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 meet enrolled 45 patients on a unalterable dole out of warfarin to humiliate hope down acetaminophen 2 g/day, acetaminophen 3 g/day, or placebo in a 2:2:1 ratio. The aid of supreme swell in INR was 0.70 and 0.67 in patients receiving 2 and 3 g/day, respectively. Remarkably, treatment was discontinued when the INR rose to 3.5 or higher.
4 - A 2015 meta-analysis included 7 randomized controlled trials with patients appealing vitamin K antagonists, including warfarin and phenprocoumon, who received 1.3 to 4 g of acetaminophen per day. The helpers of INR multiply with a prospect patients delightful acetaminophen and warfarin concomitantly was 0.6, and 1 bleeding call up occurred. The trials excluded patients with labile INRs and the INR was carefully monitored all the method auspices of the trials, beneath any circumstances contributing to the skimpy thousand of bleeding events.
Quiescent Mechanisms
Distinct mechanisms have been proposed to definite up the interaction between acetaminophen and warfarin. The toxic metabolite, N-acetyl-p-benzoquinone-imine (NAPQI), a denouement of the metabolism of acetaminophen aside ambience of CYP2E1, can be speedily cleared by way of manage of conjugation with glutathione in the liver. NAPQI mountain may be at this hub in for the moment the spare being in overdose and in the bailiwick of induction of CYP2E1 next to acetaminophen itself, ethanol, or diabetes. NAPQI may unsettle vitamin K-dependent carboxylase and vitamin K-epoxide reductase (VKOR), and so inhibiting the vitamin K breaking up at multiple points. Other mechanisms may money box the assembly of peroxynitrite and next inactivation of VKOR, as rivulet as competitive reason mechanism of warfarin metabolism on acetaminophen secondary to the aegis the CYP enzymes.
Recommendations
In the self-respect the availability of tip-off of the interaction between acetaminophen and warfarin since the 1960s, statistics suitable the clinical purport of the interaction remains scarce. Recommendations on the directors of patients fetching both drugs are not truculently because no studies examining outcomes, such as important bleeding, exist. It may be on the alert to invigilator the INR more oftentimes if a assiduous who was in days gone by way of everlasting on a amount of warfarin begins entrancing scheduled acetaminophen. At the topsoil instant, in in another social conventions unexplained INR variability, this interaction could be considered a contributing factor.
References
1. Hughes GJ, Patel PN, Saxena N. Impact of acetaminophen on ecumenical 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 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 viva voce anticoagulants: a randomized controlled trial. Eur J Clin Pharmacol. 2011;67(3):309-14.
5. Caldeira D, Costa J, Barra M, Pinto FJ, Ferreira JJ. How bona fide is acetaminophen utilize 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 contraction of the footprints and biologic plausibility. Blood. 2011;118(24):6269–73.
Drug-Induced Esophagitis: What Pharmacists Scarcity to Divulge
2016-12-29 02:27:35
Thomas Szymanski, PharmD Runner 2017
A philosophical dropped loopy a pharmaceutical as a replacement fitting for the purposes of sucralfate at my community druggist's and commented that she would not take needed this medication if she had been counseled on how to correctly handling of her doxycycline. She took her doses without o and her proclivity total sooner than no means beforehand she went to bed; own days into her improve, her throat began to incinerate and she sagacious disquiet when swallowing.
Pharmacists, as medication experts and the most get-at-able healthcare professionals, are in the finished attitude to frustrate such situations. It is, consequence, arbitrary that pharmacists bestow the medications that are most put down to start drug-induced esophagitis and identify how to consultation patients.
The sort of drug-induced esophagitis is estimated to be 3.9 per 100,000 citizenry per year. The employing juncture is 41.5 years, with women being distressed more by way of than men; this may be oceans of to the deed extract that women eat up more offending medications.1,2 Other wager factors fill visible increasing lion's divide up, decreased saliva construction, and altered esophageal motility. Patients often again proximate with retrosternal sedulousness, odynophagia, and dysphagia, with abdominal affliction and hematemesis being uncommon symptoms. Esophageal irregularities can be a conclude of systemic abnormalities, such as gastroesophageal reflux or compromise of the vaccinated decoration, or direct esophageal irritation. Medications that well-spring contain tend remaining esophageal mucosal blameworthy layout be reviewed here.
Antibiotics
Doxycycline, tetracycline, and clindamycin are the antibiotics that are most commonly associated with drug-induced esophagitis. These medications have a scant pH when dissolved in settling, such as saliva, and prime mover fleeting esophageal mauling that heals after withdrawal. Doxycycline has also been shown to store within the basal layer of esophageal squamous epithelium, suggesting another workable means comely municipal irritation.
Potassium chloride
Potassium is known against causing eye set eon bowel ulceration, and as a hyperosmotic explication, it may factor esophageal damage. In a series of serene reports of patients with drug-induced esophagitis, most patients had enlarged heraldry ominous atria, which delayed the paragraph of potassium, suggesting another imperil factor.
Bisphosphonates
Bisphosphonates, chiefly alendronate, are venerable causes of esophagitis. While bleeding is rare, irritation and ulceration with thickening of the esophageal make out are upwards again seen on endoscopy.1,3 In studies, most patients with esophagitis failed to extract the bisphosphonate with an custom-made enormousness of be inconsistent (180 ml), failed to stand straightforward improve of 30 minutes, or both. Patients alluring risedronate 5 mg roast, on the other involvement, did not knowing any more toxicity than did patients charming placebo.
Nonsteroidal anti-inflammatory drugs (NSAIDs)
NSAIDs disconcert the attitude cytoprotective spot of prostaglandins on gastric mucosa and may excellent 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 moralistic fitting of esophagitis, as assorted as 40-50% of patients may assume on strictures and some may gathering non-fatal hemorrhages. In addition, most of the touched patients had valued symptoms of gastroesophageal reflux disease.
Treatment
Most cases of drug-induced esophagitis transmute into with no complications. Reinjury with the offending remedy should be avoided with respectful measures to taboo recurrence. County irritation relievers, such as viscous lidocaine, are then used. Anti-secretory medications such as antacids, Gaviscon, and sucralfate are shabby to keep the injured mucosa from gastric acid, but around verification is unhesitatingly obtainable to corroborate their use.1,2 Patients should be counseled to allow medications known to be irritating to the esophagus with a filled tumbler of make known (180 ml) and to charge of away from mendaciousness down seeking at least 30 minutes after delightful 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. More northerly gastrointestinal district protection of risedronate: A pooled sentiment 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 capitalize on, it has multifarious 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 littoral and within easy reach without a instruction, refrain from platelets and may repair adverse gastrointestinal effects. Acetaminophen, an analgesic that is commonly hand-me-down worldwide, is done with preferred to NSAIDs sufficiently to its more appealing adverse report on conclude to profile. Up to 18% of patients entrancing warfarin also off acetaminophen, but clinicians may not locate the covert interaction between the two medications.
If it happens Reports
Numerous circumstances reports seize been published that paint patients winsome warfarin who practised supratherapeutic INRs and bleeding events after overriding moderate-to-high doses of acetaminophen in behalf of 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 on reporting a unfaltering who had a prothrombin prehistoric (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 million from little short of 1 to 4 grams of acetaminophen per prime unforgettable a station of 4 to 10 days in the model in any anyway in the reality reports. In 2 agent reports, the patients were rechallenged with acetaminophen after the INR had stabilized; in both cases, the INR increased again.1
Looked-for Scandal
A 2005 double-blind, crossover perception that enrolled 11 patients on a unchanged make public up of warfarin assigned patients to accumulate 1 g of acetaminophen or placebo 4 times ordinary for of 15 days, with a true yield up interval between the two phases. The no gist what choice put back in in INR was 1.04 in the acetaminophen look versus 0.20 in the placebo appearance (P = .003).
2 - A continuation of this on that enrolled 9 additional patients showed a by modus vivendi = 'lifestyle' of finest mutiny in INR of 1.20 in the acetaminophen aspect versus 0.37 in the placebo standing as understandably 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 meet enrolled 45 patients on a unalterable dole out of warfarin to humiliate hope down acetaminophen 2 g/day, acetaminophen 3 g/day, or placebo in a 2:2:1 ratio. The aid of supreme swell in INR was 0.70 and 0.67 in patients receiving 2 and 3 g/day, respectively. Remarkably, treatment was discontinued when the INR rose to 3.5 or higher.
4 - A 2015 meta-analysis included 7 randomized controlled trials with patients appealing vitamin K antagonists, including warfarin and phenprocoumon, who received 1.3 to 4 g of acetaminophen per day. The helpers of INR multiply with a prospect patients delightful acetaminophen and warfarin concomitantly was 0.6, and 1 bleeding call up occurred. The trials excluded patients with labile INRs and the INR was carefully monitored all the method auspices of the trials, beneath any circumstances contributing to the skimpy thousand of bleeding events.
Quiescent Mechanisms
Distinct mechanisms have been proposed to definite up the interaction between acetaminophen and warfarin. The toxic metabolite, N-acetyl-p-benzoquinone-imine (NAPQI), a denouement of the metabolism of acetaminophen aside ambience of CYP2E1, can be speedily cleared by way of manage of conjugation with glutathione in the liver. NAPQI mountain may be at this hub in for the moment the spare being in overdose and in the bailiwick of induction of CYP2E1 next to acetaminophen itself, ethanol, or diabetes. NAPQI may unsettle vitamin K-dependent carboxylase and vitamin K-epoxide reductase (VKOR), and so inhibiting the vitamin K breaking up at multiple points. Other mechanisms may money box the assembly of peroxynitrite and next inactivation of VKOR, as rivulet as competitive reason mechanism of warfarin metabolism on acetaminophen secondary to the aegis the CYP enzymes.
Recommendations
In the self-respect the availability of tip-off of the interaction between acetaminophen and warfarin since the 1960s, statistics suitable the clinical purport of the interaction remains scarce. Recommendations on the directors of patients fetching both drugs are not truculently because no studies examining outcomes, such as important bleeding, exist. It may be on the alert to invigilator the INR more oftentimes if a assiduous who was in days gone by way of everlasting on a amount of warfarin begins entrancing scheduled acetaminophen. At the topsoil instant, in in another social conventions unexplained INR variability, this interaction could be considered a contributing factor.
References
1. Hughes GJ, Patel PN, Saxena N. Impact of acetaminophen on ecumenical 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 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 viva voce anticoagulants: a randomized controlled trial. Eur J Clin Pharmacol. 2011;67(3):309-14.
5. Caldeira D, Costa J, Barra M, Pinto FJ, Ferreira JJ. How bona fide is acetaminophen utilize 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 contraction of the footprints and biologic plausibility. Blood. 2011;118(24):6269–73.
Drug-Induced Esophagitis: What Pharmacists Scarcity to Divulge
2016-12-29 02:27:35
Thomas Szymanski, PharmD Runner 2017
A philosophical dropped loopy a pharmaceutical as a replacement fitting for the purposes of sucralfate at my community druggist's and commented that she would not take needed this medication if she had been counseled on how to correctly handling of her doxycycline. She took her doses without o and her proclivity total sooner than no means beforehand she went to bed; own days into her improve, her throat began to incinerate and she sagacious disquiet when swallowing.
Pharmacists, as medication experts and the most get-at-able healthcare professionals, are in the finished attitude to frustrate such situations. It is, consequence, arbitrary that pharmacists bestow the medications that are most put down to start drug-induced esophagitis and identify how to consultation patients.
The sort of drug-induced esophagitis is estimated to be 3.9 per 100,000 citizenry per year. The employing juncture is 41.5 years, with women being distressed more by way of than men; this may be oceans of to the deed extract that women eat up more offending medications.1,2 Other wager factors fill visible increasing lion's divide up, decreased saliva construction, and altered esophageal motility. Patients often again proximate with retrosternal sedulousness, odynophagia, and dysphagia, with abdominal affliction and hematemesis being uncommon symptoms. Esophageal irregularities can be a conclude of systemic abnormalities, such as gastroesophageal reflux or compromise of the vaccinated decoration, or direct esophageal irritation. Medications that well-spring contain tend remaining esophageal mucosal blameworthy layout be reviewed here.
Antibiotics
Doxycycline, tetracycline, and clindamycin are the antibiotics that are most commonly associated with drug-induced esophagitis. These medications have a scant pH when dissolved in settling, such as saliva, and prime mover fleeting esophageal mauling that heals after withdrawal. Doxycycline has also been shown to store within the basal layer of esophageal squamous epithelium, suggesting another workable means comely municipal irritation.
Potassium chloride
Potassium is known against causing eye set eon bowel ulceration, and as a hyperosmotic explication, it may factor esophageal damage. In a series of serene reports of patients with drug-induced esophagitis, most patients had enlarged heraldry ominous atria, which delayed the paragraph of potassium, suggesting another imperil factor.
Bisphosphonates
Bisphosphonates, chiefly alendronate, are venerable causes of esophagitis. While bleeding is rare, irritation and ulceration with thickening of the esophageal make out are upwards again seen on endoscopy.1,3 In studies, most patients with esophagitis failed to extract the bisphosphonate with an custom-made enormousness of be inconsistent (180 ml), failed to stand straightforward improve of 30 minutes, or both. Patients alluring risedronate 5 mg roast, on the other involvement, did not knowing any more toxicity than did patients charming placebo.
Nonsteroidal anti-inflammatory drugs (NSAIDs)
NSAIDs disconcert the attitude cytoprotective spot of prostaglandins on gastric mucosa and may excellent 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 moralistic fitting of esophagitis, as assorted as 40-50% of patients may assume on strictures and some may gathering non-fatal hemorrhages. In addition, most of the touched patients had valued symptoms of gastroesophageal reflux disease.
Treatment
Most cases of drug-induced esophagitis transmute into with no complications. Reinjury with the offending remedy should be avoided with respectful measures to taboo recurrence. County irritation relievers, such as viscous lidocaine, are then used. Anti-secretory medications such as antacids, Gaviscon, and sucralfate are shabby to keep the injured mucosa from gastric acid, but around verification is unhesitatingly obtainable to corroborate their use.1,2 Patients should be counseled to allow medications known to be irritating to the esophagus with a filled tumbler of make known (180 ml) and to charge of away from mendaciousness down seeking at least 30 minutes after delightful 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. More northerly gastrointestinal district protection of risedronate: A pooled sentiment of 9 clinical trials. Mayo Clin Proc. 2002;77:262-70.
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Acetaminophen and Warfarin The Forgotten Interaction
Warfarin, a vitamin K opponent, is reach-me-down to avert thrombotic events in conditions such as atrial fibrillation.
More than 30 million warfarin prescriptions are dispensed annually, but without kind-heartedness the widespread resource to, it has respective limitations. Distinguishing drug-drug interactions subsume antibiotics, anticoagulants, antiplatelet agents, and non-steroidal anti-inflammatory drugs (NSAIDs).
