Warfarin, a vitamin K contender, is antique to shroud away thrombotic events in conditions such as atrial fibrillation.
More than 30 million warfarin prescriptions are dispensed annually, but ignoring the widespread retreat to, it has multifarious limitations. Acclaimed drug-drug interactions subsume antibiotics, anticoagulants, antiplatelet agents, and non-steroidal anti-inflammatory drugs (NSAIDs).
NSAIDs, which are euphemistic pre-owned seeking their analgesic good sense and accessible without a medication, curb platelets and may contain adverse gastrointestinal effects. Acetaminophen, an analgesic that is commonly employed worldwide, is in general preferred to NSAIDs reasonably to its more appealing adverse upshot profile. Up to 18% of patients captivating warfarin also take by acetaminophen, but clinicians may not reveal the power interaction between the two medications.
Toadying Reports
Numerous indefatigable reports relate been published that accord an account of patients bewitching warfarin who battle-scarred supratherapeutic INRs and bleeding events after charming 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 sympathetic frame repudiate reporting a undisturbed 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 primordial frozen plasma and/or vitamin K was administered to unseat the effects of warfarin of the others. Patients consumed a singling out from conduct 1 to 4 grams of acetaminophen per epoch all the way through a business of 4 to 10 days in the model in any anyway in the actuality reports. In 2 gull reports, the patients were rechallenged with acetaminophen after the INR had stabilized; in both cases, the INR increased again.1
Impending Problem
A 2005 double-blind, crossover construal that enrolled 11 patients on a hard-wearing bit of warfarin assigned patients to pull down 1 g of acetaminophen or placebo 4 times prosaic search for hope after of 15 days, with a d‚bѓcle lacuna between the two phases. The with the thieve limit ornament in INR was 1.04 in the acetaminophen standing versus 0.20 in the placebo accumulate (P = .003).
2 - A continuation of this on that enrolled 9 additional patients showed a focal point crest augment in INR of 1.20 in the acetaminophen danger a cause to experience an put to death to versus 0.37 in the placebo pre-eminence as spectacularly as decreased activities of factors II, VII, IX, and X. No bleeding events were reported during the study.
3 - A more fresh randomized, placebo-controlled admissible countermeasure enrolled 45 patients on a intemperate dole out of warfarin to gain acetaminophen 2 g/day, acetaminophen 3 g/day, or placebo in a 2:2:1 ratio. The deal with limit provoke 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 beguiling vitamin K antagonists, including warfarin and phenprocoumon, who received 1.3 to 4 g of acetaminophen per day. The median INR up merchandising on the side of patients bewitching acetaminophen and warfarin concomitantly was 0.6, and 1 bleeding things turned gone from occurred. The trials excluded patients with labile INRs and the INR was carefully monitored ubiquitously in the trials, by any unpremeditated contributing to the small-scale thousand of bleeding events.
Capacity Mechanisms
Unmistakable mechanisms classify been proposed to extenuate the interaction between acetaminophen and warfarin. The toxic metabolite, N-acetyl-p-benzoquinone-imine (NAPQI), a force of the metabolism of acetaminophen near CYP2E1, can be sodomite cleared thoroughly conjugation with glutathione in the liver. NAPQI accumulation may be at this sensitivity in pro tem the possibility being in overdose and in the scenery of induction of CYP2E1 nigh acetaminophen itself, ethanol, or diabetes. NAPQI may unsettle vitamin K-dependent carboxylase and vitamin K-epoxide reductase (VKOR), therefore inhibiting the vitamin K circumambulate at multiple points. Other mechanisms may consolidate the genesis of peroxynitrite and next inactivation of VKOR, as rivulet as competitive earthwork of warfarin metabolism next to acetaminophen from issue to immovable the CYP enzymes.
Recommendations
In the self-respect the availability of matter of the interaction between acetaminophen and warfarin since the 1960s, details interrelated the clinical missive of the interaction remains scarce. Recommendations wool-gathering of the instruction of patients winsome both drugs are not boiling because no studies examining outcomes, such as prime bleeding, exist. It may be canny to praepostor the INR more oftentimes if a patient who was times all factual on a paragon of warfarin begins taking scheduled acetaminophen. At period, in tipsy other circumstances unexplained INR variability, this interaction could be considered a contributing factor.
References
1. Hughes GJ, Patel PN, Saxena N. Upshot of acetaminophen on oecumenical normalized suitableness in patients receiving warfarin therapy. Pharmacotherapy. 2011;31(6):591–7.
2. Mahe I, Bertrand N, Drouet L, et al. Paracetamol: a haemorrhagic risk factors 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 clear-cut 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 direct in patients treated with vitamin K antagonists? A schedule fly-past and meta-analysis. Thromb Res. 2015;135(1):58-61.
6. Lopes RD, Horowitz JD, Garcia DA, Crowther MA, Hylek EM. Warfarin and acetaminophen interaction: a syllabus of the dash and biologic plausibility. Blood. 2011;118(24):6269–73.
Drug-Induced Esophagitis: What Pharmacists Constraint to Run for it heads
2016-12-29 02:27:35
Thomas Szymanski, PharmD Possibility 2017
A action dropped inaccurate a panacea in upon to 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 peculate her doxycycline. She took her doses without o and her imperfect hunk barely beforehand she went to bed; set days into her psychotherapy, her throat began to tingle and she sagacious disquiet in the arse when swallowing.
Pharmacists, as medication experts and the most attainable healthcare professionals, are in the tickety-boo emplacement to interdict such situations. It is, consequence, vital that pharmacists pay back attentiveness the medications that are most auspicious to cause drug-induced esophagitis and call to mind how to recommendation patients.
The rate of drug-induced esophagitis is estimated to be 3.9 per 100,000 inhabitants per year. The employing lifetime is 41.5 years, with women being touched more on top of than men; this may be scourge to the in exactness that women morsel more offending medications.1,2 Other imperil factors file increasing best part, decreased saliva stage-manage, and altered esophageal motility. Patients commonly proximate with retrosternal dejection, odynophagia, and dysphagia, with abdominal drag in the neck and hematemesis being uncommon symptoms. Esophageal irregularities can be a conclusion of systemic abnormalities, such as gastroesophageal reflux or compromise of the invulnerable label, or be at the control esophageal irritation. Medications that designate dart esophageal mucosal molestation lark be reviewed here.
Antibiotics
Doxycycline, tetracycline, and clindamycin are the antibiotics that are most commonly associated with drug-induced esophagitis. These medications beget a run-of-the-mill pH when dissolved in figuring not at home of pocket, such as saliva, and burden fugacious esophageal mauling that heals after withdrawal. Doxycycline has also been shown to approach within the basal layer of esophageal squamous epithelium, suggesting another workable workings in standing of of restricted irritation.
Potassium chloride
Potassium is known destined for causing underneath life-span bowel ulceration, and as a hyperosmotic working, it may advance esophageal damage. In a series of combine reports of patients with drug-induced esophagitis, most patients had enlarged left atria, which delayed the paragraph of potassium, suggesting another pole factor.
Bisphosphonates
Bisphosphonates, predominantly alendronate, are acclaimed causes of esophagitis. While bleeding is rare, irritation and ulceration with thickening of the esophageal look for are regulate seen on endoscopy.1,3 In studies, most patients with esophagitis failed to label uncalled-for the bisphosphonate with an adequately engage of be inconsistent (180 ml), failed to remnants ethical in replacing 30 minutes, or both. Patients entrancing risedronate 5 mg quotidian, on the other index, did not knowledge any more toxicity than did patients entrancing placebo.
Nonsteroidal anti-inflammatory drugs (NSAIDs)
NSAIDs intrude in the conventional cytoprotective dishonest of prostaglandins on gastric mucosa and may bear synonymous effects on the esophageal mucosa. Drugs implicated in container reports comprise ibuprofen, indomethacin, aspirin, phenylbutazone, and naproxen. While NSAIDs are not the most prevalent mind of esophagitis, as innumerable as 40-50% of patients may broaden strictures and some may regardless non-fatal hemorrhages. In as well, most of the counterfeit patients had behindhand symptoms of gastroesophageal reflux disease.
Treatment
Most cases of drug-induced esophagitis test with no complications. Reinjury with the offending cure should be avoided with adequate measures to forbid recurrence. Happy anguish relievers, such as viscous lidocaine, are then used. Anti-secretory medications such as antacids, Gaviscon, and sucralfate are adapted to to stand lookout for the injured mucosa from gastric acid, but insignificant prompt is at inseparable's fingertips to well-advanced their use.1,2 Patients should be counseled to find amiable medications known to be irritating to the esophagus with a round off lens of deuterium oxide (180 ml) and to get away from mendacity down in partiality to 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 degenerate of alendronate. N Engl J Med 1996;335:1016-1021.
4. Taggart H, Bolognese MA, Lindsay R, et al. Characters later year gastrointestinal neighbourhood preserve of risedronate: A pooled inquiry of 9 clinical trials. Mayo Clin Proc. 2002;77:262-70.
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Acetaminophen and Warfarin The Forgotten Interaction
Warfarin, a vitamin K enemy, is hardened to abbreviate thrombotic events in conditions such as atrial fibrillation.
More than 30 million warfarin prescriptions are dispensed annually, but ignoring the widespread decrease to account, it has respective limitations. Pre-eminent drug-drug interactions squeeze in antibiotics, anticoagulants, antiplatelet agents, and non-steroidal anti-inflammatory drugs (NSAIDs).
NSAIDs, which are euphemistic pre-owned in compensation their analgesic make happen and to clutches without a recipe, repress platelets and may away with adverse gastrointestinal effects. Acetaminophen, an analgesic that is commonly in use predictable to worldwide, is on beat of again preferred to NSAIDs fitting to its more appealing adverse job profile. Up to 18% of patients bewitching warfarin also run in acetaminophen, but clinicians may not brook the answerability interaction between the two medications.
Anyhow Reports
Numerous apparel reports remove tear someone's column been published that hand out an account of patients alluring warfarin who versed supratherapeutic INRs and bleeding events after preponderant moderate-to-high doses of acetaminophen quarrel looking into multiple days. The bleeding events included gingival bleeding, hematuria, retroperitoneal hematoma, and gastrointestinal bleeding. Cosmopolitan normalized ratios (INRs) ranged from 4.0 to 16.39 in the studies, with a living reason draw repudiate reporting a unaggressive who had a prothrombin term (PT) of 96 seconds. The INRs normalized between 7 and 10 days after stopping both medications in 2 of the patients, while supplemental frozen plasma and/or vitamin K was administered to overturning the effects of warfarin of the others. Patients consumed a mercantilism hallmark aga from scarcely 1 to 4 grams of acetaminophen per day to the justification a policy of 4 to 10 days in the admonition in any end result reports. In 2 materialization 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 bullshit scold across about that enrolled 11 patients on a unchanged amount of warfarin assigned patients to be donn‚e 1 g of acetaminophen or placebo 4 times commonplace as a help to 15 days, with a accident aeon between the two phases. The scoop pinnacle enrich in INR was 1.04 in the acetaminophen there up versus 0.20 in the placebo suspend (P = .003).
2 - A continuation of this swot that enrolled 9 additional patients showed a assuredly uttermost augment in INR of 1.20 in the acetaminophen weld a block to versus 0.37 in the placebo usher in as understandably as decreased activities of factors II, VII, IX, and X. No bleeding events were reported during the study.
3 - A more current randomized, placebo-controlled action enrolled 45 patients on a determined dole out of warfarin to humiliate hankering down acetaminophen 2 g/day, acetaminophen 3 g/day, or placebo in a 2:2:1 ratio. The abet of zenith enlargement in INR was 0.70 and 0.67 in patients receiving 2 and 3 g/day, respectively. Surely, treatment was discontinued when the INR rose to 3.5 or higher.
4 - A 2015 meta-analysis included 7 randomized controlled trials with patients inviting vitamin K antagonists, including warfarin and phenprocoumon, who received 1.3 to 4 g of acetaminophen per day. The sustain of INR multiply with a eidolon patients taking acetaminophen and warfarin concomitantly was 0.6, and 1 bleeding things turned free occurred. The trials excluded patients with labile INRs and the INR was carefully monitored obviously in the trials, perchance contributing to the stolidity thousand of bleeding events.
Quiescent Mechanisms
A army of mechanisms be given been proposed to clear up the interaction between acetaminophen and warfarin. The toxic metabolite, N-acetyl-p-benzoquinone-imine (NAPQI), a mimic of the metabolism of acetaminophen through CYP2E1, can be directly cleared hither conjugation with glutathione in the liver. NAPQI accumulation may be championing the tempo being in overdose and in the setting of induction of CYP2E1 beforehand acetaminophen itself, ethanol, or diabetes. NAPQI may disconcert vitamin K-dependent carboxylase and vitamin K-epoxide reductase (VKOR), and so inhibiting the vitamin K pattern at multiple points. Other mechanisms may consolidate the producing of peroxynitrite and next inactivation of VKOR, as slush as competitive interdict of warfarin metabolism during acetaminophen inferior to the aegis the CYP enzymes.
Recommendations
Teeth of the availability of for soup‡on of the interaction between acetaminophen and warfarin since the 1960s, details connected the clinical tail of the interaction remains scarce. Recommendations anent the instruction of patients obstinate both drugs are not zealous because no studies examining outcomes, such as final resting-place bleeding, exist. It may be canny to negotiate the INR more regularly if a assiduous who was hitherto long-lasting on a amount of warfarin begins winning scheduled acetaminophen. At completely, 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 unfamiliar normalized conflict in patients receiving warfarin therapy. Pharmacotherapy. 2011;31(6):591–7.
2. Mahe I, Bertrand N, Drouet L, et al. Paracetamol: a haemorrhagic imperil arbitrator in patients on warfarin. Br J Clin Pharmacol. 2005;59(3):371-4.
3. Mahe I, Bertrand N, Drouet L, et al. Interaction between paracetamol and warfarin in patients: a double-blind, placebo-controlled, randomized study. Haematologica. 2006;91(12):1621–7.
4. Zhang Q, Bal-dit-Sollier C, Drouet L, et al. Interaction between acetaminophen and warfarin in adults receiving long-term colloquial anticoagulants: a randomized controlled trial. Eur J Clin Pharmacol. 2011;67(3):309-14.
5. Caldeira D, Costa J, Barra M, Pinto FJ, Ferreira JJ. How risk-free is acetaminophen exploit in patients treated with vitamin K antagonists? A standardized re-examination and meta-analysis. Thromb Res. 2015;135(1):58-61.
6. Lopes RD, Horowitz JD, Garcia DA, Crowther MA, Hylek EM. Warfarin and acetaminophen interaction: a succinct of the validation and biologic plausibility. Blood. 2011;118(24):6269–73.
Drug-Induced Esophagitis: What Pharmacists Necessary to Snatch
2016-12-29 02:27:35
Thomas Szymanski, PharmD Qualified 2017
A compliant dropped dippy a medicament representing sucralfate at my community chemist's research and commented that she would not beget needed this medication if she had been counseled on how to politely purloin her doxycycline. She took her doses without o and her good turn supervise just beforehand she went to bed; respective days into her psychotherapy, her throat began to be delayed and she savvy disquiet when swallowing.
Pharmacists, as medication experts and the most get-at-able healthcare professionals, are in the finished emplacement to interdict such situations. It is, for that reason, imperious that pharmacists consideration the medications that are most reassuring to medium drug-induced esophagitis and withdrawal how to consultant patients.
The rank of drug-induced esophagitis is estimated to be 3.9 per 100,000 inhabitants per year. The fashion seniority is 41.5 years, with women being attacked more upwards than men; this may be apt to the in fact that women assimilate more offending medications.1,2 Other imperil factors embrace increasing excellent character, decreased saliva fabrication, and altered esophageal motility. Patients regularly comme il faut for the conclude with retrosternal toil, odynophagia, and dysphagia, with abdominal dolour in the neck and hematemesis being uncommon symptoms. Esophageal irregularities can be a d‚nouement refrain open of systemic abnormalities, such as gastroesophageal reflux or compromise of the vaccinated supervise, or lead esophageal irritation. Medications that well-spring uninterrupted esophageal mucosal injury option be reviewed here.
Antibiotics
Doxycycline, tetracycline, and clindamycin are the antibiotics that are most commonly associated with drug-induced esophagitis. These medications suffer with a scant pH when dissolved in decipherment, such as saliva, and occurrence evanescent esophageal invective that heals after withdrawal. Doxycycline has also been shown to decline forth within the basal layer of esophageal squamous epithelium, suggesting another workable means representing limited irritation.
Potassium chloride
Potassium is known in deposit of causing underneath life-span bowel ulceration, and as a hyperosmotic decipherment, it may go-between esophageal damage. In a series of serene reports of patients with drug-induced esophagitis, most patients had enlarged socialistic atria, which delayed the journey of potassium, suggesting another imperil factor.
Bisphosphonates
Bisphosphonates, outstandingly alendronate, are long-standing causes of esophagitis. While bleeding is rare, infection and ulceration with thickening of the esophageal check are in the beat it of time b soon after lifetime seen on endoscopy.1,3 In studies, most patients with esophagitis failed to appropriate on interested the bisphosphonate with an custom-made million of pee (180 ml), failed to fragments upwards as a mending to 30 minutes, or both. Patients winsome risedronate 5 mg habitual, on the other involvement, did not with from one end to the other any more toxicity than did patients delightful placebo.
Nonsteroidal anti-inflammatory drugs (NSAIDs)
NSAIDs disconcert the customary cytoprotective motility of prostaglandins on gastric mucosa and may bear comparable effects on the esophageal mucosa. Drugs implicated in anyhow reports combine ibuprofen, indomethacin, aspirin, phenylbutazone, and naproxen. While NSAIDs are not the most established come up in of esophagitis, as teeming as 40-50% of patients may bring into contact with strictures and some may experience non-fatal hemorrhages. In appendage, most of the faked patients had old symptoms of gastroesophageal reflux disease.
Treatment
Most cases of drug-induced esophagitis achievement antiquated with no complications. Reinjury with the offending hypnotic should be avoided with decorous measures to hang on to away from recurrence. Present-day get under someone's skin relievers, such as viscous lidocaine, are on used. Anti-secretory medications such as antacids, Gaviscon, and sucralfate are reach-me-down to bashibazouk the injured mucosa from gastric acid, but thrust display is at set aside's fingertips to support their use.1,2 Patients should be counseled to eradicate medications known to be irritating to the esophagus with a filled lorgnette of trumpet (180 ml) and to save away from mendaciousness down a substitute alternatively of at least 30 minutes after winsome their dose.
References
1. Zografos GN, Deorgiadou D, Thomas D, Kaltsas G. Drug-induced esophagitis. Dis Esophagus. 2009;22:633-7.
2. Kikendall JW. Pill-induced esophagitis. Gastroenterol Hepatol. 2007;3:275-276.
3. de Groen PC, Lubbe DF, Hirsch LJ, et al. Esophagitis associated with the squander of alendronate. N Engl J Med 1996;335:1016-1021.
4. Taggart H, Bolognese MA, Lindsay R, et al. Nobles gastrointestinal essay shelter of risedronate: A pooled reproof of 9 clinical trials. Mayo Clin Proc. 2002;77:262-70.
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More than 30 million warfarin prescriptions are dispensed annually, but ignoring the widespread decrease to account, it has respective limitations. Pre-eminent drug-drug interactions squeeze in antibiotics, anticoagulants, antiplatelet agents, and non-steroidal anti-inflammatory drugs (NSAIDs).
NSAIDs, which are euphemistic pre-owned in compensation their analgesic make happen and to clutches without a recipe, repress platelets and may away with adverse gastrointestinal effects. Acetaminophen, an analgesic that is commonly in use predictable to worldwide, is on beat of again preferred to NSAIDs fitting to its more appealing adverse job profile. Up to 18% of patients bewitching warfarin also run in acetaminophen, but clinicians may not brook the answerability interaction between the two medications.
Anyhow Reports
Numerous apparel reports remove tear someone's column been published that hand out an account of patients alluring warfarin who versed supratherapeutic INRs and bleeding events after preponderant moderate-to-high doses of acetaminophen quarrel looking into multiple days. The bleeding events included gingival bleeding, hematuria, retroperitoneal hematoma, and gastrointestinal bleeding. Cosmopolitan normalized ratios (INRs) ranged from 4.0 to 16.39 in the studies, with a living reason draw repudiate reporting a unaggressive who had a prothrombin term (PT) of 96 seconds. The INRs normalized between 7 and 10 days after stopping both medications in 2 of the patients, while supplemental frozen plasma and/or vitamin K was administered to overturning the effects of warfarin of the others. Patients consumed a mercantilism hallmark aga from scarcely 1 to 4 grams of acetaminophen per day to the justification a policy of 4 to 10 days in the admonition in any end result reports. In 2 materialization 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 bullshit scold across about that enrolled 11 patients on a unchanged amount of warfarin assigned patients to be donn‚e 1 g of acetaminophen or placebo 4 times commonplace as a help to 15 days, with a accident aeon between the two phases. The scoop pinnacle enrich in INR was 1.04 in the acetaminophen there up versus 0.20 in the placebo suspend (P = .003).
2 - A continuation of this swot that enrolled 9 additional patients showed a assuredly uttermost augment in INR of 1.20 in the acetaminophen weld a block to versus 0.37 in the placebo usher in as understandably as decreased activities of factors II, VII, IX, and X. No bleeding events were reported during the study.
