ADVERSE REACTIONS
BLEEDING
Bleeding is the most common adverse reaction associated with Xigris.
In the Phase 3 study, serious bleeding events were observed during the 28-day study period in 3.5% of Xigris-treated and 2.0% of placebo-treated patients, respectively. The difference in serious bleeding between Xigris and placebo occurred primarily during the infusion period and is shown in Table 2.1 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.
Table 2: Number of Patients Experiencing a Serious Bleeding
Event by Site of Hemorrhage During the Study Drug Infusion Period a in PROWESS1
|
|
Xigris N=850 |
Placebo N=840 |
| Total |
20 (2.4%) |
8 (1.0%) |
|
Site of Hemorrhage
|
|
Gastrointestinal
|
5
|
4
|
|
Intra-abdominal
|
2
|
3
|
|
Intra-thoracic
|
4
|
0
|
|
Retroperitoneal
|
3
|
0
|
|
Intracranial
|
2
|
0
|
|
Genitourinary
|
2
|
0
|
|
Skin/soft tissue
|
1
|
0
|
|
Other b |
1
|
1
|
| a Study drug infusion period is defined as the date of initiation of study drug to the date of study drug discontinuation plus the next calendar day. |
| b Patients requiring the administration of >/=3 units of packed red blood cells per day for 2 consecutive days without an identified site of bleeding.
|
|
In PROWESS, 2 cases of intracranial hemorrhage (ICH) occurred during the infusion period for Xigris-treated patients and no cases were reported in the placebo patients. The incidence of ICH during the 28-day study period was 0.2% for Xigris-treated patients and 0.1% for placebo-treated patients. ICH has been reported in patients receiving Xigris in non-placebo controlled trials with an incidence of approximately 1% during the infusion period. The risk of ICH may be increased in patients with risk factors for bleeding such as severe coagulopathy and severe thrombocytopenia (see WARNINGS).
In PROWESS, 25% of the Xigris-treated patients and 18% of the placebo-treated patients experienced at least one bleeding event during the 28-day study period. In both treatment groups, the majority of bleeding events were ecchymoses or gastrointestinal tract bleeding.
OTHER ADVERSE REACTIONS
Patients administered Xigris as treatment for severe sepsis experience many events which are potential sequelae of severe sepsis and may or may not be attributable to Xigris therapy. In clinical trials, there were no types of non-bleeding adverse events suggesting a causal association with Xigris.
|
