Enoxarin 40 & 60 Injection

ENOXARIN 40

Each Pre-filled syringe contains :

Enoxaparin Sodium IP 40 mg

Water for Injections IP q.s. to 0.4 ml

ENOXARIN 60

Each Pre-filled syringe contains :

Enoxaparin Sodium IP 60 mg

Water for Injections IP q.s. to 0.6 ml

ENOXARIN Injection is a sterile aqueous solutions containing Enoxaparin Sodium, a low molecular weight heparin. The average molecular weight is about 4,500 daltons.

Pharmacodynamics

In humans, Enoxaparin given at a dose of 1.5 mg/kg subcutaneously (SC) is characterized by a higher ratio of anti-Factor Xa to anti-Factor IIa activity (mean±SD, 14.0±3.1) (based on areas under anti-Factor activity versus time curves) compared to the ratios observed for heparin (mean±SD, 1.22±0.13). Increases of up to 1.8 times the control values were seen in the thrombin time (TT) and the activated partial thromboplastin time (aPTT). Enoxaparin at a 1 mg/kg dose (100 mg/mL concentration), administered SC every 12 hours to patients in a large clinical trial resulted in aPTT values of 45 seconds or less in the majority of patients (n =1607). A 30 mg IV bolus immediately followed by a 1 mg/kg SC administration resulted in aPTT post-injection values of 50 seconds. The average aPTT prolongation value on Day 1 was about 16% higher than on Day 4.

Pharmacokinetics

Absorption : Pharmacokinetic trials were conducted using the 100 mg/mL formulation. Maximum anti Factor Xa and anti-thrombin (anti-Factor IIa) activities occur 3 to 5 hours after SC injection of Enoxaparin. Mean peak anti-Factor Xa activity was 0.16 IU/mL (1.58 mcg/mL) and 0.38 IU/mL (3.83 mcg/mL) after the 20 mg and the 40 mg clinically tested SC doses, respectively. Mean (n = 46) peak anti-Factor Xa activity was 1.1 IU/mL at steady state in patients with unstable angina receiving 1 mg/kg SC every 12 hours for 14 days. Mean absolute bioavailability of Enoxaparin, after 1.5 mg/kg given SC, based on anti-Factor Xa activity is approximately 100% in healthy subjects. A 30 mg IV bolus immediately followed by a 1 mg/kg SC every 12 hours provided initial peak anti-Factor Xa levels of 1.16 IU/mL (n=16) and average exposure corresponding to 84% of steady-state levels. Steady state is achieved on the second day of treatment. Enoxaparin pharmacokinetics appear to be linear over the recommended dosage ranges. After repeated subcutaneous administration of 40 mg once daily and 1.5 mg/kg once daily regimens in healthy volunteers, the steady state is reached on day 2 with an average exposure ratio about 15% higher than after a single dose. Steady-state Enoxaparin activity levels are well predicted by single-dose pharmacokinetics. After repeated subcutaneous administration of the 1 mg/kg twice daily regimen, the steady state is reached from day 4 with mean exposure about 65% higher than after a single dose and mean peak and trough levels of about 1.2 and 0.52 IU/mL, respectively. Based on Enoxaparin Sodium pharmacokinetics, this difference in steady state is expected and within the therapeutic range.

Distribution : The volume of distribution of anti-Factor Xa activity is about 4.3 L.

Elimination : Following intravenous (IV) dosing, the total body clearance of Enoxaparin is 26 mL/min. After IV dosing of Enoxaparin labeled with the gamma-emitter, 99m Tc, 40% of radioactivity and 8 to 20% of anti-Factor Xa activity were recovered in urine in 24 hours. Elimination half-life based on antiFactor Xa activity was 4.5 hours after a single SC dose to about 7 hours after repeated dosing. Significant anti-Factor Xa activity persists in plasma for about 12 hours following a 40 mg SC once a day dose. Following SC dosing, the apparent clearance (CL/F) of Enoxaparin is approximately 15 mL/min.

Metabolism : Enoxaparin Sodium is primarily metabolized in the liver by desulfation and/or depolymerization to lower molecular weight species with much reduced biological potency. Renal clearance of active fragments represents about 10% of the administered dose and total renal excretion of active and non-active fragments 40% of the dose.

Indications :

Prophylaxis of Deep Vein Thrombosis

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.
• 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.

Treatment of Acute Deep Vein Thrombosis

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.

