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 has not been established in adult patients with severe sepsis and lower risk of death. Safety and efficacy have not been established in pediatric patients with severe sepsis.

Xigris should be administered intravenously at an infusion rate of 24 mg/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 mg/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).

1. Use appropriate aseptic technique during the preparation of Xigris for intravenous administration.
2. Calculate the approximate amount of Xigris needed based upon the patients actual body weight and duration of this infusion period. The maximum duration of infusion from one preparation step is 12 hours. Multiple infusion periods will be needed to cover the entire 96-hour duration of administration.
   
   mg of Xigris = (patient weight, kg) X 24 mcg/kg/hr X (hours of infusion) · 1000
   
   Round the actual amount of Xigris to be prepared to the nearest 5 mg increment to avoid discarding reconstituted Xigris.
3. Determine the number of vials of Xigris needed to make up this amount.
4. Reconstitute each vial of Xigris with Sterile Water for Injection, USP. The 5 mg vials must be reconstituted with 2.5 mL; the 20 mg vials with 10 mL. 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. The resulting Xigris concentration of the solution is 2 mg/mL.
5. Xigris contains no antibacterial preservatives; the intravenous solution should be prepared immediately after 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.
6. Inspect the reconstituted Xigris in the vials for particulate matter and discoloration before further dilution. Do not use vials if particulate matter is visible or the solution is discolored.
7. Xigris should be administered via a dedicated intravenous line or a dedicated lumen of a multilumen venous catheter. The ONLY other solutions that can be administered through the same line are 0.9% Sodium Chloride Injection, USP; Lactated Ringers Injection, USP; Dextrose Injection, USP; and Dextrose and Sodium Chloride Injection, USP.
8. 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.

1. Complete Preparation and Administration steps 1-8, then complete the next 6 steps.
2. 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 0.1 mg/mL and 0.2 mg/mL. Bag volumes between 50 mL and 250 mL are typical.
3. Confirm that the intended bag volume will result in an acceptable final concentration.
   
   Final concentration, mg/mL = (actual Xigris amount, mg) · (bag volume, mL)
   
   If the calculated final concentration is not between 0.1 mg/mL and 0.2 mg/mL select a different bag volume and recalculate the final concentration.
4. Slowly withdraw the reconstituted Xigris solution from the vial(s) and add the reconstituted Xigris into the 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.
5. Calculate the actual duration of the infusion period for the diluted Xigris.
   
   Infusion period, hours = (actual Xigris amount, mg) X 1000 · (patient weight, kg) · 24 mcg/kg/hr
6. Account for the added volume of reconstituted Xigris (0.5 mL per mg of Xigris used) and the volume of bag saline solution removed (if saline solution is removed prior to adding the reconstituted Xigris).
   
   Final bag volume, mL = starting bag volume, mL + reconstituted Xigris volume, mL - saline volume removed (if any), mL
   
   Calculate the actual infusion rate of the diluted Xigris.
   
   Infusion rate, mL/hr = final bag volume, mL · infusion period, hours
7. 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.

1. Complete Preparation and Administration steps 1-8, then complete the next 7 steps.
2. The solution of reconstituted Xigris must be further diluted with 0.9% Sodium Chloride Injection, USP to a final concentration of between 0.1 mg/mL and 1.0 mg/mL.
3. Confirm that the intended solution volume will result in an acceptable final concentration.
   
   Final concentration, mg/mL = (actual Xigris amount, mg) · (solution volume, mL)
   
   If the calculated final concentration is not between 0.1 to 1.0 mg/mL select a different volume and recalculate the final concentration.
4. 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 volume of diluted Xigris. Gently invert and/or rotate the syringe to obtain a homogenous solution.
5. Calculate the actual duration of the infusion period for the diluted Xigris.
   
   Infusion period, hours = (actual Xigris amount, mg) X 1000 · (patient weight, kg) · 24 mcg/kg/hr
6. Calculate the actual infusion rate of the diluted Xigris.
   
   Infusion rate, mL/hr = (solution volume, mL) · (infusion period, hours)
7. When administering Xigris using a syringe pump at low concentrations (less than approximately 0.2 mg/mL) with 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.
8. 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.

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.

REFERENCES

Literature issued November 2001

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