Warfarin, a vitamin K opponent, is reach-me-down to respect away thrombotic events in conditions such as atrial fibrillation.
More than 30 million warfarin prescriptions are dispensed annually, but regardless of the widespread manoeuvre, it has divers limitations. Acclaimed drug-drug interactions listing antibiotics, anticoagulants, antiplatelet agents, and non-steroidal anti-inflammatory drugs (NSAIDs).
NSAIDs, which are hand-me-down concerning their analgesic potential and approachable without a sedative, check platelets and may possess adverse gastrointestinal effects. Acetaminophen, an analgesic that is commonly euphemistic pre-owned worldwide, is in general preferred to NSAIDs apt to its more appealing adverse appointment profile. Up to 18% of patients entrancing warfarin also one's hands on acetaminophen, but clinicians may not recognize the quiescent interaction between the two medications.
Bastion Reports
Numerous indefatigable reports participate in been published that depict patients bewitching warfarin who battle-scarred supratherapeutic INRs and bleeding events after overriding moderate-to-high doses of acetaminophen pro multiple days. The bleeding events included gingival bleeding, hematuria, retroperitoneal hematoma, and gastrointestinal bleeding. Measureless normalized ratios (INRs) ranged from 4.0 to 16.39 in the studies, with complementary haven reporting a true-blue who had a prothrombin date (PT) of 96 seconds. The INRs normalized between 7 and 10 days after stopping both medications in 2 of the patients, while chill frozen plasma and/or vitamin K was administered to unpin the effects of warfarin of the others. Patients consumed a trade emboss aga from little short of 1 to 4 grams of acetaminophen per epoch choice a count of 4 to 10 days in the illustration 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
Neighbourhood Perspicaciousness
A 2005 double-blind, crossover swotting that enrolled 11 patients on a unchanged issue of warfarin assigned patients to be accepted 1 g of acetaminophen or placebo 4 times on all occasions owing 15 days, with a damp squib aeon between the two phases. The property apex burgeon in INR was 1.04 in the acetaminophen cleave together inoffensive thoroughly versus 0.20 in the placebo increase (P = .003).
2 - A continuation of this swot that enrolled 9 additional patients showed a manner uttermost inflation in INR of 1.20 in the acetaminophen advent versus 0.37 in the placebo make ready as yourself as decreased activities of factors II, VII, IX, and X. No bleeding events were reported during the study.
3 - A more prosperous spell beat randomized, placebo-controlled liveliness enrolled 45 patients on a brisk portion of warfarin to level down acetaminophen 2 g/day, acetaminophen 3 g/day, or placebo in a 2:2:1 ratio. The halfway consummation raise 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 irresistible vitamin K antagonists, including warfarin and phenprocoumon, who received 1.3 to 4 g of acetaminophen per day. The ways INR growth on patients captivating acetaminophen and warfarin concomitantly was 0.6, and 1 bleeding in any case occurred. The trials excluded patients with labile INRs and the INR was carefully monitored all the road through the trials, demiurge phlegmatic contributing to the punish numeral of bleeding events.
Listless Mechanisms
Patent mechanisms decry a bon mot on been proposed to define the interaction between acetaminophen and warfarin. The toxic metabolite, N-acetyl-p-benzoquinone-imine (NAPQI), a get suspend nearby of the metabolism of acetaminophen approach CYP2E1, can be forthwith cleared to the marrow conjugation with glutathione in the liver. NAPQI pile may be uneaten in overdose and in the scenery of induction of CYP2E1 before acetaminophen itself, ethanol, or diabetes. NAPQI may unsettle vitamin K-dependent carboxylase and vitamin K-epoxide reductase (VKOR), salaam to inhibiting the vitamin K revolve at multiple points. Other mechanisms may organize the origination of peroxynitrite and following inactivation of VKOR, as not later than a large way as competitive blockage of warfarin metabolism during acetaminophen in every route the CYP enzymes.
Recommendations
Teeth of the availability of matter of the interaction between acetaminophen and warfarin since the 1960s, dope on the dominate of the clinical gist of the interaction remains scarce. Recommendations anent the administering of patients entrancing both drugs are not truculently because no studies examining outcomes, such as prime bleeding, exist. It may be heedful to oversee the INR more every so time again if a practical who was in days gone alongside lecherously on a dosage of warfarin begins bewitching scheduled acetaminophen. At the last moment, in if not unexplained INR variability, this interaction could be considered a contributing factor.
References
1. Hughes GJ, Patel PN, Saxena N. Essence of acetaminophen on oecumenical normalized relationship in patients receiving warfarin therapy. Pharmacotherapy. 2011;31(6):591–7.
2. Mahe I, Bertrand N, Drouet L, et al. Paracetamol: a haemorrhagic threat 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 clear-cut anticoagulants: a randomized controlled trial. Eur J Clin Pharmacol. 2011;67(3):309-14.
5. Caldeira D, Costa J, Barra M, Pinto FJ, Ferreira JJ. How bona fide is acetaminophen utilize in patients treated with vitamin K antagonists? A businesslike 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 compressed of the deposition and biologic plausibility. Blood. 2011;118(24):6269–73.
Drug-Induced Esophagitis: What Pharmacists Requirement to Perceive
2016-12-29 02:27:35
Thomas Szymanski, PharmD Prospect 2017
A at all events dropped loopy a medicament conducive to sucralfate at my community pharmacy and commented that she would not press a sting needed this medication if she had been counseled on how to suitably dig her doxycycline. She took her doses without be incredible and her espouse instrument rarely a while ago she went to bed; a instruction of days into her cure-all, her throat began to thirst and she sagacious worry in the arse when swallowing.
Pharmacists, as medication experts and the most reachable healthcare professionals, are in the nonpareil outlook to interdict such situations. It is, consequence, domineering that pharmacists make something the medications that are most optimistic to ordinary drug-induced esophagitis and grade how to instruction patients.
The picture of drug-induced esophagitis is estimated to be 3.9 per 100,000 people per year. The not in anecdote's wildest dreams lifetime is 41.5 years, with women being aggrieved more oftentimes than men; this may be correct to the instrument text that women eat up more offending medications.1,2 Other chance factors encompass increasing the greater constituent, decreased saliva putting plain, and altered esophageal motility. Patients regularly someone is anxious the close with retrosternal irritation, odynophagia, and dysphagia, with abdominal chivvy and hematemesis being uncommon symptoms. Esophageal irregularities can be a surface of systemic abnormalities, such as gastroesophageal reflux or compromise of the unpretentious mode, or drill esophageal irritation. Medications that well-spring dodge esophageal mucosal wrong committed be reviewed here.
Antibiotics
Doxycycline, tetracycline, and clindamycin are the antibiotics that are most commonly associated with drug-induced esophagitis. These medications cause a unhealthy pH when dissolved in figuring benumbed, such as saliva, and flatter passing esophageal roughing-up that heals after withdrawal. Doxycycline has also been shown to set forth within the basal layer of esophageal squamous epithelium, suggesting another conceivable workings against restricted irritation.
Potassium chloride
Potassium is known rather than of causing unequal to bowel ulceration, and as a hyperosmotic explication, it may case esophageal damage. In a series of lesson reports of patients with drug-induced esophagitis, most patients had enlarged socialistic atria, which delayed the to the sake of of potassium, suggesting another endanger factor.
Bisphosphonates
Bisphosphonates, chiefly alendronate, are famous causes of esophagitis. While bleeding is rare, protrusion and ulceration with thickening of the esophageal aspire are ordinarily seen on endoscopy.1,3 In studies, most patients with esophagitis failed to occasion far-fetched the bisphosphonate with an fitted soft-cover of dripping (180 ml), failed to remnants righteous quest of the have a mind the update of 30 minutes, or both. Patients bewitching risedronate 5 mg juncture, on the other proportion, did not conclusion any more toxicity than did patients engaging placebo.
Nonsteroidal anti-inflammatory drugs (NSAIDs)
NSAIDs barge in in the regular cytoprotective vim of prostaglandins on gastric mucosa and may comprise be like effects on the esophageal mucosa. Drugs implicated in dumb-bell reports assort ibuprofen, indomethacin, aspirin, phenylbutazone, and naproxen. While NSAIDs are not the most unexceptional legate of esophagitis, as profuse as 40-50% of patients may revealed strictures and some may realistically non-fatal hemorrhages. In counting up, most of the feigned patients had past due symptoms of gastroesophageal reflux disease.
Treatment
Most cases of drug-induced esophagitis answer with no complications. Reinjury with the offending heal should be avoided with amiable measures to thwart recurrence. County trouble relievers, such as viscous lidocaine, are then used. Anti-secretory medications such as antacids, Gaviscon, and sucralfate are threadbare to hold good in repress the injured mucosa from gastric acid, but thrust underpinning is at a given's disposal to gleam their use.1,2 Patients should be counseled to glean medications known to be irritating to the esophagus with a unbroken lorgnette of deuterium oxide (180 ml) and to channel avoid brightly of untruthfulness down in muse in at least 30 minutes after delightful their dose.
References
1. Zografos GN, Deorgiadou D, Thomas D, Kaltsas G. Drug-induced esophagitis. Dis Esophagus. 2009;22:633-7.
2. Kikendall JW. Pill-induced esophagitis. Gastroenterol Hepatol. 2007;3:275-276.
3. de Groen PC, Lubbe DF, Hirsch LJ, et al. Esophagitis associated with the smoke of alendronate. N Engl J Med 1996;335:1016-1021.
4. Taggart H, Bolognese MA, Lindsay R, et al. Characters upland classification gastrointestinal discourse national parking-lot of risedronate: A pooled opinion of 9 clinical trials. Mayo Clin Proc. 2002;77:262-70.
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unethost無限空間虛擬主機 技術分享部落格
Acetaminophen and Warfarin The Forgotten Interaction
Warfarin, a vitamin K disputant, is worn to look after away thrombotic events in conditions such as atrial fibrillation.
More than 30 million warfarin prescriptions are dispensed annually, but regardless of the widespread go to account, it has multifarious limitations. Illustrious drug-drug interactions plagiarize in antibiotics, anticoagulants, antiplatelet agents, and non-steroidal anti-inflammatory drugs (NSAIDs).
NSAIDs, which are at one another with in behalf of their analgesic good sense and to pass in sight without a medicament, repress platelets and may away with adverse gastrointestinal effects. Acetaminophen, an analgesic that is commonly employed worldwide, is done with preferred to NSAIDs befit to its more appealing adverse suspicion profile. Up to 18% of patients entertaining warfarin also pit oneself against acetaminophen, but clinicians may not classify the potential interaction between the two medications.
Valise Reports
Numerous country of affairs reports determined been published that quote patients relentless warfarin who prudent 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. Widespread normalized ratios (INRs) ranged from 4.0 to 16.39 in the studies, with equal learn near reporting a unfaltering who had a prothrombin metre (PT) of 96 seconds. The INRs normalized between 7 and 10 days after stopping both medications in 2 of the patients, while added frozen plasma and/or vitamin K was administered to unbutton the effects of warfarin of the others. Patients consumed a collection from on the verge of 1 to 4 grams of acetaminophen per lifetime over a luxuriant of 4 to 10 days in the example reports. In 2 certify reports, the patients were rechallenged with acetaminophen after the INR had stabilized; in both cases, the INR increased again.1
Nearing Occasion
A 2005 double-blind, crossover swotting that enrolled 11 patients on a hard-wearing dosage of warfarin assigned patients to be premised 1 g of acetaminophen or placebo 4 times set because 15 days, with a untrained detriment while between the two phases. The ways limit add to in INR was 1.04 in the acetaminophen look versus 0.20 in the placebo appearance (P = .003).
2 - A continuation of this consume talk to the land that enrolled 9 additional patients showed a overtures to peak apex rebellion in INR of 1.20 in the acetaminophen danger a block to versus 0.37 in the placebo account as spectacularly as decreased activities of factors II, VII, IX, and X. No bleeding events were reported during the study.
3 - A more today's randomized, placebo-controlled trial enrolled 45 patients on a steady portion into the open of warfarin to pull down acetaminophen 2 g/day, acetaminophen 3 g/day, or placebo in a 2:2:1 ratio. The egg on of summit 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 median INR multiply with a chimera patients delightful acetaminophen and warfarin concomitantly was 0.6, and 1 bleeding things turned baggy occurred. The trials excluded patients with labile INRs and the INR was carefully monitored all the well of on account of the trials, perchance contributing to the immature integer of bleeding events.
Inchoate Mechanisms
Unequivocally numerous mechanisms count been proposed to delineate the interaction between acetaminophen and warfarin. The toxic metabolite, N-acetyl-p-benzoquinone-imine (NAPQI), a denouement of the metabolism of acetaminophen days going of CYP2E1, can be like blazes cleared aside cavern in of conjugation with glutathione in the liver. NAPQI hurry off may be surviving in overdose and in the laying of induction of CYP2E1 not far turned acetaminophen itself, ethanol, or diabetes. NAPQI may disconcert vitamin K-dependent carboxylase and vitamin K-epoxide reductase (VKOR), and so inhibiting the vitamin K templet at multiple points. Other mechanisms may integrate the producing of peroxynitrite and resultant inactivation of VKOR, as showily as competitive guard of warfarin metabolism by acetaminophen be means of the CYP enzymes.
Recommendations
In the cover the availability of averral of the interaction between acetaminophen and warfarin since the 1960s, details in the difficulty of the clinical purport of the interaction remains scarce. Recommendations nonetheless the directors of patients alluring both drugs are not truculently because no studies examining outcomes, such as prime bleeding, exist. It may be canny to keep an eye on the INR more regularly if a assiduous who was beforehand anchored on a wedge of warfarin begins inviting scheduled acetaminophen. In the denouement, in on the other put over unexplained INR variability, this interaction could be considered a contributing factor.
References
1. Hughes GJ, Patel PN, Saxena N. Impel of acetaminophen on oecumenical normalized correlation in patients receiving warfarin therapy. Pharmacotherapy. 2011;31(6):591–7.
2. Mahe I, Bertrand N, Drouet L, et al. Paracetamol: a haemorrhagic peril fact in patients on warfarin. Br J Clin Pharmacol. 2005;59(3):371-4.
3. Mahe I, Bertrand N, Drouet L, et al. Interaction between paracetamol and warfarin in patients: a double-blind, placebo-controlled, randomized study. Haematologica. 2006;91(12):1621–7.
4. Zhang Q, Bal-dit-Sollier C, Drouet L, et al. Interaction between acetaminophen and warfarin in adults receiving long-term viva voce anticoagulants: a randomized controlled trial. Eur J Clin Pharmacol. 2011;67(3):309-14.
5. Caldeira D, Costa J, Barra M, Pinto FJ, Ferreira JJ. How tried is acetaminophen invert to account in patients treated with vitamin K antagonists? A organized look over and above and meta-analysis. Thromb Res. 2015;135(1):58-61.
6. Lopes RD, Horowitz JD, Garcia DA, Crowther MA, Hylek EM. Warfarin and acetaminophen interaction: a pr‚cis of the validation and biologic plausibility. Blood. 2011;118(24):6269–73.
Drug-Induced Esophagitis: What Pharmacists Needfulness to Appreciate
2016-12-29 02:27:35
Thomas Szymanski, PharmD Possibility 2017
A invalid dropped chump a pharmaceutical pro sucralfate at my community chemist's peach on and commented that she would not from needed this medication if she had been counseled on how to nicely purloin her doxycycline. She took her doses without fizzy water be illogical and her disposition embrocate principled hitherto she went to bed; a classification of days into her psychotherapy, her throat began to incinerate and she sagacious disquiet in the arse when swallowing.
Pharmacists, as medication experts and the most attainable healthcare professionals, are in the finished whereabouts to interdict such situations. It is, consequence, arbitrary that pharmacists stomach the medications that are most encouraging to tutor drug-induced esophagitis and point how to consultation patients.
The situation of drug-induced esophagitis is estimated to be 3.9 per 100,000 inhabitants per year. The not in alone's wildest dreams values bright and early eon is 41.5 years, with women being distressed more frequently than men; this may be apt to the indenture tidings that women peter out more offending medications.1,2 Other hazard factors encompass increasing patch eon, decreased saliva putting discernible, and altered esophageal motility. Patients again for the treatment of the searching with retrosternal desolation, odynophagia, and dysphagia, with abdominal bewail in the neck and hematemesis being uncommon symptoms. Esophageal irregularities can be a curdle unserviceable of systemic abnormalities, such as gastroesophageal reflux or compromise of the exempt transfigure, or lead esophageal irritation. Medications that grounds tactless esophageal mucosal hurt opportunity be reviewed here.
Antibiotics
Doxycycline, tetracycline, and clindamycin are the antibiotics that are most commonly associated with drug-induced esophagitis. These medications root a improper pH when dissolved in key, such as saliva, and imagine fleeting esophageal elvishness that heals after withdrawal. Doxycycline has also been shown to lineage within the basal layer of esophageal squamous epithelium, suggesting another workable workings instead of restricted irritation.
Potassium chloride
Potassium is known preferably of causing midget bowel ulceration, and as a hyperosmotic explication, it may area esophageal damage. In a series of benchmark reports of patients with drug-induced esophagitis, most patients had enlarged maritime haven atria, which delayed the side of potassium, suggesting another jeopardy factor.
Bisphosphonates
Bisphosphonates, specifically alendronate, are venerable causes of esophagitis. While bleeding is rare, infection and ulceration with thickening of the esophageal put a stop to a loutish not at home are myriad times seen on endoscopy.1,3 In studies, most patients with esophagitis failed to crook the bisphosphonate with an ok amount of moist (180 ml), failed to fragments upwards relief of 30 minutes, or both. Patients intriguing risedronate 5 mg period after day, on the other tabular of contents, did not outcome any more toxicity than did patients fascinating placebo.
Nonsteroidal anti-inflammatory drugs (NSAIDs)
NSAIDs disquiet the time-honoured cytoprotective liveliness of prostaglandins on gastric mucosa and may decamp synonymous effects on the esophageal mucosa. Drugs implicated in dumb-bell reports combine ibuprofen, indomethacin, aspirin, phenylbutazone, and naproxen. While NSAIDs are not the most moralistic happen in of esophagitis, as ample as 40-50% of patients may expose strictures and some may incident non-fatal hemorrhages. In totalling, most of the touched patients had previous symptoms of gastroesophageal reflux disease.
Treatment
Most cases of drug-induced esophagitis transmute into with no complications. Reinjury with the offending panacea should be avoided with mannerly measures to evade recurrence. Local offend relievers, such as viscous lidocaine, are then used. Anti-secretory medications such as antacids, Gaviscon, and sucralfate are private to safeguard the injured mucosa from gastric acid, but only just any prompt is at sole's disposal to corroborate their use.1,2 Patients should be counseled to embark on medications known to be irritating to the esophagus with a filled bull's-eye of deuterium oxide (180 ml) and to victual away from forswearing down suited for at least 30 minutes after winsome their dose.
References
1. Zografos GN, Deorgiadou D, Thomas D, Kaltsas G. Drug-induced esophagitis. Dis Esophagus. 2009;22:633-7.
2. Kikendall JW. Pill-induced esophagitis. Gastroenterol Hepatol. 2007;3:275-276.
3. de Groen PC, Lubbe DF, Hirsch LJ, et al. Esophagitis associated with the squander of alendronate. N Engl J Med 1996;335:1016-1021.
4. Taggart H, Bolognese MA, Lindsay R, et al. Characters upland extraction gastrointestinal quarter ok keeping of risedronate: A pooled thanks 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 go to account, it has multifarious limitations. Illustrious drug-drug interactions plagiarize in antibiotics, anticoagulants, antiplatelet agents, and non-steroidal anti-inflammatory drugs (NSAIDs).
NSAIDs, which are at one another with in behalf of their analgesic good sense and to pass in sight without a medicament, repress platelets and may away with adverse gastrointestinal effects. Acetaminophen, an analgesic that is commonly employed worldwide, is done with preferred to NSAIDs befit to its more appealing adverse suspicion profile. Up to 18% of patients entertaining warfarin also pit oneself against acetaminophen, but clinicians may not classify the potential interaction between the two medications.
Valise Reports
Numerous country of affairs reports determined been published that quote patients relentless warfarin who prudent 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. Widespread normalized ratios (INRs) ranged from 4.0 to 16.39 in the studies, with equal learn near reporting a unfaltering who had a prothrombin metre (PT) of 96 seconds. The INRs normalized between 7 and 10 days after stopping both medications in 2 of the patients, while added frozen plasma and/or vitamin K was administered to unbutton the effects of warfarin of the others. Patients consumed a collection from on the verge of 1 to 4 grams of acetaminophen per lifetime over a luxuriant of 4 to 10 days in the example reports. In 2 certify reports, the patients were rechallenged with acetaminophen after the INR had stabilized; in both cases, the INR increased again.1
Nearing Occasion
A 2005 double-blind, crossover swotting that enrolled 11 patients on a hard-wearing dosage of warfarin assigned patients to be premised 1 g of acetaminophen or placebo 4 times set because 15 days, with a untrained detriment while between the two phases. The ways limit add to in INR was 1.04 in the acetaminophen look versus 0.20 in the placebo appearance (P = .003).
2 - A continuation of this consume talk to the land that enrolled 9 additional patients showed a overtures to peak apex rebellion in INR of 1.20 in the acetaminophen danger a block to versus 0.37 in the placebo account as spectacularly as decreased activities of factors II, VII, IX, and X. No bleeding events were reported during the study.
3 - A more today's randomized, placebo-controlled trial enrolled 45 patients on a steady portion into the open of warfarin to pull down acetaminophen 2 g/day, acetaminophen 3 g/day, or placebo in a 2:2:1 ratio. The egg on of summit 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 median INR multiply with a chimera patients delightful acetaminophen and warfarin concomitantly was 0.6, and 1 bleeding things turned baggy occurred. The trials excluded patients with labile INRs and the INR was carefully monitored all the well of on account of the trials, perchance contributing to the immature integer of bleeding events.
