Drotrecogin alfa- Xigris ®
|The authors make no claims of the accuracy of the information contained herein; and these suggested doses and/or guidelines are not a substitute for clinical judgment. Neither GlobalRPh Inc. nor any other party involved in the preparation of this document shall be liable for any special, consequential, or exemplary damages resulting in whole or part from any user's use of or reliance upon this material. PLEASE READ THE DISCLAIMER CAREFULLY BEFORE ACCESSING OR USING THIS SITE. BY ACCESSING OR USING THIS SITE, YOU AGREE TO BE BOUND BY THE TERMS AND CONDITIONS SET FORTH IN THE DISCLAIMER.|
|Discontinued by manufacturer|
Standard Dilutions [Amount of drug] [Infusion volume] [Infusion rate]
[See comments] [24 mcg/kg/hour]
Review contraindications to therapy
Stability / Miscellaneous
Label: Refrigerate. Do not shake.
Mechanism of Action
Activated protein C exerts an antithrombotic effect by inhibiting Factors Va and VIIIa. In vitro data indicate that activated protein C may have indirect profibrinolytic activity through its ability to inhibit plasminogen activator inhibitor-1 (PAI-1) and may exert an anti-inflammatory effect by limiting the chemotactic response of leukocytes to inflammatory cytokines, an inhibitory process mediated by leukocyte cell surface activated protein C receptor. In addition, in vivo data suggest activated protein C may reduce interactions between leukocytes and the microvascular endothelium. In vitro bacterial phagocytosis by neutrophils and monocytes is not affected.
The specific pharmacologic effects by which Xigris exerts its effect on survival in patients with severe sepsis are not completely understood. In patients with severe sepsis, Xigris infusions of 48 or 96 hours produced dose-dependent declines in D-dimer and IL-6. Compared with placebo, Xigris-treated patients experienced more rapid declines in D-dimer, PAI-1 levels, thrombin-antithrombin levels, prothrombin F1.2, IL-6, more rapid increases in protein C and antithrombin levels, and normalization of plasminogen. As assessed by infusion duration, the maximum observed pharmacodynamic effect of drotrecogin alfa (activated) on D-dimer levels occurred at the end of 96 hours of infusion for the 24 mcg/kg/hr treatment group.
Dosage and administration:
Xigris should be administered intravenously at an infusion rate of 24 mcg/kg/hr x 96 hours. If the infusion is interrupted, Xigris should be restarted at the initial infusion rate and continued to complete the recommended duration of infusion. Dose escalation or bolus doses of Xigris are not recommended. In the event of clinically important bleeding, immediately stop the infusion. No dosage adjustment is required regardless of age, hepatic impairment, or renal impairment.
Preparation: 12 hour infusion bags: Actual Patient Weight (kg) x Dose (24 mcg/kg/hr) = Amount of Xigris needed per hour.Amount of Xigris needed/hr (µg/hr) x 12 hours ÷ 1000 = mg of Xigris needed per 12 hours – round to the nearest 5-mg increment. The solution of reconstituted Xigris is typically diluted into an infusion bag (0.9% Sodium Chloride) to a final concentration of between 100 mcg/mL - 200 mcg/mL.
Vial dilution: Prior to administration, 5 mg vials must be reconstituted with 2.5 mL of Sterile Water for Injection, USP, and 20 mg vials of Xigris must be reconstituted with 10 mL of Sterile Water for Injection, USP. The resulting concentration of the solution isapproximately 2 mg/mL of Xigris. Slowly add the Sterile Water for Injection, USP tothe vial and avoid inverting or shaking the vial. Gently swirl each vial until the powder is completely dissolved. Because Xigris contains no antibacterial preservatives, the intravenous solution should be prepared immediately upon reconstitution of the Xigris in the vial(s). If the vial of reconstituted Xigris is not used immediately, it may be held at controlled room temperature 20° to 25°C (68° to 77°F), but must be used within 3 hours. Before further dilution or administration, the product should be inspectedvisually for particulate matter and discoloration. Do not use vials if particulate matter is visible or solution is discolored.
After preparation, the intravenous solution should be used at controlled room temperature 20° to 25°C within 14 hours. If the intravenous solution isnot administered immediately, the solution may be stored refrigerated 2° to 8°Cfor up to 12 hours. If the prepared solution is refrigerated prior to administration, the maximum time limit for use of the intravenous solution, including preparation, refrigeration, and administration, is 24 hours.
Instructions for a Syringe Pump: See package insert (The solution of reconstituted Xigris must be further diluted with 0.9% Sodium Chloride Injection, USP to a final concentration of between 100 µg/mL and 1000 µg/mL.)
Actions: Recombinant form of human Activated Protein C. Activated Protein C exerts an antithrombotic effect by inhibiting Factors Va and VIIIa.
Indications: reduction of mortality in adult patients with severe sepsis (sepsis associated with acute organ dysfunction) who have a high risk of death. Efficacy has not been established in adult patients with severe sepsis and lower risk of death.
Contraindications: Xigris increases the risk of bleeding. Xigris is contraindicated in the following clinical situations where bleeding could lead to significant morbidity or death:
WARNINGS AND PRECAUTIONS
Should clinically important bleeding occur, immediately stop the infusion of Xigris. Continued use of other agents affecting the coagulation system should be carefully assessed. Once adequate hemostasis has been achieved, continued use of Xigris may be reconsidered.
Source: [package insert]
|The authors make no claims of the accuracy of the information contained herein; and these suggested doses are not a substitute for clinical judgment. Neither GlobalRPh Inc. nor any other party involved in the preparation of this program shall be liable for any special, consequential, or exemplary damages resulting in whole or part from any user's use of or reliance upon this material. PLEASE READ THE DISCLAIMER CAREFULLY BEFORE ACCESSING OR USING THIS SITE. BY ACCESSING OR USING THIS SITE, YOU AGREE TO BE BOUND BY THE TERMS AND CONDITIONS SET FORTH IN THE DISCLAIMER.|