al Hematoma [see Warnings and Precautions (5.1)]
Thrombocytopenia [see Warnings and Precautions (5.2)]
Benzyl Alcohol preservative Risk to Premature Infants [see Warnings and Precautions (5.3)]
6.1 Clinical Trials ExperienceBecause clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not accurately reflect the rates observed in practice.
Hemorrhage
The incidence of hemorrhagic complications during treatment with FRAGMIN Injection has been low. The most commonly reported side effect is hematoma at the injection site. The risk for bleeding varies with the indication and may increase with higher doses.
Unstable Angina and Non-Q-Wave Myocardial Infarction
Table 5 summarizes major bleeding reactions that occurred with FRAGMIN, heparin, and placebo in clinical trials of unstable angina and non-Q-wave myocardial infarction.
Table 5
Major Bleeding Reactions in Unstable Angina and
Non-Q-Wave Myocardial Infarction
Indication Dosing Regimen
Unstable Angina and
Non-Q-Wave MI FRAGMIN
120 IU/kg/12 hr subcutaneous1
n (%) Heparin2
intravenous and subcutaneous2
n (%) Placebo
every 12 hr subcutaneous
n (%)
Major Bleeding Reactions3,4 15/1497 (1.0) 7/731 (1.0) 4/760 (0.5)
1 Treatment was administered for 5 to 8 days.
2 Heparin intravenous infusion for at least 48 hours, APTT 1.5 to 2 times control, then 12,500 U subcutaneously every 12 hours for 5 to 8 days.
3 Aspirin (75 to 165 mg per day) and beta blocker therapies were administered concurrently
4 Bleeding reactions were considered major if: 1) accompanied by a decrease in hemoglobin of ≥2 g/dL in connection with clinical symptoms; 2) a transfusion was required; 3) bleeding led to interruption of treatment or death; or 4) intracranial bleeding.
Hip Replacement Surgery
Table 6 summarizes: 1) all major bleeding reactions and, 2) other bleeding reactions possibly or probably related to treatment with FRAGMIN (preoperative dosing regimen), warfarin sodium, or heparin in two hip replacement surgery clinical trials.
Table 6
Bleeding Reactions Following Hip Replacement Surgery
Indication FRAGMIN vs
Warfarin Sodium FRAGMIN vs
Heparin
Dosing Regimen Dosing Regimen
Hip
Replacement
Surgery FRAGMIN2
5000 IU once daily subcutaneous
n (%) Warfarin
Sodium1 oral
n (%) FRAGMIN4
5000 IU once daily
subcutaneous
n (%) Heparin
5000 U three times a day subcutaneous
n (%)
Major Bleeding Reactions3 7/274 (2.6) 1/279 (0.4) 0 3/69 (4.3)
Other Bleeding Reactions5
Hematuria 8/274 (2.9) 5/279 (1.8) 0 0
Wound Hematoma 6/274 (2.2) 0 0&n