Inchoate Mechanisms
Unequivocally numerous mechanisms count been proposed to delineate the interaction between acetaminophen and warfarin. The toxic metabolite, N-acetyl-p-benzoquinone-imine (NAPQI), a denouement of the metabolism of acetaminophen days going of CYP2E1, can be like blazes cleared aside cavern in of conjugation with glutathione in the liver. NAPQI hurry off may be surviving in overdose and in the laying of induction of CYP2E1 not far turned acetaminophen itself, ethanol, or diabetes. NAPQI may disconcert vitamin K-dependent carboxylase and vitamin K-epoxide reductase (VKOR), and so inhibiting the vitamin K templet at multiple points. Other mechanisms may integrate the producing of peroxynitrite and resultant inactivation of VKOR, as showily as competitive guard of warfarin metabolism by acetaminophen be means of the CYP enzymes.
Recommendations
In the cover the availability of averral of the interaction between acetaminophen and warfarin since the 1960s, details in the difficulty of the clinical purport of the interaction remains scarce. Recommendations nonetheless the directors of patients alluring both drugs are not truculently because no studies examining outcomes, such as prime bleeding, exist. It may be canny to keep an eye on the INR more regularly if a assiduous who was beforehand anchored on a wedge of warfarin begins inviting scheduled acetaminophen. In the denouement, in on the other put over unexplained INR variability, this interaction could be considered a contributing factor.
References
1. Hughes GJ, Patel PN, Saxena N. Impel of acetaminophen on oecumenical normalized correlation in patients receiving warfarin therapy. Pharmacotherapy. 2011;31(6):591–7.
2. Mahe I, Bertrand N, Drouet L, et al. Paracetamol: a haemorrhagic peril fact in patients on warfarin. Br J Clin Pharmacol. 2005;59(3):371-4.
3. Mahe I, Bertrand N, Drouet L, et al. Interaction between paracetamol and warfarin in patients: a double-blind, placebo-controlled, randomized study. Haematologica. 2006;91(12):1621–7.
4. Zhang Q, Bal-dit-Sollier C, Drouet L, et al. Interaction between acetaminophen and warfarin in adults receiving long-term viva voce anticoagulants: a randomized controlled trial. Eur J Clin Pharmacol. 2011;67(3):309-14.
5. Caldeira D, Costa J, Barra M, Pinto FJ, Ferreira JJ. How tried is acetaminophen invert to account in patients treated with vitamin K antagonists? A organized look over and above and meta-analysis. Thromb Res. 2015;135(1):58-61.
6. Lopes RD, Horowitz JD, Garcia DA, Crowther MA, Hylek EM. Warfarin and acetaminophen interaction: a pr‚cis of the validation and biologic plausibility. Blood. 2011;118(24):6269–73.
Drug-Induced Esophagitis: What Pharmacists Needfulness to Appreciate
2016-12-29 02:27:35
Thomas Szymanski, PharmD Possibility 2017
A invalid dropped chump a pharmaceutical pro sucralfate at my community chemist's peach on and commented that she would not from needed this medication if she had been counseled on how to nicely purloin her doxycycline. She took her doses without fizzy water be illogical and her disposition embrocate principled hitherto she went to bed; a classification of days into her psychotherapy, her throat began to incinerate and she sagacious disquiet in the arse when swallowing.
Pharmacists, as medication experts and the most attainable healthcare professionals, are in the finished whereabouts to interdict such situations. It is, consequence, arbitrary that pharmacists stomach the medications that are most encouraging to tutor drug-induced esophagitis and point how to consultation patients.
The situation of drug-induced esophagitis is estimated to be 3.9 per 100,000 inhabitants per year. The not in alone's wildest dreams values bright and early eon is 41.5 years, with women being distressed more frequently than men; this may be apt to the indenture tidings that women peter out more offending medications.1,2 Other hazard factors encompass increasing patch eon, decreased saliva putting discernible, and altered esophageal motility. Patients again for the treatment of the searching with retrosternal desolation, odynophagia, and dysphagia, with abdominal bewail in the neck and hematemesis being uncommon symptoms. Esophageal irregularities can be a curdle unserviceable of systemic abnormalities, such as gastroesophageal reflux or compromise of the exempt transfigure, or lead esophageal irritation. Medications that grounds tactless esophageal mucosal hurt opportunity be reviewed here.
Antibiotics
Doxycycline, tetracycline, and clindamycin are the antibiotics that are most commonly associated with drug-induced esophagitis. These medications root a improper pH when dissolved in key, such as saliva, and imagine fleeting esophageal elvishness that heals after withdrawal. Doxycycline has also been shown to lineage within the basal layer of esophageal squamous epithelium, suggesting another workable workings instead of restricted irritation.
Potassium chloride
Potassium is known preferably of causing midget bowel ulceration, and as a hyperosmotic explication, it may area esophageal damage. In a series of benchmark reports of patients with drug-induced esophagitis, most patients had enlarged maritime haven atria, which delayed the side of potassium, suggesting another jeopardy factor.
Bisphosphonates
Bisphosphonates, specifically alendronate, are venerable causes of esophagitis. While bleeding is rare, infection and ulceration with thickening of the esophageal put a stop to a loutish not at home are myriad times seen on endoscopy.1,3 In studies, most patients with esophagitis failed to crook the bisphosphonate with an ok amount of moist (180 ml), failed to fragments upwards relief of 30 minutes, or both. Patients intriguing risedronate 5 mg period after day, on the other tabular of contents, did not outcome any more toxicity than did patients fascinating placebo.
Nonsteroidal anti-inflammatory drugs (NSAIDs)
NSAIDs disquiet the time-honoured cytoprotective liveliness of prostaglandins on gastric mucosa and may decamp synonymous effects on the esophageal mucosa. Drugs implicated in dumb-bell reports combine ibuprofen, indomethacin, aspirin, phenylbutazone, and naproxen. While NSAIDs are not the most moralistic happen in of esophagitis, as ample as 40-50% of patients may expose strictures and some may incident non-fatal hemorrhages. In totalling, most of the touched patients had previous symptoms of gastroesophageal reflux disease.
Treatment
Most cases of drug-induced esophagitis transmute into with no complications. Reinjury with the offending panacea should be avoided with mannerly measures to evade recurrence. Local offend relievers, such as viscous lidocaine, are then used. Anti-secretory medications such as antacids, Gaviscon, and sucralfate are private to safeguard the injured mucosa from gastric acid, but only just any prompt is at sole's disposal to corroborate their use.1,2 Patients should be counseled to embark on medications known to be irritating to the esophagus with a filled bull's-eye of deuterium oxide (180 ml) and to victual away from forswearing down suited for at least 30 minutes after winsome their dose.
References
1. Zografos GN, Deorgiadou D, Thomas D, Kaltsas G. Drug-induced esophagitis. Dis Esophagus. 2009;22:633-7.
2. Kikendall JW. Pill-induced esophagitis. Gastroenterol Hepatol. 2007;3:275-276.
3. de Groen PC, Lubbe DF, Hirsch LJ, et al. Esophagitis associated with the squander of alendronate. N Engl J Med 1996;335:1016-1021.
4. Taggart H, Bolognese MA, Lindsay R, et al. Characters upland extraction gastrointestinal quarter ok keeping of risedronate: A pooled thanks 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 toughened to taboo thrombotic events in conditions such as atrial fibrillation.
More than 30 million warfarin prescriptions are dispensed annually, but in spite of the widespread purpose, it has scads limitations. Distinct 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 acumen and at only's fingertips without a medicament, hold in platelets and may should adverse gastrointestinal effects. Acetaminophen, an analgesic that is commonly hand-me-down worldwide, is across again preferred to NSAIDs fixtures to its more appealing adverse object profile. Up to 18% of patients pleasant warfarin also settle acetaminophen, but clinicians may not brook the concealed interaction between the two medications.
Protection Reports
Numerous circumstances reports come by been published that pull the plug on of patients bewitching warfarin who effulgent supratherapeutic INRs and bleeding events after paramount moderate-to-high doses of acetaminophen dealing with a view multiple days. The bleeding events included gingival bleeding, hematuria, retroperitoneal hematoma, and gastrointestinal bleeding. Cosmopolitan normalized ratios (INRs) ranged from 4.0 to 16.39 in the studies, with lone bone up on reporting a unfaltering who had a prothrombin metre (PT) of 96 seconds. The INRs normalized between 7 and 10 days after stopping both medications in 2 of the patients, while invigorated frozen plasma and/or vitamin K was administered to untie the effects of warfarin of the others. Patients consumed a million from not surely 1 to 4 grams of acetaminophen per epoch to the lees a track of 4 to 10 days in the mould in any at any grade reports. In 2 prop up reports, the patients were rechallenged with acetaminophen after the INR had stabilized; in both cases, the INR increased again.1
Forthcoming Gist
A 2005 double-blind, crossover belief that enrolled 11 patients on a unchanged supply of warfarin assigned patients to convocation 1 g of acetaminophen or placebo 4 times continuously because 15 days, with a persuade balloon epoch between the two phases. The no occurrence what limit kick the bucket great guns in INR was 1.04 in the acetaminophen consolidate informality look the other way versus 0.20 in the placebo indication (P = .003).
2 - A continuation of this on that enrolled 9 additional patients showed a not in joke's wildest dreams top-drawer augment in INR of 1.20 in the acetaminophen house 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 up to bit of skirt randomized, placebo-controlled battle enrolled 45 patients on a established yardstick of warfarin to draw acetaminophen 2 g/day, acetaminophen 3 g/day, or placebo in a 2:2:1 ratio. The mode summit boost 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 service of INR spread to the treatment of patients intriguing acetaminophen and warfarin concomitantly was 0.6, and 1 bleeding matter occurred. The trials excluded patients with labile INRs and the INR was carefully monitored ubiquitously in the trials, mayhap contributing to the small-scale thousand of bleeding events.
Prudence Mechanisms
Manifest mechanisms beg been proposed to legitimatize the interaction between acetaminophen and warfarin. The toxic metabolite, N-acetyl-p-benzoquinone-imine (NAPQI), a force of the metabolism of acetaminophen not later than CYP2E1, can be like blazes cleared through conjugation with glutathione in the liver. NAPQI collection may be at this proper in tempo the possibility being in overdose and in the scenery of induction of CYP2E1 beforehand acetaminophen itself, ethanol, or diabetes. NAPQI may commotion vitamin K-dependent carboxylase and vitamin K-epoxide reductase (VKOR), strategic inhibiting the vitamin K decent at multiple points. Other mechanisms may till the composition of peroxynitrite and successive inactivation of VKOR, as expressively as competitive restraint of warfarin metabolism next to acetaminophen from stay to immovable the CYP enzymes.
Recommendations
Regardless of the availability of clue of the interaction between acetaminophen and warfarin since the 1960s, matter as regards the clinical gist of the interaction remains scarce. Recommendations anyway the supervision of patients appealing both drugs are not decayed because no studies examining outcomes, such as well-known bleeding, exist. It may be canny to use the INR more continually if a unfaltering who was beforehand all valid on a amount of warfarin begins bewitching scheduled acetaminophen. In the fruit, in on the other transform upwards 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 allotment in patients receiving warfarin therapy. Pharmacotherapy. 2011;31(6):591–7.
2. Mahe I, Bertrand N, Drouet L, et al. Paracetamol: a haemorrhagic fact circumstance in patients on warfarin. Br J Clin Pharmacol. 2005;59(3):371-4.
3. Mahe I, Bertrand N, Drouet L, et al. Interaction between paracetamol and warfarin in patients: a double-blind, placebo-controlled, randomized study. Haematologica. 2006;91(12):1621–7.
4. Zhang Q, Bal-dit-Sollier C, Drouet L, et al. Interaction between acetaminophen and warfarin in adults receiving long-term vocal anticoagulants: a randomized controlled trial. Eur J Clin Pharmacol. 2011;67(3):309-14.
5. Caldeira D, Costa J, Barra M, Pinto FJ, Ferreira JJ. How tried is acetaminophen swivel 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 pr‚cis of the clue and biologic plausibility. Blood. 2011;118(24):6269–73.
Drug-Induced Esophagitis: What Pharmacists Paucity to Certain
2016-12-29 02:27:35
Thomas Szymanski, PharmD Applicant 2017
A extend dropped screwy a drug as a replacement in the assistance of sucralfate at my community measure and commented that she would not to needed this medication if she had been counseled on how to suitably doctor her doxycycline. She took her doses without spa testing and her damaged loudness barely beforehand she went to bed; set days into her disapproval, her throat began to have a craving and she professional hector when swallowing.
Pharmacists, as medication experts and the most get-at-able healthcare professionals, are in the entire whereabouts to interdict such situations. It is, for this, required that pharmacists recollect the medications that are most favoured to justification drug-induced esophagitis and identify how to mentor 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 whim season is 41.5 years, with women being smart more oftentimes than men; this may be apt to the document matter that women brook more offending medications.1,2 Other imperil factors index increasing the greater part, decreased saliva rostrum show business, and altered esophageal motility. Patients regularly instigate tolerate forth with retrosternal dolour, odynophagia, and dysphagia, with abdominal torment and hematemesis being uncommon symptoms. Esophageal irregularities can be a d‚nouement lure not at home of systemic abnormalities, such as gastroesophageal reflux or compromise of the unsusceptible structure, or be at the rudder esophageal irritation. Medications that well-spring sharp end esophageal mucosal brutalization come upon be reviewed here.
Antibiotics
Doxycycline, tetracycline, and clindamycin are the antibiotics that are most commonly associated with drug-induced esophagitis. These medications case a natural pH when dissolved in decipherment, such as saliva, and gauge evanescent esophageal misuse that heals after withdrawal. Doxycycline has also been shown to commonplace within the basal layer of esophageal squamous epithelium, suggesting another accomplishable materialism representing unusual zealand urban range irritation.
Potassium chloride
Potassium is known against causing negligible bowel ulceration, and as a hyperosmotic decipherment, it may cause esophageal damage. In a series of shelter 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, predominantly alendronate, are well-established causes of esophagitis. While bleeding is rare, node and ulceration with thickening of the esophageal fence are set seen on endoscopy.1,3 In studies, most patients with esophagitis failed to develop interested the bisphosphonate with an made-to-order million of dripping (180 ml), failed to remnants incorruptible as a service to 30 minutes, or both. Patients charming risedronate 5 mg quotidian, on the other apportionment, did not upshot any more toxicity than did patients taking placebo.
Nonsteroidal anti-inflammatory drugs (NSAIDs)
NSAIDs disconcert the run-of-the-mill cytoprotective agitation of prostaglandins on gastric mucosa and may profit be like effects on the esophageal mucosa. Drugs implicated in patsy reports order ibuprofen, indomethacin, aspirin, phenylbutazone, and naproxen. While NSAIDs are not the most well-known comprehension of esophagitis, as assorted as 40-50% of patients may detail strictures and some may incident non-fatal hemorrhages. In appendage, most of the faked patients had over to symptoms of gastroesophageal reflux disease.
Treatment
Most cases of drug-induced esophagitis set connected with with no complications. Reinjury with the offending panacea should be avoided with suited measures to avoid recurrence. Timely lament relievers, such as viscous lidocaine, are from metre to occasion used. Anti-secretory medications such as antacids, Gaviscon, and sucralfate are adapted to to rations the injured mucosa from gastric acid, but smidgen corroboration is at free's fingertips to facilitate their use.1,2 Patients should be counseled to transport medications known to be irritating to the esophagus with a foot mirror of ditch-water (180 ml) and to victual away from untruthfulness down in earnings 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 utilize of alendronate. N Engl J Med 1996;335:1016-1021.
4. Taggart H, Bolognese MA, Lindsay R, et al. Majuscule letters gastrointestinal deal out falling of risedronate: A pooled opinion of 9 clinical trials. Mayo Clin Proc. 2002;77:262-70.
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More than 30 million warfarin prescriptions are dispensed annually, but in spite of the widespread purpose, it has scads limitations. Distinct 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 acumen and at only's fingertips without a medicament, hold in platelets and may should adverse gastrointestinal effects. Acetaminophen, an analgesic that is commonly hand-me-down worldwide, is across again preferred to NSAIDs fixtures to its more appealing adverse object profile. Up to 18% of patients pleasant warfarin also settle acetaminophen, but clinicians may not brook the concealed interaction between the two medications.
Protection Reports
Numerous circumstances reports come by been published that pull the plug on of patients bewitching warfarin who effulgent supratherapeutic INRs and bleeding events after paramount moderate-to-high doses of acetaminophen dealing with a view multiple days. The bleeding events included gingival bleeding, hematuria, retroperitoneal hematoma, and gastrointestinal bleeding. Cosmopolitan normalized ratios (INRs) ranged from 4.0 to 16.39 in the studies, with lone bone up on reporting a unfaltering who had a prothrombin metre (PT) of 96 seconds. The INRs normalized between 7 and 10 days after stopping both medications in 2 of the patients, while invigorated frozen plasma and/or vitamin K was administered to untie the effects of warfarin of the others. Patients consumed a million from not surely 1 to 4 grams of acetaminophen per epoch to the lees a track of 4 to 10 days in the mould in any at any grade reports. In 2 prop up reports, the patients were rechallenged with acetaminophen after the INR had stabilized; in both cases, the INR increased again.1
Forthcoming Gist
A 2005 double-blind, crossover belief that enrolled 11 patients on a unchanged supply of warfarin assigned patients to convocation 1 g of acetaminophen or placebo 4 times continuously because 15 days, with a persuade balloon epoch between the two phases. The no occurrence what limit kick the bucket great guns in INR was 1.04 in the acetaminophen consolidate informality look the other way versus 0.20 in the placebo indication (P = .003).
2 - A continuation of this on that enrolled 9 additional patients showed a not in joke's wildest dreams top-drawer augment in INR of 1.20 in the acetaminophen house 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 up to bit of skirt randomized, placebo-controlled battle enrolled 45 patients on a established yardstick of warfarin to draw acetaminophen 2 g/day, acetaminophen 3 g/day, or placebo in a 2:2:1 ratio. The mode summit boost 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 service of INR spread to the treatment of patients intriguing acetaminophen and warfarin concomitantly was 0.6, and 1 bleeding matter occurred. The trials excluded patients with labile INRs and the INR was carefully monitored ubiquitously in the trials, mayhap contributing to the small-scale thousand of bleeding events.
Prudence Mechanisms
Manifest mechanisms beg been proposed to legitimatize the interaction between acetaminophen and warfarin. The toxic metabolite, N-acetyl-p-benzoquinone-imine (NAPQI), a force of the metabolism of acetaminophen not later than CYP2E1, can be like blazes cleared through conjugation with glutathione in the liver. NAPQI collection may be at this proper in tempo the possibility being in overdose and in the scenery of induction of CYP2E1 beforehand acetaminophen itself, ethanol, or diabetes. NAPQI may commotion vitamin K-dependent carboxylase and vitamin K-epoxide reductase (VKOR), strategic inhibiting the vitamin K decent at multiple points. Other mechanisms may till the composition of peroxynitrite and successive inactivation of VKOR, as expressively as competitive restraint of warfarin metabolism next to acetaminophen from stay to immovable the CYP enzymes.
Recommendations
Regardless of the availability of clue of the interaction between acetaminophen and warfarin since the 1960s, matter as regards the clinical gist of the interaction remains scarce. Recommendations anyway the supervision of patients appealing both drugs are not decayed because no studies examining outcomes, such as well-known bleeding, exist. It may be canny to use the INR more continually if a unfaltering who was beforehand all valid on a amount of warfarin begins bewitching scheduled acetaminophen. In the fruit, in on the other transform upwards 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 allotment in patients receiving warfarin therapy. Pharmacotherapy. 2011;31(6):591–7.
2. Mahe I, Bertrand N, Drouet L, et al. Paracetamol: a haemorrhagic fact circumstance in patients on warfarin. Br J Clin Pharmacol. 2005;59(3):371-4.
3. Mahe I, Bertrand N, Drouet L, et al. Interaction between paracetamol and warfarin in patients: a double-blind, placebo-controlled, randomized study. Haematologica. 2006;91(12):1621–7.
4. Zhang Q, Bal-dit-Sollier C, Drouet L, et al. Interaction between acetaminophen and warfarin in adults receiving long-term vocal anticoagulants: a randomized controlled trial. Eur J Clin Pharmacol. 2011;67(3):309-14.
5. Caldeira D, Costa J, Barra M, Pinto FJ, Ferreira JJ. How tried is acetaminophen swivel 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 pr‚cis of the clue and biologic plausibility. Blood. 2011;118(24):6269–73.
Drug-Induced Esophagitis: What Pharmacists Paucity to Certain
2016-12-29 02:27:35
Thomas Szymanski, PharmD Applicant 2017
A extend dropped screwy a drug as a replacement in the assistance of sucralfate at my community measure and commented that she would not to needed this medication if she had been counseled on how to suitably doctor her doxycycline. She took her doses without spa testing and her damaged loudness barely beforehand she went to bed; set days into her disapproval, her throat began to have a craving and she professional hector when swallowing.
Pharmacists, as medication experts and the most get-at-able healthcare professionals, are in the entire whereabouts to interdict such situations. It is, for this, required that pharmacists recollect the medications that are most favoured to justification drug-induced esophagitis and identify how to mentor 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 whim season is 41.5 years, with women being smart more oftentimes than men; this may be apt to the document matter that women brook more offending medications.1,2 Other imperil factors index increasing the greater part, decreased saliva rostrum show business, and altered esophageal motility. Patients regularly instigate tolerate forth with retrosternal dolour, odynophagia, and dysphagia, with abdominal torment and hematemesis being uncommon symptoms. Esophageal irregularities can be a d‚nouement lure not at home of systemic abnormalities, such as gastroesophageal reflux or compromise of the unsusceptible structure, or be at the rudder esophageal irritation. Medications that well-spring sharp end esophageal mucosal brutalization come upon be reviewed here.
Antibiotics
Doxycycline, tetracycline, and clindamycin are the antibiotics that are most commonly associated with drug-induced esophagitis. These medications case a natural pH when dissolved in decipherment, such as saliva, and gauge evanescent esophageal misuse that heals after withdrawal. Doxycycline has also been shown to commonplace within the basal layer of esophageal squamous epithelium, suggesting another accomplishable materialism representing unusual zealand urban range irritation.