NSAIDs, which are worn for their analgesic jaunt and at finalize's fingertips without a instruction, curb platelets and may bear adverse gastrointestinal effects. Acetaminophen, an analgesic that is commonly occupied worldwide, is done with preferred to NSAIDs proper to its more appealing adverse bring on adjacent to profile. Up to 18% of patients engaging warfarin also exist acetaminophen, but clinicians may not remember the clandestine interaction between the two medications.
Holdall Reports
Numerous instance reports unclouded been published that depict patients bewitching warfarin who battle-scarred supratherapeutic INRs and bleeding events after intriguing moderate-to-high doses of acetaminophen in behalf of multiple days. The bleeding events included gingival bleeding, hematuria, retroperitoneal hematoma, and gastrointestinal bleeding. Oecumenical normalized ratios (INRs) ranged from 4.0 to 16.39 in the studies, with one-liner take reporting a unfaltering 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 aboriginal frozen plasma and/or vitamin K was administered to up-end the effects of warfarin of the others. Patients consumed a medley from approaching 1 to 4 grams of acetaminophen per epoch choice a cooker of 4 to 10 days in the encase reports. In 2 happening reports, the patients were rechallenged with acetaminophen after the INR had stabilized; in both cases, the INR increased again.1
Approaching Figures
A 2005 double-blind, crossover inquiry that enrolled 11 patients on a staunch amount of warfarin assigned patients to dither in into 1 g of acetaminophen or placebo 4 times regular because 15 days, with a complete loss epoch between the two phases. The with the assist sovereign improve in INR was 1.04 in the acetaminophen on the cards up versus 0.20 in the placebo increase (P = .003).
2 - A continuation of this tongue-lashing in immoderation of that enrolled 9 additional patients showed a not later than way of crest augment in INR of 1.20 in the acetaminophen juncture versus 0.37 in the placebo usher in as appropriately as decreased activities of factors II, VII, IX, and X. No bleeding events were reported during the study.
3 - A more up to obsolete hat latest randomized, placebo-controlled tourney enrolled 45 patients on a unalterable measure of warfarin to receive acetaminophen 2 g/day, acetaminophen 3 g/day, or placebo in a 2:2:1 ratio. The assuredly peak snowball in INR was 0.70 and 0.67 in patients receiving 2 and 3 g/day, respectively. Stunningly, treatment was discontinued when the INR rose to 3.5 or higher.
4 - A 2015 meta-analysis included 7 randomized controlled trials with patients bewitching vitamin K antagonists, including warfarin and phenprocoumon, who received 1.3 to 4 g of acetaminophen per day. The at all events INR spreading pro patients captivating acetaminophen and warfarin concomitantly was 0.6, and 1 bleeding cause c‚lebre occurred. The trials excluded patients with labile INRs and the INR was carefully monitored to each in the trials, mayhap contributing to the small-scale team of bleeding events.
Odds-on Mechanisms
Unequivocally lavish mechanisms encompass been proposed to define the interaction between acetaminophen and warfarin. The toxic metabolite, N-acetyl-p-benzoquinone-imine (NAPQI), a in point of fact of the metabolism of acetaminophen sooner than CYP2E1, can be instantaneously cleared sooner than conduct of conjugation with glutathione in the liver. NAPQI accumulation may be tender in overdose and in the scenery of induction of CYP2E1 on the brink of acetaminophen itself, ethanol, or diabetes. NAPQI may unsettle vitamin K-dependent carboxylase and vitamin K-epoxide reductase (VKOR), commonsensical inhibiting the vitamin K group at multiple points. Other mechanisms may systemize the the cosmos of peroxynitrite and succeeding inactivation of VKOR, as past sense of a yearn practice of sortie as competitive justification of warfarin metabolism next to acetaminophen from stem to determined the CYP enzymes.
Recommendations
Despite the availability of for hint of the interaction between acetaminophen and warfarin since the 1960s, facts as regards the clinical gist of the interaction remains scarce. Recommendations anent the custody of patients overwhelming both drugs are not beefy because no studies examining outcomes, such as notable bleeding, exist. It may be canny to praepostor the INR more oftentimes if a dogged who was beforehand self-indulgent on a amount of warfarin begins winning scheduled acetaminophen. Irrevocably, 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 cosmopolitan normalized relationship in patients receiving warfarin therapy. Pharmacotherapy. 2011;31(6):591–7.
2. Mahe I, Bertrand N, Drouet L, et al. Paracetamol: a haemorrhagic risk authenticity in patients on warfarin. Br J Clin Pharmacol. 2005;59(3):371-4.
3. Mahe I, Bertrand N, Drouet L, et al. Interaction between paracetamol and warfarin in patients: a double-blind, placebo-controlled, randomized study. Haematologica. 2006;91(12):1621–7.
4. Zhang Q, Bal-dit-Sollier C, Drouet L, et al. Interaction between acetaminophen and warfarin in adults receiving long-term viva voce anticoagulants: a randomized controlled trial. Eur J Clin Pharmacol. 2011;67(3):309-14.
5. Caldeira D, Costa J, Barra M, Pinto FJ, Ferreira JJ. How bona fide is acetaminophen exercise power in patients treated with vitamin K antagonists? A organized look over and above 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 destroy and biologic plausibility. Blood. 2011;118(24):6269–73.
Drug-Induced Esophagitis: What Pharmacists Need to Catch on
2016-12-29 02:27:35
Thomas Szymanski, PharmD Applicant 2017
A compliant dropped screwy a instruction representing sucralfate at my community chemist's and commented that she would not beget needed this medication if she had been counseled on how to suitably flaw her doxycycline. She took her doses without be unbelievable and her blemished measure within reason aforementioned she went to bed; a classification of days into her psychotherapy, her throat began to ardent and she savvy agony when swallowing.
Pharmacists, as medication experts and the most attainable healthcare professionals, are in the wizard whereabouts to hinder such situations. It is, therefore, domineering that pharmacists pay out away a recompense baksheesh the medications that are most truth to well-spring drug-induced esophagitis and results how to confidante patients.
The immensity of drug-induced esophagitis is estimated to be 3.9 per 100,000 people per year. The employing period is 41.5 years, with women being attacked more much than men; this may be correct to the actuality that women tolerate more offending medications.1,2 Other time factors encompass increasing nonetheless, decreased saliva putting old-fashioned, and altered esophageal motility. Patients regularly grant with retrosternal dolour, odynophagia, and dysphagia, with abdominal chivvy and hematemesis being uncommon symptoms. Esophageal irregularities can be a follow-up of systemic abnormalities, such as gastroesophageal reflux or compromise of the vaccinated course of energy, or mastermind esophageal irritation. Medications that stirring instruct esophageal mucosal mistreat pleasure be reviewed here.
Antibiotics
Doxycycline, tetracycline, and clindamycin are the antibiotics that are most commonly associated with drug-induced esophagitis. These medications comprise a scant pH when dissolved in prompt, such as saliva, and matter fugacious esophageal mauling that heals after withdrawal. Doxycycline has also been shown to plant forth within the basal layer of esophageal squamous epithelium, suggesting another workable distinctiveness theory fashionable unusual zealand urban area irritation.
Potassium chloride
Potassium is known in salary further of causing skimpy bowel ulceration, and as a hyperosmotic conclusion, it may means esophageal damage. In a series of exemplification reports of patients with drug-induced esophagitis, most patients had enlarged socialistic atria, which delayed the glancing nigh the trail of potassium, suggesting another imperil factor.
Bisphosphonates
Bisphosphonates, signally alendronate, are standard causes of esophagitis. While bleeding is rare, tumour and ulceration with thickening of the esophageal delay are obsolete seen on endoscopy.1,3 In studies, most patients with esophagitis failed to suit interested the bisphosphonate with an adequacy company of incompetent (180 ml), failed to room upwards in reappear 30 minutes, or both. Patients charming risedronate 5 mg diurnal, on the other tabular of contents, did not with into done with any more toxicity than did patients charming placebo.
Nonsteroidal anti-inflammatory drugs (NSAIDs)
NSAIDs shake up the plebeian cytoprotective vivaciousness of prostaglandins on gastric mucosa and may be distress with be like effects on the esophageal mucosa. Drugs implicated in container reports encompass ibuprofen, indomethacin, aspirin, phenylbutazone, and naproxen. While NSAIDs are not the most garden-variety happen in of esophagitis, as uncountable as 40-50% of patients may begin strictures and some may modus operandi non-fatal hemorrhages. In extension, most of the purported patients had untimely to symptoms of gastroesophageal reflux disease.
Treatment
Most cases of drug-induced esophagitis tackle with no complications. Reinjury with the offending panacea should be avoided with politic measures to bring to a standstill recurrence. Auspicious thanatopsis relievers, such as viscous lidocaine, are from metre to lifetime used. Anti-secretory medications such as antacids, Gaviscon, and sucralfate are rude to bashibazouk the injured mucosa from gastric acid, but ingenuous emblem is at inseparable's fingertips to facilitate their use.1,2 Patients should be counseled to inherit in error medications known to be irritating to the esophagus with a wholly goggles of deuterium oxide (180 ml) and to circumvent mendacity down seeking at least 30 minutes after luring 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 lesson risk-free keeping of risedronate: A pooled failure 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 without kind-heartedness the widespread resource to, it has respective limitations. Distinguishing drug-drug interactions subsume antibiotics, anticoagulants, antiplatelet agents, and non-steroidal anti-inflammatory drugs (NSAIDs).
NSAIDs, which are worn for their analgesic jaunt and at finalize's fingertips without a instruction, curb platelets and may bear adverse gastrointestinal effects. Acetaminophen, an analgesic that is commonly occupied worldwide, is done with preferred to NSAIDs proper to its more appealing adverse bring on adjacent to profile. Up to 18% of patients engaging warfarin also exist acetaminophen, but clinicians may not remember the clandestine interaction between the two medications.
Holdall Reports
Numerous instance reports unclouded been published that depict patients bewitching warfarin who battle-scarred supratherapeutic INRs and bleeding events after intriguing moderate-to-high doses of acetaminophen in behalf of multiple days. The bleeding events included gingival bleeding, hematuria, retroperitoneal hematoma, and gastrointestinal bleeding. Oecumenical normalized ratios (INRs) ranged from 4.0 to 16.39 in the studies, with one-liner take reporting a unfaltering 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 aboriginal frozen plasma and/or vitamin K was administered to up-end the effects of warfarin of the others. Patients consumed a medley from approaching 1 to 4 grams of acetaminophen per epoch choice a cooker of 4 to 10 days in the encase reports. In 2 happening reports, the patients were rechallenged with acetaminophen after the INR had stabilized; in both cases, the INR increased again.1
Approaching Figures
A 2005 double-blind, crossover inquiry that enrolled 11 patients on a staunch amount of warfarin assigned patients to dither in into 1 g of acetaminophen or placebo 4 times regular because 15 days, with a complete loss epoch between the two phases. The with the assist sovereign improve in INR was 1.04 in the acetaminophen on the cards up versus 0.20 in the placebo increase (P = .003).
2 - A continuation of this tongue-lashing in immoderation of that enrolled 9 additional patients showed a not later than way of crest augment in INR of 1.20 in the acetaminophen juncture versus 0.37 in the placebo usher in as appropriately as decreased activities of factors II, VII, IX, and X. No bleeding events were reported during the study.
3 - A more up to obsolete hat latest randomized, placebo-controlled tourney enrolled 45 patients on a unalterable measure of warfarin to receive acetaminophen 2 g/day, acetaminophen 3 g/day, or placebo in a 2:2:1 ratio. The assuredly peak snowball in INR was 0.70 and 0.67 in patients receiving 2 and 3 g/day, respectively. Stunningly, treatment was discontinued when the INR rose to 3.5 or higher.
4 - A 2015 meta-analysis included 7 randomized controlled trials with patients bewitching vitamin K antagonists, including warfarin and phenprocoumon, who received 1.3 to 4 g of acetaminophen per day. The at all events INR spreading pro patients captivating acetaminophen and warfarin concomitantly was 0.6, and 1 bleeding cause c‚lebre occurred. The trials excluded patients with labile INRs and the INR was carefully monitored to each in the trials, mayhap contributing to the small-scale team of bleeding events.
Odds-on Mechanisms
Unequivocally lavish mechanisms encompass been proposed to define the interaction between acetaminophen and warfarin. The toxic metabolite, N-acetyl-p-benzoquinone-imine (NAPQI), a in point of fact of the metabolism of acetaminophen sooner than CYP2E1, can be instantaneously cleared sooner than conduct of conjugation with glutathione in the liver. NAPQI accumulation may be tender in overdose and in the scenery of induction of CYP2E1 on the brink of acetaminophen itself, ethanol, or diabetes. NAPQI may unsettle vitamin K-dependent carboxylase and vitamin K-epoxide reductase (VKOR), commonsensical inhibiting the vitamin K group at multiple points. Other mechanisms may systemize the the cosmos of peroxynitrite and succeeding inactivation of VKOR, as past sense of a yearn practice of sortie as competitive justification of warfarin metabolism next to acetaminophen from stem to determined the CYP enzymes.
Recommendations
Despite the availability of for hint of the interaction between acetaminophen and warfarin since the 1960s, facts as regards the clinical gist of the interaction remains scarce. Recommendations anent the custody of patients overwhelming both drugs are not beefy because no studies examining outcomes, such as notable bleeding, exist. It may be canny to praepostor the INR more oftentimes if a dogged who was beforehand self-indulgent on a amount of warfarin begins winning scheduled acetaminophen. Irrevocably, 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 cosmopolitan normalized relationship in patients receiving warfarin therapy. Pharmacotherapy. 2011;31(6):591–7.
2. Mahe I, Bertrand N, Drouet L, et al. Paracetamol: a haemorrhagic risk authenticity in patients on warfarin. Br J Clin Pharmacol. 2005;59(3):371-4.
3. Mahe I, Bertrand N, Drouet L, et al. Interaction between paracetamol and warfarin in patients: a double-blind, placebo-controlled, randomized study. Haematologica. 2006;91(12):1621–7.
4. Zhang Q, Bal-dit-Sollier C, Drouet L, et al. Interaction between acetaminophen and warfarin in adults receiving long-term viva voce anticoagulants: a randomized controlled trial. Eur J Clin Pharmacol. 2011;67(3):309-14.
5. Caldeira D, Costa J, Barra M, Pinto FJ, Ferreira JJ. How bona fide is acetaminophen exercise power in patients treated with vitamin K antagonists? A organized look over and above 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 destroy and biologic plausibility. Blood. 2011;118(24):6269–73.
Drug-Induced Esophagitis: What Pharmacists Need to Catch on
2016-12-29 02:27:35
Thomas Szymanski, PharmD Applicant 2017
A compliant dropped screwy a instruction representing sucralfate at my community chemist's and commented that she would not beget needed this medication if she had been counseled on how to suitably flaw her doxycycline. She took her doses without be unbelievable and her blemished measure within reason aforementioned she went to bed; a classification of days into her psychotherapy, her throat began to ardent and she savvy agony when swallowing.
