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Xigris

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Xigris

Indications
Dosage
How Supplied

INDICATIONS

Xigris (drotrecogin alfa) ® 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 score ≥ 25) [see Clinical Studies].

Limitations of use:

Xigris (drotrecogin alfa) is not indicated in adult patients with severe sepsis and a lower risk of death (e.g., APACHE II score < 25) [see Clinical Studies].

Xigris (drotrecogin alfa) is not indicated in pediatric patients [see Clinical Studies].

DOSAGE AND ADMINISTRATION

Recommended Dosing and Administration Overview

Xigris (drotrecogin alfa) should be administered intravenously at an infusion rate of 24 mcg/kg/hr (based on actual body weight) for a total duration of infusion of 96 hours. Dose adjustment based on clinical or laboratory measurements is not recommended [see DRUG INTERACTIONS]. Dose escalation or bolus doses of Xigris (drotrecogin alfa) are not recommended.

If the infusion is interrupted, Xigris (drotrecogin alfa) should be restarted at the 24 mcg/kg/hr infusion rate.

In the event of clinically important bleeding, immediately stop the infusion [see WARNINGS AND PRECAUTIONS].

Xigris (drotrecogin alfa) 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 Ringer's Injection, USP; Dextrose Injection, USP; and Dextrose and Sodium Chloride Injection, USP.

Avoid exposing Xigris (drotrecogin alfa) solutions to heat and/or direct sunlight. Studies conducted at the recommended concentrations indicate the Xigris (drotrecogin alfa) intravenous solution to be compatible with glass infusion bottles, and infusion bags and syringes made of polyvinylchloride, polyethylene, polypropylene, or polyolefin.

Preparation of the Concentrated Solution

Note: Reconstitute vials of lyophilized Xigris (drotrecogin alfa) only with Sterile Water for Injection, USP.

  1. Use appropriate aseptic technique during the preparation of Xigris (drotrecogin alfa) for intravenous administration.
  2. Calculate the approximate amount of Xigris (drotrecogin alfa) needed based upon the patient's actual body weight and duration of infusion period. The maximum duration of infusion from one infusion bag or syringe is 12 hours. Multiple infusion periods will be needed to cover the entire 96-hour duration of administration.
    mg of Xigris (drotrecogin alfa) = (patient weight, kg) x (24 mcg/kg/hr) x (hours of infusion) (1000)
    Round the actual amount of Xigris (drotrecogin alfa) to be prepared to the nearest 5 mg increment to avoid discarding reconstituted Xigris (drotrecogin alfa) .
  3. Determine the number of vials of Xigris (drotrecogin alfa) needed to make up this amount.
  4. Reconstitute each vial of Xigris (drotrecogin alfa) only with Sterile Water for Injection, USP. The 5 mg vials must be reconstituted with 2.5 mL. The 20 mg vials must be reconstituted 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 (drotrecogin alfa) concentration of the solution is 2 mg/mL.
  5. Xigris (drotrecogin alfa) contains no antibacterial preservatives; the intravenous solution should be prepared immediately after reconstitution of the Xigris (drotrecogin alfa) in the vial(s). If the vial of reconstituted Xigris (drotrecogin alfa) 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 (drotrecogin alfa) 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.

Dilution and Administration Instructions for an Intravenous Infusion Pump Using an Infusion Bag

Complete “Preparation of Concentrated Solution” steps 1-6 above, then complete the next 7 steps.

  1. The solution of reconstituted Xigris (drotrecogin alfa) 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.
  2. Confirm that the intended bag volume will result in an acceptable final concentration.
    Final concentration, mg/mL = (actual Xigris (drotrecogin alfa) 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.
  3. Slowly withdraw the reconstituted Xigris (drotrecogin alfa) solution from the vial(s) and add the reconstituted Xigris (drotrecogin alfa) into the infusion bag of 0.9% Sodium Chloride Injection, USP. When injecting the Xigris (drotrecogin alfa) 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.
  4. Calculate the actual duration of the infusion period for the diluted Xigris (drotrecogin alfa) .
    Infusion period, hours = (actual Xigris (drotrecogin alfa) amount, mg) x (1000) (patient weight, kg) (24 mcg/kg/hr)
  5. Account for the added volume of reconstituted Xigris (drotrecogin alfa) (0.5 mL per mg of Xigris (drotrecogin alfa) used) and the volume of bag saline solution removed (if saline solution is removed prior to adding the reconstituted Xigris (drotrecogin alfa) ).
    Final bag volume, mL = (starting bag volume, mL) + (reconstituted Xigris (drotrecogin alfa) volume, mL) - [saline volume removed (if any), mL]
  6. Calculate the actual infusion rate of the diluted Xigris (drotrecogin alfa) .
    Infusion rate, mL/hr = (final bag volume, mL) (infusion period, hours)
  7. After preparation in an infusion bag, the intravenous solution should be used at controlled room temperature 20° to 25°C (68° to 77°F) within 12 hours. If the intravenous solution is not administered immediately, the solution should be refrigerated at 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 dilution, refrigeration, and administration, is 24 hours.

