drotrecogin alfa

drotrecogin alfa,

a thrombolytic agent used to treat severe sepsis associated with organ dysfunction.

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drotrecogin alfa (activated) Warning - High-alert drug!

Xigris

Pharmacologic class: Activated protein C (recombinant)

Therapeutic class: Antisepsis drug

Pregnancy risk category C

Action

Antisepsis action unknown. May produce indirect profibrinolytic activity by hindering plasminogen activator inhibitor-1 and limiting generation of activated thrombin-activatable fibrinolysis inhibitor. Produces anti-inflammatory effect by inhibiting human tumor necrosis factor production and suppressing thrombin-induced inflammatory responses.

Availability

Powder for injection (lyophilized): 5 mg, 20 mg

⊘Indications and dosages

➣ Severe sepsis

Adults: 24 mcg/kg/hour I.V. for a total duration of 96 hours

Contraindications

• Hypersensitivity to drug or its components
• Intracranial neoplasm or lesion or evidence of cerebral herniation
• Intracranial or intraspinal surgery within past 2 months
• Hemorrhagic stroke within past 3 months
• Severe head trauma or trauma with increased risk of bleeding
• Active bleeding or high risk of bleeding
• Patients undergoing bone marrow therapy
• Current use of epidural catheter

Precautions

Use cautiously in:
• intracranial arteriovenous malformation, chronic severe hepatic disease, recent GI bleeding
• concurrent use of heparin, thrombolytics, oral anticoagulants, or aspirin
• pregnant patients
• children (safety and efficacy not established).

Administration

• Mix with normal saline solution, lactated Ringer's solution, or dextrose 5% in water.
• Prepare immediately before use. Hang infusion bag within 3 hours of reconstitution; complete infusion within 12 hours after preparation.
• Administer only through infusion pump.
• Don't infuse with any other drug.
• Give entire regimen over 96 hours.
☞ Discontinue drug 2 hours before invasive procedures.
• Be aware that once hemostasis occurs, drug therapy may resume immediately after uncomplicated invasive procedures or 12 hours after major invasive procedures (such as surgery).

Route	Onset	Peak	Duration
I.V.	Rapid	Unknown	Unknown

Adverse reactions

CNS: intracranial hemorrhage

GI: intra-abdominal, retroperitoneal, or other GI tract bleeding

GU: bleeding

Hematologic: bleeding

Skin: bruising

Other: skin and soft-tissue bleeding, intrathoracic bleeding

Interactions

Drug-drug. Anticoagulants, aspirin, glycoprotein IIb/IIIa inhibitors, indomethacin, phenylbutazone, thrombolytics: increased risk of bleeding

Drug-diagnostic tests. Activated partial thromboplastin time (APTT), prothrombin time (PT): prolonged

Hematocrit: decreased

Patient monitoring

☞ Know that no antidote exists. Monitor closely for signs and symptoms of hemorrhage. Stop infusion if clinically significant bleeding occurs.
• Monitor PT and CBC (especially platelet count).
• Realize that drug may variably prolong APTT and thus doesn't reliably indicate coagulopathy.

Patient teaching

• As appropriate, review all other significant and life-threatening adverse reactions and interactions, especially those related to the drugs and tests mentioned above.