Drug interactions between Azithromycin Dose Pack and Miradon

azithromycin ↔ anisindione

Applies to:Azithromycin Dose Pack (azithromycin) and Miradon (anisindione)

MONITOR: Coadministration with azithromycin may occasionally enhance the hypoprothrombinemic effect of warfarin. The exact mechanism of interaction is unknown. Azithromycin does not inhibit CYP450 enzymes, and several studies have found no evidence of a significant, predictable interaction with warfarin. Nevertheless, a retrospective cohort study of acutely ill warfarin patients at a U.S. Veteran's Affairs Medical Center revealed an increased risk and severity of overanticoagulation following initiation of azithromycin compared to a control agent, terazosin. Specifically, a mean INR increase of 0.51 was observed in the azithromycin group (n=32), compared to a mean decrease of 0.15 in the terazosin group (n=29). Elevations in INR beyond therapeutic levels were seen in 31% of azithromycin patients versus 5% of the terazosin patients, and INR elevations beyond 4 were seen in 16% of the azithromycin patients versus 0% of the terazosin patients (the latter not statistically significant). There have also been case reports of patients stabilized on warfarin who developed PT or INR increases during or immediately following a course of azithromycin. One patient was hospitalized after coughing up blood and blood-streaked mucus two days following the completion of a 5-day course of azithromycin. Two other patients developed an intra-abdominal hematoma in association with elevated INRs shortly after the initiation of azithromycin therapy. The interaction has generally been observed within 8 days after initiation of azithromycin treatment, or 3 days after completion of a 5-day course. However, a causal relationship is difficult to establish in most cases due to confounding factors such as severe infection, fever, liver disease, hypoalbuminemia, anorexia, diarrhea, and other concomitant therapy.

MANAGEMENT: Given the potential for clinically significant interaction in the occasional, susceptible patient, close monitoring is recommended if azithromycin is prescribed during warfarin therapy. The INR should be checked frequently and warfarin dosage adjusted accordingly, particularly following initiation or discontinuation of azithromycin 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.