(dro TRE coe jin AL fa ak ti VAY ted)
Reduction of mortality from severe sepsis (associated with organ dysfunction) in adults at high risk of death (eg, APACHE II score ≥25)
Note: As of October, 2011, drotrecogin alfa has been withdrawn from the market (worldwide).
Hypersensitivity to drotrecogin alfa or any component of the formulation; active internal bleeding; recent hemorrhagic stroke (within 3 months); severe head trauma (within 2 months); recent intracranial or intraspinal surgery (within 2 months); intracranial neoplasm or mass lesion; evidence of cerebral herniation; presence of an epidural catheter; trauma with an increased risk of life-threatening bleeding
Note: As of October, 2011, drotrecogin alfa has been withdrawn from the market (worldwide).
Purpura fulminans (off-label use): IV: 24 mcg/kg/hour
Severe sepsis: IV: 24 mcg/kg/hour for a total of 96 hours; stop infusion immediately if clinically-important bleeding is identified. Note: Use actual body weight for dosing.
Refer to adult dosing.
Purpura fulminans (off-label use): Refer to adult dosing.
No specific adjustment recommended.
Reconstitute 5 mg vials with 2.5 mL and 20 mg vials with 10 mL sterile water for injection (resultant solution ~2 mg/mL). Must be further diluted (within 3 hours of reconstitution) in 0.9% sodium chloride, typically to a concentration between 100 mcg/mL and 200 mcg/mL when using infusion pump and between 100 mcg/mL and 1000 mcg/mL when infused via syringe pump. Although product information states administration must be completed within 12 hours of preparation, additional studies (data on file, Lilly Research Laboratories) show that the final solution is stable for 14 hours at 15 ‚ °C to 30 ‚ °C (59 ‚ °F to 86 ‚ °F). If not used immediately, a prepared solution may be stored in the refrigerator for up to 12 hours. The total expiration time (refrigeration and administration) should be ≤24 hours from time of preparation.
Infuse separately from all other medications. Only dextrose, normal saline, dextrose/saline combinations, and lactated Ringers solution may be infused through the same line. May administer via infusion pump. Administration of prepared solution must be completed within 12 hours of preparation. Suspend administration for 2 hours prior to invasive procedures or other procedure with significant bleeding risk; may continue treatment immediately following uncomplicated, minimally-invasive procedures, but delay for 12 hours after major invasive procedures/surgery.
Store vials under refrigeration at 2 ‚ °C to 8 ‚ °C (36 ‚ °F to 46 ‚ °F); do not freeze. Protect from light.
Excipient information presented when available (limited, particularly for generics); consult specific product labeling. [DSC] = Discontinued product
Injection, powder for reconstitution [preservative free]:
Xigris ‚ ®: 5 mg [DSC] [contains sucrose 31.8 mg]
Xigris ‚ ®: 20 mg [DSC] [contains sucrose 124.9 mg]
Stable in NS; only NS, dextrose, LR, or dextrose/saline mixtures may be infused through the same line.
Y-site administration: Incompatible with amiodarone, ciprofloxacin, cyclosporine, gentamicin, imipenem/cilastatin sodium, insulin (regular), levofloxacin, magnesium sulfate, metronidazole, midazolam, nitroprusside, norepinephrine, piperacillin/tazobactam, ticarcillin/clavulanate, tobramycin, vancomycin.