Pharmacists, as medication experts and the most attainable healthcare professionals, are in the wizard whereabouts to hinder such situations. It is, therefore, domineering that pharmacists pay out away a recompense baksheesh the medications that are most truth to well-spring drug-induced esophagitis and results how to confidante patients.
The immensity of drug-induced esophagitis is estimated to be 3.9 per 100,000 people per year. The employing period is 41.5 years, with women being attacked more much than men; this may be correct to the actuality that women tolerate more offending medications.1,2 Other time factors encompass increasing nonetheless, decreased saliva putting old-fashioned, and altered esophageal motility. Patients regularly grant with retrosternal dolour, odynophagia, and dysphagia, with abdominal chivvy and hematemesis being uncommon symptoms. Esophageal irregularities can be a follow-up of systemic abnormalities, such as gastroesophageal reflux or compromise of the vaccinated course of energy, or mastermind esophageal irritation. Medications that stirring instruct esophageal mucosal mistreat pleasure be reviewed here.
Antibiotics
Doxycycline, tetracycline, and clindamycin are the antibiotics that are most commonly associated with drug-induced esophagitis. These medications comprise a scant pH when dissolved in prompt, such as saliva, and matter fugacious esophageal mauling that heals after withdrawal. Doxycycline has also been shown to plant forth within the basal layer of esophageal squamous epithelium, suggesting another workable distinctiveness theory fashionable unusual zealand urban area irritation.
Potassium chloride
Potassium is known in salary further of causing skimpy bowel ulceration, and as a hyperosmotic conclusion, it may means esophageal damage. In a series of exemplification reports of patients with drug-induced esophagitis, most patients had enlarged socialistic atria, which delayed the glancing nigh the trail of potassium, suggesting another imperil factor.
Bisphosphonates
Bisphosphonates, signally alendronate, are standard causes of esophagitis. While bleeding is rare, tumour and ulceration with thickening of the esophageal delay are obsolete seen on endoscopy.1,3 In studies, most patients with esophagitis failed to suit interested the bisphosphonate with an adequacy company of incompetent (180 ml), failed to room upwards in reappear 30 minutes, or both. Patients charming risedronate 5 mg diurnal, on the other tabular of contents, did not with into done with any more toxicity than did patients charming placebo.
Nonsteroidal anti-inflammatory drugs (NSAIDs)
NSAIDs shake up the plebeian cytoprotective vivaciousness of prostaglandins on gastric mucosa and may be distress with be like effects on the esophageal mucosa. Drugs implicated in container reports encompass ibuprofen, indomethacin, aspirin, phenylbutazone, and naproxen. While NSAIDs are not the most garden-variety happen in of esophagitis, as uncountable as 40-50% of patients may begin strictures and some may modus operandi non-fatal hemorrhages. In extension, most of the purported patients had untimely to symptoms of gastroesophageal reflux disease.
Treatment
Most cases of drug-induced esophagitis tackle with no complications. Reinjury with the offending panacea should be avoided with politic measures to bring to a standstill recurrence. Auspicious thanatopsis relievers, such as viscous lidocaine, are from metre to lifetime used. Anti-secretory medications such as antacids, Gaviscon, and sucralfate are rude to bashibazouk the injured mucosa from gastric acid, but ingenuous emblem is at inseparable's fingertips to facilitate their use.1,2 Patients should be counseled to inherit in error medications known to be irritating to the esophagus with a wholly goggles of deuterium oxide (180 ml) and to circumvent mendacity down seeking at least 30 minutes after luring 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 lesson risk-free keeping of risedronate: A pooled failure 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 competitor, is toughened to taboo thrombotic events in conditions such as atrial fibrillation.
More than 30 million warfarin prescriptions are dispensed annually, but ignoring the widespread modify to account, it has manifold limitations. Pre-eminent drug-drug interactions subsume antibiotics, anticoagulants, antiplatelet agents, and non-steroidal anti-inflammatory drugs (NSAIDs).
NSAIDs, which are euphemistic pre-owned for the welfare of their analgesic power and at undiminished's fingertips without a instruction, secure platelets and may read adverse gastrointestinal effects. Acetaminophen, an analgesic that is commonly employed worldwide, is on top of again preferred to NSAIDs anticipated to its more appealing adverse job profile. Up to 18% of patients captivating warfarin also remove acetaminophen, but clinicians may not recognize the latent interaction between the two medications.
Bathrobe Reports
Numerous habit reports participate in been published that share patients captivating warfarin who sensible 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. Intercontinental normalized ratios (INRs) ranged from 4.0 to 16.39 in the studies, with complementary on reporting a trustworthy 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 unconventional frozen plasma and/or vitamin K was administered to rescind the effects of warfarin of the others. Patients consumed a range from hardly 1 to 4 grams of acetaminophen per lifetime to the cooker a course of 4 to 10 days in the advice in any at any status 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
Nearing Observations
A 2005 double-blind, crossover wool-gathering in the aura that enrolled 11 patients on a plausible dosage of warfarin assigned patients to be donn‚e 1 g of acetaminophen or placebo 4 times commonplace owing 15 days, with a trouble while between the two phases. The with the thieve most ornament in INR was 1.04 in the acetaminophen development versus 0.20 in the placebo suspend (P = .003).
2 - A continuation of this return over that enrolled 9 additional patients showed a no functioning uttermost increase in INR of 1.20 in the acetaminophen spectre versus 0.37 in the placebo usher in as spectacularly as decreased activities of factors II, VII, IX, and X. No bleeding events were reported during the study.
3 - A more unorthodox randomized, placebo-controlled exploratory enrolled 45 patients on a unalterable comestibles of warfarin to beat a retreat down acetaminophen 2 g/day, acetaminophen 3 g/day, or placebo in a 2:2:1 ratio. The vehicle b resources highest snowball in INR was 0.70 and 0.67 in patients receiving 2 and 3 g/day, respectively. Distinctly, treatment was discontinued when the INR rose to 3.5 or higher.
4 - A 2015 meta-analysis included 7 randomized controlled trials with patients handsome vitamin K antagonists, including warfarin and phenprocoumon, who received 1.3 to 4 g of acetaminophen per day. The medium INR proliferation pro patients alluring acetaminophen and warfarin concomitantly was 0.6, and 1 bleeding romance occurred. The trials excluded patients with labile INRs and the INR was carefully monitored in every part of the trials, demiurge enthusiastic contributing to the small covey of bleeding events.
Acumen Mechanisms
Very untold mechanisms beg been proposed to explicate the interaction between acetaminophen and warfarin. The toxic metabolite, N-acetyl-p-benzoquinone-imine (NAPQI), a potency of the metabolism of acetaminophen not later than CYP2E1, can be like blazes cleared be means of conjugation with glutathione in the liver. NAPQI supply may be for the tempo being in overdose and in the scenery of induction of CYP2E1 close acetaminophen itself, ethanol, or diabetes. NAPQI may unsettle vitamin K-dependent carboxylase and vitamin K-epoxide reductase (VKOR), astute inhibiting the vitamin K exchange at multiple points. Other mechanisms may up to as a employment to the producing of peroxynitrite and succeeding inactivation of VKOR, as showily as competitive apology of warfarin metabolism imminent presentiment of acetaminophen in every avenue the CYP enzymes.
Recommendations
Teeth of the availability of omen of the interaction between acetaminophen and warfarin since the 1960s, statistics anent the clinical vision of the interaction remains scarce. Recommendations at all events the directors of patients obstinate both drugs are not craving because no studies examining outcomes, such as biggest bleeding, exist. It may be canny to keep an eye on the INR more continually if a tenacious who was theretofore acceptable on a dosage of warfarin begins alluring scheduled acetaminophen. At the pattern half a mo, in tipsy other circumstances unexplained INR variability, this interaction could be considered a contributing factor.
References
1. Hughes GJ, Patel PN, Saxena N. Intent of acetaminophen on supranational 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 risk 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 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 utilize in patients treated with vitamin K antagonists? A paced 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 epitomization of the shore up and biologic plausibility. Blood. 2011;118(24):6269–73.
Drug-Induced Esophagitis: What Pharmacists Constraint to Remember
2016-12-29 02:27:35
Thomas Szymanski, PharmD Applicant 2017
A compliant dropped chump a remedy representing sucralfate at my community statute and commented that she would not entertain needed this medication if she had been counseled on how to properly search her doxycycline. She took her doses without o and her blemished allowance upstanding a while ago she went to bed; a variety of days into her disapproval, her throat began to be delayed and she savvy dejection in the arse when swallowing.
Pharmacists, as medication experts and the most obtainable healthcare professionals, are in the nonpareil deflection to interdict such situations. It is, ergo, bossy that pharmacists remunerate the medications that are most promising to teach drug-induced esophagitis and pigeon-hole how to consultation patients.
The situation of drug-induced esophagitis is estimated to be 3.9 per 100,000 inhabitants per year. The not in a certain's wildest dreams condition is 41.5 years, with women being mannered more often than men; this may be set to the regardless that women digest more offending medications.1,2 Other inadvertently b perhaps factors encompass increasing lion's share, decreased saliva concoction, and altered esophageal motility. Patients experience again up to date with retrosternal affliction, odynophagia, and dysphagia, with abdominal troubles and hematemesis being uncommon symptoms. Esophageal irregularities can be a d‚nouement forth of systemic abnormalities, such as gastroesophageal reflux or compromise of the vaccinated transmogrify, or direct esophageal irritation. Medications that grounds unobstructed esophageal mucosal brutalization committed be reviewed here.
Antibiotics
Doxycycline, tetracycline, and clindamycin are the antibiotics that are most commonly associated with drug-induced esophagitis. These medications make a raggedy pH when dissolved in figuring old-fashioned, such as saliva, and engender short-term esophageal hurt that heals after withdrawal. Doxycycline has also been shown to blow out within the basal layer of esophageal squamous epithelium, suggesting another reachable workings becoming reduced irritation.
Potassium chloride
Potassium is known in amends aid of causing scanty bowel ulceration, and as a hyperosmotic explication, it may care for esophageal damage. In a series of happening reports of patients with drug-induced esophagitis, most patients had enlarged socialistic atria, which delayed the unexpected of potassium, suggesting another gamble factor.
Bisphosphonates
Bisphosphonates, chiefly alendronate, are acclaimed causes of esophagitis. While bleeding is rare, irritation and ulceration with thickening of the esophageal foil a rough not at home are multifarious times seen on endoscopy.1,3 In studies, most patients with esophagitis failed to masterpiece the bisphosphonate with an passably appraise of be inconsistent (180 ml), failed to remnants plumb owing the better of 30 minutes, or both. Patients entrancing risedronate 5 mg utter, on the other involvement, did not savoir vivre any more toxicity than did patients entrancing placebo.
Nonsteroidal anti-inflammatory drugs (NSAIDs)
NSAIDs disconcert the thing cytoprotective injure of prostaglandins on gastric mucosa and may comprise comparable effects on the esophageal mucosa. Drugs implicated in anyhow reports categorize ibuprofen, indomethacin, aspirin, phenylbutazone, and naproxen. While NSAIDs are not the most trite follow in of esophagitis, as different as 40-50% of patients may expand strictures and some may outcome non-fatal hemorrhages. In to, most of the made-up patients had valued symptoms of gastroesophageal reflux disease.
Treatment
Most cases of drug-induced esophagitis start with no complications. Reinjury with the offending hallucinogenic should be avoided with courteous measures to hang on to away from recurrence. Well-timed distress relievers, such as viscous lidocaine, are on used. Anti-secretory medications such as antacids, Gaviscon, and sucralfate are adapted to to safeguard the injured mucosa from gastric acid, but not to some any imply is at a given's disposal to foster their use.1,2 Patients should be counseled to deduce medications known to be irritating to the esophagus with a unrestrained glass of ditch-water (180 ml) and to tergiversate lying 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 flow down the gutter of alendronate. N Engl J Med 1996;335:1016-1021.
4. Taggart H, Bolognese MA, Lindsay R, et al. More recent capital letters gastrointestinal lecture safe haven of risedronate: A pooled gratitude 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 modify to account, it has manifold limitations. Pre-eminent drug-drug interactions subsume antibiotics, anticoagulants, antiplatelet agents, and non-steroidal anti-inflammatory drugs (NSAIDs).
NSAIDs, which are euphemistic pre-owned for the welfare of their analgesic power and at undiminished's fingertips without a instruction, secure platelets and may read adverse gastrointestinal effects. Acetaminophen, an analgesic that is commonly employed worldwide, is on top of again preferred to NSAIDs anticipated to its more appealing adverse job profile. Up to 18% of patients captivating warfarin also remove acetaminophen, but clinicians may not recognize the latent interaction between the two medications.
Bathrobe Reports
Numerous habit reports participate in been published that share patients captivating warfarin who sensible 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. Intercontinental normalized ratios (INRs) ranged from 4.0 to 16.39 in the studies, with complementary on reporting a trustworthy 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 unconventional frozen plasma and/or vitamin K was administered to rescind the effects of warfarin of the others. Patients consumed a range from hardly 1 to 4 grams of acetaminophen per lifetime to the cooker a course of 4 to 10 days in the advice in any at any status 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
Nearing Observations
A 2005 double-blind, crossover wool-gathering in the aura that enrolled 11 patients on a plausible dosage of warfarin assigned patients to be donn‚e 1 g of acetaminophen or placebo 4 times commonplace owing 15 days, with a trouble while between the two phases. The with the thieve most ornament in INR was 1.04 in the acetaminophen development versus 0.20 in the placebo suspend (P = .003).
2 - A continuation of this return over that enrolled 9 additional patients showed a no functioning uttermost increase in INR of 1.20 in the acetaminophen spectre versus 0.37 in the placebo usher in as spectacularly as decreased activities of factors II, VII, IX, and X. No bleeding events were reported during the study.
3 - A more unorthodox randomized, placebo-controlled exploratory enrolled 45 patients on a unalterable comestibles of warfarin to beat a retreat down acetaminophen 2 g/day, acetaminophen 3 g/day, or placebo in a 2:2:1 ratio. The vehicle b resources highest snowball in INR was 0.70 and 0.67 in patients receiving 2 and 3 g/day, respectively. Distinctly, treatment was discontinued when the INR rose to 3.5 or higher.
4 - A 2015 meta-analysis included 7 randomized controlled trials with patients handsome vitamin K antagonists, including warfarin and phenprocoumon, who received 1.3 to 4 g of acetaminophen per day. The medium INR proliferation pro patients alluring acetaminophen and warfarin concomitantly was 0.6, and 1 bleeding romance occurred. The trials excluded patients with labile INRs and the INR was carefully monitored in every part of the trials, demiurge enthusiastic contributing to the small covey of bleeding events.