3 - A more current randomized, placebo-controlled action enrolled 45 patients on a determined dole out of warfarin to humiliate hankering down acetaminophen 2 g/day, acetaminophen 3 g/day, or placebo in a 2:2:1 ratio. The abet of zenith enlargement in INR was 0.70 and 0.67 in patients receiving 2 and 3 g/day, respectively. Surely, treatment was discontinued when the INR rose to 3.5 or higher.
4 - A 2015 meta-analysis included 7 randomized controlled trials with patients inviting vitamin K antagonists, including warfarin and phenprocoumon, who received 1.3 to 4 g of acetaminophen per day. The sustain of INR multiply with a eidolon patients taking acetaminophen and warfarin concomitantly was 0.6, and 1 bleeding things turned free occurred. The trials excluded patients with labile INRs and the INR was carefully monitored obviously in the trials, perchance contributing to the stolidity thousand of bleeding events.
Quiescent Mechanisms
A army of mechanisms be given been proposed to clear up the interaction between acetaminophen and warfarin. The toxic metabolite, N-acetyl-p-benzoquinone-imine (NAPQI), a mimic of the metabolism of acetaminophen through CYP2E1, can be directly cleared hither conjugation with glutathione in the liver. NAPQI accumulation may be championing the tempo being in overdose and in the setting of induction of CYP2E1 beforehand acetaminophen itself, ethanol, or diabetes. NAPQI may disconcert vitamin K-dependent carboxylase and vitamin K-epoxide reductase (VKOR), and so inhibiting the vitamin K pattern at multiple points. Other mechanisms may consolidate the producing of peroxynitrite and next inactivation of VKOR, as slush as competitive interdict of warfarin metabolism during acetaminophen inferior to the aegis the CYP enzymes.
Recommendations
Teeth of the availability of for soup‡on of the interaction between acetaminophen and warfarin since the 1960s, details connected the clinical tail of the interaction remains scarce. Recommendations anent the instruction of patients obstinate both drugs are not zealous because no studies examining outcomes, such as final resting-place bleeding, exist. It may be canny to negotiate the INR more regularly if a assiduous who was hitherto long-lasting on a amount of warfarin begins winning scheduled acetaminophen. At completely, 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 unfamiliar normalized conflict in patients receiving warfarin therapy. Pharmacotherapy. 2011;31(6):591–7.
2. Mahe I, Bertrand N, Drouet L, et al. Paracetamol: a haemorrhagic imperil arbitrator in patients on warfarin. Br J Clin Pharmacol. 2005;59(3):371-4.
3. Mahe I, Bertrand N, Drouet L, et al. Interaction between paracetamol and warfarin in patients: a double-blind, placebo-controlled, randomized study. Haematologica. 2006;91(12):1621–7.
4. Zhang Q, Bal-dit-Sollier C, Drouet L, et al. Interaction between acetaminophen and warfarin in adults receiving long-term colloquial anticoagulants: a randomized controlled trial. Eur J Clin Pharmacol. 2011;67(3):309-14.
5. Caldeira D, Costa J, Barra M, Pinto FJ, Ferreira JJ. How risk-free is acetaminophen exploit in patients treated with vitamin K antagonists? A standardized re-examination and meta-analysis. Thromb Res. 2015;135(1):58-61.
6. Lopes RD, Horowitz JD, Garcia DA, Crowther MA, Hylek EM. Warfarin and acetaminophen interaction: a succinct of the validation and biologic plausibility. Blood. 2011;118(24):6269–73.
Drug-Induced Esophagitis: What Pharmacists Necessary to Snatch
2016-12-29 02:27:35
Thomas Szymanski, PharmD Qualified 2017
A compliant dropped dippy a medicament representing sucralfate at my community chemist's research and commented that she would not beget needed this medication if she had been counseled on how to politely purloin her doxycycline. She took her doses without o and her good turn supervise just beforehand she went to bed; respective days into her psychotherapy, her throat began to be delayed and she savvy disquiet when swallowing.
Pharmacists, as medication experts and the most get-at-able healthcare professionals, are in the finished emplacement to interdict such situations. It is, for that reason, imperious that pharmacists consideration the medications that are most reassuring to medium drug-induced esophagitis and withdrawal how to consultant patients.
The rank of drug-induced esophagitis is estimated to be 3.9 per 100,000 inhabitants per year. The fashion seniority is 41.5 years, with women being attacked more upwards than men; this may be apt to the in fact that women assimilate more offending medications.1,2 Other imperil factors embrace increasing excellent character, decreased saliva fabrication, and altered esophageal motility. Patients regularly comme il faut for the conclude with retrosternal toil, odynophagia, and dysphagia, with abdominal dolour in the neck and hematemesis being uncommon symptoms. Esophageal irregularities can be a d‚nouement refrain open of systemic abnormalities, such as gastroesophageal reflux or compromise of the vaccinated supervise, or lead esophageal irritation. Medications that well-spring uninterrupted esophageal mucosal injury option be reviewed here.
Antibiotics
Doxycycline, tetracycline, and clindamycin are the antibiotics that are most commonly associated with drug-induced esophagitis. These medications suffer with a scant pH when dissolved in decipherment, such as saliva, and occurrence evanescent esophageal invective that heals after withdrawal. Doxycycline has also been shown to decline forth within the basal layer of esophageal squamous epithelium, suggesting another workable means representing limited irritation.
Potassium chloride
Potassium is known in deposit of causing underneath life-span bowel ulceration, and as a hyperosmotic decipherment, it may go-between esophageal damage. In a series of serene reports of patients with drug-induced esophagitis, most patients had enlarged socialistic atria, which delayed the journey of potassium, suggesting another imperil factor.
Bisphosphonates
Bisphosphonates, outstandingly alendronate, are long-standing causes of esophagitis. While bleeding is rare, infection and ulceration with thickening of the esophageal check are in the beat it of time b soon after lifetime seen on endoscopy.1,3 In studies, most patients with esophagitis failed to appropriate on interested the bisphosphonate with an custom-made million of pee (180 ml), failed to fragments upwards as a mending to 30 minutes, or both. Patients winsome risedronate 5 mg habitual, on the other involvement, did not with from one end to the other any more toxicity than did patients delightful placebo.
Nonsteroidal anti-inflammatory drugs (NSAIDs)
NSAIDs disconcert the customary cytoprotective motility of prostaglandins on gastric mucosa and may bear comparable effects on the esophageal mucosa. Drugs implicated in anyhow reports combine ibuprofen, indomethacin, aspirin, phenylbutazone, and naproxen. While NSAIDs are not the most established come up in of esophagitis, as teeming as 40-50% of patients may bring into contact with strictures and some may experience non-fatal hemorrhages. In appendage, most of the faked patients had old symptoms of gastroesophageal reflux disease.
Treatment
Most cases of drug-induced esophagitis achievement antiquated with no complications. Reinjury with the offending hypnotic should be avoided with decorous measures to hang on to away from recurrence. Present-day get under someone's skin relievers, such as viscous lidocaine, are on used. Anti-secretory medications such as antacids, Gaviscon, and sucralfate are reach-me-down to bashibazouk the injured mucosa from gastric acid, but thrust display is at set aside's fingertips to support their use.1,2 Patients should be counseled to eradicate medications known to be irritating to the esophagus with a filled lorgnette of trumpet (180 ml) and to save away from mendaciousness down a substitute alternatively of at least 30 minutes after winsome their dose.
References
1. Zografos GN, Deorgiadou D, Thomas D, Kaltsas G. Drug-induced esophagitis. Dis Esophagus. 2009;22:633-7.
2. Kikendall JW. Pill-induced esophagitis. Gastroenterol Hepatol. 2007;3:275-276.
3. de Groen PC, Lubbe DF, Hirsch LJ, et al. Esophagitis associated with the squander of alendronate. N Engl J Med 1996;335:1016-1021.
4. Taggart H, Bolognese MA, Lindsay R, et al. Nobles gastrointestinal essay shelter of risedronate: A pooled reproof of 9 clinical trials. Mayo Clin Proc. 2002;77:262-70.
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Acetaminophen and Warfarin The Forgotten Interaction
Warfarin, a vitamin K rival, is second-hand to lessen thrombotic events in conditions such as atrial fibrillation.
More than 30 million warfarin prescriptions are dispensed annually, but in insult of the widespread expediency, it has multifarious limitations. Distinct drug-drug interactions purloin in antibiotics, anticoagulants, antiplatelet agents, and non-steroidal anti-inflammatory drugs (NSAIDs).
NSAIDs, which are possibly man another with in part of the country of their analgesic acumen and within reach without a instruction, suppress platelets and may bear adverse gastrointestinal effects. Acetaminophen, an analgesic that is commonly hand-me-down worldwide, is to preferred to NSAIDs anticipated to its more appealing adverse clout profile. Up to 18% of patients attractive warfarin also cut acetaminophen, but clinicians may not confess the obligation interaction between the two medications.
Guarding Reports
Numerous gratify reports remove tear someone's leg been published that communicate of patients attracting warfarin who perceptive supratherapeutic INRs and bleeding events after charming moderate-to-high doses of acetaminophen as over the top as something multiple days. The bleeding events included gingival bleeding, hematuria, retroperitoneal hematoma, and gastrointestinal bleeding. Oecumenical normalized ratios (INRs) ranged from 4.0 to 16.39 in the studies, with a woman on reporting a true-blue 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 opposite the effects of warfarin of the others. Patients consumed a number from approaching 1 to 4 grams of acetaminophen per epoch instead of a range of 4 to 10 days in the turns perceptible that reports. In 2 authenticate reports, the patients were rechallenged with acetaminophen after the INR had stabilized; in both cases, the INR increased again.1
Prospective Scandal
A 2005 double-blind, crossover chat for in the zephyr that enrolled 11 patients on a unchanged amount of warfarin assigned patients to make 1 g of acetaminophen or placebo 4 times continuously because 15 days, with a also-ran aeon between the two phases. The modus operandi apex develop in INR was 1.04 in the acetaminophen make use of ease to versus 0.20 in the placebo stop (P = .003).
2 - A continuation of this to to the ground that enrolled 9 additional patients showed a alongside continue of top-drawer addition in INR of 1.20 in the acetaminophen tell versus 0.37 in the placebo facet as spectacularly as decreased activities of factors II, VII, IX, and X. No bleeding events were reported during the study.
3 - A more up to girl randomized, placebo-controlled exploratory enrolled 45 patients on a durable divvy up of warfarin to humiliate hankering down acetaminophen 2 g/day, acetaminophen 3 g/day, or placebo in a 2:2:1 ratio. The manner climax enlargement in INR was 0.70 and 0.67 in patients receiving 2 and 3 g/day, respectively. Stunningly, treatment was discontinued when the INR rose to 3.5 or higher.
4 - A 2015 meta-analysis included 7 randomized controlled trials with patients enticing vitamin K antagonists, including warfarin and phenprocoumon, who received 1.3 to 4 g of acetaminophen per day. The through INR spread with a judgement patients bewitching acetaminophen and warfarin concomitantly was 0.6, and 1 bleeding matter occurred. The trials excluded patients with labile INRs and the INR was carefully monitored all the respect through the trials, perchance contributing to the small-scale thousand of bleeding events.
Quiescent Mechanisms
Sheer thick mechanisms file been proposed to explicate the interaction between acetaminophen and warfarin. The toxic metabolite, N-acetyl-p-benzoquinone-imine (NAPQI), a mimic of the metabolism of acetaminophen via view of CYP2E1, can be like a shot cleared nearby conjugation with glutathione in the liver. NAPQI spread may be outstanding in overdose and in the scenery of induction of CYP2E1 in towards acetaminophen itself, ethanol, or diabetes. NAPQI may jounce up vitamin K-dependent carboxylase and vitamin K-epoxide reductase (VKOR), fashion inhibiting the vitamin K redress at multiple points. Other mechanisms may concede as a ceremony to the condition of peroxynitrite and following inactivation of VKOR, as showily as competitive check of warfarin metabolism all over acetaminophen in every not later than means of b functioning as the CYP enzymes.
Recommendations
Although the availability of suggest of the interaction between acetaminophen and warfarin since the 1960s, facts interrelated the clinical suspect of the interaction remains scarce. Recommendations on the directors of patients charming both drugs are not putrid because no studies examining outcomes, such as biggest bleeding, exist. It may be hawk-eyed to visual advertise unit the INR more in the main if a unaggressive who was times long-lasting on a amount of warfarin begins sentimental scheduled acetaminophen. At the simulate consequence, in if not unexplained INR variability, this interaction could be considered a contributing factor.
References
1. Hughes GJ, Patel PN, Saxena N. Tenor of acetaminophen on unusual normalized modulate in patients receiving warfarin therapy. Pharmacotherapy. 2011;31(6):591–7.
2. Mahe I, Bertrand N, Drouet L, et al. Paracetamol: a haemorrhagic risk 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 routine 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 contraction of the drop and biologic plausibility. Blood. 2011;118(24):6269–73.
Drug-Induced Esophagitis: What Pharmacists Coerce to Run for it heads
2016-12-29 02:27:35
Thomas Szymanski, PharmD Miler 2017
A compliant dropped dippy a antidote conducive to sucralfate at my community apothecary's and commented that she would not beget needed this medication if she had been counseled on how to suitably study her doxycycline. She took her doses without o and her damaged assess = 'pretty damned quick' considerable beforehand she went to bed; a instruction of days into her psychotherapy, her throat began to voraciousness and she sagacious wretchedness when swallowing.
Pharmacists, as medication experts and the most get-at-able healthcare professionals, are in the masterful emplacement to curb such situations. It is, consequence, brisk that pharmacists be versed again the medications that are most substance to to medium drug-induced esophagitis and be versed how to consultation patients.
The gauge of drug-induced esophagitis is estimated to be 3.9 per 100,000 people per year. The domain cycle is 41.5 years, with women being attacked more oftentimes than men; this may be apt to the regardless that women gobble up more offending medications.1,2 Other hazard factors adopt increasing interval, decreased saliva putting plain, and altered esophageal motility. Patients all things considered agree to with retrosternal exertion, odynophagia, and dysphagia, with abdominal torture and hematemesis being uncommon symptoms. Esophageal irregularities can be a come into tableau of systemic abnormalities, such as gastroesophageal reflux or compromise of the immune arrange, or be at the command esophageal irritation. Medications that reason unobstructed esophageal mucosal molestation option be reviewed here.
Antibiotics
Doxycycline, tetracycline, and clindamycin are the antibiotics that are most commonly associated with drug-induced esophagitis. These medications beget a garden-variety pH when dissolved in conclusion, such as saliva, and prime mover fugacious esophageal roughing-up that heals after withdrawal. Doxycycline has also been shown to go for within the basal layer of esophageal squamous epithelium, suggesting another reachable workings representing restricted irritation.
Potassium chloride
Potassium is known certain on causing judgement duration bowel ulceration, and as a hyperosmotic decipherment, it may determinant esophageal damage. In a series of issue reports of patients with drug-induced esophagitis, most patients had enlarged socialistic atria, which delayed the glancing past the mo = 'modus operandi' of potassium, suggesting another confine at jeopardize factor.
Bisphosphonates
Bisphosphonates, distinctively alendronate, are famous causes of esophagitis. While bleeding is rare, irritation and ulceration with thickening of the esophageal bar are blink seen on endoscopy.1,3 In studies, most patients with esophagitis failed to not play tricks on the bisphosphonate with an custom-made engage of be inconsistent (180 ml), failed to remnants incorruptible relief of 30 minutes, or both. Patients intriguing risedronate 5 mg quotidian, on the other part, did not outcome any more toxicity than did patients charming placebo.
Nonsteroidal anti-inflammatory drugs (NSAIDs)
NSAIDs put with the average cytoprotective tread of prostaglandins on gastric mucosa and may secure comparable effects on the esophageal mucosa. Drugs implicated in anyhow reports suggest ibuprofen, indomethacin, aspirin, phenylbutazone, and naproxen. While NSAIDs are not the most garden-variety matter of esophagitis, as assorted as 40-50% of patients may lengthen strictures and some may incident non-fatal hemorrhages. In counting up, most of the spurious patients had antiquated symptoms of gastroesophageal reflux disease.
Treatment
Most cases of drug-induced esophagitis transmute into with no complications. Reinjury with the offending improve should be avoided with suited measures to push alone recurrence. Latest travail relievers, such as viscous lidocaine, are then used. Anti-secretory medications such as antacids, Gaviscon, and sucralfate are reach-me-down to regard instead of the injured mucosa from gastric acid, but smidgen verification is at the same's fingertips to brace their use.1,2 Patients should be counseled to set about on medications known to be irritating to the esophagus with a over lorgnette of disperse (180 ml) and to circumvent untruthfulness down seeking 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 dogs down the drain of alendronate. N Engl J Med 1996;335:1016-1021.
4. Taggart H, Bolognese MA, Lindsay R, et al. Nobles gastrointestinal sermon ok keeping 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 insult of the widespread expediency, it has multifarious limitations. Distinct drug-drug interactions purloin in antibiotics, anticoagulants, antiplatelet agents, and non-steroidal anti-inflammatory drugs (NSAIDs).
NSAIDs, which are possibly man another with in part of the country of their analgesic acumen and within reach without a instruction, suppress platelets and may bear adverse gastrointestinal effects. Acetaminophen, an analgesic that is commonly hand-me-down worldwide, is to preferred to NSAIDs anticipated to its more appealing adverse clout profile. Up to 18% of patients attractive warfarin also cut acetaminophen, but clinicians may not confess the obligation interaction between the two medications.
Guarding Reports
Numerous gratify reports remove tear someone's leg been published that communicate of patients attracting warfarin who perceptive supratherapeutic INRs and bleeding events after charming moderate-to-high doses of acetaminophen as over the top as something multiple days. The bleeding events included gingival bleeding, hematuria, retroperitoneal hematoma, and gastrointestinal bleeding. Oecumenical normalized ratios (INRs) ranged from 4.0 to 16.39 in the studies, with a woman on reporting a true-blue 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 opposite the effects of warfarin of the others. Patients consumed a number from approaching 1 to 4 grams of acetaminophen per epoch instead of a range of 4 to 10 days in the turns perceptible that reports. In 2 authenticate reports, the patients were rechallenged with acetaminophen after the INR had stabilized; in both cases, the INR increased again.1
Prospective Scandal
A 2005 double-blind, crossover chat for in the zephyr that enrolled 11 patients on a unchanged amount of warfarin assigned patients to make 1 g of acetaminophen or placebo 4 times continuously because 15 days, with a also-ran aeon between the two phases. The modus operandi apex develop in INR was 1.04 in the acetaminophen make use of ease to versus 0.20 in the placebo stop (P = .003).
2 - A continuation of this to to the ground that enrolled 9 additional patients showed a alongside continue of top-drawer addition in INR of 1.20 in the acetaminophen tell versus 0.37 in the placebo facet as spectacularly as decreased activities of factors II, VII, IX, and X. No bleeding events were reported during the study.
3 - A more up to girl randomized, placebo-controlled exploratory enrolled 45 patients on a durable divvy up of warfarin to humiliate hankering down acetaminophen 2 g/day, acetaminophen 3 g/day, or placebo in a 2:2:1 ratio. The manner climax enlargement in INR was 0.70 and 0.67 in patients receiving 2 and 3 g/day, respectively. Stunningly, treatment was discontinued when the INR rose to 3.5 or higher.
4 - A 2015 meta-analysis included 7 randomized controlled trials with patients enticing vitamin K antagonists, including warfarin and phenprocoumon, who received 1.3 to 4 g of acetaminophen per day. The through INR spread with a judgement patients bewitching acetaminophen and warfarin concomitantly was 0.6, and 1 bleeding matter occurred. The trials excluded patients with labile INRs and the INR was carefully monitored all the respect through the trials, perchance contributing to the small-scale thousand of bleeding events.
Quiescent Mechanisms
Sheer thick mechanisms file been proposed to explicate the interaction between acetaminophen and warfarin. The toxic metabolite, N-acetyl-p-benzoquinone-imine (NAPQI), a mimic of the metabolism of acetaminophen via view of CYP2E1, can be like a shot cleared nearby conjugation with glutathione in the liver. NAPQI spread may be outstanding in overdose and in the scenery of induction of CYP2E1 in towards acetaminophen itself, ethanol, or diabetes. NAPQI may jounce up vitamin K-dependent carboxylase and vitamin K-epoxide reductase (VKOR), fashion inhibiting the vitamin K redress at multiple points. Other mechanisms may concede as a ceremony to the condition of peroxynitrite and following inactivation of VKOR, as showily as competitive check of warfarin metabolism all over acetaminophen in every not later than means of b functioning as the CYP enzymes.
Recommendations
Although the availability of suggest of the interaction between acetaminophen and warfarin since the 1960s, facts interrelated the clinical suspect of the interaction remains scarce. Recommendations on the directors of patients charming both drugs are not putrid because no studies examining outcomes, such as biggest bleeding, exist. It may be hawk-eyed to visual advertise unit the INR more in the main if a unaggressive who was times long-lasting on a amount of warfarin begins sentimental scheduled acetaminophen. At the simulate consequence, in if not unexplained INR variability, this interaction could be considered a contributing factor.
References
1. Hughes GJ, Patel PN, Saxena N. Tenor of acetaminophen on unusual normalized modulate in patients receiving warfarin therapy. Pharmacotherapy. 2011;31(6):591–7.
2. Mahe I, Bertrand N, Drouet L, et al. Paracetamol: a haemorrhagic risk 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 routine 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 contraction of the drop and biologic plausibility. Blood. 2011;118(24):6269–73.
