FRAGMIN®(dalteparin sodium injection) Indications
FRAGMIN® is a low molecular weight heparin (LMWH) indicated for:
- Prophylaxis of ischemic complications of unstable angina and non-Q-wave myocardial
- Prophylaxis of deep vein thrombosis (DVT) in abdominal surgery, hip replacement
surgery or medical patients with severely restricted mobility during acute illness
- Extended treatment of symptomatic venous thromboembolism (VTE) to reduce the recurrence
in patients with cancer. In these patients, the FRAGMIN® therapy
begins with the initial VTE treatment and continues for six months.
FRAGMIN® Limitations of Use
- FRAGMIN® is not indicated for the acute treatment of VTE.
WARNING: SPINAL/EPIDURAL HEMATOMA
Epidural or spinal hematomas may occur in patients who are anticoagulated with low
molecular weight heparins (LMWH) or heparinoids and are receiving neuraxial anesthesia
or undergoing spinal puncture. These hematomas may result in long-term or permanent
paralysis. Consider these risks when scheduling patients for spinal procedures.
Factors that can increase the risk of developing epidural or spinal hematomas in
these patients include:
- Use of indwelling epidural catheters
- Concomitant use of other drugs that affect hemostasis, such as non-steroidal anti-inflammatory
drugs (NSAIDs), platelet inhibitors, other anticoagulants
- A history of traumatic or repeated epidural or spinal punctures
- A history of spinal deformity or spinal surgery.
Monitor patients frequently for
signs and symptoms of neurological impairment. If neurological compromise is noted,
urgent treatment is necessary.
Consider the benefits and risks before neuraxial intervention in patients anticoagulated
or to be anticoagulated for thromboprophylaxis [see Warnings and
Precautions and Drug Interactions].
- FRAGMIN® is contraindicated in patients with active major bleeding,
history of heparin induced thrombocytopenia, hypersensitivity to dalteparin sodium,
heparin, or pork products.
- FRAGMIN® is contraindicated in patients undergoing epidural/neuraxial
anesthesia as a treatment for unstable angina and non-Q-wave MI and for prolonged
VTE prophylaxis due to an increased risk of bleeding associated with the dosage
of FRAGMIN® recommended for these indications.
- FRAGMIN®, like other anticoagulants, should be used with extreme
caution in patients who have an increased risk of hemorrhage; bleeding can occur
at any site during therapy. An unexpected drop in hematocrit or blood pressure should
lead to a search for a bleeding site.
- FRAGMIN® should be used with caution in patients with bleeding diathesis,
thrombocytopenia or platelet defects, severe liver or kidney insufficiency, hypertensive
or diabetic retinopathy, and recent gastrointestinal bleeding.
- FRAGMIN® should be used with extreme caution in patients
with history of heparin-induced thrombocytopenia.
- In FRAGMIN® clinical trials supporting non-cancer indications, platelet
count of <50,000/mm3 occurred in <1% of patients.
- In FRAGMIN® clinical trials supporting the extended treatment of
symptomatic VTE in patients with cancer, platelet counts of <100,000/mm3 occurred
in 13.6% of patients, including 6.5% who also had platelet counts less than 50,000/mm3.
In the same clinical trial, thrombocytopenia was reported as an adverse event in
10.9% of patients in the FRAGMIN® arm and 8.1% of patients in the
oral anticoagulant arm. FRAGMIN® dose was decreased or interrupted
in patients whose platelet counts fell below 100,000/mm3.
- Thrombocytopenia of any degree should be monitored closely. Heparin-induced thrombocytopenia
can occur with administration of FRAGMIN®. The incidence of this
complication is unknown at present. In clinical practice, rare cases of thrombocytopenia
with thrombosis have also been observed.
- Each multiple-dose vial of FRAGMIN® contains benzyl alcohol as a preservative. Benzyl alcohol has been reported to be associated with a fatal "Gasping Syndrome" in premature infants. Because benzyl alcohol may cross the placenta, use caution when administering FRAGMIN® preserved with benzyl alcohol to pregnant women. If anticoagulation with FRAGMIN® is needed during pregnancy, use preservative-free formulations, where possible.
- Periodic routine complete blood counts, including platelet count, blood chemistry, and stool occult blood tests are recommended during the course of treatment with FRAGMIN®.
- The most commonly reported side effect is hematoma at the injection site.
- Allergic reactions (i.e., pruritus, rash, fever, injection site reaction, bulleous eruption) have occurred. A few cases of anaphylactoid reactions have been reported.
- Use FRAGMIN® with care in patients receiving oral anticoagulants, platelet inhibitors, and thrombolytic agents because of increased risk of bleeding.
- FRAGMIN® cannot be used interchangeably (unit for unit) with unfractionated heparin or other low molecular weight heparins.
- FRAGMIN® Injection is not intended for intramuscular administration.
For more information about FRAGMIN, please see Full Product Information.
HEXALEN® (altretamine) is indicated for use as a single
agent in the palliative treatment of patients
with persistent or recurrent ovarian cancer following first-line therapy with a
cisplatin and/or alkylating agent-based
- HEXALEN® should only be given under the supervision of a
physician experienced in the use of antineoplastic agents.