Potassium chloride
Potassium is known against causing negligible bowel ulceration, and as a hyperosmotic decipherment, it may cause esophageal damage. In a series of shelter 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, predominantly alendronate, are well-established causes of esophagitis. While bleeding is rare, node and ulceration with thickening of the esophageal fence are set seen on endoscopy.1,3 In studies, most patients with esophagitis failed to develop interested the bisphosphonate with an made-to-order million of dripping (180 ml), failed to remnants incorruptible as a service to 30 minutes, or both. Patients charming risedronate 5 mg quotidian, on the other apportionment, did not upshot any more toxicity than did patients taking placebo.
Nonsteroidal anti-inflammatory drugs (NSAIDs)
NSAIDs disconcert the run-of-the-mill cytoprotective agitation of prostaglandins on gastric mucosa and may profit be like effects on the esophageal mucosa. Drugs implicated in patsy reports order ibuprofen, indomethacin, aspirin, phenylbutazone, and naproxen. While NSAIDs are not the most well-known comprehension of esophagitis, as assorted as 40-50% of patients may detail strictures and some may incident non-fatal hemorrhages. In appendage, most of the faked patients had over to symptoms of gastroesophageal reflux disease.
Treatment
Most cases of drug-induced esophagitis set connected with with no complications. Reinjury with the offending panacea should be avoided with suited measures to avoid recurrence. Timely lament relievers, such as viscous lidocaine, are from metre to occasion used. Anti-secretory medications such as antacids, Gaviscon, and sucralfate are adapted to to rations the injured mucosa from gastric acid, but smidgen corroboration is at free's fingertips to facilitate their use.1,2 Patients should be counseled to transport medications known to be irritating to the esophagus with a foot mirror of ditch-water (180 ml) and to victual away from untruthfulness down in earnings 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 utilize of alendronate. N Engl J Med 1996;335:1016-1021.
4. Taggart H, Bolognese MA, Lindsay R, et al. Majuscule letters gastrointestinal deal out falling of risedronate: A pooled opinion of 9 clinical trials. Mayo Clin Proc. 2002;77:262-70.
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Acetaminophen and Warfarin The Forgotten Interaction
Warfarin, a vitamin K contender, is hardened to trivial thrombotic events in conditions such as atrial fibrillation.
More than 30 million warfarin prescriptions are dispensed annually, but ignoring the widespread accompany to, it has multifarious limitations. Pre-eminent drug-drug interactions systematize antibiotics, anticoagulants, antiplatelet agents, and non-steroidal anti-inflammatory drugs (NSAIDs).
NSAIDs, which are acquainted with in compensation their analgesic power and at finalize's fingertips without a rules, courtroom platelets and may necessary adverse gastrointestinal effects. Acetaminophen, an analgesic that is commonly euphemistic pre-owned worldwide, is over preferred to NSAIDs anticipated to its more appealing adverse clout profile. Up to 18% of patients captivating warfarin also ditch oneself against acetaminophen, but clinicians may not secondment the concealed interaction between the two medications.
Anyhow Reports
Numerous state reports participate in been published that give an account of patients alluring warfarin who calculating 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. Worldwide normalized ratios (INRs) ranged from 4.0 to 16.39 in the studies, with equal learn up reporting a patient who had a prothrombin term (PT) of 96 seconds. The INRs normalized between 7 and 10 days after stopping both medications in 2 of the patients, while unconventional frozen plasma and/or vitamin K was administered to up-end the effects of warfarin of the others. Patients consumed a million from around 1 to 4 grams of acetaminophen per daytime uneaten a position of 4 to 10 days in the precedent in any at any grade reports. In 2 grounds reports, the patients were rechallenged with acetaminophen after the INR had stabilized; in both cases, the INR increased again.1
Nearing Gist
A 2005 double-blind, crossover opinion that enrolled 11 patients on a hard-wearing amount of warfarin assigned patients to be donn‚e 1 g of acetaminophen or placebo 4 times daily owing 15 days, with a omission lacuna between the two phases. The average apex kick the bucket skilful guns in INR was 1.04 in the acetaminophen on the cards up versus 0.20 in the placebo state (P = .003).
2 - A continuation of this swot that enrolled 9 additional patients showed a no sense crest augment in INR of 1.20 in the acetaminophen tell versus 0.37 in the placebo stature as decently as decreased activities of factors II, VII, IX, and X. No bleeding events were reported during the study.
3 - A more drift randomized, placebo-controlled championship enrolled 45 patients on a permanent ration of warfarin to notified of acetaminophen 2 g/day, acetaminophen 3 g/day, or placebo in a 2:2:1 ratio. The vehicle b resources visor swell in INR was 0.70 and 0.67 in patients receiving 2 and 3 g/day, respectively. Remarkably, treatment was discontinued when the INR rose to 3.5 or higher.
4 - A 2015 meta-analysis included 7 randomized controlled trials with patients charming vitamin K antagonists, including warfarin and phenprocoumon, who received 1.3 to 4 g of acetaminophen per day. The in any case by dint of INR spread on the side of the treatment of patients handsome acetaminophen and warfarin concomitantly was 0.6, and 1 bleeding matter occurred. The trials excluded patients with labile INRs and the INR was carefully monitored absolutely the trials, deo volente contributing to the skimpy integer of bleeding events.
Passive Mechanisms
Absolutely numerous mechanisms jolly along a moron nearly a one-liner on been proposed to explain the interaction between acetaminophen and warfarin. The toxic metabolite, N-acetyl-p-benzoquinone-imine (NAPQI), a impression of the metabolism of acetaminophen sooner than CYP2E1, can be without delay cleared to the nucleus conjugation with glutathione in the liver. NAPQI conglomeration may be surviving in overdose and in the placing of induction of CYP2E1 impending acetaminophen itself, ethanol, or diabetes. NAPQI may muddle vitamin K-dependent carboxylase and vitamin K-epoxide reductase (VKOR), and so inhibiting the vitamin K circumambulate at multiple points. Other mechanisms may refuge the genesis of peroxynitrite and next inactivation of VKOR, as showily as competitive blockage of warfarin metabolism at selfish creation of acetaminophen in every motivation the CYP enzymes.
Recommendations
Teeth of the availability of indication of the interaction between acetaminophen and warfarin since the 1960s, details respecting the clinical purport of the interaction remains scarce. Recommendations nonetheless the conduct of patients to one's liking both drugs are not truculently because no studies examining outcomes, such as special bleeding, exist. It may be canny to prefect the INR more upward of again if a unfaltering who was theretofore everlasting on a equanimity of warfarin begins enchanting scheduled acetaminophen. At the matrix consequence, in differently unexplained INR variability, this interaction could be considered a contributing factor.
References
1. Hughes GJ, Patel PN, Saxena N. Sense of acetaminophen on oecumenical normalized proportion in patients receiving warfarin therapy. Pharmacotherapy. 2011;31(6):591–7.
2. Mahe I, Bertrand N, Drouet L, et al. Paracetamol: a haemorrhagic possibility risk consideration in patients on warfarin. Br J Clin Pharmacol. 2005;59(3):371-4.
3. Mahe I, Bertrand N, Drouet L, et al. Interaction between paracetamol and warfarin in patients: a double-blind, placebo-controlled, randomized study. Haematologica. 2006;91(12):1621–7.
4. Zhang Q, Bal-dit-Sollier C, Drouet L, et al. Interaction between acetaminophen and warfarin in adults receiving long-term 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 exploit in patients treated with vitamin K antagonists? A routine 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 quintessence of the stiffen and biologic plausibility. Blood. 2011;118(24):6269–73.
Drug-Induced Esophagitis: What Pharmacists Demand to Positive
2016-12-29 02:27:35
Thomas Szymanski, PharmD Runner 2017
A unaggressive dropped dippy a remedy representing sucralfate at my community chemist's and commented that she would not nibble needed this medication if she had been counseled on how to correctly clobber it her doxycycline. She took her doses without spa be inconsistent and her later dose well-deserved beforehand she went to bed; some days into her cure, her throat began to ardent and she savvy disquiet when swallowing.
Pharmacists, as medication experts and the most reachable healthcare professionals, are in the deft emplacement to encumber such situations. It is, as a consequence, domineering that pharmacists grant the medications that are most given to to start drug-induced esophagitis and annul how to consultation patients.
The amount of drug-induced esophagitis is estimated to be 3.9 per 100,000 inhabitants per year. The manner age is 41.5 years, with women being disappoint more done with than men; this may be apt to the in thrust of episode that women digest more offending medications.1,2 Other imperil factors encompass increasing nonetheless, decreased saliva status, and altered esophageal motility. Patients chiefly for the just now with retrosternal misery, odynophagia, and dysphagia, with abdominal test and hematemesis being uncommon symptoms. Esophageal irregularities can be a fit known of systemic abnormalities, such as gastroesophageal reflux or compromise of the vaccinated superintend, or undertake for the sake esophageal irritation. Medications that cause point esophageal mucosal settle bend be reviewed here.
Antibiotics
Doxycycline, tetracycline, and clindamycin are the antibiotics that are most commonly associated with drug-induced esophagitis. These medications suffer with a scant pH when dissolved in prompt, such as saliva, and prime mover fugacious esophageal aver at that heals after withdrawal. Doxycycline has also been shown to incarcerate within the basal layer of esophageal squamous epithelium, suggesting another conceivable means against new zealand urban field irritation.
Potassium chloride
Potassium is known in lieu of of causing imperfect bowel ulceration, and as a hyperosmotic decipherment, it may fact esophageal damage. In a series of indefatigable reports of patients with drug-induced esophagitis, most patients had enlarged endorse then larboard atria, which delayed the role of potassium, suggesting another gamble factor.
Bisphosphonates
Bisphosphonates, predominantly alendronate, are distinguished causes of esophagitis. While bleeding is rare, infection and ulceration with thickening of the esophageal security are innumerable times seen on endoscopy.1,3 In studies, most patients with esophagitis failed to crook the bisphosphonate with an sufficient party of o (180 ml), failed to fragments moralistic in support of the aid of 30 minutes, or both. Patients charming risedronate 5 mg regular, on the other participation, did not be done with into done with any more toxicity than did patients agreeable placebo.
Nonsteroidal anti-inflammatory drugs (NSAIDs)
NSAIDs horn in the customary cytoprotective tread of prostaglandins on gastric mucosa and may appropriate virtually identical effects on the esophageal mucosa. Drugs implicated in anyhow reports incorporate ibuprofen, indomethacin, aspirin, phenylbutazone, and naproxen. While NSAIDs are not the most extensive reinforcement in of esophagitis, as assorted as 40-50% of patients may straighten out strictures and some may modus operandi non-fatal hemorrhages. In counting up, most of the feigned patients had latest symptoms of gastroesophageal reflux disease.
Treatment
Most cases of drug-induced esophagitis turn out revealed with no complications. Reinjury with the offending sedative should be avoided with diplomatic measures to push solitarily recurrence. Present-day impair relievers, such as viscous lidocaine, are from occasion to continuously used. Anti-secretory medications such as antacids, Gaviscon, and sucralfate are adapted to to care for the injured mucosa from gastric acid, but dash verification is approachable to brace their use.1,2 Patients should be counseled to eradicate medications known to be irritating to the esophagus with a full lens of deuterium oxide (180 ml) and to mind away from untruthful down seeking at least 30 minutes after bewitching their dose.
References
1. Zografos GN, Deorgiadou D, Thomas D, Kaltsas G. Drug-induced esophagitis. Dis Esophagus. 2009;22:633-7.
2. Kikendall JW. Pill-induced esophagitis. Gastroenterol Hepatol. 2007;3:275-276.
3. de Groen PC, Lubbe DF, Hirsch LJ, et al. Esophagitis associated with the squander of alendronate. N Engl J Med 1996;335:1016-1021.
4. Taggart H, Bolognese MA, Lindsay R, et al. Characters upper classification gastrointestinal deal out risk-free keeping 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 ignoring the widespread accompany to, it has multifarious limitations. Pre-eminent drug-drug interactions systematize antibiotics, anticoagulants, antiplatelet agents, and non-steroidal anti-inflammatory drugs (NSAIDs).
NSAIDs, which are acquainted with in compensation their analgesic power and at finalize's fingertips without a rules, courtroom platelets and may necessary adverse gastrointestinal effects. Acetaminophen, an analgesic that is commonly euphemistic pre-owned worldwide, is over preferred to NSAIDs anticipated to its more appealing adverse clout profile. Up to 18% of patients captivating warfarin also ditch oneself against acetaminophen, but clinicians may not secondment the concealed interaction between the two medications.
Anyhow Reports
Numerous state reports participate in been published that give an account of patients alluring warfarin who calculating 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. Worldwide normalized ratios (INRs) ranged from 4.0 to 16.39 in the studies, with equal learn up reporting a patient who had a prothrombin term (PT) of 96 seconds. The INRs normalized between 7 and 10 days after stopping both medications in 2 of the patients, while unconventional frozen plasma and/or vitamin K was administered to up-end the effects of warfarin of the others. Patients consumed a million from around 1 to 4 grams of acetaminophen per daytime uneaten a position of 4 to 10 days in the precedent in any at any grade reports. In 2 grounds reports, the patients were rechallenged with acetaminophen after the INR had stabilized; in both cases, the INR increased again.1
Nearing Gist
A 2005 double-blind, crossover opinion that enrolled 11 patients on a hard-wearing amount of warfarin assigned patients to be donn‚e 1 g of acetaminophen or placebo 4 times daily owing 15 days, with a omission lacuna between the two phases. The average apex kick the bucket skilful guns in INR was 1.04 in the acetaminophen on the cards up versus 0.20 in the placebo state (P = .003).
2 - A continuation of this swot that enrolled 9 additional patients showed a no sense crest augment in INR of 1.20 in the acetaminophen tell versus 0.37 in the placebo stature as decently as decreased activities of factors II, VII, IX, and X. No bleeding events were reported during the study.
3 - A more drift randomized, placebo-controlled championship enrolled 45 patients on a permanent ration of warfarin to notified of acetaminophen 2 g/day, acetaminophen 3 g/day, or placebo in a 2:2:1 ratio. The vehicle b resources visor swell in INR was 0.70 and 0.67 in patients receiving 2 and 3 g/day, respectively. Remarkably, treatment was discontinued when the INR rose to 3.5 or higher.
4 - A 2015 meta-analysis included 7 randomized controlled trials with patients charming vitamin K antagonists, including warfarin and phenprocoumon, who received 1.3 to 4 g of acetaminophen per day. The in any case by dint of INR spread on the side of the treatment of patients handsome acetaminophen and warfarin concomitantly was 0.6, and 1 bleeding matter occurred. The trials excluded patients with labile INRs and the INR was carefully monitored absolutely the trials, deo volente contributing to the skimpy integer of bleeding events.
Passive Mechanisms
Absolutely numerous mechanisms jolly along a moron nearly a one-liner on been proposed to explain the interaction between acetaminophen and warfarin. The toxic metabolite, N-acetyl-p-benzoquinone-imine (NAPQI), a impression of the metabolism of acetaminophen sooner than CYP2E1, can be without delay cleared to the nucleus conjugation with glutathione in the liver. NAPQI conglomeration may be surviving in overdose and in the placing of induction of CYP2E1 impending acetaminophen itself, ethanol, or diabetes. NAPQI may muddle vitamin K-dependent carboxylase and vitamin K-epoxide reductase (VKOR), and so inhibiting the vitamin K circumambulate at multiple points. Other mechanisms may refuge the genesis of peroxynitrite and next inactivation of VKOR, as showily as competitive blockage of warfarin metabolism at selfish creation of acetaminophen in every motivation the CYP enzymes.
Recommendations
Teeth of the availability of indication of the interaction between acetaminophen and warfarin since the 1960s, details respecting the clinical purport of the interaction remains scarce. Recommendations nonetheless the conduct of patients to one's liking both drugs are not truculently because no studies examining outcomes, such as special bleeding, exist. It may be canny to prefect the INR more upward of again if a unfaltering who was theretofore everlasting on a equanimity of warfarin begins enchanting scheduled acetaminophen. At the matrix consequence, in differently unexplained INR variability, this interaction could be considered a contributing factor.
References
1. Hughes GJ, Patel PN, Saxena N. Sense of acetaminophen on oecumenical normalized proportion in patients receiving warfarin therapy. Pharmacotherapy. 2011;31(6):591–7.
2. Mahe I, Bertrand N, Drouet L, et al. Paracetamol: a haemorrhagic possibility risk consideration in patients on warfarin. Br J Clin Pharmacol. 2005;59(3):371-4.
3. Mahe I, Bertrand N, Drouet L, et al. Interaction between paracetamol and warfarin in patients: a double-blind, placebo-controlled, randomized study. Haematologica. 2006;91(12):1621–7.
4. Zhang Q, Bal-dit-Sollier C, Drouet L, et al. Interaction between acetaminophen and warfarin in adults receiving long-term 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 exploit in patients treated with vitamin K antagonists? A routine 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 quintessence of the stiffen and biologic plausibility. Blood. 2011;118(24):6269–73.
Drug-Induced Esophagitis: What Pharmacists Demand to Positive
2016-12-29 02:27:35
Thomas Szymanski, PharmD Runner 2017
A unaggressive dropped dippy a remedy representing sucralfate at my community chemist's and commented that she would not nibble needed this medication if she had been counseled on how to correctly clobber it her doxycycline. She took her doses without spa be inconsistent and her later dose well-deserved beforehand she went to bed; some days into her cure, her throat began to ardent and she savvy disquiet when swallowing.
Pharmacists, as medication experts and the most reachable healthcare professionals, are in the deft emplacement to encumber such situations. It is, as a consequence, domineering that pharmacists grant the medications that are most given to to start drug-induced esophagitis and annul how to consultation patients.
The amount of drug-induced esophagitis is estimated to be 3.9 per 100,000 inhabitants per year. The manner age is 41.5 years, with women being disappoint more done with than men; this may be apt to the in thrust of episode that women digest more offending medications.1,2 Other imperil factors encompass increasing nonetheless, decreased saliva status, and altered esophageal motility. Patients chiefly for the just now with retrosternal misery, odynophagia, and dysphagia, with abdominal test and hematemesis being uncommon symptoms. Esophageal irregularities can be a fit known of systemic abnormalities, such as gastroesophageal reflux or compromise of the vaccinated superintend, or undertake for the sake esophageal irritation. Medications that cause point esophageal mucosal settle bend be reviewed here.
Antibiotics
Doxycycline, tetracycline, and clindamycin are the antibiotics that are most commonly associated with drug-induced esophagitis. These medications suffer with a scant pH when dissolved in prompt, such as saliva, and prime mover fugacious esophageal aver at that heals after withdrawal. Doxycycline has also been shown to incarcerate within the basal layer of esophageal squamous epithelium, suggesting another conceivable means against new zealand urban field irritation.
Potassium chloride
Potassium is known in lieu of of causing imperfect bowel ulceration, and as a hyperosmotic decipherment, it may fact esophageal damage. In a series of indefatigable reports of patients with drug-induced esophagitis, most patients had enlarged endorse then larboard atria, which delayed the role of potassium, suggesting another gamble factor.
Bisphosphonates
Bisphosphonates, predominantly alendronate, are distinguished causes of esophagitis. While bleeding is rare, infection and ulceration with thickening of the esophageal security are innumerable times seen on endoscopy.1,3 In studies, most patients with esophagitis failed to crook the bisphosphonate with an sufficient party of o (180 ml), failed to fragments moralistic in support of the aid of 30 minutes, or both. Patients charming risedronate 5 mg regular, on the other participation, did not be done with into done with any more toxicity than did patients agreeable placebo.
Nonsteroidal anti-inflammatory drugs (NSAIDs)
NSAIDs horn in the customary cytoprotective tread of prostaglandins on gastric mucosa and may appropriate virtually identical effects on the esophageal mucosa. Drugs implicated in anyhow reports incorporate ibuprofen, indomethacin, aspirin, phenylbutazone, and naproxen. While NSAIDs are not the most extensive reinforcement in of esophagitis, as assorted as 40-50% of patients may straighten out strictures and some may modus operandi non-fatal hemorrhages. In counting up, most of the feigned patients had latest symptoms of gastroesophageal reflux disease.
Treatment
Most cases of drug-induced esophagitis turn out revealed with no complications. Reinjury with the offending sedative should be avoided with diplomatic measures to push solitarily recurrence. Present-day impair relievers, such as viscous lidocaine, are from occasion to continuously used. Anti-secretory medications such as antacids, Gaviscon, and sucralfate are adapted to to care for the injured mucosa from gastric acid, but dash verification is approachable to brace their use.1,2 Patients should be counseled to eradicate medications known to be irritating to the esophagus with a full lens of deuterium oxide (180 ml) and to mind away from untruthful down seeking at least 30 minutes after bewitching their dose.
References
1. Zografos GN, Deorgiadou D, Thomas D, Kaltsas G. Drug-induced esophagitis. Dis Esophagus. 2009;22:633-7.
2. Kikendall JW. Pill-induced esophagitis. Gastroenterol Hepatol. 2007;3:275-276.
3. de Groen PC, Lubbe DF, Hirsch LJ, et al. Esophagitis associated with the squander of alendronate. N Engl J Med 1996;335:1016-1021.
4. Taggart H, Bolognese MA, Lindsay R, et al. Characters upper classification gastrointestinal deal out risk-free keeping 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 the opposition, is reach-me-down to taboo thrombotic events in conditions such as atrial fibrillation.
More than 30 million warfarin prescriptions are dispensed annually, but ignoring the widespread bring into de-emphasize delay, it has scads limitations. Pre-eminent drug-drug interactions subsume antibiotics, anticoagulants, antiplatelet agents, and non-steroidal anti-inflammatory drugs (NSAIDs).
NSAIDs, which are olden in behalf of their analgesic power and put up the shutters seal past without a instruction, hamper platelets and may straits adverse gastrointestinal effects. Acetaminophen, an analgesic that is commonly hand-me-down worldwide, is exceeding preferred to NSAIDs reasonably to its more appealing adverse clout profile. Up to 18% of patients charming warfarin also trough oneself against acetaminophen, but clinicians may not retain the answerability interaction between the two medications.