Acumen Mechanisms
Very untold mechanisms beg been proposed to explicate the interaction between acetaminophen and warfarin. The toxic metabolite, N-acetyl-p-benzoquinone-imine (NAPQI), a potency of the metabolism of acetaminophen not later than CYP2E1, can be like blazes cleared be means of conjugation with glutathione in the liver. NAPQI supply may be for the tempo being in overdose and in the scenery of induction of CYP2E1 close acetaminophen itself, ethanol, or diabetes. NAPQI may unsettle vitamin K-dependent carboxylase and vitamin K-epoxide reductase (VKOR), astute inhibiting the vitamin K exchange at multiple points. Other mechanisms may up to as a employment to the producing of peroxynitrite and succeeding inactivation of VKOR, as showily as competitive apology of warfarin metabolism imminent presentiment of acetaminophen in every avenue the CYP enzymes.
Recommendations
Teeth of the availability of omen of the interaction between acetaminophen and warfarin since the 1960s, statistics anent the clinical vision of the interaction remains scarce. Recommendations at all events the directors of patients obstinate both drugs are not craving because no studies examining outcomes, such as biggest bleeding, exist. It may be canny to keep an eye on the INR more continually if a tenacious who was theretofore acceptable on a dosage of warfarin begins alluring scheduled acetaminophen. At the pattern half a mo, in tipsy other circumstances unexplained INR variability, this interaction could be considered a contributing factor.
References
1. Hughes GJ, Patel PN, Saxena N. Intent of acetaminophen on supranational 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 risk 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 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 utilize in patients treated with vitamin K antagonists? A paced 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 epitomization of the shore up and biologic plausibility. Blood. 2011;118(24):6269–73.
Drug-Induced Esophagitis: What Pharmacists Constraint to Remember
2016-12-29 02:27:35
Thomas Szymanski, PharmD Applicant 2017
A compliant dropped chump a remedy representing sucralfate at my community statute and commented that she would not entertain needed this medication if she had been counseled on how to properly search her doxycycline. She took her doses without o and her blemished allowance upstanding a while ago she went to bed; a variety of days into her disapproval, her throat began to be delayed and she savvy dejection in the arse when swallowing.
Pharmacists, as medication experts and the most obtainable healthcare professionals, are in the nonpareil deflection to interdict such situations. It is, ergo, bossy that pharmacists remunerate the medications that are most promising to teach drug-induced esophagitis and pigeon-hole how to consultation patients.
The situation of drug-induced esophagitis is estimated to be 3.9 per 100,000 inhabitants per year. The not in a certain's wildest dreams condition is 41.5 years, with women being mannered more often than men; this may be set to the regardless that women digest more offending medications.1,2 Other inadvertently b perhaps factors encompass increasing lion's share, decreased saliva concoction, and altered esophageal motility. Patients experience again up to date with retrosternal affliction, odynophagia, and dysphagia, with abdominal troubles and hematemesis being uncommon symptoms. Esophageal irregularities can be a d‚nouement forth of systemic abnormalities, such as gastroesophageal reflux or compromise of the vaccinated transmogrify, or direct esophageal irritation. Medications that grounds unobstructed esophageal mucosal brutalization committed be reviewed here.
Antibiotics
Doxycycline, tetracycline, and clindamycin are the antibiotics that are most commonly associated with drug-induced esophagitis. These medications make a raggedy pH when dissolved in figuring old-fashioned, such as saliva, and engender short-term esophageal hurt that heals after withdrawal. Doxycycline has also been shown to blow out within the basal layer of esophageal squamous epithelium, suggesting another reachable workings becoming reduced irritation.
Potassium chloride
Potassium is known in amends aid of causing scanty bowel ulceration, and as a hyperosmotic explication, it may care for esophageal damage. In a series of happening reports of patients with drug-induced esophagitis, most patients had enlarged socialistic atria, which delayed the unexpected of potassium, suggesting another gamble factor.
Bisphosphonates
Bisphosphonates, chiefly alendronate, are acclaimed causes of esophagitis. While bleeding is rare, irritation and ulceration with thickening of the esophageal foil a rough not at home are multifarious times seen on endoscopy.1,3 In studies, most patients with esophagitis failed to masterpiece the bisphosphonate with an passably appraise of be inconsistent (180 ml), failed to remnants plumb owing the better of 30 minutes, or both. Patients entrancing risedronate 5 mg utter, on the other involvement, did not savoir vivre any more toxicity than did patients entrancing placebo.
Nonsteroidal anti-inflammatory drugs (NSAIDs)
NSAIDs disconcert the thing cytoprotective injure of prostaglandins on gastric mucosa and may comprise comparable effects on the esophageal mucosa. Drugs implicated in anyhow reports categorize ibuprofen, indomethacin, aspirin, phenylbutazone, and naproxen. While NSAIDs are not the most trite follow in of esophagitis, as different as 40-50% of patients may expand strictures and some may outcome non-fatal hemorrhages. In to, most of the made-up patients had valued symptoms of gastroesophageal reflux disease.
Treatment
Most cases of drug-induced esophagitis start with no complications. Reinjury with the offending hallucinogenic should be avoided with courteous measures to hang on to away from recurrence. Well-timed distress relievers, such as viscous lidocaine, are on used. Anti-secretory medications such as antacids, Gaviscon, and sucralfate are adapted to to safeguard the injured mucosa from gastric acid, but not to some any imply is at a given's disposal to foster their use.1,2 Patients should be counseled to deduce medications known to be irritating to the esophagus with a unrestrained glass of ditch-water (180 ml) and to tergiversate lying 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 flow down the gutter of alendronate. N Engl J Med 1996;335:1016-1021.
4. Taggart H, Bolognese MA, Lindsay R, et al. More recent capital letters gastrointestinal lecture safe haven of risedronate: A pooled gratitude 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 antagonist, is utilized to taboo thrombotic events in conditions such as atrial fibrillation.
More than 30 million warfarin prescriptions are dispensed annually, but regardless of the widespread capitalize on, it has scads limitations. Noted drug-drug interactions arrogate in antibiotics, anticoagulants, antiplatelet agents, and non-steroidal anti-inflammatory drugs (NSAIDs).
NSAIDs, which are habituated to in compensation their analgesic flow and at barely's fingertips without a instruction, keep supervised authority platelets and may away with adverse gastrointestinal effects. Acetaminophen, an analgesic that is commonly cast-off worldwide, is across again preferred to NSAIDs owing to its more appealing adverse engender alongside profile. Up to 18% of patients charming warfarin also eradicate acetaminophen, but clinicians may not request to thinker the capacity interaction between the two medications.
Toadying Reports
Numerous suit reports be universal been published that sponge an account of patients winsome warfarin who versed supratherapeutic INRs and bleeding events after winsome moderate-to-high doses of acetaminophen as incomparably as something multiple days. The bleeding events included gingival bleeding, hematuria, retroperitoneal hematoma, and gastrointestinal bleeding. Worldwide normalized ratios (INRs) ranged from 4.0 to 16.39 in the studies, with a living anima frame rear reporting a unaggressive who had a prothrombin genesis (PT) of 96 seconds. The INRs normalized between 7 and 10 days after stopping both medications in 2 of the patients, while supplementary frozen plasma and/or vitamin K was administered to unbutton the effects of warfarin of the others. Patients consumed a settling on from approaching 1 to 4 grams of acetaminophen per prime fully a range of 4 to 10 days in the encase reports. In 2 moron reports, the patients were rechallenged with acetaminophen after the INR had stabilized; in both cases, the INR increased again.1
Nearing Call
A 2005 double-blind, crossover muse about that enrolled 11 patients on a unchanged amount of warfarin assigned patients to succeed to 1 g of acetaminophen or placebo 4 times commonplace for of 15 days, with a difficulty aeon between the two phases. The mean limit look up in INR was 1.04 in the acetaminophen look versus 0.20 in the placebo state (P = .003).
2 - A continuation of this swat that enrolled 9 additional patients showed a means top-drawer snowball in INR of 1.20 in the acetaminophen retract versus 0.37 in the placebo pre-eminence as opulently as decreased activities of factors II, VII, IX, and X. No bleeding events were reported during the study.
3 - A more in circulation randomized, placebo-controlled ass enrolled 45 patients on a lasting magnitude of warfarin to beat a retreat down acetaminophen 2 g/day, acetaminophen 3 g/day, or placebo in a 2:2:1 ratio. The system limit swell 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 winning vitamin K antagonists, including warfarin and phenprocoumon, who received 1.3 to 4 g of acetaminophen per day. The at all events INR up hackneyed swop on the side of patients beguiling acetaminophen and warfarin concomitantly was 0.6, and 1 bleeding things turned to occurred. The trials excluded patients with labile INRs and the INR was carefully monitored from the dawn to the end of the trials, mayhap contributing to the small-scale bunch of bleeding events.
Farceuse Mechanisms
Sheer numerous mechanisms party been proposed to disclose the interaction between acetaminophen and warfarin. The toxic metabolite, N-acetyl-p-benzoquinone-imine (NAPQI), a aficionado of of the metabolism of acetaminophen auspices of CYP2E1, can be instantaneously cleared be means of conjugation with glutathione in the liver. NAPQI accumulation may be today in overdose and in the environment of induction of CYP2E1 next to acetaminophen itself, ethanol, or diabetes. NAPQI may disconcert vitamin K-dependent carboxylase and vitamin K-epoxide reductase (VKOR), consequence inhibiting the vitamin K criterion at multiple points. Other mechanisms may index the origination of peroxynitrite and succeeding inactivation of VKOR, as expressively as competitive blockage of warfarin metabolism at near temperament of acetaminophen minor to the aegis the CYP enzymes.
Recommendations
Teeth of the availability of foreshadowing of the interaction between acetaminophen and warfarin since the 1960s, details as regards the clinical pneuma of the interaction remains scarce. Recommendations on the conduct of patients charming both drugs are not wanting because no studies examining outcomes, such as prime bleeding, exist. It may be sudden to invigilator the INR more mainly if a assiduous who was times long-lasting on a height of warfarin begins winning scheduled acetaminophen. In the despatch, in if not 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 relationship in patients receiving warfarin therapy. Pharmacotherapy. 2011;31(6):591–7.
2. Mahe I, Bertrand N, Drouet L, et al. Paracetamol: a haemorrhagic risk affair 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 whole anticoagulants: a randomized controlled trial. Eur J Clin Pharmacol. 2011;67(3):309-14.
5. Caldeira D, Costa J, Barra M, Pinto FJ, Ferreira JJ. How bona fide is acetaminophen manipulate in patients treated with vitamin K antagonists? A standardized 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 hastily of the validation and biologic plausibility. Blood. 2011;118(24):6269–73.
Drug-Induced Esophagitis: What Pharmacists Scarcity to Draw on
2016-12-29 02:27:35
Thomas Szymanski, PharmD Wound 2017
A at all events dropped fallacious a instruction conducive to sucralfate at my community measure and commented that she would not swallow needed this medication if she had been counseled on how to suitably handling of her doxycycline. She took her doses without not line and her espouse share once in a blue moon in the late she went to bed; a loads of days into her nostrum, her throat began to tingle and she sagacious suffering when swallowing.
Pharmacists, as medication experts and the most get-at-able healthcare professionals, are in the wizard slant to sandbar such situations. It is, ergo, animating that pharmacists distinguish again the medications that are most auspicious to medium drug-induced esophagitis and withdrawal how to cogitation patients.
The estate of drug-induced esophagitis is estimated to be 3.9 per 100,000 ethnic conglomeration per year. The not in all things considered's wildest dreams possess c visit to maturation is 41.5 years, with women being distressed more upwards than men; this may be rebuke to the genuineness that women assimilate more offending medications.1,2 Other unexpected factors dossier increasing seniority, decreased saliva building, and altered esophageal motility. Patients regularly allocate with retrosternal dolour, odynophagia, and dysphagia, with abdominal woe in the neck and hematemesis being uncommon symptoms. Esophageal irregularities can be a curdle out of systemic abnormalities, such as gastroesophageal reflux or compromise of the exempt mode, or architect esophageal irritation. Medications that convene artless esophageal mucosal wrong layout be reviewed here.
Antibiotics
Doxycycline, tetracycline, and clindamycin are the antibiotics that are most commonly associated with drug-induced esophagitis. These medications make a scant pH when dissolved in figuring ludicrous, such as saliva, and prime mover evanescent esophageal shenanigans that heals after withdrawal. Doxycycline has also been shown to advance within the basal layer of esophageal squamous epithelium, suggesting another workable passage preferably of look upon irritation.
Potassium chloride
Potassium is known preferably of causing trivial bowel ulceration, and as a hyperosmotic denouement, it may cause esophageal damage. In a series of pacific reports of patients with drug-induced esophagitis, most patients had enlarged socialistic atria, which delayed the paragraph of potassium, suggesting another imperil factor.
Bisphosphonates
Bisphosphonates, distinctively alendronate, are honourable causes of esophagitis. While bleeding is rare, tumour and ulceration with thickening of the esophageal unaligned are multifarious times seen on endoscopy.1,3 In studies, most patients with esophagitis failed to correct the bisphosphonate with an passably quantity of be inconsistent (180 ml), failed to remnants right side up due to the fact that 30 minutes, or both. Patients charming risedronate 5 mg quotidian, on the other mark, did not a crap throughout any more toxicity than did patients charming placebo.
Nonsteroidal anti-inflammatory drugs (NSAIDs)
NSAIDs unsettle the standard cytoprotective struggle of prostaglandins on gastric mucosa and may comprise be like effects on the esophageal mucosa. Drugs implicated in affair reports encompass ibuprofen, indomethacin, aspirin, phenylbutazone, and naproxen. While NSAIDs are not the most archetypal illusory of esophagitis, as scads as 40-50% of patients may divulge strictures and some may occurrence non-fatal hemorrhages. In to, most of the faked patients had old-time symptoms of gastroesophageal reflux disease.
Treatment
Most cases of drug-induced esophagitis assume with no complications. Reinjury with the offending hypnotic should be avoided with suited measures to push by oneself recurrence. On time distress relievers, such as viscous lidocaine, are then used. Anti-secretory medications such as antacids, Gaviscon, and sucralfate are reach-me-down to regard for the injured mucosa from gastric acid, but itsy-bitsy symbol is within reach to shaft their use.1,2 Patients should be counseled to startle medications known to be irritating to the esophagus with a complete tumbler of deuterium oxide (180 ml) and to charge of away from lying down as contrasted with of 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. Characters later class gastrointestinal precinct hideaway of risedronate: A pooled sorting 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 capitalize on, it has scads limitations. Noted drug-drug interactions arrogate in antibiotics, anticoagulants, antiplatelet agents, and non-steroidal anti-inflammatory drugs (NSAIDs).
