drug-information.ru

|Drotrecogin Alfa

Drotrecogin Alfa (Activated)

Trade Names:
Xigris
- Powder for infusion, lyophilized 5 mg
- Powder for infusion, lyophilized 20 mg

Mechanism of Action

Pharmacology

Exerts antithrombotic effect by inhibiting Factors Va and VIIIa.

Pharmacokinetics

Absorption

Steady-state concentration of 45 ng/mL attained within 2 hr.

Elimination

Cl is approximately 40 L/hr.

Special Populations

Cl is approximately 50% higher. Dosage adjustment is not required.

Indications and Usage

Reduction of mortality in adult patients with severe sepsis who have a high risk of death.

Contraindications

Patients with the following situations in whom bleeding could be associated with a high risk of death or significant morbidity: active internal bleeding; recent (within 3 mo) hemorrhagic stroke; recent (within 2 mo) intracranial or intraspinal surgery or severe head trauma; trauma with an increased risk of life-threatening bleeding; presence of an epidural catheter; intracranial neoplasm, mass lesion, or evidence of cerebral herniation. Hypersensitivity to drotrecogin alfa (activated) or any component of the product.

Dosage and Administration

IV 24 mcg/kg/hr for a total infusion duration of 96 hr. If infusion is interrupted, restart at the 24 mcg/kg/hr infusion rate.

General Advice

• For IV infusion only.
• Drotrecogin alfa is administered at an infusion rate of 24 mcg/kg/hr (based on actual body weight) for 96 hr. If infusion is interrupted, restart drotrecogin alfa at the 24 mcg/kg/hr infusion rate. Do not escalate dose or administer bolus dose to catch up.
• Drotrecogin alfa is administered as multiple infusion periods. The max infusion period duration is 12 hr. Multiple infusion periods will be needed to cover the entire 96-hr duration of administration.
• Calculate the approximate amount of drotrecogin alfa needed for an infusion period based upon the patient"s actual body weight and duration of the infusion period using the following formula: mg of drotrecogin alfa = (patient weight in kg) × 24 mcg/kg/hr × (hours of infusion) ÷ 1,000 .
• Round the actual amount of drotrecogin alfa to be prepared to the nearest 5 mg increment to avoid preparing more drotrecogin alfa than needed and having to discard unneeded reconstituted solution. Determine the number of vials of drotrecogin alfa needed to prepare infusion solution for the infusion period.
• Reconstitute each vial of drotrecogin alfa with sterile water for injection. Slowly add sterile water for injection (2.5 mL for 5 mg vial, or 10 mL for 20 mg vial) and gently swirl each vial until the powder is completely dissolved. Do not invert or shake the vial. Reconstituted solution contains drotrecogin alfa 2 mg/mL. Reconstituted solution contains no preservatives and must be immediately diluted for IV infusion. If reconstituted solution is not used immediately it may be stored at controlled room temperature (68° to 77°F), but must be used within 3 hr.
• Reconstituted solution must be further diluted in 0.9% sodium chloride for administration via IV infusion pump or syringe pump through a dedicated IV line or dedicated lumen of a multilumen central venous catheter.
• Visually inspect reconstituted solution before further dilution. Do not use reconstituted solution if particulate matter, cloudiness, or discoloration is noted.
• Discard any unused portion of reconstituted solution. Do not combine unused portions or save unused portions for future use.
• Do not mix drotrecogin alfa with other drug solutions. The only other solutions that can be administered through the same IV line as drotrecogin alfa are lactated Ringer"s injection, 0.9% sodium chloride injection, dextrose injection, or dextrose and sodium chloride injection.

• Preparation of solution for infusion pump administration
• Prepare infusion solution by adding reconstituted drotrecogin alfa solution to 0.9% sodium chloride injection to provide a final concentration of drotrecogin between 0.1 and 0.2 mg/mL. Slowly withdraw prescribed amount of reconstituted drotrecogin alfa from the vial(s) and add to infusion bag of 0.9% sodium chloride for injection by directing the stream to the side of the infusion bag to minimize agitation. Gently invert the infusion bag to mix. Do not agitate the infusion solution or transport using mechanical delivery systems (eg, pneumatic-tube system) that could cause vigorous agitation of the solution.
• Begin administration of the IV infusion solution immediately after preparation. The IV infusion solution should be infused at controlled room temperature (68° to 77°F) with the infusion being completed within 14 hr of initial preparation. If the IV infusion solution is not administered immediately, the solution may be stored refrigerated (36° to 46°F) for up to 12 hr. If prepared solution is refrigerated prior to administration, the max time limit for use of the IV infusion solution, including preparation, refrigeration, and administration, is 24 hr.

• Preparation of solution for syringe pump administration
• Prepare syringe pump infusion solution by adding reconstituted drotrecogin alfa solution to 0.9% sodium chloride injection to provide a final concentration of drotrecogin between 0.1 and 1 mg/mL. Slowly withdraw prescribed amount of reconstituted alfa 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 to obtain the desired volume of diluted drotrecogin alfa. Gently invert or rotate the syringe to obtain a homogenous solution.
• After the preparation for the syringe pump, use the IV infusion solution at controlled room temperature within 12 hr. The max time limit for use of the IV solution, including preparation and administration, is 12 hr.

Storage/Stability

If the IV infusion solution is not administered immediately, the solution may be stored refrigerated (36° to 46°F) for up to 12 hr. If prepared solution is refrigerated prior to administration, the max time limit for use of the IV infusion solution, including preparation, refrigeration, and administration, is 24 hr. Store unreconstituted vials in refrigerator. Do not freeze. Protect unreconstituted vials from light. Retain in carton until time of use. Do not use beyond expiration date stamped on vial. Avoid exposing drotrecogin alfa solutions to heat and/or direct sunlight.

Drug Interactions

Increased risk of bleeding.

Incompatibility

Administer through a dedicated line or dedicated lumen of a multilumen central venous catheter. Only 0.9% sodium chloride for injection, lactated Ringer"s injection, dextrose, or dextrose and saline mixtures can be administered through the same line as drotrecogin alfa.

Laboratory Test Interactions

Because drotrecogin alfa may variably prolong the APTT, APTT cannot be reliably used to assess the status of coagulopathy during drotrecogin alfa administration; drotrecogin alfa present in plasma samples may interfere with 1-stage coagulation assay based on the APTT (eg, factor VIII, IX, and XI) assays.

Adverse Reactions

Hematologic

Bleeding/hemorrhage (eg, GI, GU, intra-abdominal, intracranial, intrathoracic, retroperitoneal, skin/soft tissue, other sites).

Precautions

Pregnancy

Category C .

Lactation

Undetermined.

Children

Safety and efficacy not established.

Bleeding

Severe bleeding may occur.

Immunogenicity

As with all therapeutic proteins, immunogenicity may occur.

Overdosage

Symptoms

Monitor closely for hemorrhagic complications.

Patient Information

• Explain name, dose, action, and potential side effects of drug.
• Advise patient, family, or caregiver that medication will be prepared and administered by health care professionals while the patient is in the intensive care unit.