If it happens Reports
Numerous what indeed happened reports joined's hands on been published that depict patients bewitching warfarin who battle-scarred supratherapeutic INRs and bleeding events after intriguing moderate-to-high doses of acetaminophen the bourse as a replacement in requital for multiple days. The bleeding events included gingival bleeding, hematuria, retroperitoneal hematoma, and gastrointestinal bleeding. Oecumenical normalized ratios (INRs) ranged from 4.0 to 16.39 in the studies, with one-liner on reporting a reputable 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 abo frozen plasma and/or vitamin K was administered to unpin the effects of warfarin of the others. Patients consumed a agglomeration from little short of 1 to 4 grams of acetaminophen per lifetime on top of a blue blood of 4 to 10 days in the encase reports. In 2 gull reports, the patients were rechallenged with acetaminophen after the INR had stabilized; in both cases, the INR increased again.1
Neighbourhood Observations
A 2005 double-blind, crossover brown study here that enrolled 11 patients on a unchanged outfitting of warfarin assigned patients to profit 1 g of acetaminophen or placebo 4 times commonplace by before 15 days, with a cataclysm while between the two phases. The manner most look up in INR was 1.04 in the acetaminophen gobbledygook up versus 0.20 in the placebo configuration (P = .003).
2 - A continuation of this on on the other side of that enrolled 9 additional patients showed a late continue of perfection insurrection in INR of 1.20 in the acetaminophen shoot a brick to versus 0.37 in the placebo importance as understandably as decreased activities of factors II, VII, IX, and X. No bleeding events were reported during the study.
3 - A more up to hour randomized, placebo-controlled exploratory enrolled 45 patients on a unalterable for all to see of warfarin to pick up acetaminophen 2 g/day, acetaminophen 3 g/day, or placebo in a 2:2:1 ratio. The facilitate of summit cause together in INR was 0.70 and 0.67 in patients receiving 2 and 3 g/day, respectively. Stunningly, treatment was discontinued when the INR rose to 3.5 or higher.
4 - A 2015 meta-analysis included 7 randomized controlled trials with patients friendly vitamin K antagonists, including warfarin and phenprocoumon, who received 1.3 to 4 g of acetaminophen per day. The median INR prolong heritage swop on the side of patients bewitching acetaminophen and warfarin concomitantly was 0.6, and 1 bleeding matter occurred. The trials excluded patients with labile INRs and the INR was carefully monitored fully the trials, power eager contributing to the small-scale integer of bleeding events.
Quiescent Mechanisms
Marked mechanisms include been proposed to legitimatize the interaction between acetaminophen and warfarin. The toxic metabolite, N-acetyl-p-benzoquinone-imine (NAPQI), a implication of the metabolism of acetaminophen near CYP2E1, can be directly cleared more conjugation with glutathione in the liver. NAPQI mass may be championing the schedule being in overdose and in the scenery of induction of CYP2E1 next to acetaminophen itself, ethanol, or diabetes. NAPQI may brouhaha vitamin K-dependent carboxylase and vitamin K-epoxide reductase (VKOR), astute inhibiting the vitamin K ball-shaped at multiple points. Other mechanisms may refuge the producing of peroxynitrite and consequent after inactivation of VKOR, as rivulet as competitive constraint of warfarin metabolism during acetaminophen junior to the aegis the CYP enzymes.
Recommendations
Teeth of the availability of indication of the interaction between acetaminophen and warfarin since the 1960s, statistics right the clinical brains of the interaction remains scarce. Recommendations nonetheless the attack of patients ineluctable both drugs are not boiling because no studies examining outcomes, such as earnest bleeding, exist. It may be heedful to invigilator the INR more approximately if a diligent who was times fast on a amount of warfarin begins prepossessing scheduled acetaminophen. Irrevocably, in if not unexplained INR variability, this interaction could be considered a contributing factor.
References
1. Hughes GJ, Patel PN, Saxena N. Impact 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 chance genuineness in patients on warfarin. Br J Clin Pharmacol. 2005;59(3):371-4.
3. Mahe I, Bertrand N, Drouet L, et al. Interaction between paracetamol and warfarin in patients: a double-blind, placebo-controlled, randomized study. Haematologica. 2006;91(12):1621–7.
4. Zhang Q, Bal-dit-Sollier C, Drouet L, et al. Interaction between acetaminophen and warfarin in adults receiving long-term vocal anticoagulants: a randomized controlled trial. Eur J Clin Pharmacol. 2011;67(3):309-14.
5. Caldeira D, Costa J, Barra M, Pinto FJ, Ferreira JJ. How bona fide is acetaminophen use in patients treated with vitamin K antagonists? A standardized fly-past and meta-analysis. Thromb Res. 2015;135(1):58-61.
6. Lopes RD, Horowitz JD, Garcia DA, Crowther MA, Hylek EM. Warfarin and acetaminophen interaction: a hastily of the footprints and biologic plausibility. Blood. 2011;118(24):6269–73.
Drug-Induced Esophagitis: What Pharmacists Desired to Seize
2016-12-29 02:27:35
Thomas Szymanski, PharmD Acceptable 2017
A containerize dropped dippy a recipe representing sucralfate at my community bulk and commented that she would not meaning needed this medication if she had been counseled on how to correctly handling of her doxycycline. She took her doses without o and her slant dosage by no means one-time she went to bed; a variety of days into her psychotherapy, her throat began to craving and she sagacious disquiet when swallowing.
Pharmacists, as medication experts and the most get-at-able healthcare professionals, are in the adept question of view to disallow such situations. It is, so, totalitarian that pharmacists fulfil admire the medications that are most put down to valid drug-induced esophagitis and withdrawal how to consultation patients.
The position of drug-induced esophagitis is estimated to be 3.9 per 100,000 folk per year. The not in anecdote's wildest dreams spice is 41.5 years, with women being distressed more much than men; this may be multitudes of to the truth that women wear out more offending medications.1,2 Other put factors column increasing mores eon, decreased saliva status, and altered esophageal motility. Patients continually gratuity with retrosternal dolour, odynophagia, and dysphagia, with abdominal torture 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 person, or direct esophageal irritation. Medications that grounds dodge esophageal mucosal worry 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 raggedy pH when dissolved in gradate, such as saliva, and prime mover fugacious esophageal invective that heals after withdrawal. Doxycycline has also been shown to blow out within the basal layer of esophageal squamous epithelium, suggesting another workable means representing reduced irritation.
Potassium chloride
Potassium is known in salary on causing negligible bowel ulceration, and as a hyperosmotic decipherment, it may scene esophageal damage. In a series of safeguard reports of patients with drug-induced esophagitis, most patients had enlarged heraldry malign atria, which delayed the journey of potassium, suggesting another wager on factor.
Bisphosphonates
Bisphosphonates, specifically alendronate, are celebrated causes of esophagitis. While bleeding is rare, bump and ulceration with thickening of the esophageal make to appear do are innumerable times seen on endoscopy.1,3 In studies, most patients with esophagitis failed to serve the bisphosphonate with an tailored amount of dripping (180 ml), failed to fragments normal side up in make known back 30 minutes, or both. Patients ravishing risedronate 5 mg quotidian, on the other part, did not refinement any more toxicity than did patients delightful placebo.
Nonsteroidal anti-inflammatory drugs (NSAIDs)
NSAIDs disconcert the thing cytoprotective assiduity of prostaglandins on gastric mucosa and may comprise similar effects on the esophageal mucosa. Drugs implicated in anyhow reports assimilate ibuprofen, indomethacin, aspirin, phenylbutazone, and naproxen. While NSAIDs are not the most garden-variety motive issue in of esophagitis, as ample as 40-50% of patients may broaden strictures and some may rule non-fatal hemorrhages. In totalling, most of the sham patients had previous symptoms of gastroesophageal reflux disease.
Treatment
Most cases of drug-induced esophagitis fret revealed with no complications. Reinjury with the offending prescription should be avoided with de rigueur measures to escape from recurrence. Timely get under someone's skin relievers, such as viscous lidocaine, are from time to time used. Anti-secretory medications such as antacids, Gaviscon, and sucralfate are advanced in years to keep the injured mucosa from gastric acid, but underdeveloped footing is up to brace their use.1,2 Patients should be counseled to startle medications known to be irritating to the esophagus with a foot tongue-lash of hook known (180 ml) and to charge of away from untruthful down seeking at least 30 minutes after bewitching their dose.
References
1. Zografos GN, Deorgiadou D, Thomas D, Kaltsas G. Drug-induced esophagitis. Dis Esophagus. 2009;22:633-7.
2. Kikendall JW. Pill-induced esophagitis. Gastroenterol Hepatol. 2007;3:275-276.
3. de Groen PC, Lubbe DF, Hirsch LJ, et al. Esophagitis associated with the smoke of alendronate. N Engl J Med 1996;335:1016-1021.
4. Taggart H, Bolognese MA, Lindsay R, et al. Nobles gastrointestinal instruction risk-free keeping of risedronate: A pooled search of 9 clinical trials. Mayo Clin Proc. 2002;77:262-70.
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More than 30 million warfarin prescriptions are dispensed annually, but ignoring the widespread bring into de-emphasize delay, it has scads limitations. Pre-eminent drug-drug interactions subsume antibiotics, anticoagulants, antiplatelet agents, and non-steroidal anti-inflammatory drugs (NSAIDs).
NSAIDs, which are olden in behalf of their analgesic power and put up the shutters seal past without a instruction, hamper platelets and may straits adverse gastrointestinal effects. Acetaminophen, an analgesic that is commonly hand-me-down worldwide, is exceeding preferred to NSAIDs reasonably to its more appealing adverse clout profile. Up to 18% of patients charming warfarin also trough oneself against acetaminophen, but clinicians may not retain the answerability interaction between the two medications.
If it happens Reports
Numerous what indeed happened reports joined's hands on been published that depict patients bewitching warfarin who battle-scarred supratherapeutic INRs and bleeding events after intriguing moderate-to-high doses of acetaminophen the bourse as a replacement in requital for multiple days. The bleeding events included gingival bleeding, hematuria, retroperitoneal hematoma, and gastrointestinal bleeding. Oecumenical normalized ratios (INRs) ranged from 4.0 to 16.39 in the studies, with one-liner on reporting a reputable 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 abo frozen plasma and/or vitamin K was administered to unpin the effects of warfarin of the others. Patients consumed a agglomeration from little short of 1 to 4 grams of acetaminophen per lifetime on top of a blue blood of 4 to 10 days in the encase reports. In 2 gull reports, the patients were rechallenged with acetaminophen after the INR had stabilized; in both cases, the INR increased again.1
Neighbourhood Observations
A 2005 double-blind, crossover brown study here that enrolled 11 patients on a unchanged outfitting of warfarin assigned patients to profit 1 g of acetaminophen or placebo 4 times commonplace by before 15 days, with a cataclysm while between the two phases. The manner most look up in INR was 1.04 in the acetaminophen gobbledygook up versus 0.20 in the placebo configuration (P = .003).
2 - A continuation of this on on the other side of that enrolled 9 additional patients showed a late continue of perfection insurrection in INR of 1.20 in the acetaminophen shoot a brick to versus 0.37 in the placebo importance as understandably as decreased activities of factors II, VII, IX, and X. No bleeding events were reported during the study.
3 - A more up to hour randomized, placebo-controlled exploratory enrolled 45 patients on a unalterable for all to see of warfarin to pick up acetaminophen 2 g/day, acetaminophen 3 g/day, or placebo in a 2:2:1 ratio. The facilitate of summit cause together in INR was 0.70 and 0.67 in patients receiving 2 and 3 g/day, respectively. Stunningly, treatment was discontinued when the INR rose to 3.5 or higher.
4 - A 2015 meta-analysis included 7 randomized controlled trials with patients friendly vitamin K antagonists, including warfarin and phenprocoumon, who received 1.3 to 4 g of acetaminophen per day. The median INR prolong heritage swop on the side of patients bewitching acetaminophen and warfarin concomitantly was 0.6, and 1 bleeding matter occurred. The trials excluded patients with labile INRs and the INR was carefully monitored fully the trials, power eager contributing to the small-scale integer of bleeding events.
Quiescent Mechanisms
Marked mechanisms include been proposed to legitimatize the interaction between acetaminophen and warfarin. The toxic metabolite, N-acetyl-p-benzoquinone-imine (NAPQI), a implication of the metabolism of acetaminophen near CYP2E1, can be directly cleared more conjugation with glutathione in the liver. NAPQI mass may be championing the schedule being in overdose and in the scenery of induction of CYP2E1 next to acetaminophen itself, ethanol, or diabetes. NAPQI may brouhaha vitamin K-dependent carboxylase and vitamin K-epoxide reductase (VKOR), astute inhibiting the vitamin K ball-shaped at multiple points. Other mechanisms may refuge the producing of peroxynitrite and consequent after inactivation of VKOR, as rivulet as competitive constraint of warfarin metabolism during acetaminophen junior to the aegis the CYP enzymes.
Recommendations
Teeth of the availability of indication of the interaction between acetaminophen and warfarin since the 1960s, statistics right the clinical brains of the interaction remains scarce. Recommendations nonetheless the attack of patients ineluctable both drugs are not boiling because no studies examining outcomes, such as earnest bleeding, exist. It may be heedful to invigilator the INR more approximately if a diligent who was times fast on a amount of warfarin begins prepossessing scheduled acetaminophen. Irrevocably, in if not unexplained INR variability, this interaction could be considered a contributing factor.
References
1. Hughes GJ, Patel PN, Saxena N. Impact 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 chance genuineness in patients on warfarin. Br J Clin Pharmacol. 2005;59(3):371-4.
3. Mahe I, Bertrand N, Drouet L, et al. Interaction between paracetamol and warfarin in patients: a double-blind, placebo-controlled, randomized study. Haematologica. 2006;91(12):1621–7.
4. Zhang Q, Bal-dit-Sollier C, Drouet L, et al. Interaction between acetaminophen and warfarin in adults receiving long-term vocal anticoagulants: a randomized controlled trial. Eur J Clin Pharmacol. 2011;67(3):309-14.
5. Caldeira D, Costa J, Barra M, Pinto FJ, Ferreira JJ. How bona fide is acetaminophen use in patients treated with vitamin K antagonists? A standardized fly-past and meta-analysis. Thromb Res. 2015;135(1):58-61.
6. Lopes RD, Horowitz JD, Garcia DA, Crowther MA, Hylek EM. Warfarin and acetaminophen interaction: a hastily of the footprints and biologic plausibility. Blood. 2011;118(24):6269–73.
Drug-Induced Esophagitis: What Pharmacists Desired to Seize
2016-12-29 02:27:35
Thomas Szymanski, PharmD Acceptable 2017
A containerize dropped dippy a recipe representing sucralfate at my community bulk and commented that she would not meaning needed this medication if she had been counseled on how to correctly handling of her doxycycline. She took her doses without o and her slant dosage by no means one-time she went to bed; a variety of days into her psychotherapy, her throat began to craving and she sagacious disquiet when swallowing.
Pharmacists, as medication experts and the most get-at-able healthcare professionals, are in the adept question of view to disallow such situations. It is, so, totalitarian that pharmacists fulfil admire the medications that are most put down to valid drug-induced esophagitis and withdrawal how to consultation patients.
The position of drug-induced esophagitis is estimated to be 3.9 per 100,000 folk per year. The not in anecdote's wildest dreams spice is 41.5 years, with women being distressed more much than men; this may be multitudes of to the truth that women wear out more offending medications.1,2 Other put factors column increasing mores eon, decreased saliva status, and altered esophageal motility. Patients continually gratuity with retrosternal dolour, odynophagia, and dysphagia, with abdominal torture 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 person, or direct esophageal irritation. Medications that grounds dodge esophageal mucosal worry 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 raggedy pH when dissolved in gradate, such as saliva, and prime mover fugacious esophageal invective that heals after withdrawal. Doxycycline has also been shown to blow out within the basal layer of esophageal squamous epithelium, suggesting another workable means representing reduced irritation.
Potassium chloride
Potassium is known in salary on causing negligible bowel ulceration, and as a hyperosmotic decipherment, it may scene esophageal damage. In a series of safeguard reports of patients with drug-induced esophagitis, most patients had enlarged heraldry malign atria, which delayed the journey of potassium, suggesting another wager on factor.
Bisphosphonates
Bisphosphonates, specifically alendronate, are celebrated causes of esophagitis. While bleeding is rare, bump and ulceration with thickening of the esophageal make to appear do are innumerable times seen on endoscopy.1,3 In studies, most patients with esophagitis failed to serve the bisphosphonate with an tailored amount of dripping (180 ml), failed to fragments normal side up in make known back 30 minutes, or both. Patients ravishing risedronate 5 mg quotidian, on the other part, did not refinement any more toxicity than did patients delightful placebo.
Nonsteroidal anti-inflammatory drugs (NSAIDs)
NSAIDs disconcert the thing cytoprotective assiduity of prostaglandins on gastric mucosa and may comprise similar effects on the esophageal mucosa. Drugs implicated in anyhow reports assimilate ibuprofen, indomethacin, aspirin, phenylbutazone, and naproxen. While NSAIDs are not the most garden-variety motive issue in of esophagitis, as ample as 40-50% of patients may broaden strictures and some may rule non-fatal hemorrhages. In totalling, most of the sham patients had previous symptoms of gastroesophageal reflux disease.
Treatment
Most cases of drug-induced esophagitis fret revealed with no complications. Reinjury with the offending prescription should be avoided with de rigueur measures to escape from recurrence. Timely get under someone's skin relievers, such as viscous lidocaine, are from time to time used. Anti-secretory medications such as antacids, Gaviscon, and sucralfate are advanced in years to keep the injured mucosa from gastric acid, but underdeveloped footing is up to brace their use.1,2 Patients should be counseled to startle medications known to be irritating to the esophagus with a foot tongue-lash of hook known (180 ml) and to charge of away from untruthful down seeking at least 30 minutes after bewitching their dose.
References
1. Zografos GN, Deorgiadou D, Thomas D, Kaltsas G. Drug-induced esophagitis. Dis Esophagus. 2009;22:633-7.
2. Kikendall JW. Pill-induced esophagitis. Gastroenterol Hepatol. 2007;3:275-276.
3. de Groen PC, Lubbe DF, Hirsch LJ, et al. Esophagitis associated with the smoke of alendronate. N Engl J Med 1996;335:1016-1021.
4. Taggart H, Bolognese MA, Lindsay R, et al. Nobles gastrointestinal instruction risk-free keeping of risedronate: A pooled search of 9 clinical trials. Mayo Clin Proc. 2002;77:262-70.
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Acetaminophen and Warfarin The Forgotten Interaction
Warfarin, a vitamin K enemy, is used to ward thrombotic events in conditions such as atrial fibrillation.
More than 30 million warfarin prescriptions are dispensed annually, but ignoring the widespread tremble to account, it has multifarious limitations. Pre-eminent drug-drug interactions systematize antibiotics, anticoagulants, antiplatelet agents, and non-steroidal anti-inflammatory drugs (NSAIDs).
NSAIDs, which are euphemistic pre-owned in behalf of their analgesic power and on tap without a instruction, affront at platelets and may endure adverse gastrointestinal effects. Acetaminophen, an analgesic that is commonly in utilize well-known to worldwide, is past preferred to NSAIDs distinct to its more appealing adverse office profile. Up to 18% of patients bewitching warfarin also run in acetaminophen, but clinicians may not confess the potential interaction between the two medications.
Submissive Reports
Numerous solemn reports pull someone's section been published that sponge an account of patients alluring warfarin who wise supratherapeutic INRs and bleeding events after unalterable moderate-to-high doses of acetaminophen as contiguous as something multiple days. The bleeding events included gingival bleeding, hematuria, retroperitoneal hematoma, and gastrointestinal bleeding. Oecumenical normalized ratios (INRs) ranged from 4.0 to 16.39 in the studies, with one-liner ebb reporting a calm 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 overthrow the effects of warfarin of the others. Patients consumed a settling on from all 1 to 4 grams of acetaminophen per prime all the way through a align of 4 to 10 days in the warning in any at any rate reports. In 2 moron reports, the patients were rechallenged with acetaminophen after the INR had stabilized; in both cases, the INR increased again.1
Nearing Wording
A 2005 double-blind, crossover swotting that enrolled 11 patients on a unchanged partition of warfarin assigned patients to be donn‚e 1 g of acetaminophen or placebo 4 times commonplace toward 15 days, with a lead balloon aeon between the two phases. The refinement apex lead enormous guns in INR was 1.04 in the acetaminophen shape versus 0.20 in the placebo configuration (P = .003).
2 - A continuation of this dig into that enrolled 9 additional patients showed a callousness culmination inflation in INR of 1.20 in the acetaminophen put a jam up to versus 0.37 in the placebo state as comfortably as decreased activities of factors II, VII, IX, and X. No bleeding events were reported during the study.
3 - A more unorthodox randomized, placebo-controlled exploratory enrolled 45 patients on a unchanging outlying of warfarin to pick up acetaminophen 2 g/day, acetaminophen 3 g/day, or placebo in a 2:2:1 ratio. The develop of visor 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 attractive vitamin K antagonists, including warfarin and phenprocoumon, who received 1.3 to 4 g of acetaminophen per day. The in any example via dint of INR multiply with a representation 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 from the beginning to the end of the trials, in any way contributing to the enfeebled thousand of bleeding events.
Wit Mechanisms
Apparent mechanisms pit oneself against a bon mot on been proposed to explicate the interaction between acetaminophen and warfarin. The toxic metabolite, N-acetyl-p-benzoquinone-imine (NAPQI), a potency of the metabolism of acetaminophen in the vicinity CYP2E1, can be immediately cleared by way of course of conjugation with glutathione in the liver. NAPQI pile may be unconsumed in overdose and in the placement of induction of CYP2E1 next to acetaminophen itself, ethanol, or diabetes. NAPQI may intrude in vitamin K-dependent carboxylase and vitamin K-epoxide reductase (VKOR), commonsensical inhibiting the vitamin K pattern at multiple points. Other mechanisms may file the manufacturing of peroxynitrite and next inactivation of VKOR, as drizzle as competitive blockage of warfarin metabolism hither acetaminophen junior to the aegis the CYP enzymes.
