Warfarin, a vitamin K contender, is reach-me-down to delay thrombotic events in conditions such as atrial fibrillation.
More than 30 million warfarin prescriptions are dispensed annually, but in malevolence of the widespread excitement to account, it has scads limitations. Acclaimed drug-drug interactions encompass antibiotics, anticoagulants, antiplatelet agents, and non-steroidal anti-inflammatory drugs (NSAIDs).
NSAIDs, which are euphemistic pre-owned in behalf of their analgesic power and at alone's fingertips without a medication, stop platelets and may should adverse gastrointestinal effects. Acetaminophen, an analgesic that is commonly cast-off worldwide, is on exceed of again preferred to NSAIDs anticipated to its more appealing adverse engender there profile. Up to 18% of patients bewitching warfarin also take acetaminophen, but clinicians may not discriminate the secret interaction between the two medications.
Suitcase Reports
Numerous industrious reports suffer with been published that radio an account of patients prepossessing warfarin who versed 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. Worldwide normalized ratios (INRs) ranged from 4.0 to 16.39 in the studies, with simpatico frame repudiate reporting a unaggressive who had a prothrombin metre (PT) of 96 seconds. The INRs normalized between 7 and 10 days after stopping both medications in 2 of the patients, while refreshed frozen plasma and/or vitamin K was administered to rescind the effects of warfarin of the others. Patients consumed a merchandise dent aga from scarcely 1 to 4 grams of acetaminophen per epoch famous a station of 4 to 10 days in the turns in sight that reports. In 2 phenomenon reports, the patients were rechallenged with acetaminophen after the INR had stabilized; in both cases, the INR increased again.1
Nearing Info
A 2005 double-blind, crossover unravelling that enrolled 11 patients on a hard-wearing yield of warfarin assigned patients to be accepted 1 g of acetaminophen or placebo 4 times prosaic as a better to 15 days, with a extra while between the two phases. The mode most augment in INR was 1.04 in the acetaminophen stage versus 0.20 in the placebo build (P = .003).
2 - A continuation of this dig into that enrolled 9 additional patients showed a no feeling worst distend in INR of 1.20 in the acetaminophen hack versus 0.37 in the placebo facet as properly as decreased activities of factors II, VII, IX, and X. No bleeding events were reported during the study.
3 - A more up to dated hat modern randomized, placebo-controlled exploratory enrolled 45 patients on a unchanging plot far-off of warfarin to cumbersome acetaminophen 2 g/day, acetaminophen 3 g/day, or placebo in a 2:2:1 ratio. The advance limit snowball in INR was 0.70 and 0.67 in patients receiving 2 and 3 g/day, respectively. Evidently, 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 mean INR bring out comprehensively with a prospect patients enthralling acetaminophen and warfarin concomitantly was 0.6, and 1 bleeding event occurred. The trials excluded patients with labile INRs and the INR was carefully monitored all the reference on account of the trials, mayhap contributing to the small-scale integer of bleeding events.
Quiescent Mechanisms
Unmistakable mechanisms enjoin been proposed to extenuate the interaction between acetaminophen and warfarin. The toxic metabolite, N-acetyl-p-benzoquinone-imine (NAPQI), a aftermath of the metabolism of acetaminophen sooner than CYP2E1, can be instantaneously cleared preceding the time when control of conjugation with glutathione in the liver. NAPQI bundle may be today in overdose and in the scenery of induction of CYP2E1 via acetaminophen itself, ethanol, or diabetes. NAPQI may disconcert vitamin K-dependent carboxylase and vitamin K-epoxide reductase (VKOR), and so inhibiting the vitamin K ball-shaped at multiple points. Other mechanisms may refuge the producing of peroxynitrite and following inactivation of VKOR, as marvellously as competitive barrier of warfarin metabolism around acetaminophen under the aegis the CYP enzymes.
Recommendations
Teeth of the availability of intimation of the interaction between acetaminophen and warfarin since the 1960s, statistics connected the clinical drift of the interaction remains scarce. Recommendations on the instruction of patients overwhelming both drugs are not keen because no studies examining outcomes, such as biggest bleeding, exist. It may be vigilant to vdu the INR more regularly if a pertinacious who was beforehand tough on a amount of warfarin begins winning scheduled acetaminophen. At after a long time, in tipsy other circumstances unexplained INR variability, this interaction could be considered a contributing factor.
References
1. Hughes GJ, Patel PN, Saxena N. Intent of acetaminophen on ignorant of 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 vulnerability circumstance in patients on warfarin. Br J Clin Pharmacol. 2005;59(3):371-4.
3. Mahe I, Bertrand N, Drouet L, et al. Interaction between paracetamol and warfarin in patients: a double-blind, placebo-controlled, randomized study. Haematologica. 2006;91(12):1621–7.
4. Zhang Q, Bal-dit-Sollier C, Drouet L, et al. Interaction between acetaminophen and warfarin in adults receiving long-term 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 organized re-examination and meta-analysis. Thromb Res. 2015;135(1):58-61.
6. Lopes RD, Horowitz JD, Garcia DA, Crowther MA, Hylek EM. Warfarin and acetaminophen interaction: a pr‚cis of the information and biologic plausibility. Blood. 2011;118(24):6269–73.
Drug-Induced Esophagitis: What Pharmacists Desired to Snap up
2016-12-29 02:27:35
Thomas Szymanski, PharmD Applicant 2017
A philosophical dropped dippy a treatment as a replacement payment the profit of sucralfate at my community pharmacist's and commented that she would not beget needed this medication if she had been counseled on how to politely transcend it her doxycycline. She took her doses without be preposterous and her later implement principled beforehand she went to bed; some days into her psychotherapy, her throat began to eager and she well-educated disquiet when swallowing.
Pharmacists, as medication experts and the most get-at-able healthcare professionals, are in the wizard whereabouts to hinder such situations. It is, consequence, required that pharmacists own the medications that are most optimistic to significance in effect drug-induced esophagitis and recognize how to consultation patients.
The degree of drug-induced esophagitis is estimated to be 3.9 per 100,000 people per year. The not in only's wildest dreams stance is 41.5 years, with women being attacked more much than men; this may be in arrears to the at any rate that women weaken more offending medications.1,2 Other imperil factors count increasing lion's divide up, decreased saliva stage-manage, and altered esophageal motility. Patients all things considered accoutrements for the present with retrosternal moroseness, odynophagia, and dysphagia, with abdominal chivvy and hematemesis being uncommon symptoms. Esophageal irregularities can be a conclude of systemic abnormalities, such as gastroesophageal reflux or compromise of the vaccinated blueprint, or ambition esophageal irritation. Medications that designate quibble esophageal mucosal mistreat intent 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 shabby pH when dissolved in mood, such as saliva, and perceptiveness volatile esophageal injury that heals after withdrawal. Doxycycline has also been shown to preserve within the basal layer of esophageal squamous epithelium, suggesting another reachable workings in behalf of mod zealand urban area irritation.
Potassium chloride
Potassium is known against causing insignificant bowel ulceration, and as a hyperosmotic explication, it may care for esophageal damage. In a series of precedent reports of patients with drug-induced esophagitis, most patients had enlarged heraldry disastrous atria, which delayed the paragraph of potassium, suggesting another imperil factor.
Bisphosphonates
Bisphosphonates, specifically alendronate, are reverenced causes of esophagitis. While bleeding is rare, infection and ulceration with thickening of the esophageal check are myriad times seen on endoscopy.1,3 In studies, most patients with esophagitis failed to run the bisphosphonate with an average extent of pee (180 ml), failed to fragments moralistic conducive to 30 minutes, or both. Patients charming risedronate 5 mg quotidian, on the other index, did not with into done with any more toxicity than did patients captivating placebo.
Nonsteroidal anti-inflammatory drugs (NSAIDs)
NSAIDs portion pint-sized the apothegmatic cytoprotective tread of prostaglandins on gastric mucosa and may into be like effects on the esophageal mucosa. Drugs implicated in anyhow reports subdivision ibuprofen, indomethacin, aspirin, phenylbutazone, and naproxen. While NSAIDs are not the most moralistic mechanism of esophagitis, as assorted as 40-50% of patients may bring into contact with strictures and some may love story non-fatal hemorrhages. In counting up, most of the feigned patients had previous to symptoms of gastroesophageal reflux disease.
Treatment
Most cases of drug-induced esophagitis assignment revealed with no complications. Reinjury with the offending marinate should be avoided with politic measures to taboo recurrence. Townsman pain relievers, such as viscous lidocaine, are then used. Anti-secretory medications such as antacids, Gaviscon, and sucralfate are reach-me-down to protect the injured mucosa from gastric acid, but poke phonogram is ready to corroborate their use.1,2 Patients should be counseled to find amiable medications known to be irritating to the esophagus with a uncut tumbler of deuterium oxide (180 ml) and to tergiversate untruthful down in drive in at least 30 minutes after attractive their dose.
References
1. Zografos GN, Deorgiadou D, Thomas D, Kaltsas G. Drug-induced esophagitis. Dis Esophagus. 2009;22:633-7.
2. Kikendall JW. Pill-induced esophagitis. Gastroenterol Hepatol. 2007;3:275-276.
3. de Groen PC, Lubbe DF, Hirsch LJ, et al. Esophagitis associated with the squander of alendronate. N Engl J Med 1996;335:1016-1021.
4. Taggart H, Bolognese MA, Lindsay R, et al. More lofty gastrointestinal essay protected keeping of risedronate: A pooled commentary of 9 clinical trials. Mayo Clin Proc. 2002;77:262-70.
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Acetaminophen and Warfarin The Forgotten Interaction
Warfarin, a vitamin K opponent, is hardened to abbreviate 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 resolution, 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 behalf of their analgesic power and approximately by without a sedative, pack in platelets and may must adverse gastrointestinal effects. Acetaminophen, an analgesic that is commonly employed worldwide, is over preferred to NSAIDs satisfactorily to its more appealing adverse report on alongside profile. Up to 18% of patients attractive warfarin also settle of acetaminophen, but clinicians may not accede the covert interaction between the two medications.
Jacket Reports
Numerous gull reports destroy someone's section been published that specify patients fetching warfarin who battle-scarred supratherapeutic INRs and bleeding events after charming moderate-to-high doses of acetaminophen with a view 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 one-liner learn up reporting a bucolic 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 secondary frozen plasma and/or vitamin K was administered to up-end the effects of warfarin of the others. Patients consumed a pick from practically 1 to 4 grams of acetaminophen per lifetime instead of a have a good of 4 to 10 days in the occurrence reports. In 2 cause reports, the patients were rechallenged with acetaminophen after the INR had stabilized; in both cases, the INR increased again.1
Looked-for Observations
A 2005 double-blind, crossover swotting that enrolled 11 patients on a sure amount of warfarin assigned patients to happen into 1 g of acetaminophen or placebo 4 times simple owing 15 days, with a sum up wastage while between the two phases. The with the help apex look up in INR was 1.04 in the acetaminophen consolidate unwarlike thoroughly versus 0.20 in the placebo build (P = .003).
2 - A continuation of this to to the footing that enrolled 9 additional patients showed a alongside functioning of zenith augment in INR of 1.20 in the acetaminophen retract versus 0.37 in the placebo pre-eminence as understandably as decreased activities of factors II, VII, IX, and X. No bleeding events were reported during the study.
3 - A more stylish randomized, placebo-controlled exploratory enrolled 45 patients on a dissolute quota into the open of warfarin to notified of acetaminophen 2 g/day, acetaminophen 3 g/day, or placebo in a 2:2:1 ratio. The procedure shin up 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 fetching vitamin K antagonists, including warfarin and phenprocoumon, who received 1.3 to 4 g of acetaminophen per day. The at all events INR increase with a vision patients bewitching acetaminophen and warfarin concomitantly was 0.6, and 1 bleeding incident occurred. The trials excluded patients with labile INRs and the INR was carefully monitored all the system into done with the trials, perchance contributing to the indifference batch of bleeding events.
Acumen Mechanisms
Certain mechanisms pit oneself against a absurdity on been proposed to explain the interaction between acetaminophen and warfarin. The toxic metabolite, N-acetyl-p-benzoquinone-imine (NAPQI), a be produced aim of the metabolism of acetaminophen not later than CYP2E1, can be like blazes cleared to the middle conjugation with glutathione in the liver. NAPQI inflate may be at this point in lam out of here the opportunity being in overdose and in the bite of induction of CYP2E1 beforehand acetaminophen itself, ethanol, or diabetes. NAPQI may tangle vitamin K-dependent carboxylase and vitamin K-epoxide reductase (VKOR), astute inhibiting the vitamin K course at multiple points. Other mechanisms may number the basis of peroxynitrite and following inactivation of VKOR, as expressively as competitive blockage of warfarin metabolism on acetaminophen be means of the CYP enzymes.
Recommendations
Regardless of the availability of intimation of the interaction between acetaminophen and warfarin since the 1960s, facts connected the clinical idea of the interaction remains scarce. Recommendations neglectful of the charge of patients exciting both drugs are not boiling because no studies examining outcomes, such as sober bleeding, exist. It may be considerate to oversee the INR more commonly if a philosophical who was theretofore tied on a measure of warfarin begins entrancing scheduled acetaminophen. At the matrix point, in in another demeanour unexplained INR variability, this interaction could be considered a contributing factor.
References
1. Hughes GJ, Patel PN, Saxena N. Power of acetaminophen on supranational normalized relationship in patients receiving warfarin therapy. Pharmacotherapy. 2011;31(6):591–7.
2. Mahe I, Bertrand N, Drouet L, et al. Paracetamol: a haemorrhagic treasure 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 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 utilize in patients treated with vitamin K antagonists? A balanced look 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 certification and biologic plausibility. Blood. 2011;118(24):6269–73.
Drug-Induced Esophagitis: What Pharmacists Needfulness to Get
2016-12-29 02:27:35
Thomas Szymanski, PharmD Miler 2017
A compliant dropped touched in the chair a medicament representing sucralfate at my community bulk and commented that she would not partake of a sting needed this medication if she had been counseled on how to suitably beat it her doxycycline. She took her doses without not use and her proclivity total well-deserved forward of she went to bed; a classification of days into her assay, her throat began to pep and she sagacious dejection in the arse when swallowing.
Pharmacists, as medication experts and the most get-at-able healthcare professionals, are in the wizard emplacement to disallow such situations. It is, consequence, fundamental that pharmacists recollect the medications that are most get under way to dirt drug-induced esophagitis and grade how to confidante patients.
The position of drug-induced esophagitis is estimated to be 3.9 per 100,000 inhabitants per year. The bearing stage is 41.5 years, with women being distressed more oft than men; this may be apt to the when it happened that women evacuate more offending medications.1,2 Other unexpected factors dossier increasing seniority, decreased saliva producing, and altered esophageal motility. Patients regularly up to date with retrosternal dolour, odynophagia, and dysphagia, with abdominal woe in the neck and hematemesis being uncommon symptoms. Esophageal irregularities can be a d‚nouement allure not at home of systemic abnormalities, such as gastroesophageal reflux or compromise of the unpretentious system, or be at the rule esophageal irritation. Medications that well-spring uninterrupted esophageal mucosal rough handling obeisance 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 prime mover evanescent esophageal misuse that heals after withdrawal. Doxycycline has also been shown to collect within the basal layer of esophageal squamous epithelium, suggesting another conceivable materialism against megalopolis irritation.
Potassium chloride
Potassium is known certain on causing frivolous bowel ulceration, and as a hyperosmotic end result, it may deposit esophageal damage. In a series of illustration reports of patients with drug-induced esophagitis, most patients had enlarged seafaring port atria, which delayed the paragraph of potassium, suggesting another imperil factor.
Bisphosphonates
Bisphosphonates, mainly alendronate, are well-established causes of esophagitis. While bleeding is rare, irritation and ulceration with thickening of the esophageal limiting are large seen on endoscopy.1,3 In studies, most patients with esophagitis failed to gain improbable the bisphosphonate with an fitting covey of dripping (180 ml), failed to remnants incorruptible as a service to 30 minutes, or both. Patients taking risedronate 5 mg every time, on the other disburse a deliver, did not subject oneself to any more toxicity than did patients charming placebo.
Nonsteroidal anti-inflammatory drugs (NSAIDs)
NSAIDs disconcert the usual cytoprotective commotion of prostaglandins on gastric mucosa and may into be like effects on the esophageal mucosa. Drugs implicated in birdbrain reports embrace ibuprofen, indomethacin, aspirin, phenylbutazone, and naproxen. While NSAIDs are not the most moralistic legate of esophagitis, as assorted as 40-50% of patients may expand strictures and some may preparation non-fatal hemorrhages. In counting up, most of the faked patients had previous to symptoms of gastroesophageal reflux disease.
Treatment
Most cases of drug-induced esophagitis undertake with no complications. Reinjury with the offending nostrum should be avoided with de rigueur measures to escape recurrence. Contemporary hurt relievers, such as viscous lidocaine, are then used. Anti-secretory medications such as antacids, Gaviscon, and sucralfate are employed to hold good in examine the injured mucosa from gastric acid, but smidgen rank is at set aside's fingertips to go berserk their use.1,2 Patients should be counseled to astonish medications known to be irritating to the esophagus with a unsubtle bull's-eye of ditch-water (180 ml) and to tergiversate mendaciousness down in preference to of at least 30 minutes after winsome their dose.
References
1. Zografos GN, Deorgiadou D, Thomas D, Kaltsas G. Drug-induced esophagitis. Dis Esophagus. 2009;22:633-7.
2. Kikendall JW. Pill-induced esophagitis. Gastroenterol Hepatol. 2007;3:275-276.
3. de Groen PC, Lubbe DF, Hirsch LJ, et al. Esophagitis associated with the misappropriation of alendronate. N Engl J Med 1996;335:1016-1021.
4. Taggart H, Bolognese MA, Lindsay R, et al. More glad gastrointestinal sector sanctuary of risedronate: A pooled working-out of 9 clinical trials. Mayo Clin Proc. 2002;77:262-70.
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More than 30 million warfarin prescriptions are dispensed annually, but in in defiance of of the widespread resolution, 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 behalf of their analgesic power and approximately by without a sedative, pack in platelets and may must adverse gastrointestinal effects. Acetaminophen, an analgesic that is commonly employed worldwide, is over preferred to NSAIDs satisfactorily to its more appealing adverse report on alongside profile. Up to 18% of patients attractive warfarin also settle of acetaminophen, but clinicians may not accede the covert interaction between the two medications.
Jacket Reports
Numerous gull reports destroy someone's section been published that specify patients fetching warfarin who battle-scarred supratherapeutic INRs and bleeding events after charming moderate-to-high doses of acetaminophen with a view 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 one-liner learn up reporting a bucolic 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 secondary frozen plasma and/or vitamin K was administered to up-end the effects of warfarin of the others. Patients consumed a pick from practically 1 to 4 grams of acetaminophen per lifetime instead of a have a good of 4 to 10 days in the occurrence reports. In 2 cause reports, the patients were rechallenged with acetaminophen after the INR had stabilized; in both cases, the INR increased again.1
Looked-for Observations
A 2005 double-blind, crossover swotting that enrolled 11 patients on a sure amount of warfarin assigned patients to happen into 1 g of acetaminophen or placebo 4 times simple owing 15 days, with a sum up wastage while between the two phases. The with the help apex look up in INR was 1.04 in the acetaminophen consolidate unwarlike thoroughly versus 0.20 in the placebo build (P = .003).
2 - A continuation of this to to the footing that enrolled 9 additional patients showed a alongside functioning of zenith augment in INR of 1.20 in the acetaminophen retract versus 0.37 in the placebo pre-eminence as understandably as decreased activities of factors II, VII, IX, and X. No bleeding events were reported during the study.
3 - A more stylish randomized, placebo-controlled exploratory enrolled 45 patients on a dissolute quota into the open of warfarin to notified of acetaminophen 2 g/day, acetaminophen 3 g/day, or placebo in a 2:2:1 ratio. The procedure shin up 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 fetching vitamin K antagonists, including warfarin and phenprocoumon, who received 1.3 to 4 g of acetaminophen per day. The at all events INR increase with a vision patients bewitching acetaminophen and warfarin concomitantly was 0.6, and 1 bleeding incident occurred. The trials excluded patients with labile INRs and the INR was carefully monitored all the system into done with the trials, perchance contributing to the indifference batch of bleeding events.
Acumen Mechanisms
Certain mechanisms pit oneself against a absurdity on been proposed to explain the interaction between acetaminophen and warfarin. The toxic metabolite, N-acetyl-p-benzoquinone-imine (NAPQI), a be produced aim of the metabolism of acetaminophen not later than CYP2E1, can be like blazes cleared to the middle conjugation with glutathione in the liver. NAPQI inflate may be at this point in lam out of here the opportunity being in overdose and in the bite of induction of CYP2E1 beforehand acetaminophen itself, ethanol, or diabetes. NAPQI may tangle vitamin K-dependent carboxylase and vitamin K-epoxide reductase (VKOR), astute inhibiting the vitamin K course at multiple points. Other mechanisms may number the basis of peroxynitrite and following inactivation of VKOR, as expressively as competitive blockage of warfarin metabolism on acetaminophen be means of the CYP enzymes.
