ENOXAPARIN SODIUM injection

Krajina: Spojené štáty

Jazyk: angličtina

Zdroj: NLM (National Library of Medicine)

Aktívna zložka:

enoxaparin sodium (UNII: 8NZ41MIK1O) (enoxaparin - UNII:E47C0NF7LV)

Dostupné z:

Meitheal Pharmaceuticals Inc.

Spôsob podávania:

SUBCUTANEOUS

Typ predpisu:

PRESCRIPTION DRUG

Terapeutické indikácie:

Enoxaparin Sodium Injection is indicated for the prophylaxis of deep vein thrombosis (DVT), which may lead to pulmonary embolism (PE): - in patients undergoing abdominal surgery who are at risk for thromboembolic complications [see Clinical Studies (14.1)] - in patients undergoing hip replacement surgery, during and following hospitalization - in patients undergoing knee replacement surgery - in medical patients who are at risk for thromboembolic complications due to severely restricted mobility during acute illness Enoxaparin Sodium Injection is indicated for: - the inpatient treatment of acute deep vein thrombosis with or without pulmonary embolism , when administered in conjunction with warfarin sodium - the outpatient treatment of acute deep vein thrombosis without pulmonary embolism , when administered in conjunction with warfarin sodium Enoxaparin Sodium Injection is indicated for the prophylaxis of ischemic complications of unstable angina and non-Q-wave myocardial infarction, when concurrently administered with aspirin. Enoxaparin Sodium Injection, when administered concurrently with aspirin, has been shown to reduce the rate of the combined endpoint of recurrent myocardial infarction or death in patients with acute ST-segment elevation myocardial infarction (STEMI) receiving thrombolysis and being managed medically or with percutaneous coronary intervention (PCI). Enoxaparin sodium is contraindicated in patients with: - Active major bleeding - History of immune-mediated heparin-induced thrombocytopenia (HIT) within the past 100 days or in the presence of circulating antibodies [see Warnings and Precautions (5.4)] - Known hypersensitivity to enoxaparin sodium (e.g., pruritus, urticaria, anaphylactic/anaphylactoid reactions) [see Adverse Reactions (6.2)] - Known hypersensitivity to heparin or pork products - Known hypersensitivity to benzyl alcohol [see Warnings and Precautions (5.8)] Risk Summary Placental transfer of enoxaparin was observed in the animal studies. Human data from a retrospective cohort study, which included 693 live births, suggest that enoxaparin does not increase the risk of major developmental abnormalities (see Data) . Based on animal data, enoxaparin sodium is not predicted to increase the risk of major developmental abnormalities (see Data) . Adverse outcomes in pregnancy occur regardless of the health of the mother or the use of medications. The estimated background risk of major birth defects and miscarriage for the indicated populations is unknown. In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2% to 4% and 15% to 20%, respectively. Clinical Considerations Pregnancy alone confers an increased risk for thromboembolism that is even higher for women with thromboembolic disease and certain high risk pregnancy conditions. While not adequately studied, pregnant women with mechanical prosthetic heart valves may be at even higher risk for thrombosis [see Warnings and Precautions (5.7) and Use in Specific Populations (8.6)] . Pregnant women with thromboembolic disease, including those with mechanical prosthetic heart valves and those with inherited or acquired thrombophilias, have an increased risk of other maternal complications and fetal loss regardless of the type of anticoagulant used. All patients receiving anticoagulants, including pregnant women, are at risk for bleeding. Pregnant women receiving enoxaparin sodium should be carefully monitored for evidence of bleeding or excessive anticoagulation. Consideration for use of a shorter acting anticoagulant should be specifically addressed as delivery approaches [see Boxed Warning] . Hemorrhage can occur at any site and may lead to death of mother and/or fetus. Pregnant women should be apprised of the potential hazard to the fetus and the mother if enoxaparin sodium is administered during pregnancy. It is not known if monitoring of anti-Factor Xa activity and dose adjustment (by weight or anti-Factor Xa activity) of enoxaparin sodium affect the safety and the efficacy of the drug during pregnancy. Cases of “gasping syndrome” have occurred in premature infants when large amounts of benzyl alcohol have been administered (99-405 mg/kg/day). The multi-dose vial of enoxaparin sodium contains 15 mg benzyl alcohol per 1 mL as a preservative [see Warnings and Precautions (5.8)] . Data Human Data There are no adequate and well-controlled studies in pregnant women. A retrospective study reviewed the records of 604 women who used enoxaparin sodium during pregnancy. A total of 624 pregnancies resulted in 693 live births. There were 72 hemorrhagic events (11 serious) in 63 women. There were 14 cases of neonatal hemorrhage. Major congenital anomalies in live births occurred at rates (2.5%) similar to background rates. There have been postmarketing reports of fetal death when pregnant women received enoxaparin sodium. Causality for these cases has not been determined. Insufficient data, the underlying disease, and the possibility of inadequate anticoagulation complicate the evaluation of these cases. A clinical study using enoxaparin sodium in pregnant women with mechanical prosthetic heart valves has been conducted [see Warnings and Precautions (5.7)] . Animal Data Teratology studies have been conducted in pregnant rats and rabbits at subcutaneous doses of enoxaparin up to 15 times the recommended human dose (by comparison with 2 mg/kg as the maximum recommended daily dose). There was no evidence of teratogenic effects or fetotoxicity due to enoxaparin. Because animal reproduction studies are not always predictive of human response, this drug should be used during pregnancy only if clearly needed. Risk Summary It is unknown whether enoxaparin sodium is excreted in human milk. In