XIGRIS Powder for solution for infusion Ref.[9395] Active ingredients: Drotrecogin alfa

Xigris should be used by experienced doctors in institutions skilled in the care of patients with severe sepsis.

Treatment should be started within 48 hours, and preferably within 24 hours, of onset of the first documented sepsis-induced organ dysfunction (see section 5.1).

The recommended dose of Xigris is 24 μg/kg/hr (based on actual body weight) given as a continuous intravenous infusion for a total duration of 96 hours. It is recommended that Xigris be infused with an infusion pump to accurately control the infusion rate. If the infusion is interrupted for any reason, Xigris should be restarted at the 24 μg/kg/hr infusion rate and continued to complete the full recommended 96 hours of dosing administration. Dose escalation or bolus doses of Xigris are not necessary to account for the interruption in the infusion.

No dose adjustments are required in adult patients with severe sepsis with regard to age, gender, hepatic function (as measured by transaminase levels), renal function, obesity or co-administration of prophylactic heparin. The pharmacokinetics of drotrecogin alfa (activated) have not been studied in patients with severe sepsis and pre-existing end stage renal disease and chronic hepatic disease.

Paediatrics

Data from a placebo-controlled clinical trial which was stopped for futility after 477 patients 0 to 17 years-old had received the study treatment did not establish efficacy of Xigris in paediatric patients and showed a higher rate of central nervous system bleeding in the Xigris versus placebo group. Xigris is contraindicated in children below the age of 18 (see section 4.3 and 5.1).

In clinical trials and in post marketing experience there have been reports of accidental overdosing. In the majority of cases, no reactions have been observed. For the other reports, the observed events were consistent with known undesirable effects of the drug (see section 4.8), effects of the drug on laboratory tests (see section 4.4), or consequences of the underlying condition of sepsis.

There is no known antidote for drotrecogin alfa (activated). In case of overdose, immediately stop the infusion (see section 5.2).

Shelf life: 3 years.

After reconstitution, immediate use is recommended. However, the reconstituted solution in the vial may be held for up to 3 hours at room temperature (15°C-30°C).

After preparation, the intravenous infusion solution can be used at room temperature (15°C-30°C) for a period up to 14 hours.

Store in a refrigerator (2°C-8°C). Keep the vial in the outer carton in order to protect from light.

Powder in Type I glass vial. Pack of 1 vial.

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 Xigris vial contains 20 mg of drotrecogin alfa (activated). The vial contains an excess of drotrecogin alfa (activated) to facilitate delivery of the label amount.
3. Prior to administration, 20 mg vials of Xigris must be reconstituted with 10 ml of Sterile Water for Injection, resulting in a solution with a concentration of approximately 2 mg/ml drotrecogin alfa (activated). Slowly add the Sterile Water for Injection to the vial and avoid inverting or shaking the vial. Gently swirl each vial until the powder is completely dissolved.
4. The solution of reconstituted Xigris must be further diluted with sterile 0.9% Sodium Chloride Injection to a final concentration of between 100 μg/ml and 200 μg/ml. Slowly withdraw the appropriate amount of reconstituted drotrecogin alfa (activated) solution from the vial. Add the reconstituted drotrecogin alfa (activated) into a prepared infusion bag of sterile 0.9% Sodium Chloride Injection. When adding the reconstituted drotrecogin alfa (activated) into the infusion bag, direct the stream to the side of the bag to minimise the agitation of the solution. Gently invert the infusion bag to obtain a homogeneous solution. Do not transport the infusion bag between locations using mechanical delivery systems.
5. After reconstitution, immediate use is recommended. However, the reconstituted solution in the vial may be held for up to 3 hours at room temperature (15 to 30°C). After preparation, the intravenous infusion solution can be used at room temperature (15 to 30°C) for a period up to 14 hours.
6. Parenteral drug products should be inspected visually for particulate matter and discolouration prior to administration.
7. It is recommended that Xigris be infused with an infusion pump to accurately control the infusion rate. The solution of reconstituted Xigris should be diluted into an infusion bag containing sterile 0.9% Sodium Chloride Injection to a final concentration of between 100 μg/ml and 200 μg/ml.
8. When administering drotrecogin alfa (activated) 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.
9. 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, Lactated Ringer’s Injection, Dextrose or Dextrose and Saline mixtures.
10. Avoid exposing drotrecogin alfa (activated) solutions to heat and/or direct sunlight. No incompatibilities have been observed between drotrecogin alfa (activated) and glass infusion bottles or infusion bags made of polyvinylchloride, polyethylene, polypropylene, or polyolefin. The use of other types of infusion sets could have a negative impact on the amount and potency of drotrecogin alfa (activated) administered.
11. Care should be taken to administer Xigris at the appropriate rate, calculated based on kg of bodyweight and infused for the correct duration. It is recommended that the bag be labelled accordingly.