Coumadin and Zafirlukast

In the database of official manuals used in the service creation an interaction registered by statistical results of studies was found, which can either lead to negative consequences for the patient health or strengthen a mutual positive effect. A doctor should be consulted to address the issue of joint drug administration.

Zafirlukast can increase the levels of warfarin in your body. You may need a dose adjustment and more frequent testing of your prothrombin time or International Normalized Ratio (INR) if you have been taking warfarin and are starting treatment with zafirlukast. Call your doctor promptly if you experience any unusual bleeding or bruising, vomiting, swelling, blood in your urine or stools, headache, dizziness, or weakness while taking these medications. It is important to tell your doctor about all other medications you use, including vitamins and herbs. Do not stop using any medications without first talking to your doctor.

MONITOR: Coadministration with zafirlukast may increase the plasma concentrations and hypoprothrombinemic effect of warfarin. The proposed mechanism is zafirlukast inhibition of CYP450 2C9, the isoenzyme responsible for the metabolic clearance of the more active S(-) enantiomer of warfarin. In a drug interaction study conducted in 16 healthy volunteers, coadministration of multiple doses of zafirlukast (160 mg/day) to steady-state with a single 25 mg dose of warfarin resulted in a 63% increase in the mean systemic exposure (AUC) and a 36% increase in the half-life of S(-) warfarin. These changes were accompanied by an approximately 35% increase in mean prothrombin time. In contrast, warfarin had no significant effect on the pharmacokinetics of zafirlukast. No data are available regarding coadministration of other oral anticoagulants with zafirlukast, although at least one other coumarin derivative is known to be metabolized by CYP450 2C9.

MANAGEMENT: Given the potential for interaction and the high degree of interpatient variability with respect to warfarin metabolism, patients should be closely monitored during concomitant therapy with zafirlukast. The INR should be checked frequently and warfarin dosage adjusted accordingly, particularly following initiation or discontinuation of zafirlukast in patients who are stabilized on their warfarin regimen. The same precaution may be applicable during therapy with other oral anticoagulants, although clinical data are lacking. Patients should be advised to promptly report any signs of bleeding to their physician, including pain, swelling, headache, dizziness, weakness, prolonged bleeding from cuts, increased menstrual flow, vaginal bleeding, nosebleeds, bleeding of gums from brushing, unusual bleeding or bruising, red or brown urine, or red or black stools.

Coumadin

Generic Name: warfarin

Brand name: Coumadin, Jantoven

Synonyms: n.a.

What is Coumadin?

Zafirlukast

Generic Name: zafirlukast

Brand name: Accolate

Synonyms: n.a.

What is Zafirlukast?