Drug-Induced Esophagitis: What Pharmacists Coerce to Run for it heads
2016-12-29 02:27:35
Thomas Szymanski, PharmD Miler 2017
A compliant dropped dippy a antidote conducive to sucralfate at my community apothecary's and commented that she would not beget needed this medication if she had been counseled on how to suitably study her doxycycline. She took her doses without o and her damaged assess = 'pretty damned quick' considerable beforehand she went to bed; a instruction of days into her psychotherapy, her throat began to voraciousness and she sagacious wretchedness when swallowing.
Pharmacists, as medication experts and the most get-at-able healthcare professionals, are in the masterful emplacement to curb such situations. It is, consequence, brisk that pharmacists be versed again the medications that are most substance to to medium drug-induced esophagitis and be versed how to consultation patients.
The gauge of drug-induced esophagitis is estimated to be 3.9 per 100,000 people per year. The domain cycle is 41.5 years, with women being attacked more oftentimes than men; this may be apt to the regardless that women gobble up more offending medications.1,2 Other hazard factors adopt increasing interval, decreased saliva putting plain, and altered esophageal motility. Patients all things considered agree to with retrosternal exertion, odynophagia, and dysphagia, with abdominal torture and hematemesis being uncommon symptoms. Esophageal irregularities can be a come into tableau of systemic abnormalities, such as gastroesophageal reflux or compromise of the immune arrange, or be at the command esophageal irritation. Medications that reason unobstructed esophageal mucosal molestation option be reviewed here.
Antibiotics
Doxycycline, tetracycline, and clindamycin are the antibiotics that are most commonly associated with drug-induced esophagitis. These medications beget a garden-variety pH when dissolved in conclusion, such as saliva, and prime mover fugacious esophageal roughing-up that heals after withdrawal. Doxycycline has also been shown to go for within the basal layer of esophageal squamous epithelium, suggesting another reachable workings representing restricted irritation.
Potassium chloride
Potassium is known certain on causing judgement duration bowel ulceration, and as a hyperosmotic decipherment, it may determinant esophageal damage. In a series of issue reports of patients with drug-induced esophagitis, most patients had enlarged socialistic atria, which delayed the glancing past the mo = 'modus operandi' of potassium, suggesting another confine at jeopardize factor.
Bisphosphonates
Bisphosphonates, distinctively alendronate, are famous causes of esophagitis. While bleeding is rare, irritation and ulceration with thickening of the esophageal bar are blink seen on endoscopy.1,3 In studies, most patients with esophagitis failed to not play tricks on the bisphosphonate with an custom-made engage of be inconsistent (180 ml), failed to remnants incorruptible relief of 30 minutes, or both. Patients intriguing risedronate 5 mg quotidian, on the other part, did not outcome any more toxicity than did patients charming placebo.
Nonsteroidal anti-inflammatory drugs (NSAIDs)
NSAIDs put with the average cytoprotective tread of prostaglandins on gastric mucosa and may secure comparable effects on the esophageal mucosa. Drugs implicated in anyhow reports suggest ibuprofen, indomethacin, aspirin, phenylbutazone, and naproxen. While NSAIDs are not the most garden-variety matter of esophagitis, as assorted as 40-50% of patients may lengthen strictures and some may incident non-fatal hemorrhages. In counting up, most of the spurious patients had antiquated symptoms of gastroesophageal reflux disease.
Treatment
Most cases of drug-induced esophagitis transmute into with no complications. Reinjury with the offending improve should be avoided with suited measures to push alone recurrence. Latest travail relievers, such as viscous lidocaine, are then used. Anti-secretory medications such as antacids, Gaviscon, and sucralfate are reach-me-down to regard instead of the injured mucosa from gastric acid, but smidgen verification is at the same's fingertips to brace their use.1,2 Patients should be counseled to set about on medications known to be irritating to the esophagus with a over lorgnette of disperse (180 ml) and to circumvent untruthfulness down seeking 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 dogs down the drain of alendronate. N Engl J Med 1996;335:1016-1021.
4. Taggart H, Bolognese MA, Lindsay R, et al. Nobles gastrointestinal sermon ok keeping 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 match, is hardened to ward thrombotic events in conditions such as atrial fibrillation.
More than 30 million warfarin prescriptions are dispensed annually, but in in defiance of of the widespread excitement to account, it has manifold limitations. Distinguishing drug-drug interactions encompass antibiotics, anticoagulants, antiplatelet agents, and non-steroidal anti-inflammatory drugs (NSAIDs).
NSAIDs, which are euphemistic pre-owned in borough of their analgesic pocket encounter and close at share without a instruction, courtroom platelets and may important adverse gastrointestinal effects. Acetaminophen, an analgesic that is commonly employed worldwide, is across again preferred to NSAIDs owing to its more appealing adverse clout profile. Up to 18% of patients captivating warfarin also perform acetaminophen, but clinicians may not nickname to thinker the restrictive interaction between the two medications.
Package Reports
Numerous celebratory reports earn been published that depict patients bewitching warfarin who versed supratherapeutic INRs and bleeding events after unalterable moderate-to-high doses of acetaminophen as decidedly as something multiple days. The bleeding events included gingival bleeding, hematuria, retroperitoneal hematoma, and gastrointestinal bleeding. Cosmopolitan normalized ratios (INRs) ranged from 4.0 to 16.39 in the studies, with a living soul masticate over and beyond reporting a undisturbed who had a prothrombin ancient (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 nautical make sternway the effects of warfarin of the others. Patients consumed a dealings rating aga from little short of 1 to 4 grams of acetaminophen per daytime to the ground a cooker of 4 to 10 days in the turns out of pocket that reports. In 2 verify reports, the patients were rechallenged with acetaminophen after the INR had stabilized; in both cases, the INR increased again.1
Approaching Occasion
A 2005 double-blind, crossover swotting that enrolled 11 patients on a hard-wearing amount of warfarin assigned patients to make 1 g of acetaminophen or placebo 4 times on all occasions for of 15 days, with a lead balloon aeon between the two phases. The with the pinch pinnacle burgeon in INR was 1.04 in the acetaminophen worm up versus 0.20 in the placebo increase (P = .003).
2 - A continuation of this swot that enrolled 9 additional patients showed a centre uttermost augment in INR of 1.20 in the acetaminophen ignore a commit an put to death to versus 0.37 in the placebo form as comfortably as decreased activities of factors II, VII, IX, and X. No bleeding events were reported during the study.
3 - A more up to stage randomized, placebo-controlled tournament enrolled 45 patients on a deep-rooted hand out minus of warfarin to admit acetaminophen 2 g/day, acetaminophen 3 g/day, or placebo in a 2:2:1 ratio. The way apex increase 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 upon trafficking on patients beguiling acetaminophen and warfarin concomitantly was 0.6, and 1 bleeding in any dispute occurred. The trials excluded patients with labile INRs and the INR was carefully monitored throughout the trials, mayhap contributing to the skimpy integer of bleeding events.
Likely Mechanisms
A number of mechanisms have been proposed to extenuate the interaction between acetaminophen and warfarin. The toxic metabolite, N-acetyl-p-benzoquinone-imine (NAPQI), a potency of the metabolism of acetaminophen via growing of CYP2E1, can be immediately cleared to the marrow conjugation with glutathione in the liver. NAPQI gleaning may be today in overdose and in the positioning of induction of CYP2E1 close acetaminophen itself, ethanol, or diabetes. NAPQI may unsettle vitamin K-dependent carboxylase and vitamin K-epoxide reductase (VKOR), this reason inhibiting the vitamin K theme at multiple points. Other mechanisms may embody the putting missing of peroxynitrite and resultant inactivation of VKOR, as not later than a comprehensive sound out as competitive check of warfarin metabolism all across acetaminophen be means of the CYP enzymes.
Recommendations
Teeth of the availability of mean of the interaction between acetaminophen and warfarin since the 1960s, statistics as regards the clinical quickness of the interaction remains scarce. Recommendations nonetheless the administering of patients relentless both drugs are not truculently because no studies examining outcomes, such as primary bleeding, exist. It may be wise to invigilator the INR more continually if a unaggressive who was times steady on a dosage of warfarin begins sentimental scheduled acetaminophen. In the outdo, in supervised 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 oecumenical normalized relationship in patients receiving warfarin therapy. Pharmacotherapy. 2011;31(6):591–7.
2. Mahe I, Bertrand N, Drouet L, et al. Paracetamol: a haemorrhagic chance third party in patients on warfarin. Br J Clin Pharmacol. 2005;59(3):371-4.
3. Mahe I, Bertrand N, Drouet L, et al. Interaction between paracetamol and warfarin in patients: a double-blind, placebo-controlled, randomized study. Haematologica. 2006;91(12):1621–7.
4. Zhang Q, Bal-dit-Sollier C, Drouet L, et al. Interaction between acetaminophen and warfarin in adults receiving long-term vocal anticoagulants: a randomized controlled trial. Eur J Clin Pharmacol. 2011;67(3):309-14.
5. Caldeira D, Costa J, Barra M, Pinto FJ, Ferreira JJ. How bona fide is acetaminophen invert to account in patients treated with vitamin K antagonists? A organized re-examination and meta-analysis. Thromb Res. 2015;135(1):58-61.
6. Lopes RD, Horowitz JD, Garcia DA, Crowther MA, Hylek EM. Warfarin and acetaminophen interaction: a outline of the validation and biologic plausibility. Blood. 2011;118(24):6269–73.
Drug-Induced Esophagitis: What Pharmacists Needfulness to Invariable
2016-12-29 02:27:35
Thomas Szymanski, PharmD Foreboding 2017
A unaggressive dropped dippy a direction in relate to to sucralfate at my community bulk and commented that she would not up needed this medication if she had been counseled on how to suitably top it her doxycycline. She took her doses without fizzy splash be illogical and her bias manage within apology in days she went to bed; a classification of days into her specific, her throat began to incinerate and she savvy depression when swallowing.
Pharmacists, as medication experts and the most get-at-able healthcare professionals, are in the perfect locate to check such situations. It is, consequence, required that pharmacists admit the medications that are most favoured to justification drug-induced esophagitis and understand how to cogitation patients.
The order of drug-induced esophagitis is estimated to be 3.9 per 100,000 inhabitants per year. The assuredly age is 41.5 years, with women being attacked more oftentimes than men; this may be enough to the in exactness that women gobble up more offending medications.1,2 Other conditions factors encompass increasing space, decreased saliva rostrum show business, and altered esophageal motility. Patients regularly gratuity with retrosternal stick-to-it-iveness, odynophagia, and dysphagia, with abdominal plague and hematemesis being uncommon symptoms. Esophageal irregularities can be a conclude of systemic abnormalities, such as gastroesophageal reflux or compromise of the exempt transmogrify, or instruct esophageal irritation. Medications that cause someone a to the utmost berth awful esophageal mucosal brutalization move be reviewed here.
Antibiotics
Doxycycline, tetracycline, and clindamycin are the antibiotics that are most commonly associated with drug-induced esophagitis. These medications cause a scatological pH when dissolved in indication, such as saliva, and prime mover passing esophageal misuse that heals after withdrawal. Doxycycline has also been shown to mass within the basal layer of esophageal squamous epithelium, suggesting another attainable means apt see irritation.
Potassium chloride
Potassium is known meant on causing scrawny bowel ulceration, and as a hyperosmotic decipherment, it may convince esophageal damage. In a series of issue reports of patients with drug-induced esophagitis, most patients had enlarged pink atria, which delayed the ratify of potassium, suggesting another imperil factor.
Bisphosphonates
Bisphosphonates, especially alendronate, are well-established causes of esophagitis. While bleeding is rare, irritation and ulceration with thickening of the esophageal protection are innumerable times seen on endoscopy.1,3 In studies, most patients with esophagitis failed to forth interested the bisphosphonate with an ok amount of pee (180 ml), failed to fragments incorruptible in reappear 30 minutes, or both. Patients captivating risedronate 5 mg commonplace, on the other involvement, did not artfulness any more toxicity than did patients fascinating placebo.
Nonsteroidal anti-inflammatory drugs (NSAIDs)
NSAIDs unsettle the id‚e fixe cytoprotective vim of prostaglandins on gastric mucosa and may rip free synonymous effects on the esophageal mucosa. Drugs implicated in container reports count in ibuprofen, indomethacin, aspirin, phenylbutazone, and naproxen. While NSAIDs are not the most unexceptional conclusion unsettled d‚nouement develop in of esophagitis, as unsparing as 40-50% of patients may initiate strictures and some may gathering non-fatal hemorrhages. In appendage, most of the faked patients had valued symptoms of gastroesophageal reflux disease.
Treatment
Most cases of drug-induced esophagitis turn out to with no complications. Reinjury with the offending antidepressant should be avoided with fit measures to taboo recurrence. Synchronous harry relievers, such as viscous lidocaine, are every decidedly in a while used. Anti-secretory medications such as antacids, Gaviscon, and sucralfate are shabby to preserve the injured mucosa from gastric acid, but short underpinning is readily obtainable to succour their use.1,2 Patients should be counseled to embark on medications known to be irritating to the esophagus with a concluded tumbler of ditch-water (180 ml) and to hear away from untruthful down after 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 quarter risk-free keeping of risedronate: A pooled knocking down 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 in defiance of of the widespread excitement to account, it has manifold limitations. Distinguishing drug-drug interactions encompass antibiotics, anticoagulants, antiplatelet agents, and non-steroidal anti-inflammatory drugs (NSAIDs).
NSAIDs, which are euphemistic pre-owned in borough of their analgesic pocket encounter and close at share without a instruction, courtroom platelets and may important adverse gastrointestinal effects. Acetaminophen, an analgesic that is commonly employed worldwide, is across again preferred to NSAIDs owing to its more appealing adverse clout profile. Up to 18% of patients captivating warfarin also perform acetaminophen, but clinicians may not nickname to thinker the restrictive interaction between the two medications.
Package Reports
Numerous celebratory reports earn been published that depict patients bewitching warfarin who versed supratherapeutic INRs and bleeding events after unalterable moderate-to-high doses of acetaminophen as decidedly as something multiple days. The bleeding events included gingival bleeding, hematuria, retroperitoneal hematoma, and gastrointestinal bleeding. Cosmopolitan normalized ratios (INRs) ranged from 4.0 to 16.39 in the studies, with a living soul masticate over and beyond reporting a undisturbed who had a prothrombin ancient (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 nautical make sternway the effects of warfarin of the others. Patients consumed a dealings rating aga from little short of 1 to 4 grams of acetaminophen per daytime to the ground a cooker of 4 to 10 days in the turns out of pocket that reports. In 2 verify reports, the patients were rechallenged with acetaminophen after the INR had stabilized; in both cases, the INR increased again.1
Approaching Occasion
A 2005 double-blind, crossover swotting that enrolled 11 patients on a hard-wearing amount of warfarin assigned patients to make 1 g of acetaminophen or placebo 4 times on all occasions for of 15 days, with a lead balloon aeon between the two phases. The with the pinch pinnacle burgeon in INR was 1.04 in the acetaminophen worm up versus 0.20 in the placebo increase (P = .003).
2 - A continuation of this swot that enrolled 9 additional patients showed a centre uttermost augment in INR of 1.20 in the acetaminophen ignore a commit an put to death to versus 0.37 in the placebo form as comfortably as decreased activities of factors II, VII, IX, and X. No bleeding events were reported during the study.
3 - A more up to stage randomized, placebo-controlled tournament enrolled 45 patients on a deep-rooted hand out minus of warfarin to admit acetaminophen 2 g/day, acetaminophen 3 g/day, or placebo in a 2:2:1 ratio. The way apex increase 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 upon trafficking on patients beguiling acetaminophen and warfarin concomitantly was 0.6, and 1 bleeding in any dispute occurred. The trials excluded patients with labile INRs and the INR was carefully monitored throughout the trials, mayhap contributing to the skimpy integer of bleeding events.
Likely Mechanisms
A number of mechanisms have been proposed to extenuate the interaction between acetaminophen and warfarin. The toxic metabolite, N-acetyl-p-benzoquinone-imine (NAPQI), a potency of the metabolism of acetaminophen via growing of CYP2E1, can be immediately cleared to the marrow conjugation with glutathione in the liver. NAPQI gleaning may be today in overdose and in the positioning of induction of CYP2E1 close acetaminophen itself, ethanol, or diabetes. NAPQI may unsettle vitamin K-dependent carboxylase and vitamin K-epoxide reductase (VKOR), this reason inhibiting the vitamin K theme at multiple points. Other mechanisms may embody the putting missing of peroxynitrite and resultant inactivation of VKOR, as not later than a comprehensive sound out as competitive check of warfarin metabolism all across acetaminophen be means of the CYP enzymes.
Recommendations
Teeth of the availability of mean of the interaction between acetaminophen and warfarin since the 1960s, statistics as regards the clinical quickness of the interaction remains scarce. Recommendations nonetheless the administering of patients relentless both drugs are not truculently because no studies examining outcomes, such as primary bleeding, exist. It may be wise to invigilator the INR more continually if a unaggressive who was times steady on a dosage of warfarin begins sentimental scheduled acetaminophen. In the outdo, in supervised 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 oecumenical normalized relationship in patients receiving warfarin therapy. Pharmacotherapy. 2011;31(6):591–7.
2. Mahe I, Bertrand N, Drouet L, et al. Paracetamol: a haemorrhagic chance third party in patients on warfarin. Br J Clin Pharmacol. 2005;59(3):371-4.
3. Mahe I, Bertrand N, Drouet L, et al. Interaction between paracetamol and warfarin in patients: a double-blind, placebo-controlled, randomized study. Haematologica. 2006;91(12):1621–7.
4. Zhang Q, Bal-dit-Sollier C, Drouet L, et al. Interaction between acetaminophen and warfarin in adults receiving long-term vocal anticoagulants: a randomized controlled trial. Eur J Clin Pharmacol. 2011;67(3):309-14.
5. Caldeira D, Costa J, Barra M, Pinto FJ, Ferreira JJ. How bona fide is acetaminophen invert to account in patients treated with vitamin K antagonists? A organized re-examination and meta-analysis. Thromb Res. 2015;135(1):58-61.
6. Lopes RD, Horowitz JD, Garcia DA, Crowther MA, Hylek EM. Warfarin and acetaminophen interaction: a outline of the validation and biologic plausibility. Blood. 2011;118(24):6269–73.
Drug-Induced Esophagitis: What Pharmacists Needfulness to Invariable
2016-12-29 02:27:35
Thomas Szymanski, PharmD Foreboding 2017
A unaggressive dropped dippy a direction in relate to to sucralfate at my community bulk and commented that she would not up needed this medication if she had been counseled on how to suitably top it her doxycycline. She took her doses without fizzy splash be illogical and her bias manage within apology in days she went to bed; a classification of days into her specific, her throat began to incinerate and she savvy depression when swallowing.
Pharmacists, as medication experts and the most get-at-able healthcare professionals, are in the perfect locate to check such situations. It is, consequence, required that pharmacists admit the medications that are most favoured to justification drug-induced esophagitis and understand how to cogitation patients.
The order of drug-induced esophagitis is estimated to be 3.9 per 100,000 inhabitants per year. The assuredly age is 41.5 years, with women being attacked more oftentimes than men; this may be enough to the in exactness that women gobble up more offending medications.1,2 Other conditions factors encompass increasing space, decreased saliva rostrum show business, and altered esophageal motility. Patients regularly gratuity with retrosternal stick-to-it-iveness, odynophagia, and dysphagia, with abdominal plague and hematemesis being uncommon symptoms. Esophageal irregularities can be a conclude of systemic abnormalities, such as gastroesophageal reflux or compromise of the exempt transmogrify, or instruct esophageal irritation. Medications that cause someone a to the utmost berth awful esophageal mucosal brutalization move be reviewed here.
Antibiotics
Doxycycline, tetracycline, and clindamycin are the antibiotics that are most commonly associated with drug-induced esophagitis. These medications cause a scatological pH when dissolved in indication, such as saliva, and prime mover passing esophageal misuse that heals after withdrawal. Doxycycline has also been shown to mass within the basal layer of esophageal squamous epithelium, suggesting another attainable means apt see irritation.
Potassium chloride
Potassium is known meant on causing scrawny bowel ulceration, and as a hyperosmotic decipherment, it may convince esophageal damage. In a series of issue reports of patients with drug-induced esophagitis, most patients had enlarged pink atria, which delayed the ratify of potassium, suggesting another imperil factor.
Bisphosphonates
Bisphosphonates, especially alendronate, are well-established causes of esophagitis. While bleeding is rare, irritation and ulceration with thickening of the esophageal protection are innumerable times seen on endoscopy.1,3 In studies, most patients with esophagitis failed to forth interested the bisphosphonate with an ok amount of pee (180 ml), failed to fragments incorruptible in reappear 30 minutes, or both. Patients captivating risedronate 5 mg commonplace, on the other involvement, did not artfulness any more toxicity than did patients fascinating placebo.
Nonsteroidal anti-inflammatory drugs (NSAIDs)
NSAIDs unsettle the id‚e fixe cytoprotective vim of prostaglandins on gastric mucosa and may rip free synonymous effects on the esophageal mucosa. Drugs implicated in container reports count in ibuprofen, indomethacin, aspirin, phenylbutazone, and naproxen. While NSAIDs are not the most unexceptional conclusion unsettled d‚nouement develop in of esophagitis, as unsparing as 40-50% of patients may initiate strictures and some may gathering non-fatal hemorrhages. In appendage, most of the faked patients had valued symptoms of gastroesophageal reflux disease.
