Warfarin, drug interactions

TABLE 7-8. Clinically Significant Warfarin Drug Interactions... 

Rettie AE, Korzekwa KR, Kunze KL, et al. Hydroxylation of warfarin by human cDNA-expressed cytochrome P-450 a role for P-4502C9 in the etiology of (S)-warfarin-drug interactions. Chem Res Toxicol 1992 5(1 ) 54—59. 

Rindone JP, Keng HC. Gemfibrozil-warfarin drug interaction resulting in profound hypoprothrombinemia. Chest 1998 114(2) 641-2. 

Chan E, McLachlan AJ, O Reilly R, et al. Stereochemical aspects of warfarin drug interactions use of a combined pharmacokinetic-pharmacodynamic model. Clin Pharmacol Ther 1994 56 286-294. 

Morkunas A, Graeme K. Zafirlukast warfarin drug interaction with gastrointestinal bleeding. J Toxicol 1997 35 501. 

In healthy subjects given warfarin until at steady state, felodipine 10 mg daily for 14 days did not alter the dose of warfarin required to maintain a stable INR, or the pharmacokinetics of 5- or R-warfarin. Because felodipine does not interact with warfarin it has been used as a control drug in retrospective cohort studies assessing warfarin drug interactions. ... 

Maya JF, Callaghan JT, Bergstrom RF, Cerimele BJ, Kassahun K, Nyhart EH, Brater DC. Olanzapine and warfarin drug interaction. ClmPhcumacol Ther 99T)6 182. 

Barry M. Rosuvastatin-warfarin drug interaction. Lancet (2004) 363, 328. 

Colucci VJ, Rivey MP. Tolterodine-warfarin drug interaction.. dn/jP/ianmacoi/ier (1999) 33, 1173-6. 

Chan TY. Life-threatening retroperitoneal bleeding due to warfarin-drug interactions. Pharmacoepidemiol Drug Saf 2009 f8(5) 420-2. 

Identify and analyze warfarin drug-drug and drug-food interactions. 

Inform the patient about the potential drug-drug interactions with warfarin, including over-the-counter medications and dietary supplements (Tables 7-8, 7-9, and 7-10). Instruct the patient to call the health care practitioner responsible for monitoring warfarin therapy before starting any new medications or dietary supplements. 

Use of zileuton is uncommon due to the need for dosing four times a day, potential drug interactions, and the potential for hepatotoxicity with the resulting need for frequent monitoring of liver enzymes. In patients started on zileuton, serum alanine aminotransferase concentrations should be monitored before treatment begins, monthly for the first 3 months, every 2 to 3 months for the remainder of the first year, and then periodically thereafter for as long as the patient continues to receive the medication. Zileuton also inhibits the cytochrome P-450 (CYP) mixed function enzyme system and has been shown to decrease the clearance of theophylline, R-warfarin and propranolol.34... 

While generally not of major concern, omeprazole may inhibit the metabolism of warfarin, diazepam, and phenytoin lansoprazole may decrease theophylline concentrations. Drug interactions with omeprazole are of particular concern in patients who are considered slow metabolizers, as are approximately 3% of the Caucasian population. Unfortunately, it is unclear which patients have the polymorphic gene variation that makes them slow metabolizers.17 The metabolism of esomeprazole may also be altered in patients with this polymorphic gene variation. Patients on potentially interacting drugs should be monitored for development of drug-related problems. 

Only a small number of drug interactions have been reported with donepezil. In vitro studies show a low rate of binding of donepezil to cytochrome P-450 (CYP)3A4 or 2D6. Whether or not donepezil has the potential for enzyme induction is not known. No interactions with theophylline, cimeti-dine, warfarin, digoxin, or ketoconazole have been documented. In vitro studies show that inhibitors of CYP3A4 and 2D6 have the potential to inhibit the metabolism of donepezil. The clinical relevance of this is unknown. However, monitoring for possible increased peripheral side effects is advised... 

Vigilance for drug-drug interactions is required because of the greater number of medications prescribed to elderly patients and enhanced sensitivity to adverse effects. Pharmacokinetic interactions include metabolic enzyme induction or inhibition and protein binding displacement interactions (e.g., divalproex and warfarin). Pharmacodynamic interactions include additive sedation and cognitive toxicity, which increases risk of falls and other impairments. 

COX-2 inhibitors are susceptible to the same drug interactions as nonselective agents. However, the interaction with warfarin is less pronounced because platelet function is affected to a lesser degree. 

There are several important drug-drug interactions with allopurinol. The effects of both theophylline and warfarin may be potentiated by allopurinol. Azathioprine and 6-mercaptopurine are purines whose metabolism is inhibited... 

---