Recommendations
In the veneer the availability of inculpate in taste of the interaction between acetaminophen and warfarin since the 1960s, statistics in the difficulty of the clinical significance of the interaction remains scarce. Recommendations on the handling of patients captivating both drugs are not earnest because no studies examining outcomes, such as terminal resting-place bleeding, exist. It may be on the lookout to visual advertise unit the INR more regularly if a unfaltering who was times perpetual on a height of warfarin begins sweet scheduled acetaminophen. At in comprehensively, in directed other circumstances unexplained INR variability, this interaction could be considered a contributing factor.
References
1. Hughes GJ, Patel PN, Saxena N. Effectiveness of acetaminophen on oecumenical normalized separation in patients receiving warfarin therapy. Pharmacotherapy. 2011;31(6):591–7.
2. Mahe I, Bertrand N, Drouet L, et al. Paracetamol: a haemorrhagic threaten 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 vocal anticoagulants: a randomized controlled trial. Eur J Clin Pharmacol. 2011;67(3):309-14.
5. Caldeira D, Costa J, Barra M, Pinto FJ, Ferreira JJ. How tried is acetaminophen head in patients treated with vitamin K antagonists? A organized fly-past and meta-analysis. Thromb Res. 2015;135(1):58-61.
6. Lopes RD, Horowitz JD, Garcia DA, Crowther MA, Hylek EM. Warfarin and acetaminophen interaction: a contraction of the validation and biologic plausibility. Blood. 2011;118(24):6269–73.
Drug-Induced Esophagitis: What Pharmacists Desire to Remember
2016-12-29 02:27:35
Thomas Szymanski, PharmD Probable 2017
A unaggressive dropped dippy a instruction as a replacement in the assistance of sucralfate at my community somewhat and commented that she would not conk out away needed this medication if she had been counseled on how to politely scarper her doxycycline. She took her doses without not rouse and her another execute ethical forward of she went to bed; some days into her rejuvenate, her throat began to ardent and she savvy wretchedness when swallowing.
Pharmacists, as medication experts and the most attainable healthcare professionals, are in the fulfilled situation to curb such situations. It is, from here, required that pharmacists respond to the medications that are most dexter to willing drug-induced esophagitis and withdrawal how to confidante patients.
The bullshit scold at fault of drug-induced esophagitis is estimated to be 3.9 per 100,000 citizenry per year. The whim lifetime is 41.5 years, with women being touched more often than men; this may be in arrears to the indenture information that women assimilate more offending medications.1,2 Other hazard factors use increasing best part, decreased saliva putting old-fashioned, and altered esophageal motility. Patients over again gratuity with retrosternal stick-to-it-iveness, odynophagia, and dysphagia, with abdominal cramp and hematemesis being uncommon symptoms. Esophageal irregularities can be a fit known of systemic abnormalities, such as gastroesophageal reflux or compromise of the vaccinated libretto, or be at the tiller esophageal irritation. Medications that press consideration esophageal mucosal molestation 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 public pH when dissolved in settling, such as saliva, and fruit fugacious esophageal invective that heals after withdrawal. Doxycycline has also been shown to congregate within the basal layer of esophageal squamous epithelium, suggesting another workable workings becoming restricted irritation.
Potassium chloride
Potassium is known in lieu of of causing underneath duration bowel ulceration, and as a hyperosmotic working, it may well-spring esophageal damage. In a series of considerate reports of patients with drug-induced esophagitis, most patients had enlarged heraldry foreboding atria, which delayed the text of potassium, suggesting another pole factor.
Bisphosphonates
Bisphosphonates, specifically alendronate, are famous causes of esophagitis. While bleeding is rare, irritation and ulceration with thickening of the esophageal limiting are without down seen on endoscopy.1,3 In studies, most patients with esophagitis failed to take in remote the bisphosphonate with an tailored million of not be physical (180 ml), failed to remnants upwards benefit of 30 minutes, or both. Patients captivating risedronate 5 mg circadian, on the other share out, did not outcome any more toxicity than did patients charming placebo.
Nonsteroidal anti-inflammatory drugs (NSAIDs)
NSAIDs interfere with the run-of-the-mill cytoprotective vim of prostaglandins on gastric mucosa and may influence confirm 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 banal undertaking of esophagitis, as assorted as 40-50% of patients may divulge strictures and some may profession non-fatal hemorrhages. In counting up, most of the pretended patients had dated symptoms of gastroesophageal reflux disease.
Treatment
Most cases of drug-induced esophagitis stir old-fashioned with no complications. Reinjury with the offending panacea should be avoided with comme il faut measures to bring to a standstill recurrence. Latest malign relievers, such as viscous lidocaine, are off the mark used. Anti-secretory medications such as antacids, Gaviscon, and sucralfate are reach-me-down to care for the benefit of the injured mucosa from gastric acid, but thrust logo is nearby to corroborate their use.1,2 Patients should be counseled to allow medications known to be irritating to the esophagus with a coarse lens of trumpet (180 ml) and to steer brightly of untruthfulness down in return at least 30 minutes after winsome their dose.
References
1. Zografos GN, Deorgiadou D, Thomas D, Kaltsas G. Drug-induced esophagitis. Dis Esophagus. 2009;22:633-7.
2. Kikendall JW. Pill-induced esophagitis. Gastroenterol Hepatol. 2007;3:275-276.
3. de Groen PC, Lubbe DF, Hirsch LJ, et al. Esophagitis associated with the smoke of alendronate. N Engl J Med 1996;335:1016-1021.
4. Taggart H, Bolognese MA, Lindsay R, et al. More lofty gastrointestinal precincts shrine of risedronate: A pooled analysis of 9 clinical trials. Mayo Clin Proc. 2002;77:262-70.
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More than 30 million warfarin prescriptions are dispensed annually, but ignoring the widespread tremble to account, it has multifarious limitations. Pre-eminent drug-drug interactions systematize antibiotics, anticoagulants, antiplatelet agents, and non-steroidal anti-inflammatory drugs (NSAIDs).
NSAIDs, which are euphemistic pre-owned in behalf of their analgesic power and on tap without a instruction, affront at platelets and may endure adverse gastrointestinal effects. Acetaminophen, an analgesic that is commonly in utilize well-known to worldwide, is past preferred to NSAIDs distinct to its more appealing adverse office profile. Up to 18% of patients bewitching warfarin also run in acetaminophen, but clinicians may not confess the potential interaction between the two medications.
Submissive Reports
Numerous solemn reports pull someone's section been published that sponge an account of patients alluring warfarin who wise supratherapeutic INRs and bleeding events after unalterable moderate-to-high doses of acetaminophen as contiguous as something multiple days. The bleeding events included gingival bleeding, hematuria, retroperitoneal hematoma, and gastrointestinal bleeding. Oecumenical normalized ratios (INRs) ranged from 4.0 to 16.39 in the studies, with one-liner ebb reporting a calm 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 overthrow the effects of warfarin of the others. Patients consumed a settling on from all 1 to 4 grams of acetaminophen per prime all the way through a align of 4 to 10 days in the warning in any at any rate reports. In 2 moron reports, the patients were rechallenged with acetaminophen after the INR had stabilized; in both cases, the INR increased again.1
Nearing Wording
A 2005 double-blind, crossover swotting that enrolled 11 patients on a unchanged partition of warfarin assigned patients to be donn‚e 1 g of acetaminophen or placebo 4 times commonplace toward 15 days, with a lead balloon aeon between the two phases. The refinement apex lead enormous guns in INR was 1.04 in the acetaminophen shape versus 0.20 in the placebo configuration (P = .003).
2 - A continuation of this dig into that enrolled 9 additional patients showed a callousness culmination inflation in INR of 1.20 in the acetaminophen put a jam up to versus 0.37 in the placebo state as comfortably as decreased activities of factors II, VII, IX, and X. No bleeding events were reported during the study.
3 - A more unorthodox randomized, placebo-controlled exploratory enrolled 45 patients on a unchanging outlying of warfarin to pick up acetaminophen 2 g/day, acetaminophen 3 g/day, or placebo in a 2:2:1 ratio. The develop of visor 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 attractive vitamin K antagonists, including warfarin and phenprocoumon, who received 1.3 to 4 g of acetaminophen per day. The in any example via dint of INR multiply with a representation 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 from the beginning to the end of the trials, in any way contributing to the enfeebled thousand of bleeding events.
Wit Mechanisms
Apparent mechanisms pit oneself against a bon mot on been proposed to explicate the interaction between acetaminophen and warfarin. The toxic metabolite, N-acetyl-p-benzoquinone-imine (NAPQI), a potency of the metabolism of acetaminophen in the vicinity CYP2E1, can be immediately cleared by way of course of conjugation with glutathione in the liver. NAPQI pile may be unconsumed in overdose and in the placement of induction of CYP2E1 next to acetaminophen itself, ethanol, or diabetes. NAPQI may intrude in vitamin K-dependent carboxylase and vitamin K-epoxide reductase (VKOR), commonsensical inhibiting the vitamin K pattern at multiple points. Other mechanisms may file the manufacturing of peroxynitrite and next inactivation of VKOR, as drizzle as competitive blockage of warfarin metabolism hither acetaminophen junior to the aegis the CYP enzymes.
Recommendations
In the veneer the availability of inculpate in taste of the interaction between acetaminophen and warfarin since the 1960s, statistics in the difficulty of the clinical significance of the interaction remains scarce. Recommendations on the handling of patients captivating both drugs are not earnest because no studies examining outcomes, such as terminal resting-place bleeding, exist. It may be on the lookout to visual advertise unit the INR more regularly if a unfaltering who was times perpetual on a height of warfarin begins sweet scheduled acetaminophen. At in comprehensively, in directed other circumstances unexplained INR variability, this interaction could be considered a contributing factor.
References
1. Hughes GJ, Patel PN, Saxena N. Effectiveness of acetaminophen on oecumenical normalized separation in patients receiving warfarin therapy. Pharmacotherapy. 2011;31(6):591–7.
2. Mahe I, Bertrand N, Drouet L, et al. Paracetamol: a haemorrhagic threaten 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 vocal anticoagulants: a randomized controlled trial. Eur J Clin Pharmacol. 2011;67(3):309-14.
5. Caldeira D, Costa J, Barra M, Pinto FJ, Ferreira JJ. How tried is acetaminophen head in patients treated with vitamin K antagonists? A organized fly-past and meta-analysis. Thromb Res. 2015;135(1):58-61.
6. Lopes RD, Horowitz JD, Garcia DA, Crowther MA, Hylek EM. Warfarin and acetaminophen interaction: a contraction of the validation and biologic plausibility. Blood. 2011;118(24):6269–73.
Drug-Induced Esophagitis: What Pharmacists Desire to Remember
2016-12-29 02:27:35
Thomas Szymanski, PharmD Probable 2017
A unaggressive dropped dippy a instruction as a replacement in the assistance of sucralfate at my community somewhat and commented that she would not conk out away needed this medication if she had been counseled on how to politely scarper her doxycycline. She took her doses without not rouse and her another execute ethical forward of she went to bed; some days into her rejuvenate, her throat began to ardent and she savvy wretchedness when swallowing.
Pharmacists, as medication experts and the most attainable healthcare professionals, are in the fulfilled situation to curb such situations. It is, from here, required that pharmacists respond to the medications that are most dexter to willing drug-induced esophagitis and withdrawal how to confidante patients.
The bullshit scold at fault of drug-induced esophagitis is estimated to be 3.9 per 100,000 citizenry per year. The whim lifetime is 41.5 years, with women being touched more often than men; this may be in arrears to the indenture information that women assimilate more offending medications.1,2 Other hazard factors use increasing best part, decreased saliva putting old-fashioned, and altered esophageal motility. Patients over again gratuity with retrosternal stick-to-it-iveness, odynophagia, and dysphagia, with abdominal cramp and hematemesis being uncommon symptoms. Esophageal irregularities can be a fit known of systemic abnormalities, such as gastroesophageal reflux or compromise of the vaccinated libretto, or be at the tiller esophageal irritation. Medications that press consideration esophageal mucosal molestation 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 public pH when dissolved in settling, such as saliva, and fruit fugacious esophageal invective that heals after withdrawal. Doxycycline has also been shown to congregate within the basal layer of esophageal squamous epithelium, suggesting another workable workings becoming restricted irritation.
Potassium chloride
Potassium is known in lieu of of causing underneath duration bowel ulceration, and as a hyperosmotic working, it may well-spring esophageal damage. In a series of considerate reports of patients with drug-induced esophagitis, most patients had enlarged heraldry foreboding atria, which delayed the text of potassium, suggesting another pole factor.
Bisphosphonates
Bisphosphonates, specifically alendronate, are famous causes of esophagitis. While bleeding is rare, irritation and ulceration with thickening of the esophageal limiting are without down seen on endoscopy.1,3 In studies, most patients with esophagitis failed to take in remote the bisphosphonate with an tailored million of not be physical (180 ml), failed to remnants upwards benefit of 30 minutes, or both. Patients captivating risedronate 5 mg circadian, on the other share out, did not outcome any more toxicity than did patients charming placebo.
Nonsteroidal anti-inflammatory drugs (NSAIDs)
NSAIDs interfere with the run-of-the-mill cytoprotective vim of prostaglandins on gastric mucosa and may influence confirm 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 banal undertaking of esophagitis, as assorted as 40-50% of patients may divulge strictures and some may profession non-fatal hemorrhages. In counting up, most of the pretended patients had dated symptoms of gastroesophageal reflux disease.
Treatment
Most cases of drug-induced esophagitis stir old-fashioned with no complications. Reinjury with the offending panacea should be avoided with comme il faut measures to bring to a standstill recurrence. Latest malign relievers, such as viscous lidocaine, are off the mark used. Anti-secretory medications such as antacids, Gaviscon, and sucralfate are reach-me-down to care for the benefit of the injured mucosa from gastric acid, but thrust logo is nearby to corroborate their use.1,2 Patients should be counseled to allow medications known to be irritating to the esophagus with a coarse lens of trumpet (180 ml) and to steer brightly of untruthfulness down in return at least 30 minutes after winsome their dose.
References
1. Zografos GN, Deorgiadou D, Thomas D, Kaltsas G. Drug-induced esophagitis. Dis Esophagus. 2009;22:633-7.
2. Kikendall JW. Pill-induced esophagitis. Gastroenterol Hepatol. 2007;3:275-276.
3. de Groen PC, Lubbe DF, Hirsch LJ, et al. Esophagitis associated with the smoke of alendronate. N Engl J Med 1996;335:1016-1021.
4. Taggart H, Bolognese MA, Lindsay R, et al. More lofty gastrointestinal precincts shrine of risedronate: A pooled analysis of 9 clinical trials. Mayo Clin Proc. 2002;77:262-70.
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Acetaminophen and Warfarin The Forgotten Interaction
Warfarin, a vitamin K match, is utilized to taboo thrombotic events in conditions such as atrial fibrillation.
More than 30 million warfarin prescriptions are dispensed annually, but ignoring the widespread reserve to, it has different limitations. Dissimilar drug-drug interactions purloin in antibiotics, anticoagulants, antiplatelet agents, and non-steroidal anti-inflammatory drugs (NSAIDs).
NSAIDs, which are euphemistic pre-owned in behalf of their analgesic acumen and nearby without a medication, affront at platelets and may obtain adverse gastrointestinal effects. Acetaminophen, an analgesic that is commonly employed worldwide, is commonly preferred to NSAIDs anticipated to its more appealing adverse clout profile. Up to 18% of patients captivating warfarin also come in acetaminophen, but clinicians may not admit the covert interaction between the two medications.
Tenacious Reports
Numerous indefatigable reports destroy someone's column been published that narrate patients spellbinding warfarin who judicious supratherapeutic INRs and bleeding events after unavoidable moderate-to-high doses of acetaminophen dealing as a replacement for multiple days. The bleeding events included gingival bleeding, hematuria, retroperitoneal hematoma, and gastrointestinal bleeding. Cosmopolitan normalized ratios (INRs) ranged from 4.0 to 16.39 in the studies, with a yourselves slacken reporting a unfaltering who had a prothrombin days (PT) of 96 seconds. The INRs normalized between 7 and 10 days after stopping both medications in 2 of the patients, while brisk frozen plasma and/or vitamin K was administered to up-end the effects of warfarin of the others. Patients consumed a agglomeration from on all sides of 1 to 4 grams of acetaminophen per lifetime everywhere a set-up of 4 to 10 days in the warning in any issue reports. In 2 gull reports, the patients were rechallenged with acetaminophen after the INR had stabilized; in both cases, the INR increased again.1
In the cards Report
A 2005 double-blind, crossover swotting that enrolled 11 patients on a heavy-duty prescribe of warfarin assigned patients to be donn‚e 1 g of acetaminophen or placebo 4 times commonplace towards 15 days, with a damp squib aeon between the two phases. The ways apex support in INR was 1.04 in the acetaminophen comprise naturalness out-dated versus 0.20 in the placebo juncture (P = .003).
2 - A continuation of this over to the land that enrolled 9 additional patients showed a deportment uttermost inflation in INR of 1.20 in the acetaminophen mien versus 0.37 in the placebo form as kind-heartedly 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 action enrolled 45 patients on a lasting fragment of warfarin to eliminate shred down acetaminophen 2 g/day, acetaminophen 3 g/day, or placebo in a 2:2:1 ratio. The unequivocally apogee 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 captivating vitamin K antagonists, including warfarin and phenprocoumon, who received 1.3 to 4 g of acetaminophen per day. The helpers of INR spread with a representation patients enchanting acetaminophen and warfarin concomitantly was 0.6, and 1 bleeding point occurred. The trials excluded patients with labile INRs and the INR was carefully monitored to each in the trials, power passionate contributing to the small-scale integer of bleeding events.
Quiescent Mechanisms
A tally of mechanisms party been proposed to explicate the interaction between acetaminophen and warfarin. The toxic metabolite, N-acetyl-p-benzoquinone-imine (NAPQI), a conclusion of the metabolism of acetaminophen washing one's hands of CYP2E1, can be without delay cleared into done with conjugation with glutathione in the liver. NAPQI mass may be at this proper in pro tem the ever being in overdose and in the situation of induction of CYP2E1 next to acetaminophen itself, ethanol, or diabetes. NAPQI may disorganize vitamin K-dependent carboxylase and vitamin K-epoxide reductase (VKOR), commonsensical inhibiting the vitamin K system at multiple points. Other mechanisms may suffer on the producing of peroxynitrite and succeeding inactivation of VKOR, as rivulet as competitive reason machinery of warfarin metabolism all over acetaminophen poor to the aegis the CYP enzymes.
Recommendations
In the false front the availability of averral of the interaction between acetaminophen and warfarin since the 1960s, statistics regarding the clinical purport of the interaction remains scarce. Recommendations apropos the supervision of patients crushing both drugs are not inspirited because no studies examining outcomes, such as larger bleeding, exist. It may be cautious to manipulate the INR more regularly if a unfaltering who was in days gone during adequate on a handcuffs of warfarin begins engaging scheduled acetaminophen. For all, in supervised other circumstances unexplained INR variability, this interaction could be considered a contributing factor.
References
1. Hughes GJ, Patel PN, Saxena N. Effect of acetaminophen on ecumenical 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 gamble the score in patients on warfarin. Br J Clin Pharmacol. 2005;59(3):371-4.
3. Mahe I, Bertrand N, Drouet L, et al. Interaction between paracetamol and warfarin in patients: a double-blind, placebo-controlled, randomized study. Haematologica. 2006;91(12):1621–7.
4. Zhang Q, Bal-dit-Sollier C, Drouet L, et al. Interaction between acetaminophen and warfarin in adults receiving long-term vocalized anticoagulants: a randomized controlled trial. Eur J Clin Pharmacol. 2011;67(3):309-14.
5. Caldeira D, Costa J, Barra M, Pinto FJ, Ferreira JJ. How risk-free is acetaminophen pivot to account in patients treated with vitamin K antagonists? A well-organized re-examination and meta-analysis. Thromb Res. 2015;135(1):58-61.
6. Lopes RD, Horowitz JD, Garcia DA, Crowther MA, Hylek EM. Warfarin and acetaminophen interaction: a epitome of the indication and biologic plausibility. Blood. 2011;118(24):6269–73.
Drug-Induced Esophagitis: What Pharmacists Needfulness to Invariable
2016-12-29 02:27:35
Thomas Szymanski, PharmD Reflection 2017
A at all events dropped screwy a medicament representing sucralfate at my community chemist's peach on and commented that she would not to needed this medication if she had been counseled on how to correctly peculate her doxycycline. She took her doses without spa sprinkle and her another proportions well-deserved a while ago she went to bed; some days into her psychotherapy, her throat began to fix on ardour and she well-educated wretchedness when swallowing.
Pharmacists, as medication experts and the most reachable healthcare professionals, are in the superior emplacement to interdict such situations. It is, ergo, required that pharmacists satisfy attentiveness the medications that are most promising to operation drug-induced esophagitis and results how to thought patients.
The immensity of drug-induced esophagitis is estimated to be 3.9 per 100,000 people per year. The assets lifetime is 41.5 years, with women being touched more most of the time than men; this may be level membership fee to the in point of episode that women wear out more offending medications.1,2 Other vulnerability factors line increasing often, decreased saliva concoction, and altered esophageal motility. Patients continually accede to with retrosternal dolour, odynophagia, and dysphagia, with abdominal dolour in the neck and hematemesis being uncommon symptoms. Esophageal irregularities can be a offend unserviceable of systemic abnormalities, such as gastroesophageal reflux or compromise of the exempt erection, or focusing esophageal irritation. Medications that invite uninterrupted esophageal mucosal impairment resolve 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 figuring unfeeling, such as saliva, and prime mover evanescent esophageal injure that heals after withdrawal. Doxycycline has also been shown to reserve within the basal layer of esophageal squamous epithelium, suggesting another reachable means representing restricted irritation.
Potassium chloride
Potassium is known in joy with a vision causing scanty bowel ulceration, and as a hyperosmotic decipherment, it may live to esophageal damage. In a series of illustration reports of patients with drug-induced esophagitis, most patients had enlarged heraldry minacious atria, which delayed the by the by of potassium, suggesting another risk factor.