Agents with Antiplatelet Properties (e.g., P2Y12 inhibitors, NSAIDs, SSRIs, etc.): May enhance the adverse/toxic effect of Drotrecogin Alfa (Activated). Bleeding may occur. Management: When 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. Consider therapy modification
Anticoagulants: May enhance the anticoagulant effect of other Anticoagulants. Monitor therapy
Antithrombin: May enhance the adverse/toxic effect of Drotrecogin Alfa (Activated). Bleeding may occur. Management: When possible, avoid use of drotrecogin in patients who have recently received treatment with antithrombin. Consider therapy modification
Apixaban: May enhance the anticoagulant effect of Anticoagulants. Avoid combination
Collagenase (Systemic): Anticoagulants may enhance the adverse/toxic effect of Collagenase (Systemic). Specifically, the risk of injection site bruising and/or bleeding may be increased. Monitor therapy
Dabigatran Etexilate: May enhance the anticoagulant effect of Anticoagulants. Avoid combination
Danaparoid: May enhance the adverse/toxic effect of Drotrecogin Alfa (Activated). Bleeding may occur. Consider therapy modification
Dasatinib: May enhance the anticoagulant effect of Anticoagulants. Monitor therapy
Deferasirox: Anticoagulants may enhance the adverse/toxic effect of Deferasirox. Specifically, the risk for GI ulceration/irritation or GI bleeding may be increased. Monitor therapy
Fondaparinux: Drotrecogin Alfa (Activated) may enhance the adverse/toxic effect of Fondaparinux. Bleeding may occur. Management: Monitor for increased risk of bleeding during concomitant therapy. Consider avoiding concomitant use, when possible. Consider therapy modification
Heparin: May enhance the adverse/toxic effect of Drotrecogin Alfa (Activated). Bleeding may occur. Management: Potential benefits of therapeutic heparin doses should be weighed against an increased risk of bleeding in patients who receive drotrecogin alfa. In patients receiving prophylactic heparin doses consider continuing this during drotrecogin. Consider therapy modification
Heparin (Low Molecular Weight): May enhance the adverse/toxic effect of Drotrecogin Alfa (Activated). Bleeding may occur. Management: Potential benefits of therapeutic doses of LMW heparins should be weighed against an increased risk of bleeding in patients who receive drotrecogin alfa. In patients receiving prophylactic LMW heparin doses consider continuing this during drotrecogin. Consider therapy modification
Herbs (Anticoagulant/Antiplatelet Properties) (eg, Alfalfa, Anise, Bilberry): May enhance the adverse/toxic effect of Anticoagulants. Bleeding may occur. Consider therapy modification
Ibritumomab: Anticoagulants may enhance the adverse/toxic effect of Ibritumomab. Both agents may contribute to an increased risk of bleeding. Monitor therapy
Nonsteroidal Anti-Inflammatory Agents: May enhance the anticoagulant effect of Anticoagulants. Monitor therapy
Omacetaxine: Anticoagulants may enhance the adverse/toxic effect of Omacetaxine. Specifically, the risk for bleeding-related events may be increased. Management: Avoid concurrent use of anticoagulants with omacetaxine in patients with a platelet count of less than 50,000/uL. Avoid combination
Omega-3 Fatty Acids: May enhance the anticoagulant effect of Anticoagulants. Monitor therapy
Pentosan Polysulfate Sodium: May enhance the anticoagulant effect of Anticoagulants. Monitor therapy
Prostacyclin Analogues: May enhance the adverse/toxic effect of Anticoagulants. Specifically, the antiplatelet effects of these agents may lead to an increased risk of bleeding with the combination. Monitor therapy
Rivaroxaban: Anticoagulants may enhance the anticoagulant effect of Rivaroxaban. Avoid combination
Salicylates: May enhance the adverse/toxic effect of Drotrecogin Alfa (Activated). Bleeding may occur. Management: Weigh potential benefits of drotrecogin against increased bleeding risk in patients who have received platelet inhibitors including aspirin (over 650 mg daily within 1 week). Monitor for bleeding and stop infusion if clinically important bleeding occurs. Consider therapy modification
Sugammadex: May enhance the anticoagulant effect of Anticoagulants. Monitor therapy
Thrombolytic Agents: May enhance the adverse/toxic effect of Drotrecogin Alfa (Activated). Bleeding may occur. Management: Whenever possible, avoid use of drotrecogin within 3 days of a thrombolytic agent. Consider therapy modification
Tibolone: May enhance the anticoagulant effect of Anticoagulants. Monitor therapy
Tipranavir: May enhance the anticoagulant effect of Anticoagulants. Monitor therapy
Tositumomab and Iodine I 131 Tositumomab: Anticoagulants may enhance the adverse/toxic effect of Tositumomab and Iodine I 131 Tositumomab. Specifically, the risk of bleeding-related adverse effects may be increased. Monitor therapy
Vitamin E: May enhance the anticoagulant effect of Anticoagulants. Vitamin E may also increase the overall risk for bleeding. Monitor therapy
Vitamin K Antagonists (eg, warfarin): May enhance the adverse/toxic effect of Drotrecogin Alfa (Activated). Bleeding may occur. Management: Weigh potential benefits of drotrecogin against increased bleeding risk in patients who have received oral anticoagulants within 1 week or have INR 3 or greater. Monitor for bleeding and immediately stop infusion if clinically important bleeding occurs. Consider therapy modification
Monitor for signs and symptoms of bleeding, hemoglobin/hematocrit, PT/INR, platelet count
May interfere with one-stage coagulation assays based on the aPTT (such as factor VIII, IX, and XI assays).