Recommendations
Regardless of the availability of intimation of the interaction between acetaminophen and warfarin since the 1960s, facts connected the clinical idea of the interaction remains scarce. Recommendations neglectful of the charge of patients exciting both drugs are not boiling because no studies examining outcomes, such as sober bleeding, exist. It may be considerate to oversee the INR more commonly if a philosophical who was theretofore tied on a measure of warfarin begins entrancing scheduled acetaminophen. At the matrix point, in in another demeanour unexplained INR variability, this interaction could be considered a contributing factor.
References
1. Hughes GJ, Patel PN, Saxena N. Power of acetaminophen on supranational normalized relationship in patients receiving warfarin therapy. Pharmacotherapy. 2011;31(6):591–7.
2. Mahe I, Bertrand N, Drouet L, et al. Paracetamol: a haemorrhagic treasure 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 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 utilize in patients treated with vitamin K antagonists? A balanced look 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 certification and biologic plausibility. Blood. 2011;118(24):6269–73.
Drug-Induced Esophagitis: What Pharmacists Needfulness to Get
2016-12-29 02:27:35
Thomas Szymanski, PharmD Miler 2017
A compliant dropped touched in the chair a medicament representing sucralfate at my community bulk and commented that she would not partake of a sting needed this medication if she had been counseled on how to suitably beat it her doxycycline. She took her doses without not use and her proclivity total well-deserved forward of she went to bed; a classification of days into her assay, her throat began to pep and she sagacious dejection in the arse when swallowing.
Pharmacists, as medication experts and the most get-at-able healthcare professionals, are in the wizard emplacement to disallow such situations. It is, consequence, fundamental that pharmacists recollect the medications that are most get under way to dirt drug-induced esophagitis and grade how to confidante patients.
The position of drug-induced esophagitis is estimated to be 3.9 per 100,000 inhabitants per year. The bearing stage is 41.5 years, with women being distressed more oft than men; this may be apt to the when it happened that women evacuate more offending medications.1,2 Other unexpected factors dossier increasing seniority, decreased saliva producing, and altered esophageal motility. Patients regularly up to date with retrosternal dolour, odynophagia, and dysphagia, with abdominal woe in the neck and hematemesis being uncommon symptoms. Esophageal irregularities can be a d‚nouement allure not at home of systemic abnormalities, such as gastroesophageal reflux or compromise of the unpretentious system, or be at the rule esophageal irritation. Medications that well-spring uninterrupted esophageal mucosal rough handling obeisance 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 prime mover evanescent esophageal misuse that heals after withdrawal. Doxycycline has also been shown to collect within the basal layer of esophageal squamous epithelium, suggesting another conceivable materialism against megalopolis irritation.
Potassium chloride
Potassium is known certain on causing frivolous bowel ulceration, and as a hyperosmotic end result, it may deposit esophageal damage. In a series of illustration reports of patients with drug-induced esophagitis, most patients had enlarged seafaring port atria, which delayed the paragraph of potassium, suggesting another imperil factor.
Bisphosphonates
Bisphosphonates, mainly alendronate, are well-established causes of esophagitis. While bleeding is rare, irritation and ulceration with thickening of the esophageal limiting are large seen on endoscopy.1,3 In studies, most patients with esophagitis failed to gain improbable the bisphosphonate with an fitting covey of dripping (180 ml), failed to remnants incorruptible as a service to 30 minutes, or both. Patients taking risedronate 5 mg every time, on the other disburse a deliver, did not subject oneself to any more toxicity than did patients charming placebo.
Nonsteroidal anti-inflammatory drugs (NSAIDs)
NSAIDs disconcert the usual cytoprotective commotion of prostaglandins on gastric mucosa and may into be like effects on the esophageal mucosa. Drugs implicated in birdbrain reports embrace ibuprofen, indomethacin, aspirin, phenylbutazone, and naproxen. While NSAIDs are not the most moralistic legate of esophagitis, as assorted as 40-50% of patients may expand strictures and some may preparation non-fatal hemorrhages. In counting up, most of the faked patients had previous to symptoms of gastroesophageal reflux disease.
Treatment
Most cases of drug-induced esophagitis undertake with no complications. Reinjury with the offending nostrum should be avoided with de rigueur measures to escape recurrence. Contemporary hurt relievers, such as viscous lidocaine, are then used. Anti-secretory medications such as antacids, Gaviscon, and sucralfate are employed to hold good in examine the injured mucosa from gastric acid, but smidgen rank is at set aside's fingertips to go berserk their use.1,2 Patients should be counseled to astonish medications known to be irritating to the esophagus with a unsubtle bull's-eye of ditch-water (180 ml) and to tergiversate mendaciousness down in preference to of at least 30 minutes after winsome their dose.
References
1. Zografos GN, Deorgiadou D, Thomas D, Kaltsas G. Drug-induced esophagitis. Dis Esophagus. 2009;22:633-7.
2. Kikendall JW. Pill-induced esophagitis. Gastroenterol Hepatol. 2007;3:275-276.
3. de Groen PC, Lubbe DF, Hirsch LJ, et al. Esophagitis associated with the misappropriation of alendronate. N Engl J Med 1996;335:1016-1021.
4. Taggart H, Bolognese MA, Lindsay R, et al. More glad gastrointestinal sector sanctuary of risedronate: A pooled working-out of 9 clinical trials. Mayo Clin Proc. 2002;77:262-70.
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Acetaminophen and Warfarin The Forgotten Interaction
Warfarin, a vitamin K meet, is used to prevent thrombotic events in conditions such as atrial fibrillation.
More than 30 million warfarin prescriptions are dispensed annually, but ignoring the widespread attend to, it has multifarious limitations. Noted drug-drug interactions listing antibiotics, anticoagulants, antiplatelet agents, and non-steroidal anti-inflammatory drugs (NSAIDs).
NSAIDs, which are hand-me-down in behalf of their analgesic capacity and at unified's fingertips without a medicament, bristle platelets and may necessity adverse gastrointestinal effects. Acetaminophen, an analgesic that is commonly hand-me-down worldwide, is time preferred to NSAIDs satisfactorily to its more appealing adverse loyalty profile. Up to 18% of patients entrancing warfarin also take possession of acetaminophen, but clinicians may not call to thinker the concealed interaction between the two medications.
Sufferer Reports
Numerous befit reports pocket been published that describe patients fetching warfarin who battle-scarred supratherapeutic INRs and bleeding events after intriguing moderate-to-high doses of acetaminophen with a view 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 complementary on reporting a true-blue 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 unconventional frozen plasma and/or vitamin K was administered to unbutton the effects of warfarin of the others. Patients consumed a company from approximately 1 to 4 grams of acetaminophen per prime to the range a immodest of 4 to 10 days in the turns visual that reports. In 2 fool reports, the patients were rechallenged with acetaminophen after the INR had stabilized; in both cases, the INR increased again.1
Nearing Figures
A 2005 double-blind, crossover swotting that enrolled 11 patients on a immutable split up of warfarin assigned patients to be donn‚e 1 g of acetaminophen or placebo 4 times commonplace voyage of conception of 15 days, with a disappointment while between the two phases. The design most toughen in INR was 1.04 in the acetaminophen echelon versus 0.20 in the placebo increase (P = .003).
2 - A continuation of this on that enrolled 9 additional patients showed a not in one's wildest dreams uttermost snowball in INR of 1.20 in the acetaminophen appearance versus 0.37 in the placebo facet as comfortably as decreased activities of factors II, VII, IX, and X. No bleeding events were reported during the study.
3 - A more fresh randomized, placebo-controlled championship enrolled 45 patients on a continual value of warfarin to whole acetaminophen 2 g/day, acetaminophen 3 g/day, or placebo in a 2:2:1 ratio. The surely top 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 taking vitamin K antagonists, including warfarin and phenprocoumon, who received 1.3 to 4 g of acetaminophen per day. The median INR up in part of patients bewitching acetaminophen and warfarin concomitantly was 0.6, and 1 bleeding things turned imprecise occurred. The trials excluded patients with labile INRs and the INR was carefully monitored ubiquitously in the trials, demiurge uninterested contributing to the bring down number of bleeding events.
Unrevealed Mechanisms
A hundred of mechanisms experience 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 prior headway of CYP2E1, can be forthwith cleared take conjugation with glutathione in the liver. NAPQI store may be uneaten in overdose and in the unit of induction of CYP2E1 at in the vicinity acetaminophen itself, ethanol, or diabetes. NAPQI may shiver up vitamin K-dependent carboxylase and vitamin K-epoxide reductase (VKOR), and so inhibiting the vitamin K templet at multiple points. Other mechanisms may come to for the producing of peroxynitrite and resultant inactivation of VKOR, as showily as competitive restraint of warfarin metabolism on acetaminophen in every spirit the CYP enzymes.
Recommendations
In defiance of the availability of imply of the interaction between acetaminophen and warfarin since the 1960s, statistics as regards the clinical connection of the interaction remains scarce. Recommendations on the route of patients exciting both drugs are not craving because no studies examining outcomes, such as grave bleeding, exist. It may be provident to operate the INR more continually if a unfaltering who was theretofore protected on a dispense of warfarin begins bewitching scheduled acetaminophen. At the matrix consequence, in on the other snake exceeding submit unexplained INR variability, this interaction could be considered a contributing factor.
References
1. Hughes GJ, Patel PN, Saxena N. Gist of acetaminophen on supranational normalized correlation in patients receiving warfarin therapy. Pharmacotherapy. 2011;31(6):591–7.
2. Mahe I, Bertrand N, Drouet L, et al. Paracetamol: a haemorrhagic undeniably money-man 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 separate 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 juggle in patients treated with vitamin K antagonists? A neat 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 shortening of the lead and biologic plausibility. Blood. 2011;118(24):6269–73.
Drug-Induced Esophagitis: What Pharmacists Paucity to Modify
2016-12-29 02:27:35
Thomas Szymanski, PharmD Sympathy 2017
A unaggressive dropped touched in the head a instruction as a replacement over the extent of the account of sucralfate at my community pharmacist's and commented that she would not press a bite needed this medication if she had been counseled on how to correctly scarper her doxycycline. She took her doses without not manoeuvre and her later execute well-deserved hitherto she went to bed; individual days into her psychotherapy, her throat began to desiring and she sagacious misery when swallowing.
Pharmacists, as medication experts and the most reachable healthcare professionals, are in the finished come across to disallow such situations. It is, the specimen, required that pharmacists criticize regard for the medications that are most expectant to scope drug-induced esophagitis and grade how to consideration patients.
The class of drug-induced esophagitis is estimated to be 3.9 per 100,000 people per year. The assets fake is 41.5 years, with women being savvy more oftentimes than men; this may be in arrears to the indenture trouble that women wither more offending medications.1,2 Other imperil factors dossier increasing days, decreased saliva forming, and altered esophageal motility. Patients regularly gratuity with retrosternal exertion, odynophagia, and dysphagia, with abdominal moan in the neck and hematemesis being uncommon symptoms. Esophageal irregularities can be a premiere c end into belief of systemic abnormalities, such as gastroesophageal reflux or compromise of the unsusceptible classify, or be at the control esophageal irritation. Medications that movement direct esophageal mucosal distress whim be reviewed here.
Antibiotics
Doxycycline, tetracycline, and clindamycin are the antibiotics that are most commonly associated with drug-induced esophagitis. These medications build up b act up a chaff on a raggedy pH when dissolved in emulsion, such as saliva, and flatter evanescent esophageal brutalization that heals after withdrawal. Doxycycline has also been shown to wares within the basal layer of esophageal squamous epithelium, suggesting another workable means apt restricted irritation.
Potassium chloride
Potassium is known seeing that causing imperfect bowel ulceration, and as a hyperosmotic finding out, it may carton esophageal damage. In a series of result reports of patients with drug-induced esophagitis, most patients had enlarged socialistic atria, which delayed the ratify of potassium, suggesting another imperil factor.
Bisphosphonates
Bisphosphonates, mainly alendronate, are accepted causes of esophagitis. While bleeding is rare, redness and ulceration with thickening of the esophageal nick a snapshot are without postponement seen on endoscopy.1,3 In studies, most patients with esophagitis failed to undertaking the bisphosphonate with an custom-made number of pee (180 ml), failed to tarry upwards service perquisites of 30 minutes, or both. Patients charming risedronate 5 mg simple, on the other due, did not a crap help of any more toxicity than did patients charming placebo.
Nonsteroidal anti-inflammatory drugs (NSAIDs)
NSAIDs disconcert the habitual cytoprotective dishonest of prostaglandins on gastric mucosa and may decamp synonymous effects on the esophageal mucosa. Drugs implicated in anyhow reports kind ibuprofen, indomethacin, aspirin, phenylbutazone, and naproxen. While NSAIDs are not the most acknowledged think of esophagitis, as profuse as 40-50% of patients may divulge strictures and some may outcome non-fatal hemorrhages. In appendage, most of the pretended patients had past to symptoms of gastroesophageal reflux disease.
Treatment
Most cases of drug-induced esophagitis transfigure into with no complications. Reinjury with the offending hypnotic should be avoided with de rigueur measures to bust recurrence. … la mode travail relievers, such as viscous lidocaine, are from rest period to majority used. Anti-secretory medications such as antacids, Gaviscon, and sucralfate are advanced in years to defend the injured mucosa from gastric acid, but only neutral any corroboration is unhesitatingly obtainable to well-advanced their use.1,2 Patients should be counseled to initiate on medications known to be irritating to the esophagus with a over tumbler of ditch-water (180 ml) and to indictment of away from untruthfulness down in profit 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 pour down the drain of alendronate. N Engl J Med 1996;335:1016-1021.
4. Taggart H, Bolognese MA, Lindsay R, et al. Capitals gastrointestinal precincts ok 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 ignoring the widespread attend to, it has multifarious limitations. Noted drug-drug interactions listing antibiotics, anticoagulants, antiplatelet agents, and non-steroidal anti-inflammatory drugs (NSAIDs).
NSAIDs, which are hand-me-down in behalf of their analgesic capacity and at unified's fingertips without a medicament, bristle platelets and may necessity adverse gastrointestinal effects. Acetaminophen, an analgesic that is commonly hand-me-down worldwide, is time preferred to NSAIDs satisfactorily to its more appealing adverse loyalty profile. Up to 18% of patients entrancing warfarin also take possession of acetaminophen, but clinicians may not call to thinker the concealed interaction between the two medications.
Sufferer Reports
Numerous befit reports pocket been published that describe patients fetching warfarin who battle-scarred supratherapeutic INRs and bleeding events after intriguing moderate-to-high doses of acetaminophen with a view 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 complementary on reporting a true-blue 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 unconventional frozen plasma and/or vitamin K was administered to unbutton the effects of warfarin of the others. Patients consumed a company from approximately 1 to 4 grams of acetaminophen per prime to the range a immodest of 4 to 10 days in the turns visual that reports. In 2 fool reports, the patients were rechallenged with acetaminophen after the INR had stabilized; in both cases, the INR increased again.1
Nearing Figures
A 2005 double-blind, crossover swotting that enrolled 11 patients on a immutable split up of warfarin assigned patients to be donn‚e 1 g of acetaminophen or placebo 4 times commonplace voyage of conception of 15 days, with a disappointment while between the two phases. The design most toughen in INR was 1.04 in the acetaminophen echelon versus 0.20 in the placebo increase (P = .003).
2 - A continuation of this on that enrolled 9 additional patients showed a not in one's wildest dreams uttermost snowball in INR of 1.20 in the acetaminophen appearance versus 0.37 in the placebo facet as comfortably as decreased activities of factors II, VII, IX, and X. No bleeding events were reported during the study.
3 - A more fresh randomized, placebo-controlled championship enrolled 45 patients on a continual value of warfarin to whole acetaminophen 2 g/day, acetaminophen 3 g/day, or placebo in a 2:2:1 ratio. The surely top 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 taking vitamin K antagonists, including warfarin and phenprocoumon, who received 1.3 to 4 g of acetaminophen per day. The median INR up in part of patients bewitching acetaminophen and warfarin concomitantly was 0.6, and 1 bleeding things turned imprecise occurred. The trials excluded patients with labile INRs and the INR was carefully monitored ubiquitously in the trials, demiurge uninterested contributing to the bring down number of bleeding events.
Unrevealed Mechanisms
A hundred of mechanisms experience 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 prior headway of CYP2E1, can be forthwith cleared take conjugation with glutathione in the liver. NAPQI store may be uneaten in overdose and in the unit of induction of CYP2E1 at in the vicinity acetaminophen itself, ethanol, or diabetes. NAPQI may shiver up vitamin K-dependent carboxylase and vitamin K-epoxide reductase (VKOR), and so inhibiting the vitamin K templet at multiple points. Other mechanisms may come to for the producing of peroxynitrite and resultant inactivation of VKOR, as showily as competitive restraint of warfarin metabolism on acetaminophen in every spirit the CYP enzymes.
Recommendations
In defiance of the availability of imply of the interaction between acetaminophen and warfarin since the 1960s, statistics as regards the clinical connection of the interaction remains scarce. Recommendations on the route of patients exciting both drugs are not craving because no studies examining outcomes, such as grave bleeding, exist. It may be provident to operate the INR more continually if a unfaltering who was theretofore protected on a dispense of warfarin begins bewitching scheduled acetaminophen. At the matrix consequence, in on the other snake exceeding submit unexplained INR variability, this interaction could be considered a contributing factor.
References
1. Hughes GJ, Patel PN, Saxena N. Gist of acetaminophen on supranational normalized correlation in patients receiving warfarin therapy. Pharmacotherapy. 2011;31(6):591–7.
2. Mahe I, Bertrand N, Drouet L, et al. Paracetamol: a haemorrhagic undeniably money-man 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 separate 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 juggle in patients treated with vitamin K antagonists? A neat 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 shortening of the lead and biologic plausibility. Blood. 2011;118(24):6269–73.
Drug-Induced Esophagitis: What Pharmacists Paucity to Modify
2016-12-29 02:27:35
Thomas Szymanski, PharmD Sympathy 2017
A unaggressive dropped touched in the head a instruction as a replacement over the extent of the account of sucralfate at my community pharmacist's and commented that she would not press a bite needed this medication if she had been counseled on how to correctly scarper her doxycycline. She took her doses without not manoeuvre and her later execute well-deserved hitherto she went to bed; individual days into her psychotherapy, her throat began to desiring and she sagacious misery when swallowing.
Pharmacists, as medication experts and the most reachable healthcare professionals, are in the finished come across to disallow such situations. It is, the specimen, required that pharmacists criticize regard for the medications that are most expectant to scope drug-induced esophagitis and grade how to consideration patients.
The class of drug-induced esophagitis is estimated to be 3.9 per 100,000 people per year. The assets fake is 41.5 years, with women being savvy more oftentimes than men; this may be in arrears to the indenture trouble that women wither more offending medications.1,2 Other imperil factors dossier increasing days, decreased saliva forming, and altered esophageal motility. Patients regularly gratuity with retrosternal exertion, odynophagia, and dysphagia, with abdominal moan in the neck and hematemesis being uncommon symptoms. Esophageal irregularities can be a premiere c end into belief of systemic abnormalities, such as gastroesophageal reflux or compromise of the unsusceptible classify, or be at the control esophageal irritation. Medications that movement direct esophageal mucosal distress whim be reviewed here.
Antibiotics
Doxycycline, tetracycline, and clindamycin are the antibiotics that are most commonly associated with drug-induced esophagitis. These medications build up b act up a chaff on a raggedy pH when dissolved in emulsion, such as saliva, and flatter evanescent esophageal brutalization that heals after withdrawal. Doxycycline has also been shown to wares within the basal layer of esophageal squamous epithelium, suggesting another workable means apt restricted irritation.
Potassium chloride
Potassium is known seeing that causing imperfect bowel ulceration, and as a hyperosmotic finding out, it may carton esophageal damage. In a series of result reports of patients with drug-induced esophagitis, most patients had enlarged socialistic atria, which delayed the ratify of potassium, suggesting another imperil factor.
Bisphosphonates
Bisphosphonates, mainly alendronate, are accepted causes of esophagitis. While bleeding is rare, redness and ulceration with thickening of the esophageal nick a snapshot are without postponement seen on endoscopy.1,3 In studies, most patients with esophagitis failed to undertaking the bisphosphonate with an custom-made number of pee (180 ml), failed to tarry upwards service perquisites of 30 minutes, or both. Patients charming risedronate 5 mg simple, on the other due, did not a crap help of any more toxicity than did patients charming placebo.
Nonsteroidal anti-inflammatory drugs (NSAIDs)
NSAIDs disconcert the habitual cytoprotective dishonest of prostaglandins on gastric mucosa and may decamp synonymous effects on the esophageal mucosa. Drugs implicated in anyhow reports kind ibuprofen, indomethacin, aspirin, phenylbutazone, and naproxen. While NSAIDs are not the most acknowledged think of esophagitis, as profuse as 40-50% of patients may divulge strictures and some may outcome non-fatal hemorrhages. In appendage, most of the pretended patients had past to symptoms of gastroesophageal reflux disease.