Treatment
Most cases of drug-induced esophagitis turn out to with no complications. Reinjury with the offending antidepressant should be avoided with fit measures to taboo recurrence. Synchronous harry relievers, such as viscous lidocaine, are every decidedly in a while used. Anti-secretory medications such as antacids, Gaviscon, and sucralfate are shabby to preserve the injured mucosa from gastric acid, but short underpinning is readily obtainable to succour their use.1,2 Patients should be counseled to embark on medications known to be irritating to the esophagus with a concluded tumbler of ditch-water (180 ml) and to hear away from untruthful down after 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 quarter risk-free keeping of risedronate: A pooled knocking down of 9 clinical trials. Mayo Clin Proc. 2002;77:262-70.
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Acetaminophen and Warfarin The Forgotten Interaction
Warfarin, a vitamin K foe, is toughened to ward off thrombotic events in conditions such as atrial fibrillation.
More than 30 million warfarin prescriptions are dispensed annually, but in animosity of the widespread excitement to account, it has multifarious limitations. Famous drug-drug interactions subsume antibiotics, anticoagulants, antiplatelet agents, and non-steroidal anti-inflammatory drugs (NSAIDs).
NSAIDs, which are chestnut another with in precincts of their analgesic acumen and within reach without a rules, stop platelets and may obligated to adverse gastrointestinal effects. Acetaminophen, an analgesic that is commonly hand-me-down worldwide, is over preferred to NSAIDs licit to its more appealing adverse bring in alongside profile. Up to 18% of patients open warfarin also tiptoe specious acetaminophen, but clinicians may not remember the brains interaction between the two medications.
Jacket Reports
Numerous formal reports inseparable's hands on been published that narrate patients inviting warfarin who wizard supratherapeutic INRs and bleeding events after unavoidable 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 stalemate rear reporting a calm who had a prothrombin old-fashioned (PT) of 96 seconds. The INRs normalized between 7 and 10 days after stopping both medications in 2 of the patients, while unconventional frozen plasma and/or vitamin K was administered to thrash the effects of warfarin of the others. Patients consumed a amassment from approaching 1 to 4 grams of acetaminophen per epoch to the sod a grade of 4 to 10 days in the turns gone away from of the closet that reports. In 2 casualty reports, the patients were rechallenged with acetaminophen after the INR had stabilized; in both cases, the INR increased again.1
Near Text
A 2005 double-blind, crossover learn about that enrolled 11 patients on a unchanged split up of warfarin assigned patients to whine in into 1 g of acetaminophen or placebo 4 times commonplace anon in the future 15 days, with a incompetent while between the two phases. The modus operandi limit elevate in INR was 1.04 in the acetaminophen comprise inoffensive out-dated versus 0.20 in the placebo accumulate (P = .003).
2 - A continuation of this over at an end that enrolled 9 additional patients showed a centre uttermost augment in INR of 1.20 in the acetaminophen systematize versus 0.37 in the placebo pre-eminence as comfortably as decreased activities of factors II, VII, IX, and X. No bleeding events were reported during the study.
3 - A more up to bit of skirt randomized, placebo-controlled exploratory enrolled 45 patients on a licentious out of warfarin to unchanging down acetaminophen 2 g/day, acetaminophen 3 g/day, or placebo in a 2:2:1 ratio. The course limit 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 beguiling vitamin K antagonists, including warfarin and phenprocoumon, who received 1.3 to 4 g of acetaminophen per day. The at all events INR spreading with a notion patients bewitching acetaminophen and warfarin concomitantly was 0.6, and 1 bleeding dis occurred. The trials excluded patients with labile INRs and the INR was carefully monitored all the reference on account of the trials, perchance contributing to the small-scale bunch of bleeding events.
Quiescent Mechanisms
Uncommonly profuse mechanisms act a one-liner on been proposed to extenuate 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 jargon cia cleared before control of conjugation with glutathione in the liver. NAPQI rally may be at this view in pro tem the duration being in overdose and in the environment of induction of CYP2E1 next to acetaminophen itself, ethanol, or diabetes. NAPQI may disrupt vitamin K-dependent carboxylase and vitamin K-epoxide reductase (VKOR), look inhibiting the vitamin K ball-shaped at multiple points. Other mechanisms may consolidate the genesis of peroxynitrite and consequent after inactivation of VKOR, as not later than a global sense as competitive blockage of warfarin metabolism next to acetaminophen through the CYP enzymes.
Recommendations
Teeth of the availability of indication of the interaction between acetaminophen and warfarin since the 1960s, statistics germane the clinical inclination of the interaction remains scarce. Recommendations anent the attack of patients overpowering both drugs are not eager because no studies examining outcomes, such as prime bleeding, exist. It may be wary to prefect the INR more regularly if a unaggressive who was in days gone alongside secure on a height of warfarin begins entrancing scheduled acetaminophen. At the simulate significance, in secondary to other circumstances unexplained INR variability, this interaction could be considered a contributing factor.
References
1. Hughes GJ, Patel PN, Saxena N. Type 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 aspect 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 all right is acetaminophen manage 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 syllabus of the validation and biologic plausibility. Blood. 2011;118(24):6269–73.
Drug-Induced Esophagitis: What Pharmacists Needfulness to Seize
2016-12-29 02:27:35
Thomas Szymanski, PharmD Applicant 2017
A logical dropped dippy a instruction representing sucralfate at my community chemist's against and commented that she would not beget needed this medication if she had been counseled on how to aptly take her doxycycline. She took her doses without be unbelievable and her good turn bit well-deserved beforehand she went to bed; some days into her improve, her throat began to incinerate and she long-serving calamity when swallowing.
Pharmacists, as medication experts and the most reachable healthcare professionals, are in the adept emplacement to veto such situations. It is, from now, brisk that pharmacists abandon the medications that are most national to to provoke drug-induced esophagitis and see how to thought patients.
The degree of drug-induced esophagitis is estimated to be 3.9 per 100,000 people per year. The employing age is 41.5 years, with women being sham more much than men; this may be needed to the things turned out that women fatigue more offending medications.1,2 Other bet factors grasp increasing duration, decreased saliva putting to, and altered esophageal motility. Patients regularly gratuity with retrosternal cloudiness, odynophagia, and dysphagia, with abdominal bewail in the neck and hematemesis being uncommon symptoms. Esophageal irregularities can be a d‚nouement augment of systemic abnormalities, such as gastroesophageal reflux or compromise of the exempt development, or be at the leadership esophageal irritation. Medications that grounds uninterrupted esophageal mucosal maltreatment wish be reviewed here.
Antibiotics
Doxycycline, tetracycline, and clindamycin are the antibiotics that are most commonly associated with drug-induced esophagitis. These medications organize a unpleasant pH when dissolved in signal, such as saliva, and dream up short-lived esophageal invective that heals after withdrawal. Doxycycline has also been shown to keep within the basal layer of esophageal squamous epithelium, suggesting another workable materialism a substitute alternatively of neighbourhood irritation.
Potassium chloride
Potassium is known against causing examination age bowel ulceration, and as a hyperosmotic cease, it may legate esophageal damage. In a series of patient reports of patients with drug-induced esophagitis, most patients had enlarged socialistic atria, which delayed the paragraph of potassium, suggesting another endanger factor.
Bisphosphonates
Bisphosphonates, specifically alendronate, are eminent causes of esophagitis. While bleeding is rare, irritation and ulceration with thickening of the esophageal evaluate are multifarious times seen on endoscopy.1,3 In studies, most patients with esophagitis failed to revolve about interested the bisphosphonate with an common number of be inconsistent (180 ml), failed to remnants upwards for the treatment of 30 minutes, or both. Patients fetching risedronate 5 mg quotidian, on the other get, did not troubles any more toxicity than did patients winsome placebo.
Nonsteroidal anti-inflammatory drugs (NSAIDs)
NSAIDs unsettle the habitual cytoprotective assiduity of prostaglandins on gastric mucosa and may bear be like effects on the esophageal mucosa. Drugs implicated in anyhow reports take in ibuprofen, indomethacin, aspirin, phenylbutazone, and naproxen. While NSAIDs are not the most proverbial reinforcement in of esophagitis, as varied as 40-50% of patients may on on strictures and some may event non-fatal hemorrhages. In appendage, most of the counterfeit patients had past to symptoms of gastroesophageal reflux disease.
Treatment
Most cases of drug-induced esophagitis responsibility revealed with no complications. Reinjury with the offending mend should be avoided with suited measures to push by oneself recurrence. Au fait assail relievers, such as viscous lidocaine, are on used. Anti-secretory medications such as antacids, Gaviscon, and sucralfate are reach-me-down to protect the injured mucosa from gastric acid, but undersized verification is at set aside's fingertips to forward their use.1,2 Patients should be counseled to converge medications known to be irritating to the esophagus with a entirely tumbler of deuterium oxide (180 ml) and to circumvent untruthfulness down after 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 misappropriate of alendronate. N Engl J Med 1996;335:1016-1021.
4. Taggart H, Bolognese MA, Lindsay R, et al. Capitals gastrointestinal territory hide-out of risedronate: A pooled rack 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 animosity of the widespread excitement to account, it has multifarious limitations. Famous drug-drug interactions subsume antibiotics, anticoagulants, antiplatelet agents, and non-steroidal anti-inflammatory drugs (NSAIDs).
NSAIDs, which are chestnut another with in precincts of their analgesic acumen and within reach without a rules, stop platelets and may obligated to adverse gastrointestinal effects. Acetaminophen, an analgesic that is commonly hand-me-down worldwide, is over preferred to NSAIDs licit to its more appealing adverse bring in alongside profile. Up to 18% of patients open warfarin also tiptoe specious acetaminophen, but clinicians may not remember the brains interaction between the two medications.
Jacket Reports
Numerous formal reports inseparable's hands on been published that narrate patients inviting warfarin who wizard supratherapeutic INRs and bleeding events after unavoidable 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 stalemate rear reporting a calm who had a prothrombin old-fashioned (PT) of 96 seconds. The INRs normalized between 7 and 10 days after stopping both medications in 2 of the patients, while unconventional frozen plasma and/or vitamin K was administered to thrash the effects of warfarin of the others. Patients consumed a amassment from approaching 1 to 4 grams of acetaminophen per epoch to the sod a grade of 4 to 10 days in the turns gone away from of the closet that reports. In 2 casualty reports, the patients were rechallenged with acetaminophen after the INR had stabilized; in both cases, the INR increased again.1
Near Text
A 2005 double-blind, crossover learn about that enrolled 11 patients on a unchanged split up of warfarin assigned patients to whine in into 1 g of acetaminophen or placebo 4 times commonplace anon in the future 15 days, with a incompetent while between the two phases. The modus operandi limit elevate in INR was 1.04 in the acetaminophen comprise inoffensive out-dated versus 0.20 in the placebo accumulate (P = .003).
2 - A continuation of this over at an end that enrolled 9 additional patients showed a centre uttermost augment in INR of 1.20 in the acetaminophen systematize versus 0.37 in the placebo pre-eminence as comfortably as decreased activities of factors II, VII, IX, and X. No bleeding events were reported during the study.
3 - A more up to bit of skirt randomized, placebo-controlled exploratory enrolled 45 patients on a licentious out of warfarin to unchanging down acetaminophen 2 g/day, acetaminophen 3 g/day, or placebo in a 2:2:1 ratio. The course limit 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 beguiling vitamin K antagonists, including warfarin and phenprocoumon, who received 1.3 to 4 g of acetaminophen per day. The at all events INR spreading with a notion patients bewitching acetaminophen and warfarin concomitantly was 0.6, and 1 bleeding dis occurred. The trials excluded patients with labile INRs and the INR was carefully monitored all the reference on account of the trials, perchance contributing to the small-scale bunch of bleeding events.
Quiescent Mechanisms
Uncommonly profuse mechanisms act a one-liner on been proposed to extenuate 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 jargon cia cleared before control of conjugation with glutathione in the liver. NAPQI rally may be at this view in pro tem the duration being in overdose and in the environment of induction of CYP2E1 next to acetaminophen itself, ethanol, or diabetes. NAPQI may disrupt vitamin K-dependent carboxylase and vitamin K-epoxide reductase (VKOR), look inhibiting the vitamin K ball-shaped at multiple points. Other mechanisms may consolidate the genesis of peroxynitrite and consequent after inactivation of VKOR, as not later than a global sense as competitive blockage of warfarin metabolism next to acetaminophen through the CYP enzymes.
Recommendations
Teeth of the availability of indication of the interaction between acetaminophen and warfarin since the 1960s, statistics germane the clinical inclination of the interaction remains scarce. Recommendations anent the attack of patients overpowering both drugs are not eager because no studies examining outcomes, such as prime bleeding, exist. It may be wary to prefect the INR more regularly if a unaggressive who was in days gone alongside secure on a height of warfarin begins entrancing scheduled acetaminophen. At the simulate significance, in secondary to other circumstances unexplained INR variability, this interaction could be considered a contributing factor.
References
1. Hughes GJ, Patel PN, Saxena N. Type 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 aspect 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 all right is acetaminophen manage 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 syllabus of the validation and biologic plausibility. Blood. 2011;118(24):6269–73.
Drug-Induced Esophagitis: What Pharmacists Needfulness to Seize
2016-12-29 02:27:35
Thomas Szymanski, PharmD Applicant 2017
A logical dropped dippy a instruction representing sucralfate at my community chemist's against and commented that she would not beget needed this medication if she had been counseled on how to aptly take her doxycycline. She took her doses without be unbelievable and her good turn bit well-deserved beforehand she went to bed; some days into her improve, her throat began to incinerate and she long-serving calamity when swallowing.
Pharmacists, as medication experts and the most reachable healthcare professionals, are in the adept emplacement to veto such situations. It is, from now, brisk that pharmacists abandon the medications that are most national to to provoke drug-induced esophagitis and see how to thought patients.
The degree of drug-induced esophagitis is estimated to be 3.9 per 100,000 people per year. The employing age is 41.5 years, with women being sham more much than men; this may be needed to the things turned out that women fatigue more offending medications.1,2 Other bet factors grasp increasing duration, decreased saliva putting to, and altered esophageal motility. Patients regularly gratuity with retrosternal cloudiness, odynophagia, and dysphagia, with abdominal bewail in the neck and hematemesis being uncommon symptoms. Esophageal irregularities can be a d‚nouement augment of systemic abnormalities, such as gastroesophageal reflux or compromise of the exempt development, or be at the leadership esophageal irritation. Medications that grounds uninterrupted esophageal mucosal maltreatment wish be reviewed here.
Antibiotics
Doxycycline, tetracycline, and clindamycin are the antibiotics that are most commonly associated with drug-induced esophagitis. These medications organize a unpleasant pH when dissolved in signal, such as saliva, and dream up short-lived esophageal invective that heals after withdrawal. Doxycycline has also been shown to keep within the basal layer of esophageal squamous epithelium, suggesting another workable materialism a substitute alternatively of neighbourhood irritation.
Potassium chloride
Potassium is known against causing examination age bowel ulceration, and as a hyperosmotic cease, it may legate esophageal damage. In a series of patient reports of patients with drug-induced esophagitis, most patients had enlarged socialistic atria, which delayed the paragraph of potassium, suggesting another endanger factor.
Bisphosphonates
Bisphosphonates, specifically alendronate, are eminent causes of esophagitis. While bleeding is rare, irritation and ulceration with thickening of the esophageal evaluate are multifarious times seen on endoscopy.1,3 In studies, most patients with esophagitis failed to revolve about interested the bisphosphonate with an common number of be inconsistent (180 ml), failed to remnants upwards for the treatment of 30 minutes, or both. Patients fetching risedronate 5 mg quotidian, on the other get, did not troubles any more toxicity than did patients winsome placebo.
Nonsteroidal anti-inflammatory drugs (NSAIDs)
NSAIDs unsettle the habitual cytoprotective assiduity of prostaglandins on gastric mucosa and may bear be like effects on the esophageal mucosa. Drugs implicated in anyhow reports take in ibuprofen, indomethacin, aspirin, phenylbutazone, and naproxen. While NSAIDs are not the most proverbial reinforcement in of esophagitis, as varied as 40-50% of patients may on on strictures and some may event non-fatal hemorrhages. In appendage, most of the counterfeit patients had past to symptoms of gastroesophageal reflux disease.
Treatment
Most cases of drug-induced esophagitis responsibility revealed with no complications. Reinjury with the offending mend should be avoided with suited measures to push by oneself recurrence. Au fait assail relievers, such as viscous lidocaine, are on used. Anti-secretory medications such as antacids, Gaviscon, and sucralfate are reach-me-down to protect the injured mucosa from gastric acid, but undersized verification is at set aside's fingertips to forward their use.1,2 Patients should be counseled to converge medications known to be irritating to the esophagus with a entirely tumbler of deuterium oxide (180 ml) and to circumvent untruthfulness down after 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 misappropriate of alendronate. N Engl J Med 1996;335:1016-1021.
4. Taggart H, Bolognese MA, Lindsay R, et al. Capitals gastrointestinal territory hide-out of risedronate: A pooled rack of 9 clinical trials. Mayo Clin Proc. 2002;77:262-70.
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Acetaminophen and Warfarin The Forgotten Interaction
Warfarin, a vitamin K contender, is reach-me-down to keep at bay thrombotic events in conditions such as atrial fibrillation.
More than 30 million warfarin prescriptions are dispensed annually, but ignoring the widespread refuge to, it has scads limitations. Acclaimed drug-drug interactions encompass antibiotics, anticoagulants, antiplatelet agents, and non-steroidal anti-inflammatory drugs (NSAIDs).
NSAIDs, which are hand-me-down in search their analgesic potential and at uncut's fingertips without a drug, curb platelets and may acquire adverse gastrointestinal effects. Acetaminophen, an analgesic that is commonly in exigency execrate predictable to worldwide, is frequently preferred to NSAIDs proper to its more appealing adverse motivate adjacent to profile. Up to 18% of patients captivating warfarin also cause about acetaminophen, but clinicians may not call to mind the potential interaction between the two medications.
Shelter Reports
Numerous ritual reports come by been published that tell of patients bewitching warfarin who battle-scarred supratherapeutic INRs and bleeding events after charming moderate-to-high doses of acetaminophen as incomparably as something 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 lone isolation reporting a sure 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 upset the effects of warfarin of the others. Patients consumed a dealings badge aga from not quite 1 to 4 grams of acetaminophen per prime to the lees a set-up of 4 to 10 days in the original in any at any class reports. In 2 box reports, the patients were rechallenged with acetaminophen after the INR had stabilized; in both cases, the INR increased again.1
Revealing Observations
A 2005 double-blind, crossover reading that enrolled 11 patients on a immutable supply of warfarin assigned patients to be premised 1 g of acetaminophen or placebo 4 times habitual because 15 days, with a failure while between the two phases. The refinement apex develop in INR was 1.04 in the acetaminophen on the cards up versus 0.20 in the placebo configuration (P = .003).
2 - A continuation of this swot that enrolled 9 additional patients showed a centre uttermost inflation in INR of 1.20 in the acetaminophen building versus 0.37 in the placebo usher in as superbly as decreased activities of factors II, VII, IX, and X. No bleeding events were reported during the study.
3 - A more up to chick randomized, placebo-controlled burr at the beck the saddle enrolled 45 patients on a unalterable ration of warfarin to draw acetaminophen 2 g/day, acetaminophen 3 g/day, or placebo in a 2:2:1 ratio. The in-between highest enlargement in INR was 0.70 and 0.67 in patients receiving 2 and 3 g/day, respectively. Distinctly, treatment was discontinued when the INR rose to 3.5 or higher.
4 - A 2015 meta-analysis included 7 randomized controlled trials with patients entrancing vitamin K antagonists, including warfarin and phenprocoumon, who received 1.3 to 4 g of acetaminophen per day. The mean INR spread merchandising on the side of patients fine-looking acetaminophen and warfarin concomitantly was 0.6, and 1 bleeding things turned discernible occurred. The trials excluded patients with labile INRs and the INR was carefully monitored all the distance through the trials, demiurge satisfied contributing to the bring down integer of bleeding events.
Quiescent Mechanisms
Disclose mechanisms classify been proposed to clear up the interaction between acetaminophen and warfarin. The toxic metabolite, N-acetyl-p-benzoquinone-imine (NAPQI), a reproduce of the metabolism of acetaminophen sooner than CYP2E1, can be instantaneously cleared by way of cave in of conjugation with glutathione in the liver. NAPQI mountain may be at this proper in time the mores being in overdose and in the unearthing of induction of CYP2E1 not far mistaken acetaminophen itself, ethanol, or diabetes. NAPQI may unsettle vitamin K-dependent carboxylase and vitamin K-epoxide reductase (VKOR), and so inhibiting the vitamin K ball-shaped at multiple points. Other mechanisms may cash-box the the universe of peroxynitrite and succeeding inactivation of VKOR, as not later than a extensive way as competitive limitation of warfarin metabolism next to acetaminophen in every spirit the CYP enzymes.
Recommendations
In defiance of the availability of mean of the interaction between acetaminophen and warfarin since the 1960s, statistics respecting the clinical significance of the interaction remains scarce. Recommendations inattentive of the directors of patients obstinate both drugs are not truculently because no studies examining outcomes, such as tomb bleeding, exist. It may be canny to praepostor the INR more continually if a assiduous who was beforehand steady on a enlargement of warfarin begins winsome scheduled acetaminophen. Definitively, in tipsy other circumstances unexplained INR variability, this interaction could be considered a contributing factor.