lactating rats, the passage of enoxaparin or its metabolites in the milk is very limited. There is no information available on the effect of enoxaparin or its metabolites on the breastfed child, or on the milk production. The developmental and health benefits of breastfeeding should be considered along with the mother's clinical need for enoxaparin sodium and any potential adverse effects on the breastfed child from enoxaparin sodium or from the underlying maternal condition. Safety and effectiveness of enoxaparin sodium in pediatric patients have not been established. Enoxaparin sodium is not approved for use in neonates or infants. Serious adverse reactions including fatal reactions and the “gasping syndrome” occurred in premature neonates and low-birth-weight infants in the neonatal intensive care unit who received drugs containing benzyl alcohol as a preservative. In these cases, benzyl alcohol dosages of 99 to 234 mg/kg/day produced high levels of benzyl alcohol and its metabolites in the blood and urine (blood levels of benzyl alcohol were 0.61 to 1.378 mmol/L). Additional adverse reactions included gradual neurological deterioration, seizures, intracranial hemorrhage, hematologic abnormalities, skin breakdown, hepatic and renal failure, hypotension, bradycardia, and cardiovascular collapse. Preterm, low-birth-weight infants may be more likely to develop these reactions because they may be less able to metabolize benzyl alcohol. The minimum amount of benzyl alcohol at which serious adverse reactions may occur is not known. Enoxaparin sodium multi-dose vials contain 15 mg/mL of benzyl alcohol (at the dose of 1.5 mg/kg twice a day, benzyl alcohol exposure in patients is 0.45 mg/kg daily) [see Warnings and Precautions (5.8)] . Prevention of Deep Vein Thrombosis in Hip, Knee and Abdominal Surgery; Treatment of Deep Vein Thrombosis, Prevention of Ischemic Complications of Unstable Angina and Non-Q-Wave Myocardial Infarction Over 2800 patients, 65 years and older, have received enoxaparin sodium in clinical trials. The efficacy of enoxaparin sodium in the geriatric (≥65 years) was similar to that seen in younger patients (<65 years). The incidence of bleeding complications was similar between geriatric and younger patients when 30 mg every 12 hours or 40 mg once a day doses of enoxaparin sodium were employed. The incidence of bleeding complications was higher in geriatric patients as compared to younger patients when enoxaparin sodium was administered at doses of 1.5 mg/kg once a day or 1 mg/kg every 12 hours. The risk of enoxaparin sodium-associated bleeding increased with age. Serious adverse events increased with age for patients receiving enoxaparin sodium. Other clinical experience (including postmarketing surveillance and literature reports) has not revealed additional differences in the safety of enoxaparin sodium between geriatric and younger patients. Careful attention to dosing intervals and concomitant medications (especially antiplatelet medications) is advised. Enoxaparin sodium should be used with care in geriatric patients who may show delayed elimination of enoxaparin. Monitoring of geriatric patients with low body weight (<45 kg) and those predisposed to decreased renal function should be considered [see Warnings and Precautions (2.6) and Clinical Pharmacology (12.3)] . Treatment of Acute ST-Segment Elevation Myocardial Infarction In the clinical study for treatment of acute ST-segment elevation myocardial infarction, there was no evidence of difference in efficacy between patients ≥75 years of age (n=1241) and patients less than 75 years of age (n=9015). Patients ≥75 years of age did not receive a 30 mg intravenous bolus prior to the normal dosage regimen and had their subcutaneous dose adjusted to 0.75 mg/kg every 12 hours [see Dosage and Administration (2.4)] . The incidence of bleeding complications was higher in patients ≥65 years of age as compared to younger patients (<65 years). The use of enoxaparin sodium has not been adequately studied for thromboprophylaxis in patients with mechanical prosthetic heart valves and has not been adequately studied for long-term use in this patient population. Isolated cases of prosthetic heart valve thrombosis have been reported in patients with mechanical prosthetic heart valves who have received enoxaparin sodium for thromboprophylaxis. Some of these cases were pregnant women in whom thrombosis led to maternal and fetal deaths. Insufficient data, the underlying disease and the possibility of inadequate anticoagulation complicate the evaluation of these cases. Pregnant women with mechanical prosthetic heart valves may be at higher risk for thromboembolism [see Warnings and Precautions (5.7)] . In patients with renal impairment, there is an increase in exposure of enoxaparin sodium. All such patients should be observed carefully for signs and symptoms of bleeding. Because exposure of enoxaparin sodium is significantly increased in patients with severe renal impairment (creatinine clearance <30 mL/min), a dosage adjustment is recommended for therapeutic and prophylactic dosage ranges. No dosage adjustment is recommended in patients with creatinine clearance 30 to <50 mL/min and creatinine clearance 50 to 80 mL/min [see Dosage and Administration (2.3) and Clinical Pharmacology (12.3)] . In patients with renal failure, treatment with enoxaparin sodium has been associated with the development of hyperkalemia [see Adverse Reactions (6.2)]. An increase in exposure of enoxaparin sodium with prophylactic dosages (non-weight adjusted) has been observed in low-weight women (<45 kg) and low-weight men (<57 kg). Observe low-weight patients frequently for signs and symptoms of bleeding [see Clinical Pharmacology (12.3)] . Obese patients are at higher risk for thromboembolism. The safety and efficacy of prophylactic doses of enoxaparin sodium in obese patients (BMI >30 kg/m2 ) has not been fully determined and there is no consensus for dose adjustment. Observe these patients carefully for signs and symptoms of thromboembolism.