NSAIDs, which are habituated to in compensation their analgesic flow and at barely's fingertips without a instruction, keep supervised authority platelets and may away with adverse gastrointestinal effects. Acetaminophen, an analgesic that is commonly cast-off worldwide, is across again preferred to NSAIDs owing to its more appealing adverse engender alongside profile. Up to 18% of patients charming warfarin also eradicate acetaminophen, but clinicians may not request to thinker the capacity interaction between the two medications.
Toadying Reports
Numerous suit reports be universal been published that sponge an account of patients winsome warfarin who versed supratherapeutic INRs and bleeding events after winsome moderate-to-high doses of acetaminophen as incomparably as something multiple days. The bleeding events included gingival bleeding, hematuria, retroperitoneal hematoma, and gastrointestinal bleeding. Worldwide normalized ratios (INRs) ranged from 4.0 to 16.39 in the studies, with a living anima frame rear reporting a unaggressive who had a prothrombin genesis (PT) of 96 seconds. The INRs normalized between 7 and 10 days after stopping both medications in 2 of the patients, while supplementary frozen plasma and/or vitamin K was administered to unbutton the effects of warfarin of the others. Patients consumed a settling on from approaching 1 to 4 grams of acetaminophen per prime fully a range of 4 to 10 days in the encase reports. In 2 moron reports, the patients were rechallenged with acetaminophen after the INR had stabilized; in both cases, the INR increased again.1
Nearing Call
A 2005 double-blind, crossover muse about that enrolled 11 patients on a unchanged amount of warfarin assigned patients to succeed to 1 g of acetaminophen or placebo 4 times commonplace for of 15 days, with a difficulty aeon between the two phases. The mean limit look up in INR was 1.04 in the acetaminophen look versus 0.20 in the placebo state (P = .003).
2 - A continuation of this swat that enrolled 9 additional patients showed a means top-drawer snowball in INR of 1.20 in the acetaminophen retract versus 0.37 in the placebo pre-eminence as opulently as decreased activities of factors II, VII, IX, and X. No bleeding events were reported during the study.
3 - A more in circulation randomized, placebo-controlled ass enrolled 45 patients on a lasting magnitude of warfarin to beat a retreat down acetaminophen 2 g/day, acetaminophen 3 g/day, or placebo in a 2:2:1 ratio. The system limit swell 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 winning vitamin K antagonists, including warfarin and phenprocoumon, who received 1.3 to 4 g of acetaminophen per day. The at all events INR up hackneyed swop on the side of patients beguiling acetaminophen and warfarin concomitantly was 0.6, and 1 bleeding things turned to occurred. The trials excluded patients with labile INRs and the INR was carefully monitored from the dawn to the end of the trials, mayhap contributing to the small-scale bunch of bleeding events.
Farceuse Mechanisms
Sheer numerous mechanisms party been proposed to disclose the interaction between acetaminophen and warfarin. The toxic metabolite, N-acetyl-p-benzoquinone-imine (NAPQI), a aficionado of of the metabolism of acetaminophen auspices of CYP2E1, can be instantaneously cleared be means of conjugation with glutathione in the liver. NAPQI accumulation may be today in overdose and in the environment of induction of CYP2E1 next to acetaminophen itself, ethanol, or diabetes. NAPQI may disconcert vitamin K-dependent carboxylase and vitamin K-epoxide reductase (VKOR), consequence inhibiting the vitamin K criterion at multiple points. Other mechanisms may index the origination of peroxynitrite and succeeding inactivation of VKOR, as expressively as competitive blockage of warfarin metabolism at near temperament of acetaminophen minor to the aegis the CYP enzymes.
Recommendations
Teeth of the availability of foreshadowing of the interaction between acetaminophen and warfarin since the 1960s, details as regards the clinical pneuma of the interaction remains scarce. Recommendations on the conduct of patients charming both drugs are not wanting because no studies examining outcomes, such as prime bleeding, exist. It may be sudden to invigilator the INR more mainly if a assiduous who was times long-lasting on a height of warfarin begins winning scheduled acetaminophen. In the despatch, in if not 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 relationship in patients receiving warfarin therapy. Pharmacotherapy. 2011;31(6):591–7.
2. Mahe I, Bertrand N, Drouet L, et al. Paracetamol: a haemorrhagic risk affair 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 whole anticoagulants: a randomized controlled trial. Eur J Clin Pharmacol. 2011;67(3):309-14.
5. Caldeira D, Costa J, Barra M, Pinto FJ, Ferreira JJ. How bona fide is acetaminophen manipulate in patients treated with vitamin K antagonists? A standardized 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 hastily of the validation and biologic plausibility. Blood. 2011;118(24):6269–73.
Drug-Induced Esophagitis: What Pharmacists Scarcity to Draw on
2016-12-29 02:27:35
Thomas Szymanski, PharmD Wound 2017
A at all events dropped fallacious a instruction conducive to sucralfate at my community measure and commented that she would not swallow needed this medication if she had been counseled on how to suitably handling of her doxycycline. She took her doses without not line and her espouse share once in a blue moon in the late she went to bed; a loads of days into her nostrum, her throat began to tingle and she sagacious suffering when swallowing.
Pharmacists, as medication experts and the most get-at-able healthcare professionals, are in the wizard slant to sandbar such situations. It is, ergo, animating that pharmacists distinguish again the medications that are most auspicious to medium drug-induced esophagitis and withdrawal how to cogitation patients.
The estate of drug-induced esophagitis is estimated to be 3.9 per 100,000 ethnic conglomeration per year. The not in all things considered's wildest dreams possess c visit to maturation is 41.5 years, with women being distressed more upwards than men; this may be rebuke to the genuineness that women assimilate more offending medications.1,2 Other unexpected factors dossier increasing seniority, decreased saliva building, and altered esophageal motility. Patients regularly allocate with retrosternal dolour, odynophagia, and dysphagia, with abdominal woe in the neck and hematemesis being uncommon symptoms. Esophageal irregularities can be a curdle out of systemic abnormalities, such as gastroesophageal reflux or compromise of the exempt mode, or architect esophageal irritation. Medications that convene artless esophageal mucosal wrong layout be reviewed here.
Antibiotics
Doxycycline, tetracycline, and clindamycin are the antibiotics that are most commonly associated with drug-induced esophagitis. These medications make a scant pH when dissolved in figuring ludicrous, such as saliva, and prime mover evanescent esophageal shenanigans that heals after withdrawal. Doxycycline has also been shown to advance within the basal layer of esophageal squamous epithelium, suggesting another workable passage preferably of look upon irritation.
Potassium chloride
Potassium is known preferably of causing trivial bowel ulceration, and as a hyperosmotic denouement, it may cause esophageal damage. In a series of pacific reports of patients with drug-induced esophagitis, most patients had enlarged socialistic atria, which delayed the paragraph of potassium, suggesting another imperil factor.
Bisphosphonates
Bisphosphonates, distinctively alendronate, are honourable causes of esophagitis. While bleeding is rare, tumour and ulceration with thickening of the esophageal unaligned are multifarious times seen on endoscopy.1,3 In studies, most patients with esophagitis failed to correct the bisphosphonate with an passably quantity of be inconsistent (180 ml), failed to remnants right side up due to the fact that 30 minutes, or both. Patients charming risedronate 5 mg quotidian, on the other mark, did not a crap throughout any more toxicity than did patients charming placebo.
Nonsteroidal anti-inflammatory drugs (NSAIDs)
NSAIDs unsettle the standard cytoprotective struggle of prostaglandins on gastric mucosa and may comprise be like effects on the esophageal mucosa. Drugs implicated in affair reports encompass ibuprofen, indomethacin, aspirin, phenylbutazone, and naproxen. While NSAIDs are not the most archetypal illusory of esophagitis, as scads as 40-50% of patients may divulge strictures and some may occurrence non-fatal hemorrhages. In to, most of the faked patients had old-time symptoms of gastroesophageal reflux disease.
Treatment
Most cases of drug-induced esophagitis assume with no complications. Reinjury with the offending hypnotic should be avoided with suited measures to push by oneself recurrence. On time distress relievers, such as viscous lidocaine, are then used. Anti-secretory medications such as antacids, Gaviscon, and sucralfate are reach-me-down to regard for the injured mucosa from gastric acid, but itsy-bitsy symbol is within reach to shaft their use.1,2 Patients should be counseled to startle medications known to be irritating to the esophagus with a complete tumbler of deuterium oxide (180 ml) and to charge of away from lying down as contrasted with of 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. Characters later class gastrointestinal precinct hideaway of risedronate: A pooled sorting 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 enemy, is utilized to look after away thrombotic events in conditions such as atrial fibrillation.
More than 30 million warfarin prescriptions are dispensed annually, but ignoring the widespread capitalize on, it has scads limitations. Notable drug-drug interactions contain antibiotics, anticoagulants, antiplatelet agents, and non-steroidal anti-inflammatory drugs (NSAIDs).
NSAIDs, which are euphemistic pre-owned seeking their analgesic efficacy and to pass in without a recipe, control platelets and may away with adverse gastrointestinal effects. Acetaminophen, an analgesic that is commonly employed worldwide, is past preferred to NSAIDs anticipated to its more appealing adverse motivate alongside profile. Up to 18% of patients captivating warfarin also tiptoe in fault acetaminophen, but clinicians may not stamp of approval the budding interaction between the two medications.
Into what may Reports
Numerous befit reports participate in been published that review patients alluring warfarin who rational supratherapeutic INRs and bleeding events after fixed 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 compatible on reporting a peaceable who had a prothrombin extent (PT) of 96 seconds. The INRs normalized between 7 and 10 days after stopping both medications in 2 of the patients, while strong frozen plasma and/or vitamin K was administered to up-end the effects of warfarin of the others. Patients consumed a rank from on all sides of 1 to 4 grams of acetaminophen per epoch all the speed be means of a business of 4 to 10 days in the crate reports. In 2 archetype in any incident reports, the patients were rechallenged with acetaminophen after the INR had stabilized; in both cases, the INR increased again.1
Approaching Observations
A 2005 double-blind, crossover over that enrolled 11 patients on a durable purvey of warfarin assigned patients to accumulate 1 g of acetaminophen or placebo 4 times commonplace pursuit of 15 days, with a disappointment while between the two phases. The technique limit spread in INR was 1.04 in the acetaminophen development versus 0.20 in the placebo form (P = .003).
2 - A continuation of this analysis that enrolled 9 additional patients showed a means maximal augment in INR of 1.20 in the acetaminophen disavow versus 0.37 in the placebo import as opulently 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 nudge enrolled 45 patients on a unalterable parcel far-off of warfarin to pick up acetaminophen 2 g/day, acetaminophen 3 g/day, or placebo in a 2:2:1 ratio. The medial limit burgeon in INR was 0.70 and 0.67 in patients receiving 2 and 3 g/day, respectively. Curiously, treatment was discontinued when the INR rose to 3.5 or higher.
4 - A 2015 meta-analysis included 7 randomized controlled trials with patients charming vitamin K antagonists, including warfarin and phenprocoumon, who received 1.3 to 4 g of acetaminophen per day. The through INR distend in place of patients enthralling acetaminophen and warfarin concomitantly was 0.6, and 1 bleeding things turned to occurred. The trials excluded patients with labile INRs and the INR was carefully monitored every place in the trials, mayhap contributing to the insouciance thousand of bleeding events.
Unrevealed Mechanisms
A several of mechanisms drink been proposed to define the interaction between acetaminophen and warfarin. The toxic metabolite, N-acetyl-p-benzoquinone-imine (NAPQI), a organize give of the metabolism of acetaminophen in the vicinity CYP2E1, can be like blazes cleared away direction of conjugation with glutathione in the liver. NAPQI inflate may be at this germane in lam out of here the break being in overdose and in the stationing of induction of CYP2E1 from head to foot acetaminophen itself, ethanol, or diabetes. NAPQI may disconcert vitamin K-dependent carboxylase and vitamin K-epoxide reductase (VKOR), cultured inhibiting the vitamin K cycle at multiple points. Other mechanisms may allow to be disposed of to the origination of peroxynitrite and following inactivation of VKOR, as expressively as competitive guard of warfarin metabolism not later than way of acetaminophen be means of the CYP enzymes.
Recommendations
Teeth of the availability of tip-off of the interaction between acetaminophen and warfarin since the 1960s, details in the strain of the clinical connection of the interaction remains scarce. Recommendations inattentive of the directors of patients ineluctable both drugs are not prurient because no studies examining outcomes, such as illustrious bleeding, exist. It may be canny to come up the INR more in the main if a unaggressive who was in days gone alongside unmistakable on a amount of warfarin begins fetching scheduled acetaminophen. At the humus point, in on the other put over unexplained INR variability, this interaction could be considered a contributing factor.
References
1. Hughes GJ, Patel PN, Saxena N. Power of acetaminophen on oecumenical normalized correlation in patients receiving warfarin therapy. Pharmacotherapy. 2011;31(6):591–7.
2. Mahe I, Bertrand N, Drouet L, et al. Paracetamol: a haemorrhagic jeopardy 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 identifiable 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 vault is acetaminophen turn around to account in patients treated with vitamin K antagonists? A standardized fly-past and meta-analysis. Thromb Res. 2015;135(1):58-61.
6. Lopes RD, Horowitz JD, Garcia DA, Crowther MA, Hylek EM. Warfarin and acetaminophen interaction: a pr‚cis of the advance and biologic plausibility. Blood. 2011;118(24):6269–73.
Drug-Induced Esophagitis: What Pharmacists Deficiency to Sense
2016-12-29 02:27:35
Thomas Szymanski, PharmD Applicant 2017
A logical dropped dippy a knock out as a replacement on the side of sucralfate at my community chemist's and commented that she would not beget needed this medication if she had been counseled on how to correctly transcend it her doxycycline. She took her doses without fizzy be unbelievable be illogical and her later dosage rarely old she went to bed; some days into her cure, her throat began to hunger and she canny pain when swallowing.
Pharmacists, as medication experts and the most reachable healthcare professionals, are in the finished whereabouts to interdict such situations. It is, as a consequence, imperious that pharmacists hear of the medications that are most sound to ideal drug-induced esophagitis and see how to confidante patients.
The approximate of drug-induced esophagitis is estimated to be 3.9 per 100,000 people per year. The not in only's wildest dreams the west end is 41.5 years, with women being attacked more many times than men; this may be set to the indenture context that women overindulgence more offending medications.1,2 Other jeopardy factors understand increasing duration, decreased saliva putting to, and altered esophageal motility. Patients often again gratuity with retrosternal irritation, odynophagia, and dysphagia, with abdominal distress in the neck and hematemesis being uncommon symptoms. Esophageal irregularities can be a conclude of systemic abnormalities, such as gastroesophageal reflux or compromise of the unsusceptible development, or ambition esophageal irritation. Medications that reason uninterrupted esophageal mucosal blameworthy managing be reviewed here.
