indication

For reduction of mortality in patients with severe sepsis.

pharmacology

Drotrecogin alfa is activated human protein C that is synthesized by recombinant DNA technology. It is a glycoprotein of approximately 55 kilodalton molecular weight, consisting of a heavy chain and a light chain linked by a disulfide bond. Drotrecogin alfa inhibits factor Va and VIIIa, thereby reducing the coagulability of blood.

mechanism of action

Activated protein C combines with protein S on platelet surfaces and then degrades factor Va and factor VIIIa, thereby reducing blood coagulability.

half life

5.5 hours (mammalian reticulocytes, in vitro).

drug interactions

Clopidogrel: Antiplatelet agents such as clopidogrel may enhance the adverse/toxic effect of Drotrecogin Alfa. Bleeding may occur. Increase monitoring for signs/symptoms of bleeding during concomitant therapy. If possible, avoid use of drotrecogin within 7 days of use of any IIb/IIIa antagonists, higher dose aspirin (more than 650 mg/day), or use of other antiplatelet agents.

Dalteparin: Low molecular weight heparin (LMWH) such as dalteparin may enhance the adverse/toxic effect of drotrecogin alfa. Bleeding may occur.

Enoxaparin: Combination should be used with caution after weighing advantages and disadvantages. Low molecular weight heparins such as enoxaparin may increase the adverse effects of drotrecogin. Monitor for bleeding if used concomitantly.

Fondaparinux sodium: Drotrecogin alfa may increase the adverse effects of fondaparinux, resulting in excessive bleeding. Concomitant use should be avoided.

Heparin: The potential benefits of drotrecogin alfa should be weighed against an increased risk of bleeding in patients receiving therapeutic doses of heparin. Monitor for bleeding during concomitant therapy, and immediately stop infusion of drotrecogin if clinically important bleeding occurs. In patients receiving prophylactic heparin doses, consider continuing this during drotrecogin.

Ketoprofen: The antiplatelet effect of ketoprofen may increase the bleed risk associated with drotrecogin alfa. Consider spacing use of the two agents by at least 7 days. Increase monitoring for signs and symptoms of bleeding during concomitant therapy.

Nadroparin: The potential benefits of drotrecogin alfa should be weighed against an increased risk of bleeding in patients receiving therapeutic doses of low molecular weight heparins such as nadroparin. Monitor for bleeding during concomitant therapy, and immediately stop infusion of drotrecogin if clinically important bleeding occurs. In patients receiving prophylactic heparin doses, consider continuing this during drotrecogin.

Tenecteplase: Increased risk of bleeding.

Tinzaparin: Low molecular weight heparins (LMWHs) such as tinzaparin may enhance the adverse/toxic effects of drotrecogin alfa. Bleeding may occur. The potential benefits of drotrecogin alfa should be weighed against the increased risk of bleeding in patients on therapeutic doses of LMWHs.

Tolmetin: Increased risk of bleeding. Monitor for increased bleeding during concomitant therapy.

Treprostinil: The prostacyclin analogue, Treprostinil, increases the risk of bleeding when combined with the anticoagulant, Drotrecogin alfa. Monitor for increased bleeding during concomitant thearpy.

Urokinase: Increased risk of bleeding.

Vilazodone: Increase monitoring for signs/symptoms of bleeding during concomitant therapy. If possible, avoid use of drotrecogin within 7 days of use of any IIb/IIIa antagonists, higher dose aspirin (more than 650 mg/day), or use of other antiplatelet agents.

Warfarin: Increased risk of bleeding.