Xigris (Drotrecogin Alfa (Activated)) - Drug Interactions, Contraindications, Overdosage

DRUG INTERACTIONS

Drug interaction studies with Xigris have not been performed in patients with severe sepsis. However, since there is an increased risk of bleeding with Xigris, caution should be employed when Xigris is used with other drugs that affect hemostasis (see CLINICAL PHARMACOLOGY, WARNINGS). Approximately 2/3 of the patients in the Phase 3 study received either prophylactic low dose heparin (unfractionated heparin up to 15,000 units/day) or prophylactic doses of low molecular weight heparins as indicated in the prescribing information for the specific products. Concomitant use of prophylactic low dose heparin did not appear to affect safety, however, its effects on the efficacy of Xigris have not been evaluated in an adequate and well-controlled clinical trial.

OVERDOSAGE

There is no known antidote for Xigris. In case of overdose, immediately stop the infusion and monitor closely for hemorrhagic complications (see Human Pharmacokinetics).

Post-marketing experience: There have been some reports of accidental overdosing. In the majority of these cases (which included patients receiving up to 60 times the recommended dose administration rate), no reactions have been observed. For the other reports, the observed events were consistent with known effects of the drug and/or sequelae of the underlying condition of sepsis.

CONTRAINDICATIONS

Xigris increases the risk of bleeding. Xigris is contraindicated in patients with the following clinical situations in which bleeding could be associated with a high risk of death or significant morbidity:

• Active internal bleeding
• Recent (within 3 months) hemorrhagic stroke
• Recent (within 2 months) intracranial or intraspinal surgery, or severe head trauma
• Trauma with an increased risk of life-threatening bleeding
• Presence of an epidural catheter
• Intracranial neoplasm or mass lesion or evidence of cerebral herniation

Xigris is contraindicated in patients with known hypersensitivity to drotrecogin alfa (activated) or any component of this product.