ng was classified as clinically overt bleeding that did not meet criteria for major bleeding.
At the end of the six-month study, a total of 46 (13.6%) patients in the FRAGMIN arm and 62 (18.5%) patients in the OAC arm experienced any bleeding event. One bleeding event (hemoptysis in a patient in the FRAGMIN arm at Day 71) was fatal.
Table 9
Bleeding Reactions (Major and Any) (As treated population)1
Study
period FRAGMIN
200 IU/kg (max. 18,000 IU)
subcutaneous once daily x 1
month, then 150 IU/kg (max.
18,000 IU) subcutaneous once
daily x 5 months OAC
FRAGMIN 200 IU/kg (max
18,000 IU) subcutaneous once
daily x 5-7 days and OAC for 6
months (target INR 2-3)
Number
at risk Patients
with
Major
Bleeding
n (%) Patients
with Any
Bleeding
n (%) Number
at risk Patients
with
Major
Bleeding
n (%) Patients
with Any
Bleeding
n (%)
Total during study 338 19 (5.6) 46 (13.6) 335 12 (3.6) 62 (18.5)
Week 1 338 4 (1.2) 15 (4.4) 335 4 (1.2) 12 (3.6)
Weeks 2-4 332 9 (2.7) 17 (5.1) 321 1 (0.3) 12 (3.7)
Weeks 5-28 297 9 (3.0) 26 (8.8) 267 8 (3.0) 40 (15.0)
1 Patients with multiple bleeding episodes within any time interval were counted only once in that interval. However, patients with multiple bleeding episodes that occurred at different time intervals were counted once in each interval in which the event occurred.
Thrombocytopenia
[see Warnings and Precautions (5.2)]
Elevations of Serum Transaminases
In FRAGMIN clinical trials supporting non-cancer indications, where hepatic transaminases were measured, asymptomatic increases in transaminase levels (SGOT/AST and SGPT/ALT) greater than three times the upper limit of normal of the laboratory reference range were seen in 4.7% and 4.2%, respectively, of patients during treatment with FRAGMIN.
In the FRAGMIN clinical trial of patients with cancer and acute symptomatic venous thromboembolism treated with FRAGMIN for up to 6 months, asymptomatic increases in transaminase levels, AST and ALT, greater than three times the upper limit of normal of the laboratory reference range were reported in 8.9% and 9.5% of patients, respectively. The frequencies of Grades 3 and 4 increases in AST and ALT, as classified by the National Cancer Institute, Common Toxicity Criteria (NCI-CTC) Scoring System, were 3% and 3.8%, respectively. Grades 2, 3 & 4 combined have been reported in 12% and 14% of patients, respectively.
Other
Allergic Reactions: Allergic reactions (i.e., pruritus, rash, fever, injection site reaction, bullous eruption) have occurred. Cases of anaphylactoid reactions have been reported.
Local Reactions: Pain at the injection site, the only non-bleeding ev |
