Safety Information
If you are considering therapy with Xigris for your patient, here is an overview of safety information to consider.
Xigris has a low incidence of serious adverse events.
Adverse reactions
In the PROWESS Phase 3 study, bleeding was the most common serious adverse effect associated with Xigris therapy:
- Among high-risk (APACHE II score ≥25) patients, the rate of serious bleeding events* attributable to Xigris during infusion was limited to 1.5% (2.2% vs 0.7%, P=NS)
- One (0.2%) intracranial hemorrhage was observed in a Xigris patient and was associated with severe thrombocytopenia (platelet count <30,000/mm³).†
- Use of Xigris was not associated with any other adverse events
Predisposing factors
Most serious bleeding events occurred in patients with the following predisposing factors:
- Gastrointestinal ulceration1
- Traumatic injury of a blood vessel or highly vascular organ injury1
- Markedly abnormal values for indicators of coagulation‡ (ie, INR >3.0 or platelet count <30,000/mm³)1
- Invasive procedures
Contraindications
Xigris is contraindicated in patients with the following clinical situations:
- Active internal bleeding
- Recent — within 3 months — hemorrhagic stroke
- Recent — within 2 months — intracranial or intraspinal surgery, or severe head trauma
- Trauma with increased risk of life-threatening bleeding
- Presence of an epidural catheter
- Intracranial neoplasm or mass lesion or evidence of cerebral herniation
- Known hypersensitivity to drotrecogin alfa (activated) or any component of this product
Overdose
There is no known antidote for Xigris. In the case of overdose, immediately stop the infusion and monitor closely for hemorrhagic complications.
In postmarketing experience, there have been a limited number of medication error reports of excessive rate of Xigris infusion for short periods of time (median 2 hours). No unexpected adverse events were observed during the overdose period. However, this information is insufficient to assess whether Xigris overdose is associated with an increased hemorrhage risk beyond that observed with Xigris administered at the recommended dose.
Bleeding is the most common adverse reaction associated with Xigris therapy. Please see Important Safety Information and full Prescribing Information for Xigris.
*Serious bleeding events were defined as any intracranial hemorrhage, any life-threatening bleed, any bleeding event requiring the administration of ≥3 units of packed red blood cells per day for 2 consecutive days, or any bleeding event assessed as a serious adverse event.
†At the time of enrollment in the PROWESS study, the patient had a platelet count above 30,000/mm3. The patient's platelet count fell to less than 30,000/mm3 after Xigris therapy was initiated.
‡Abnormal values for indicators of coagulation were INR >3.0 or platelet count <30,000/mm3.
Reference:
- Bernard GR, Vincent JL, Laterre PF, et al. Efficacy and safety of recombinant human activated protein C for severe sepsis. N Engl J Med. 2001;344(10):699-709.