As with all drugs which may affect hemostasis, bleeding is the major adverse effect associated with drotrecogin alfa. Hemorrhage may occur at virtually any site. Risk is dependent on multiple variables, including the dosage administered, concurrent use of multiple agents which alter hemostasis, and patient predisposition.
>10%:
Dermatologic: Bruising
Gastrointestinal: Gastrointestinal bleeding
1% to 10%: Hematologic: Bleeding (serious 2.4% during infusion vs 3.5% during 28-day study period; individual events listed as <1%)
<1% (Limited to important or life-threatening): Gastrointestinal hemorrhage, genitourinary bleeding, immune reaction (antibody production), intracranial hemorrhage (0.2%; frequencies up to 2% noted in a previous trial without placebo control), intrathoracic hemorrhage, retroperitoneal bleeding, skin/soft tissue bleeding
Cl is approximately 50% higher. Dosage adjustment is not required.
Concerns related to adverse effects:
- Bleeding: Increases risk of bleeding; careful evaluation of risks and benefit is required prior to initiation. Bleeding risk is increased in patients receiving concurrent therapeutic heparin, oral anticoagulants, glycoprotein IIb/IIIa antagonists, platelet aggregation inhibitors, or aspirin at a dosage of >650 mg/day (within 7 days). In addition, an increased bleeding risk is associated with prolonged INR (>3), gastrointestinal bleeding (within 6 weeks), decreased platelet count (<30,000/mm3), thrombolytic therapy (within 3 days), recent ischemic stroke (within 3 months), intracranial AV malformation or aneurysm, known bleeding diathesis, severe hepatic disease (chronic), or other condition where bleeding is a significant hazard or difficult to manage due to its location. Discontinue if significant bleeding occurs (may consider continued use after stabilization). Suspend administration for 2 hours prior to invasive procedures or other procedure with significant bleeding risk; may continue treatment immediately following uncomplicated, minimally-invasive procedures, but delay for 12 hours after major invasive procedures/surgery. During treatment, aPTT cannot be used to assess coagulopathy (PT/INR not affected).
Disease-related concerns:
- Conditions excluded from clinical trial: Efficacy not established in adult patients at a low risk of death (APACHE II score <25). Patients with pre-existing nonsepsis-related medical conditions with a poor prognosis (anticipated survival <28 days), patients with acute pancreatitis (no established source of infection), HIV-infected patients with a CD4 count ≤50 cells/mm3, chronic dialysis patients, pre-existing hypercoagulable conditions, and patients who had received bone marrow, liver, lung, pancreas, or small bowel transplants were excluded from the clinical trial which established benefit. In addition, patients weighing >135 kg were not evaluated.
Special populations:
- Pediatrics: Safety and efficacy have not been established in children.
C
Animal reproduction studies have not been conducted. No adverse effects were seen in a limited number of case reports using drotrecogin alfa in pregnant women (Eppert, 2011; Gupta, 2011).
Inhibits factors Va and VIIIa, limiting thrombotic effects. Additional in vitro data suggest inhibition of plasminogen activator inhibitor-1 (PAF-1) resulting in profibrinolytic activity, inhibition of macrophage production of tumor necrosis factor, blocking of leukocyte adhesion, and limitation of thrombin-induced inflammatory responses. Relative contribution of effects on the reduction of mortality from sepsis is not completely understood.
Inactivated by endogenous plasma protease inhibitors; mean clearance: 40 L/hour; increased with severe sepsis (~50%)
Plasma nondetectable within 2 hours of discontinuation
1.6 hours
This medication can only be administered by infusion. You will be monitored closely.