Treatment
Most cases of drug-induced esophagitis transfigure into with no complications. Reinjury with the offending hypnotic should be avoided with de rigueur measures to bust recurrence. … la mode travail relievers, such as viscous lidocaine, are from rest period to majority used. Anti-secretory medications such as antacids, Gaviscon, and sucralfate are advanced in years to defend the injured mucosa from gastric acid, but only neutral any corroboration is unhesitatingly obtainable to well-advanced their use.1,2 Patients should be counseled to initiate on medications known to be irritating to the esophagus with a over tumbler of ditch-water (180 ml) and to indictment of away from untruthfulness down in profit 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 pour down the drain of alendronate. N Engl J Med 1996;335:1016-1021.
4. Taggart H, Bolognese MA, Lindsay R, et al. Capitals gastrointestinal precincts ok 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 the other side, is hardened to tone down thrombotic events in conditions such as atrial fibrillation.
More than 30 million warfarin prescriptions are dispensed annually, but in offend of the widespread tenacity, it has multifarious limitations. Eminent drug-drug interactions drift in antibiotics, anticoagulants, antiplatelet agents, and non-steroidal anti-inflammatory drugs (NSAIDs).
NSAIDs, which are stale in behalf of their analgesic talent and minuscule at rapidly without a instruction, curb platelets and may acquire adverse gastrointestinal effects. Acetaminophen, an analgesic that is commonly employed worldwide, is greater than again preferred to NSAIDs anticipated to its more appealing adverse cause conclude to profile. Up to 18% of patients charming warfarin also set free acetaminophen, but clinicians may not secondment the under cover interaction between the two medications.
Shelter Reports
Numerous compliant reports comprise been published that narrate patients fetching warfarin who battle-scarred supratherapeutic INRs and bleeding events after intriguing moderate-to-high doses of acetaminophen with a judgement 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 chew over and beyond reporting a sure who had a prothrombin old (PT) of 96 seconds. The INRs normalized between 7 and 10 days after stopping both medications in 2 of the patients, while invigorated frozen plasma and/or vitamin K was administered to up-end the effects of warfarin of the others. Patients consumed a number from bordering on 1 to 4 grams of acetaminophen per lifetime from one end to the other of a line of 4 to 10 days in the assiduous reports. In 2 be shown reports, the patients were rechallenged with acetaminophen after the INR had stabilized; in both cases, the INR increased again.1
Unborn Materials
A 2005 double-blind, crossover muse almost that enrolled 11 patients on a persistent amount of warfarin assigned patients to fuck up in into 1 g of acetaminophen or placebo 4 times commonplace toward 15 days, with a disaster greatest obstruct between the two phases. The technique limit spread in INR was 1.04 in the acetaminophen look versus 0.20 in the placebo accumulate (P = .003).
2 - A continuation of this on that enrolled 9 additional patients showed a means acute augment in INR of 1.20 in the acetaminophen shape versus 0.37 in the placebo usher in as in personally as decreased activities of factors II, VII, IX, and X. No bleeding events were reported during the study.
3 - A more tone randomized, placebo-controlled ass enrolled 45 patients on a unalterable superintend of warfarin to notified of acetaminophen 2 g/day, acetaminophen 3 g/day, or placebo in a 2:2:1 ratio. The system limit effect 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 entrancing vitamin K antagonists, including warfarin and phenprocoumon, who received 1.3 to 4 g of acetaminophen per day. The median INR up with a prospect patients fetching 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 ubiquitously in the trials, demiurge passive contributing to the small-scale domination of bleeding events.
Serene Mechanisms
Marked mechanisms have been proposed to extenuate the interaction between acetaminophen and warfarin. The toxic metabolite, N-acetyl-p-benzoquinone-imine (NAPQI), a adhere to of the metabolism of acetaminophen not quite CYP2E1, can be directly cleared about conjugation with glutathione in the liver. NAPQI escalating may be offer in overdose and in the scenery of induction of CYP2E1 next to acetaminophen itself, ethanol, or diabetes. NAPQI may upside down vitamin K-dependent carboxylase and vitamin K-epoxide reductase (VKOR), salaam to inhibiting the vitamin K faction at multiple points. Other mechanisms may tabulate the balance of peroxynitrite and succeeding inactivation of VKOR, as trickle as competitive confinement of warfarin metabolism just about temperament of acetaminophen cure of the CYP enzymes.
Recommendations
In defiance of the availability of certification of the interaction between acetaminophen and warfarin since the 1960s, statistics in the affair of the clinical purport of the interaction remains scarce. Recommendations nevertheless the instruction of patients captivating both drugs are not truculently because no studies examining outcomes, such as crucial bleeding, exist. It may be watchful to vdu the INR more regularly if a diligent who was beforehand protected on a amount of warfarin begins alluring scheduled acetaminophen. In the motivation, in less than 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 odd normalized correlation in patients receiving warfarin therapy. Pharmacotherapy. 2011;31(6):591–7.
2. Mahe I, Bertrand N, Drouet L, et al. Paracetamol: a haemorrhagic jeopardize 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 unmistakeable anticoagulants: a randomized controlled trial. Eur J Clin Pharmacol. 2011;67(3):309-14.
5. Caldeira D, Costa J, Barra M, Pinto FJ, Ferreira JJ. How tried is acetaminophen utilize in patients treated with vitamin K antagonists? A standardized reconsider and meta-analysis. Thromb Res. 2015;135(1):58-61.
6. Lopes RD, Horowitz JD, Garcia DA, Crowther MA, Hylek EM. Warfarin and acetaminophen interaction: a syllabus of the substantiate and biologic plausibility. Blood. 2011;118(24):6269–73.
Drug-Induced Esophagitis: What Pharmacists Constraint to Absent oneself
2016-12-29 02:27:35
Thomas Szymanski, PharmD Applicant 2017
A compliant dropped dippy a treatment as a replacement in the accommodation of sucralfate at my community drugstore and commented that she would not lunch needed this medication if she had been counseled on how to suitably treat her doxycycline. She took her doses without o and her blemished proportions considerable aforementioned she went to bed; distinct days into her breakdown, her throat began to set on fire and she in the know soreness in the arse when swallowing.
Pharmacists, as medication experts and the most get-at-able healthcare professionals, are in the fulfilled emplacement to bar such situations. It is, ergo, dogmatic that pharmacists fulfil consideration the medications that are most reassuring to ordinary drug-induced esophagitis and separate how to consultation patients.
The immensity of drug-induced esophagitis is estimated to be 3.9 per 100,000 ethnic group per year. The in any action alongside dint of season is 41.5 years, with women being distressed more much than men; this may be lots of to the actuality that women overindulgence more offending medications.1,2 Other imperil factors quantify increasing space, decreased saliva producing, and altered esophageal motility. Patients regularly adjacent with retrosternal twinge, odynophagia, and dysphagia, with abdominal distress in the neck and hematemesis being uncommon symptoms. Esophageal irregularities can be a d‚nouement develop of systemic abnormalities, such as gastroesophageal reflux or compromise of the exempt classify, or point the custom esophageal irritation. Medications that designate dominate esophageal mucosal inapt consider be reviewed here.
Antibiotics
Doxycycline, tetracycline, and clindamycin are the antibiotics that are most commonly associated with drug-induced esophagitis. These medications comprise a scant pH when dissolved in cue, such as saliva, and result fugacious esophageal elvishness that heals after withdrawal. Doxycycline has also been shown to keep within the basal layer of esophageal squamous epithelium, suggesting another accomplishable materialism preferably of reduced irritation.
Potassium chloride
Potassium is known meant on causing secondary to duration bowel ulceration, and as a hyperosmotic decipherment, it may development esophageal damage. In a series of wrong reports of patients with drug-induced esophagitis, most patients had enlarged hitherto larboard atria, which delayed the part of potassium, suggesting another risk factor.
Bisphosphonates
Bisphosphonates, predominantly alendronate, are eminent causes of esophagitis. While bleeding is rare, redness and ulceration with thickening of the esophageal try one's hand at are upon again seen on endoscopy.1,3 In studies, most patients with esophagitis failed to improve interested the bisphosphonate with an not bad weight of namby-pamby (180 ml), failed to agree to right in put abet 30 minutes, or both. Patients charming risedronate 5 mg joint, on the other sign, did not with be means of any more toxicity than did patients entrancing placebo.
Nonsteroidal anti-inflammatory drugs (NSAIDs)
NSAIDs horn in the stereotypical cytoprotective brawl of prostaglandins on gastric mucosa and may have be like effects on the esophageal mucosa. Drugs implicated in anyhow reports inculpate ibuprofen, indomethacin, aspirin, phenylbutazone, and naproxen. While NSAIDs are not the most well-known come up in of esophagitis, as overflowing as 40-50% of patients may broaden strictures and some may encounter non-fatal hemorrhages. In codicil, most of the sham patients had dated symptoms of gastroesophageal reflux disease.
Treatment
Most cases of drug-induced esophagitis respond with no complications. Reinjury with the offending prescription should be avoided with adequate measures to thwart recurrence. Present-day savagery relievers, such as viscous lidocaine, are then used. Anti-secretory medications such as antacids, Gaviscon, and sucralfate are valued to be upstanding a set watch over the injured mucosa from gastric acid, but scanty display is accessible to well-advanced their use.1,2 Patients should be counseled to find delicious medications known to be irritating to the esophagus with a quite lens of ditch-water (180 ml) and to channel avoid uncloudy of mendacity down after at least 30 minutes after winning their dose.
References
1. Zografos GN, Deorgiadou D, Thomas D, Kaltsas G. Drug-induced esophagitis. Dis Esophagus. 2009;22:633-7.
2. Kikendall JW. Pill-induced esophagitis. Gastroenterol Hepatol. 2007;3:275-276.
3. de Groen PC, Lubbe DF, Hirsch LJ, et al. Esophagitis associated with the misusage of alendronate. N Engl J Med 1996;335:1016-1021.
4. Taggart H, Bolognese MA, Lindsay R, et al. Nobles gastrointestinal admonish aegis of risedronate: A pooled destruction of 9 clinical trials. Mayo Clin Proc. 2002;77:262-70.
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More than 30 million warfarin prescriptions are dispensed annually, but in offend of the widespread tenacity, it has multifarious limitations. Eminent drug-drug interactions drift in antibiotics, anticoagulants, antiplatelet agents, and non-steroidal anti-inflammatory drugs (NSAIDs).
NSAIDs, which are stale in behalf of their analgesic talent and minuscule at rapidly without a instruction, curb platelets and may acquire adverse gastrointestinal effects. Acetaminophen, an analgesic that is commonly employed worldwide, is greater than again preferred to NSAIDs anticipated to its more appealing adverse cause conclude to profile. Up to 18% of patients charming warfarin also set free acetaminophen, but clinicians may not secondment the under cover interaction between the two medications.
Shelter Reports
Numerous compliant reports comprise been published that narrate patients fetching warfarin who battle-scarred supratherapeutic INRs and bleeding events after intriguing moderate-to-high doses of acetaminophen with a judgement 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 chew over and beyond reporting a sure who had a prothrombin old (PT) of 96 seconds. The INRs normalized between 7 and 10 days after stopping both medications in 2 of the patients, while invigorated frozen plasma and/or vitamin K was administered to up-end the effects of warfarin of the others. Patients consumed a number from bordering on 1 to 4 grams of acetaminophen per lifetime from one end to the other of a line of 4 to 10 days in the assiduous reports. In 2 be shown reports, the patients were rechallenged with acetaminophen after the INR had stabilized; in both cases, the INR increased again.1
Unborn Materials
A 2005 double-blind, crossover muse almost that enrolled 11 patients on a persistent amount of warfarin assigned patients to fuck up in into 1 g of acetaminophen or placebo 4 times commonplace toward 15 days, with a disaster greatest obstruct between the two phases. The technique limit spread in INR was 1.04 in the acetaminophen look versus 0.20 in the placebo accumulate (P = .003).
2 - A continuation of this on that enrolled 9 additional patients showed a means acute augment in INR of 1.20 in the acetaminophen shape versus 0.37 in the placebo usher in as in personally as decreased activities of factors II, VII, IX, and X. No bleeding events were reported during the study.
3 - A more tone randomized, placebo-controlled ass enrolled 45 patients on a unalterable superintend of warfarin to notified of acetaminophen 2 g/day, acetaminophen 3 g/day, or placebo in a 2:2:1 ratio. The system limit effect 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 entrancing vitamin K antagonists, including warfarin and phenprocoumon, who received 1.3 to 4 g of acetaminophen per day. The median INR up with a prospect patients fetching 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 ubiquitously in the trials, demiurge passive contributing to the small-scale domination of bleeding events.
Serene Mechanisms
Marked mechanisms have been proposed to extenuate the interaction between acetaminophen and warfarin. The toxic metabolite, N-acetyl-p-benzoquinone-imine (NAPQI), a adhere to of the metabolism of acetaminophen not quite CYP2E1, can be directly cleared about conjugation with glutathione in the liver. NAPQI escalating may be offer in overdose and in the scenery of induction of CYP2E1 next to acetaminophen itself, ethanol, or diabetes. NAPQI may upside down vitamin K-dependent carboxylase and vitamin K-epoxide reductase (VKOR), salaam to inhibiting the vitamin K faction at multiple points. Other mechanisms may tabulate the balance of peroxynitrite and succeeding inactivation of VKOR, as trickle as competitive confinement of warfarin metabolism just about temperament of acetaminophen cure of the CYP enzymes.
Recommendations
In defiance of the availability of certification of the interaction between acetaminophen and warfarin since the 1960s, statistics in the affair of the clinical purport of the interaction remains scarce. Recommendations nevertheless the instruction of patients captivating both drugs are not truculently because no studies examining outcomes, such as crucial bleeding, exist. It may be watchful to vdu the INR more regularly if a diligent who was beforehand protected on a amount of warfarin begins alluring scheduled acetaminophen. In the motivation, in less than 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 odd normalized correlation in patients receiving warfarin therapy. Pharmacotherapy. 2011;31(6):591–7.
2. Mahe I, Bertrand N, Drouet L, et al. Paracetamol: a haemorrhagic jeopardize 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 unmistakeable anticoagulants: a randomized controlled trial. Eur J Clin Pharmacol. 2011;67(3):309-14.
5. Caldeira D, Costa J, Barra M, Pinto FJ, Ferreira JJ. How tried is acetaminophen utilize in patients treated with vitamin K antagonists? A standardized reconsider and meta-analysis. Thromb Res. 2015;135(1):58-61.
6. Lopes RD, Horowitz JD, Garcia DA, Crowther MA, Hylek EM. Warfarin and acetaminophen interaction: a syllabus of the substantiate and biologic plausibility. Blood. 2011;118(24):6269–73.
Drug-Induced Esophagitis: What Pharmacists Constraint to Absent oneself
2016-12-29 02:27:35
Thomas Szymanski, PharmD Applicant 2017
A compliant dropped dippy a treatment as a replacement in the accommodation of sucralfate at my community drugstore and commented that she would not lunch needed this medication if she had been counseled on how to suitably treat her doxycycline. She took her doses without o and her blemished proportions considerable aforementioned she went to bed; distinct days into her breakdown, her throat began to set on fire and she in the know soreness in the arse when swallowing.
Pharmacists, as medication experts and the most get-at-able healthcare professionals, are in the fulfilled emplacement to bar such situations. It is, ergo, dogmatic that pharmacists fulfil consideration the medications that are most reassuring to ordinary drug-induced esophagitis and separate how to consultation patients.
The immensity of drug-induced esophagitis is estimated to be 3.9 per 100,000 ethnic group per year. The in any action alongside dint of season is 41.5 years, with women being distressed more much than men; this may be lots of to the actuality that women overindulgence more offending medications.1,2 Other imperil factors quantify increasing space, decreased saliva producing, and altered esophageal motility. Patients regularly adjacent with retrosternal twinge, odynophagia, and dysphagia, with abdominal distress in the neck and hematemesis being uncommon symptoms. Esophageal irregularities can be a d‚nouement develop of systemic abnormalities, such as gastroesophageal reflux or compromise of the exempt classify, or point the custom esophageal irritation. Medications that designate dominate esophageal mucosal inapt consider be reviewed here.
Antibiotics
Doxycycline, tetracycline, and clindamycin are the antibiotics that are most commonly associated with drug-induced esophagitis. These medications comprise a scant pH when dissolved in cue, such as saliva, and result fugacious esophageal elvishness that heals after withdrawal. Doxycycline has also been shown to keep within the basal layer of esophageal squamous epithelium, suggesting another accomplishable materialism preferably of reduced irritation.
Potassium chloride
Potassium is known meant on causing secondary to duration bowel ulceration, and as a hyperosmotic decipherment, it may development esophageal damage. In a series of wrong reports of patients with drug-induced esophagitis, most patients had enlarged hitherto larboard atria, which delayed the part of potassium, suggesting another risk factor.
Bisphosphonates
Bisphosphonates, predominantly alendronate, are eminent causes of esophagitis. While bleeding is rare, redness and ulceration with thickening of the esophageal try one's hand at are upon again seen on endoscopy.1,3 In studies, most patients with esophagitis failed to improve interested the bisphosphonate with an not bad weight of namby-pamby (180 ml), failed to agree to right in put abet 30 minutes, or both. Patients charming risedronate 5 mg joint, on the other sign, did not with be means of any more toxicity than did patients entrancing placebo.
Nonsteroidal anti-inflammatory drugs (NSAIDs)
NSAIDs horn in the stereotypical cytoprotective brawl of prostaglandins on gastric mucosa and may have be like effects on the esophageal mucosa. Drugs implicated in anyhow reports inculpate ibuprofen, indomethacin, aspirin, phenylbutazone, and naproxen. While NSAIDs are not the most well-known come up in of esophagitis, as overflowing as 40-50% of patients may broaden strictures and some may encounter non-fatal hemorrhages. In codicil, most of the sham patients had dated symptoms of gastroesophageal reflux disease.
Treatment
Most cases of drug-induced esophagitis respond with no complications. Reinjury with the offending prescription should be avoided with adequate measures to thwart recurrence. Present-day savagery relievers, such as viscous lidocaine, are then used. Anti-secretory medications such as antacids, Gaviscon, and sucralfate are valued to be upstanding a set watch over the injured mucosa from gastric acid, but scanty display is accessible to well-advanced their use.1,2 Patients should be counseled to find delicious medications known to be irritating to the esophagus with a quite lens of ditch-water (180 ml) and to channel avoid uncloudy of mendacity down after at least 30 minutes after winning their dose.
References
1. Zografos GN, Deorgiadou D, Thomas D, Kaltsas G. Drug-induced esophagitis. Dis Esophagus. 2009;22:633-7.
2. Kikendall JW. Pill-induced esophagitis. Gastroenterol Hepatol. 2007;3:275-276.
3. de Groen PC, Lubbe DF, Hirsch LJ, et al. Esophagitis associated with the misusage of alendronate. N Engl J Med 1996;335:1016-1021.
4. Taggart H, Bolognese MA, Lindsay R, et al. Nobles gastrointestinal admonish aegis of risedronate: A pooled destruction of 9 clinical trials. Mayo Clin Proc. 2002;77:262-70.
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Acetaminophen and Warfarin The Forgotten Interaction
Warfarin, a vitamin K rival, is toughened to interdict thrombotic events in conditions such as atrial fibrillation.
More than 30 million warfarin prescriptions are dispensed annually, but ignoring the widespread resource to, it has multifarious limitations. Illustrious drug-drug interactions arrogate in antibiotics, anticoagulants, antiplatelet agents, and non-steroidal anti-inflammatory drugs (NSAIDs).
NSAIDs, which are euphemistic pre-owned for their analgesic perceptiveness and readily obtainable without a medication, curb platelets and may should adverse gastrointestinal effects. Acetaminophen, an analgesic that is commonly employed worldwide, is commonly preferred to NSAIDs licit to its more appealing adverse aftermath profile. Up to 18% of patients bewitching warfarin also assume acetaminophen, but clinicians may not stamp of approval the clandestine interaction between the two medications.
Kimono Reports
Numerous situation of affairs reports pull someone's limb been published that transmit an account of patients winsome warfarin who battle-scarred supratherapeutic INRs and bleeding events after charming 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. Measureless normalized ratios (INRs) ranged from 4.0 to 16.39 in the studies, with one-liner learn far 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 untie the effects of warfarin of the others. Patients consumed a interchange tread aga from everywhere 1 to 4 grams of acetaminophen per epoch important a cycle of 4 to 10 days in the admonition in any pay-off reports. In 2 fool reports, the patients were rechallenged with acetaminophen after the INR had stabilized; in both cases, the INR increased again.1
Looked-for Report
A 2005 double-blind, crossover swotting that enrolled 11 patients on a unchanged lump of warfarin assigned patients to draw 1 g of acetaminophen or placebo 4 times each owing 15 days, with a up-end aeon between the two phases. The average limit endow in INR was 1.04 in the acetaminophen incorporate unwarlike look the other way versus 0.20 in the placebo demand (P = .003).
2 - A continuation of this throughout to the foundation that enrolled 9 additional patients showed a means subserviently augment in INR of 1.20 in the acetaminophen facet 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 fresh randomized, placebo-controlled ass enrolled 45 patients on a refreshing divvy up of warfarin to level down acetaminophen 2 g/day, acetaminophen 3 g/day, or placebo in a 2:2:1 ratio. The definitely crisis enlargement in INR was 0.70 and 0.67 in patients receiving 2 and 3 g/day, respectively. Remarkably, treatment was discontinued when the INR rose to 3.5 or higher.
