OBJECT DRUGS

Anticoagulants, Oral:

• Acenocoumarol
• Warfarin (Coumadin, etc.)

PRECIPITANT DRUGS

Antibiotics:

• Chloramphenicol (Chloromycetin)
• Co-trimoxazole (Septra)
• Metronidazole (Flagyl, etc.)
• Sulfamethizole (Urobiotic)
• Sulfaphenazole

Comment:

Sulfamethoxazole (in co-trimoxazole) and metronidazole are known inhibitors of CYP2C9 and can substantially increase warfarin plasma concentrations and hypoprothrombinemic response. Chloramphenicol, also a CYP2C9 inhibitor, increases the hypoprothrombinemic response of dicumarol and probably also of warfarin. Many other antibiotics have been reported to increase warfarin response in isolated case reports, but these reports can be difficult to evaluate because such patients may have other risk factors for increased warfarin effect such as fever, poor oral intake, and acute illness. (See the Table Effect of Other Antibiotics on Warfarin at the end of the monographs.) Epidemiologic studies suggest that patients on warfarin who receive any antibiotic may be at increased risk for gastrointestinal bleeding.

Class 2: Use Only if Benefit Felt to Outweigh Risk

• Use Alternative: Almost all antibiotics have been associated with increased warfarin response in at least a few patients, but most of them appear less likely to interact with warfarin than the antibiotics listed above.
• Monitor: If one of the antibiotics listed above must be used in a patient on warfarin, monitor anticoagulation carefully; an adjustment in warfarin dosage may be needed. Other antibiotics appear less likely to interact, but one should still monitor for altered effect.