Drug Interaction Report

MONITOR CLOSELY: Coadministration of drotrecogin alfa and other drugs that interfere with coagulation or platelet function may potentiate the risk of bleeding complications. Drotrecogin alfa inactivates blood clotting factors Va and VIIIa and may prolong the activated partial thromboplastin time (APTT). Treatment with drotrecogin alfa alone has been associated with serious and life-threatening bleeding episodes, including gastrointestinal, intracranial and retroperitoneal hemorrhage, although most severely ill septic patients are already at a high risk of bleeding because of coagulopathies associated with prolonged APTT and prothrombin time (PT). In a phase 3 study, the incidence of serious bleeding events during the 28-day study period was 3.5% for drotrecogin alfa versus 2.0% for placebo, with the difference occurring primarily during the infusion period.

MANAGEMENT: The potentially increased risk of bleeding versus the benefits of drotrecogin alfa therapy should be carefully considered in seriously ill septic patients who have recently (within 7 days) received oral anticoagulants, platelet inhibitors, or aspirin (more than 650 mg/day). Close clinical and laboratory monitoring for bleeding complications is recommended if concurrent therapy is required. Drotrecogin alfa should be discontinued immediately if clinically significant bleeding occurs. Continued use of other agents that may have contributed to the bleeding should be carefully assessed. Once adequate hemostasis is attained, drotrecogin alfa may be resumed if necessary.

ADJUST DOSING INTERVAL: The bioavailability and gastrointestinal tolerance of ticlopidine is enhanced by food.

MANAGEMENT: Patients may be advised to take ticlopidine with meals.