DROTRECOGIN ALFA (ACTIVATED)
(dro-tree'co-gin)
Xigris
Classifications: immunomodulator; recombinant human activated protein c
Pregnancy Category: C

Availability

5 mg, 20 mg vials

Actions

Drotrecogin alfa is a recombinant form of Human Activated Protein C. Protein C deficiencies are found in most septic patients and result in a higher mortality rate. Activated Protein C exerts antithrombotic and anticoagulant effects by inhibiting clotting Factor Va and VIIIa. Activated Protein C may exert an antiinflammatory effect by inhibiting human tumor necrosis factor (TNF) produced by monocytes, and by limiting the thrombin-induced inflammatory responses of the endothelial lining of the vasculature.

Therapeutic Effects

Drotrecogin alfa possesses anticoagulant, profibrinolytic and antiinflammatory properties.

Uses

Reduction in mortality in patients with severe sepsis and evidence of organ dysfunction.

Contraindications

Prior hypersensitivity to drotrecogin alfa; chronic severe hepatic disease; active internal bleeding or trauma; recent hemorrhagic stroke (within 3 months); invasive surgery or invasive procedures; recent intracranial or intraspinal surgery, or severe head trauma (within 2 mo); intracranial neoplasm, lesion, aneurysm, or herniation; presence of an epidural catheter; pregnancy (category C), lactation.

Cautious Use

Immunosuppression; increased risk of bleeding, hypercoagulability; concurrent use of anticoagulants, or aspirin; children <18; recent ischemic stroke, or intracranial aneurysm.

Route & Dosage

Sepsis
Adult: IV 24 mcg/kg/h continuous infusion for 96 h

Administration

Intravenous

PREPARE: Continuous: Prepare immediately prior to use. Reconstitute 5 mg or 20 mg vials with 2.5 mL or 10 mL, respectively, of sterile water for injection to yield approximate concentration of 2 mg/mL. Slowly add sterile water to vial, avoid inverting or shaking vial, gently swirl until powder is completely dissolved. Slowly withdraw calculated dose from vial, add to infusion bag of NS by directing stream to side of bag to minimize agitation, then gently invert to mix. Final concentration should be 100–200 mcg/mL. Do not transport infusion bag between locations attached to mechanical pump. Note: When using a syringe pump, solution is typically diluted to a final concentration of 100–1000 mcg/mL.

ADMINISTER: Continuous: Give over 96 h. Dose adjustment based on clinical or laboratory parameters is not recommended. IV must be completed within 12 h after solution is prepared.

INCOMPATIBILITIES Solution/additive: Do not mix with any other drugs. Y-site: Do not infuse with any other drugs.

Storage: Reconstituted vial may be held at 15°–30° C (59°–86° F), but must be used within 3 h of preparation.

Adverse Effects (1%)

Hematologic: Bleeding (including intracranial).

Diagnostic Test Interference

May affect the APTT assay. This interference may result in an apparent factor concentration that is lower than the true concentration.

Interactions

Drug: anticoagulants, nsaids, antiplatelet agents may increase risk of bleeding.

Pharmacokinetics

Absorption: Steady state reached in 2 h. Duration: Serum levels undetectable 2 h after end of infusion. Half-Life: 1.6 h.

Nursing Implications

Assessment & Drug Effects

Monitor closely for S&S of hemorrhage. Stop infusion immediately should clinically important bleeding occur. There is no antidote for drotrecogin alfa.
Discontinue drotrecogin alfa 2 h prior to invasive procedures with an inherent risk of bleeding. Reinitiation may be reconsidered 12 h after major invasive procedure or immediately after uncomplicated less invasive procedures.
Lab tests: Monitor closely PT; APTT is not a reliable indication of coagulation.

Common adverse effects in italic, life-threatening effects underlined; generic names in bold; classifications in SMALL CAPS; Canadian drug name; Prototype drug