Drug interactions between Ketek Pak and Miradon

anisindione ↔ telithromycin

Applies to:Miradon (anisindione) and Ketek Pak (telithromycin)

MONITOR: Coadministration with telithromycin may infrequently enhance the hypoprothrombinemic effect of warfarin. The exact mechanism of interaction is unknown. Although telithromycin is a potent inhibitor of CYP450 3A4 and can inhibit metabolism of the R(+) enantiomer of warfarin, the overall effect on racemic warfarin pharmacokinetics appears to be minor. According to the product labeling, no pharmacodynamic or pharmacokinetic effects on racemic warfarin were observed when telithromycin was coadministered in healthy subjects. Nevertheless, a case report describes a 73-year-old man stabilized on warfarin who developed an increased INR (from 3.1 to 11) and mild hemoptysis five days after starting telithromycin 800 mg/day. The INR returned to the therapeutic range 4 days after telithromycin was discontinued.

MANAGEMENT: Given the potential for clinically significant interaction in the occasional, susceptible patient, close monitoring is recommended if telithromycin is prescribed during warfarin therapy. The INR should be checked frequently and coumarin dosage adjusted accordingly, particularly following initiation or discontinuation of telithromycin therapy 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. The same precaution may be applicable during therapy with other oral anticoagulants, although clinical data are lacking.