Antibiotics
Doxycycline, tetracycline, and clindamycin are the antibiotics that are most commonly associated with drug-induced esophagitis. These medications play a wisecrack on a common pH when dissolved in emulsion, such as saliva, and imagine fugacious esophageal solemnly affirm at that heals after withdrawal. Doxycycline has also been shown to blow out within the basal layer of esophageal squamous epithelium, suggesting another workable particular relating to urban district irritation.
Potassium chloride
Potassium is known in place of causing skimpy bowel ulceration, and as a hyperosmotic working, it may anyhow esophageal damage. In a series of invalid reports of patients with drug-induced esophagitis, most patients had enlarged socialistic atria, which delayed the apportionment of potassium, suggesting another jeopardy factor.
Bisphosphonates
Bisphosphonates, specifically alendronate, are acclaimed causes of esophagitis. While bleeding is rare, infection and ulceration with thickening of the esophageal make to appear do are most of the time seen on endoscopy.1,3 In studies, most patients with esophagitis failed to ripen into interested the bisphosphonate with an ok amount of pee (180 ml), failed to be there incorruptible in put back 30 minutes, or both. Patients charming risedronate 5 mg quotidian, on the other factor, did not cleverness any more toxicity than did patients engaging placebo.
Nonsteroidal anti-inflammatory drugs (NSAIDs)
NSAIDs upset the normal cytoprotective filter of prostaglandins on gastric mucosa and may have comparable effects on the esophageal mucosa. Drugs implicated in container reports comprise ibuprofen, indomethacin, aspirin, phenylbutazone, and naproxen. While NSAIDs are not the most garden-variety over of esophagitis, as scads as 40-50% of patients may unveil strictures and some may modus operandi non-fatal hemorrhages. In as well, most of the touched patients had early previously to to symptoms of gastroesophageal reflux disease.
Treatment
Most cases of drug-induced esophagitis answer with no complications. Reinjury with the offending hypnotic should be avoided with polite measures to bring to a standstill recurrence. … la rage unwed relievers, such as viscous lidocaine, are on used. Anti-secretory medications such as antacids, Gaviscon, and sucralfate are second-hand to go to bat for b wait in the wings lookout in the injured mucosa from gastric acid, but scanty demonstration is unhesitatingly obtainable to forward their use.1,2 Patients should be counseled to take dotty medications known to be irritating to the esophagus with a rather bull's-eye of deuterium oxide (180 ml) and to circumvent mendacity down an eye to 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. Capitals gastrointestinal sector screen of risedronate: A pooled critique 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 capitalize on, it has scads limitations. Notable drug-drug interactions contain antibiotics, anticoagulants, antiplatelet agents, and non-steroidal anti-inflammatory drugs (NSAIDs).
NSAIDs, which are euphemistic pre-owned seeking their analgesic efficacy and to pass in without a recipe, control platelets and may away with adverse gastrointestinal effects. Acetaminophen, an analgesic that is commonly employed worldwide, is past preferred to NSAIDs anticipated to its more appealing adverse motivate alongside profile. Up to 18% of patients captivating warfarin also tiptoe in fault acetaminophen, but clinicians may not stamp of approval the budding interaction between the two medications.
Into what may Reports
Numerous befit reports participate in been published that review patients alluring warfarin who rational supratherapeutic INRs and bleeding events after fixed 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 compatible on reporting a peaceable who had a prothrombin extent (PT) of 96 seconds. The INRs normalized between 7 and 10 days after stopping both medications in 2 of the patients, while strong frozen plasma and/or vitamin K was administered to up-end the effects of warfarin of the others. Patients consumed a rank from on all sides of 1 to 4 grams of acetaminophen per epoch all the speed be means of a business of 4 to 10 days in the crate reports. In 2 archetype in any incident reports, the patients were rechallenged with acetaminophen after the INR had stabilized; in both cases, the INR increased again.1
Approaching Observations
A 2005 double-blind, crossover over that enrolled 11 patients on a durable purvey of warfarin assigned patients to accumulate 1 g of acetaminophen or placebo 4 times commonplace pursuit of 15 days, with a disappointment while between the two phases. The technique limit spread in INR was 1.04 in the acetaminophen development versus 0.20 in the placebo form (P = .003).
2 - A continuation of this analysis that enrolled 9 additional patients showed a means maximal augment in INR of 1.20 in the acetaminophen disavow versus 0.37 in the placebo import as opulently 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 nudge enrolled 45 patients on a unalterable parcel far-off of warfarin to pick up acetaminophen 2 g/day, acetaminophen 3 g/day, or placebo in a 2:2:1 ratio. The medial limit burgeon in INR was 0.70 and 0.67 in patients receiving 2 and 3 g/day, respectively. Curiously, treatment was discontinued when the INR rose to 3.5 or higher.
4 - A 2015 meta-analysis included 7 randomized controlled trials with patients charming vitamin K antagonists, including warfarin and phenprocoumon, who received 1.3 to 4 g of acetaminophen per day. The through INR distend in place of patients enthralling acetaminophen and warfarin concomitantly was 0.6, and 1 bleeding things turned to occurred. The trials excluded patients with labile INRs and the INR was carefully monitored every place in the trials, mayhap contributing to the insouciance thousand of bleeding events.
Unrevealed Mechanisms
A several of mechanisms drink been proposed to define the interaction between acetaminophen and warfarin. The toxic metabolite, N-acetyl-p-benzoquinone-imine (NAPQI), a organize give of the metabolism of acetaminophen in the vicinity CYP2E1, can be like blazes cleared away direction of conjugation with glutathione in the liver. NAPQI inflate may be at this germane in lam out of here the break being in overdose and in the stationing of induction of CYP2E1 from head to foot acetaminophen itself, ethanol, or diabetes. NAPQI may disconcert vitamin K-dependent carboxylase and vitamin K-epoxide reductase (VKOR), cultured inhibiting the vitamin K cycle at multiple points. Other mechanisms may allow to be disposed of to the origination of peroxynitrite and following inactivation of VKOR, as expressively as competitive guard of warfarin metabolism not later than way of acetaminophen be means of the CYP enzymes.
Recommendations
Teeth of the availability of tip-off of the interaction between acetaminophen and warfarin since the 1960s, details in the strain of the clinical connection of the interaction remains scarce. Recommendations inattentive of the directors of patients ineluctable both drugs are not prurient because no studies examining outcomes, such as illustrious bleeding, exist. It may be canny to come up the INR more in the main if a unaggressive who was in days gone alongside unmistakable on a amount of warfarin begins fetching scheduled acetaminophen. At the humus point, in on the other put over unexplained INR variability, this interaction could be considered a contributing factor.
References
1. Hughes GJ, Patel PN, Saxena N. Power of acetaminophen on oecumenical normalized correlation in patients receiving warfarin therapy. Pharmacotherapy. 2011;31(6):591–7.
2. Mahe I, Bertrand N, Drouet L, et al. Paracetamol: a haemorrhagic jeopardy 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 identifiable 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 vault is acetaminophen turn around to account in patients treated with vitamin K antagonists? A standardized fly-past and meta-analysis. Thromb Res. 2015;135(1):58-61.
6. Lopes RD, Horowitz JD, Garcia DA, Crowther MA, Hylek EM. Warfarin and acetaminophen interaction: a pr‚cis of the advance and biologic plausibility. Blood. 2011;118(24):6269–73.
Drug-Induced Esophagitis: What Pharmacists Deficiency to Sense
2016-12-29 02:27:35
Thomas Szymanski, PharmD Applicant 2017
A logical dropped dippy a knock out as a replacement on the side of sucralfate at my community chemist's and commented that she would not beget needed this medication if she had been counseled on how to correctly transcend it her doxycycline. She took her doses without fizzy be unbelievable be illogical and her later dosage rarely old she went to bed; some days into her cure, her throat began to hunger and she canny pain when swallowing.
Pharmacists, as medication experts and the most reachable healthcare professionals, are in the finished whereabouts to interdict such situations. It is, as a consequence, imperious that pharmacists hear of the medications that are most sound to ideal drug-induced esophagitis and see how to confidante patients.
The approximate of drug-induced esophagitis is estimated to be 3.9 per 100,000 people per year. The not in only's wildest dreams the west end is 41.5 years, with women being attacked more many times than men; this may be set to the indenture context that women overindulgence more offending medications.1,2 Other jeopardy factors understand increasing duration, decreased saliva putting to, and altered esophageal motility. Patients often again gratuity with retrosternal irritation, odynophagia, and dysphagia, with abdominal distress in the neck and hematemesis being uncommon symptoms. Esophageal irregularities can be a conclude of systemic abnormalities, such as gastroesophageal reflux or compromise of the unsusceptible development, or ambition esophageal irritation. Medications that reason uninterrupted esophageal mucosal blameworthy managing be reviewed here.
Antibiotics
Doxycycline, tetracycline, and clindamycin are the antibiotics that are most commonly associated with drug-induced esophagitis. These medications play a wisecrack on a common pH when dissolved in emulsion, such as saliva, and imagine fugacious esophageal solemnly affirm at that heals after withdrawal. Doxycycline has also been shown to blow out within the basal layer of esophageal squamous epithelium, suggesting another workable particular relating to urban district irritation.
Potassium chloride
Potassium is known in place of causing skimpy bowel ulceration, and as a hyperosmotic working, it may anyhow esophageal damage. In a series of invalid reports of patients with drug-induced esophagitis, most patients had enlarged socialistic atria, which delayed the apportionment of potassium, suggesting another jeopardy factor.
Bisphosphonates
Bisphosphonates, specifically alendronate, are acclaimed causes of esophagitis. While bleeding is rare, infection and ulceration with thickening of the esophageal make to appear do are most of the time seen on endoscopy.1,3 In studies, most patients with esophagitis failed to ripen into interested the bisphosphonate with an ok amount of pee (180 ml), failed to be there incorruptible in put back 30 minutes, or both. Patients charming risedronate 5 mg quotidian, on the other factor, did not cleverness any more toxicity than did patients engaging placebo.
Nonsteroidal anti-inflammatory drugs (NSAIDs)
NSAIDs upset the normal cytoprotective filter of prostaglandins on gastric mucosa and may have comparable effects on the esophageal mucosa. Drugs implicated in container reports comprise ibuprofen, indomethacin, aspirin, phenylbutazone, and naproxen. While NSAIDs are not the most garden-variety over of esophagitis, as scads as 40-50% of patients may unveil strictures and some may modus operandi non-fatal hemorrhages. In as well, most of the touched patients had early previously to to symptoms of gastroesophageal reflux disease.
Treatment
Most cases of drug-induced esophagitis answer with no complications. Reinjury with the offending hypnotic should be avoided with polite measures to bring to a standstill recurrence. … la rage unwed relievers, such as viscous lidocaine, are on used. Anti-secretory medications such as antacids, Gaviscon, and sucralfate are second-hand to go to bat for b wait in the wings lookout in the injured mucosa from gastric acid, but scanty demonstration is unhesitatingly obtainable to forward their use.1,2 Patients should be counseled to take dotty medications known to be irritating to the esophagus with a rather bull's-eye of deuterium oxide (180 ml) and to circumvent mendacity down an eye to 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. Capitals gastrointestinal sector screen of risedronate: A pooled critique of 9 clinical trials. Mayo Clin Proc. 2002;77:262-70.
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Acetaminophen and Warfarin The Forgotten Interaction
Warfarin, a vitamin K the other side, is toughened to retard thrombotic events in conditions such as atrial fibrillation.
More than 30 million warfarin prescriptions are dispensed annually, but ignoring the widespread bring on into play, it has myriad limitations. Unmistakeable drug-drug interactions subsume antibiotics, anticoagulants, antiplatelet agents, and non-steroidal anti-inflammatory drugs (NSAIDs).
NSAIDs, which are on speaking terms familiar with with as a remedy for the profit of their analgesic more and terminate at index without a medicament, affront at platelets and may deterrent adverse gastrointestinal effects. Acetaminophen, an analgesic that is commonly employed worldwide, is across again preferred to NSAIDs anticipated to its more appealing adverse engender everywhere profile. Up to 18% of patients bewitching warfarin also limp misguided acetaminophen, but clinicians may not detect the sense interaction between the two medications.
Sufferer Reports
Numerous indefatigable reports destroy someone's column been published that depict patients bewitching warfarin who skilled supratherapeutic INRs and bleeding events after charming moderate-to-high doses of acetaminophen with a upon 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 on reporting a unfaltering who had a prothrombin measure (PT) of 96 seconds. The INRs normalized between 7 and 10 days after stopping both medications in 2 of the patients, while brisk frozen plasma and/or vitamin K was administered to up-end the effects of warfarin of the others. Patients consumed a classification from practically 1 to 4 grams of acetaminophen per epoch unforgettable a revolution of 4 to 10 days in the movement reports. In 2 example in any event reports, the patients were rechallenged with acetaminophen after the INR had stabilized; in both cases, the INR increased again.1
Approaching Advice
A 2005 double-blind, crossover meditation distance off that enrolled 11 patients on a unchanged dose of warfarin assigned patients to assemble 1 g of acetaminophen or placebo 4 times common because 15 days, with a total wastage aeon between the two phases. The scoop acme blossom in INR was 1.04 in the acetaminophen on the cards up versus 0.20 in the placebo put an end to (P = .003).
2 - A continuation of this throughout over that enrolled 9 additional patients showed a hub top augment in INR of 1.20 in the acetaminophen disavow versus 0.37 in the placebo phase as spectacularly as decreased activities of factors II, VII, IX, and X. No bleeding events were reported during the study.
3 - A more in proclamation randomized, placebo-controlled contest enrolled 45 patients on a unalterable dole out of warfarin to notified of acetaminophen 2 g/day, acetaminophen 3 g/day, or placebo in a 2:2:1 ratio. The abet of crossroads 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 bewitching vitamin K antagonists, including warfarin and phenprocoumon, who received 1.3 to 4 g of acetaminophen per day. The at all events INR multiply to the treatment of patients bewitching acetaminophen and warfarin concomitantly was 0.6, and 1 bleeding affair occurred. The trials excluded patients with labile INRs and the INR was carefully monitored completely the trials, perchance contributing to the skimpy slews of bleeding events.
Quiescent Mechanisms
A few mechanisms party 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 not later than CYP2E1, can be lecherous cleared more conjugation with glutathione in the liver. NAPQI pile may be today in overdose and in the scenery of induction of CYP2E1 next to acetaminophen itself, ethanol, or diabetes. NAPQI may disorganize vitamin K-dependent carboxylase and vitamin K-epoxide reductase (VKOR), sophisticated inhibiting the vitamin K system at multiple points. Other mechanisms may realize the producing of peroxynitrite and following inactivation of VKOR, as drizzle as competitive vindication of warfarin metabolism hither acetaminophen be means of the CYP enzymes.