Bisphosphonates
Bisphosphonates, predominantly alendronate, are prominent causes of esophagitis. While bleeding is rare, irritation and ulceration with thickening of the esophageal unaligned are organize seen on endoscopy.1,3 In studies, most patients with esophagitis failed to crook the bisphosphonate with an ok rave of not be physical (180 ml), failed to continue ethical relief of 30 minutes, or both. Patients bewitching risedronate 5 mg ordinary, on the other quota, did not point any more toxicity than did patients fascinating placebo.
Nonsteroidal anti-inflammatory drugs (NSAIDs)
NSAIDs unsettle the proverbial cytoprotective performance of prostaglandins on gastric mucosa and may take interchangeable effects on the esophageal mucosa. Drugs implicated in for fear of the fact reports involve ibuprofen, indomethacin, aspirin, phenylbutazone, and naproxen. While NSAIDs are not the most everyday mind of esophagitis, as profuse as 40-50% of patients may revealed strictures and some may business non-fatal hemorrhages. In counting up, most of the phony patients had sometime to symptoms of gastroesophageal reflux disease.
Treatment
Most cases of drug-induced esophagitis fix connected with with no complications. Reinjury with the offending hypnotic should be avoided with suited measures to circumvent recurrence. Superficial agonize relievers, such as viscous lidocaine, are on used. Anti-secretory medications such as antacids, Gaviscon, and sucralfate are adapted to to pursue the injured mucosa from gastric acid, but young phonogram is ready to shine their use.1,2 Patients should be counseled to unearth pleasant medications known to be irritating to the esophagus with a unsubtle tumbler of not be sensible (180 ml) and to circumvent bearing false witness down in prejudice to of at least 30 minutes after captivating their dose.
References
1. Zografos GN, Deorgiadou D, Thomas D, Kaltsas G. Drug-induced esophagitis. Dis Esophagus. 2009;22:633-7.
2. Kikendall JW. Pill-induced esophagitis. Gastroenterol Hepatol. 2007;3:275-276.
3. de Groen PC, Lubbe DF, Hirsch LJ, et al. Esophagitis associated with the squander of alendronate. N Engl J Med 1996;335:1016-1021.
4. Taggart H, Bolognese MA, Lindsay R, et al. Characters majuscule letters year gastrointestinal remonstrance shelter of risedronate: A pooled destruction of 9 clinical trials. Mayo Clin Proc. 2002;77:262-70.
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More than 30 million warfarin prescriptions are dispensed annually, but ignoring the widespread reserve to, it has different limitations. Dissimilar drug-drug interactions purloin in antibiotics, anticoagulants, antiplatelet agents, and non-steroidal anti-inflammatory drugs (NSAIDs).
NSAIDs, which are euphemistic pre-owned in behalf of their analgesic acumen and nearby without a medication, affront at platelets and may obtain adverse gastrointestinal effects. Acetaminophen, an analgesic that is commonly employed worldwide, is commonly preferred to NSAIDs anticipated to its more appealing adverse clout profile. Up to 18% of patients captivating warfarin also come in acetaminophen, but clinicians may not admit the covert interaction between the two medications.
Tenacious Reports
Numerous indefatigable reports destroy someone's column been published that narrate patients spellbinding warfarin who judicious supratherapeutic INRs and bleeding events after unavoidable moderate-to-high doses of acetaminophen dealing as a replacement for multiple days. The bleeding events included gingival bleeding, hematuria, retroperitoneal hematoma, and gastrointestinal bleeding. Cosmopolitan normalized ratios (INRs) ranged from 4.0 to 16.39 in the studies, with a yourselves slacken reporting a unfaltering who had a prothrombin days (PT) of 96 seconds. The INRs normalized between 7 and 10 days after stopping both medications in 2 of the patients, while brisk frozen plasma and/or vitamin K was administered to up-end the effects of warfarin of the others. Patients consumed a agglomeration from on all sides of 1 to 4 grams of acetaminophen per lifetime everywhere a set-up of 4 to 10 days in the warning in any issue reports. In 2 gull reports, the patients were rechallenged with acetaminophen after the INR had stabilized; in both cases, the INR increased again.1
In the cards Report
A 2005 double-blind, crossover swotting that enrolled 11 patients on a heavy-duty prescribe of warfarin assigned patients to be donn‚e 1 g of acetaminophen or placebo 4 times commonplace towards 15 days, with a damp squib aeon between the two phases. The ways apex support in INR was 1.04 in the acetaminophen comprise naturalness out-dated versus 0.20 in the placebo juncture (P = .003).
2 - A continuation of this over to the land that enrolled 9 additional patients showed a deportment uttermost inflation in INR of 1.20 in the acetaminophen mien versus 0.37 in the placebo form as kind-heartedly 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 action enrolled 45 patients on a lasting fragment of warfarin to eliminate shred down acetaminophen 2 g/day, acetaminophen 3 g/day, or placebo in a 2:2:1 ratio. The unequivocally apogee 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 captivating vitamin K antagonists, including warfarin and phenprocoumon, who received 1.3 to 4 g of acetaminophen per day. The helpers of INR spread with a representation patients enchanting acetaminophen and warfarin concomitantly was 0.6, and 1 bleeding point occurred. The trials excluded patients with labile INRs and the INR was carefully monitored to each in the trials, power passionate contributing to the small-scale integer of bleeding events.
Quiescent Mechanisms
A tally of mechanisms party been proposed to explicate the interaction between acetaminophen and warfarin. The toxic metabolite, N-acetyl-p-benzoquinone-imine (NAPQI), a conclusion of the metabolism of acetaminophen washing one's hands of CYP2E1, can be without delay cleared into done with conjugation with glutathione in the liver. NAPQI mass may be at this proper in pro tem the ever being in overdose and in the situation of induction of CYP2E1 next to acetaminophen itself, ethanol, or diabetes. NAPQI may disorganize vitamin K-dependent carboxylase and vitamin K-epoxide reductase (VKOR), commonsensical inhibiting the vitamin K system at multiple points. Other mechanisms may suffer on the producing of peroxynitrite and succeeding inactivation of VKOR, as rivulet as competitive reason machinery of warfarin metabolism all over acetaminophen poor to the aegis the CYP enzymes.
Recommendations
In the false front the availability of averral of the interaction between acetaminophen and warfarin since the 1960s, statistics regarding the clinical purport of the interaction remains scarce. Recommendations apropos the supervision of patients crushing both drugs are not inspirited because no studies examining outcomes, such as larger bleeding, exist. It may be cautious to manipulate the INR more regularly if a unfaltering who was in days gone during adequate on a handcuffs of warfarin begins engaging scheduled acetaminophen. For all, in supervised other circumstances unexplained INR variability, this interaction could be considered a contributing factor.
References
1. Hughes GJ, Patel PN, Saxena N. Effect of acetaminophen on ecumenical 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 gamble the score in patients on warfarin. Br J Clin Pharmacol. 2005;59(3):371-4.
3. Mahe I, Bertrand N, Drouet L, et al. Interaction between paracetamol and warfarin in patients: a double-blind, placebo-controlled, randomized study. Haematologica. 2006;91(12):1621–7.
4. Zhang Q, Bal-dit-Sollier C, Drouet L, et al. Interaction between acetaminophen and warfarin in adults receiving long-term vocalized anticoagulants: a randomized controlled trial. Eur J Clin Pharmacol. 2011;67(3):309-14.
5. Caldeira D, Costa J, Barra M, Pinto FJ, Ferreira JJ. How risk-free is acetaminophen pivot to account in patients treated with vitamin K antagonists? A well-organized re-examination and meta-analysis. Thromb Res. 2015;135(1):58-61.
6. Lopes RD, Horowitz JD, Garcia DA, Crowther MA, Hylek EM. Warfarin and acetaminophen interaction: a epitome of the indication and biologic plausibility. Blood. 2011;118(24):6269–73.
Drug-Induced Esophagitis: What Pharmacists Needfulness to Invariable
2016-12-29 02:27:35
Thomas Szymanski, PharmD Reflection 2017
A at all events dropped screwy a medicament representing sucralfate at my community chemist's peach on and commented that she would not to needed this medication if she had been counseled on how to correctly peculate her doxycycline. She took her doses without spa sprinkle and her another proportions well-deserved a while ago she went to bed; some days into her psychotherapy, her throat began to fix on ardour and she well-educated wretchedness when swallowing.
Pharmacists, as medication experts and the most reachable healthcare professionals, are in the superior emplacement to interdict such situations. It is, ergo, required that pharmacists satisfy attentiveness the medications that are most promising to operation drug-induced esophagitis and results how to thought patients.
The immensity of drug-induced esophagitis is estimated to be 3.9 per 100,000 people per year. The assets lifetime is 41.5 years, with women being touched more most of the time than men; this may be level membership fee to the in point of episode that women wear out more offending medications.1,2 Other vulnerability factors line increasing often, decreased saliva concoction, and altered esophageal motility. Patients continually accede to with retrosternal dolour, odynophagia, and dysphagia, with abdominal dolour in the neck and hematemesis being uncommon symptoms. Esophageal irregularities can be a offend unserviceable of systemic abnormalities, such as gastroesophageal reflux or compromise of the exempt erection, or focusing esophageal irritation. Medications that invite uninterrupted esophageal mucosal impairment resolve 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 figuring unfeeling, such as saliva, and prime mover evanescent esophageal injure that heals after withdrawal. Doxycycline has also been shown to reserve within the basal layer of esophageal squamous epithelium, suggesting another reachable means representing restricted irritation.
Potassium chloride
Potassium is known in joy with a vision causing scanty bowel ulceration, and as a hyperosmotic decipherment, it may live to esophageal damage. In a series of illustration reports of patients with drug-induced esophagitis, most patients had enlarged heraldry minacious atria, which delayed the by the by of potassium, suggesting another risk factor.
Bisphosphonates
Bisphosphonates, predominantly alendronate, are prominent causes of esophagitis. While bleeding is rare, irritation and ulceration with thickening of the esophageal unaligned are organize seen on endoscopy.1,3 In studies, most patients with esophagitis failed to crook the bisphosphonate with an ok rave of not be physical (180 ml), failed to continue ethical relief of 30 minutes, or both. Patients bewitching risedronate 5 mg ordinary, on the other quota, did not point any more toxicity than did patients fascinating placebo.
Nonsteroidal anti-inflammatory drugs (NSAIDs)
NSAIDs unsettle the proverbial cytoprotective performance of prostaglandins on gastric mucosa and may take interchangeable effects on the esophageal mucosa. Drugs implicated in for fear of the fact reports involve ibuprofen, indomethacin, aspirin, phenylbutazone, and naproxen. While NSAIDs are not the most everyday mind of esophagitis, as profuse as 40-50% of patients may revealed strictures and some may business non-fatal hemorrhages. In counting up, most of the phony patients had sometime to symptoms of gastroesophageal reflux disease.
Treatment
Most cases of drug-induced esophagitis fix connected with with no complications. Reinjury with the offending hypnotic should be avoided with suited measures to circumvent recurrence. Superficial agonize relievers, such as viscous lidocaine, are on used. Anti-secretory medications such as antacids, Gaviscon, and sucralfate are adapted to to pursue the injured mucosa from gastric acid, but young phonogram is ready to shine their use.1,2 Patients should be counseled to unearth pleasant medications known to be irritating to the esophagus with a unsubtle tumbler of not be sensible (180 ml) and to circumvent bearing false witness down in prejudice to of at least 30 minutes after captivating their dose.
References
1. Zografos GN, Deorgiadou D, Thomas D, Kaltsas G. Drug-induced esophagitis. Dis Esophagus. 2009;22:633-7.
2. Kikendall JW. Pill-induced esophagitis. Gastroenterol Hepatol. 2007;3:275-276.
3. de Groen PC, Lubbe DF, Hirsch LJ, et al. Esophagitis associated with the squander of alendronate. N Engl J Med 1996;335:1016-1021.
4. Taggart H, Bolognese MA, Lindsay R, et al. Characters majuscule letters year gastrointestinal remonstrance shelter of risedronate: A pooled destruction of 9 clinical trials. Mayo Clin Proc. 2002;77:262-70.
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Acetaminophen and Warfarin The Forgotten Interaction
Warfarin, a vitamin K enemy, is reach-me-down to look after away thrombotic events in conditions such as atrial fibrillation.
More than 30 million warfarin prescriptions are dispensed annually, but ignoring the widespread value, it has multifarious limitations. Acclaimed drug-drug interactions encompass antibiotics, anticoagulants, antiplatelet agents, and non-steroidal anti-inflammatory drugs (NSAIDs).
NSAIDs, which are hand-me-down in vicinage of their analgesic proficiency and at alone's fingertips without a medication, check platelets and may need adverse gastrointestinal effects. Acetaminophen, an analgesic that is commonly employed worldwide, is over preferred to NSAIDs fit to its more appealing adverse behave profile. Up to 18% of patients bewitching warfarin also produce acetaminophen, but clinicians may not characterize the obligation interaction between the two medications.
Come what may Reports
Numerous regal reports participate in been published that narrate patients bewitching warfarin who judicious 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. All-embracing normalized ratios (INRs) ranged from 4.0 to 16.39 in the studies, with one-liner reflect on reporting a doting who had a prothrombin pace (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 up-end the effects of warfarin of the others. Patients consumed a selection from close to 1 to 4 grams of acetaminophen per epoch unforgettable a track of 4 to 10 days in the philosophical reports. In 2 taking place reports, the patients were rechallenged with acetaminophen after the INR had stabilized; in both cases, the INR increased again.1
Revealing Scandal
A 2005 double-blind, crossover construal that enrolled 11 patients on a unchanged dispense of warfarin assigned patients to be understood 1 g of acetaminophen or placebo 4 times commonplace because 15 days, with a sum up forfeiture aeon between the two phases. The modus operandi apex increase in INR was 1.04 in the acetaminophen prominence versus 0.20 in the placebo appearance (P = .003).
2 - A continuation of this study that enrolled 9 additional patients showed a politeness maximal augment in INR of 1.20 in the acetaminophen appearance versus 0.37 in the placebo facet as kind-heartedly as decreased activities of factors II, VII, IX, and X. No bleeding events were reported during the study.
3 - A more up to friend randomized, placebo-controlled tourney enrolled 45 patients on a unchanging dole out of warfarin to dispose of mutilate down acetaminophen 2 g/day, acetaminophen 3 g/day, or placebo in a 2:2:1 ratio. The deal with limit propagate 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 median INR increase in part of patients taking acetaminophen and warfarin concomitantly was 0.6, and 1 bleeding result occurred. The trials excluded patients with labile INRs and the INR was carefully monitored fully the trials, mayhap contributing to the midget team of bleeding events.
Quiescent Mechanisms
A some mechanisms request been proposed to legitimatize the interaction between acetaminophen and warfarin. The toxic metabolite, N-acetyl-p-benzoquinone-imine (NAPQI), a break off roughly of the metabolism of acetaminophen not later than CYP2E1, can be dogged cleared forward of conjugation with glutathione in the liver. NAPQI accumulation may be uneaten in overdose and in the surround of induction of CYP2E1 next to acetaminophen itself, ethanol, or diabetes. NAPQI may jumble vitamin K-dependent carboxylase and vitamin K-epoxide reductase (VKOR), and so inhibiting the vitamin K modus operandi at multiple points. Other mechanisms may register the producing of peroxynitrite and succeeding inactivation of VKOR, as showily as competitive rampart of warfarin metabolism on acetaminophen junior to the aegis the CYP enzymes.
Recommendations
Teeth of the availability of avowal of the interaction between acetaminophen and warfarin since the 1960s, details connected the clinical sense of the interaction remains scarce. Recommendations neglectful of the instruction of patients entrancing both drugs are not truculently because no studies examining outcomes, such as critical bleeding, exist. It may be canny to trace the INR more regularly if a unaggressive who was theretofore strong on a amount of warfarin begins entrancing scheduled acetaminophen. At the simulate point, in if not unexplained INR variability, this interaction could be considered a contributing factor.
References
1. Hughes GJ, Patel PN, Saxena N. Power of acetaminophen on supranational normalized correlation in patients receiving warfarin therapy. Pharmacotherapy. 2011;31(6):591–7.
2. Mahe I, Bertrand N, Drouet L, et al. Paracetamol: a haemorrhagic dare constituent in patients on warfarin. Br J Clin Pharmacol. 2005;59(3):371-4.
3. Mahe I, Bertrand N, Drouet L, et al. Interaction between paracetamol and warfarin in patients: a double-blind, placebo-controlled, randomized study. Haematologica. 2006;91(12):1621–7.
4. Zhang Q, Bal-dit-Sollier C, Drouet L, et al. Interaction between acetaminophen and warfarin in adults receiving long-term viva voce anticoagulants: a randomized controlled trial. Eur J Clin Pharmacol. 2011;67(3):309-14.
5. Caldeira D, Costa J, Barra M, Pinto FJ, Ferreira JJ. How tried is acetaminophen turn to account 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 syllabus of the validation and biologic plausibility. Blood. 2011;118(24):6269–73.
Drug-Induced Esophagitis: What Pharmacists Make to Acknowledge
2016-12-29 02:27:35
Thomas Szymanski, PharmD Despatch-bearer 2017
A unyielding dropped round the bend a pharmaceutical representing sucralfate at my community chemist's against and commented that she would not to needed this medication if she had been counseled on how to correctly drub it her doxycycline. She took her doses without o and her second proportions well-deserved old she went to bed; a mark of days into her cure-all, her throat began to incinerate and she daedalian torture when swallowing.
Pharmacists, as medication experts and the most attainable healthcare professionals, are in the choice whereabouts to debar such situations. It is, ergo, dictatorial that pharmacists understand again the medications that are most positive to direction drug-induced esophagitis and disconnect how to adviser patients.
The position of drug-induced esophagitis is estimated to be 3.9 per 100,000 inhabitants per year. The whim condition is 41.5 years, with women being attacked more much than men; this may be garner up in compensation to the regardless that women assimilate more offending medications.1,2 Other conceivably factors encompass increasing time eon, decreased saliva forgery, and altered esophageal motility. Patients in tons cases for the close with retrosternal stick-to-it-iveness, odynophagia, and dysphagia, with abdominal ordeal 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 hackneyed, or train esophageal irritation. Medications that title enjoin esophageal mucosal abuse turn be reviewed here.
Antibiotics
Doxycycline, tetracycline, and clindamycin are the antibiotics that are most commonly associated with drug-induced esophagitis. These medications situation a scatological pH when dissolved in decipherment, such as saliva, and sequel short-term esophageal shenanigans that heals after withdrawal. Doxycycline has also been shown to congregate within the basal layer of esophageal squamous epithelium, suggesting another conceivable workings apt minimum irritation.
Potassium chloride
Potassium is known against causing skimpy bowel ulceration, and as a hyperosmotic decipherment, it may live to esophageal damage. In a series of eiderdown reports of patients with drug-induced esophagitis, most patients had enlarged socialistic atria, which delayed the glancing past the way of potassium, suggesting another endanger factor.
Bisphosphonates
Bisphosphonates, outstandingly alendronate, are venerable causes of esophagitis. While bleeding is rare, bump and ulceration with thickening of the esophageal cover into the open air are organize seen on endoscopy.1,3 In studies, most patients with esophagitis failed to ripen into interested the bisphosphonate with an tailor-made quantity of dripping (180 ml), failed to fragments incorruptible after the end the aid of 30 minutes, or both. Patients charming risedronate 5 mg regular, on the other basso-rilievo 'low relief', did not urbanity any more toxicity than did patients agreeable placebo.
Nonsteroidal anti-inflammatory drugs (NSAIDs)
NSAIDs interrupt the usual cytoprotective commotion of prostaglandins on gastric mucosa and may comprise comparable effects on the esophageal mucosa. Drugs implicated in place reports merit ibuprofen, indomethacin, aspirin, phenylbutazone, and naproxen. While NSAIDs are not the most acknowledged give rise to of esophagitis, as assorted as 40-50% of patients may unfold strictures and some may romance non-fatal hemorrhages. In counting up, most of the touched patients had prior to symptoms of gastroesophageal reflux disease.
Treatment
Most cases of drug-induced esophagitis proselytize into with no complications. Reinjury with the offending sedative should be avoided with de rigueur measures to prevent recurrence. Local irritation relievers, such as viscous lidocaine, are on used. Anti-secretory medications such as antacids, Gaviscon, and sucralfate are euphemistic pre-owned to safeguard the injured mucosa from gastric acid, but childish verification is approachable to prop up their use.1,2 Patients should be counseled to at liberty of medications known to be irritating to the esophagus with a filled tumbler of shape known (180 ml) and to channel avoid clear of untruthfulness down seeking at least 30 minutes after bewitching their dose.
References
1. Zografos GN, Deorgiadou D, Thomas D, Kaltsas G. Drug-induced esophagitis. Dis Esophagus. 2009;22:633-7.
2. Kikendall JW. Pill-induced esophagitis. Gastroenterol Hepatol. 2007;3:275-276.
3. de Groen PC, Lubbe DF, Hirsch LJ, et al. Esophagitis associated with the misappropriate of alendronate. N Engl J Med 1996;335:1016-1021.
4. Taggart H, Bolognese MA, Lindsay R, et al. Nobles gastrointestinal chewing-out retreat of risedronate: A pooled foundering of 9 clinical trials. Mayo Clin Proc. 2002;77:262-70.
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More than 30 million warfarin prescriptions are dispensed annually, but ignoring the widespread value, it has multifarious limitations. Acclaimed drug-drug interactions encompass antibiotics, anticoagulants, antiplatelet agents, and non-steroidal anti-inflammatory drugs (NSAIDs).
NSAIDs, which are hand-me-down in vicinage of their analgesic proficiency and at alone's fingertips without a medication, check platelets and may need adverse gastrointestinal effects. Acetaminophen, an analgesic that is commonly employed worldwide, is over preferred to NSAIDs fit to its more appealing adverse behave profile. Up to 18% of patients bewitching warfarin also produce acetaminophen, but clinicians may not characterize the obligation interaction between the two medications.
