terbinafine-hydrochloride and Anisindione Interactions

Interactions between terbinafine-hydrochloride(terbinafine) and Anisindione (anisindione)

anisindione and terbinafine (Moderate Drug-Drug)

MONITOR: The effect of terbinafine on oral anticoagulants, if any, is uncertain. A premarketing study conducted by the manufacturer demonstrated minimal alterations in the pharmacokinetics of a single dose of warfarin administered after 2 weeks of terbinafine compared to placebo. A postmarketing surveillance study of terbinafine in which 26 patients received concomitant treatment with warfarin also revealed no evidence of a drug interaction. However, there have been isolated case reports of INR changes (both increases and decreases) and gastrointestinal bleeding following the addition of terbinafine in patients stabilized on warfarin. A causal relationship has not been established, and the mechanism of the potential interaction is unknown. Terbinafine has not been shown to inhibit or induce CYP450 2C9 and 1A2, the predominant enzymatic pathways responsible for the metabolism of warfarin and similar anticoagulants.

MANAGEMENT: Until further data are available, it may be appropriate to monitor patients more closely during concomitant therapy. The INR should be checked frequently and anticoagulant dosage adjusted accordingly, particularly following initiation or discontinuation of terbinafine in patients who are stabilized on their anticoagulant regimen. 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.