Drotrecogin alfa (activated)

Intravenous
Severe sepsis

Reconstitute 5 mg vials with 2.5 mL and 20 mg vials with 10 mL sterile water for inj (resultant solution ~2 mg/mL). Further dilute (within 3 hr of reconstitution) in 0.9% sodium chloride, typically to a concentration of 100-200 mcg/mL when using infusion pump or 100-1000 mcg/mL when infused via syringe pump.

Y-site incompatibility: Adrenaline hydrochloride, albumin, amiodarone hydrochloride, ampicillin with sulbactam, ceftazidime, ciclosporin, ciprofloxacin, clindamycin, dobutamine hydrochloride, dopamine hydrochloride, fosphenytoin, furosemide, gentamicin sulfate, heparin sodium, imipenem with cilastatin, insulin, levofloxacin, magnesium sulfate, metronidazole, midazolam hydrochloride, nitroprusside sodium, noradrenaline acid tartrate, piperacillin with tazobactam, potassium phosphate, ranitidine hydrochloride, ticarcillin with clavulanic acid, tobramycin sulfate and vancomycin hydrochloride.

Active internal bleeding. Patients with intracranial neoplasm, mass lesion or cerebral herniation. Patients at increased risk of bleeding including major surgery. Recent (within 2 mth) severe head trauma, intracranial or intraspinal surgery; haemorrhagic stroke within 3 mth, history of intracerebral aneurysm or CNS mass lesion, presence of epidural catheter, congenital bleeding diathesis, GI bleeding, trauma with increased risk of life-threatening bleeding. Hypersensitivity.

Recent (within 3 days) treatment with thrombolytics or within 7 days of oral anticoagulants or glycoprotein IIb/IIIa inhibitors. Recent (within 7 days) treatment with aspirin >650 mg/day or other platelet inhibitors. Recent (within 3 mth) ischaemic stroke. Concurrent heparin therapy to treat an active thrombotic or embolic event. Platelet count <30,000 x 10⁶/L, even if platelet count is increased after transfusions. Intracranial arteriovenous malformation or aneurysm. Known bleeding diathesis, chronic severe hepatic disease. Any other condition in which bleeding may pose a significant hazard or would be difficult to manage because of its location. Stop infusion immediately if any clinically important bleeding occurs; may consider continued use if adequate haemostasis is achieved. Pregnancy and lactation. Safety and efficacy in children have not been established.

Brusing, GI bleeding. Skin/soft tissue bleeding, immune reaction, retroperitoneal bleeding, genitourinary bleeding, intracranial bleeding, intrathoracic haemorrhage.

May increase the anticoagulant effect of other anticoagulants. Concurrent use with ibritumomab or prostacyclin analogues may increase risk of bleeding. NSAIDs and pentosan polysulfate sodium may increase the anticoagulant effect of anticoagulants. Salicylates may increase the adverse effect of drotrecogin alfa. May increase the adverse effect of tositumomab and iodine I 131 tositumomab.
Potentially Fatal: Concurrent use with antiplatelet agents, antithrombin III, danaparoid, fondaparinux, heparin, low molecular weight heparin, thrombolytic agents or vitamin K antagonists (e.g. warfarin) may increase the adverse effect of drotrecogin alfa.

Concurrent use with herbs with anticoagulant or antiplatelet activity (e.g. cat's claw ginseng, feverfew, garlic or horse chestnut seed) may increase bleeding risk.

May interfere with assay for activated partial thromboplastin time (aPTT), thus cannot be reliably used to assess the status of coagulopathy in these patients.

Description: Drotrecogin alfa (activated) is a recombinant form of human activated protein C which has antithrombotic, anti-inflammatory and profibrinolytic properties.
Duration: Nondetectable in plasma within 2 hr after stopping infusion.
Pharmacokinetics:
Absorption: Steady-state plasma concentrations are reached in about 2 hr during continuous infusion.
Metabolism: Inactivated by endogenous plasma protease inhibitors.
Excretion: Half-life elimination: 1.6 hr.

Lyophilized powder: Store at 2-8°C. Protect from light. Reconstituted solution: Store at 20-25°C but must be used within 3 hr once reconstituted. After final dilution and preparation, the IV solution should be used at controlled room temperature 20-25°C within 12 hr; if it is not used immediately, it may be stored at 2-8°C for up to 12 hr. The max time limit for the use of the IV solution (including dilution, refrigeration and administration) is ≤24 hr.

Anticoagulants, Antiplatelets & Fibrinolytics (Thrombolytics)