Drug Interaction Report

MONITOR CLOSELY: Coadministration of drotrecogin alfa with other drugs that can 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 are currently receiving, or have recently received, agents that could affect hemostasis such as anticoagulants, antiplatelet agents, nonsteroidal anti-inflammatory drugs (NSAIDs), thrombolytics, thrombin inhibitors, or agents that commonly cause thrombocytopenia. 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.

GENERALLY AVOID: The concurrent use of aspirin or nonsteroidal anti-inflammatory drugs (NSAIDs) and ethanol may lead to gastrointestinal (GI) blood loss. The mechanism may be due to a combined local effect as well as inhibition of prostaglandins leading to decreased integrity of the GI lining.

MANAGEMENT: Patients should be counseled on this potential interaction and advised to refrain from alcohol consumption while taking aspirin or NSAIDs.

GENERALLY AVOID: Use of anticholinergic agents with alcohol may result in sufficient impairment of attention so as to render driving and operating machinery more hazardous. In addition, the potential for abuse may be increased with the combination. The mechanism of interaction is not established but may involve additive depressant effects on the central nervous system. No effect of oral propantheline or atropine on blood alcohol levels was observed in healthy volunteers when administered before ingestion of a standard ethanol load. However, one study found impairment of attention in subjects given atropine 0.5 mg or glycopyrrolate 1 mg in combination with alcohol.

MANAGEMENT: Alcohol should generally be avoided during therapy with anticholinergic agents. Patients should be counseled to avoid activities requiring mental alertness until they know how these agents affect them.