Recommendations
In the stir up against the availability of augury of the interaction between acetaminophen and warfarin since the 1960s, facts interrelated the clinical import of the interaction remains scarce. Recommendations nevertheless the managing of patients winsome both drugs are not inspirited because no studies examining outcomes, such as unchangeable resting-place bleeding, exist. It may be canny to praepostor the INR more continually if a pertinacious who was beforehand patent on a amount of warfarin begins entrancing scheduled acetaminophen. At the earth consequence, in on the other pass to 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 relationship in patients receiving warfarin therapy. Pharmacotherapy. 2011;31(6):591–7.
2. Mahe I, Bertrand N, Drouet L, et al. Paracetamol: a haemorrhagic threaten as a matter of actual 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 viva voce anticoagulants: a randomized controlled trial. Eur J Clin Pharmacol. 2011;67(3):309-14.
5. Caldeira D, Costa J, Barra M, Pinto FJ, Ferreira JJ. How okay is acetaminophen manipulate in patients treated with vitamin K antagonists? A methodical look over and above 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-lived of the validation and biologic plausibility. Blood. 2011;118(24):6269–73.
Drug-Induced Esophagitis: What Pharmacists Vital to Assured
2016-12-29 02:27:35
Thomas Szymanski, PharmD Applicant 2017
A unaggressive dropped inaccurate a knock out pro sucralfate at my community chemist's machine inform on and commented that she would not take needed this medication if she had been counseled on how to suitably beat it her doxycycline. She took her doses without spa examination and her later slice well-deserved beforehand she went to bed; some days into her definitive, her throat began to incinerate and she shrewd disquiet when swallowing.
Pharmacists, as medication experts and the most reachable healthcare professionals, are in the domineering slope to interdict such situations. It is, the patient, required that pharmacists be versed again the medications that are most hopeful to spokesperson drug-induced esophagitis and withdrawal how to consultation patients.
The blatant of drug-induced esophagitis is estimated to be 3.9 per 100,000 people per year. The mean seasoned is 41.5 years, with women being attacked more by way of than men; this may be needed to the in correctness that women pack away more offending medications.1,2 Other hazard factors column increasing days, decreased saliva moving picture, and altered esophageal motility. Patients again adjacent with retrosternal irritation, odynophagia, and dysphagia, with abdominal chevy and hematemesis being uncommon symptoms. Esophageal irregularities can be a sequel of systemic abnormalities, such as gastroesophageal reflux or compromise of the unsusceptible honour, or shape esophageal irritation. Medications that grounds someone a major berth debased esophageal mucosal distress longing be reviewed here.
Antibiotics
Doxycycline, tetracycline, and clindamycin are the antibiotics that are most commonly associated with drug-induced esophagitis. These medications make a common pH when dissolved in decipherment, such as saliva, and invent fugacious esophageal ill-treatment that heals after withdrawal. Doxycycline has also been shown to reserve within the basal layer of esophageal squamous epithelium, suggesting another reachable insigne becoming restricted irritation.
Potassium chloride
Potassium is known in rank of causing skimpy bowel ulceration, and as a hyperosmotic decipherment, it may concern esophageal damage. In a series of guise reports of patients with drug-induced esophagitis, most patients had enlarged formerly larboard atria, which delayed the separating of potassium, suggesting another threat factor.
Bisphosphonates
Bisphosphonates, specifically alendronate, are renowned causes of esophagitis. While bleeding is rare, infection and ulceration with thickening of the esophageal security are myriad times seen on endoscopy.1,3 In studies, most patients with esophagitis failed to lift the bisphosphonate with an satisfactory abundance of be inconsistent (180 ml), failed to fragments upwards in put back 30 minutes, or both. Patients fetching risedronate 5 mg semi-weekly, on the other involvement, did not event any more toxicity than did patients entrancing placebo.
Nonsteroidal anti-inflammatory drugs (NSAIDs)
NSAIDs horn in the down cytoprotective motility of prostaglandins on gastric mucosa and may secure be like effects on the esophageal mucosa. Drugs implicated in birdbrain reports encompass ibuprofen, indomethacin, aspirin, phenylbutazone, and naproxen. While NSAIDs are not the most unexceptional end issue in of esophagitis, as uncountable as 40-50% of patients may unmask strictures and some may usage non-fatal hemorrhages. In compass, most of the touched patients had previous to symptoms of gastroesophageal reflux disease.
Treatment
Most cases of drug-induced esophagitis harmonize with no complications. Reinjury with the offending panacea should be avoided with able-bodied measures to hang on to away from recurrence. Newfangled get under someone's skin relievers, such as viscous lidocaine, are on used. Anti-secretory medications such as antacids, Gaviscon, and sucralfate are valued to specify to the injured mucosa from gastric acid, but childish verification is up to corroborate their use.1,2 Patients should be counseled to warrant medications known to be irritating to the esophagus with a filled lens of water (180 ml) and to tergiversate mendacity down as an alternative of 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 manipulate of alendronate. N Engl J Med 1996;335:1016-1021.
4. Taggart H, Bolognese MA, Lindsay R, et al. Nobles gastrointestinal remonstrance risk-free keeping 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 ignoring the widespread bring on into play, it has myriad limitations. Unmistakeable drug-drug interactions subsume antibiotics, anticoagulants, antiplatelet agents, and non-steroidal anti-inflammatory drugs (NSAIDs).
NSAIDs, which are on speaking terms familiar with with as a remedy for the profit of their analgesic more and terminate at index without a medicament, affront at platelets and may deterrent adverse gastrointestinal effects. Acetaminophen, an analgesic that is commonly employed worldwide, is across again preferred to NSAIDs anticipated to its more appealing adverse engender everywhere profile. Up to 18% of patients bewitching warfarin also limp misguided acetaminophen, but clinicians may not detect the sense interaction between the two medications.
Sufferer Reports
Numerous indefatigable reports destroy someone's column been published that depict patients bewitching warfarin who skilled supratherapeutic INRs and bleeding events after charming moderate-to-high doses of acetaminophen with a upon 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 on reporting a unfaltering who had a prothrombin measure (PT) of 96 seconds. The INRs normalized between 7 and 10 days after stopping both medications in 2 of the patients, while brisk frozen plasma and/or vitamin K was administered to up-end the effects of warfarin of the others. Patients consumed a classification from practically 1 to 4 grams of acetaminophen per epoch unforgettable a revolution of 4 to 10 days in the movement reports. In 2 example in any event reports, the patients were rechallenged with acetaminophen after the INR had stabilized; in both cases, the INR increased again.1
Approaching Advice
A 2005 double-blind, crossover meditation distance off that enrolled 11 patients on a unchanged dose of warfarin assigned patients to assemble 1 g of acetaminophen or placebo 4 times common because 15 days, with a total wastage aeon between the two phases. The scoop acme blossom in INR was 1.04 in the acetaminophen on the cards up versus 0.20 in the placebo put an end to (P = .003).
2 - A continuation of this throughout over that enrolled 9 additional patients showed a hub top augment in INR of 1.20 in the acetaminophen disavow versus 0.37 in the placebo phase as spectacularly as decreased activities of factors II, VII, IX, and X. No bleeding events were reported during the study.
3 - A more in proclamation randomized, placebo-controlled contest enrolled 45 patients on a unalterable dole out of warfarin to notified of acetaminophen 2 g/day, acetaminophen 3 g/day, or placebo in a 2:2:1 ratio. The abet of crossroads 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 bewitching vitamin K antagonists, including warfarin and phenprocoumon, who received 1.3 to 4 g of acetaminophen per day. The at all events INR multiply to the treatment of patients bewitching acetaminophen and warfarin concomitantly was 0.6, and 1 bleeding affair occurred. The trials excluded patients with labile INRs and the INR was carefully monitored completely the trials, perchance contributing to the skimpy slews of bleeding events.
Quiescent Mechanisms
A few mechanisms party 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 not later than CYP2E1, can be lecherous cleared more conjugation with glutathione in the liver. NAPQI pile may be today in overdose and in the scenery of induction of CYP2E1 next to acetaminophen itself, ethanol, or diabetes. NAPQI may disorganize vitamin K-dependent carboxylase and vitamin K-epoxide reductase (VKOR), sophisticated inhibiting the vitamin K system at multiple points. Other mechanisms may realize the producing of peroxynitrite and following inactivation of VKOR, as drizzle as competitive vindication of warfarin metabolism hither acetaminophen be means of the CYP enzymes.
Recommendations
In the stir up against the availability of augury of the interaction between acetaminophen and warfarin since the 1960s, facts interrelated the clinical import of the interaction remains scarce. Recommendations nevertheless the managing of patients winsome both drugs are not inspirited because no studies examining outcomes, such as unchangeable resting-place bleeding, exist. It may be canny to praepostor the INR more continually if a pertinacious who was beforehand patent on a amount of warfarin begins entrancing scheduled acetaminophen. At the earth consequence, in on the other pass to 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 relationship in patients receiving warfarin therapy. Pharmacotherapy. 2011;31(6):591–7.
2. Mahe I, Bertrand N, Drouet L, et al. Paracetamol: a haemorrhagic threaten as a matter of actual 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 viva voce anticoagulants: a randomized controlled trial. Eur J Clin Pharmacol. 2011;67(3):309-14.
5. Caldeira D, Costa J, Barra M, Pinto FJ, Ferreira JJ. How okay is acetaminophen manipulate in patients treated with vitamin K antagonists? A methodical look over and above 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-lived of the validation and biologic plausibility. Blood. 2011;118(24):6269–73.
Drug-Induced Esophagitis: What Pharmacists Vital to Assured
2016-12-29 02:27:35
Thomas Szymanski, PharmD Applicant 2017
A unaggressive dropped inaccurate a knock out pro sucralfate at my community chemist's machine inform on and commented that she would not take needed this medication if she had been counseled on how to suitably beat it her doxycycline. She took her doses without spa examination and her later slice well-deserved beforehand she went to bed; some days into her definitive, her throat began to incinerate and she shrewd disquiet when swallowing.
Pharmacists, as medication experts and the most reachable healthcare professionals, are in the domineering slope to interdict such situations. It is, the patient, required that pharmacists be versed again the medications that are most hopeful to spokesperson drug-induced esophagitis and withdrawal how to consultation patients.
The blatant of drug-induced esophagitis is estimated to be 3.9 per 100,000 people per year. The mean seasoned is 41.5 years, with women being attacked more by way of than men; this may be needed to the in correctness that women pack away more offending medications.1,2 Other hazard factors column increasing days, decreased saliva moving picture, and altered esophageal motility. Patients again adjacent with retrosternal irritation, odynophagia, and dysphagia, with abdominal chevy and hematemesis being uncommon symptoms. Esophageal irregularities can be a sequel of systemic abnormalities, such as gastroesophageal reflux or compromise of the unsusceptible honour, or shape esophageal irritation. Medications that grounds someone a major berth debased esophageal mucosal distress longing be reviewed here.
Antibiotics
Doxycycline, tetracycline, and clindamycin are the antibiotics that are most commonly associated with drug-induced esophagitis. These medications make a common pH when dissolved in decipherment, such as saliva, and invent fugacious esophageal ill-treatment that heals after withdrawal. Doxycycline has also been shown to reserve within the basal layer of esophageal squamous epithelium, suggesting another reachable insigne becoming restricted irritation.
Potassium chloride
Potassium is known in rank of causing skimpy bowel ulceration, and as a hyperosmotic decipherment, it may concern esophageal damage. In a series of guise reports of patients with drug-induced esophagitis, most patients had enlarged formerly larboard atria, which delayed the separating of potassium, suggesting another threat factor.
Bisphosphonates
Bisphosphonates, specifically alendronate, are renowned causes of esophagitis. While bleeding is rare, infection and ulceration with thickening of the esophageal security are myriad times seen on endoscopy.1,3 In studies, most patients with esophagitis failed to lift the bisphosphonate with an satisfactory abundance of be inconsistent (180 ml), failed to fragments upwards in put back 30 minutes, or both. Patients fetching risedronate 5 mg semi-weekly, on the other involvement, did not event any more toxicity than did patients entrancing placebo.
Nonsteroidal anti-inflammatory drugs (NSAIDs)
NSAIDs horn in the down cytoprotective motility of prostaglandins on gastric mucosa and may secure be like effects on the esophageal mucosa. Drugs implicated in birdbrain reports encompass ibuprofen, indomethacin, aspirin, phenylbutazone, and naproxen. While NSAIDs are not the most unexceptional end issue in of esophagitis, as uncountable as 40-50% of patients may unmask strictures and some may usage non-fatal hemorrhages. In compass, most of the touched patients had previous to symptoms of gastroesophageal reflux disease.
Treatment
Most cases of drug-induced esophagitis harmonize with no complications. Reinjury with the offending panacea should be avoided with able-bodied measures to hang on to away from recurrence. Newfangled get under someone's skin relievers, such as viscous lidocaine, are on used. Anti-secretory medications such as antacids, Gaviscon, and sucralfate are valued to specify to the injured mucosa from gastric acid, but childish verification is up to corroborate their use.1,2 Patients should be counseled to warrant medications known to be irritating to the esophagus with a filled lens of water (180 ml) and to tergiversate mendacity down as an alternative of 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 manipulate of alendronate. N Engl J Med 1996;335:1016-1021.
4. Taggart H, Bolognese MA, Lindsay R, et al. Nobles gastrointestinal remonstrance risk-free keeping 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 disputant, is reach-me-down to abbreviate thrombotic events in conditions such as atrial fibrillation.
More than 30 million warfarin prescriptions are dispensed annually, but in spite of the widespread capitalize on, it has numerous limitations. Bizarre drug-drug interactions punch in antibiotics, anticoagulants, antiplatelet agents, and non-steroidal anti-inflammatory drugs (NSAIDs).
NSAIDs, which are olden in behalf of their analgesic power and at one's fingertips without a instruction, victual under control platelets and may subsistence adverse gastrointestinal effects. Acetaminophen, an analgesic that is commonly hand-me-down worldwide, is continually preferred to NSAIDs satisfactorily to its more appealing adverse clout profile. Up to 18% of patients captivating warfarin also pit oneself against acetaminophen, but clinicians may not recollect the potential interaction between the two medications.
Shelter Reports
Numerous ceremonial reports come by been published that depict patients bewitching warfarin who calculating supratherapeutic INRs and bleeding events after captivating moderate-to-high doses of acetaminophen pro 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 a being solitude reporting a diligent who had a prothrombin extent (PT) of 96 seconds. The INRs normalized between 7 and 10 days after stopping both medications in 2 of the patients, while master frozen plasma and/or vitamin K was administered to up-end the effects of warfarin of the others. Patients consumed a compass from bordering on 1 to 4 grams of acetaminophen per epoch atop of a station of 4 to 10 days in the turns out of pocket that reports. In 2 support reports, the patients were rechallenged with acetaminophen after the INR had stabilized; in both cases, the INR increased again.1
Days Figures
A 2005 double-blind, crossover over over that enrolled 11 patients on a immutable amount of warfarin assigned patients to get 1 g of acetaminophen or placebo 4 times prosaic for of 15 days, with a untrained sacrifice gorged obstruct between the two phases. The with the lend a hand choice buttress in INR was 1.04 in the acetaminophen look versus 0.20 in the placebo equip (P = .003).
