adverse events that were considered to have a possible or probable relationship to Humate-P. These included chills, phlebitis, vasodilation, paresthesia, pruritus, rash, and urticaria. All were mild in intensity with the exception of a moderate case of pruritus.
In a prospective, open-label safety and efficacy study of Humate-P in VWD subjects with serious life- or limb-threatening bleeding or undergoing emergency surgery, seven of 71 (10%) subjects experienced nine adverse reactions. These were one occurrence each of mild vasodilation and mild pruritis; two occurrences of mild paresthesia; and one occurrence each of moderate peripheral edema and extremity pain and severe pseudothrombocytopenia (platelet clumping with a false low reading). Humate-P was discontinued in the subject who experienced the peripheral edema and extremity pain.
Prevention of Excessive Bleeding During and After Surgery in VWD
Among the 63 VWD subjects who received Humate-P for prevention of excessive bleeding during and after surgery, including one subject who underwent colonoscopy without the planned polypectomy, the most common adverse events were postoperative hemorrhage (35 events in 19 subjects with five subjects experiencing bleeding at up to three different sites), postoperative nausea (15 subjects), and postoperative pain (11 subjects). Table 5 presents the postoperative hemorrhagic adverse events.
Table 5: Hemorrhagic Adverse Events in 63 Surgical Subjects Adverse Event Surgical Procedure Category Number of Subjects/Events Onset*
(Number of Events) Severity
(Number of Events)
On Post Mild Mod Severe
*
On = on-therapy; onset while receiving Humate-P or within 1 day of completing Humate-P administration. Post = post-therapy; onset at least one day after completing Humate-P administration.
†
Reported as serious adverse events following intracranial surgery.
‡
Two of these events were reported as serious adverse events following gastrojejunal bypass.
§
Reported as a serious adverse event requiring hysterectomy following hysteroscopy and dilation and curettage.
Wound/injection site bleeding Major 8/11 7 4 9 – 2
Minor 2/2 2 – 1 1 –
Oral 2/6 – 6 3 3 –
Epistaxis Major 4/4 2 2 3 1 –
Minor 1/1 1 – 1 – –
Cerebral hemorrhage/
subdural hematoma Major 1/2 2† – – 2 –
Gastrointestinal bleeding Major 1/3 3‡
– – 2 1
Menorrhagia Major 1/1 1§ – – 1 –
Groin bleed Oral 1/1 – 1 1 – –
Ear bleed Major 1/1 1 – 1 – –
Hemoptysis Major 1/1 1 – 1 – –
Hematuria Major 1/1 1 – 1 – –
Shoulder bleed Major 1/1 1 – 1 – –
Table 6 lists the non-hemorrhagic adverse events reported in at least two subjects, regardless of causality, and the adverse events that were possibly related to Humate-P. Pulmonary embolus considered possibly related to Humate-P occurred in one elderly subject who underwent bilateral knee replacement.
Table 6: Non-Hemorrhagic and Possibly Related Adverse Events in 63 Surgical Subjects Body System Adverse Event (AE) Number of Subjects With an AE Possibly Related to Humate-P Number of Subjects With an AE Regardless of Causality*
*
Events occurring in two or more subjects.
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