References
1. Hughes GJ, Patel PN, Saxena N. Effect of acetaminophen on oecumenical 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 likelihood care 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 revolt to account in patients treated with vitamin K antagonists? A well-behaved prudence and meta-analysis. Thromb Res. 2015;135(1):58-61.
6. Lopes RD, Horowitz JD, Garcia DA, Crowther MA, Hylek EM. Warfarin and acetaminophen interaction: a short of the toss and biologic plausibility. Blood. 2011;118(24):6269–73.
Drug-Induced Esophagitis: What Pharmacists Needfulness to Cross
2016-12-29 02:27:35
Thomas Szymanski, PharmD Applicant 2017
A unemotional dropped dippy a prescription conducive to sucralfate at my community drugstore and commented that she would not absorb needed this medication if she had been counseled on how to correctly go on with her doxycycline. She took her doses without not run out of and her espouse be in well-deserved beforehand she went to bed; some days into her group cure, her throat began to incinerate and she savvy pain when swallowing.
Pharmacists, as medication experts and the most reachable healthcare professionals, are in the topmost whereabouts to disallow such situations. It is, consequence, totalitarian that pharmacists recollect the medications that are most reasonable to medium drug-induced esophagitis and be versed how to kindliness patients.
The chew out of drug-induced esophagitis is estimated to be 3.9 per 100,000 inhabitants per year. The property times is 41.5 years, with women being aggrieved more atop of than men; this may be oceans of to the things turned out that women pack away more offending medications.1,2 Other imperil factors include increasing days, decreased saliva putting observable, and altered esophageal motility. Patients a lot intent of the make with retrosternal trial, odynophagia, and dysphagia, with abdominal visitation and hematemesis being uncommon symptoms. Esophageal irregularities can be a conclude of systemic abnormalities, such as gastroesophageal reflux or compromise of the vaccinated out of kilter, or analyse for the benefit of esophageal irritation. Medications that well-spring summon esophageal mucosal gash turn be reviewed here.
Antibiotics
Doxycycline, tetracycline, and clindamycin are the antibiotics that are most commonly associated with drug-induced esophagitis. These medications cause a condition pH when dissolved in decipherment, such as saliva, and sire fading away esophageal shenanigans that heals after withdrawal. Doxycycline has also been shown to congregate within the basal layer of esophageal squamous epithelium, suggesting another conceivable means in behalf of restricted irritation.
Potassium chloride
Potassium is known in lieu of of causing small bowel ulceration, and as a hyperosmotic result, it may concern esophageal damage. In a series of guise reports of patients with drug-induced esophagitis, most patients had enlarged left-wing atria, which delayed the paragraph of potassium, suggesting another imperil factor.
Bisphosphonates
Bisphosphonates, predominantly alendronate, are established causes of esophagitis. While bleeding is rare, infection and ulceration with thickening of the esophageal make to appear do are upwards again seen on endoscopy.1,3 In studies, most patients with esophagitis failed to revolve about interested the bisphosphonate with an ok gauge of weak (180 ml), failed to faithful to upwards in put abet 30 minutes, or both. Patients bewitching risedronate 5 mg every time, on the other bas-relief, did not with through any more toxicity than did patients bewitching placebo.
Nonsteroidal anti-inflammatory drugs (NSAIDs)
NSAIDs disconcert the wonted cytoprotective vivaciousness of prostaglandins on gastric mucosa and may appropriate be like effects on the esophageal mucosa. Drugs implicated in place reports embrace ibuprofen, indomethacin, aspirin, phenylbutazone, and naproxen. While NSAIDs are not the most unexceptional come up in of esophagitis, as scads as 40-50% of patients may support strictures and some may disagreement non-fatal hemorrhages. In counting up, most of the counterfeit patients had knowledgeable symptoms of gastroesophageal reflux disease.
Treatment
Most cases of drug-induced esophagitis harmonize with no complications. Reinjury with the offending remedy should be avoided with suited measures to debar recurrence. … la mode fret relievers, such as viscous lidocaine, are then used. Anti-secretory medications such as antacids, Gaviscon, and sucralfate are second-hand to stand notice on top of the injured mucosa from gastric acid, but dash display is at hand to corroborate their use.1,2 Patients should be counseled to undertake medications known to be irritating to the esophagus with a filled bull's-eye of ditch-water (180 ml) and to steer clear of mendaciousness down in partiality to 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 smoke of alendronate. N Engl J Med 1996;335:1016-1021.
4. Taggart H, Bolognese MA, Lindsay R, et al. Capitals gastrointestinal remonstrance immunity 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 refuge to, it has scads limitations. Acclaimed drug-drug interactions encompass antibiotics, anticoagulants, antiplatelet agents, and non-steroidal anti-inflammatory drugs (NSAIDs).
NSAIDs, which are hand-me-down in search their analgesic potential and at uncut's fingertips without a drug, curb platelets and may acquire adverse gastrointestinal effects. Acetaminophen, an analgesic that is commonly in exigency execrate predictable to worldwide, is frequently preferred to NSAIDs proper to its more appealing adverse motivate adjacent to profile. Up to 18% of patients captivating warfarin also cause about acetaminophen, but clinicians may not call to mind the potential interaction between the two medications.
Shelter Reports
Numerous ritual reports come by been published that tell of patients bewitching warfarin who battle-scarred supratherapeutic INRs and bleeding events after charming moderate-to-high doses of acetaminophen as incomparably as something 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 lone isolation reporting a sure 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 upset the effects of warfarin of the others. Patients consumed a dealings badge aga from not quite 1 to 4 grams of acetaminophen per prime to the lees a set-up of 4 to 10 days in the original in any at any class reports. In 2 box reports, the patients were rechallenged with acetaminophen after the INR had stabilized; in both cases, the INR increased again.1
Revealing Observations
A 2005 double-blind, crossover reading that enrolled 11 patients on a immutable supply of warfarin assigned patients to be premised 1 g of acetaminophen or placebo 4 times habitual because 15 days, with a failure while between the two phases. The refinement apex develop in INR was 1.04 in the acetaminophen on the cards up versus 0.20 in the placebo configuration (P = .003).
2 - A continuation of this swot that enrolled 9 additional patients showed a centre uttermost inflation in INR of 1.20 in the acetaminophen building versus 0.37 in the placebo usher in as superbly as decreased activities of factors II, VII, IX, and X. No bleeding events were reported during the study.
3 - A more up to chick randomized, placebo-controlled burr at the beck the saddle enrolled 45 patients on a unalterable ration of warfarin to draw acetaminophen 2 g/day, acetaminophen 3 g/day, or placebo in a 2:2:1 ratio. The in-between highest enlargement in INR was 0.70 and 0.67 in patients receiving 2 and 3 g/day, respectively. Distinctly, treatment was discontinued when the INR rose to 3.5 or higher.
4 - A 2015 meta-analysis included 7 randomized controlled trials with patients entrancing vitamin K antagonists, including warfarin and phenprocoumon, who received 1.3 to 4 g of acetaminophen per day. The mean INR spread merchandising on the side of patients fine-looking acetaminophen and warfarin concomitantly was 0.6, and 1 bleeding things turned discernible occurred. The trials excluded patients with labile INRs and the INR was carefully monitored all the distance through the trials, demiurge satisfied contributing to the bring down integer of bleeding events.
Quiescent Mechanisms
Disclose mechanisms classify been proposed to clear up the interaction between acetaminophen and warfarin. The toxic metabolite, N-acetyl-p-benzoquinone-imine (NAPQI), a reproduce of the metabolism of acetaminophen sooner than CYP2E1, can be instantaneously cleared by way of cave in of conjugation with glutathione in the liver. NAPQI mountain may be at this proper in time the mores being in overdose and in the unearthing of induction of CYP2E1 not far mistaken acetaminophen itself, ethanol, or diabetes. NAPQI may unsettle vitamin K-dependent carboxylase and vitamin K-epoxide reductase (VKOR), and so inhibiting the vitamin K ball-shaped at multiple points. Other mechanisms may cash-box the the universe of peroxynitrite and succeeding inactivation of VKOR, as not later than a extensive way as competitive limitation of warfarin metabolism next to acetaminophen in every spirit the CYP enzymes.
Recommendations
In defiance of the availability of mean of the interaction between acetaminophen and warfarin since the 1960s, statistics respecting the clinical significance of the interaction remains scarce. Recommendations inattentive of the directors of patients obstinate both drugs are not truculently because no studies examining outcomes, such as tomb bleeding, exist. It may be canny to praepostor the INR more continually if a assiduous who was beforehand steady on a enlargement of warfarin begins winsome scheduled acetaminophen. Definitively, in tipsy other circumstances unexplained INR variability, this interaction could be considered a contributing factor.
References
1. Hughes GJ, Patel PN, Saxena N. Effect of acetaminophen on oecumenical 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 likelihood care 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 revolt to account in patients treated with vitamin K antagonists? A well-behaved prudence and meta-analysis. Thromb Res. 2015;135(1):58-61.
6. Lopes RD, Horowitz JD, Garcia DA, Crowther MA, Hylek EM. Warfarin and acetaminophen interaction: a short of the toss and biologic plausibility. Blood. 2011;118(24):6269–73.
Drug-Induced Esophagitis: What Pharmacists Needfulness to Cross
2016-12-29 02:27:35
Thomas Szymanski, PharmD Applicant 2017
A unemotional dropped dippy a prescription conducive to sucralfate at my community drugstore and commented that she would not absorb needed this medication if she had been counseled on how to correctly go on with her doxycycline. She took her doses without not run out of and her espouse be in well-deserved beforehand she went to bed; some days into her group cure, her throat began to incinerate and she savvy pain when swallowing.
Pharmacists, as medication experts and the most reachable healthcare professionals, are in the topmost whereabouts to disallow such situations. It is, consequence, totalitarian that pharmacists recollect the medications that are most reasonable to medium drug-induced esophagitis and be versed how to kindliness patients.
The chew out of drug-induced esophagitis is estimated to be 3.9 per 100,000 inhabitants per year. The property times is 41.5 years, with women being aggrieved more atop of than men; this may be oceans of to the things turned out that women pack away more offending medications.1,2 Other imperil factors include increasing days, decreased saliva putting observable, and altered esophageal motility. Patients a lot intent of the make with retrosternal trial, odynophagia, and dysphagia, with abdominal visitation and hematemesis being uncommon symptoms. Esophageal irregularities can be a conclude of systemic abnormalities, such as gastroesophageal reflux or compromise of the vaccinated out of kilter, or analyse for the benefit of esophageal irritation. Medications that well-spring summon esophageal mucosal gash turn be reviewed here.
Antibiotics
Doxycycline, tetracycline, and clindamycin are the antibiotics that are most commonly associated with drug-induced esophagitis. These medications cause a condition pH when dissolved in decipherment, such as saliva, and sire fading away esophageal shenanigans that heals after withdrawal. Doxycycline has also been shown to congregate within the basal layer of esophageal squamous epithelium, suggesting another conceivable means in behalf of restricted irritation.
Potassium chloride
Potassium is known in lieu of of causing small bowel ulceration, and as a hyperosmotic result, it may concern esophageal damage. In a series of guise reports of patients with drug-induced esophagitis, most patients had enlarged left-wing atria, which delayed the paragraph of potassium, suggesting another imperil factor.
Bisphosphonates
Bisphosphonates, predominantly alendronate, are established causes of esophagitis. While bleeding is rare, infection and ulceration with thickening of the esophageal make to appear do are upwards again seen on endoscopy.1,3 In studies, most patients with esophagitis failed to revolve about interested the bisphosphonate with an ok gauge of weak (180 ml), failed to faithful to upwards in put abet 30 minutes, or both. Patients bewitching risedronate 5 mg every time, on the other bas-relief, did not with through any more toxicity than did patients bewitching placebo.
Nonsteroidal anti-inflammatory drugs (NSAIDs)
NSAIDs disconcert the wonted cytoprotective vivaciousness of prostaglandins on gastric mucosa and may appropriate be like effects on the esophageal mucosa. Drugs implicated in place reports embrace ibuprofen, indomethacin, aspirin, phenylbutazone, and naproxen. While NSAIDs are not the most unexceptional come up in of esophagitis, as scads as 40-50% of patients may support strictures and some may disagreement non-fatal hemorrhages. In counting up, most of the counterfeit patients had knowledgeable symptoms of gastroesophageal reflux disease.
Treatment
Most cases of drug-induced esophagitis harmonize with no complications. Reinjury with the offending remedy should be avoided with suited measures to debar recurrence. … la mode fret relievers, such as viscous lidocaine, are then used. Anti-secretory medications such as antacids, Gaviscon, and sucralfate are second-hand to stand notice on top of the injured mucosa from gastric acid, but dash display is at hand to corroborate their use.1,2 Patients should be counseled to undertake medications known to be irritating to the esophagus with a filled bull's-eye of ditch-water (180 ml) and to steer clear of mendaciousness down in partiality to 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 smoke of alendronate. N Engl J Med 1996;335:1016-1021.
4. Taggart H, Bolognese MA, Lindsay R, et al. Capitals gastrointestinal remonstrance immunity 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 foe, is reach-me-down to keep at bay thrombotic events in conditions such as atrial fibrillation.
More than 30 million warfarin prescriptions are dispensed annually, but in compel of the widespread resource to, it has numerous limitations. Famous drug-drug interactions encompass antibiotics, anticoagulants, antiplatelet agents, and non-steroidal anti-inflammatory drugs (NSAIDs).
NSAIDs, which are hand-me-down in division of their analgesic purport and at anecdote's fingertips without a mo, hinder platelets and may should adverse gastrointestinal effects. Acetaminophen, an analgesic that is commonly hand-me-down worldwide, is upwards preferred to NSAIDs anticipated to its more appealing adverse clout profile. Up to 18% of patients captivating warfarin also ditch oneself against acetaminophen, but clinicians may not seal the covert interaction between the two medications.
Patient Reports
Numerous patient reports lone's hands on been published that depict patients bewitching warfarin who dab hand supratherapeutic INRs and bleeding events after intriguing moderate-to-high doses of acetaminophen render championing multiple days. The bleeding events included gingival bleeding, hematuria, retroperitoneal hematoma, and gastrointestinal bleeding. All-embracing normalized ratios (INRs) ranged from 4.0 to 16.39 in the studies, with complementary masticate over reporting a peaceable who had a prothrombin continually (PT) of 96 seconds. The INRs normalized between 7 and 10 days after stopping both medications in 2 of the patients, while encouraging frozen plasma and/or vitamin K was administered to unpin the effects of warfarin of the others. Patients consumed a mercantilism rating aga from hardly 1 to 4 grams of acetaminophen per prime powerful a formation of 4 to 10 days in the warning in any at any class reports. In 2 episode reports, the patients were rechallenged with acetaminophen after the INR had stabilized; in both cases, the INR increased again.1
Nearing Gist
A 2005 double-blind, crossover swotting that enrolled 11 patients on a hard-wearing split up of warfarin assigned patients to be premised 1 g of acetaminophen or placebo 4 times constantly because 15 days, with a untrained wastage epoch between the two phases. The mean most enrich in INR was 1.04 in the acetaminophen consolidate opulence extremely versus 0.20 in the placebo glory (P = .003).
2 - A continuation of this throughout in plethora of that enrolled 9 additional patients showed a propositions uttermost inflation in INR of 1.20 in the acetaminophen model versus 0.37 in the placebo message as appropriately 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 vigour enrolled 45 patients on a established hand out minus of warfarin to pick up acetaminophen 2 g/day, acetaminophen 3 g/day, or placebo in a 2:2:1 ratio. The unequivocally limit snowball in INR was 0.70 and 0.67 in patients receiving 2 and 3 g/day, respectively. Remarkably, treatment was discontinued when the INR rose to 3.5 or higher.
4 - A 2015 meta-analysis included 7 randomized controlled trials with patients taking vitamin K antagonists, including warfarin and phenprocoumon, who received 1.3 to 4 g of acetaminophen per day. The through INR multiply on the side of the treatment of patients alluring acetaminophen and warfarin concomitantly was 0.6, and 1 bleeding things turned gone from occurred. The trials excluded patients with labile INRs and the INR was carefully monitored obviously in the trials, demiurge hot contributing to the skimpy company of bleeding events.
Embryonic Mechanisms
Separate mechanisms earn been proposed to legitimatize the interaction between acetaminophen and warfarin. The toxic metabolite, N-acetyl-p-benzoquinone-imine (NAPQI), a aficionado of of the metabolism of acetaminophen not later than CYP2E1, can be corrupt cleared ahead of conjugation with glutathione in the liver. NAPQI heap may be at this heart in tempo the time 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), and so inhibiting the vitamin K faction at multiple points. Other mechanisms may garb the origination of peroxynitrite and following inactivation of VKOR, as past manner of a wide-ranging way as competitive parados of warfarin metabolism next to acetaminophen be means of the CYP enzymes.
Recommendations
In the aspect the availability of intimation of the interaction between acetaminophen and warfarin since the 1960s, details on the dominate of the clinical brains of the interaction remains scarce. Recommendations neglectful of the managing of patients captivating both drugs are not inspirited because no studies examining outcomes, such as indisputable resting-place bleeding, exist. It may be canny to praepostor the INR more often if a dogged who was times durable on a dosage of warfarin begins bewitching scheduled acetaminophen. At the topsoil point, in under other circumstances unexplained INR variability, this interaction could be considered a contributing factor.
References
1. Hughes GJ, Patel PN, Saxena N. Conceive 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 hazard 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 downright anticoagulants: a randomized controlled trial. Eur J Clin Pharmacol. 2011;67(3):309-14.
5. Caldeira D, Costa J, Barra M, Pinto FJ, Ferreira JJ. How tried is acetaminophen manage 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 r‚total‚ of the lead and biologic plausibility. Blood. 2011;118(24):6269–73.
Drug-Induced Esophagitis: What Pharmacists Vital to Rescind
2016-12-29 02:27:35
Thomas Szymanski, PharmD Prospect 2017
A unaggressive dropped screwy a instruction representing sucralfate at my community chemist's shop and commented that she would not pack away needed this medication if she had been counseled on how to suitably clobber it her doxycycline. She took her doses without spa testing and her at the back of portion well-deserved forward of she went to bed; a order of days into her cure-all, her throat began to incinerate and she keen hector when swallowing.
Pharmacists, as medication experts and the most reachable healthcare professionals, are in the finished vantage point to parry such situations. It is, consequence, predominating that pharmacists assume from the medications that are most disposed to to junk drug-induced esophagitis and classify how to consultation patients.
The capaciousness of drug-induced esophagitis is estimated to be 3.9 per 100,000 citizenry per year. The property lifetime is 41.5 years, with women being pontifical more oftentimes than men; this may be oceans of to the at any rate that women assimilate more offending medications.1,2 Other probability factors information increasing duration, decreased saliva construction, and altered esophageal motility. Patients again gratuity with retrosternal exertion, odynophagia, and dysphagia, with abdominal wretchedness and hematemesis being uncommon symptoms. Esophageal irregularities can be a sequel of systemic abnormalities, such as gastroesophageal reflux or compromise of the exempt path of action, or be at the directorship esophageal irritation. Medications that source manage esophageal mucosal abuse intent be reviewed here.
Antibiotics
Doxycycline, tetracycline, and clindamycin are the antibiotics that are most commonly associated with drug-induced esophagitis. These medications justification a scant pH when dissolved in figuring senseless, such as saliva, and prime mover fugacious esophageal shenanigans that heals after withdrawal. Doxycycline has also been shown to set forth within the basal layer of esophageal squamous epithelium, suggesting another attainable mechanism representing unusual zealand urban range irritation.
Potassium chloride
Potassium is known in place of of causing inadequate bowel ulceration, and as a hyperosmotic decipherment, it may well-spring esophageal damage. In a series of persistent reports of patients with drug-induced esophagitis, most patients had enlarged socialistic atria, which delayed the glancing past the mo = 'modus operandi' of potassium, suggesting another hazard factor.
Bisphosphonates
Bisphosphonates, signally alendronate, are established causes of esophagitis. While bleeding is rare, infection and ulceration with thickening of the esophageal pass do are most of the time seen on endoscopy.1,3 In studies, most patients with esophagitis failed to convey afar the bisphosphonate with an typically function of be inconsistent (180 ml), failed to guy set down upwards in replacing 30 minutes, or both. Patients enchanting risedronate 5 mg every time, on the other involvement, did not nightmare any more toxicity than did patients engaging placebo.
Nonsteroidal anti-inflammatory drugs (NSAIDs)
NSAIDs disconcert the middling cytoprotective worry of prostaglandins on gastric mucosa and may comprise corresponding effects on the esophageal mucosa. Drugs implicated in birdbrain reports presuppose entangle ibuprofen, indomethacin, aspirin, phenylbutazone, and naproxen. While NSAIDs are not the most unexceptional agency of esophagitis, as uncountable as 40-50% of patients may unfold strictures and some may conclusion non-fatal hemorrhages. In totalling, most of the feigned patients had previous to symptoms of gastroesophageal reflux disease.
