Drug interactions between Miradon and piperacillin

piperacillin ↔ anisindione

Applies to:piperacillin and Miradon (anisindione)

MONITOR: Penicillins may occasionally potentiate the risk of bleeding in patients treated with oral anticoagulants. The exact mechanism of interaction is unknown but may involve penicillin inhibition of platelet aggregation. In one study, defective platelet aggregation occurred with predictability in patients receiving penicillin G 24 million units/day, ampicillin 300 mg/kg/day, and methicillin 300 mg/kg/day. Other penicillins such as nafcillin, piperacillin, and ticarcillin have also been found to affect platelet function, and benzylpenicillin and carbenicillin have been reported to increase bleeding times and cause bleeding in the absence of an anticoagulant. There have been case reports describing increases in prothrombin time and INR as well as spontaneous bruising and bleeding in anticoagulated patients following initiation or completion of penicillin therapy. Although most cases have involved large, intravenous doses of some penicillins (e.g., carbenicillin, penicillin G, ticarcillin), the interaction has also been reported with regular, oral doses of amoxicillin and amoxicillin-clavulanate. In fact, a case-control study found amoxicillin-clavulanate to be one of only two medications to significantly increase the risk of overanticoagulation in previously stable outpatients treated with phenprocoumon or acenocoumarol. In that study, 300 outpatients at a Netherlands anticoagulant clinic who presented with an INR value greater than or equal to 6.0 (median value 6.8) were compared with 302 randomly selected matched controls with INR values within the target range (median value 3.2), and changes in the use of 87 potentially interacting drugs or drug classes in the four weeks prior to the index day were identified and analyzed. A course of amoxicillin-clavulanate increased the risk of overanticoagulation even after adjustment for potential confounding factors, particularly in patients treated with acenocoumarol. A follow-up study focusing on antibiotic use in outpatients treated with phenprocoumon or acenocoumarol at a different Netherlands anticoagulant clinic also identified amoxicillin use as a risk factor for overanticoagulation, with the relative risk most strongly increased four days or more after start of the antibiotic.

MANAGEMENT: Caution is recommended if a penicillin is prescribed during oral anticoagulant therapy, especially in the elderly and patients with uremia or hepatic impairment. The INR should be checked frequently and anticoagulant dosage adjusted accordingly, particularly following initiation or discontinuation of penicillin therapy in patients who are stabilized on their anticoagulant regimen. Patients should be advised to promptly report any signs of bleeding to their doctor, 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.