Phenylbutazone and its analogs enhance the hypoprothrombinemic effect of warfarin through a pharmacokinetic interaction by inhibiting the hepatic metabolism of warfarin. Ellingrod VL.
McLachlan AJ, Xarelto (rivaroxaban) [prescribing information]. Stephens JC, Various scoring systems to stratify the risk of bleeding in patients on warfarin have been proposed.In one study, patients classified as high risk had a 48% risk for major bleeding during 12 months of warfarin therapy. Babu K, Coadministration of nonsteroidal anti-inflammatory drugs (NSAIDs) and warfarin increases the risk of bleeding.
Kantola T, A wide range of drugs, including over-the-counter and herbal products, interact with warfarin.Antimicrobials can inhibit CYP450 isozymes, alter protein binding, and diminish absorption of vitamin K by altering the gut flora.Antimicrobial agents with a lower likelihood of affecting the INR include penicillin G benzathine, clindamycin, and first- and fourth-generation cephalosporins.Empiric warfarin dosage adjustments should be considered with concomitant use of trimethoprim/sulfamethoxazole, rifampin, fluconazole, and/or metronidazole.The interaction between warfarin and amiodarone is mediated by inhibition of CYP2C9, 1A2, and 3A4 enzymes, leading to increased warfarin concentrations and increased bleeding risk.Fluvastatin (Lescol), lovastatin (Mevacor), rosuvastatin (Crestor), and simvastatin (Zocor) inhibit warfarin metabolism by the inhibition of CYP2C9, leading to increased warfarin concentrations and increased bleeding risk.Nonsteroidal anti-inflammatory drugs (NSAIDs) increase gastric irritation and erosion of the protective lining of the stomach, potentially leading to the formation of gastrointestinal ulcers, which could result in gastrointestinal bleeding.
Strategies for reducing the risk of drug-drug interactions include minimizing the number of drugs prescribed, re-evaluating therapy on a regular basis, considering nonpharmacologic options, monitoring for signs and symptoms of toxicity and/or effectiveness, adjusting dosages of medications when indicated, and adjusting administration times.Communication between primary care physicians and subspecialist physicians is critical to mutually understand the goals of drug therapy and to avoid or modify drug combinations that may put patients at risk. Kamali F.
Kushner FG, New York, NY: Pfizer Inc. Understanding and preventing drug-drug and drug-gene interactions. Bäcklund T, There are no safety data from clinical trials as patients on warfarin have been excluded from studies of glycoprotein IIb/IIIa receptor antagonists. In patients receiving warfarin who also require NSAIDs, phenylbutazone and its analogs, high-dose aspirin, mefenamic acid, excessive use of topical methyl salicylate, and NSAIDs that are associated with a higher risk of bleeding peptic ulcers should be avoided.
Alexander GC, Updated August 2018. 1990 Jul;19(1):44-66. doi: 10.2165/00003088-199019010-00004.J Manag Care Pharm.
Comparative pharmacokinetic interaction profiles of pravastatin, simvastatin, and atorvastatin when coadministered with cytochrome P450 inhibitors. Braunwald E, Manzoor BS, The antithrombotic effect, and mechanism of haemorrhage, relates to low levels of these coagulation factors and a reduction in their activity in thrombus formation. Life-threatening hyperkalemia during combined therapy with angiotensin-converting enzyme inhibitors and spironolactone: an analysis of 25 cases. Copyright © 2019 by the American Academy of Family Physicians.Copyright © 2020 American Academy of Family Physicians. Preemptive dose reduction of warfarin in patients initiating metronidazole. Most analgesics can increase the bleeding risk when given with warfarin but by different mechanisms. The mechanism of the interaction between amiodarone and warfarin in humans. La phénylbutazone et les substances analogues augmentent l'action de la warfarine par l'inhibition du métabolisme hépatique de celle-ci.
A change in a patients health or medications should prompt their doctor to monitor the INR more frequently.
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