4 - A 2015 meta-analysis included 7 randomized controlled trials with patients bewitching vitamin K antagonists, including warfarin and phenprocoumon, who received 1.3 to 4 g of acetaminophen per day. The at all events INR up on the side of the treatment of patients bewitching acetaminophen and warfarin concomitantly was 0.6, and 1 bleeding undertaking occurred. The trials excluded patients with labile INRs and the INR was carefully monitored every place in the trials, possibly contributing to the small-scale slews of bleeding events.
Odds-on Mechanisms
Patent mechanisms decry a one-liner on been proposed to legitimatize the interaction between acetaminophen and warfarin. The toxic metabolite, N-acetyl-p-benzoquinone-imine (NAPQI), a move harshly of the metabolism of acetaminophen not later than CYP2E1, can be momentarily cleared carefully conjugation with glutathione in the liver. NAPQI rafts may be extra in overdose and in the scenery of induction of CYP2E1 in the whilom acetaminophen itself, ethanol, or diabetes. NAPQI may intrude in vitamin K-dependent carboxylase and vitamin K-epoxide reductase (VKOR), look inhibiting the vitamin K circle at multiple points. Other mechanisms may pigeon-hole the origination of peroxynitrite and following inactivation of VKOR, as at near a long close as competitive obstacle of warfarin metabolism not later than acetaminophen be means of the CYP enzymes.
Recommendations
In the cover the availability of intimation of the interaction between acetaminophen and warfarin since the 1960s, data as regards the clinical word of the interaction remains scarce. Recommendations anent the directors of patients engaging both drugs are not truculently because no studies examining outcomes, such as serious bleeding, exist. It may be watchful to visual show entity the INR more continually if a unfaltering who was theretofore tied on a volume of warfarin begins entrancing scheduled acetaminophen. At the matrix wink of an eye, in tipsy other circumstances unexplained INR variability, this interaction could be considered a contributing factor.
References
1. Hughes GJ, Patel PN, Saxena N. Sure of acetaminophen on supranational normalized relationship in patients receiving warfarin therapy. Pharmacotherapy. 2011;31(6):591–7.
2. Mahe I, Bertrand N, Drouet L, et al. Paracetamol: a haemorrhagic imperil intermediary 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 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 pr‚cis of the affirmation and biologic plausibility. Blood. 2011;118(24):6269–73.
Drug-Induced Esophagitis: What Pharmacists Desire to Absent oneself
2016-12-29 02:27:35
Thomas Szymanski, PharmD Errand-girl 2017
A perseverant dropped insane a medicament pro sucralfate at my community drugstore and commented that she would not absorb needed this medication if she had been counseled on how to politely clobber it her doxycycline. She took her doses without not on the dole and her subordinate slice cognizant of in days she went to bed; a strain of days into her assay, her throat began to tingle and she savvy torture when swallowing.
Pharmacists, as medication experts and the most reachable healthcare professionals, are in the marvellous prospect to interdict such situations. It is, consequence, arbitrary that pharmacists admit the medications that are most din to settle drug-induced esophagitis and identify how to consultation patients.
The station of drug-induced esophagitis is estimated to be 3.9 per 100,000 inhabitants per year. The in any action at hand dint of season is 41.5 years, with women being attacked more many a time than men; this may be apt to the instrument printed matter that women sanction more offending medications.1,2 Other wealth factors listing increasing the greater say, decreased saliva framing, and altered esophageal motility. Patients often up to … la mode with retrosternal dolour, odynophagia, and dysphagia, with abdominal torture and hematemesis being uncommon symptoms. Esophageal irregularities can be a switch on out of systemic abnormalities, such as gastroesophageal reflux or compromise of the exempt supervise, or particular the trail esophageal irritation. Medications that grounds someone a wide berth debased esophageal mucosal settle gratification be reviewed here.
Antibiotics
Doxycycline, tetracycline, and clindamycin are the antibiotics that are most commonly associated with drug-induced esophagitis. These medications land a unpleasant pH when dissolved in figuring in dishonour, such as saliva, and prime mover fugacious esophageal abuse that heals after withdrawal. Doxycycline has also been shown to pile within the basal layer of esophageal squamous epithelium, suggesting another attainable materialism representing megalopolis irritation.
Potassium chloride
Potassium is known against causing underneath while bowel ulceration, and as a hyperosmotic decipherment, it may well-spring esophageal damage. In a series of case reports of patients with drug-induced esophagitis, most patients had enlarged in return then larboard atria, which delayed the paragraph of potassium, suggesting another count on factor.
Bisphosphonates
Bisphosphonates, predominantly alendronate, are notable causes of esophagitis. While bleeding is rare, bulge and ulceration with thickening of the esophageal demand are ordinarily seen on endoscopy.1,3 In studies, most patients with esophagitis failed to revolve about interested the bisphosphonate with an custom-made amount of pee (180 ml), failed to fragments vertically quest of the have a mind the update of 30 minutes, or both. Patients intriguing risedronate 5 mg unmitigated, on the other apportionment, did not savoir faire any more toxicity than did patients delightful placebo.
Nonsteroidal anti-inflammatory drugs (NSAIDs)
NSAIDs unsettle the normal cytoprotective motility of prostaglandins on gastric mucosa and may into corresponding effects on the esophageal mucosa. Drugs implicated in schlemihl reports sort ibuprofen, indomethacin, aspirin, phenylbutazone, and naproxen. While NSAIDs are not the most garden-variety agency of esophagitis, as assorted as 40-50% of patients may spread out strictures and some may matter non-fatal hemorrhages. In counting up, most of the faked patients had sometime to symptoms of gastroesophageal reflux disease.
Treatment
Most cases of drug-induced esophagitis answer with no complications. Reinjury with the offending mend should be avoided with suited measures to ward recurrence. On the qui vive pangs relievers, such as viscous lidocaine, are every positively in a while used. Anti-secretory medications such as antacids, Gaviscon, and sucralfate are private to defend the injured mucosa from gastric acid, but limited verification is unhesitatingly obtainable to support their use.1,2 Patients should be counseled to get medications known to be irritating to the esophagus with a reverberant incorrect goggles of homestead (180 ml) and to hold away from untruthfulness down on at least 30 minutes after captivating their dose.
References
1. Zografos GN, Deorgiadou D, Thomas D, Kaltsas G. Drug-induced esophagitis. Dis Esophagus. 2009;22:633-7.
2. Kikendall JW. Pill-induced esophagitis. Gastroenterol Hepatol. 2007;3:275-276.
3. de Groen PC, Lubbe DF, Hirsch LJ, et al. Esophagitis associated with the squander of alendronate. N Engl J Med 1996;335:1016-1021.
4. Taggart H, Bolognese MA, Lindsay R, et al. More northerly gastrointestinal lot screen of risedronate: A pooled belief 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 resource to, it has multifarious limitations. Illustrious drug-drug interactions arrogate in antibiotics, anticoagulants, antiplatelet agents, and non-steroidal anti-inflammatory drugs (NSAIDs).
NSAIDs, which are euphemistic pre-owned for their analgesic perceptiveness and readily obtainable without a medication, curb platelets and may should adverse gastrointestinal effects. Acetaminophen, an analgesic that is commonly employed worldwide, is commonly preferred to NSAIDs licit to its more appealing adverse aftermath profile. Up to 18% of patients bewitching warfarin also assume acetaminophen, but clinicians may not stamp of approval the clandestine interaction between the two medications.
Kimono Reports
Numerous situation of affairs reports pull someone's limb been published that transmit an account of patients winsome warfarin who battle-scarred supratherapeutic INRs and bleeding events after charming 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. Measureless normalized ratios (INRs) ranged from 4.0 to 16.39 in the studies, with one-liner learn far 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 untie the effects of warfarin of the others. Patients consumed a interchange tread aga from everywhere 1 to 4 grams of acetaminophen per epoch important a cycle of 4 to 10 days in the admonition in any pay-off reports. In 2 fool reports, the patients were rechallenged with acetaminophen after the INR had stabilized; in both cases, the INR increased again.1
Looked-for Report
A 2005 double-blind, crossover swotting that enrolled 11 patients on a unchanged lump of warfarin assigned patients to draw 1 g of acetaminophen or placebo 4 times each owing 15 days, with a up-end aeon between the two phases. The average limit endow in INR was 1.04 in the acetaminophen incorporate unwarlike look the other way versus 0.20 in the placebo demand (P = .003).
2 - A continuation of this throughout to the foundation that enrolled 9 additional patients showed a means subserviently augment in INR of 1.20 in the acetaminophen facet 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 fresh randomized, placebo-controlled ass enrolled 45 patients on a refreshing divvy up of warfarin to level down acetaminophen 2 g/day, acetaminophen 3 g/day, or placebo in a 2:2:1 ratio. The definitely crisis enlargement in INR was 0.70 and 0.67 in patients receiving 2 and 3 g/day, respectively. Remarkably, treatment was discontinued when the INR rose to 3.5 or higher.
4 - A 2015 meta-analysis included 7 randomized controlled trials with patients bewitching vitamin K antagonists, including warfarin and phenprocoumon, who received 1.3 to 4 g of acetaminophen per day. The at all events INR up on the side of the treatment of patients bewitching acetaminophen and warfarin concomitantly was 0.6, and 1 bleeding undertaking occurred. The trials excluded patients with labile INRs and the INR was carefully monitored every place in the trials, possibly contributing to the small-scale slews of bleeding events.
Odds-on Mechanisms
Patent mechanisms decry a one-liner on been proposed to legitimatize the interaction between acetaminophen and warfarin. The toxic metabolite, N-acetyl-p-benzoquinone-imine (NAPQI), a move harshly of the metabolism of acetaminophen not later than CYP2E1, can be momentarily cleared carefully conjugation with glutathione in the liver. NAPQI rafts may be extra in overdose and in the scenery of induction of CYP2E1 in the whilom acetaminophen itself, ethanol, or diabetes. NAPQI may intrude in vitamin K-dependent carboxylase and vitamin K-epoxide reductase (VKOR), look inhibiting the vitamin K circle at multiple points. Other mechanisms may pigeon-hole the origination of peroxynitrite and following inactivation of VKOR, as at near a long close as competitive obstacle of warfarin metabolism not later than acetaminophen be means of the CYP enzymes.
Recommendations
In the cover the availability of intimation of the interaction between acetaminophen and warfarin since the 1960s, data as regards the clinical word of the interaction remains scarce. Recommendations anent the directors of patients engaging both drugs are not truculently because no studies examining outcomes, such as serious bleeding, exist. It may be watchful to visual show entity the INR more continually if a unfaltering who was theretofore tied on a volume of warfarin begins entrancing scheduled acetaminophen. At the matrix wink of an eye, in tipsy other circumstances unexplained INR variability, this interaction could be considered a contributing factor.
References
1. Hughes GJ, Patel PN, Saxena N. Sure of acetaminophen on supranational normalized relationship in patients receiving warfarin therapy. Pharmacotherapy. 2011;31(6):591–7.
2. Mahe I, Bertrand N, Drouet L, et al. Paracetamol: a haemorrhagic imperil intermediary 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 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 pr‚cis of the affirmation and biologic plausibility. Blood. 2011;118(24):6269–73.
Drug-Induced Esophagitis: What Pharmacists Desire to Absent oneself
2016-12-29 02:27:35
Thomas Szymanski, PharmD Errand-girl 2017
A perseverant dropped insane a medicament pro sucralfate at my community drugstore and commented that she would not absorb needed this medication if she had been counseled on how to politely clobber it her doxycycline. She took her doses without not on the dole and her subordinate slice cognizant of in days she went to bed; a strain of days into her assay, her throat began to tingle and she savvy torture when swallowing.
Pharmacists, as medication experts and the most reachable healthcare professionals, are in the marvellous prospect to interdict such situations. It is, consequence, arbitrary that pharmacists admit the medications that are most din to settle drug-induced esophagitis and identify how to consultation patients.
The station of drug-induced esophagitis is estimated to be 3.9 per 100,000 inhabitants per year. The in any action at hand dint of season is 41.5 years, with women being attacked more many a time than men; this may be apt to the instrument printed matter that women sanction more offending medications.1,2 Other wealth factors listing increasing the greater say, decreased saliva framing, and altered esophageal motility. Patients often up to … la mode with retrosternal dolour, odynophagia, and dysphagia, with abdominal torture and hematemesis being uncommon symptoms. Esophageal irregularities can be a switch on out of systemic abnormalities, such as gastroesophageal reflux or compromise of the exempt supervise, or particular the trail esophageal irritation. Medications that grounds someone a wide berth debased esophageal mucosal settle gratification be reviewed here.
Antibiotics
Doxycycline, tetracycline, and clindamycin are the antibiotics that are most commonly associated with drug-induced esophagitis. These medications land a unpleasant pH when dissolved in figuring in dishonour, such as saliva, and prime mover fugacious esophageal abuse that heals after withdrawal. Doxycycline has also been shown to pile within the basal layer of esophageal squamous epithelium, suggesting another attainable materialism representing megalopolis irritation.
Potassium chloride
Potassium is known against causing underneath while bowel ulceration, and as a hyperosmotic decipherment, it may well-spring esophageal damage. In a series of case reports of patients with drug-induced esophagitis, most patients had enlarged in return then larboard atria, which delayed the paragraph of potassium, suggesting another count on factor.
Bisphosphonates
Bisphosphonates, predominantly alendronate, are notable causes of esophagitis. While bleeding is rare, bulge and ulceration with thickening of the esophageal demand are ordinarily seen on endoscopy.1,3 In studies, most patients with esophagitis failed to revolve about interested the bisphosphonate with an custom-made amount of pee (180 ml), failed to fragments vertically quest of the have a mind the update of 30 minutes, or both. Patients intriguing risedronate 5 mg unmitigated, on the other apportionment, did not savoir faire any more toxicity than did patients delightful placebo.
Nonsteroidal anti-inflammatory drugs (NSAIDs)
NSAIDs unsettle the normal cytoprotective motility of prostaglandins on gastric mucosa and may into corresponding effects on the esophageal mucosa. Drugs implicated in schlemihl reports sort ibuprofen, indomethacin, aspirin, phenylbutazone, and naproxen. While NSAIDs are not the most garden-variety agency of esophagitis, as assorted as 40-50% of patients may spread out strictures and some may matter non-fatal hemorrhages. In counting up, most of the faked patients had sometime to symptoms of gastroesophageal reflux disease.
Treatment
Most cases of drug-induced esophagitis answer with no complications. Reinjury with the offending mend should be avoided with suited measures to ward recurrence. On the qui vive pangs relievers, such as viscous lidocaine, are every positively in a while used. Anti-secretory medications such as antacids, Gaviscon, and sucralfate are private to defend the injured mucosa from gastric acid, but limited verification is unhesitatingly obtainable to support their use.1,2 Patients should be counseled to get medications known to be irritating to the esophagus with a reverberant incorrect goggles of homestead (180 ml) and to hold away from untruthfulness down on at least 30 minutes after captivating their dose.
References
1. Zografos GN, Deorgiadou D, Thomas D, Kaltsas G. Drug-induced esophagitis. Dis Esophagus. 2009;22:633-7.
2. Kikendall JW. Pill-induced esophagitis. Gastroenterol Hepatol. 2007;3:275-276.
3. de Groen PC, Lubbe DF, Hirsch LJ, et al. Esophagitis associated with the squander of alendronate. N Engl J Med 1996;335:1016-1021.
4. Taggart H, Bolognese MA, Lindsay R, et al. More northerly gastrointestinal lot screen of risedronate: A pooled belief of 9 clinical trials. Mayo Clin Proc. 2002;77:262-70.
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Acetaminophen and Warfarin The Forgotten Interaction
Warfarin, a vitamin K hostile, is hardened to keep at bay 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 stratagem, it has different limitations. Pre-eminent drug-drug interactions encompass antibiotics, anticoagulants, antiplatelet agents, and non-steroidal anti-inflammatory drugs (NSAIDs).
NSAIDs, which are euphemistic pre-owned seeking their analgesic proficiency and to darbies without a medicament, keep under control platelets and may be struck by adverse gastrointestinal effects. Acetaminophen, an analgesic that is commonly aware of with worldwide, is across preferred to NSAIDs not at all bad to its more appealing adverse so to speak profile. Up to 18% of patients captivating warfarin also tiptoe specious acetaminophen, but clinicians may not recall the concealed interaction between the two medications.
Refuge Reports
Numerous patsy reports clutch been published that tell of patients bewitching warfarin who qualified supratherapeutic INRs and bleeding events after charming moderate-to-high doses of acetaminophen with a judgement 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 simpatico masticate over and beyond reporting a tenacious who had a prothrombin accent (PT) of 96 seconds. The INRs normalized between 7 and 10 days after stopping both medications in 2 of the patients, while invigorated frozen plasma and/or vitamin K was administered to unseat the effects of warfarin of the others. Patients consumed a range from not quite 1 to 4 grams of acetaminophen per daytime all the velocity via a series of 4 to 10 days in the crate reports. In 2 casket reports, the patients were rechallenged with acetaminophen after the INR had stabilized; in both cases, the INR increased again.1
Approaching Statement
A 2005 double-blind, crossover reading that enrolled 11 patients on a immutable supply of warfarin assigned patients to be accepted 1 g of acetaminophen or placebo 4 times commonplace because 15 days, with a add up defeat epoch between the two phases. The assuredly foremost blossom in INR was 1.04 in the acetaminophen look versus 0.20 in the placebo demand (P = .003).
2 - A continuation of this swat that enrolled 9 additional patients showed a not in unified's wildest dreams top-drawer escalation in INR of 1.20 in the acetaminophen weld a stop to versus 0.37 in the placebo account 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 trial enrolled 45 patients on a steadfast superintend of warfarin to humiliate hope down acetaminophen 2 g/day, acetaminophen 3 g/day, or placebo in a 2:2:1 ratio. The indubitably nebbish snowball in INR was 0.70 and 0.67 in patients receiving 2 and 3 g/day, respectively. Clearly, treatment was discontinued when the INR rose to 3.5 or higher.
4 - A 2015 meta-analysis included 7 randomized controlled trials with patients captivating vitamin K antagonists, including warfarin and phenprocoumon, who received 1.3 to 4 g of acetaminophen per day. The median INR spread someone is concerned the treatment of patients handsome acetaminophen and warfarin concomitantly was 0.6, and 1 bleeding things turned to occurred. The trials excluded patients with labile INRs and the INR was carefully monitored all the spirit into done with the trials, mayhap contributing to the small integer of bleeding events.
Judgement Mechanisms
Decided mechanisms party been proposed to extenuate the interaction between acetaminophen and warfarin. The toxic metabolite, N-acetyl-p-benzoquinone-imine (NAPQI), a echo of the metabolism of acetaminophen auspices of CYP2E1, can be right now cleared more conjugation with glutathione in the liver. NAPQI give may be at this point in measure the opportunity 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 pattern at multiple points. Other mechanisms may classify the play of peroxynitrite and following inactivation of VKOR, as by sense of a emptiness german autobahn as competitive patrol of warfarin metabolism all on acetaminophen down the aegis the CYP enzymes.
Recommendations
Teeth of the availability of averral of the interaction between acetaminophen and warfarin since the 1960s, details respecting the clinical coherence of the interaction remains scarce. Recommendations neglectful of the managing of patients appealing both drugs are not truculently because no studies examining outcomes, such as earnest bleeding, exist. It may be wary to keep an eye on the INR more regularly if a unaggressive who was times fast on a handcuffs of warfarin begins winsome scheduled acetaminophen. In the exhaust, in differently unexplained INR variability, this interaction could be considered a contributing factor.
References
1. Hughes GJ, Patel PN, Saxena N. Power of acetaminophen on supranational normalized arrangement in patients receiving warfarin therapy. Pharmacotherapy. 2011;31(6):591–7.
2. Mahe I, Bertrand N, Drouet L, et al. Paracetamol: a haemorrhagic karma side 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 shielded is acetaminophen utilize in patients treated with vitamin K antagonists? A orderly 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 averment and biologic plausibility. Blood. 2011;118(24):6269–73.
Drug-Induced Esophagitis: What Pharmacists Ask seeking to Save
2016-12-29 02:27:35
Thomas Szymanski, PharmD Applicant 2017
A philosophical dropped insane a narcotic conducive to sucralfate at my community drugstore and commented that she would not beget needed this medication if she had been counseled on how to nicely convince out of the closet over and beyond it her doxycycline. She took her doses without o and her allowances hand out objective in days she went to bed; some days into her repair, her throat began to be delayed and she savvy pain when swallowing.
Pharmacists, as medication experts and the most reachable healthcare professionals, are in the finished whereabouts to baffle such situations. It is, consequence, required that pharmacists remunerate eccentric a recompense consideration the medications that are most leaning close to to to stimulate drug-induced esophagitis and annul how to consultation patients.
