ent determined to be possibly or probably related to treatment with FRAGMIN and reported at a rate of at least 2% in the group treated with FRAGMIN, was reported in 4.5% of patients treated with FRAGMIN 5000 IU once daily vs 11.8% of patients treated with heparin 5000 U twice daily in the abdominal surgery trials. In the hip replacement trials, pain at injection site was reported in 12% of patients treated with FRAGMIN 5000 IU once daily vs 13% of patients treated with heparin 5000 U three times a day.
6.2 Post-Marketing ExperienceThe following adverse reactions have been identified during postapproval use of FRAGMIN. Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure.
Since first international market introduction in 1985, there have been more than 15 reports of epidural or spinal hematoma formation with concurrent use of dalteparin sodium and spinal/epidural anesthesia or spinal puncture. The majority of patients had postoperative indwelling epidural catheters placed for analgesia or received additional drugs affecting hemostasis. In some cases the hematoma resulted in long-term or permanent paralysis (partial or complete) [see Boxed Warning].
Skin necrosis has occurred. There have been cases of alopecia reported that improved on drug discontinuation.
7 DRUG INTERACTIONS
Use FRAGMIN with care in patients receiving oral anticoagulants, platelet inhibitors, and thrombolytic agents because of increased risk of bleeding [see Warning and Precautions (5)].
8 USE IN SPECIFIC POPULATIONS
8.1 Pregnancy Pregnancy Category B
There are no adequate and well-controlled studies of FRAGMIN use in pregnant women. In reproductive and developmental toxicity studies, pregnant rats and rabbits received dalteparin sodium at intravenous doses up to 2400 IU/kg (14,160 IU/m2) (rats) and 4800 IU/kg (40,800 IU/m2) (rabbits). These exposures were 2 to 4 times (rats) and 4 times (rabbits) the human dose of 100 IU/kg dalteparin based on the body surface area. No evidence of impaired fertility or harm to the fetuses occurred in these studies. Because animal reproduction studies are not always predictive of human response, this drug should be used during pregnancy only if clearly needed.
Cases of "Gasping Syndrome" have occurred in premature infants when large amounts of benzyl alcohol have been administered (99-404 mg/kg/day). The 9.5 mL and the 3.8 mL multiple-dose vials of FRAGMIN contain 14 mg/mL of benzyl alcohol [see Warnings and Precautions (5.3)].
8.3 Nursing MothersBased on limited published data dalteparin is minimally excreted in human milk. One study of 15 lactating women receiving prophylactic doses of dalteparin, in the immediate postpartum period, detected small amounts of anti-Xa activity (range < 0.005 to 0.037 IU/ml) in breast milk that were equivalent to a milk/plasma ratio of < 0.025-0.224. Oral absorption of LMWH is extremely low, but the clinical implications, if any, of this small amount of anticoagulant activity on a nursing infant are unknown. Caution should be exercised when FRAGMIN is administered to a nursing woman.
8.4 Pediatric Use Safety and effectiveness in pediatric patients have not been established.
8.5 Geriatric UseOf the total number of patients in clinical studies of FRAGMIN, 5516 patients were 65 years of age or older and 2237 were 75 or older. No overall differences |