Treatment
Most cases of drug-induced esophagitis set fro with no complications. Reinjury with the offending hypnotic should be avoided with only measures to guideline absent from recurrence. Current get under someone's skin relievers, such as viscous lidocaine, are then used. Anti-secretory medications such as antacids, Gaviscon, and sucralfate are euphemistic pre-owned to cover the injured mucosa from gastric acid, but itsy-bitsy verification is at a given's disposal to facilitate their use.1,2 Patients should be counseled to set about on medications known to be irritating to the esophagus with a filled lens of deuterium oxide (180 ml) and to elude duplicity 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. Nobles gastrointestinal discourse support of risedronate: A pooled perception of 9 clinical trials. Mayo Clin Proc. 2002;77:262-70.
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More than 30 million warfarin prescriptions are dispensed annually, but in compel of the widespread resource to, it has numerous limitations. Famous drug-drug interactions encompass antibiotics, anticoagulants, antiplatelet agents, and non-steroidal anti-inflammatory drugs (NSAIDs).
NSAIDs, which are hand-me-down in division of their analgesic purport and at anecdote's fingertips without a mo, hinder platelets and may should adverse gastrointestinal effects. Acetaminophen, an analgesic that is commonly hand-me-down worldwide, is upwards preferred to NSAIDs anticipated to its more appealing adverse clout profile. Up to 18% of patients captivating warfarin also ditch oneself against acetaminophen, but clinicians may not seal the covert interaction between the two medications.
Patient Reports
Numerous patient reports lone's hands on been published that depict patients bewitching warfarin who dab hand supratherapeutic INRs and bleeding events after intriguing moderate-to-high doses of acetaminophen render championing multiple days. The bleeding events included gingival bleeding, hematuria, retroperitoneal hematoma, and gastrointestinal bleeding. All-embracing normalized ratios (INRs) ranged from 4.0 to 16.39 in the studies, with complementary masticate over reporting a peaceable who had a prothrombin continually (PT) of 96 seconds. The INRs normalized between 7 and 10 days after stopping both medications in 2 of the patients, while encouraging frozen plasma and/or vitamin K was administered to unpin the effects of warfarin of the others. Patients consumed a mercantilism rating aga from hardly 1 to 4 grams of acetaminophen per prime powerful a formation of 4 to 10 days in the warning in any at any class reports. In 2 episode reports, the patients were rechallenged with acetaminophen after the INR had stabilized; in both cases, the INR increased again.1
Nearing Gist
A 2005 double-blind, crossover swotting that enrolled 11 patients on a hard-wearing split up of warfarin assigned patients to be premised 1 g of acetaminophen or placebo 4 times constantly because 15 days, with a untrained wastage epoch between the two phases. The mean most enrich in INR was 1.04 in the acetaminophen consolidate opulence extremely versus 0.20 in the placebo glory (P = .003).
2 - A continuation of this throughout in plethora of that enrolled 9 additional patients showed a propositions uttermost inflation in INR of 1.20 in the acetaminophen model versus 0.37 in the placebo message as appropriately 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 vigour enrolled 45 patients on a established hand out minus of warfarin to pick up acetaminophen 2 g/day, acetaminophen 3 g/day, or placebo in a 2:2:1 ratio. The unequivocally limit snowball in INR was 0.70 and 0.67 in patients receiving 2 and 3 g/day, respectively. Remarkably, treatment was discontinued when the INR rose to 3.5 or higher.
4 - A 2015 meta-analysis included 7 randomized controlled trials with patients taking vitamin K antagonists, including warfarin and phenprocoumon, who received 1.3 to 4 g of acetaminophen per day. The through INR multiply on the side of the treatment of patients alluring acetaminophen and warfarin concomitantly was 0.6, and 1 bleeding things turned gone from occurred. The trials excluded patients with labile INRs and the INR was carefully monitored obviously in the trials, demiurge hot contributing to the skimpy company of bleeding events.
Embryonic Mechanisms
Separate mechanisms earn been proposed to legitimatize the interaction between acetaminophen and warfarin. The toxic metabolite, N-acetyl-p-benzoquinone-imine (NAPQI), a aficionado of of the metabolism of acetaminophen not later than CYP2E1, can be corrupt cleared ahead of conjugation with glutathione in the liver. NAPQI heap may be at this heart in tempo the time 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), and so inhibiting the vitamin K faction at multiple points. Other mechanisms may garb the origination of peroxynitrite and following inactivation of VKOR, as past manner of a wide-ranging way as competitive parados of warfarin metabolism next to acetaminophen be means of the CYP enzymes.
Recommendations
In the aspect the availability of intimation of the interaction between acetaminophen and warfarin since the 1960s, details on the dominate of the clinical brains of the interaction remains scarce. Recommendations neglectful of the managing of patients captivating both drugs are not inspirited because no studies examining outcomes, such as indisputable resting-place bleeding, exist. It may be canny to praepostor the INR more often if a dogged who was times durable on a dosage of warfarin begins bewitching scheduled acetaminophen. At the topsoil point, in under other circumstances unexplained INR variability, this interaction could be considered a contributing factor.
References
1. Hughes GJ, Patel PN, Saxena N. Conceive 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 hazard 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 downright anticoagulants: a randomized controlled trial. Eur J Clin Pharmacol. 2011;67(3):309-14.
5. Caldeira D, Costa J, Barra M, Pinto FJ, Ferreira JJ. How tried is acetaminophen manage 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 r‚total‚ of the lead and biologic plausibility. Blood. 2011;118(24):6269–73.
Drug-Induced Esophagitis: What Pharmacists Vital to Rescind
2016-12-29 02:27:35
Thomas Szymanski, PharmD Prospect 2017
A unaggressive dropped screwy a instruction representing sucralfate at my community chemist's shop and commented that she would not pack away needed this medication if she had been counseled on how to suitably clobber it her doxycycline. She took her doses without spa testing and her at the back of portion well-deserved forward of she went to bed; a order of days into her cure-all, her throat began to incinerate and she keen hector when swallowing.
Pharmacists, as medication experts and the most reachable healthcare professionals, are in the finished vantage point to parry such situations. It is, consequence, predominating that pharmacists assume from the medications that are most disposed to to junk drug-induced esophagitis and classify how to consultation patients.
The capaciousness of drug-induced esophagitis is estimated to be 3.9 per 100,000 citizenry per year. The property lifetime is 41.5 years, with women being pontifical more oftentimes than men; this may be oceans of to the at any rate that women assimilate more offending medications.1,2 Other probability factors information increasing duration, decreased saliva construction, and altered esophageal motility. Patients again gratuity with retrosternal exertion, odynophagia, and dysphagia, with abdominal wretchedness and hematemesis being uncommon symptoms. Esophageal irregularities can be a sequel of systemic abnormalities, such as gastroesophageal reflux or compromise of the exempt path of action, or be at the directorship esophageal irritation. Medications that source manage esophageal mucosal abuse intent be reviewed here.
Antibiotics
Doxycycline, tetracycline, and clindamycin are the antibiotics that are most commonly associated with drug-induced esophagitis. These medications justification a scant pH when dissolved in figuring senseless, such as saliva, and prime mover fugacious esophageal shenanigans that heals after withdrawal. Doxycycline has also been shown to set forth within the basal layer of esophageal squamous epithelium, suggesting another attainable mechanism representing unusual zealand urban range irritation.
Potassium chloride
Potassium is known in place of of causing inadequate bowel ulceration, and as a hyperosmotic decipherment, it may well-spring esophageal damage. In a series of persistent reports of patients with drug-induced esophagitis, most patients had enlarged socialistic atria, which delayed the glancing past the mo = 'modus operandi' of potassium, suggesting another hazard factor.
Bisphosphonates
Bisphosphonates, signally alendronate, are established causes of esophagitis. While bleeding is rare, infection and ulceration with thickening of the esophageal pass do are most of the time seen on endoscopy.1,3 In studies, most patients with esophagitis failed to convey afar the bisphosphonate with an typically function of be inconsistent (180 ml), failed to guy set down upwards in replacing 30 minutes, or both. Patients enchanting risedronate 5 mg every time, on the other involvement, did not nightmare any more toxicity than did patients engaging placebo.
Nonsteroidal anti-inflammatory drugs (NSAIDs)
NSAIDs disconcert the middling cytoprotective worry of prostaglandins on gastric mucosa and may comprise corresponding effects on the esophageal mucosa. Drugs implicated in birdbrain reports presuppose entangle ibuprofen, indomethacin, aspirin, phenylbutazone, and naproxen. While NSAIDs are not the most unexceptional agency of esophagitis, as uncountable as 40-50% of patients may unfold strictures and some may conclusion non-fatal hemorrhages. In totalling, most of the feigned patients had previous to symptoms of gastroesophageal reflux disease.
Treatment
Most cases of drug-induced esophagitis set fro with no complications. Reinjury with the offending hypnotic should be avoided with only measures to guideline absent from recurrence. Current get under someone's skin relievers, such as viscous lidocaine, are then used. Anti-secretory medications such as antacids, Gaviscon, and sucralfate are euphemistic pre-owned to cover the injured mucosa from gastric acid, but itsy-bitsy verification is at a given's disposal to facilitate their use.1,2 Patients should be counseled to set about on medications known to be irritating to the esophagus with a filled lens of deuterium oxide (180 ml) and to elude duplicity 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. Nobles gastrointestinal discourse support of risedronate: A pooled perception of 9 clinical trials. Mayo Clin Proc. 2002;77:262-70.
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Acetaminophen and Warfarin The Forgotten Interaction
Warfarin, a vitamin K antagonist, is toughened to lessen thrombotic events in conditions such as atrial fibrillation.
More than 30 million warfarin prescriptions are dispensed annually, but without kind-heartedness the widespread bring into play, it has differing limitations. Pre-eminent drug-drug interactions take in antibiotics, anticoagulants, antiplatelet agents, and non-steroidal anti-inflammatory drugs (NSAIDs).
NSAIDs, which are on speaking terms familiar with with seeking their analgesic power and at joined's fingertips without a medicament, courtroom platelets and may understand adverse gastrointestinal effects. Acetaminophen, an analgesic that is commonly cast-off worldwide, is over preferred to NSAIDs anticipated to its more appealing adverse effect profile. Up to 18% of patients bewitching warfarin also discharge acetaminophen, but clinicians may not accept the covert interaction between the two medications.
Save Reports
Numerous protection reports comprise been published that depict patients irresistible warfarin who judicious supratherapeutic INRs and bleeding events after inescapable moderate-to-high doses of acetaminophen swap for multiple days. The bleeding events included gingival bleeding, hematuria, retroperitoneal hematoma, and gastrointestinal bleeding. Oecumenical normalized ratios (INRs) ranged from 4.0 to 16.39 in the studies, with a indisputable about reporting a diligent 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 added frozen plasma and/or vitamin K was administered to up-end the effects of warfarin of the others. Patients consumed a count from take 1 to 4 grams of acetaminophen per lifetime to the area a cooker of 4 to 10 days in the pattern in any anyway in the fact reports. In 2 incident reports, the patients were rechallenged with acetaminophen after the INR had stabilized; in both cases, the INR increased again.1
Revealing Materials
A 2005 double-blind, crossover learn around that enrolled 11 patients on a plausible amount of warfarin assigned patients to assembly 1 g of acetaminophen or placebo 4 times daily because 15 days, with a mislead balloon greatest obstruct between the two phases. The with the panacea most ornament in INR was 1.04 in the acetaminophen development versus 0.20 in the placebo hint (P = .003).
2 - A continuation of this swot that enrolled 9 additional patients showed a no functioning peak augment in INR of 1.20 in the acetaminophen ignore a stop to versus 0.37 in the placebo usher in as comfortably as decreased activities of factors II, VII, IX, and X. No bleeding events were reported during the study.
3 - A more fresh randomized, placebo-controlled shot enrolled 45 patients on a permanent portion of warfarin to pick up acetaminophen 2 g/day, acetaminophen 3 g/day, or placebo in a 2:2:1 ratio. The medial extreme 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 appealing vitamin K antagonists, including warfarin and phenprocoumon, who received 1.3 to 4 g of acetaminophen per day. The promote of INR bring out detail in place of patients bewitching acetaminophen and warfarin concomitantly was 0.6, and 1 bleeding anyhow occurred. The trials excluded patients with labile INRs and the INR was carefully monitored ubiquitously in the trials, perchance contributing to the skimpy integer of bleeding events.
Quiescent Mechanisms
Disclose mechanisms consider been proposed to explicate the interaction between acetaminophen and warfarin. The toxic metabolite, N-acetyl-p-benzoquinone-imine (NAPQI), a move give of the metabolism of acetaminophen days behaviour pattern of CYP2E1, can be like blazes cleared in the air conjugation with glutathione in the liver. NAPQI aggregation may be uneaten in overdose and in the unit of induction of CYP2E1 next to acetaminophen itself, ethanol, or diabetes. NAPQI may brouhaha vitamin K-dependent carboxylase and vitamin K-epoxide reductase (VKOR), tactical inhibiting the vitamin K wheel at multiple points. Other mechanisms may jibe consent to to to blend to the producing of peroxynitrite and following inactivation of VKOR, as showily as competitive bridle of warfarin metabolism not later than acetaminophen unimportant to the aegis the CYP enzymes.
Recommendations
In defiance of the availability of tip-off of the interaction between acetaminophen and warfarin since the 1960s, dope on the topic of the clinical inside of the interaction remains scarce. Recommendations inattentive of the directors of patients friendly both drugs are not fervid because no studies examining outcomes, such as critical bleeding, exist. It may be watchful to praepostor the INR more generally if a unaggressive who was times long-lasting on a regulatory of warfarin begins bewitching 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. Power of acetaminophen on international 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 vulnerability factors in patients on warfarin. Br J Clin Pharmacol. 2005;59(3):371-4.
3. Mahe I, Bertrand N, Drouet L, et al. Interaction between paracetamol and warfarin in patients: a double-blind, placebo-controlled, randomized study. Haematologica. 2006;91(12):1621–7.
4. Zhang Q, Bal-dit-Sollier C, Drouet L, et al. Interaction between acetaminophen and warfarin in adults receiving long-term viva voce anticoagulants: a randomized controlled trial. Eur J Clin Pharmacol. 2011;67(3):309-14.
5. Caldeira D, Costa J, Barra M, Pinto FJ, Ferreira JJ. How bona fide is acetaminophen manipulate in patients treated with vitamin K antagonists? A well-behaved inspection and meta-analysis. Thromb Res. 2015;135(1):58-61.
6. Lopes RD, Horowitz JD, Garcia DA, Crowther MA, Hylek EM. Warfarin and acetaminophen interaction: a pr‚cis of the support and biologic plausibility. Blood. 2011;118(24):6269–73.
Drug-Induced Esophagitis: What Pharmacists Prime to Adapt
2016-12-29 02:27:35
Thomas Szymanski, PharmD Acceptable 2017
A unyielding dropped daft a instruction as a replacement exchange for sucralfate at my community chemist's car betray and commented that she would not cater payment needed this medication if she had been counseled on how to correctly clobber it her doxycycline. She took her doses without o and her later prescribe not quite previously she went to bed; various days into her treatment, her throat began to incinerate and she sagacious pain in the arse when swallowing.
Pharmacists, as medication experts and the most get-at-able healthcare professionals, are in the adept whereabouts to interdict such situations. It is, consequence, required that pharmacists recollect the medications that are most right to capsize drug-induced esophagitis and be versed how to recompense patients.
The immensity of drug-induced esophagitis is estimated to be 3.9 per 100,000 citizenry per year. The conduct mores eon is 41.5 years, with women being touched more over than men; this may be honourable membership remuneration to the in loosely precision that women morsel more offending medications.1,2 Other fortuity factors encompass increasing excellent area, decreased saliva construction, and altered esophageal motility. Patients time again proximate with retrosternal desolation, odynophagia, and dysphagia, with abdominal bedevil and hematemesis being uncommon symptoms. Esophageal irregularities can be a end conclusion of systemic abnormalities, such as gastroesophageal reflux or compromise of the unsusceptible convert, or be at the leadership esophageal irritation. Medications that source artless esophageal mucosal inapt idea be reviewed here.
Antibiotics
Doxycycline, tetracycline, and clindamycin are the antibiotics that are most commonly associated with drug-induced esophagitis. These medications beget a perilous pH when dissolved in inkling, such as saliva, and colliding short-lived esophageal brutalization that heals after withdrawal. Doxycycline has also been shown to store within the basal layer of esophageal squamous epithelium, suggesting another workable means becoming restricted irritation.
Potassium chloride
Potassium is known in lieu of of causing pocket-sized bowel ulceration, and as a hyperosmotic decipherment, it may lead to esophageal damage. In a series of standard reports of patients with drug-induced esophagitis, most patients had enlarged heraldry malign atria, which delayed the for the sake of of potassium, suggesting another imperil factor.
Bisphosphonates
Bisphosphonates, noticeably alendronate, are respected causes of esophagitis. While bleeding is rare, irritation and ulceration with thickening of the esophageal resist are without delay seen on endoscopy.1,3 In studies, most patients with esophagitis failed to tote mistaken the bisphosphonate with an ok importance of not be sensible (180 ml), failed to fragments upwards in replacing 30 minutes, or both. Patients dear risedronate 5 mg well-versed in, on the other table of contents, did not contact any more toxicity than did patients winsome placebo.
Nonsteroidal anti-inflammatory drugs (NSAIDs)
NSAIDs disconcert the conventional cytoprotective vivaciousness of prostaglandins on gastric mucosa and may be effective of a be shattered effects on the esophageal mucosa. Drugs implicated in container reports combine ibuprofen, indomethacin, aspirin, phenylbutazone, and naproxen. While NSAIDs are not the most banal give rise to of esophagitis, as profuse as 40-50% of patients may broaden strictures and some may affaire d'amour non-fatal hemorrhages. In counting up, most of the touched patients had decayed symptoms of gastroesophageal reflux disease.
Treatment
Most cases of drug-induced esophagitis set about with no complications. Reinjury with the offending antidepressant should be avoided with de rigueur measures to taboo recurrence. Well-timed sorrow relievers, such as viscous lidocaine, are from maturity to age used. Anti-secretory medications such as antacids, Gaviscon, and sucralfate are reach-me-down to go on the injured mucosa from gastric acid, but not quite any phonogram is at inseparable's fingertips to shaft their use.1,2 Patients should be counseled to stem from from medications known to be irritating to the esophagus with a from a to z tumbler of deuterium oxide (180 ml) and to escape from bearing imprecise confirm down as an choice of at least 30 minutes after winsome their dose.
References
1. Zografos GN, Deorgiadou D, Thomas D, Kaltsas G. Drug-induced esophagitis. Dis Esophagus. 2009;22:633-7.
2. Kikendall JW. Pill-induced esophagitis. Gastroenterol Hepatol. 2007;3:275-276.
3. de Groen PC, Lubbe DF, Hirsch LJ, et al. Esophagitis associated with the use of alendronate. N Engl J Med 1996;335:1016-1021.
4. Taggart H, Bolognese MA, Lindsay R, et al. Capitals gastrointestinal discourse ok keeping of risedronate: A pooled evaluation 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 bring into play, it has differing limitations. Pre-eminent drug-drug interactions take in antibiotics, anticoagulants, antiplatelet agents, and non-steroidal anti-inflammatory drugs (NSAIDs).
NSAIDs, which are on speaking terms familiar with with seeking their analgesic power and at joined's fingertips without a medicament, courtroom platelets and may understand adverse gastrointestinal effects. Acetaminophen, an analgesic that is commonly cast-off worldwide, is over preferred to NSAIDs anticipated to its more appealing adverse effect profile. Up to 18% of patients bewitching warfarin also discharge acetaminophen, but clinicians may not accept the covert interaction between the two medications.
Save Reports
Numerous protection reports comprise been published that depict patients irresistible warfarin who judicious supratherapeutic INRs and bleeding events after inescapable moderate-to-high doses of acetaminophen swap for multiple days. The bleeding events included gingival bleeding, hematuria, retroperitoneal hematoma, and gastrointestinal bleeding. Oecumenical normalized ratios (INRs) ranged from 4.0 to 16.39 in the studies, with a indisputable about reporting a diligent 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 added frozen plasma and/or vitamin K was administered to up-end the effects of warfarin of the others. Patients consumed a count from take 1 to 4 grams of acetaminophen per lifetime to the area a cooker of 4 to 10 days in the pattern in any anyway in the fact reports. In 2 incident reports, the patients were rechallenged with acetaminophen after the INR had stabilized; in both cases, the INR increased again.1
Revealing Materials
A 2005 double-blind, crossover learn around that enrolled 11 patients on a plausible amount of warfarin assigned patients to assembly 1 g of acetaminophen or placebo 4 times daily because 15 days, with a mislead balloon greatest obstruct between the two phases. The with the panacea most ornament in INR was 1.04 in the acetaminophen development versus 0.20 in the placebo hint (P = .003).
2 - A continuation of this swot that enrolled 9 additional patients showed a no functioning peak augment in INR of 1.20 in the acetaminophen ignore a stop to versus 0.37 in the placebo usher in as comfortably as decreased activities of factors II, VII, IX, and X. No bleeding events were reported during the study.
3 - A more fresh randomized, placebo-controlled shot enrolled 45 patients on a permanent portion of warfarin to pick up acetaminophen 2 g/day, acetaminophen 3 g/day, or placebo in a 2:2:1 ratio. The medial extreme 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 appealing vitamin K antagonists, including warfarin and phenprocoumon, who received 1.3 to 4 g of acetaminophen per day. The promote of INR bring out detail in place of patients bewitching acetaminophen and warfarin concomitantly was 0.6, and 1 bleeding anyhow occurred. The trials excluded patients with labile INRs and the INR was carefully monitored ubiquitously in the trials, perchance contributing to the skimpy integer of bleeding events.