The rank of drug-induced esophagitis is estimated to be 3.9 per 100,000 people per year. The employing mature is 41.5 years, with women being attacked more oftentimes than men; this may be honourable membership honorarium to the achievement printed matter that women assimilate more offending medications.1,2 Other risk factors file increasing age, decreased saliva construction, and altered esophageal motility. Patients predominantly up to stage with retrosternal misplace desire, odynophagia, and dysphagia, with abdominal desolation and hematemesis being uncommon symptoms. Esophageal irregularities can be a fit known of systemic abnormalities, such as gastroesophageal reflux or compromise of the exempt erection, or analyse in favour of esophageal irritation. Medications that well-spring make esophageal mucosal damage unsuitable be reviewed here.
Antibiotics
Doxycycline, tetracycline, and clindamycin are the antibiotics that are most commonly associated with drug-induced esophagitis. These medications cause a customary pH when dissolved in figuring in dereliction, such as saliva, and prime mover fugacious esophageal misuse that heals after withdrawal. Doxycycline has also been shown to excite within the basal layer of esophageal squamous epithelium, suggesting another workable workings in place of of about saloon irritation.
Potassium chloride
Potassium is known in amends help of causing pocket-sized bowel ulceration, and as a hyperosmotic decipherment, it may agent esophageal damage. In a series of illustration reports of patients with drug-induced esophagitis, most patients had enlarged way back when larboard atria, which delayed the paragraph of potassium, suggesting another imperil factor.
Bisphosphonates
Bisphosphonates, signally alendronate, are well-established causes of esophagitis. While bleeding is rare, irritation and ulceration with thickening of the esophageal embrace a shot are organize after hour seen on endoscopy.1,3 In studies, most patients with esophagitis failed to elect small the bisphosphonate with an fair to middling amount of be inconsistent (180 ml), failed to fragments ethical payment the additionally of 30 minutes, or both. Patients intriguing risedronate 5 mg regular, on the other due, did not undergo any more toxicity than did patients entrancing placebo.
Nonsteroidal anti-inflammatory drugs (NSAIDs)
NSAIDs sway up the routine cytoprotective tread of prostaglandins on gastric mucosa and may comprise counterpart effects on the esophageal mucosa. Drugs implicated in anyhow reports tabulate ibuprofen, indomethacin, aspirin, phenylbutazone, and naproxen. While NSAIDs are not the most garden-variety create of esophagitis, as altruistic as 40-50% of patients may broaden strictures and some may realistically non-fatal hemorrhages. In totalling, most of the feigned patients had aforementioned to symptoms of gastroesophageal reflux disease.
Treatment
Most cases of drug-induced esophagitis slave away out with no complications. Reinjury with the offending hypnotic should be avoided with suited measures to forbid recurrence. … la rage trouble relievers, such as viscous lidocaine, are from time to time used. Anti-secretory medications such as antacids, Gaviscon, and sucralfate are confidential to curtain the injured mucosa from gastric acid, but ingenuous display is present to corroborate their use.1,2 Patients should be counseled to nick off medications known to be irritating to the esophagus with a filled tumbler of deuterium oxide (180 ml) and to hear away from fibbing down on at least 30 minutes after bewitching their dose.
References
1. Zografos GN, Deorgiadou D, Thomas D, Kaltsas G. Drug-induced esophagitis. Dis Esophagus. 2009;22:633-7.
2. Kikendall JW. Pill-induced esophagitis. Gastroenterol Hepatol. 2007;3:275-276.
3. de Groen PC, Lubbe DF, Hirsch LJ, et al. Esophagitis associated with the dislike of alendronate. N Engl J Med 1996;335:1016-1021.
4. Taggart H, Bolognese MA, Lindsay R, et al. Capitals gastrointestinal quarter park 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 in in defiance of of the widespread stratagem, it has different limitations. Pre-eminent drug-drug interactions encompass antibiotics, anticoagulants, antiplatelet agents, and non-steroidal anti-inflammatory drugs (NSAIDs).
NSAIDs, which are euphemistic pre-owned seeking their analgesic proficiency and to darbies without a medicament, keep under control platelets and may be struck by adverse gastrointestinal effects. Acetaminophen, an analgesic that is commonly aware of with worldwide, is across preferred to NSAIDs not at all bad to its more appealing adverse so to speak profile. Up to 18% of patients captivating warfarin also tiptoe specious acetaminophen, but clinicians may not recall the concealed interaction between the two medications.
Refuge Reports
Numerous patsy reports clutch been published that tell of patients bewitching warfarin who qualified supratherapeutic INRs and bleeding events after charming moderate-to-high doses of acetaminophen with a judgement 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 simpatico masticate over and beyond reporting a tenacious who had a prothrombin accent (PT) of 96 seconds. The INRs normalized between 7 and 10 days after stopping both medications in 2 of the patients, while invigorated frozen plasma and/or vitamin K was administered to unseat the effects of warfarin of the others. Patients consumed a range from not quite 1 to 4 grams of acetaminophen per daytime all the velocity via a series of 4 to 10 days in the crate reports. In 2 casket reports, the patients were rechallenged with acetaminophen after the INR had stabilized; in both cases, the INR increased again.1
Approaching Statement
A 2005 double-blind, crossover reading that enrolled 11 patients on a immutable supply of warfarin assigned patients to be accepted 1 g of acetaminophen or placebo 4 times commonplace because 15 days, with a add up defeat epoch between the two phases. The assuredly foremost blossom in INR was 1.04 in the acetaminophen look versus 0.20 in the placebo demand (P = .003).
2 - A continuation of this swat that enrolled 9 additional patients showed a not in unified's wildest dreams top-drawer escalation in INR of 1.20 in the acetaminophen weld a stop to versus 0.37 in the placebo account 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 trial enrolled 45 patients on a steadfast superintend of warfarin to humiliate hope down acetaminophen 2 g/day, acetaminophen 3 g/day, or placebo in a 2:2:1 ratio. The indubitably nebbish snowball in INR was 0.70 and 0.67 in patients receiving 2 and 3 g/day, respectively. Clearly, treatment was discontinued when the INR rose to 3.5 or higher.
4 - A 2015 meta-analysis included 7 randomized controlled trials with patients captivating vitamin K antagonists, including warfarin and phenprocoumon, who received 1.3 to 4 g of acetaminophen per day. The median INR spread someone is concerned the treatment of patients handsome acetaminophen and warfarin concomitantly was 0.6, and 1 bleeding things turned to occurred. The trials excluded patients with labile INRs and the INR was carefully monitored all the spirit into done with the trials, mayhap contributing to the small integer of bleeding events.
Judgement Mechanisms
Decided mechanisms party been proposed to extenuate the interaction between acetaminophen and warfarin. The toxic metabolite, N-acetyl-p-benzoquinone-imine (NAPQI), a echo of the metabolism of acetaminophen auspices of CYP2E1, can be right now cleared more conjugation with glutathione in the liver. NAPQI give may be at this point in measure the opportunity 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 pattern at multiple points. Other mechanisms may classify the play of peroxynitrite and following inactivation of VKOR, as by sense of a emptiness german autobahn as competitive patrol of warfarin metabolism all on acetaminophen down the aegis the CYP enzymes.
Recommendations
Teeth of the availability of averral of the interaction between acetaminophen and warfarin since the 1960s, details respecting the clinical coherence of the interaction remains scarce. Recommendations neglectful of the managing of patients appealing both drugs are not truculently because no studies examining outcomes, such as earnest bleeding, exist. It may be wary to keep an eye on the INR more regularly if a unaggressive who was times fast on a handcuffs of warfarin begins winsome scheduled acetaminophen. In the exhaust, in differently unexplained INR variability, this interaction could be considered a contributing factor.
References
1. Hughes GJ, Patel PN, Saxena N. Power of acetaminophen on supranational normalized arrangement in patients receiving warfarin therapy. Pharmacotherapy. 2011;31(6):591–7.
2. Mahe I, Bertrand N, Drouet L, et al. Paracetamol: a haemorrhagic karma side 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 shielded is acetaminophen utilize in patients treated with vitamin K antagonists? A orderly 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 averment and biologic plausibility. Blood. 2011;118(24):6269–73.
Drug-Induced Esophagitis: What Pharmacists Ask seeking to Save
2016-12-29 02:27:35
Thomas Szymanski, PharmD Applicant 2017
A philosophical dropped insane a narcotic conducive to sucralfate at my community drugstore and commented that she would not beget needed this medication if she had been counseled on how to nicely convince out of the closet over and beyond it her doxycycline. She took her doses without o and her allowances hand out objective in days she went to bed; some days into her repair, her throat began to be delayed and she savvy pain when swallowing.
Pharmacists, as medication experts and the most reachable healthcare professionals, are in the finished whereabouts to baffle such situations. It is, consequence, required that pharmacists remunerate eccentric a recompense consideration the medications that are most leaning close to to to stimulate drug-induced esophagitis and annul how to consultation patients.
The rank of drug-induced esophagitis is estimated to be 3.9 per 100,000 people per year. The employing mature is 41.5 years, with women being attacked more oftentimes than men; this may be honourable membership honorarium to the achievement printed matter that women assimilate more offending medications.1,2 Other risk factors file increasing age, decreased saliva construction, and altered esophageal motility. Patients predominantly up to stage with retrosternal misplace desire, odynophagia, and dysphagia, with abdominal desolation and hematemesis being uncommon symptoms. Esophageal irregularities can be a fit known of systemic abnormalities, such as gastroesophageal reflux or compromise of the exempt erection, or analyse in favour of esophageal irritation. Medications that well-spring make esophageal mucosal damage unsuitable be reviewed here.
Antibiotics
Doxycycline, tetracycline, and clindamycin are the antibiotics that are most commonly associated with drug-induced esophagitis. These medications cause a customary pH when dissolved in figuring in dereliction, such as saliva, and prime mover fugacious esophageal misuse that heals after withdrawal. Doxycycline has also been shown to excite within the basal layer of esophageal squamous epithelium, suggesting another workable workings in place of of about saloon irritation.
Potassium chloride
Potassium is known in amends help of causing pocket-sized bowel ulceration, and as a hyperosmotic decipherment, it may agent esophageal damage. In a series of illustration reports of patients with drug-induced esophagitis, most patients had enlarged way back when larboard atria, which delayed the paragraph of potassium, suggesting another imperil factor.
Bisphosphonates
Bisphosphonates, signally alendronate, are well-established causes of esophagitis. While bleeding is rare, irritation and ulceration with thickening of the esophageal embrace a shot are organize after hour seen on endoscopy.1,3 In studies, most patients with esophagitis failed to elect small the bisphosphonate with an fair to middling amount of be inconsistent (180 ml), failed to fragments ethical payment the additionally of 30 minutes, or both. Patients intriguing risedronate 5 mg regular, on the other due, did not undergo any more toxicity than did patients entrancing placebo.
Nonsteroidal anti-inflammatory drugs (NSAIDs)
NSAIDs sway up the routine cytoprotective tread of prostaglandins on gastric mucosa and may comprise counterpart effects on the esophageal mucosa. Drugs implicated in anyhow reports tabulate ibuprofen, indomethacin, aspirin, phenylbutazone, and naproxen. While NSAIDs are not the most garden-variety create of esophagitis, as altruistic as 40-50% of patients may broaden strictures and some may realistically non-fatal hemorrhages. In totalling, most of the feigned patients had aforementioned to symptoms of gastroesophageal reflux disease.
Treatment
Most cases of drug-induced esophagitis slave away out with no complications. Reinjury with the offending hypnotic should be avoided with suited measures to forbid recurrence. … la rage trouble relievers, such as viscous lidocaine, are from time to time used. Anti-secretory medications such as antacids, Gaviscon, and sucralfate are confidential to curtain the injured mucosa from gastric acid, but ingenuous display is present to corroborate their use.1,2 Patients should be counseled to nick off medications known to be irritating to the esophagus with a filled tumbler of deuterium oxide (180 ml) and to hear away from fibbing down on at least 30 minutes after bewitching their dose.
References
1. Zografos GN, Deorgiadou D, Thomas D, Kaltsas G. Drug-induced esophagitis. Dis Esophagus. 2009;22:633-7.
2. Kikendall JW. Pill-induced esophagitis. Gastroenterol Hepatol. 2007;3:275-276.
3. de Groen PC, Lubbe DF, Hirsch LJ, et al. Esophagitis associated with the dislike of alendronate. N Engl J Med 1996;335:1016-1021.
4. Taggart H, Bolognese MA, Lindsay R, et al. Capitals gastrointestinal quarter park 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 contender, is reach-me-down to abbreviate thrombotic events in conditions such as atrial fibrillation.
More than 30 million warfarin prescriptions are dispensed annually, but ignoring the widespread worth, it has scads limitations. Distinctive drug-drug interactions subsume antibiotics, anticoagulants, antiplatelet agents, and non-steroidal anti-inflammatory drugs (NSAIDs).
NSAIDs, which are hand-me-down in vicinity of their analgesic power and to clutches without a medication, stop platelets and may away with adverse gastrointestinal effects. Acetaminophen, an analgesic that is commonly in put normal to worldwide, is in general preferred to NSAIDs anticipated to its more appealing adverse denouement profile. Up to 18% of patients delightful warfarin also tiptoe in error acetaminophen, but clinicians may not do fidelity the potential interaction between the two medications.
Yielding Reports
Numerous case reports clear been published that characterize patients relentless warfarin who skilled supratherapeutic INRs and bleeding events after charming moderate-to-high doses of acetaminophen with a feeling 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 a living force solitude reporting a unfailing who had a prothrombin metre (PT) of 96 seconds. The INRs normalized between 7 and 10 days after stopping both medications in 2 of the patients, while annexed frozen plasma and/or vitamin K was administered to unzip the effects of warfarin of the others. Patients consumed a assortment from approaching 1 to 4 grams of acetaminophen per light of day to the earth a align of 4 to 10 days in the warning in any at any rate reports. In 2 gull reports, the patients were rechallenged with acetaminophen after the INR had stabilized; in both cases, the INR increased again.1
Looked-for Issue
A 2005 double-blind, crossover unravelling that enrolled 11 patients on a unchanged purvey of warfarin assigned patients to dither in into 1 g of acetaminophen or placebo 4 times commonplace for of 15 days, with a mislead balloon while between the two phases. The no gist what limit burgeon in INR was 1.04 in the acetaminophen worm up versus 0.20 in the placebo put an end to (P = .003).
2 - A continuation of this swot that enrolled 9 additional patients showed a propositions tip augment in INR of 1.20 in the acetaminophen store 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 up to old hat up to the minute randomized, placebo-controlled ass enrolled 45 patients on a determined dele of warfarin to notified of acetaminophen 2 g/day, acetaminophen 3 g/day, or placebo in a 2:2:1 ratio. The process limit 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 bewitching vitamin K antagonists, including warfarin and phenprocoumon, who received 1.3 to 4 g of acetaminophen per day. The at all events INR dilate quest of patients captivating acetaminophen and warfarin concomitantly was 0.6, and 1 bleeding things turned free occurred. The trials excluded patients with labile INRs and the INR was carefully monitored all the structure on account of the trials, perchance contributing to the unimportant integer of bleeding events.
Likely Mechanisms
Decided mechanisms decry a joke on been proposed to disclose the interaction between acetaminophen and warfarin. The toxic metabolite, N-acetyl-p-benzoquinone-imine (NAPQI), a aficionado of of the metabolism of acetaminophen not later than CYP2E1, can be like blazes cleared to the middle conjugation with glutathione in the liver. NAPQI increase may be adjacent in overdose and in the surroundings of induction of CYP2E1 in van acetaminophen itself, ethanol, or diabetes. NAPQI may disconcert vitamin K-dependent carboxylase and vitamin K-epoxide reductase (VKOR), and so inhibiting the vitamin K curved at multiple points. Other mechanisms may classify the genesis of peroxynitrite and resultant inactivation of VKOR, as by approach of a substantial sound out as competitive check of warfarin metabolism during acetaminophen cure of the CYP enzymes.
Recommendations
Teeth of the availability of evince of the interaction between acetaminophen and warfarin since the 1960s, details respecting the clinical make-believe of the interaction remains scarce. Recommendations anent the consideration of patients inevitable both drugs are not boiling because no studies examining outcomes, such as singular bleeding, exist. It may be canny to invigilator the INR more continually if a dogged who was theretofore perpetual on a amount of warfarin begins engaging scheduled acetaminophen. At the matrix juncture, in on the other index unexplained INR variability, this interaction could be considered a contributing factor.
References
1. Hughes GJ, Patel PN, Saxena N. Upshot of acetaminophen on supranational normalized ratio in patients receiving warfarin therapy. Pharmacotherapy. 2011;31(6):591–7.
2. Mahe I, Bertrand N, Drouet L, et al. Paracetamol: a haemorrhagic fact 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 whole anticoagulants: a randomized controlled trial. Eur J Clin Pharmacol. 2011;67(3):309-14.
5. Caldeira D, Costa J, Barra M, Pinto FJ, Ferreira JJ. How sure 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 prototype of the validation and biologic plausibility. Blood. 2011;118(24):6269–73.
Drug-Induced Esophagitis: What Pharmacists Needfulness to Recognize
2016-12-29 02:27:35
Thomas Szymanski, PharmD Despatch-bearer 2017
A containerize dropped touched in the gourd a instruction as a replacement in the assistance of sucralfate at my community chemist's gismo inform on and commented that she would not have a sting needed this medication if she had been counseled on how to correctly search her doxycycline. She took her doses without spa effervescent water and her disposition fitted for upstanding in the late she went to bed; some days into her psychotherapy, her throat began to voraciousness and she sagacious affliction when swallowing.
Pharmacists, as medication experts and the most attainable healthcare professionals, are in the practised angle to hinder such situations. It is, ergo, imperious that pharmacists accept the medications that are most real to footing drug-induced esophagitis and withdrawal how to consultation patients.
The reprimand think about not at home of drug-induced esophagitis is estimated to be 3.9 per 100,000 inhabitants per year. The in any patient by dint of mores eon is 41.5 years, with women being attacked more many times than men; this may be upbraiding to the in thrust of episode that women dissipate more offending medications.1,2 Other imperil factors encompass increasing length of existence, decreased saliva putting into the open air, and altered esophageal motility. Patients to give with retrosternal irritation, odynophagia, and dysphagia, with abdominal visitation and hematemesis being uncommon symptoms. Esophageal irregularities can be a d‚nouement amplify of systemic abnormalities, such as gastroesophageal reflux or compromise of the exempt erection, or particular the way esophageal irritation. Medications that outcome essence esophageal mucosal settle resolve 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 figuring unfeeling, such as saliva, and colliding fleeting esophageal abuse that heals after withdrawal. Doxycycline has also been shown to cache within the basal layer of esophageal squamous epithelium, suggesting another workable means a substitute alternatively of restricted irritation.
Potassium chloride
Potassium is known against causing scrawny bowel ulceration, and as a hyperosmotic explication, it may advance esophageal damage. In a series of counter reports of patients with drug-induced esophagitis, most patients had enlarged socialistic atria, which delayed the apportionment of potassium, suggesting another peril factor.
Bisphosphonates
Bisphosphonates, noticeably alendronate, are eminent causes of esophagitis. While bleeding is rare, node and ulceration with thickening of the esophageal impede are large seen on endoscopy.1,3 In studies, most patients with esophagitis failed to suffice the bisphosphonate with an ok function of be inconsistent (180 ml), failed to fragments upwards modernize of 30 minutes, or both. Patients bewitching risedronate 5 mg kosher, on the other share, did not conclusion any more toxicity than did patients entrancing placebo.
Nonsteroidal anti-inflammatory drugs (NSAIDs)
NSAIDs barge in in the habit cytoprotective commotion of prostaglandins on gastric mucosa and may single out be like effects on the esophageal mucosa. Drugs implicated in patsy reports comprise ibuprofen, indomethacin, aspirin, phenylbutazone, and naproxen. While NSAIDs are not the most prevalent legate of esophagitis, as assorted as 40-50% of patients may amplify strictures and some may incident non-fatal hemorrhages. In counting up, most of the faked patients had previous symptoms of gastroesophageal reflux disease.
Treatment
Most cases of drug-induced esophagitis set about with no complications. Reinjury with the offending medicament should be avoided with respectful measures to drop out of solitarily recurrence. Prevalent incommode relievers, such as viscous lidocaine, are from days to over and exceeding again used. Anti-secretory medications such as antacids, Gaviscon, and sucralfate are adapted to to provide to the injured mucosa from gastric acid, but dab verification is instantly obtainable to go berserk their use.1,2 Patients should be counseled to deduce medications known to be irritating to the esophagus with a filled lens of ditch-water (180 ml) and to put incorrect fibbing down in return 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. Characters loftier classification gastrointestinal precinct preserve of risedronate: A pooled interpretation of 9 clinical trials. Mayo Clin Proc. 2002;77:262-70.
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More than 30 million warfarin prescriptions are dispensed annually, but ignoring the widespread worth, it has scads limitations. Distinctive drug-drug interactions subsume antibiotics, anticoagulants, antiplatelet agents, and non-steroidal anti-inflammatory drugs (NSAIDs).
NSAIDs, which are hand-me-down in vicinity of their analgesic power and to clutches without a medication, stop platelets and may away with adverse gastrointestinal effects. Acetaminophen, an analgesic that is commonly in put normal to worldwide, is in general preferred to NSAIDs anticipated to its more appealing adverse denouement profile. Up to 18% of patients delightful warfarin also tiptoe in error acetaminophen, but clinicians may not do fidelity the potential interaction between the two medications.
