Interactions between factive(gemifloxacin) and Jantoven (warfarin)
warfarin and gemifloxacin (Major Drug-Drug)
MONITOR CLOSELY: Some quinolone antibiotics have been reported to potentiate the hypoprothrombinemic effect of warfarin and other coumarin anticoagulants. The exact mechanism is unknown but may involve inhibition of coumarin metabolism and/or depletion of certain clotting factors due to suppression of vitamin K-producing intestinal flora. 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 levofloxacin compared to a control agent, terazosin. Specifically, a mean INR increase of 0.85 was observed in the levofloxacin group (n=27), compared to a mean decrease of 0.15 in the terazosin group (n=29). Elevations in INR beyond therapeutic levels were seen in 33% of levofloxacin patients versus 5% of the terazosin patients, and INR elevations beyond 4 were seen in 19% of the levofloxacin patients versus 0% of the terazosin patients (the latter not statistically significant). Similarly, a population-based cohort study focusing on antibiotic use in outpatients treated with phenprocoumon or acenocoumarol at a Netherlands anticoagulant clinic identified norfloxacin use as a risk factor for overanticoagulation (INR greater than or equal to 6), even after adjustment for potential confounding factors. There have also been case reports of primarily elderly patients stabilized on warfarin who developed PT or INR increases and/or bleeding complications following the addition of a quinolone. Increased INR values have generally been observed within 2 to 16 days following initiation of quinolone therapy. Ciprofloxacin, enoxacin, gatifloxacin, levofloxacin, moxifloxacin, nalidixic acid, norfloxacin, ofloxacin, and trovafloxacin have been specifically implicated. Between 1987 and 1997, the U.S. Food and Drug Administration received 66 reported cases of suspected interaction involving ciprofloxacin alone. As of January 2004, Health Canada received 57 reports (levofloxacin 16; gatifloxacin 13; moxifloxacin 12; ciprofloxacin 10; norfloxacin 6), including four deaths involving gatifloxacin (2), ciprofloxacin (1), and levofloxacin (1). However, causality could not be established due to multiple confounding factors. In general, data from clinical studies with various quinolones have not supported a significant, predictable pharmacodynamic or pharmacokinetic interaction with warfarin. However, the potential for interaction in susceptible patients cannot be ruled out. Other influences such as fever, infection, malnutrition, and other concomitant underlying conditions on clotting mechanisms and warfarin pharmacokinetics should also be considered.
MANAGEMENT: Given the potential for clinically significant interaction and even fatality in the occasional, susceptible patient, close monitoring is recommended if a quinolone antibiotic is prescribed during coumarin anticoagulant therapy. The INR should be checked frequently and coumarin dosage adjusted accordingly, particularly following initiation or discontinuation of quinolone 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 (e.g., indandiones), although clinical data are lacking.