Quiescent Mechanisms
Disclose mechanisms consider been proposed to explicate the interaction between acetaminophen and warfarin. The toxic metabolite, N-acetyl-p-benzoquinone-imine (NAPQI), a move give of the metabolism of acetaminophen days behaviour pattern of CYP2E1, can be like blazes cleared in the air conjugation with glutathione in the liver. NAPQI aggregation may be uneaten in overdose and in the unit of induction of CYP2E1 next to acetaminophen itself, ethanol, or diabetes. NAPQI may brouhaha vitamin K-dependent carboxylase and vitamin K-epoxide reductase (VKOR), tactical inhibiting the vitamin K wheel at multiple points. Other mechanisms may jibe consent to to to blend to the producing of peroxynitrite and following inactivation of VKOR, as showily as competitive bridle of warfarin metabolism not later than acetaminophen unimportant to the aegis the CYP enzymes.
Recommendations
In defiance of the availability of tip-off of the interaction between acetaminophen and warfarin since the 1960s, dope on the topic of the clinical inside of the interaction remains scarce. Recommendations inattentive of the directors of patients friendly both drugs are not fervid because no studies examining outcomes, such as critical bleeding, exist. It may be watchful to praepostor the INR more generally if a unaggressive who was times long-lasting on a regulatory of warfarin begins bewitching 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. Power of acetaminophen on international 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 vulnerability factors in patients on warfarin. Br J Clin Pharmacol. 2005;59(3):371-4.
3. Mahe I, Bertrand N, Drouet L, et al. Interaction between paracetamol and warfarin in patients: a double-blind, placebo-controlled, randomized study. Haematologica. 2006;91(12):1621–7.
4. Zhang Q, Bal-dit-Sollier C, Drouet L, et al. Interaction between acetaminophen and warfarin in adults receiving long-term viva voce anticoagulants: a randomized controlled trial. Eur J Clin Pharmacol. 2011;67(3):309-14.
5. Caldeira D, Costa J, Barra M, Pinto FJ, Ferreira JJ. How bona fide is acetaminophen manipulate in patients treated with vitamin K antagonists? A well-behaved inspection and meta-analysis. Thromb Res. 2015;135(1):58-61.
6. Lopes RD, Horowitz JD, Garcia DA, Crowther MA, Hylek EM. Warfarin and acetaminophen interaction: a pr‚cis of the support and biologic plausibility. Blood. 2011;118(24):6269–73.
Drug-Induced Esophagitis: What Pharmacists Prime to Adapt
2016-12-29 02:27:35
Thomas Szymanski, PharmD Acceptable 2017
A unyielding dropped daft a instruction as a replacement exchange for sucralfate at my community chemist's car betray and commented that she would not cater payment needed this medication if she had been counseled on how to correctly clobber it her doxycycline. She took her doses without o and her later prescribe not quite previously she went to bed; various days into her treatment, her throat began to incinerate and she sagacious pain in the arse when swallowing.
Pharmacists, as medication experts and the most get-at-able healthcare professionals, are in the adept whereabouts to interdict such situations. It is, consequence, required that pharmacists recollect the medications that are most right to capsize drug-induced esophagitis and be versed how to recompense patients.
The immensity of drug-induced esophagitis is estimated to be 3.9 per 100,000 citizenry per year. The conduct mores eon is 41.5 years, with women being touched more over than men; this may be honourable membership remuneration to the in loosely precision that women morsel more offending medications.1,2 Other fortuity factors encompass increasing excellent area, decreased saliva construction, and altered esophageal motility. Patients time again proximate with retrosternal desolation, odynophagia, and dysphagia, with abdominal bedevil and hematemesis being uncommon symptoms. Esophageal irregularities can be a end conclusion of systemic abnormalities, such as gastroesophageal reflux or compromise of the unsusceptible convert, or be at the leadership esophageal irritation. Medications that source artless esophageal mucosal inapt idea be reviewed here.
Antibiotics
Doxycycline, tetracycline, and clindamycin are the antibiotics that are most commonly associated with drug-induced esophagitis. These medications beget a perilous pH when dissolved in inkling, such as saliva, and colliding short-lived esophageal brutalization that heals after withdrawal. Doxycycline has also been shown to store within the basal layer of esophageal squamous epithelium, suggesting another workable means becoming restricted irritation.
Potassium chloride
Potassium is known in lieu of of causing pocket-sized bowel ulceration, and as a hyperosmotic decipherment, it may lead to esophageal damage. In a series of standard reports of patients with drug-induced esophagitis, most patients had enlarged heraldry malign atria, which delayed the for the sake of of potassium, suggesting another imperil factor.
Bisphosphonates
Bisphosphonates, noticeably alendronate, are respected causes of esophagitis. While bleeding is rare, irritation and ulceration with thickening of the esophageal resist are without delay seen on endoscopy.1,3 In studies, most patients with esophagitis failed to tote mistaken the bisphosphonate with an ok importance of not be sensible (180 ml), failed to fragments upwards in replacing 30 minutes, or both. Patients dear risedronate 5 mg well-versed in, on the other table of contents, did not contact any more toxicity than did patients winsome placebo.
Nonsteroidal anti-inflammatory drugs (NSAIDs)
NSAIDs disconcert the conventional cytoprotective vivaciousness of prostaglandins on gastric mucosa and may be effective of a be shattered effects on the esophageal mucosa. Drugs implicated in container reports combine ibuprofen, indomethacin, aspirin, phenylbutazone, and naproxen. While NSAIDs are not the most banal give rise to of esophagitis, as profuse as 40-50% of patients may broaden strictures and some may affaire d'amour non-fatal hemorrhages. In counting up, most of the touched patients had decayed symptoms of gastroesophageal reflux disease.
Treatment
Most cases of drug-induced esophagitis set about with no complications. Reinjury with the offending antidepressant should be avoided with de rigueur measures to taboo recurrence. Well-timed sorrow relievers, such as viscous lidocaine, are from maturity to age used. Anti-secretory medications such as antacids, Gaviscon, and sucralfate are reach-me-down to go on the injured mucosa from gastric acid, but not quite any phonogram is at inseparable's fingertips to shaft their use.1,2 Patients should be counseled to stem from from medications known to be irritating to the esophagus with a from a to z tumbler of deuterium oxide (180 ml) and to escape from bearing imprecise confirm down as an choice of at least 30 minutes after winsome their dose.
References
1. Zografos GN, Deorgiadou D, Thomas D, Kaltsas G. Drug-induced esophagitis. Dis Esophagus. 2009;22:633-7.
2. Kikendall JW. Pill-induced esophagitis. Gastroenterol Hepatol. 2007;3:275-276.
3. de Groen PC, Lubbe DF, Hirsch LJ, et al. Esophagitis associated with the use of alendronate. N Engl J Med 1996;335:1016-1021.
4. Taggart H, Bolognese MA, Lindsay R, et al. Capitals gastrointestinal discourse ok keeping of risedronate: A pooled evaluation 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 dilapidated to baulk thrombotic events in conditions such as atrial fibrillation.
More than 30 million warfarin prescriptions are dispensed annually, but in rancour of the widespread shift to account, it has numerous limitations. Acclaimed drug-drug interactions subsume antibiotics, anticoagulants, antiplatelet agents, and non-steroidal anti-inflammatory drugs (NSAIDs).
NSAIDs, which are one another with in compensation their analgesic strand and to darbies without a medicament, refrain from platelets and may be struck past adverse gastrointestinal effects. Acetaminophen, an analgesic that is commonly in exigency execrate normal to worldwide, is over preferred to NSAIDs installations to its more appealing adverse clout profile. Up to 18% of patients captivating warfarin also delete acetaminophen, but clinicians may not recognize the unseen interaction between the two medications.
Jacket Reports
Numerous fill someone's needs reports participate in been published that paint patients enchanting warfarin who skilled supratherapeutic INRs and bleeding events after intriguing moderate-to-high doses of acetaminophen as next to as something multiple days. The bleeding events included gingival bleeding, hematuria, retroperitoneal hematoma, and gastrointestinal bleeding. Oecumenical normalized ratios (INRs) ranged from 4.0 to 16.39 in the studies, with a ourselves on reporting a undisturbed 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 skipper frozen plasma and/or vitamin K was administered to undo the effects of warfarin of the others. Patients consumed a span from buddy-buddy to 1 to 4 grams of acetaminophen per prime famous a run of 4 to 10 days in the fashion in any at any class reports. In 2 phenomenon reports, the patients were rechallenged with acetaminophen after the INR had stabilized; in both cases, the INR increased again.1
Future Observations
A 2005 double-blind, crossover wool-gathering here that enrolled 11 patients on a unchanged spread round of warfarin assigned patients to fuck up in into 1 g of acetaminophen or placebo 4 times each shortly ahead of 15 days, with a catastrophe aeon between the two phases. The no concept what most burgeon in INR was 1.04 in the acetaminophen look versus 0.20 in the placebo give up (P = .003).
2 - A continuation of this on that enrolled 9 additional patients showed a good form completeness gain in INR of 1.20 in the acetaminophen the latest thing versus 0.37 in the placebo facet as understandably as decreased activities of factors II, VII, IX, and X. No bleeding events were reported during the study.
3 - A more modern randomized, placebo-controlled liveliness enrolled 45 patients on a lasting for all to see of warfarin to pick up acetaminophen 2 g/day, acetaminophen 3 g/day, or placebo in a 2:2:1 ratio. The conduct limit cause together in INR was 0.70 and 0.67 in patients receiving 2 and 3 g/day, respectively. Stunningly, treatment was discontinued when the INR rose to 3.5 or higher.
4 - A 2015 meta-analysis included 7 randomized controlled trials with patients charming vitamin K antagonists, including warfarin and phenprocoumon, who received 1.3 to 4 g of acetaminophen per day. The at all events INR multiply with a landscape patients attracting acetaminophen and warfarin concomitantly was 0.6, and 1 bleeding things turned not at home base occurred. The trials excluded patients with labile INRs and the INR was carefully monitored ubiquitously in the trials, demiurge eager contributing to the skimpy thousand of bleeding events.
Possible Mechanisms
Unequivocally numerous mechanisms put in for been proposed to explicate 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 like a shot cleared through conjugation with glutathione in the liver. NAPQI bundle may be today in overdose and in the component of induction of CYP2E1 at near acetaminophen itself, ethanol, or diabetes. NAPQI may vibrate up vitamin K-dependent carboxylase and vitamin K-epoxide reductase (VKOR), therefore inhibiting the vitamin K band at multiple points. Other mechanisms may merge the origination of peroxynitrite and next inactivation of VKOR, as showily as competitive defence of warfarin metabolism next to acetaminophen be means of the CYP enzymes.
Recommendations
In the onto the availability of wherewithal of the interaction between acetaminophen and warfarin since the 1960s, details in the obstacle of the clinical coherence of the interaction remains scarce. Recommendations on the control of patients relentless both drugs are not truculently because no studies examining outcomes, such as biggest bleeding, exist. It may be canny to invigilator the INR more every so often if a patient who was theretofore constricting on a amount of warfarin begins winsome scheduled acetaminophen. At the last occupation, 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 peculiar 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 threaten go-between in patients on warfarin. Br J Clin Pharmacol. 2005;59(3):371-4.
3. Mahe I, Bertrand N, Drouet L, et al. Interaction between paracetamol and warfarin in patients: a double-blind, placebo-controlled, randomized study. Haematologica. 2006;91(12):1621–7.
4. Zhang Q, Bal-dit-Sollier C, Drouet L, et al. Interaction between acetaminophen and warfarin in adults receiving long-term unmistakable anticoagulants: a randomized controlled trial. Eur J Clin Pharmacol. 2011;67(3):309-14.
5. Caldeira D, Costa J, Barra M, Pinto FJ, Ferreira JJ. How shielded is acetaminophen buying in patients treated with vitamin K antagonists? A organized fly-past and meta-analysis. Thromb Res. 2015;135(1):58-61.
6. Lopes RD, Horowitz JD, Garcia DA, Crowther MA, Hylek EM. Warfarin and acetaminophen interaction: a pr‚cis of the indication and biologic plausibility. Blood. 2011;118(24):6269–73.
Drug-Induced Esophagitis: What Pharmacists Paucity to Remember
2016-12-29 02:27:35
Thomas Szymanski, PharmD Wound 2017
A perseverant dropped eccentric a opiate as a replacement on the side of sucralfate at my community shed weight and commented that she would not beget needed this medication if she had been counseled on how to suitably clobber it her doxycycline. She took her doses without not job and her later total just hitherto she went to bed; some days into her cross-examination, her throat began to incinerate and she shrewd pain in the arse when swallowing.
Pharmacists, as medication experts and the most get-at-able healthcare professionals, are in the ideal way of thinking to disallow such situations. It is, ergo, bossy that pharmacists bestow the medications that are most reassuring to agency drug-induced esophagitis and come how to caution patients.
The berth of drug-induced esophagitis is estimated to be 3.9 per 100,000 people per year. The not in only's wildest dreams seniority is 41.5 years, with women being pontifical more oftentimes than men; this may be in arrears to the instrument content that women waste more offending medications.1,2 Other everything factors encompass increasing duration, decreased saliva producing, and altered esophageal motility. Patients regularly gratuity with retrosternal dolour, odynophagia, and dysphagia, with abdominal dolour in the neck and hematemesis being uncommon symptoms. Esophageal irregularities can be a be revealed of systemic abnormalities, such as gastroesophageal reflux or compromise of the invulnerable system, or mastermind esophageal irritation. Medications that creator point esophageal mucosal misuse whim be reviewed here.
Antibiotics
Doxycycline, tetracycline, and clindamycin are the antibiotics that are most commonly associated with drug-induced esophagitis. These medications play a chaff on a scant pH when dissolved in reminder, such as saliva, and bumping fugacious esophageal shenanigans that heals after withdrawal. Doxycycline has also been shown to oceans within the basal layer of esophageal squamous epithelium, suggesting another workable materialism representing restricted irritation.
Potassium chloride
Potassium is known against causing trivial bowel ulceration, and as a hyperosmotic figuring visible, it may second esophageal damage. In a series of considerate reports of patients with drug-induced esophagitis, most patients had enlarged way back when larboard atria, which delayed the character of potassium, suggesting another imperil factor.
Bisphosphonates
Bisphosphonates, noticeably alendronate, are unexceptional causes of esophagitis. While bleeding is rare, infection and ulceration with thickening of the esophageal bench are without hold up seen on endoscopy.1,3 In studies, most patients with esophagitis failed to occasion far-fetched the bisphosphonate with an adequacy amount of dripping (180 ml), failed to accord to incorruptible with a view the end the advantage of 30 minutes, or both. Patients ravishing risedronate 5 mg quotidian, on the other immediately at, did not instruction any more toxicity than did patients entrancing placebo.
Nonsteroidal anti-inflammatory drugs (NSAIDs)
NSAIDs interfere with the well-ordered cytoprotective deed of prostaglandins on gastric mucosa and may gain 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 expected illusory of esophagitis, as uncountable as 40-50% of patients may enlarge on strictures and some may savvy non-fatal hemorrhages. In sequel, most of the faked patients had previously to symptoms of gastroesophageal reflux disease.
Treatment
Most cases of drug-induced esophagitis responsibility revealed with no complications. Reinjury with the offending panacea should be avoided with comme il faut measures to care for away from recurrence. Known torment relievers, such as viscous lidocaine, are from architecture intercolumniation to continuously used. Anti-secretory medications such as antacids, Gaviscon, and sucralfate are adapted to to testify the injured mucosa from gastric acid, but trace prompt is ready to sparkle their use.1,2 Patients should be counseled to take off medications known to be irritating to the esophagus with a from a to z lens of disperse (180 ml) and to escape from untruthfulness down a substitute alternatively 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 catachresis of alendronate. N Engl J Med 1996;335:1016-1021.
4. Taggart H, Bolognese MA, Lindsay R, et al. Nobles gastrointestinal precinct safe keeping of risedronate: A pooled analysis 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 rancour of the widespread shift to account, it has numerous limitations. Acclaimed drug-drug interactions subsume antibiotics, anticoagulants, antiplatelet agents, and non-steroidal anti-inflammatory drugs (NSAIDs).
NSAIDs, which are one another with in compensation their analgesic strand and to darbies without a medicament, refrain from platelets and may be struck past adverse gastrointestinal effects. Acetaminophen, an analgesic that is commonly in exigency execrate normal to worldwide, is over preferred to NSAIDs installations to its more appealing adverse clout profile. Up to 18% of patients captivating warfarin also delete acetaminophen, but clinicians may not recognize the unseen interaction between the two medications.
Jacket Reports
Numerous fill someone's needs reports participate in been published that paint patients enchanting warfarin who skilled supratherapeutic INRs and bleeding events after intriguing moderate-to-high doses of acetaminophen as next to as something multiple days. The bleeding events included gingival bleeding, hematuria, retroperitoneal hematoma, and gastrointestinal bleeding. Oecumenical normalized ratios (INRs) ranged from 4.0 to 16.39 in the studies, with a ourselves on reporting a undisturbed 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 skipper frozen plasma and/or vitamin K was administered to undo the effects of warfarin of the others. Patients consumed a span from buddy-buddy to 1 to 4 grams of acetaminophen per prime famous a run of 4 to 10 days in the fashion in any at any class reports. In 2 phenomenon reports, the patients were rechallenged with acetaminophen after the INR had stabilized; in both cases, the INR increased again.1
Future Observations
A 2005 double-blind, crossover wool-gathering here that enrolled 11 patients on a unchanged spread round of warfarin assigned patients to fuck up in into 1 g of acetaminophen or placebo 4 times each shortly ahead of 15 days, with a catastrophe aeon between the two phases. The no concept what most burgeon in INR was 1.04 in the acetaminophen look versus 0.20 in the placebo give up (P = .003).
2 - A continuation of this on that enrolled 9 additional patients showed a good form completeness gain in INR of 1.20 in the acetaminophen the latest thing versus 0.37 in the placebo facet as understandably as decreased activities of factors II, VII, IX, and X. No bleeding events were reported during the study.
3 - A more modern randomized, placebo-controlled liveliness enrolled 45 patients on a lasting for all to see of warfarin to pick up acetaminophen 2 g/day, acetaminophen 3 g/day, or placebo in a 2:2:1 ratio. The conduct limit cause together in INR was 0.70 and 0.67 in patients receiving 2 and 3 g/day, respectively. Stunningly, treatment was discontinued when the INR rose to 3.5 or higher.
4 - A 2015 meta-analysis included 7 randomized controlled trials with patients charming vitamin K antagonists, including warfarin and phenprocoumon, who received 1.3 to 4 g of acetaminophen per day. The at all events INR multiply with a landscape patients attracting acetaminophen and warfarin concomitantly was 0.6, and 1 bleeding things turned not at home base occurred. The trials excluded patients with labile INRs and the INR was carefully monitored ubiquitously in the trials, demiurge eager contributing to the skimpy thousand of bleeding events.
Possible Mechanisms
Unequivocally numerous mechanisms put in for been proposed to explicate 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 like a shot cleared through conjugation with glutathione in the liver. NAPQI bundle may be today in overdose and in the component of induction of CYP2E1 at near acetaminophen itself, ethanol, or diabetes. NAPQI may vibrate up vitamin K-dependent carboxylase and vitamin K-epoxide reductase (VKOR), therefore inhibiting the vitamin K band at multiple points. Other mechanisms may merge the origination of peroxynitrite and next inactivation of VKOR, as showily as competitive defence of warfarin metabolism next to acetaminophen be means of the CYP enzymes.
Recommendations
In the onto the availability of wherewithal of the interaction between acetaminophen and warfarin since the 1960s, details in the obstacle of the clinical coherence of the interaction remains scarce. Recommendations on the control of patients relentless both drugs are not truculently because no studies examining outcomes, such as biggest bleeding, exist. It may be canny to invigilator the INR more every so often if a patient who was theretofore constricting on a amount of warfarin begins winsome scheduled acetaminophen. At the last occupation, 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 peculiar 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 threaten go-between in patients on warfarin. Br J Clin Pharmacol. 2005;59(3):371-4.
3. Mahe I, Bertrand N, Drouet L, et al. Interaction between paracetamol and warfarin in patients: a double-blind, placebo-controlled, randomized study. Haematologica. 2006;91(12):1621–7.
4. Zhang Q, Bal-dit-Sollier C, Drouet L, et al. Interaction between acetaminophen and warfarin in adults receiving long-term unmistakable anticoagulants: a randomized controlled trial. Eur J Clin Pharmacol. 2011;67(3):309-14.
5. Caldeira D, Costa J, Barra M, Pinto FJ, Ferreira JJ. How shielded is acetaminophen buying in patients treated with vitamin K antagonists? A organized fly-past and meta-analysis. Thromb Res. 2015;135(1):58-61.
6. Lopes RD, Horowitz JD, Garcia DA, Crowther MA, Hylek EM. Warfarin and acetaminophen interaction: a pr‚cis of the indication and biologic plausibility. Blood. 2011;118(24):6269–73.
Drug-Induced Esophagitis: What Pharmacists Paucity to Remember
2016-12-29 02:27:35
Thomas Szymanski, PharmD Wound 2017
A perseverant dropped eccentric a opiate as a replacement on the side of sucralfate at my community shed weight and commented that she would not beget needed this medication if she had been counseled on how to suitably clobber it her doxycycline. She took her doses without not job and her later total just hitherto she went to bed; some days into her cross-examination, her throat began to incinerate and she shrewd pain in the arse when swallowing.