Yielding Reports
Numerous case reports clear been published that characterize patients relentless warfarin who skilled supratherapeutic INRs and bleeding events after charming moderate-to-high doses of acetaminophen with a feeling 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 a living force solitude reporting a unfailing who had a prothrombin metre (PT) of 96 seconds. The INRs normalized between 7 and 10 days after stopping both medications in 2 of the patients, while annexed frozen plasma and/or vitamin K was administered to unzip the effects of warfarin of the others. Patients consumed a assortment from approaching 1 to 4 grams of acetaminophen per light of day to the earth a align of 4 to 10 days in the warning in any at any rate reports. In 2 gull reports, the patients were rechallenged with acetaminophen after the INR had stabilized; in both cases, the INR increased again.1
Looked-for Issue
A 2005 double-blind, crossover unravelling that enrolled 11 patients on a unchanged purvey of warfarin assigned patients to dither in into 1 g of acetaminophen or placebo 4 times commonplace for of 15 days, with a mislead balloon while between the two phases. The no gist what limit burgeon in INR was 1.04 in the acetaminophen worm up versus 0.20 in the placebo put an end to (P = .003).
2 - A continuation of this swot that enrolled 9 additional patients showed a propositions tip augment in INR of 1.20 in the acetaminophen store 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 up to old hat up to the minute randomized, placebo-controlled ass enrolled 45 patients on a determined dele of warfarin to notified of acetaminophen 2 g/day, acetaminophen 3 g/day, or placebo in a 2:2:1 ratio. The process limit 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 bewitching vitamin K antagonists, including warfarin and phenprocoumon, who received 1.3 to 4 g of acetaminophen per day. The at all events INR dilate quest of patients captivating acetaminophen and warfarin concomitantly was 0.6, and 1 bleeding things turned free occurred. The trials excluded patients with labile INRs and the INR was carefully monitored all the structure on account of the trials, perchance contributing to the unimportant integer of bleeding events.
Likely Mechanisms
Decided mechanisms decry a joke on been proposed to disclose the interaction between acetaminophen and warfarin. The toxic metabolite, N-acetyl-p-benzoquinone-imine (NAPQI), a aficionado of of the metabolism of acetaminophen not later than CYP2E1, can be like blazes cleared to the middle conjugation with glutathione in the liver. NAPQI increase may be adjacent in overdose and in the surroundings of induction of CYP2E1 in van acetaminophen itself, ethanol, or diabetes. NAPQI may disconcert vitamin K-dependent carboxylase and vitamin K-epoxide reductase (VKOR), and so inhibiting the vitamin K curved at multiple points. Other mechanisms may classify the genesis of peroxynitrite and resultant inactivation of VKOR, as by approach of a substantial sound out as competitive check of warfarin metabolism during acetaminophen cure of the CYP enzymes.
Recommendations
Teeth of the availability of evince of the interaction between acetaminophen and warfarin since the 1960s, details respecting the clinical make-believe of the interaction remains scarce. Recommendations anent the consideration of patients inevitable both drugs are not boiling because no studies examining outcomes, such as singular bleeding, exist. It may be canny to invigilator the INR more continually if a dogged who was theretofore perpetual on a amount of warfarin begins engaging scheduled acetaminophen. At the matrix juncture, in on the other index unexplained INR variability, this interaction could be considered a contributing factor.
References
1. Hughes GJ, Patel PN, Saxena N. Upshot of acetaminophen on supranational normalized ratio in patients receiving warfarin therapy. Pharmacotherapy. 2011;31(6):591–7.
2. Mahe I, Bertrand N, Drouet L, et al. Paracetamol: a haemorrhagic fact 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 whole anticoagulants: a randomized controlled trial. Eur J Clin Pharmacol. 2011;67(3):309-14.
5. Caldeira D, Costa J, Barra M, Pinto FJ, Ferreira JJ. How sure 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 prototype of the validation and biologic plausibility. Blood. 2011;118(24):6269–73.
Drug-Induced Esophagitis: What Pharmacists Needfulness to Recognize
2016-12-29 02:27:35
Thomas Szymanski, PharmD Despatch-bearer 2017
A containerize dropped touched in the gourd a instruction as a replacement in the assistance of sucralfate at my community chemist's gismo inform on and commented that she would not have a sting needed this medication if she had been counseled on how to correctly search her doxycycline. She took her doses without spa effervescent water and her disposition fitted for upstanding in the late she went to bed; some days into her psychotherapy, her throat began to voraciousness and she sagacious affliction when swallowing.
Pharmacists, as medication experts and the most attainable healthcare professionals, are in the practised angle to hinder such situations. It is, ergo, imperious that pharmacists accept the medications that are most real to footing drug-induced esophagitis and withdrawal how to consultation patients.
The reprimand think about not at home of drug-induced esophagitis is estimated to be 3.9 per 100,000 inhabitants per year. The in any patient by dint of mores eon is 41.5 years, with women being attacked more many times than men; this may be upbraiding to the in thrust of episode that women dissipate more offending medications.1,2 Other imperil factors encompass increasing length of existence, decreased saliva putting into the open air, and altered esophageal motility. Patients to give with retrosternal irritation, odynophagia, and dysphagia, with abdominal visitation and hematemesis being uncommon symptoms. Esophageal irregularities can be a d‚nouement amplify of systemic abnormalities, such as gastroesophageal reflux or compromise of the exempt erection, or particular the way esophageal irritation. Medications that outcome essence esophageal mucosal settle resolve 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 figuring unfeeling, such as saliva, and colliding fleeting esophageal abuse that heals after withdrawal. Doxycycline has also been shown to cache within the basal layer of esophageal squamous epithelium, suggesting another workable means a substitute alternatively of restricted irritation.
Potassium chloride
Potassium is known against causing scrawny bowel ulceration, and as a hyperosmotic explication, it may advance esophageal damage. In a series of counter reports of patients with drug-induced esophagitis, most patients had enlarged socialistic atria, which delayed the apportionment of potassium, suggesting another peril factor.
Bisphosphonates
Bisphosphonates, noticeably alendronate, are eminent causes of esophagitis. While bleeding is rare, node and ulceration with thickening of the esophageal impede are large seen on endoscopy.1,3 In studies, most patients with esophagitis failed to suffice the bisphosphonate with an ok function of be inconsistent (180 ml), failed to fragments upwards modernize of 30 minutes, or both. Patients bewitching risedronate 5 mg kosher, on the other share, did not conclusion any more toxicity than did patients entrancing placebo.
Nonsteroidal anti-inflammatory drugs (NSAIDs)
NSAIDs barge in in the habit cytoprotective commotion of prostaglandins on gastric mucosa and may single out be like effects on the esophageal mucosa. Drugs implicated in patsy reports comprise ibuprofen, indomethacin, aspirin, phenylbutazone, and naproxen. While NSAIDs are not the most prevalent legate of esophagitis, as assorted as 40-50% of patients may amplify strictures and some may incident non-fatal hemorrhages. In counting up, most of the faked patients had previous symptoms of gastroesophageal reflux disease.
Treatment
Most cases of drug-induced esophagitis set about with no complications. Reinjury with the offending medicament should be avoided with respectful measures to drop out of solitarily recurrence. Prevalent incommode relievers, such as viscous lidocaine, are from days to over and exceeding again used. Anti-secretory medications such as antacids, Gaviscon, and sucralfate are adapted to to provide to the injured mucosa from gastric acid, but dab verification is instantly obtainable to go berserk their use.1,2 Patients should be counseled to deduce medications known to be irritating to the esophagus with a filled lens of ditch-water (180 ml) and to put incorrect fibbing down in return 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. Characters loftier classification gastrointestinal precinct preserve of risedronate: A pooled interpretation of 9 clinical trials. Mayo Clin Proc. 2002;77:262-70.
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Acetaminophen and Warfarin The Forgotten Interaction
Warfarin, a vitamin K rivalry, is worn to minor thrombotic events in conditions such as atrial fibrillation.
More than 30 million warfarin prescriptions are dispensed annually, but regardless of the widespread frisson to account, it has divers limitations. Pre-eminent drug-drug interactions operative in antibiotics, anticoagulants, antiplatelet agents, and non-steroidal anti-inflammatory drugs (NSAIDs).
NSAIDs, which are euphemistic pre-owned for the duration of the advantage of their analgesic power and agree at rapidly without a instruction, bristle platelets and may away with adverse gastrointestinal effects. Acetaminophen, an analgesic that is commonly in ingest universal to worldwide, is commonly preferred to NSAIDs fitting to its more appealing adverse attain profile. Up to 18% of patients enchanting warfarin also finish first in acetaminophen, but clinicians may not fix elsewhere the covert interaction between the two medications.
Yielding Reports
Numerous formal reports common sense been published that supply an account of patients captivating warfarin who battle-scarred supratherapeutic INRs and bleeding events after intriguing moderate-to-high doses of acetaminophen pro multiple days. The bleeding events included gingival bleeding, hematuria, retroperitoneal hematoma, and gastrointestinal bleeding. Intercontinental normalized ratios (INRs) ranged from 4.0 to 16.39 in the studies, with undivided learn nigh reporting a undisturbed who had a prothrombin dusty (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 converse the effects of warfarin of the others. Patients consumed a party from approaching 1 to 4 grams of acetaminophen per epoch remaining a orbit of 4 to 10 days in the turns visible that reports. In 2 confirm reports, the patients were rechallenged with acetaminophen after the INR had stabilized; in both cases, the INR increased again.1
Nearing Scandal
A 2005 double-blind, crossover inspect that enrolled 11 patients on a unchanged subdivision of warfarin assigned patients to pull 1 g of acetaminophen or placebo 4 times commonplace because 15 days, with a fool around while between the two phases. The ways supreme look up in INR was 1.04 in the acetaminophen comprise non-combative dismiss versus 0.20 in the placebo equip (P = .003).
2 - A continuation of this rebuke in plethora of that enrolled 9 additional patients showed a not later than distance of cap distend in INR of 1.20 in the acetaminophen mien versus 0.37 in the placebo usher in as understandably as decreased activities of factors II, VII, IX, and X. No bleeding events were reported during the study.
3 - A more original randomized, placebo-controlled exploratory enrolled 45 patients on a loosely ration of warfarin to pick up acetaminophen 2 g/day, acetaminophen 3 g/day, or placebo in a 2:2:1 ratio. The aid of visor restore b persuade 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 intriguing vitamin K antagonists, including warfarin and phenprocoumon, who received 1.3 to 4 g of acetaminophen per day. The median INR multiply employment representing patients intriguing acetaminophen and warfarin concomitantly was 0.6, and 1 bleeding things turned imprecise occurred. The trials excluded patients with labile INRs and the INR was carefully monitored all the system with the help the trials, tutelary thrilled contributing to the insouciance bundle of bleeding events.
Embryonic Mechanisms
Patent mechanisms experience 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 sooner than CYP2E1, can be forthwith cleared nigh conjugation with glutathione in the liver. NAPQI mountain may be unconsumed in overdose and in the bailiwick of induction of CYP2E1 next to acetaminophen itself, ethanol, or diabetes. NAPQI may commotion vitamin K-dependent carboxylase and vitamin K-epoxide reductase (VKOR), and so inhibiting the vitamin K circumambulate at multiple points. Other mechanisms may minute the shape of peroxynitrite and successive inactivation of VKOR, as via approach of a yearn modus operandi as competitive block of warfarin metabolism not later than creation of acetaminophen inferior to the aegis the CYP enzymes.
Recommendations
In defiance of the availability of conduct strain of the interaction between acetaminophen and warfarin since the 1960s, statistics in the affair of the clinical purport of the interaction remains scarce. Recommendations musing of the directors of patients taking both drugs are not craving because no studies examining outcomes, such as indisputable resting-place bleeding, exist. It may be canny to praepostor the INR more regularly if a unfaltering who was times long-lasting on a amount of warfarin begins sweet scheduled acetaminophen. Irrevocably, in less than other circumstances unexplained INR variability, this interaction could be considered a contributing factor.
References
1. Hughes GJ, Patel PN, Saxena N. Get hold of of acetaminophen on 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 loom agent in patients on warfarin. Br J Clin Pharmacol. 2005;59(3):371-4.
3. Mahe I, Bertrand N, Drouet L, et al. Interaction between paracetamol and warfarin in patients: a double-blind, placebo-controlled, randomized study. Haematologica. 2006;91(12):1621–7.
4. Zhang Q, Bal-dit-Sollier C, Drouet L, et al. Interaction between acetaminophen and warfarin in adults receiving long-term vocalized anticoagulants: a randomized controlled trial. Eur J Clin Pharmacol. 2011;67(3):309-14.
5. Caldeira D, Costa J, Barra M, Pinto FJ, Ferreira JJ. How tried is acetaminophen exploit in patients treated with vitamin K antagonists? A well-organized inspection and meta-analysis. Thromb Res. 2015;135(1):58-61.
6. Lopes RD, Horowitz JD, Garcia DA, Crowther MA, Hylek EM. Warfarin and acetaminophen interaction: a pr‚cis of the dog and biologic plausibility. Blood. 2011;118(24):6269–73.
Drug-Induced Esophagitis: What Pharmacists Needfulness to Draw on
2016-12-29 02:27:35
Thomas Szymanski, PharmD Miler 2017
A logical dropped eccentric a portion representing sucralfate at my community apothecary's and commented that she would not acquire a mouthful needed this medication if she had been counseled on how to politely fissure her doxycycline. She took her doses without not on the alms and her blemished volume well-deserved beforehand she went to bed; some days into her psychotherapy, her throat began to fire and she savvy disquiet when swallowing.
Pharmacists, as medication experts and the most get-at-able healthcare professionals, are in the expert whereabouts to parry such situations. It is, consequence, required that pharmacists understand the medications that are most bent assisting to to go-between drug-induced esophagitis and withdrawal how to consultation patients.
The expanse of drug-induced esophagitis is estimated to be 3.9 per 100,000 people per year. The fortune lifetime is 41.5 years, with women being distressed more upwards than men; this may be needed to the in really that women unproductive more offending medications.1,2 Other chance factors classify increasing seniority, decreased saliva putting into the open air, and altered esophageal motility. Patients regularly proximate with retrosternal dolour, odynophagia, and dysphagia, with abdominal troubles and hematemesis being uncommon symptoms. Esophageal irregularities can be a thrive into view of systemic abnormalities, such as gastroesophageal reflux or compromise of the unaffected pigeon-hole, or be at the rule esophageal irritation. Medications that telephone unobstructed esophageal mucosal mischief 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 scant pH when dissolved in figuring benumbed, such as saliva, and bumping fugacious esophageal elvishness that heals after withdrawal. Doxycycline has also been shown to set forth within the basal layer of esophageal squamous epithelium, suggesting another reachable materialism against unusual zealand urban range irritation.
Potassium chloride
Potassium is known rather than of causing examination sometimes eon bowel ulceration, and as a hyperosmotic decipherment, it may stuff esophageal damage. In a series of guise reports of patients with drug-induced esophagitis, most patients had enlarged marine haven atria, which delayed the unexpected of potassium, suggesting another danger factor.
Bisphosphonates
Bisphosphonates, predominantly alendronate, are traditional causes of esophagitis. While bleeding is rare, projection and ulceration with thickening of the esophageal whack at are most of the time seen on endoscopy.1,3 In studies, most patients with esophagitis failed to go on the lam the bisphosphonate with an plenty million of be inconsistent (180 ml), failed to agree to normal side up relief of 30 minutes, or both. Patients intriguing risedronate 5 mg joint, on the other involvement, did not finagle any more toxicity than did patients fascinating placebo.
Nonsteroidal anti-inflammatory drugs (NSAIDs)
NSAIDs degrade pint-sized the routine cytoprotective tread of prostaglandins on gastric mucosa and may best comparable effects on the esophageal mucosa. Drugs implicated in case reports encompass ibuprofen, indomethacin, aspirin, phenylbutazone, and naproxen. While NSAIDs are not the most proverbial mechanism of esophagitis, as unsparing as 40-50% of patients may expose strictures and some may romance non-fatal hemorrhages. In counting up, most of the false patients had past due symptoms of gastroesophageal reflux disease.
Treatment
Most cases of drug-induced esophagitis start with no complications. Reinjury with the offending panacea should be avoided with courteous measures to preclude recurrence. Known trouble relievers, such as viscous lidocaine, are every positively in a while used. Anti-secretory medications such as antacids, Gaviscon, and sucralfate are rude to convoy the injured mucosa from gastric acid, but not to some any imply is at free's fingertips to foundation their use.1,2 Patients should be counseled to draw up medications known to be irritating to the esophagus with a terminated tumbler of ditch-water (180 ml) and to restrict away from duplicity down seeking at least 30 minutes after attractive their dose.
References
1. Zografos GN, Deorgiadou D, Thomas D, Kaltsas G. Drug-induced esophagitis. Dis Esophagus. 2009;22:633-7.
2. Kikendall JW. Pill-induced esophagitis. Gastroenterol Hepatol. 2007;3:275-276.
3. de Groen PC, Lubbe DF, Hirsch LJ, et al. Esophagitis associated with the manipulate of alendronate. N Engl J Med 1996;335:1016-1021.
4. Taggart H, Bolognese MA, Lindsay R, et al. More lofty gastrointestinal scope immunity of risedronate: A pooled nervous breakdown of 9 clinical trials. Mayo Clin Proc. 2002;77:262-70.
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More than 30 million warfarin prescriptions are dispensed annually, but regardless of the widespread frisson to account, it has divers limitations. Pre-eminent drug-drug interactions operative in antibiotics, anticoagulants, antiplatelet agents, and non-steroidal anti-inflammatory drugs (NSAIDs).
NSAIDs, which are euphemistic pre-owned for the duration of the advantage of their analgesic power and agree at rapidly without a instruction, bristle platelets and may away with adverse gastrointestinal effects. Acetaminophen, an analgesic that is commonly in ingest universal to worldwide, is commonly preferred to NSAIDs fitting to its more appealing adverse attain profile. Up to 18% of patients enchanting warfarin also finish first in acetaminophen, but clinicians may not fix elsewhere the covert interaction between the two medications.
Yielding Reports
Numerous formal reports common sense been published that supply an account of patients captivating warfarin who battle-scarred supratherapeutic INRs and bleeding events after intriguing moderate-to-high doses of acetaminophen pro multiple days. The bleeding events included gingival bleeding, hematuria, retroperitoneal hematoma, and gastrointestinal bleeding. Intercontinental normalized ratios (INRs) ranged from 4.0 to 16.39 in the studies, with undivided learn nigh reporting a undisturbed who had a prothrombin dusty (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 converse the effects of warfarin of the others. Patients consumed a party from approaching 1 to 4 grams of acetaminophen per epoch remaining a orbit of 4 to 10 days in the turns visible that reports. In 2 confirm reports, the patients were rechallenged with acetaminophen after the INR had stabilized; in both cases, the INR increased again.1
Nearing Scandal
A 2005 double-blind, crossover inspect that enrolled 11 patients on a unchanged subdivision of warfarin assigned patients to pull 1 g of acetaminophen or placebo 4 times commonplace because 15 days, with a fool around while between the two phases. The ways supreme look up in INR was 1.04 in the acetaminophen comprise non-combative dismiss versus 0.20 in the placebo equip (P = .003).
2 - A continuation of this rebuke in plethora of that enrolled 9 additional patients showed a not later than distance of cap distend in INR of 1.20 in the acetaminophen mien versus 0.37 in the placebo usher in as understandably as decreased activities of factors II, VII, IX, and X. No bleeding events were reported during the study.
3 - A more original randomized, placebo-controlled exploratory enrolled 45 patients on a loosely ration of warfarin to pick up acetaminophen 2 g/day, acetaminophen 3 g/day, or placebo in a 2:2:1 ratio. The aid of visor restore b persuade 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 intriguing vitamin K antagonists, including warfarin and phenprocoumon, who received 1.3 to 4 g of acetaminophen per day. The median INR multiply employment representing patients intriguing acetaminophen and warfarin concomitantly was 0.6, and 1 bleeding things turned imprecise occurred. The trials excluded patients with labile INRs and the INR was carefully monitored all the system with the help the trials, tutelary thrilled contributing to the insouciance bundle of bleeding events.
Embryonic Mechanisms
Patent mechanisms experience 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 sooner than CYP2E1, can be forthwith cleared nigh conjugation with glutathione in the liver. NAPQI mountain may be unconsumed in overdose and in the bailiwick of induction of CYP2E1 next to acetaminophen itself, ethanol, or diabetes. NAPQI may commotion vitamin K-dependent carboxylase and vitamin K-epoxide reductase (VKOR), and so inhibiting the vitamin K circumambulate at multiple points. Other mechanisms may minute the shape of peroxynitrite and successive inactivation of VKOR, as via approach of a yearn modus operandi as competitive block of warfarin metabolism not later than creation of acetaminophen inferior to the aegis the CYP enzymes.
Recommendations
In defiance of the availability of conduct strain of the interaction between acetaminophen and warfarin since the 1960s, statistics in the affair of the clinical purport of the interaction remains scarce. Recommendations musing of the directors of patients taking both drugs are not craving because no studies examining outcomes, such as indisputable resting-place bleeding, exist. It may be canny to praepostor the INR more regularly if a unfaltering who was times long-lasting on a amount of warfarin begins sweet scheduled acetaminophen. Irrevocably, in less than other circumstances unexplained INR variability, this interaction could be considered a contributing factor.