Prehľad produktov:

Enoxaparin Sodium Injection, USP is a clear, colorless to pale yellow solution and is supplied as follows: * Strength represents the number of milligrams of enoxaparin sodium in Water for Injection. † Approximate anti-Factor Xa activity based on reference to the W.H.O. First International Low Molecular Weight Heparin Reference Standard. § Each Enoxaparin Sodium Injection, USP multi-dose vial contains 15 mg benzyl alcohol per 1 mL as a preservative. Store at 20° to 25°C (68° to 77°F); excursions permitted between 15° to 30°C (59° to 86°F). [See USP Controlled Room Temperature.] Store in the original carton or packaging until ready to use. Do not store the multi-dose vials for more than 28 days after the first use. Sterile, Nonpyrogenic. The container closure is not made with natural rubber latex.

Stav Autorizácia:

Abbreviated New Drug Application

Súhrn charakteristických

ENOXAPARIN SODIUM- ENOXAPARIN SODIUM INJECTION
MEITHEAL PHARMACEUTICALS INC.
----------
HIGHLIGHTS OF PRESCRIBING INFORMATION
THESE HIGHLIGHTS DO NOT INCLUDE ALL THE INFORMATION NEEDED TO USE
ENOXAPARIN SODIUM
INJECTION SAFELY AND EFFECTIVELY. SEE FULL PRESCRIBING INFORMATION FOR
ENOXAPARIN SODIUM
INJECTION.
ENOXAPARIN SODIUM INJECTION, FOR SUBCUTANEOUS AND INTRAVENOUS USE
INITIAL U.S. APPROVAL: 1993
WARNING: SPINAL/EPIDURAL HEMATOMAS
_SEE FULL PRESCRIBING INFORMATION FOR COMPLETE BOXED WARNING._
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, AND OTHER
ANTICOAGULANTS
A HISTORY OF TRAUMATIC OR REPEATED EPIDURAL OR SPINAL PUNCTURES
A HISTORY OF SPINAL DEFORMITY OR SPINAL SURGERY
OPTIMAL TIMING BETWEEN THE ADMINISTRATION OF ENOXAPARIN SODIUM AND
NEURAXIAL
PROCEDURES IS NOT KNOWN
MONITOR PATIENTS FREQUENTLY FOR SIGNS AND SYMPTOMS OF NEUROLOGICAL
IMPAIRMENT. IF
NEUROLOGICAL COMPROMISE IS NOTED, URGENT TREATMENT IS NECESSARY. (5.1,
7)
INDICATIONS AND USAGE
Enoxaparin Sodium Injection is a low molecular weight heparin (LMWH)
indicated for:
Prophylaxis of deep vein thrombosis (DVT) in abdominal surgery, hip
replacement surgery, knee
replacement surgery, or medical patients with severely restricted
mobility during acute illness (1.1)
Inpatient treatment of acute DVT with or without pulmonary embolism
(1.2)
Outpatient treatment of acute DVT without pulmonary embolism (1.2)
Prophylaxis of ischemic complications of unstable angina and
non-Q-wave myocardial infarction (MI)
(