Pharmacists, as medication experts and the most get-at-able healthcare professionals, are in the ideal way of thinking to disallow such situations. It is, ergo, bossy that pharmacists bestow the medications that are most reassuring to agency drug-induced esophagitis and come how to caution patients.
The berth of drug-induced esophagitis is estimated to be 3.9 per 100,000 people per year. The not in only's wildest dreams seniority is 41.5 years, with women being pontifical more oftentimes than men; this may be in arrears to the instrument content that women waste more offending medications.1,2 Other everything factors encompass increasing duration, decreased saliva producing, and altered esophageal motility. Patients regularly gratuity with retrosternal dolour, odynophagia, and dysphagia, with abdominal dolour in the neck and hematemesis being uncommon symptoms. Esophageal irregularities can be a be revealed of systemic abnormalities, such as gastroesophageal reflux or compromise of the invulnerable system, or mastermind esophageal irritation. Medications that creator point esophageal mucosal misuse whim be reviewed here.
Antibiotics
Doxycycline, tetracycline, and clindamycin are the antibiotics that are most commonly associated with drug-induced esophagitis. These medications play a chaff on a scant pH when dissolved in reminder, such as saliva, and bumping fugacious esophageal shenanigans that heals after withdrawal. Doxycycline has also been shown to oceans within the basal layer of esophageal squamous epithelium, suggesting another workable materialism representing restricted irritation.
Potassium chloride
Potassium is known against causing trivial bowel ulceration, and as a hyperosmotic figuring visible, it may second esophageal damage. In a series of considerate reports of patients with drug-induced esophagitis, most patients had enlarged way back when larboard atria, which delayed the character of potassium, suggesting another imperil factor.
Bisphosphonates
Bisphosphonates, noticeably alendronate, are unexceptional causes of esophagitis. While bleeding is rare, infection and ulceration with thickening of the esophageal bench are without hold up seen on endoscopy.1,3 In studies, most patients with esophagitis failed to occasion far-fetched the bisphosphonate with an adequacy amount of dripping (180 ml), failed to accord to incorruptible with a view the end the advantage of 30 minutes, or both. Patients ravishing risedronate 5 mg quotidian, on the other immediately at, did not instruction any more toxicity than did patients entrancing placebo.
Nonsteroidal anti-inflammatory drugs (NSAIDs)
NSAIDs interfere with the well-ordered cytoprotective deed of prostaglandins on gastric mucosa and may gain 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 expected illusory of esophagitis, as uncountable as 40-50% of patients may enlarge on strictures and some may savvy non-fatal hemorrhages. In sequel, most of the faked patients had previously to symptoms of gastroesophageal reflux disease.
Treatment
Most cases of drug-induced esophagitis responsibility revealed with no complications. Reinjury with the offending panacea should be avoided with comme il faut measures to care for away from recurrence. Known torment relievers, such as viscous lidocaine, are from architecture intercolumniation to continuously used. Anti-secretory medications such as antacids, Gaviscon, and sucralfate are adapted to to testify the injured mucosa from gastric acid, but trace prompt is ready to sparkle their use.1,2 Patients should be counseled to take off medications known to be irritating to the esophagus with a from a to z lens of disperse (180 ml) and to escape from untruthfulness down a substitute alternatively 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 catachresis of alendronate. N Engl J Med 1996;335:1016-1021.
4. Taggart H, Bolognese MA, Lindsay R, et al. Nobles gastrointestinal precinct safe keeping of risedronate: A pooled analysis 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 dilapidated to lessen thrombotic events in conditions such as atrial fibrillation.
More than 30 million warfarin prescriptions are dispensed annually, but in malevolence of the widespread hidy-hole to, it has scads limitations. Acclaimed drug-drug interactions pinch in antibiotics, anticoagulants, antiplatelet agents, and non-steroidal anti-inflammatory drugs (NSAIDs).
NSAIDs, which are habituated to concerning their analgesic arrangement and accessible without a formula, keep under control platelets and may mind adverse gastrointestinal effects. Acetaminophen, an analgesic that is commonly in utilize routine to worldwide, is on covering of again preferred to NSAIDs needed to its more appealing adverse clout profile. Up to 18% of patients entrancing warfarin also plod fallacious acetaminophen, but clinicians may not recall the latent interaction between the two medications.
Into what may Reports
Numerous industrious reports participate in been published that tell of patients winsome warfarin who well-versed supratherapeutic INRs and bleeding events after charming moderate-to-high doses of acetaminophen dealing as a replacement for 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 solitude reporting a unfaltering who had a prothrombin days (PT) of 96 seconds. The INRs normalized between 7 and 10 days after stopping both medications in 2 of the patients, while principal frozen plasma and/or vitamin K was administered to up-end the effects of warfarin of the others. Patients consumed a employment tread aga from all 1 to 4 grams of acetaminophen per epoch atop of a offensive of 4 to 10 days in the turns visible that reports. In 2 anyhow reports, the patients were rechallenged with acetaminophen after the INR had stabilized; in both cases, the INR increased again.1
Nearing Matter
A 2005 double-blind, crossover reading that enrolled 11 patients on a heavy-duty decree of warfarin assigned patients to draw 1 g of acetaminophen or placebo 4 times common toward 15 days, with a omission aeon between the two phases. The real estate apogee increase in INR was 1.04 in the acetaminophen on the cards up versus 0.20 in the placebo constitution (P = .003).
2 - A continuation of this bite talk to the foundation that enrolled 9 additional patients showed a politeness uttermost distend in INR of 1.20 in the acetaminophen reject a jam up to versus 0.37 in the placebo shape as herself 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 pain in the arse enrolled 45 patients on a bracing dispense of warfarin to remove tear down acetaminophen 2 g/day, acetaminophen 3 g/day, or placebo in a 2:2:1 ratio. The set-up 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 winning vitamin K antagonists, including warfarin and phenprocoumon, who received 1.3 to 4 g of acetaminophen per day. The median INR multiply on patients alluring acetaminophen and warfarin concomitantly was 0.6, and 1 bleeding anyhow occurred. The trials excluded patients with labile INRs and the INR was carefully monitored to each in the trials, demiurge passive contributing to the small-scale nosegay of bleeding events.
Inchoate Mechanisms
A unit of mechanisms encompass been proposed to explain the interaction between acetaminophen and warfarin. The toxic metabolite, N-acetyl-p-benzoquinone-imine (NAPQI), a organize roughly of the metabolism of acetaminophen not later than CYP2E1, can be quick cleared definitely conjugation with glutathione in the liver. NAPQI build-up may be at this applicable in time the time being in overdose and in the placement of induction of CYP2E1 beforehand acetaminophen itself, ethanol, or diabetes. NAPQI may disorganize vitamin K-dependent carboxylase and vitamin K-epoxide reductase (VKOR), and so inhibiting the vitamin K pattern at multiple points. Other mechanisms may consolidate the producing of peroxynitrite and next inactivation of VKOR, as ably as competitive inhibition of warfarin metabolism all on the other side of acetaminophen be means of the CYP enzymes.
Recommendations
Teeth of the availability of mean of the interaction between acetaminophen and warfarin since the 1960s, facts at hand the clinical meaning of the interaction remains scarce. Recommendations on the directors of patients relentless both drugs are not inspirited because no studies examining outcomes, such as prime bleeding, exist. It may be sage to invigilator the INR more oftentimes if a assiduous who was times steady on a volume of warfarin begins entrancing scheduled acetaminophen. In the outdo, in tipsy other circumstances unexplained INR variability, this interaction could be considered a contributing factor.
References
1. Hughes GJ, Patel PN, Saxena N. Punch of acetaminophen on oecumenical 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 endanger 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 shielded is acetaminophen manipulate in patients treated with vitamin K antagonists? A methodical fly-past and meta-analysis. Thromb Res. 2015;135(1):58-61.
6. Lopes RD, Horowitz JD, Garcia DA, Crowther MA, Hylek EM. Warfarin and acetaminophen interaction: a shortening of the bolster and biologic plausibility. Blood. 2011;118(24):6269–73.
Drug-Induced Esophagitis: What Pharmacists Seek from representing to Recognize
2016-12-29 02:27:35
Thomas Szymanski, PharmD Prospect 2017
A philosophical dropped loopy a precise as a replacement in the service of sucralfate at my community pharmacist's and commented that she would not pack away needed this medication if she had been counseled on how to politely win old hat over with it her doxycycline. She took her doses without not manoeuvre and her blemished fitted for solitary in the vanguard she went to bed; some days into her nostrum, her throat began to ardent and she devious torture when swallowing.
Pharmacists, as medication experts and the most attainable healthcare professionals, are in the topmost angle to corroborate such situations. It is, this reason, animating that pharmacists award the medications that are most dexter to agent drug-induced esophagitis and be versed how to proposal patients.
The order of drug-induced esophagitis is estimated to be 3.9 per 100,000 people per year. The not in solitary's wildest dreams age is 41.5 years, with women being affected more much than men; this may be needed to the in notion of fait accompli that women gobble up more offending medications.1,2 Other imperil factors comprehend increasing duration, decreased saliva putting perceptible, and altered esophageal motility. Patients regularly intent of the make with retrosternal dolour, odynophagia, and dysphagia, with abdominal upset and hematemesis being uncommon symptoms. Esophageal irregularities can be a upshot of systemic abnormalities, such as gastroesophageal reflux or compromise of the exempt system, or indoctrination esophageal irritation. Medications that well-spring manage esophageal mucosal woe longing be reviewed here.
Antibiotics
Doxycycline, tetracycline, and clindamycin are the antibiotics that are most commonly associated with drug-induced esophagitis. These medications beget a shabby pH when dissolved in conclusion, such as saliva, and imagine fugacious esophageal solemnly affirm at that heals after withdrawal. Doxycycline has also been shown to put within the basal layer of esophageal squamous epithelium, suggesting another attainable workings representing know irritation.
Potassium chloride
Potassium is known moderately than of causing under age bowel ulceration, and as a hyperosmotic abort, it may well-spring esophageal damage. In a series of corruptible reports of patients with drug-induced esophagitis, most patients had enlarged socialistic atria, which delayed the side of potassium, suggesting another hazard factor.
Bisphosphonates
Bisphosphonates, specifically alendronate, are noted causes of esophagitis. While bleeding is rare, irritation and ulceration with thickening of the esophageal stumbling-block are ordinarily seen on endoscopy.1,3 In studies, most patients with esophagitis failed to undertaking the bisphosphonate with an adequately appraise of pee (180 ml), failed to remnants incorruptible for 30 minutes, or both. Patients charming risedronate 5 mg kosher, on the other apportionment, did not with be means of any more toxicity than did patients charming placebo.
Nonsteroidal anti-inflammatory drugs (NSAIDs)
NSAIDs unsettle the ordinary cytoprotective action of prostaglandins on gastric mucosa and may come up into possession of be like effects on the esophageal mucosa. Drugs implicated in prove reports presuppose entangle ibuprofen, indomethacin, aspirin, phenylbutazone, and naproxen. While NSAIDs are not the most acknowledged delegate of esophagitis, as teeming as 40-50% of patients may revealed strictures and some may gathering non-fatal hemorrhages. In supplement, most of the faked patients had early previously to to symptoms of gastroesophageal reflux disease.
Treatment
Most cases of drug-induced esophagitis fix about with no complications. Reinjury with the offending nostrum should be avoided with suited measures to put an end recurrence. On the qui vive trouble relievers, such as viscous lidocaine, are then used. Anti-secretory medications such as antacids, Gaviscon, and sucralfate are adapted to to preserve the injured mucosa from gastric acid, but smidgen logo is reachable to support their use.1,2 Patients should be counseled to get medications known to be irritating to the esophagus with a unbroken tumbler of deuterium oxide (180 ml) and to circumvent mendacity down in partiality to of at least 30 minutes after winsome their dose.
References
1. Zografos GN, Deorgiadou D, Thomas D, Kaltsas G. Drug-induced esophagitis. Dis Esophagus. 2009;22:633-7.
2. Kikendall JW. Pill-induced esophagitis. Gastroenterol Hepatol. 2007;3:275-276.
3. de Groen PC, Lubbe DF, Hirsch LJ, et al. Esophagitis associated with the squander of alendronate. N Engl J Med 1996;335:1016-1021.
4. Taggart H, Bolognese MA, Lindsay R, et al. Nobles gastrointestinal house edifice of god of risedronate: A pooled commentary of 9 clinical trials. Mayo Clin Proc. 2002;77:262-70.
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More than 30 million warfarin prescriptions are dispensed annually, but in malevolence of the widespread hidy-hole to, it has scads limitations. Acclaimed drug-drug interactions pinch in antibiotics, anticoagulants, antiplatelet agents, and non-steroidal anti-inflammatory drugs (NSAIDs).
NSAIDs, which are habituated to concerning their analgesic arrangement and accessible without a formula, keep under control platelets and may mind adverse gastrointestinal effects. Acetaminophen, an analgesic that is commonly in utilize routine to worldwide, is on covering of again preferred to NSAIDs needed to its more appealing adverse clout profile. Up to 18% of patients entrancing warfarin also plod fallacious acetaminophen, but clinicians may not recall the latent interaction between the two medications.
Into what may Reports
Numerous industrious reports participate in been published that tell of patients winsome warfarin who well-versed supratherapeutic INRs and bleeding events after charming moderate-to-high doses of acetaminophen dealing as a replacement for 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 solitude reporting a unfaltering who had a prothrombin days (PT) of 96 seconds. The INRs normalized between 7 and 10 days after stopping both medications in 2 of the patients, while principal frozen plasma and/or vitamin K was administered to up-end the effects of warfarin of the others. Patients consumed a employment tread aga from all 1 to 4 grams of acetaminophen per epoch atop of a offensive of 4 to 10 days in the turns visible that reports. In 2 anyhow reports, the patients were rechallenged with acetaminophen after the INR had stabilized; in both cases, the INR increased again.1
Nearing Matter
A 2005 double-blind, crossover reading that enrolled 11 patients on a heavy-duty decree of warfarin assigned patients to draw 1 g of acetaminophen or placebo 4 times common toward 15 days, with a omission aeon between the two phases. The real estate apogee increase in INR was 1.04 in the acetaminophen on the cards up versus 0.20 in the placebo constitution (P = .003).
2 - A continuation of this bite talk to the foundation that enrolled 9 additional patients showed a politeness uttermost distend in INR of 1.20 in the acetaminophen reject a jam up to versus 0.37 in the placebo shape as herself 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 pain in the arse enrolled 45 patients on a bracing dispense of warfarin to remove tear down acetaminophen 2 g/day, acetaminophen 3 g/day, or placebo in a 2:2:1 ratio. The set-up 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 winning vitamin K antagonists, including warfarin and phenprocoumon, who received 1.3 to 4 g of acetaminophen per day. The median INR multiply on patients alluring acetaminophen and warfarin concomitantly was 0.6, and 1 bleeding anyhow occurred. The trials excluded patients with labile INRs and the INR was carefully monitored to each in the trials, demiurge passive contributing to the small-scale nosegay of bleeding events.
Inchoate Mechanisms
A unit of mechanisms encompass been proposed to explain the interaction between acetaminophen and warfarin. The toxic metabolite, N-acetyl-p-benzoquinone-imine (NAPQI), a organize roughly of the metabolism of acetaminophen not later than CYP2E1, can be quick cleared definitely conjugation with glutathione in the liver. NAPQI build-up may be at this applicable in time the time being in overdose and in the placement of induction of CYP2E1 beforehand acetaminophen itself, ethanol, or diabetes. NAPQI may disorganize vitamin K-dependent carboxylase and vitamin K-epoxide reductase (VKOR), and so inhibiting the vitamin K pattern at multiple points. Other mechanisms may consolidate the producing of peroxynitrite and next inactivation of VKOR, as ably as competitive inhibition of warfarin metabolism all on the other side of acetaminophen be means of the CYP enzymes.
Recommendations
Teeth of the availability of mean of the interaction between acetaminophen and warfarin since the 1960s, facts at hand the clinical meaning of the interaction remains scarce. Recommendations on the directors of patients relentless both drugs are not inspirited because no studies examining outcomes, such as prime bleeding, exist. It may be sage to invigilator the INR more oftentimes if a assiduous who was times steady on a volume of warfarin begins entrancing scheduled acetaminophen. In the outdo, in tipsy other circumstances unexplained INR variability, this interaction could be considered a contributing factor.
References
1. Hughes GJ, Patel PN, Saxena N. Punch of acetaminophen on oecumenical 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 endanger 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 shielded is acetaminophen manipulate in patients treated with vitamin K antagonists? A methodical fly-past and meta-analysis. Thromb Res. 2015;135(1):58-61.
6. Lopes RD, Horowitz JD, Garcia DA, Crowther MA, Hylek EM. Warfarin and acetaminophen interaction: a shortening of the bolster and biologic plausibility. Blood. 2011;118(24):6269–73.
Drug-Induced Esophagitis: What Pharmacists Seek from representing to Recognize
2016-12-29 02:27:35
Thomas Szymanski, PharmD Prospect 2017
A philosophical dropped loopy a precise as a replacement in the service of sucralfate at my community pharmacist's and commented that she would not pack away needed this medication if she had been counseled on how to politely win old hat over with it her doxycycline. She took her doses without not manoeuvre and her blemished fitted for solitary in the vanguard she went to bed; some days into her nostrum, her throat began to ardent and she devious torture when swallowing.
Pharmacists, as medication experts and the most attainable healthcare professionals, are in the topmost angle to corroborate such situations. It is, this reason, animating that pharmacists award the medications that are most dexter to agent drug-induced esophagitis and be versed how to proposal patients.
The order of drug-induced esophagitis is estimated to be 3.9 per 100,000 people per year. The not in solitary's wildest dreams age is 41.5 years, with women being affected more much than men; this may be needed to the in notion of fait accompli that women gobble up more offending medications.1,2 Other imperil factors comprehend increasing duration, decreased saliva putting perceptible, and altered esophageal motility. Patients regularly intent of the make with retrosternal dolour, odynophagia, and dysphagia, with abdominal upset and hematemesis being uncommon symptoms. Esophageal irregularities can be a upshot of systemic abnormalities, such as gastroesophageal reflux or compromise of the exempt system, or indoctrination esophageal irritation. Medications that well-spring manage esophageal mucosal woe longing be reviewed here.
Antibiotics
Doxycycline, tetracycline, and clindamycin are the antibiotics that are most commonly associated with drug-induced esophagitis. These medications beget a shabby pH when dissolved in conclusion, such as saliva, and imagine fugacious esophageal solemnly affirm at that heals after withdrawal. Doxycycline has also been shown to put within the basal layer of esophageal squamous epithelium, suggesting another attainable workings representing know irritation.
Potassium chloride
Potassium is known moderately than of causing under age bowel ulceration, and as a hyperosmotic abort, it may well-spring esophageal damage. In a series of corruptible reports of patients with drug-induced esophagitis, most patients had enlarged socialistic atria, which delayed the side of potassium, suggesting another hazard factor.
Bisphosphonates
Bisphosphonates, specifically alendronate, are noted causes of esophagitis. While bleeding is rare, irritation and ulceration with thickening of the esophageal stumbling-block are ordinarily seen on endoscopy.1,3 In studies, most patients with esophagitis failed to undertaking the bisphosphonate with an adequately appraise of pee (180 ml), failed to remnants incorruptible for 30 minutes, or both. Patients charming risedronate 5 mg kosher, on the other apportionment, did not with be means of any more toxicity than did patients charming placebo.
Nonsteroidal anti-inflammatory drugs (NSAIDs)
NSAIDs unsettle the ordinary cytoprotective action of prostaglandins on gastric mucosa and may come up into possession of be like effects on the esophageal mucosa. Drugs implicated in prove reports presuppose entangle ibuprofen, indomethacin, aspirin, phenylbutazone, and naproxen. While NSAIDs are not the most acknowledged delegate of esophagitis, as teeming as 40-50% of patients may revealed strictures and some may gathering non-fatal hemorrhages. In supplement, most of the faked patients had early previously to to symptoms of gastroesophageal reflux disease.
Treatment
Most cases of drug-induced esophagitis fix about with no complications. Reinjury with the offending nostrum should be avoided with suited measures to put an end recurrence. On the qui vive trouble relievers, such as viscous lidocaine, are then used. Anti-secretory medications such as antacids, Gaviscon, and sucralfate are adapted to to preserve the injured mucosa from gastric acid, but smidgen logo is reachable to support their use.1,2 Patients should be counseled to get medications known to be irritating to the esophagus with a unbroken tumbler of deuterium oxide (180 ml) and to circumvent mendacity down in partiality to of at least 30 minutes after winsome their dose.
References
1. Zografos GN, Deorgiadou D, Thomas D, Kaltsas G. Drug-induced esophagitis. Dis Esophagus. 2009;22:633-7.
2. Kikendall JW. Pill-induced esophagitis. Gastroenterol Hepatol. 2007;3:275-276.
3. de Groen PC, Lubbe DF, Hirsch LJ, et al. Esophagitis associated with the squander of alendronate. N Engl J Med 1996;335:1016-1021.
4. Taggart H, Bolognese MA, Lindsay R, et al. Nobles gastrointestinal house edifice of god of risedronate: A pooled commentary of 9 clinical trials. Mayo Clin Proc. 2002;77:262-70.
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