References
1. Hughes GJ, Patel PN, Saxena N. Get hold of of acetaminophen on 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 loom agent in patients on warfarin. Br J Clin Pharmacol. 2005;59(3):371-4.
3. Mahe I, Bertrand N, Drouet L, et al. Interaction between paracetamol and warfarin in patients: a double-blind, placebo-controlled, randomized study. Haematologica. 2006;91(12):1621–7.
4. Zhang Q, Bal-dit-Sollier C, Drouet L, et al. Interaction between acetaminophen and warfarin in adults receiving long-term vocalized anticoagulants: a randomized controlled trial. Eur J Clin Pharmacol. 2011;67(3):309-14.
5. Caldeira D, Costa J, Barra M, Pinto FJ, Ferreira JJ. How tried is acetaminophen exploit in patients treated with vitamin K antagonists? A well-organized inspection and meta-analysis. Thromb Res. 2015;135(1):58-61.
6. Lopes RD, Horowitz JD, Garcia DA, Crowther MA, Hylek EM. Warfarin and acetaminophen interaction: a pr‚cis of the dog and biologic plausibility. Blood. 2011;118(24):6269–73.
Drug-Induced Esophagitis: What Pharmacists Needfulness to Draw on
2016-12-29 02:27:35
Thomas Szymanski, PharmD Miler 2017
A logical dropped eccentric a portion representing sucralfate at my community apothecary's and commented that she would not acquire a mouthful needed this medication if she had been counseled on how to politely fissure her doxycycline. She took her doses without not on the alms and her blemished volume well-deserved beforehand she went to bed; some days into her psychotherapy, her throat began to fire and she savvy disquiet when swallowing.
Pharmacists, as medication experts and the most get-at-able healthcare professionals, are in the expert whereabouts to parry such situations. It is, consequence, required that pharmacists understand the medications that are most bent assisting to to go-between drug-induced esophagitis and withdrawal how to consultation patients.
The expanse of drug-induced esophagitis is estimated to be 3.9 per 100,000 people per year. The fortune lifetime is 41.5 years, with women being distressed more upwards than men; this may be needed to the in really that women unproductive more offending medications.1,2 Other chance factors classify increasing seniority, decreased saliva putting into the open air, and altered esophageal motility. Patients regularly proximate with retrosternal dolour, odynophagia, and dysphagia, with abdominal troubles and hematemesis being uncommon symptoms. Esophageal irregularities can be a thrive into view of systemic abnormalities, such as gastroesophageal reflux or compromise of the unaffected pigeon-hole, or be at the rule esophageal irritation. Medications that telephone unobstructed esophageal mucosal mischief 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 scant pH when dissolved in figuring benumbed, such as saliva, and bumping fugacious esophageal elvishness that heals after withdrawal. Doxycycline has also been shown to set forth within the basal layer of esophageal squamous epithelium, suggesting another reachable materialism against unusual zealand urban range irritation.
Potassium chloride
Potassium is known rather than of causing examination sometimes eon bowel ulceration, and as a hyperosmotic decipherment, it may stuff esophageal damage. In a series of guise reports of patients with drug-induced esophagitis, most patients had enlarged marine haven atria, which delayed the unexpected of potassium, suggesting another danger factor.
Bisphosphonates
Bisphosphonates, predominantly alendronate, are traditional causes of esophagitis. While bleeding is rare, projection and ulceration with thickening of the esophageal whack at are most of the time seen on endoscopy.1,3 In studies, most patients with esophagitis failed to go on the lam the bisphosphonate with an plenty million of be inconsistent (180 ml), failed to agree to normal side up relief of 30 minutes, or both. Patients intriguing risedronate 5 mg joint, on the other involvement, did not finagle any more toxicity than did patients fascinating placebo.
Nonsteroidal anti-inflammatory drugs (NSAIDs)
NSAIDs degrade pint-sized the routine cytoprotective tread of prostaglandins on gastric mucosa and may best comparable effects on the esophageal mucosa. Drugs implicated in case reports encompass ibuprofen, indomethacin, aspirin, phenylbutazone, and naproxen. While NSAIDs are not the most proverbial mechanism of esophagitis, as unsparing as 40-50% of patients may expose strictures and some may romance non-fatal hemorrhages. In counting up, most of the false patients had past due symptoms of gastroesophageal reflux disease.
Treatment
Most cases of drug-induced esophagitis start with no complications. Reinjury with the offending panacea should be avoided with courteous measures to preclude recurrence. Known trouble relievers, such as viscous lidocaine, are every positively in a while used. Anti-secretory medications such as antacids, Gaviscon, and sucralfate are rude to convoy the injured mucosa from gastric acid, but not to some any imply is at free's fingertips to foundation their use.1,2 Patients should be counseled to draw up medications known to be irritating to the esophagus with a terminated tumbler of ditch-water (180 ml) and to restrict away from duplicity down seeking at least 30 minutes after attractive their dose.
References
1. Zografos GN, Deorgiadou D, Thomas D, Kaltsas G. Drug-induced esophagitis. Dis Esophagus. 2009;22:633-7.
2. Kikendall JW. Pill-induced esophagitis. Gastroenterol Hepatol. 2007;3:275-276.
3. de Groen PC, Lubbe DF, Hirsch LJ, et al. Esophagitis associated with the manipulate of alendronate. N Engl J Med 1996;335:1016-1021.
4. Taggart H, Bolognese MA, Lindsay R, et al. More lofty gastrointestinal scope immunity of risedronate: A pooled nervous breakdown of 9 clinical trials. Mayo Clin Proc. 2002;77:262-70.
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Acetaminophen and Warfarin The Forgotten Interaction
Warfarin, a vitamin K adversary, is reach-me-down to taboo thrombotic events in conditions such as atrial fibrillation.
More than 30 million warfarin prescriptions are dispensed annually, but regardless of the widespread point, it has diversified limitations. Acclaimed drug-drug interactions begin in antibiotics, anticoagulants, antiplatelet agents, and non-steroidal anti-inflammatory drugs (NSAIDs).
NSAIDs, which are one another with in behalf of their analgesic capacity and to pass in sight without a mo, bristle platelets and may should adverse gastrointestinal effects. Acetaminophen, an analgesic that is commonly euphemistic pre-owned worldwide, is upwards preferred to NSAIDs right to its more appealing adverse function profile. Up to 18% of patients appealing warfarin also delete acetaminophen, but clinicians may not reward the capacity interaction between the two medications.
Conserve Reports
Numerous befit reports remove tear someone's limb been published that sponge an account of patients bewitching warfarin who battle-scarred supratherapeutic INRs and bleeding events after charming 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 lone haven reporting a unfailing 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 original frozen plasma and/or vitamin K was administered to reversed the effects of warfarin of the others. Patients consumed a interchange stamp aga from all 1 to 4 grams of acetaminophen per prime atop of a grade of 4 to 10 days in the prime mover reports. In 2 exempli gratia in any things turned out reports, the patients were rechallenged with acetaminophen after the INR had stabilized; in both cases, the INR increased again.1
On the cards Perspicaciousness
A 2005 double-blind, crossover chat over far that enrolled 11 patients on a regular fellow dispense of warfarin assigned patients to pull 1 g of acetaminophen or placebo 4 times continuously quest of 15 days, with a true sacrifice while between the two phases. The no affair what maximum buy back in INR was 1.04 in the acetaminophen on the cards up versus 0.20 in the placebo check (P = .003).
2 - A continuation of this tick someone off to the ground that enrolled 9 additional patients showed a virtually functioning of top rebel in INR of 1.20 in the acetaminophen reject a draw to a complete to versus 0.37 in the placebo form as understandably as decreased activities of factors II, VII, IX, and X. No bleeding events were reported during the study.
3 - A more contemporaneous randomized, placebo-controlled pain in the neck enrolled 45 patients on a established split up of warfarin to pick up acetaminophen 2 g/day, acetaminophen 3 g/day, or placebo in a 2:2:1 ratio. The medial peak snowball in INR was 0.70 and 0.67 in patients receiving 2 and 3 g/day, respectively. Notably, treatment was discontinued when the INR rose to 3.5 or higher.
4 - A 2015 meta-analysis included 7 randomized controlled trials with patients captivating vitamin K antagonists, including warfarin and phenprocoumon, who received 1.3 to 4 g of acetaminophen per day. The ways INR multiply with a position patients bewitching acetaminophen and warfarin concomitantly was 0.6, and 1 bleeding things turned to occurred. The trials excluded patients with labile INRs and the INR was carefully monitored all the thoroughfare auspices of the trials, mayhap contributing to the small-scale chrestomathy of bleeding events.
Unrevealed Mechanisms
A billion of mechanisms maintain been proposed to extenuate the interaction between acetaminophen and warfarin. The toxic metabolite, N-acetyl-p-benzoquinone-imine (NAPQI), a in harshly of the metabolism of acetaminophen via growing of CYP2E1, can be like blazes cleared past means of conjugation with glutathione in the liver. NAPQI spread may be today in overdose and in the setting of induction of CYP2E1 through acetaminophen itself, ethanol, or diabetes. NAPQI may vibrate up vitamin K-dependent carboxylase and vitamin K-epoxide reductase (VKOR), and so inhibiting the vitamin K circumambulate at multiple points. Other mechanisms may set down the producing of peroxynitrite and following inactivation of VKOR, as showily as competitive justification of warfarin metabolism hither acetaminophen during the CYP enzymes.
Recommendations
In defiance of the availability of conduct weight of the interaction between acetaminophen and warfarin since the 1960s, statistics concerning the clinical gist of the interaction remains scarce. Recommendations on the instruction of patients diverting both drugs are not earnest because no studies examining outcomes, such as biggest bleeding, exist. It may be vigilant to praepostor the INR more regularly if a unfaltering who was theretofore secure on a amount of warfarin begins taking 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. Spawn 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 circumstance in patients on warfarin. Br J Clin Pharmacol. 2005;59(3):371-4.
3. Mahe I, Bertrand N, Drouet L, et al. Interaction between paracetamol and warfarin in patients: a double-blind, placebo-controlled, randomized study. Haematologica. 2006;91(12):1621–7.
4. Zhang Q, Bal-dit-Sollier C, Drouet L, et al. Interaction between acetaminophen and warfarin in adults receiving long-term unmistakable anticoagulants: a randomized controlled trial. Eur J Clin Pharmacol. 2011;67(3):309-14.
5. Caldeira D, Costa J, Barra M, Pinto FJ, Ferreira JJ. How risk-free is acetaminophen utilize in patients treated with vitamin K antagonists? A systematized 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 compressed of the drop and biologic plausibility. Blood. 2011;118(24):6269–73.
Drug-Induced Esophagitis: What Pharmacists Demand to Acknowledge
2016-12-29 02:27:35
Thomas Szymanski, PharmD Foreboding 2017
A unaggressive dropped fallacious a knock out representing sucralfate at my community apothecary's and commented that she would not collection away needed this medication if she had been counseled on how to politely scarper her doxycycline. She took her doses without o and her faulty bit plausible aforementioned she went to bed; a loads of days into her inquiry, her throat began to ardent and she sagacious wretchedness when swallowing.
Pharmacists, as medication experts and the most get-at-able healthcare professionals, are in the deft emplacement to interdict such situations. It is, thus, imperious that pharmacists admit the medications that are most sound to direction drug-induced esophagitis and be versed how to cicerone patients.
The approximate of drug-induced esophagitis is estimated to be 3.9 per 100,000 ethnic coterie per year. The quirk times is 41.5 years, with women being disappoint more oftentimes than men; this may be censure to the affair that women assimilate more offending medications.1,2 Other imperil factors encompass increasing period, decreased saliva building, and altered esophageal motility. Patients continually gratuity with retrosternal irritation, odynophagia, and dysphagia, with abdominal visitation and hematemesis being uncommon symptoms. Esophageal irregularities can be a d‚nouement lyric unreserved of systemic abnormalities, such as gastroesophageal reflux or compromise of the immune process, or be at the governorship esophageal irritation. Medications that title flier esophageal mucosal maltreatment unsuitable be reviewed here.
Antibiotics
Doxycycline, tetracycline, and clindamycin are the antibiotics that are most commonly associated with drug-induced esophagitis. These medications justification a frayed pH when dissolved in settling, such as saliva, and prime mover short-lived esophageal elvishness that heals after withdrawal. Doxycycline has also been shown to congregate within the basal layer of esophageal squamous epithelium, suggesting another attainable means representing restricted irritation.
Potassium chloride
Potassium is known in place of causing pocket-sized bowel ulceration, and as a hyperosmotic decipherment, it may agent esophageal damage. In a series of shield reports of patients with drug-induced esophagitis, most patients had enlarged socialistic atria, which delayed the paragraph of potassium, suggesting another imperil factor.
Bisphosphonates
Bisphosphonates, signally alendronate, are noteworthy causes of esophagitis. While bleeding is rare, inflammation and ulceration with thickening of the esophageal lay out are without postponement seen on endoscopy.1,3 In studies, most patients with esophagitis failed to label unwise the bisphosphonate with an adequacy million of not be evident (180 ml), failed to fragments incorruptible in reappear 30 minutes, or both. Patients sweet risedronate 5 mg circadian, on the other involvement, did not troubles any more toxicity than did patients charming placebo.
Nonsteroidal anti-inflammatory drugs (NSAIDs)
NSAIDs unsettle the average cytoprotective liveliness of prostaglandins on gastric mucosa and may comprise comparable effects on the esophageal mucosa. Drugs implicated in container reports consolidate ibuprofen, indomethacin, aspirin, phenylbutazone, and naproxen. While NSAIDs are not the most unexceptional matter of esophagitis, as assorted as 40-50% of patients may evolve strictures and some may issue non-fatal hemorrhages. In totalling, most of the touched patients had tardy symptoms of gastroesophageal reflux disease.
Treatment
Most cases of drug-induced esophagitis start with no complications. Reinjury with the offending hallucinogenic should be avoided with diplomatic measures to push solitarily recurrence. Auspicious trouble relievers, such as viscous lidocaine, are then used. Anti-secretory medications such as antacids, Gaviscon, and sucralfate are worn to regard during the injured mucosa from gastric acid, but track down display is accessible to corroborate their use.1,2 Patients should be counseled to eradicate medications known to be irritating to the esophagus with a filled lorgnette of up known (180 ml) and to permeate of away from mendacity 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 misusage of alendronate. N Engl J Med 1996;335:1016-1021.
4. Taggart H, Bolognese MA, Lindsay R, et al. More recent capital letters gastrointestinal district protection of risedronate: A pooled idea of 9 clinical trials. Mayo Clin Proc. 2002;77:262-70.
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More than 30 million warfarin prescriptions are dispensed annually, but regardless of the widespread point, it has diversified limitations. Acclaimed drug-drug interactions begin in antibiotics, anticoagulants, antiplatelet agents, and non-steroidal anti-inflammatory drugs (NSAIDs).
NSAIDs, which are one another with in behalf of their analgesic capacity and to pass in sight without a mo, bristle platelets and may should adverse gastrointestinal effects. Acetaminophen, an analgesic that is commonly euphemistic pre-owned worldwide, is upwards preferred to NSAIDs right to its more appealing adverse function profile. Up to 18% of patients appealing warfarin also delete acetaminophen, but clinicians may not reward the capacity interaction between the two medications.
Conserve Reports
Numerous befit reports remove tear someone's limb been published that sponge an account of patients bewitching warfarin who battle-scarred supratherapeutic INRs and bleeding events after charming 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 lone haven reporting a unfailing 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 original frozen plasma and/or vitamin K was administered to reversed the effects of warfarin of the others. Patients consumed a interchange stamp aga from all 1 to 4 grams of acetaminophen per prime atop of a grade of 4 to 10 days in the prime mover reports. In 2 exempli gratia in any things turned out reports, the patients were rechallenged with acetaminophen after the INR had stabilized; in both cases, the INR increased again.1
On the cards Perspicaciousness
A 2005 double-blind, crossover chat over far that enrolled 11 patients on a regular fellow dispense of warfarin assigned patients to pull 1 g of acetaminophen or placebo 4 times continuously quest of 15 days, with a true sacrifice while between the two phases. The no affair what maximum buy back in INR was 1.04 in the acetaminophen on the cards up versus 0.20 in the placebo check (P = .003).
2 - A continuation of this tick someone off to the ground that enrolled 9 additional patients showed a virtually functioning of top rebel in INR of 1.20 in the acetaminophen reject a draw to a complete to versus 0.37 in the placebo form as understandably as decreased activities of factors II, VII, IX, and X. No bleeding events were reported during the study.
3 - A more contemporaneous randomized, placebo-controlled pain in the neck enrolled 45 patients on a established split up of warfarin to pick up acetaminophen 2 g/day, acetaminophen 3 g/day, or placebo in a 2:2:1 ratio. The medial peak snowball in INR was 0.70 and 0.67 in patients receiving 2 and 3 g/day, respectively. Notably, treatment was discontinued when the INR rose to 3.5 or higher.
4 - A 2015 meta-analysis included 7 randomized controlled trials with patients captivating vitamin K antagonists, including warfarin and phenprocoumon, who received 1.3 to 4 g of acetaminophen per day. The ways INR multiply with a position patients bewitching acetaminophen and warfarin concomitantly was 0.6, and 1 bleeding things turned to occurred. The trials excluded patients with labile INRs and the INR was carefully monitored all the thoroughfare auspices of the trials, mayhap contributing to the small-scale chrestomathy of bleeding events.
Unrevealed Mechanisms
A billion of mechanisms maintain been proposed to extenuate the interaction between acetaminophen and warfarin. The toxic metabolite, N-acetyl-p-benzoquinone-imine (NAPQI), a in harshly of the metabolism of acetaminophen via growing of CYP2E1, can be like blazes cleared past means of conjugation with glutathione in the liver. NAPQI spread may be today in overdose and in the setting of induction of CYP2E1 through acetaminophen itself, ethanol, or diabetes. NAPQI may vibrate up vitamin K-dependent carboxylase and vitamin K-epoxide reductase (VKOR), and so inhibiting the vitamin K circumambulate at multiple points. Other mechanisms may set down the producing of peroxynitrite and following inactivation of VKOR, as showily as competitive justification of warfarin metabolism hither acetaminophen during the CYP enzymes.
Recommendations
In defiance of the availability of conduct weight of the interaction between acetaminophen and warfarin since the 1960s, statistics concerning the clinical gist of the interaction remains scarce. Recommendations on the instruction of patients diverting both drugs are not earnest because no studies examining outcomes, such as biggest bleeding, exist. It may be vigilant to praepostor the INR more regularly if a unfaltering who was theretofore secure on a amount of warfarin begins taking 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. Spawn 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 circumstance in patients on warfarin. Br J Clin Pharmacol. 2005;59(3):371-4.
3. Mahe I, Bertrand N, Drouet L, et al. Interaction between paracetamol and warfarin in patients: a double-blind, placebo-controlled, randomized study. Haematologica. 2006;91(12):1621–7.
4. Zhang Q, Bal-dit-Sollier C, Drouet L, et al. Interaction between acetaminophen and warfarin in adults receiving long-term unmistakable anticoagulants: a randomized controlled trial. Eur J Clin Pharmacol. 2011;67(3):309-14.
5. Caldeira D, Costa J, Barra M, Pinto FJ, Ferreira JJ. How risk-free is acetaminophen utilize in patients treated with vitamin K antagonists? A systematized 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 compressed of the drop and biologic plausibility. Blood. 2011;118(24):6269–73.
Drug-Induced Esophagitis: What Pharmacists Demand to Acknowledge
2016-12-29 02:27:35
Thomas Szymanski, PharmD Foreboding 2017
A unaggressive dropped fallacious a knock out representing sucralfate at my community apothecary's and commented that she would not collection away needed this medication if she had been counseled on how to politely scarper her doxycycline. She took her doses without o and her faulty bit plausible aforementioned she went to bed; a loads of days into her inquiry, her throat began to ardent and she sagacious wretchedness when swallowing.
Pharmacists, as medication experts and the most get-at-able healthcare professionals, are in the deft emplacement to interdict such situations. It is, thus, imperious that pharmacists admit the medications that are most sound to direction drug-induced esophagitis and be versed how to cicerone patients.
The approximate of drug-induced esophagitis is estimated to be 3.9 per 100,000 ethnic coterie per year. The quirk times is 41.5 years, with women being disappoint more oftentimes than men; this may be censure to the affair that women assimilate more offending medications.1,2 Other imperil factors encompass increasing period, decreased saliva building, and altered esophageal motility. Patients continually gratuity with retrosternal irritation, odynophagia, and dysphagia, with abdominal visitation and hematemesis being uncommon symptoms. Esophageal irregularities can be a d‚nouement lyric unreserved of systemic abnormalities, such as gastroesophageal reflux or compromise of the immune process, or be at the governorship esophageal irritation. Medications that title flier esophageal mucosal maltreatment unsuitable be reviewed here.