- Peripheral blood counts should be monitored at least monthly, prior to the initiation
of each course of HEXALEN®, and as clinically indicated
(see Adverse Reactions).
- Because of the possibility of HEXALEN®-related neurotoxicity,
neurologic examination should be performed regularly during HEXALEN®
administration (see Adverse Reactions).
- HEXALEN® is contraindicated in patients who have shown hypersensitivity
to it. HEXALEN® should not be employed in patients with
preexisting severe bone marrow depression or severe neurologic toxicity. HEXALEN®
has been administered safely, however, to patients heavily pretreated with
cisplatin and/or alkylating agents, including patients with preexisting cisplatin
neuropathies. Careful monitoring of neurologic function in these patients is essential.
Pregnancy: Category D
- HEXALEN® has been shown to be embryotoxic and teratogenic
in rats and rabbits when given at doses 2 and 10 times the human dose. HEXALEN®
may cause fetal damage when administered to a pregnant woman. If HEXALEN®
is used during pregnancy, or if the patient becomes pregnant while taking
the drug, the patient should be apprised of the potential hazard to the fetus. Women
of childbearing potential should be advised to avoid becoming pregnant.
- Neurologic examination should be performed regularly (see Adverse Reactions).
- Laboratory Tests
- Peripheral blood counts should be monitored at least monthly, prior to the initiation
of each course of
HEXALEN®, and as clinically indicated (see Adverse Reactions).
- Drug Interactions
- Concurrent administration of HEXALEN® and antidepressants
of the MAO inhibitor class may cause severe orthostatic hypotension (see Warnings
section). Cimetidine, an inhibitor of microsomal drug
metabolism, increased altretamine’s half-life and toxicity in a rat model.
- Data from a randomized trial of HEXALEN® and cisplatin plus
or minus pyridoxine in ovarian cancer indicated that pyridoxine significantly reduced
neurotoxicity; however, it adversely affected response duration suggesting that
pyridoxine should not be administered with HEXALEN® and/or
- Carcinogenesis, Mutagenesis and Impairment of Fertility
- The carcinogenic potential of HEXALEN® has not been studied
in animals, but drugs with similar mechanisms of action have been shown to be carcinogenic.
HEXALEN® was weakly mutagenic when tested in strain TA100
of Salmonella typhimurium. HEXALEN® administered to female
days prior to breeding through the gestation period had no adverse effect on fertility,
but decreased post-natal survival at 120 mg/m2/day and was embryocidal at 240 mg/m2/day.
Administration of 120 mg/m2/day HEXALEN® to male rats for
60 days prior to mating resulted in testicular atrophy, reduced fertility and a
possible dominant lethal mutagenic effect. Male rats treated with HEXALEN®
at 450 mg/m2/day for 10 days had decreased spermatogenesis, atrophy of
testes, seminal vesicles and ventral prostate.
- Pregnancy: Category D under CONTRAINDICATIONS.
- It is not known whether altretamine is excreted in human milk. Because there is
a possibility of toxicity in nursing infants secondary to HEXALEN®
treatment of the mother, it is recommended that breast feeding be discontinued
if the mother is treated with HEXALEN®.
- The safety and effectiveness of HEXALEN® in children have
not been established.
- With continuous high-dose daily HEXALEN®, nausea and vomiting
of gradual onset occur frequently. Although in most instances these symptoms are
controllable with anti-emetics, at times the severity requires HEXALEN®
dose reduction or, rarely, discontinuation of HEXALEN®
therapy. In some instances, a tolerance of these symptoms develops after several
weeks of therapy. The incidence and severity of nausea and vomiting are reduced
with moderate-dose administration of HEXALEN®. In 2 clinical
studies of single-agent HEXALEN® utilizing a moderate, intermittent
dose and schedule, only 1 patient (1%) discontinued HEXALEN®
due to severe nausea and vomiting.
- Peripheral neuropathy and central nervous system symptoms (mood disorders, disorders
of consciousness, ataxia, dizziness, vertigo) have been reported. They are more
likely to occur in patients receiving continuous high-dose daily HEXALEN®
(altretamine) than moderate-dose HEXALEN® administered
on an intermittent schedule. Neurologic toxicity has been reported to be reversible
when therapy is discontinued. Data from a randomized trial of HEXALEN®
and cisplatin plus or minus pyridoxine in ovarian cancer indicated that
pyridoxine significantly reduced neurotoxicity; however, it adversely affected response
duration suggesting that pyridoxine should not be administered with HEXALEN®
and/or cisplatin (1).
- HEXALEN® causes mild to moderate dose-related myelosuppression.
Leukopenia below 3000 WBC/mm3 occurred in <15% of patients on a variety of intermittent
or continuous dose regimens. Less than 1% had leukopenia below 1000 WBC/mm3. Thrombocytopenia
below 50,000 platelets/mm3 was seen in <10% of patients. When given in doses
of 8-12 mg/kg/day over a 21 day course, nadirs of leukocyte and platelet counts
were reached by 3-4 weeks, and normal counts were regained by 6 weeks. With continuous
administration at doses of 6-8 mg/kg/day, nadirs are reached in 6-8 weeks (median).
Please see the HEXALEN® full prescribing information including Boxed WARNINGS
and additional important safety information.
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This site was last modified on : January 24, 2013 at 4:30m ET