Dilution and Administration Instructions for a Syringe Pump

Complete “Preparation of Concentrated Solution” steps 1-6 above, then complete the next 7 steps.

  1. The solution of reconstituted Xigris (drotrecogin alfa) must be further diluted with 0.9% Sodium Chloride Injection, USP to a final concentration of between 0.1 mg/mL and 0.2 mg/mL.
  2. Confirm that the intended solution volume will result in an acceptable final concentration.
    Final concentration, mg/mL = (actual Xigris (drotrecogin alfa) amount, mg) (solution volume, mL)
    If the calculated final concentration is not between 0.1 to 0.2 mg/mL, select a different volume and recalculate the final concentration.
  3. Slowly withdraw the reconstituted Xigris (drotrecogin alfa) 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 (drotrecogin alfa) . Gently invert and/or rotate the syringe to obtain a homogeneous solution.
  4. Calculate the actual duration of the infusion period for the diluted Xigris (drotrecogin alfa) .
    Infusion period, hours = (actual Xigris (drotrecogin alfa) amount, mg) x (1000) (patient weight, kg) (24 mcg/kg/hr)
  5. Calculate the actual infusion rate of the diluted Xigris (drotrecogin alfa) .
    Infusion rate, mL/hr = (solution volume, mL) (infusion period, hours)
  6. When administering Xigris (drotrecogin alfa) using a syringe pump 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.
  7. After preparation in a syringe, the intravenous solution should be used at controlled room temperature 20° to 25°C (68° to 77°F) within 12 hours. If the intravenous solution is not administered immediately, the solution should be refrigerated at 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 dilution, refrigeration, and administration, is 24 hours.

HOW SUPPLIED

Dosage Forms And Strengths

Xigris (drotrecogin alfa) is supplied in single-use vials of 5 mg and 20 mg drotrecogin alfa (activated) as a sterile, preservative-free, lyophilized white to off-white powder for reconstitution.

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

5 mg vial individually packaged in a carton — NDC 0002-7559-01

20 mg vial individually packaged in a carton — NDC 0002-7561-01

Storage and Handling

Lyophilized Powder

Xigris (drotrecogin alfa) vials should be stored in a refrigerator 2° to 8°C (36° to 46°F). Do not freeze. Protect vials of Xigris (drotrecogin alfa) from light. Retain in carton until time of use.

Reconstituted Solution

Avoid exposing Xigris (drotrecogin alfa) solutions to heat and/or direct sunlight. The intravenous solution should be prepared immediately after reconstitution of the Xigris (drotrecogin alfa) in the vial(s). If the vial of reconstituted Xigris (drotrecogin alfa) 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 [see DOSAGE AND ADMINISTRATION].

Intravenous infusion pump using an infusion bag — After final dilution and preparation, the intravenous solution should be used at controlled room temperature 20° to 25°C (68° to 77°F) within 12 hours. If the intravenous solution is not administered immediately, the solution should be refrigerated at 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 with an infusion bag, including dilution, refrigeration, and administration, is 24 hours [see DOSAGE AND ADMINISTRATION].

Intravenous infusion using a syringe pump — After final dilution and preparation, the intravenous solution should be used at controlled room temperature 20° to 25°C (68° to 77°F) within 12 hours. If the intravenous solution is not administered immediately, the solution should be refrigerated at 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 with a syringe pump, including dilution, refrigeration, and administration, is 24 hours [see DOSAGE AND ADMINISTRATION].

Eli Lilly and Company Indianapolis, IN 46285. Literature Revised October 9, 2008.

Last reviewed on RxList: 9/1/2009
This monograph has been modified to include the generic and brand name in many instances.

Indications
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