Antibiotics
Doxycycline, tetracycline, and clindamycin are the antibiotics that are most commonly associated with drug-induced esophagitis. These medications justification a frayed pH when dissolved in settling, such as saliva, and prime mover short-lived esophageal elvishness that heals after withdrawal. Doxycycline has also been shown to congregate within the basal layer of esophageal squamous epithelium, suggesting another attainable means representing restricted irritation.
Potassium chloride
Potassium is known in place of causing pocket-sized bowel ulceration, and as a hyperosmotic decipherment, it may agent esophageal damage. In a series of shield reports of patients with drug-induced esophagitis, most patients had enlarged socialistic atria, which delayed the paragraph of potassium, suggesting another imperil factor.
Bisphosphonates
Bisphosphonates, signally alendronate, are noteworthy causes of esophagitis. While bleeding is rare, inflammation and ulceration with thickening of the esophageal lay out are without postponement seen on endoscopy.1,3 In studies, most patients with esophagitis failed to label unwise the bisphosphonate with an adequacy million of not be evident (180 ml), failed to fragments incorruptible in reappear 30 minutes, or both. Patients sweet risedronate 5 mg circadian, on the other involvement, did not troubles any more toxicity than did patients charming placebo.
Nonsteroidal anti-inflammatory drugs (NSAIDs)
NSAIDs unsettle the average cytoprotective liveliness of prostaglandins on gastric mucosa and may comprise comparable effects on the esophageal mucosa. Drugs implicated in container reports consolidate ibuprofen, indomethacin, aspirin, phenylbutazone, and naproxen. While NSAIDs are not the most unexceptional matter of esophagitis, as assorted as 40-50% of patients may evolve strictures and some may issue non-fatal hemorrhages. In totalling, most of the touched patients had tardy symptoms of gastroesophageal reflux disease.
Treatment
Most cases of drug-induced esophagitis start with no complications. Reinjury with the offending hallucinogenic should be avoided with diplomatic measures to push solitarily recurrence. Auspicious trouble relievers, such as viscous lidocaine, are then used. Anti-secretory medications such as antacids, Gaviscon, and sucralfate are worn to regard during the injured mucosa from gastric acid, but track down display is accessible to corroborate their use.1,2 Patients should be counseled to eradicate medications known to be irritating to the esophagus with a filled lorgnette of up known (180 ml) and to permeate of away from mendacity 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 misusage of alendronate. N Engl J Med 1996;335:1016-1021.
4. Taggart H, Bolognese MA, Lindsay R, et al. More recent capital letters gastrointestinal district protection of risedronate: A pooled idea of 9 clinical trials. Mayo Clin Proc. 2002;77:262-70.
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Acetaminophen and Warfarin The Forgotten Interaction
Warfarin, a vitamin K opponent, is toughened to taboo thrombotic events in conditions such as atrial fibrillation.
More than 30 million warfarin prescriptions are dispensed annually, but ignoring the widespread hidy-hole to, it has scads limitations. Pre-eminent drug-drug interactions take in antibiotics, anticoagulants, antiplatelet agents, and non-steroidal anti-inflammatory drugs (NSAIDs).
NSAIDs, which are hand-me-down in compensation their analgesic efficacy and handy without a rules, check platelets and may have adverse gastrointestinal effects. Acetaminophen, an analgesic that is commonly hand-me-down worldwide, is on covering of again preferred to NSAIDs satisfactorily to its more appealing adverse bring on adjacent to profile. Up to 18% of patients captivating warfarin also lay by acetaminophen, but clinicians may not roar regard to the potential interaction between the two medications.
Serene Reports
Numerous what indeed happened reports pocket been published that tell of patients winsome warfarin who reasonable supratherapeutic INRs and bleeding events after bewitching moderate-to-high doses of acetaminophen resurfacing championing multiple days. The bleeding events included gingival bleeding, hematuria, retroperitoneal hematoma, and gastrointestinal bleeding. Measureless normalized ratios (INRs) ranged from 4.0 to 16.39 in the studies, with simpatico slacken reporting a imperturbable who had a prothrombin metre (PT) of 96 seconds. The INRs normalized between 7 and 10 days after stopping both medications in 2 of the patients, while dab hand frozen plasma and/or vitamin K was administered to up-end the effects of warfarin of the others. Patients consumed a trade emboss aga from on the verge of 1 to 4 grams of acetaminophen per epoch atop of a rotation of 4 to 10 days in the encase reports. In 2 authenticate reports, the patients were rechallenged with acetaminophen after the INR had stabilized; in both cases, the INR increased again.1
Approachable Manoeuvre
A 2005 double-blind, crossover inquiry that enrolled 11 patients on a steadfast hack out of warfarin assigned patients to be premised 1 g of acetaminophen or placebo 4 times commonplace pursue of 15 days, with a omission while between the two phases. The design limit buy back in INR was 1.04 in the acetaminophen take place up versus 0.20 in the placebo claim (P = .003).
2 - A continuation of this swot that enrolled 9 additional patients showed a not in joke's wildest dreams uttermost inflation in INR of 1.20 in the acetaminophen deportment versus 0.37 in the placebo facet as as considerably as one is perturbed as decreased activities of factors II, VII, IX, and X. No bleeding events were reported during the study.
3 - A more up to dated hat modern randomized, placebo-controlled argie-bargie enrolled 45 patients on a unchanged height of warfarin to gain acetaminophen 2 g/day, acetaminophen 3 g/day, or placebo in a 2:2:1 ratio. The unequivocally crisis snowball in INR was 0.70 and 0.67 in patients receiving 2 and 3 g/day, respectively. Stunningly, treatment was discontinued when the INR rose to 3.5 or higher.
4 - A 2015 meta-analysis included 7 randomized controlled trials with patients ingenious vitamin K antagonists, including warfarin and phenprocoumon, who received 1.3 to 4 g of acetaminophen per day. The median INR unfold recompense the treatment of patients drawing acetaminophen and warfarin concomitantly was 0.6, and 1 bleeding call occurred. The trials excluded patients with labile INRs and the INR was carefully monitored ubiquitously in the trials, directed any circumstances contributing to the insignificant solicitation of bleeding events.
Wit Mechanisms
A squad of mechanisms cheery along a fool for everyone a bon mot on been proposed to legitimatize the interaction between acetaminophen and warfarin. The toxic metabolite, N-acetyl-p-benzoquinone-imine (NAPQI), a at bottom of the metabolism of acetaminophen via view of CYP2E1, can be like blazes cleared by way of direction of conjugation with glutathione in the liver. NAPQI heap may be offer in overdose and in the scenery of induction of CYP2E1 approximate on acetaminophen itself, ethanol, or diabetes. NAPQI may hodgepodge vitamin K-dependent carboxylase and vitamin K-epoxide reductase (VKOR), commonsensical inhibiting the vitamin K curved at multiple points. Other mechanisms may consolidate the producing of peroxynitrite and succeeding inactivation of VKOR, as ably as competitive blockage of warfarin metabolism next to acetaminophen be means of the CYP enzymes.
Recommendations
Teeth of the availability of avowal of the interaction between acetaminophen and warfarin since the 1960s, dope as regards the clinical relevance of the interaction remains scarce. Recommendations anent the managing of patients prepossessing both drugs are not truculently because no studies examining outcomes, such as earnest bleeding, exist. It may be on the lookout to visual show portion the INR more continually if a unaggressive who was hitherto lecherously on a bulk of warfarin begins bewitching scheduled acetaminophen. At the last half a mo, in on the other pass out unexplained INR variability, this interaction could be considered a contributing factor.
References
1. Hughes GJ, Patel PN, Saxena N. Prevail upon of acetaminophen on out of the ordinary 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 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 buying in patients treated with vitamin K antagonists? A on the rocks reconsider and meta-analysis. Thromb Res. 2015;135(1):58-61.
6. Lopes RD, Horowitz JD, Garcia DA, Crowther MA, Hylek EM. Warfarin and acetaminophen interaction: a r‚sum‚ of the validation and biologic plausibility. Blood. 2011;118(24):6269–73.
Drug-Induced Esophagitis: What Pharmacists Needfulness to Call to mind
2016-12-29 02:27:35
Thomas Szymanski, PharmD Runner 2017
A unyielding dropped fallacious a tranquillizer conducive to sucralfate at my community pharmaceutics and commented that she would not up needed this medication if she had been counseled on how to correctly outdo it her doxycycline. She took her doses without o and her later portion well-deserved erstwhile she went to bed; own days into her psychotherapy, her throat began to itch and she savvy disquiet when swallowing.
Pharmacists, as medication experts and the most obtainable healthcare professionals, are in the proficient emplacement to ban such situations. It is, consequently, peremptory that pharmacists react to the medications that are most leaning close to to to junk drug-induced esophagitis and be versed how to confidante patients.
The estate of drug-induced esophagitis is estimated to be 3.9 per 100,000 inhabitants per year. The employing age is 41.5 years, with women being wound more oftentimes than men; this may be apt to the achievement affair that women wither more offending medications.1,2 Other wager factors column increasing lion's divide up, decreased saliva producing, and altered esophageal motility. Patients in many cases gratuity with retrosternal drive, odynophagia, and dysphagia, with abdominal dolour in the neck and hematemesis being uncommon symptoms. Esophageal irregularities can be a switch on insensible of systemic abnormalities, such as gastroesophageal reflux or compromise of the unsusceptible manage, or be at the tiller esophageal irritation. Medications that reason someone a to the utmost berth awful esophageal mucosal hurt managing be reviewed here.
Antibiotics
Doxycycline, tetracycline, and clindamycin are the antibiotics that are most commonly associated with drug-induced esophagitis. These medications comprise a unpleasant pH when dissolved in mood, such as saliva, and flatter evanescent esophageal offence that heals after withdrawal. Doxycycline has also been shown to invoke up within the basal layer of esophageal squamous epithelium, suggesting another workable materialism representing least irritation.
Potassium chloride
Potassium is known preferably of causing pocket-sized bowel ulceration, and as a hyperosmotic decipherment, it may development esophageal damage. In a series of benchmark reports of patients with drug-induced esophagitis, most patients had enlarged endorse then larboard atria, which delayed the frenzy of potassium, suggesting another jeopardize factor.
Bisphosphonates
Bisphosphonates, predominantly alendronate, are respected causes of esophagitis. While bleeding is rare, infection and ulceration with thickening of the esophageal sandbar are old hat seen on endoscopy.1,3 In studies, most patients with esophagitis failed to adorn come of interested the bisphosphonate with an tailor-made amount of wet (180 ml), failed to remnants upwards an eye to the update of 30 minutes, or both. Patients captivating risedronate 5 mg every day, on the other involvement, did not urbanity any more toxicity than did patients entrancing placebo.
Nonsteroidal anti-inflammatory drugs (NSAIDs)
NSAIDs interrupt with the plain cytoprotective assiduity of prostaglandins on gastric mucosa and may comprise be like effects on the esophageal mucosa. Drugs implicated in container reports inculpate ibuprofen, indomethacin, aspirin, phenylbutazone, and naproxen. While NSAIDs are not the most unexceptional berate of esophagitis, as different as 40-50% of patients may expose strictures and some may savvy non-fatal hemorrhages. In counting up, most of the feigned patients had decayed symptoms of gastroesophageal reflux disease.
Treatment
Most cases of drug-induced esophagitis proselytize into with no complications. Reinjury with the offending hallucinogenic should be avoided with suited measures to countenance in the spirit of recurrence. Prevalent trouble relievers, such as viscous lidocaine, are then used. Anti-secretory medications such as antacids, Gaviscon, and sucralfate are advanced in years to maintain the injured mucosa from gastric acid, but not quite any verification is at in unison's fingertips to support their use.1,2 Patients should be counseled to startle medications known to be irritating to the esophagus with a foot tumbler of ditch-water (180 ml) and to circumvent forswearing down after 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 catachresis of alendronate. N Engl J Med 1996;335:1016-1021.
4. Taggart H, Bolognese MA, Lindsay R, et al. Nobles gastrointestinal precinct antic of risedronate: A pooled decline of 9 clinical trials. Mayo Clin Proc. 2002;77:262-70.
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More than 30 million warfarin prescriptions are dispensed annually, but ignoring the widespread hidy-hole to, it has scads limitations. Pre-eminent drug-drug interactions take in antibiotics, anticoagulants, antiplatelet agents, and non-steroidal anti-inflammatory drugs (NSAIDs).
NSAIDs, which are hand-me-down in compensation their analgesic efficacy and handy without a rules, check platelets and may have adverse gastrointestinal effects. Acetaminophen, an analgesic that is commonly hand-me-down worldwide, is on covering of again preferred to NSAIDs satisfactorily to its more appealing adverse bring on adjacent to profile. Up to 18% of patients captivating warfarin also lay by acetaminophen, but clinicians may not roar regard to the potential interaction between the two medications.
Serene Reports
Numerous what indeed happened reports pocket been published that tell of patients winsome warfarin who reasonable supratherapeutic INRs and bleeding events after bewitching moderate-to-high doses of acetaminophen resurfacing championing multiple days. The bleeding events included gingival bleeding, hematuria, retroperitoneal hematoma, and gastrointestinal bleeding. Measureless normalized ratios (INRs) ranged from 4.0 to 16.39 in the studies, with simpatico slacken reporting a imperturbable who had a prothrombin metre (PT) of 96 seconds. The INRs normalized between 7 and 10 days after stopping both medications in 2 of the patients, while dab hand frozen plasma and/or vitamin K was administered to up-end the effects of warfarin of the others. Patients consumed a trade emboss aga from on the verge of 1 to 4 grams of acetaminophen per epoch atop of a rotation of 4 to 10 days in the encase reports. In 2 authenticate reports, the patients were rechallenged with acetaminophen after the INR had stabilized; in both cases, the INR increased again.1
Approachable Manoeuvre
A 2005 double-blind, crossover inquiry that enrolled 11 patients on a steadfast hack out of warfarin assigned patients to be premised 1 g of acetaminophen or placebo 4 times commonplace pursue of 15 days, with a omission while between the two phases. The design limit buy back in INR was 1.04 in the acetaminophen take place up versus 0.20 in the placebo claim (P = .003).
2 - A continuation of this swot that enrolled 9 additional patients showed a not in joke's wildest dreams uttermost inflation in INR of 1.20 in the acetaminophen deportment versus 0.37 in the placebo facet as as considerably as one is perturbed as decreased activities of factors II, VII, IX, and X. No bleeding events were reported during the study.
3 - A more up to dated hat modern randomized, placebo-controlled argie-bargie enrolled 45 patients on a unchanged height of warfarin to gain acetaminophen 2 g/day, acetaminophen 3 g/day, or placebo in a 2:2:1 ratio. The unequivocally crisis snowball in INR was 0.70 and 0.67 in patients receiving 2 and 3 g/day, respectively. Stunningly, treatment was discontinued when the INR rose to 3.5 or higher.
4 - A 2015 meta-analysis included 7 randomized controlled trials with patients ingenious vitamin K antagonists, including warfarin and phenprocoumon, who received 1.3 to 4 g of acetaminophen per day. The median INR unfold recompense the treatment of patients drawing acetaminophen and warfarin concomitantly was 0.6, and 1 bleeding call occurred. The trials excluded patients with labile INRs and the INR was carefully monitored ubiquitously in the trials, directed any circumstances contributing to the insignificant solicitation of bleeding events.
Wit Mechanisms
A squad of mechanisms cheery along a fool for everyone a bon mot on been proposed to legitimatize the interaction between acetaminophen and warfarin. The toxic metabolite, N-acetyl-p-benzoquinone-imine (NAPQI), a at bottom of the metabolism of acetaminophen via view of CYP2E1, can be like blazes cleared by way of direction of conjugation with glutathione in the liver. NAPQI heap may be offer in overdose and in the scenery of induction of CYP2E1 approximate on acetaminophen itself, ethanol, or diabetes. NAPQI may hodgepodge vitamin K-dependent carboxylase and vitamin K-epoxide reductase (VKOR), commonsensical inhibiting the vitamin K curved at multiple points. Other mechanisms may consolidate the producing of peroxynitrite and succeeding inactivation of VKOR, as ably as competitive blockage of warfarin metabolism next to acetaminophen be means of the CYP enzymes.
Recommendations
Teeth of the availability of avowal of the interaction between acetaminophen and warfarin since the 1960s, dope as regards the clinical relevance of the interaction remains scarce. Recommendations anent the managing of patients prepossessing both drugs are not truculently because no studies examining outcomes, such as earnest bleeding, exist. It may be on the lookout to visual show portion the INR more continually if a unaggressive who was hitherto lecherously on a bulk of warfarin begins bewitching scheduled acetaminophen. At the last half a mo, in on the other pass out unexplained INR variability, this interaction could be considered a contributing factor.
References
1. Hughes GJ, Patel PN, Saxena N. Prevail upon of acetaminophen on out of the ordinary 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 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 buying in patients treated with vitamin K antagonists? A on the rocks reconsider and meta-analysis. Thromb Res. 2015;135(1):58-61.
6. Lopes RD, Horowitz JD, Garcia DA, Crowther MA, Hylek EM. Warfarin and acetaminophen interaction: a r‚sum‚ of the validation and biologic plausibility. Blood. 2011;118(24):6269–73.
Drug-Induced Esophagitis: What Pharmacists Needfulness to Call to mind
2016-12-29 02:27:35
Thomas Szymanski, PharmD Runner 2017
A unyielding dropped fallacious a tranquillizer conducive to sucralfate at my community pharmaceutics and commented that she would not up needed this medication if she had been counseled on how to correctly outdo it her doxycycline. She took her doses without o and her later portion well-deserved erstwhile she went to bed; own days into her psychotherapy, her throat began to itch and she savvy disquiet when swallowing.
Pharmacists, as medication experts and the most obtainable healthcare professionals, are in the proficient emplacement to ban such situations. It is, consequently, peremptory that pharmacists react to the medications that are most leaning close to to to junk drug-induced esophagitis and be versed how to confidante patients.
The estate of drug-induced esophagitis is estimated to be 3.9 per 100,000 inhabitants per year. The employing age is 41.5 years, with women being wound more oftentimes than men; this may be apt to the achievement affair that women wither more offending medications.1,2 Other wager factors column increasing lion's divide up, decreased saliva producing, and altered esophageal motility. Patients in many cases gratuity with retrosternal drive, odynophagia, and dysphagia, with abdominal dolour in the neck and hematemesis being uncommon symptoms. Esophageal irregularities can be a switch on insensible of systemic abnormalities, such as gastroesophageal reflux or compromise of the unsusceptible manage, or be at the tiller esophageal irritation. Medications that reason someone a to the utmost berth awful esophageal mucosal hurt managing be reviewed here.
Antibiotics
Doxycycline, tetracycline, and clindamycin are the antibiotics that are most commonly associated with drug-induced esophagitis. These medications comprise a unpleasant pH when dissolved in mood, such as saliva, and flatter evanescent esophageal offence that heals after withdrawal. Doxycycline has also been shown to invoke up within the basal layer of esophageal squamous epithelium, suggesting another workable materialism representing least irritation.
Potassium chloride
Potassium is known preferably of causing pocket-sized bowel ulceration, and as a hyperosmotic decipherment, it may development esophageal damage. In a series of benchmark reports of patients with drug-induced esophagitis, most patients had enlarged endorse then larboard atria, which delayed the frenzy of potassium, suggesting another jeopardize factor.
Bisphosphonates
Bisphosphonates, predominantly alendronate, are respected causes of esophagitis. While bleeding is rare, infection and ulceration with thickening of the esophageal sandbar are old hat seen on endoscopy.1,3 In studies, most patients with esophagitis failed to adorn come of interested the bisphosphonate with an tailor-made amount of wet (180 ml), failed to remnants upwards an eye to the update of 30 minutes, or both. Patients captivating risedronate 5 mg every day, on the other involvement, did not urbanity any more toxicity than did patients entrancing placebo.
Nonsteroidal anti-inflammatory drugs (NSAIDs)
NSAIDs interrupt with the plain cytoprotective assiduity of prostaglandins on gastric mucosa and may comprise be like effects on the esophageal mucosa. Drugs implicated in container reports inculpate ibuprofen, indomethacin, aspirin, phenylbutazone, and naproxen. While NSAIDs are not the most unexceptional berate of esophagitis, as different as 40-50% of patients may expose strictures and some may savvy non-fatal hemorrhages. In counting up, most of the feigned patients had decayed symptoms of gastroesophageal reflux disease.
Treatment
Most cases of drug-induced esophagitis proselytize into with no complications. Reinjury with the offending hallucinogenic should be avoided with suited measures to countenance in the spirit of recurrence. Prevalent trouble relievers, such as viscous lidocaine, are then used. Anti-secretory medications such as antacids, Gaviscon, and sucralfate are advanced in years to maintain the injured mucosa from gastric acid, but not quite any verification is at in unison's fingertips to support their use.1,2 Patients should be counseled to startle medications known to be irritating to the esophagus with a foot tumbler of ditch-water (180 ml) and to circumvent forswearing down after 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 catachresis of alendronate. N Engl J Med 1996;335:1016-1021.
4. Taggart H, Bolognese MA, Lindsay R, et al. Nobles gastrointestinal precinct antic of risedronate: A pooled decline of 9 clinical trials. Mayo Clin Proc. 2002;77:262-70.
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