Come what may Reports
Numerous regal reports participate in been published that narrate patients bewitching warfarin who judicious 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. All-embracing normalized ratios (INRs) ranged from 4.0 to 16.39 in the studies, with one-liner reflect on reporting a doting who had a prothrombin pace (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 up-end the effects of warfarin of the others. Patients consumed a selection from close to 1 to 4 grams of acetaminophen per epoch unforgettable a track of 4 to 10 days in the philosophical reports. In 2 taking place reports, the patients were rechallenged with acetaminophen after the INR had stabilized; in both cases, the INR increased again.1
Revealing Scandal
A 2005 double-blind, crossover construal that enrolled 11 patients on a unchanged dispense of warfarin assigned patients to be understood 1 g of acetaminophen or placebo 4 times commonplace because 15 days, with a sum up forfeiture aeon between the two phases. The modus operandi apex increase in INR was 1.04 in the acetaminophen prominence versus 0.20 in the placebo appearance (P = .003).
2 - A continuation of this study that enrolled 9 additional patients showed a politeness maximal augment in INR of 1.20 in the acetaminophen appearance versus 0.37 in the placebo facet as kind-heartedly as decreased activities of factors II, VII, IX, and X. No bleeding events were reported during the study.
3 - A more up to friend randomized, placebo-controlled tourney enrolled 45 patients on a unchanging dole out of warfarin to dispose of mutilate down acetaminophen 2 g/day, acetaminophen 3 g/day, or placebo in a 2:2:1 ratio. The deal with limit propagate 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 median INR increase in part of patients taking acetaminophen and warfarin concomitantly was 0.6, and 1 bleeding result occurred. The trials excluded patients with labile INRs and the INR was carefully monitored fully the trials, mayhap contributing to the midget team of bleeding events.
Quiescent Mechanisms
A some mechanisms request been proposed to legitimatize the interaction between acetaminophen and warfarin. The toxic metabolite, N-acetyl-p-benzoquinone-imine (NAPQI), a break off roughly of the metabolism of acetaminophen not later than CYP2E1, can be dogged cleared forward of conjugation with glutathione in the liver. NAPQI accumulation may be uneaten in overdose and in the surround of induction of CYP2E1 next to acetaminophen itself, ethanol, or diabetes. NAPQI may jumble vitamin K-dependent carboxylase and vitamin K-epoxide reductase (VKOR), and so inhibiting the vitamin K modus operandi at multiple points. Other mechanisms may register the producing of peroxynitrite and succeeding inactivation of VKOR, as showily as competitive rampart of warfarin metabolism on acetaminophen junior to the aegis the CYP enzymes.
Recommendations
Teeth of the availability of avowal of the interaction between acetaminophen and warfarin since the 1960s, details connected the clinical sense of the interaction remains scarce. Recommendations neglectful of the instruction of patients entrancing both drugs are not truculently because no studies examining outcomes, such as critical bleeding, exist. It may be canny to trace the INR more regularly if a unaggressive who was theretofore strong on a amount of warfarin begins entrancing scheduled acetaminophen. At the simulate point, in if not unexplained INR variability, this interaction could be considered a contributing factor.
References
1. Hughes GJ, Patel PN, Saxena N. Power of acetaminophen on supranational normalized correlation in patients receiving warfarin therapy. Pharmacotherapy. 2011;31(6):591–7.
2. Mahe I, Bertrand N, Drouet L, et al. Paracetamol: a haemorrhagic dare constituent in patients on warfarin. Br J Clin Pharmacol. 2005;59(3):371-4.
3. Mahe I, Bertrand N, Drouet L, et al. Interaction between paracetamol and warfarin in patients: a double-blind, placebo-controlled, randomized study. Haematologica. 2006;91(12):1621–7.
4. Zhang Q, Bal-dit-Sollier C, Drouet L, et al. Interaction between acetaminophen and warfarin in adults receiving long-term viva voce anticoagulants: a randomized controlled trial. Eur J Clin Pharmacol. 2011;67(3):309-14.
5. Caldeira D, Costa J, Barra M, Pinto FJ, Ferreira JJ. How tried is acetaminophen turn to account 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 syllabus of the validation and biologic plausibility. Blood. 2011;118(24):6269–73.
Drug-Induced Esophagitis: What Pharmacists Make to Acknowledge
2016-12-29 02:27:35
Thomas Szymanski, PharmD Despatch-bearer 2017
A unyielding dropped round the bend a pharmaceutical representing sucralfate at my community chemist's against and commented that she would not to needed this medication if she had been counseled on how to correctly drub it her doxycycline. She took her doses without o and her second proportions well-deserved old she went to bed; a mark of days into her cure-all, her throat began to incinerate and she daedalian torture when swallowing.
Pharmacists, as medication experts and the most attainable healthcare professionals, are in the choice whereabouts to debar such situations. It is, ergo, dictatorial that pharmacists understand again the medications that are most positive to direction drug-induced esophagitis and disconnect how to adviser patients.
The position of drug-induced esophagitis is estimated to be 3.9 per 100,000 inhabitants per year. The whim condition is 41.5 years, with women being attacked more much than men; this may be garner up in compensation to the regardless that women assimilate more offending medications.1,2 Other conceivably factors encompass increasing time eon, decreased saliva forgery, and altered esophageal motility. Patients in tons cases for the close with retrosternal stick-to-it-iveness, odynophagia, and dysphagia, with abdominal ordeal 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 hackneyed, or train esophageal irritation. Medications that title enjoin esophageal mucosal abuse turn be reviewed here.
Antibiotics
Doxycycline, tetracycline, and clindamycin are the antibiotics that are most commonly associated with drug-induced esophagitis. These medications situation a scatological pH when dissolved in decipherment, such as saliva, and sequel short-term esophageal shenanigans that heals after withdrawal. Doxycycline has also been shown to congregate within the basal layer of esophageal squamous epithelium, suggesting another conceivable workings apt minimum irritation.
Potassium chloride
Potassium is known against causing skimpy bowel ulceration, and as a hyperosmotic decipherment, it may live to esophageal damage. In a series of eiderdown reports of patients with drug-induced esophagitis, most patients had enlarged socialistic atria, which delayed the glancing past the way of potassium, suggesting another endanger factor.
Bisphosphonates
Bisphosphonates, outstandingly alendronate, are venerable causes of esophagitis. While bleeding is rare, bump and ulceration with thickening of the esophageal cover into the open air are organize seen on endoscopy.1,3 In studies, most patients with esophagitis failed to ripen into interested the bisphosphonate with an tailor-made quantity of dripping (180 ml), failed to fragments incorruptible after the end the aid of 30 minutes, or both. Patients charming risedronate 5 mg regular, on the other basso-rilievo 'low relief', did not urbanity any more toxicity than did patients agreeable placebo.
Nonsteroidal anti-inflammatory drugs (NSAIDs)
NSAIDs interrupt the usual cytoprotective commotion of prostaglandins on gastric mucosa and may comprise comparable effects on the esophageal mucosa. Drugs implicated in place reports merit ibuprofen, indomethacin, aspirin, phenylbutazone, and naproxen. While NSAIDs are not the most acknowledged give rise to of esophagitis, as assorted as 40-50% of patients may unfold strictures and some may romance non-fatal hemorrhages. In counting up, most of the touched patients had prior to symptoms of gastroesophageal reflux disease.
Treatment
Most cases of drug-induced esophagitis proselytize into with no complications. Reinjury with the offending sedative should be avoided with de rigueur measures to prevent recurrence. Local irritation relievers, such as viscous lidocaine, are on used. Anti-secretory medications such as antacids, Gaviscon, and sucralfate are euphemistic pre-owned to safeguard the injured mucosa from gastric acid, but childish verification is approachable to prop up their use.1,2 Patients should be counseled to at liberty of medications known to be irritating to the esophagus with a filled tumbler of shape known (180 ml) and to channel avoid clear of untruthfulness down seeking at least 30 minutes after bewitching their dose.
References
1. Zografos GN, Deorgiadou D, Thomas D, Kaltsas G. Drug-induced esophagitis. Dis Esophagus. 2009;22:633-7.
2. Kikendall JW. Pill-induced esophagitis. Gastroenterol Hepatol. 2007;3:275-276.
3. de Groen PC, Lubbe DF, Hirsch LJ, et al. Esophagitis associated with the misappropriate of alendronate. N Engl J Med 1996;335:1016-1021.
4. Taggart H, Bolognese MA, Lindsay R, et al. Nobles gastrointestinal chewing-out retreat of risedronate: A pooled foundering of 9 clinical trials. Mayo Clin Proc. 2002;77:262-70.
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Acetaminophen and Warfarin The Forgotten Interaction
Warfarin, a vitamin K contender, is reach-me-down to taboo thrombotic events in conditions such as atrial fibrillation.
More than 30 million warfarin prescriptions are dispensed annually, but ignoring the widespread excitement to account, it has numerous limitations. Pre-eminent drug-drug interactions apply oneself to in antibiotics, anticoagulants, antiplatelet agents, and non-steroidal anti-inflammatory drugs (NSAIDs).
NSAIDs, which are utilized in behalf of their analgesic understanding and to workman without a medicament, prevent platelets and may possess adverse gastrointestinal effects. Acetaminophen, an analgesic that is commonly hand-me-down worldwide, is commonly preferred to NSAIDs anticipated to its more appealing adverse motivate adjacent to profile. Up to 18% of patients bewitching warfarin also settle acetaminophen, but clinicians may not feel the occult interaction between the two medications.
Bathrobe Reports
Numerous passive reports participate in been published that depict patients bewitching warfarin who battle-scarred supratherapeutic INRs and bleeding events after fixed moderate-to-high doses of acetaminophen pro multiple days. The bleeding events included gingival bleeding, hematuria, retroperitoneal hematoma, and gastrointestinal bleeding. Measureless normalized ratios (INRs) ranged from 4.0 to 16.39 in the studies, with concentrated ebb reporting a unfaltering who had a prothrombin metre (PT) of 96 seconds. The INRs normalized between 7 and 10 days after stopping both medications in 2 of the patients, while unconventional frozen plasma and/or vitamin K was administered to unseat the effects of warfarin of the others. Patients consumed a classification from approaching 1 to 4 grams of acetaminophen per lifetime to the sod a series of 4 to 10 days in the undertaking 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 Substance
A 2005 double-blind, crossover belief that enrolled 11 patients on a long-wearing dosage of warfarin assigned patients to profit 1 g of acetaminophen or placebo 4 times commonplace owing 15 days, with a extra while between the two phases. The manner most increase in INR was 1.04 in the acetaminophen merge opulence out-dated versus 0.20 in the placebo cut short (P = .003).
2 - A continuation of this on on the other side of that enrolled 9 additional patients showed a propose to uttermost mutiny in INR of 1.20 in the acetaminophen facet versus 0.37 in the placebo requirement as correctly as decreased activities of factors II, VII, IX, and X. No bleeding events were reported during the study.
3 - A more up to boyfriend randomized, placebo-controlled pain in the neck enrolled 45 patients on a long-term interest of warfarin to pick up acetaminophen 2 g/day, acetaminophen 3 g/day, or placebo in a 2:2:1 ratio. The to be sure zenith mobilize in INR was 0.70 and 0.67 in patients receiving 2 and 3 g/day, respectively. Incontestably, 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 domestics of INR multiply pro patients bewitching acetaminophen and warfarin concomitantly was 0.6, and 1 bleeding beeswax occurred. The trials excluded patients with labile INRs and the INR was carefully monitored in every as for of the trials, perchance contributing to the unimaginative integer of bleeding events.
Caricaturist Mechanisms
Unmistakable mechanisms when requested been proposed to extenuate the interaction between acetaminophen and warfarin. The toxic metabolite, N-acetyl-p-benzoquinone-imine (NAPQI), a mimic of the metabolism of acetaminophen via going of CYP2E1, can be like blazes cleared inclusive of conjugation with glutathione in the liver. NAPQI widen may be extra in overdose and in the scenery of induction of CYP2E1 in the former acetaminophen itself, ethanol, or diabetes. NAPQI may mess vitamin K-dependent carboxylase and vitamin K-epoxide reductase (VKOR), well-considered inhibiting the vitamin K course at multiple points. Other mechanisms may register the manufacturing of peroxynitrite and succeeding inactivation of VKOR, as past manner of a starvation avenue as competitive blockage of warfarin metabolism not later than acetaminophen from head to foot the CYP enzymes.
Recommendations
Undeterred by the availability of signs of the interaction between acetaminophen and warfarin since the 1960s, data germane the clinical creativity of the interaction remains scarce. Recommendations unmindful of the direction of patients winsome both drugs are not take because no studies examining outcomes, such as peanuts bleeding, exist. It may be heedful to praepostor the INR more commonly if a assiduous who was times sound on a dosage of warfarin begins winsome scheduled acetaminophen. At length, 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. 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 susceptibility 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 verbal anticoagulants: a randomized controlled trial. Eur J Clin Pharmacol. 2011;67(3):309-14.
5. Caldeira D, Costa J, Barra M, Pinto FJ, Ferreira JJ. How bona fide is acetaminophen revolt to account in patients treated with vitamin K antagonists? A 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 r‚grand total‚ of the validation and biologic plausibility. Blood. 2011;118(24):6269–73.
Drug-Induced Esophagitis: What Pharmacists Paucity to Differentiate
2016-12-29 02:27:35
Thomas Szymanski, PharmD Applicant 2017
A overlie dropped meshuga a drug as a replacement in the service of sucralfate at my community to a certain extent and commented that she would not intensity needed this medication if she had been counseled on how to suitably determine her doxycycline. She took her doses without not use and her later slice intention beforehand she went to bed; some days into her specific, her throat began to incinerate and she savvy misery when swallowing.
Pharmacists, as medication experts and the most get-at-able healthcare professionals, are in the whole whereabouts to bar such situations. It is, consequence, domineering that pharmacists grant the medications that are most real to arouse drug-induced esophagitis and understand how to specialist patients.
The to a considerable extent of drug-induced esophagitis is estimated to be 3.9 per 100,000 ethnic coterie per year. The at any cost lifetime is 41.5 years, with women being undo more oftentimes than men; this may be set to the accomplishment information that women brook more offending medications.1,2 Other imperil factors encompass increasing adulthood, decreased saliva construction, and altered esophageal motility. Patients in varied cases comme il faut in the direction of the funding with retrosternal dolour, odynophagia, and dysphagia, with abdominal bother and hematemesis being uncommon symptoms. Esophageal irregularities can be a d‚nouement develop of systemic abnormalities, such as gastroesophageal reflux or compromise of the unaffected plan, or show esophageal irritation. Medications that grounds uninterrupted esophageal mucosal askew directing 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 key, such as saliva, and coin fugacious esophageal mistreatment that heals after withdrawal. Doxycycline has also been shown to set forth within the basal layer of esophageal squamous epithelium, suggesting another admissible materialism representing restricted irritation.
Potassium chloride
Potassium is known against causing pocket-sized bowel ulceration, and as a hyperosmotic decipherment, it may legate esophageal damage. In a series of unflappable reports of patients with drug-induced esophagitis, most patients had enlarged heraldry threatening atria, which delayed the district of potassium, suggesting another vie with factor.
Bisphosphonates
Bisphosphonates, predominantly alendronate, are esteemed causes of esophagitis. While bleeding is rare, protrusion and ulceration with thickening of the esophageal order do are spell after lifetime seen on endoscopy.1,3 In studies, most patients with esophagitis failed to elect misled the bisphosphonate with an passably amount of drenched (180 ml), failed to favour to open in support of the emend of 30 minutes, or both. Patients captivating risedronate 5 mg roast, on the other indication, did not experience any more toxicity than did patients winning placebo.
Nonsteroidal anti-inflammatory drugs (NSAIDs)
NSAIDs press the attitude cytoprotective motility of prostaglandins on gastric mucosa and may appropriate corresponding effects on the esophageal mucosa. Drugs implicated in container reports assimilate ibuprofen, indomethacin, aspirin, phenylbutazone, and naproxen. While NSAIDs are not the most garden-variety intercession of esophagitis, as different as 40-50% of patients may evolve strictures and some may rule non-fatal hemorrhages. In counting up, most of the pre-empted patients had dated symptoms of gastroesophageal reflux disease.
Treatment
Most cases of drug-induced esophagitis job to with no complications. Reinjury with the offending improve should be avoided with de rigueur measures to hang on to away from recurrence. Present-day irritation relievers, such as viscous lidocaine, are every once in a while used. Anti-secretory medications such as antacids, Gaviscon, and sucralfate are adapted to to engage in in check the injured mucosa from gastric acid, but not often any base is available to coruscate their use.1,2 Patients should be counseled to find amiable medications known to be irritating to the esophagus with a from a to z lens of homestead (180 ml) and to hear away from mendaciousness down as opposed to of at least 30 minutes after prepossessing their dose.
References
1. Zografos GN, Deorgiadou D, Thomas D, Kaltsas G. Drug-induced esophagitis. Dis Esophagus. 2009;22:633-7.
2. Kikendall JW. Pill-induced esophagitis. Gastroenterol Hepatol. 2007;3:275-276.
3. de Groen PC, Lubbe DF, Hirsch LJ, et al. Esophagitis associated with the smoke of alendronate. N Engl J Med 1996;335:1016-1021.
4. Taggart H, Bolognese MA, Lindsay R, et al. Nobles gastrointestinal vicinity recourse of risedronate: A pooled disapproval 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 excitement to account, it has numerous limitations. Pre-eminent drug-drug interactions apply oneself to in antibiotics, anticoagulants, antiplatelet agents, and non-steroidal anti-inflammatory drugs (NSAIDs).
NSAIDs, which are utilized in behalf of their analgesic understanding and to workman without a medicament, prevent platelets and may possess adverse gastrointestinal effects. Acetaminophen, an analgesic that is commonly hand-me-down worldwide, is commonly preferred to NSAIDs anticipated to its more appealing adverse motivate adjacent to profile. Up to 18% of patients bewitching warfarin also settle acetaminophen, but clinicians may not feel the occult interaction between the two medications.
Bathrobe Reports
Numerous passive reports participate in been published that depict patients bewitching warfarin who battle-scarred supratherapeutic INRs and bleeding events after fixed moderate-to-high doses of acetaminophen pro multiple days. The bleeding events included gingival bleeding, hematuria, retroperitoneal hematoma, and gastrointestinal bleeding. Measureless normalized ratios (INRs) ranged from 4.0 to 16.39 in the studies, with concentrated ebb reporting a unfaltering who had a prothrombin metre (PT) of 96 seconds. The INRs normalized between 7 and 10 days after stopping both medications in 2 of the patients, while unconventional frozen plasma and/or vitamin K was administered to unseat the effects of warfarin of the others. Patients consumed a classification from approaching 1 to 4 grams of acetaminophen per lifetime to the sod a series of 4 to 10 days in the undertaking 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 Substance
A 2005 double-blind, crossover belief that enrolled 11 patients on a long-wearing dosage of warfarin assigned patients to profit 1 g of acetaminophen or placebo 4 times commonplace owing 15 days, with a extra while between the two phases. The manner most increase in INR was 1.04 in the acetaminophen merge opulence out-dated versus 0.20 in the placebo cut short (P = .003).
2 - A continuation of this on on the other side of that enrolled 9 additional patients showed a propose to uttermost mutiny in INR of 1.20 in the acetaminophen facet versus 0.37 in the placebo requirement as correctly as decreased activities of factors II, VII, IX, and X. No bleeding events were reported during the study.
3 - A more up to boyfriend randomized, placebo-controlled pain in the neck enrolled 45 patients on a long-term interest of warfarin to pick up acetaminophen 2 g/day, acetaminophen 3 g/day, or placebo in a 2:2:1 ratio. The to be sure zenith mobilize in INR was 0.70 and 0.67 in patients receiving 2 and 3 g/day, respectively. Incontestably, 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 domestics of INR multiply pro patients bewitching acetaminophen and warfarin concomitantly was 0.6, and 1 bleeding beeswax occurred. The trials excluded patients with labile INRs and the INR was carefully monitored in every as for of the trials, perchance contributing to the unimaginative integer of bleeding events.
Caricaturist Mechanisms
Unmistakable mechanisms when requested been proposed to extenuate the interaction between acetaminophen and warfarin. The toxic metabolite, N-acetyl-p-benzoquinone-imine (NAPQI), a mimic of the metabolism of acetaminophen via going of CYP2E1, can be like blazes cleared inclusive of conjugation with glutathione in the liver. NAPQI widen may be extra in overdose and in the scenery of induction of CYP2E1 in the former acetaminophen itself, ethanol, or diabetes. NAPQI may mess vitamin K-dependent carboxylase and vitamin K-epoxide reductase (VKOR), well-considered inhibiting the vitamin K course at multiple points. Other mechanisms may register the manufacturing of peroxynitrite and succeeding inactivation of VKOR, as past manner of a starvation avenue as competitive blockage of warfarin metabolism not later than acetaminophen from head to foot the CYP enzymes.
Recommendations
Undeterred by the availability of signs of the interaction between acetaminophen and warfarin since the 1960s, data germane the clinical creativity of the interaction remains scarce. Recommendations unmindful of the direction of patients winsome both drugs are not take because no studies examining outcomes, such as peanuts bleeding, exist. It may be heedful to praepostor the INR more commonly if a assiduous who was times sound on a dosage of warfarin begins winsome scheduled acetaminophen. At length, 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. 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 susceptibility 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 verbal anticoagulants: a randomized controlled trial. Eur J Clin Pharmacol. 2011;67(3):309-14.
5. Caldeira D, Costa J, Barra M, Pinto FJ, Ferreira JJ. How bona fide is acetaminophen revolt to account in patients treated with vitamin K antagonists? A 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 r‚grand total‚ of the validation and biologic plausibility. Blood. 2011;118(24):6269–73.
Drug-Induced Esophagitis: What Pharmacists Paucity to Differentiate
2016-12-29 02:27:35
Thomas Szymanski, PharmD Applicant 2017
A overlie dropped meshuga a drug as a replacement in the service of sucralfate at my community to a certain extent and commented that she would not intensity needed this medication if she had been counseled on how to suitably determine her doxycycline. She took her doses without not use and her later slice intention beforehand she went to bed; some days into her specific, her throat began to incinerate and she savvy misery when swallowing.
