Xigris Dosage

Recommended Dosing and Administration Overview

Xigris 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 (7.3)]. Dose escalation or bolus doses of Xigris are not recommended.

If the infusion is interrupted, Xigris 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 (5.1)].

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 Ringer's Injection, USP; Dextrose Injection, USP; and Dextrose and Sodium Chloride Injection, USP.

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.

Preparation of the Concentrated Solution

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

1. Use appropriate aseptic technique during the preparation of Xigris for intravenous administration.
2. Calculate the approximate amount of Xigris 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 = (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 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 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.

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 [see Dosage and Administration (2.2)].

1. 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.
2. 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.
3. 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.
4. 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)
   
   

5. 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]
   
   

6. Calculate the actual infusion rate of the diluted Xigris.

   
   
   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 [see Dosage and Administration (2.2)].

1. ​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 0.2 mg/mL.
2. ​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 0.2 mg/mL, select a different volume and recalculate the final concentration.
3. 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 homogeneous solution.
4. 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)
   
   

5. Calculate the actual infusion rate of the diluted Xigris.

   
   
   Infusion rate, mL/hr = (solution volume, mL) ÷ (infusion period, hours)
   
   

6. When administering Xigris 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.