Xigris (Drotrecogin Alfa (Activated)) - Indications and Dosage

INDICATIONS AND USAGE

Xigris is indicated for the reduction of mortality in adult patients with severe sepsis (sepsis associated with acute organ dysfunction) who have a high risk of death (e.g., as determined by APACHE II, see CLINICAL STUDIES).

Safety and efficacy have not been established in adult patients with severe sepsis and lower risk of death (see CLINICAL STUDIES, Long-Term Follow-Up). Safety and efficacy have not been established in pediatric patients with severe sepsis.

DOSAGE AND ADMINISTRATION

Xigris should be administered intravenously at an infusion rate of 24 µg/kg/hr for a total duration of infusion of 96 hours. Dose adjustment based on clinical or laboratory parameters is not recommended (see PRECAUTIONS).

If the infusion is interrupted, Xigris should be restarted at the 24 µg/kg/hr infusion rate. Dose escalation or bolus doses of Xigris are not recommended.

In the event of clinically important bleeding, immediately stop the infusion (see WARNINGS).

PREPARATION AND ADMINISTRATION INSTRUCTIONS:

1. Use appropriate aseptic technique during the preparation of Xigris for intravenous administration.
2. Calculate the dose and the number of Xigris vials needed. Each 5 mg and 20 mg vial of Xigris contains an excess of Xigris to facilitate delivery of the labeled amount.
3. 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 is approximately 2 mg/mL of Xigris. Slowly add the Sterile Water for Injection, USP to the vial and avoid inverting or shaking the vial. Gently swirl each vial until the powder is completely dissolved.
4. 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.
5. Before further dilution or administration, the product should be inspected visually for particulate matter and discoloration. Do not use vials if particulate matter is visible or solution is discolored.
6. Xigris should be administered via a dedicated intravenous line or a dedicated lumen of a multilumen central venous catheter. The ONLY other solutions that can be administered through the same line are 0.9% Sodium Chloride Injection, USP; Lactated Ringer's Injection, USP; Dextrose Injection, USP; and Dextrose and Sodium Chloride Injection, USP.
7. Avoid exposing Xigris solutions to heat and/or direct sunlight. Studies conducted at the recommended concentrations indicate the Xigris intravenous solution to be compatible with glass infusion bottles, and infusion bags and syringes made of polyvinylchloride, polyethylene, polypropylene, or polyolefin.
   Dilution and Administration Instructions for an Intravenous Infusion Pump:
8. The solution of reconstituted Xigris must be further diluted into an infusion bag containing 0.9% Sodium Chloride Injection, USP to a final concentration of between 100 µg/mL and 200 µg/mL. Slowly withdraw the reconstituted Xigris solution from the vial(s) and add the reconstituted Xigris into a prepared infusion bag of 0.9% Sodium Chloride Injection, USP. When injecting the Xigris into the infusion bag, direct the stream to the side of the bag to minimize the agitation of the solution. Gently invert the infusion bag to obtain a homogeneous solution. Do not transport the infusion bag using mechanical transport systems such as pneumatic-tube systems that may cause vigorous agitation of the solution.
9. After preparation, the intravenous solution should be used at controlled room temperature 20° to 25°C (68° to 77°F) within 14 hours. If the intravenous solution is not administered immediately, the solution may be stored refrigerated 2° to 8°C (36° to 46°F) for 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.
   Dilution and Administration Instructions for a Syringe Pump:
10. 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. Slowly withdraw the reconstituted Xigris solution from the vial(s) into a syringe that will be used in the syringe pump. Into the same syringe, slowly withdraw 0.9% Sodium Chloride Injection, USP to obtain the desired final concentration of Xigris. Gently invert and/or rotate the syringe to obtain a homogenous solution. When administering Xigris using a syringe pump at low concentrations (less than approximately 200 µg/mL) at low flow rates (less than approximately 5 mL/hr), the infusion set must be primed for approximately 15 minutes at a flow rate of approximately 5 mL/hr.
11. After preparation, the intravenous solution should be used at controlled room temperature 20° to 25°C (68° to 77°F) within 12 hours. The maximum time limit for use of the intravenous solution, including preparation and administration, is 12 hours.

HOW SUPPLIED

Xigris is available in 5 mg and 20 mg single-use vials containing sterile, preservative-free, lyophilized drotrecogin alfa (activated).

VIALS:

5 mg Vials

NDC 0002-7559-01

20 mg Vials

NDC 0002-7561-01

Xigris should be stored in a refrigerator 2° to 8°C (36° to 46°F). Do not freeze. Protect unreconstituted vials of Xigris from light. Retain in carton until time of use. Do not use beyond the expiration date stamped on the vial.