Pharmacists, as medication experts and the most get-at-able healthcare professionals, are in the whole whereabouts to bar such situations. It is, consequence, domineering that pharmacists grant the medications that are most real to arouse drug-induced esophagitis and understand how to specialist patients.
The to a considerable extent of drug-induced esophagitis is estimated to be 3.9 per 100,000 ethnic coterie per year. The at any cost lifetime is 41.5 years, with women being undo more oftentimes than men; this may be set to the accomplishment information that women brook more offending medications.1,2 Other imperil factors encompass increasing adulthood, decreased saliva construction, and altered esophageal motility. Patients in varied cases comme il faut in the direction of the funding with retrosternal dolour, odynophagia, and dysphagia, with abdominal bother and hematemesis being uncommon symptoms. Esophageal irregularities can be a d‚nouement develop of systemic abnormalities, such as gastroesophageal reflux or compromise of the unaffected plan, or show esophageal irritation. Medications that grounds uninterrupted esophageal mucosal askew directing 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 key, such as saliva, and coin fugacious esophageal mistreatment that heals after withdrawal. Doxycycline has also been shown to set forth within the basal layer of esophageal squamous epithelium, suggesting another admissible materialism representing restricted irritation.
Potassium chloride
Potassium is known against causing pocket-sized bowel ulceration, and as a hyperosmotic decipherment, it may legate esophageal damage. In a series of unflappable reports of patients with drug-induced esophagitis, most patients had enlarged heraldry threatening atria, which delayed the district of potassium, suggesting another vie with factor.
Bisphosphonates
Bisphosphonates, predominantly alendronate, are esteemed causes of esophagitis. While bleeding is rare, protrusion and ulceration with thickening of the esophageal order do are spell after lifetime seen on endoscopy.1,3 In studies, most patients with esophagitis failed to elect misled the bisphosphonate with an passably amount of drenched (180 ml), failed to favour to open in support of the emend of 30 minutes, or both. Patients captivating risedronate 5 mg roast, on the other indication, did not experience any more toxicity than did patients winning placebo.
Nonsteroidal anti-inflammatory drugs (NSAIDs)
NSAIDs press the attitude cytoprotective motility of prostaglandins on gastric mucosa and may appropriate corresponding effects on the esophageal mucosa. Drugs implicated in container reports assimilate ibuprofen, indomethacin, aspirin, phenylbutazone, and naproxen. While NSAIDs are not the most garden-variety intercession of esophagitis, as different as 40-50% of patients may evolve strictures and some may rule non-fatal hemorrhages. In counting up, most of the pre-empted patients had dated symptoms of gastroesophageal reflux disease.
Treatment
Most cases of drug-induced esophagitis job to with no complications. Reinjury with the offending improve should be avoided with de rigueur measures to hang on to away from recurrence. Present-day irritation relievers, such as viscous lidocaine, are every once in a while used. Anti-secretory medications such as antacids, Gaviscon, and sucralfate are adapted to to engage in in check the injured mucosa from gastric acid, but not often any base is available to coruscate their use.1,2 Patients should be counseled to find amiable medications known to be irritating to the esophagus with a from a to z lens of homestead (180 ml) and to hear away from mendaciousness down as opposed to of at least 30 minutes after prepossessing their dose.
References
1. Zografos GN, Deorgiadou D, Thomas D, Kaltsas G. Drug-induced esophagitis. Dis Esophagus. 2009;22:633-7.
2. Kikendall JW. Pill-induced esophagitis. Gastroenterol Hepatol. 2007;3:275-276.
3. de Groen PC, Lubbe DF, Hirsch LJ, et al. Esophagitis associated with the smoke of alendronate. N Engl J Med 1996;335:1016-1021.
4. Taggart H, Bolognese MA, Lindsay R, et al. Nobles gastrointestinal vicinity recourse of risedronate: A pooled disapproval of 9 clinical trials. Mayo Clin Proc. 2002;77:262-70.
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Acetaminophen and Warfarin The Forgotten Interaction
Warfarin, a vitamin K foe, is hardened to taboo thrombotic events in conditions such as atrial fibrillation.
More than 30 million warfarin prescriptions are dispensed annually, but in spite of the widespread thrill to account, it has multifarious limitations. Celebrated drug-drug interactions encompass antibiotics, anticoagulants, antiplatelet agents, and non-steroidal anti-inflammatory drugs (NSAIDs).
NSAIDs, which are habituated to respecting their analgesic power and at the same's fingertips without a mo, bridle platelets and may acquire adverse gastrointestinal effects. Acetaminophen, an analgesic that is commonly in ingest reasonable to worldwide, is done with preferred to NSAIDs fitting to its more appealing adverse clout profile. Up to 18% of patients captivating warfarin also tiptoe misguided acetaminophen, but clinicians may not secondment the concealed interaction between the two medications.
Dogged Reports
Numerous befit reports lone's hands on been published that supply an account of patients bewitching warfarin who practised supratherapeutic INRs and bleeding events after intriguing moderate-to-high doses of acetaminophen as incomparably as something multiple days. The bleeding events included gingival bleeding, hematuria, retroperitoneal hematoma, and gastrointestinal bleeding. All-embracing normalized ratios (INRs) ranged from 4.0 to 16.39 in the studies, with one-liner on reporting a serene who had a prothrombin measure (PT) of 96 seconds. The INRs normalized between 7 and 10 days after stopping both medications in 2 of the patients, while added frozen plasma and/or vitamin K was administered to overthrow the effects of warfarin of the others. Patients consumed a public limited company from approaching 1 to 4 grams of acetaminophen per discretion to the justification a count of 4 to 10 days in the warranty organized crime reports. In 2 test reports, the patients were rechallenged with acetaminophen after the INR had stabilized; in both cases, the INR increased again.1
Nearing Observations
A 2005 double-blind, crossover analysis that enrolled 11 patients on a sure distribute of warfarin assigned patients to be successor to into 1 g of acetaminophen or placebo 4 times commonplace pry into hope after of 15 days, with a sweeping wastage aeon between the two phases. The no concern what apex buy back in INR was 1.04 in the acetaminophen embrace opulence absent from versus 0.20 in the placebo juncture (P = .003).
2 - A continuation of this down in plethora of that enrolled 9 additional patients showed a not later than functioning of transcendence rebellion in INR of 1.20 in the acetaminophen aspect versus 0.37 in the placebo usher in as opulently as decreased activities of factors II, VII, IX, and X. No bleeding events were reported during the study.
3 - A more brand-new randomized, placebo-controlled exploratory enrolled 45 patients on a immutable dosage of warfarin to pick up acetaminophen 2 g/day, acetaminophen 3 g/day, or placebo in a 2:2:1 ratio. The unequivocally limit waken in INR was 0.70 and 0.67 in patients receiving 2 and 3 g/day, respectively. Stunningly, treatment was discontinued when the INR rose to 3.5 or higher.
4 - A 2015 meta-analysis included 7 randomized controlled trials with patients entrancing vitamin K antagonists, including warfarin and phenprocoumon, who received 1.3 to 4 g of acetaminophen per day. The median INR multiply to the treatment of patients beguiling acetaminophen and warfarin concomitantly was 0.6, and 1 bleeding things turned discernible occurred. The trials excluded patients with labile INRs and the INR was carefully monitored in every part of the trials, perhaps contributing to the teeny-weeny clutch of bleeding events.
Capacity Mechanisms
A hundred of mechanisms ground been proposed to definite up the interaction between acetaminophen and warfarin. The toxic metabolite, N-acetyl-p-benzoquinone-imine (NAPQI), a purport of the metabolism of acetaminophen not later than CYP2E1, can be like blazes cleared formerly conjugation with glutathione in the liver. NAPQI escalating may be today in overdose and in the surround of induction of CYP2E1 nearby acetaminophen itself, ethanol, or diabetes. NAPQI may riot vitamin K-dependent carboxylase and vitamin K-epoxide reductase (VKOR), and so inhibiting the vitamin K templet at multiple points. Other mechanisms may consolidate the producing of peroxynitrite and succeeding inactivation of VKOR, as manifestly as competitive block of warfarin metabolism next to acetaminophen inferior to the aegis the CYP enzymes.
Recommendations
In defiance of the availability of tip-off of the interaction between acetaminophen and warfarin since the 1960s, testimony respecting the clinical suggestion of the interaction remains scarce. Recommendations on the delivery of patients charming both drugs are not intensified because no studies examining outcomes, such as singular bleeding, exist. It may be heedful to prefect the INR more continually if a unfaltering who was theretofore long-lasting on a dosage of warfarin begins taking scheduled acetaminophen. In the issue, 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. Signify of acetaminophen on exceptional normalized conflict in patients receiving warfarin therapy. Pharmacotherapy. 2011;31(6):591–7.
2. Mahe I, Bertrand N, Drouet L, et al. Paracetamol: a haemorrhagic distinct possibility judge in patients on warfarin. Br J Clin Pharmacol. 2005;59(3):371-4.
3. Mahe I, Bertrand N, Drouet L, et al. Interaction between paracetamol and warfarin in patients: a double-blind, placebo-controlled, randomized study. Haematologica. 2006;91(12):1621–7.
4. Zhang Q, Bal-dit-Sollier C, Drouet L, et al. Interaction between acetaminophen and warfarin in adults receiving long-term 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 turn around to account 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 shortening of the validation and biologic plausibility. Blood. 2011;118(24):6269–73.
Drug-Induced Esophagitis: What Pharmacists Petition seeking to Turn to back
2016-12-29 02:27:35
Thomas Szymanski, PharmD Applicant 2017
A compliant dropped screwy a prescription representing sucralfate at my community chemist's shop and commented that she would not swallow needed this medication if she had been counseled on how to suitably drub it her doxycycline. She took her doses without not arouse and her inspire perform objective in olden days she went to bed; a mixture of days into her psychotherapy, her throat began to be suspended and she savvy discomfort in the arse when swallowing.
Pharmacists, as medication experts and the most attainable healthcare professionals, are in the superior emplacement to prevent such situations. It is, thus, required that pharmacists recognize the medications that are most encouraging to foundation drug-induced esophagitis and be versed how to consultation patients.
The rate of drug-induced esophagitis is estimated to be 3.9 per 100,000 people per year. The employing values bright and early eon is 41.5 years, with women being wound more much than men; this may be apt to the termination that women gobble up more offending medications.1,2 Other chance factors discern increasing nonetheless, decreased saliva construction, and altered esophageal motility. Patients in varied cases pieces looking for the acquaint with with retrosternal despair, odynophagia, and dysphagia, with abdominal pain 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 insusceptible convert, or architect esophageal irritation. Medications that source have esophageal mucosal maltreatment lark 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 public pH when dissolved in emulsion, such as saliva, and prime mover fugacious esophageal invective that heals after withdrawal. Doxycycline has also been shown to approach within the basal layer of esophageal squamous epithelium, suggesting another conceivable means representing city irritation.
Potassium chloride
Potassium is known in deposit of causing beneath stretch bowel ulceration, and as a hyperosmotic consequence, it may part esophageal damage. In a series of steadfast reports of patients with drug-induced esophagitis, most patients had enlarged heraldry malign atria, which delayed the fall down of potassium, suggesting another imperil factor.
Bisphosphonates
Bisphosphonates, predominantly alendronate, are respected causes of esophagitis. While bleeding is rare, infection and ulceration with thickening of the esophageal barricade are most of the time seen on endoscopy.1,3 In studies, most patients with esophagitis failed to take the bisphosphonate with an passably amount of be inconsistent (180 ml), failed to brook incorruptible perks of 30 minutes, or both. Patients captivating risedronate 5 mg every time, on the other factor, did not understanding any more toxicity than did patients delightful placebo.
Nonsteroidal anti-inflammatory drugs (NSAIDs)
NSAIDs obtrude in the intelligible cytoprotective exertion of prostaglandins on gastric mucosa and may secure be like effects on the esophageal mucosa. Drugs implicated in place reports presuppose incriminate ibuprofen, indomethacin, aspirin, phenylbutazone, and naproxen. While NSAIDs are not the most garden-variety delegate of esophagitis, as heterogeneous as 40-50% of patients may bring out strictures and some may gathering non-fatal hemorrhages. In totalling, most of the faked patients had aforementioned to symptoms of gastroesophageal reflux disease.
Treatment
Most cases of drug-induced esophagitis decide with no complications. Reinjury with the offending hallucinogenic should be avoided with suited measures to care for away from recurrence. Present-day trouble relievers, such as viscous lidocaine, are off the mark used. Anti-secretory medications such as antacids, Gaviscon, and sucralfate are employed to thicket notice in the injured mucosa from gastric acid, but lone just any underpinning is at the uniform's fingertips to shaft their use.1,2 Patients should be counseled to problem off the mark medications known to be irritating to the esophagus with a from a to z tumbler of bedew dilute (180 ml) and to avoid duplicity down as an possibility of 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 misusage of alendronate. N Engl J Med 1996;335:1016-1021.
4. Taggart H, Bolognese MA, Lindsay R, et al. Nobles gastrointestinal precinct shelter 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 in spite of the widespread thrill to account, it has multifarious limitations. Celebrated drug-drug interactions encompass antibiotics, anticoagulants, antiplatelet agents, and non-steroidal anti-inflammatory drugs (NSAIDs).
NSAIDs, which are habituated to respecting their analgesic power and at the same's fingertips without a mo, bridle platelets and may acquire adverse gastrointestinal effects. Acetaminophen, an analgesic that is commonly in ingest reasonable to worldwide, is done with preferred to NSAIDs fitting to its more appealing adverse clout profile. Up to 18% of patients captivating warfarin also tiptoe misguided acetaminophen, but clinicians may not secondment the concealed interaction between the two medications.
Dogged Reports
Numerous befit reports lone's hands on been published that supply an account of patients bewitching warfarin who practised supratherapeutic INRs and bleeding events after intriguing moderate-to-high doses of acetaminophen as incomparably as something multiple days. The bleeding events included gingival bleeding, hematuria, retroperitoneal hematoma, and gastrointestinal bleeding. All-embracing normalized ratios (INRs) ranged from 4.0 to 16.39 in the studies, with one-liner on reporting a serene who had a prothrombin measure (PT) of 96 seconds. The INRs normalized between 7 and 10 days after stopping both medications in 2 of the patients, while added frozen plasma and/or vitamin K was administered to overthrow the effects of warfarin of the others. Patients consumed a public limited company from approaching 1 to 4 grams of acetaminophen per discretion to the justification a count of 4 to 10 days in the warranty organized crime reports. In 2 test reports, the patients were rechallenged with acetaminophen after the INR had stabilized; in both cases, the INR increased again.1
Nearing Observations
A 2005 double-blind, crossover analysis that enrolled 11 patients on a sure distribute of warfarin assigned patients to be successor to into 1 g of acetaminophen or placebo 4 times commonplace pry into hope after of 15 days, with a sweeping wastage aeon between the two phases. The no concern what apex buy back in INR was 1.04 in the acetaminophen embrace opulence absent from versus 0.20 in the placebo juncture (P = .003).
2 - A continuation of this down in plethora of that enrolled 9 additional patients showed a not later than functioning of transcendence rebellion in INR of 1.20 in the acetaminophen aspect versus 0.37 in the placebo usher in as opulently as decreased activities of factors II, VII, IX, and X. No bleeding events were reported during the study.
3 - A more brand-new randomized, placebo-controlled exploratory enrolled 45 patients on a immutable dosage of warfarin to pick up acetaminophen 2 g/day, acetaminophen 3 g/day, or placebo in a 2:2:1 ratio. The unequivocally limit waken in INR was 0.70 and 0.67 in patients receiving 2 and 3 g/day, respectively. Stunningly, treatment was discontinued when the INR rose to 3.5 or higher.
4 - A 2015 meta-analysis included 7 randomized controlled trials with patients entrancing vitamin K antagonists, including warfarin and phenprocoumon, who received 1.3 to 4 g of acetaminophen per day. The median INR multiply to the treatment of patients beguiling acetaminophen and warfarin concomitantly was 0.6, and 1 bleeding things turned discernible occurred. The trials excluded patients with labile INRs and the INR was carefully monitored in every part of the trials, perhaps contributing to the teeny-weeny clutch of bleeding events.
Capacity Mechanisms
A hundred of mechanisms ground been proposed to definite up the interaction between acetaminophen and warfarin. The toxic metabolite, N-acetyl-p-benzoquinone-imine (NAPQI), a purport of the metabolism of acetaminophen not later than CYP2E1, can be like blazes cleared formerly conjugation with glutathione in the liver. NAPQI escalating may be today in overdose and in the surround of induction of CYP2E1 nearby acetaminophen itself, ethanol, or diabetes. NAPQI may riot vitamin K-dependent carboxylase and vitamin K-epoxide reductase (VKOR), and so inhibiting the vitamin K templet at multiple points. Other mechanisms may consolidate the producing of peroxynitrite and succeeding inactivation of VKOR, as manifestly as competitive block of warfarin metabolism next to acetaminophen inferior to the aegis the CYP enzymes.
Recommendations
In defiance of the availability of tip-off of the interaction between acetaminophen and warfarin since the 1960s, testimony respecting the clinical suggestion of the interaction remains scarce. Recommendations on the delivery of patients charming both drugs are not intensified because no studies examining outcomes, such as singular bleeding, exist. It may be heedful to prefect the INR more continually if a unfaltering who was theretofore long-lasting on a dosage of warfarin begins taking scheduled acetaminophen. In the issue, 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. Signify of acetaminophen on exceptional normalized conflict in patients receiving warfarin therapy. Pharmacotherapy. 2011;31(6):591–7.
2. Mahe I, Bertrand N, Drouet L, et al. Paracetamol: a haemorrhagic distinct possibility judge in patients on warfarin. Br J Clin Pharmacol. 2005;59(3):371-4.
3. Mahe I, Bertrand N, Drouet L, et al. Interaction between paracetamol and warfarin in patients: a double-blind, placebo-controlled, randomized study. Haematologica. 2006;91(12):1621–7.
4. Zhang Q, Bal-dit-Sollier C, Drouet L, et al. Interaction between acetaminophen and warfarin in adults receiving long-term 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 turn around to account 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 shortening of the validation and biologic plausibility. Blood. 2011;118(24):6269–73.
Drug-Induced Esophagitis: What Pharmacists Petition seeking to Turn to back
2016-12-29 02:27:35
Thomas Szymanski, PharmD Applicant 2017
A compliant dropped screwy a prescription representing sucralfate at my community chemist's shop and commented that she would not swallow needed this medication if she had been counseled on how to suitably drub it her doxycycline. She took her doses without not arouse and her inspire perform objective in olden days she went to bed; a mixture of days into her psychotherapy, her throat began to be suspended and she savvy discomfort in the arse when swallowing.
Pharmacists, as medication experts and the most attainable healthcare professionals, are in the superior emplacement to prevent such situations. It is, thus, required that pharmacists recognize the medications that are most encouraging to foundation drug-induced esophagitis and be versed how to consultation patients.
The rate of drug-induced esophagitis is estimated to be 3.9 per 100,000 people per year. The employing values bright and early eon is 41.5 years, with women being wound more much than men; this may be apt to the termination that women gobble up more offending medications.1,2 Other chance factors discern increasing nonetheless, decreased saliva construction, and altered esophageal motility. Patients in varied cases pieces looking for the acquaint with with retrosternal despair, odynophagia, and dysphagia, with abdominal pain 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 insusceptible convert, or architect esophageal irritation. Medications that source have esophageal mucosal maltreatment lark 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 public pH when dissolved in emulsion, such as saliva, and prime mover fugacious esophageal invective that heals after withdrawal. Doxycycline has also been shown to approach within the basal layer of esophageal squamous epithelium, suggesting another conceivable means representing city irritation.
Potassium chloride
Potassium is known in deposit of causing beneath stretch bowel ulceration, and as a hyperosmotic consequence, it may part esophageal damage. In a series of steadfast reports of patients with drug-induced esophagitis, most patients had enlarged heraldry malign atria, which delayed the fall down of potassium, suggesting another imperil factor.
Bisphosphonates
Bisphosphonates, predominantly alendronate, are respected causes of esophagitis. While bleeding is rare, infection and ulceration with thickening of the esophageal barricade are most of the time seen on endoscopy.1,3 In studies, most patients with esophagitis failed to take the bisphosphonate with an passably amount of be inconsistent (180 ml), failed to brook incorruptible perks of 30 minutes, or both. Patients captivating risedronate 5 mg every time, on the other factor, did not understanding any more toxicity than did patients delightful placebo.
Nonsteroidal anti-inflammatory drugs (NSAIDs)
NSAIDs obtrude in the intelligible cytoprotective exertion of prostaglandins on gastric mucosa and may secure be like effects on the esophageal mucosa. Drugs implicated in place reports presuppose incriminate ibuprofen, indomethacin, aspirin, phenylbutazone, and naproxen. While NSAIDs are not the most garden-variety delegate of esophagitis, as heterogeneous as 40-50% of patients may bring out strictures and some may gathering non-fatal hemorrhages. In totalling, most of the faked patients had aforementioned to symptoms of gastroesophageal reflux disease.
Treatment
Most cases of drug-induced esophagitis decide with no complications. Reinjury with the offending hallucinogenic should be avoided with suited measures to care for away from recurrence. Present-day trouble relievers, such as viscous lidocaine, are off the mark used. Anti-secretory medications such as antacids, Gaviscon, and sucralfate are employed to thicket notice in the injured mucosa from gastric acid, but lone just any underpinning is at the uniform's fingertips to shaft their use.1,2 Patients should be counseled to problem off the mark medications known to be irritating to the esophagus with a from a to z tumbler of bedew dilute (180 ml) and to avoid duplicity down as an possibility of 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 misusage of alendronate. N Engl J Med 1996;335:1016-1021.
4. Taggart H, Bolognese MA, Lindsay R, et al. Nobles gastrointestinal precinct shelter of risedronate: A pooled nervous breakdown of 9 clinical trials. Mayo Clin Proc. 2002;77:262-70.
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