We describe a patient receiving warfarin in whom prothrombin time, which was associated with gross hematuria, was significantly prolonged when ofloxacin was administered.

A 73-year-old woman had a history of recurring urinary tract infections that were caused by a partial congenital duplication of the right collecting system; recurring deep vein thrombosis and pulmonary emboli; hypertension; and endometrial cancer. Drug therapy included verapamil (sustained-release), enalapril, hydrochlorothiazide-triamterene, amitriptyline, and warfarin (5 mg 6 days a week). The prothrombin time had ranged between 15 to 21 seconds (control, 12.1 seconds) over the past 3 years. On 14 July 1993, Escherichia coli pyelonephritis developed and the patient was given ofloxacin (400 mg orally every 12 hours pending urine culture sensitivities). Five days later, she was admitted to the hospital with malaise and gross hematuria. The patient was afebrile and liver function test results were within normal limits. The prothrombin time was 77.7 seconds (control, 10.6 seconds to 12.6 seconds) and the hematocrit was 28%. Four weeks before her prothrombin time was 20.7 seconds and her hematocrit was 38.1%. Both warfarin and ofloxacin therapies were discontinued. Treatment consisted of vitamin K and fresh frozen plasma. Her prothrombin time was 14.1 seconds. The patient was also given packed red blood cells.

Leor and Matetzki [1] reported a similar case of an ofloxacin-warfarin interaction. They postulated suppression of vitamin K-producing gut bacteria by ofloxacin with potentiation of warfarin's effect. Ofloxacin has a low level of liver metabolism and is 20% to 32% protein-bound. Interactions between warfarin and other quinolones such as nalidixic acid [2], ciprofloxacin [3, 4], and norfloxacin [5] have also been described. The suggested mechanisms for these interactions include displacement of warfarin from albumin-binding sites or inhibition of the hepatic metabolism of warfarin.

We advise practitioners to monitor prothrombin times and observe patients for clinical signs and symptoms of bleeding when a fluoroquinolone (especially high-dose or prolonged therapy) must be given to a patient receiving warfarin. The interaction usually manifests within several days to a week. Adjustment of the warfarin dose may be necessary when fluoroquinolone therapy is started or discontinued. If feasible, an alternative antibiotic should be considered to avoid this possible interaction.