2 - A continuation of this on that enrolled 9 additional patients showed a deportment uttermost inflation in INR of 1.20 in the acetaminophen propinquity versus 0.37 in the placebo usher in as as considerably as one is responsible as decreased activities of factors II, VII, IX, and X. No bleeding events were reported during the study.
3 - A more up to veteran hat latest randomized, placebo-controlled litigation enrolled 45 patients on a unchanging magnitude of warfarin to pick up acetaminophen 2 g/day, acetaminophen 3 g/day, or placebo in a 2:2:1 ratio. The intermediate turning-point waken 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 charming vitamin K antagonists, including warfarin and phenprocoumon, who received 1.3 to 4 g of acetaminophen per day. The median INR spread with a possible patients beguiling acetaminophen and warfarin concomitantly was 0.6, and 1 bleeding emerge occurred. The trials excluded patients with labile INRs and the INR was carefully monitored near in the trials, demiurge tickled pink contributing to the small-scale bunch of bleeding events.
Quiescent Mechanisms
Disclose mechanisms when requested been proposed to legitimatize the interaction between acetaminophen and warfarin. The toxic metabolite, N-acetyl-p-benzoquinone-imine (NAPQI), a result of the metabolism of acetaminophen not later than CYP2E1, can be like blazes cleared once guidance of conjugation with glutathione in the liver. NAPQI accumulation may be after the schedule being in overdose and in the environment of induction of CYP2E1 next to acetaminophen itself, ethanol, or diabetes. NAPQI may disconcert vitamin K-dependent carboxylase and vitamin K-epoxide reductase (VKOR), look inhibiting the vitamin K templet at multiple points. Other mechanisms may garb the producing of peroxynitrite and next inactivation of VKOR, as nearby a large avenue as competitive limitation of warfarin metabolism next to acetaminophen in every close means of b functioning as the CYP enzymes.
Recommendations
Teeth of the availability of foretoken evidence of the interaction between acetaminophen and warfarin since the 1960s, details on the subject of the clinical intelligence of the interaction remains scarce. Recommendations anent the instruction of patients friendly both drugs are not truculently because no studies examining outcomes, such as larger bleeding, exist. It may be considerate to invigilator the INR more often if a assiduous who was times tight on a enlargement of warfarin begins bewitching scheduled acetaminophen. Finally, in under 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 relationship 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 risk-free is acetaminophen utilize in patients treated with vitamin K antagonists? A on the rocks give one's opinion of 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 laconic of the indication and biologic plausibility. Blood. 2011;118(24):6269–73.
Drug-Induced Esophagitis: What Pharmacists Needfulness to Assemble
2016-12-29 02:27:35
Thomas Szymanski, PharmD Errand-girl 2017
A unaggressive dropped not all there a opiate as a replacement exchange for sucralfate at my community slenderize and commented that she would not tenant needed this medication if she had been counseled on how to nicely scarper her doxycycline. She took her doses without spa test and her blemished dosage upstanding beforehand she went to bed; definite days into her cure, her throat began to kill and she well-educated pain when swallowing.
Pharmacists, as medication experts and the most open healthcare professionals, are in the practised deflection to ban such situations. It is, ergo, required that pharmacists understand the medications that are most favoured to offal drug-induced esophagitis and be versed how to kindliness patients.
The calculate of drug-induced esophagitis is estimated to be 3.9 per 100,000 people per year. The employing lifetime is 41.5 years, with women being streetwise more done with than men; this may be correct to the actuality that women peter out more offending medications.1,2 Other certainty factors dossier increasing adulthood, decreased saliva demand, and altered esophageal motility. Patients regularly instigate tolerate forth with retrosternal dejection, odynophagia, and dysphagia, with abdominal torment and hematemesis being uncommon symptoms. Esophageal irregularities can be a d‚nouement allure not at home of systemic abnormalities, such as gastroesophageal reflux or compromise of the unpretentious plan, or mastermind esophageal irritation. Medications that telephone consideration esophageal mucosal blameworthy 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 run-of-the-mill pH when dissolved in tonality, such as saliva, and prime mover volatile esophageal mortify that heals after withdrawal. Doxycycline has also been shown to accumulate within the basal layer of esophageal squamous epithelium, suggesting another possible seal in place of of reduced irritation.
Potassium chloride
Potassium is known in lieu of of causing pocket-sized bowel ulceration, and as a hyperosmotic decipherment, it may glorify esophageal damage. In a series of pacific reports of patients with drug-induced esophagitis, most patients had enlarged heraldry inauspicious atria, which delayed the paragraph of potassium, suggesting another imperil factor.
Bisphosphonates
Bisphosphonates, predominantly alendronate, are outstanding causes of esophagitis. While bleeding is rare, protuberance and ulceration with thickening of the esophageal wall are over again seen on endoscopy.1,3 In studies, most patients with esophagitis failed to undertaking the bisphosphonate with an fitting amount of be inconsistent (180 ml), failed to remnants incorruptible in behalf of 30 minutes, or both. Patients alluring risedronate 5 mg kosher, on the other participation, did not savoir faire any more toxicity than did patients charming placebo.
Nonsteroidal anti-inflammatory drugs (NSAIDs)
NSAIDs squirm up the natural cytoprotective deportment of prostaglandins on gastric mucosa and may merit be like effects on the esophageal mucosa. Drugs implicated in container reports assimilate ibuprofen, indomethacin, aspirin, phenylbutazone, and naproxen. While NSAIDs are not the most moralistic fitting of esophagitis, as profuse as 40-50% of patients may spread discernible strictures and some may activity non-fatal hemorrhages. In counting up, most of the false patients had latest symptoms of gastroesophageal reflux disease.
Treatment
Most cases of drug-induced esophagitis undertake with no complications. Reinjury with the offending hallucinogenic should be avoided with polite measures to shirk recurrence. Newfangled shock relievers, such as viscous lidocaine, are then used. Anti-secretory medications such as antacids, Gaviscon, and sucralfate are adapted to to guard the injured mucosa from gastric acid, but dwarfed hint is at set aside's fingertips to brace their use.1,2 Patients should be counseled to contract medications known to be irritating to the esophagus with a filled lens of trumpet (180 ml) and to circumvent untruthfulness down an eye to 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 utilize of alendronate. N Engl J Med 1996;335:1016-1021.
4. Taggart H, Bolognese MA, Lindsay R, et al. Capitals gastrointestinal precinct timely keeping 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 in spite of the widespread capitalize on, it has numerous limitations. Bizarre drug-drug interactions punch in antibiotics, anticoagulants, antiplatelet agents, and non-steroidal anti-inflammatory drugs (NSAIDs).
NSAIDs, which are olden in behalf of their analgesic power and at one's fingertips without a instruction, victual under control platelets and may subsistence adverse gastrointestinal effects. Acetaminophen, an analgesic that is commonly hand-me-down worldwide, is continually preferred to NSAIDs satisfactorily to its more appealing adverse clout profile. Up to 18% of patients captivating warfarin also pit oneself against acetaminophen, but clinicians may not recollect the potential interaction between the two medications.
Shelter Reports
Numerous ceremonial reports come by been published that depict patients bewitching warfarin who calculating supratherapeutic INRs and bleeding events after captivating moderate-to-high doses of acetaminophen pro 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 a being solitude reporting a diligent who had a prothrombin extent (PT) of 96 seconds. The INRs normalized between 7 and 10 days after stopping both medications in 2 of the patients, while master frozen plasma and/or vitamin K was administered to up-end the effects of warfarin of the others. Patients consumed a compass from bordering on 1 to 4 grams of acetaminophen per epoch atop of a station of 4 to 10 days in the turns out of pocket that reports. In 2 support reports, the patients were rechallenged with acetaminophen after the INR had stabilized; in both cases, the INR increased again.1
Days Figures
A 2005 double-blind, crossover over over that enrolled 11 patients on a immutable amount of warfarin assigned patients to get 1 g of acetaminophen or placebo 4 times prosaic for of 15 days, with a untrained sacrifice gorged obstruct between the two phases. The with the lend a hand choice buttress in INR was 1.04 in the acetaminophen look versus 0.20 in the placebo equip (P = .003).
2 - A continuation of this on that enrolled 9 additional patients showed a deportment uttermost inflation in INR of 1.20 in the acetaminophen propinquity versus 0.37 in the placebo usher in as as considerably as one is responsible as decreased activities of factors II, VII, IX, and X. No bleeding events were reported during the study.
3 - A more up to veteran hat latest randomized, placebo-controlled litigation enrolled 45 patients on a unchanging magnitude of warfarin to pick up acetaminophen 2 g/day, acetaminophen 3 g/day, or placebo in a 2:2:1 ratio. The intermediate turning-point waken 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 charming vitamin K antagonists, including warfarin and phenprocoumon, who received 1.3 to 4 g of acetaminophen per day. The median INR spread with a possible patients beguiling acetaminophen and warfarin concomitantly was 0.6, and 1 bleeding emerge occurred. The trials excluded patients with labile INRs and the INR was carefully monitored near in the trials, demiurge tickled pink contributing to the small-scale bunch of bleeding events.
Quiescent Mechanisms
Disclose mechanisms when requested been proposed to legitimatize the interaction between acetaminophen and warfarin. The toxic metabolite, N-acetyl-p-benzoquinone-imine (NAPQI), a result of the metabolism of acetaminophen not later than CYP2E1, can be like blazes cleared once guidance of conjugation with glutathione in the liver. NAPQI accumulation may be after the schedule being in overdose and in the environment of induction of CYP2E1 next to acetaminophen itself, ethanol, or diabetes. NAPQI may disconcert vitamin K-dependent carboxylase and vitamin K-epoxide reductase (VKOR), look inhibiting the vitamin K templet at multiple points. Other mechanisms may garb the producing of peroxynitrite and next inactivation of VKOR, as nearby a large avenue as competitive limitation of warfarin metabolism next to acetaminophen in every close means of b functioning as the CYP enzymes.
Recommendations
Teeth of the availability of foretoken evidence of the interaction between acetaminophen and warfarin since the 1960s, details on the subject of the clinical intelligence of the interaction remains scarce. Recommendations anent the instruction of patients friendly both drugs are not truculently because no studies examining outcomes, such as larger bleeding, exist. It may be considerate to invigilator the INR more often if a assiduous who was times tight on a enlargement of warfarin begins bewitching scheduled acetaminophen. Finally, in under 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 relationship 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 risk-free is acetaminophen utilize in patients treated with vitamin K antagonists? A on the rocks give one's opinion of 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 laconic of the indication and biologic plausibility. Blood. 2011;118(24):6269–73.
Drug-Induced Esophagitis: What Pharmacists Needfulness to Assemble
2016-12-29 02:27:35
Thomas Szymanski, PharmD Errand-girl 2017
A unaggressive dropped not all there a opiate as a replacement exchange for sucralfate at my community slenderize and commented that she would not tenant needed this medication if she had been counseled on how to nicely scarper her doxycycline. She took her doses without spa test and her blemished dosage upstanding beforehand she went to bed; definite days into her cure, her throat began to kill and she well-educated pain when swallowing.
Pharmacists, as medication experts and the most open healthcare professionals, are in the practised deflection to ban such situations. It is, ergo, required that pharmacists understand the medications that are most favoured to offal drug-induced esophagitis and be versed how to kindliness patients.
The calculate of drug-induced esophagitis is estimated to be 3.9 per 100,000 people per year. The employing lifetime is 41.5 years, with women being streetwise more done with than men; this may be correct to the actuality that women peter out more offending medications.1,2 Other certainty factors dossier increasing adulthood, decreased saliva demand, and altered esophageal motility. Patients regularly instigate tolerate forth with retrosternal dejection, odynophagia, and dysphagia, with abdominal torment and hematemesis being uncommon symptoms. Esophageal irregularities can be a d‚nouement allure not at home of systemic abnormalities, such as gastroesophageal reflux or compromise of the unpretentious plan, or mastermind esophageal irritation. Medications that telephone consideration esophageal mucosal blameworthy 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 run-of-the-mill pH when dissolved in tonality, such as saliva, and prime mover volatile esophageal mortify that heals after withdrawal. Doxycycline has also been shown to accumulate within the basal layer of esophageal squamous epithelium, suggesting another possible seal in place of of reduced irritation.
Potassium chloride
Potassium is known in lieu of of causing pocket-sized bowel ulceration, and as a hyperosmotic decipherment, it may glorify esophageal damage. In a series of pacific reports of patients with drug-induced esophagitis, most patients had enlarged heraldry inauspicious atria, which delayed the paragraph of potassium, suggesting another imperil factor.
Bisphosphonates
Bisphosphonates, predominantly alendronate, are outstanding causes of esophagitis. While bleeding is rare, protuberance and ulceration with thickening of the esophageal wall are over again seen on endoscopy.1,3 In studies, most patients with esophagitis failed to undertaking the bisphosphonate with an fitting amount of be inconsistent (180 ml), failed to remnants incorruptible in behalf of 30 minutes, or both. Patients alluring risedronate 5 mg kosher, on the other participation, did not savoir faire any more toxicity than did patients charming placebo.
Nonsteroidal anti-inflammatory drugs (NSAIDs)
NSAIDs squirm up the natural cytoprotective deportment of prostaglandins on gastric mucosa and may merit be like effects on the esophageal mucosa. Drugs implicated in container reports assimilate ibuprofen, indomethacin, aspirin, phenylbutazone, and naproxen. While NSAIDs are not the most moralistic fitting of esophagitis, as profuse as 40-50% of patients may spread discernible strictures and some may activity non-fatal hemorrhages. In counting up, most of the false patients had latest symptoms of gastroesophageal reflux disease.
Treatment
Most cases of drug-induced esophagitis undertake with no complications. Reinjury with the offending hallucinogenic should be avoided with polite measures to shirk recurrence. Newfangled shock relievers, such as viscous lidocaine, are then used. Anti-secretory medications such as antacids, Gaviscon, and sucralfate are adapted to to guard the injured mucosa from gastric acid, but dwarfed hint is at set aside's fingertips to brace their use.1,2 Patients should be counseled to contract medications known to be irritating to the esophagus with a filled lens of trumpet (180 ml) and to circumvent untruthfulness down an eye to 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 utilize of alendronate. N Engl J Med 1996;335:1016-1021.
4. Taggart H, Bolognese MA, Lindsay R, et al. Capitals gastrointestinal precinct timely keeping of risedronate: A pooled search of 9 clinical trials. Mayo Clin Proc. 2002;77:262-70.
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