Prophylaxis of Ischemic Complications of Unstable Angina and Non-Q-Wave Myocardial Infarction

Treatment of Acute ST-Segment Elevation Myocardial Infarction

Contraindications:

• Active major bleeding
• Thrombocytopenia associated with a positive in vitro test for anti-platelet antibody in the presence of Enoxaparin Sodium
• Known hypersensitivity to Enoxaparin Sodium (e.g., pruritus, urticaria, anaphylactic/ anaphylactoid reactions)
• Known hypersensitivity to heparin or pork products

Dosage & Administration :

Abdominal Surgery : In patients undergoing abdominal surgery who are at risk for thromboembolic complications, the recommended dose of Enoxaparin Sodium Injection is 40 mg once a day administered by SC injection with the initial dose given 2 hours prior to surgery. The usual duration of administration is 7 to 10 days; up to 12 days administration has been administered in clinical trials.

Hip or Knee Replacement Surgery : In patients undergoing hip or knee replacement surgery, the recommended dose of Enoxaparin Sodium Injection is 30 mg every 12 hours administered by SC injection. Provided that hemostasis has been established, the initial dose should be given 12 to 24 hours after surgery. For hip replacement surgery, a dose of 40 mg once a day SC, given initially 12 (±3) hours prior to surgery, may be considered. Following the initial phase of thromboprophylaxis in hip replacement surgery patients, it is recommended that continued prophylaxis with Enoxaparin Sodium Injection 40 mg once a day be administered by SC injection for 3 weeks. The usual duration of administration is 7 to 10 days; up to 14 days administration has been administered in clinical trials.

Medical Patients During Acute Illness : In medical patients at risk for thromboembolic complications due to severely restricted mobility during acute illness, the recommended dose of Enoxaparin Sodium Injection is 40 mg once a day administered by SC injection. The usual duration of administration is 6 to 11 days; up to 14 days of Enoxaparin Sodium Injection has been administered in the controlled clinical trial.

Treatment of Deep Vein Thrombosis with or without Pulmonary Embolism : In outpatient treatment, patients with acute deep vein thrombosis without pulmonary embolism who can be treated at home, the recommended dose of Enoxaparin Sodium Injection is 1 mg/kg every 12 hours administered SC. In inpatient (hospital) treatment, patients with acute deep vein thrombosis with pulmonary embolism or patients with acute deep vein thrombosis without pulmonary embolism (who are not candidates for outpatient treatment), the recommended dose of Enoxaparin Sodium Injection is 1 mg/kg every 12 hours administered SC or 1.5 mg/kg once a day administered SC at the same time every day. In both outpatient and inpatient (hospital) treatments, warfarin Sodium therapy should be initiated when appropriate (usually within 72 hours of Enoxaparin Sodium Injection). Enoxaparin Sodium Injection should be continued for a minimum of 5 days and until a therapeutic oral anticoagulant effect has been achieved (International Normalization Ratio 2.0 to 3.0). The average duration of administration is 7 days; up to 17 days of Enoxaparin Sodium Injection administration has been administered in controlled clinical trials.

Unstable Angina and Non-Q-Wave Myocardial Infarction : In patients with unstable angina or non-Q-wave myocardial infarction, the recommended dose of Enoxaparin Sodium Injection is 1 mg/kg administered SC every 12 hours in conjunction with oral aspirin therapy (100 to 325 mg once daily). Treatment with Enoxaparin Sodium Injection should be prescribed for a minimum of 2 days and continued until clinical stabilization. The usual duration of treatment is 2 to 8 days; up to 12.5 days of Enoxaparin Sodium Injection has been administered in clinical trials.

Treatment of Acute ST-Segment Elevation Myocardial Infarction : In patients with acute ST-segment elevation myocardial infarction, the recommended dose of Enoxaparin Sodium Injection is a single IV bolus of 30 mg plus a 1 mg/kg SC dose followed by 1 mg/kg administered SC every 12 hours (maximum 100 mg for the first two doses only, followed by 1 mg/kg dosing for the remaining doses). Dosage adjustments are recommended in patients ≥75 years of age. All patients should receive aspirin as soon as they are identified as having STEMI and maintained with 75 to 325 mg once daily unless contraindicated. When administered in conjunction with a thrombolytic (fibrin-specific or non-fibrin specific), Enoxaparin Sodium Injection should be given between 15 minutes before and 30 minutes after the start of fibrinolytic therapy. In the pivotal clinical study, the Enoxaparin Sodium Injection treatment duration was 8 days or until hospital discharge, whichever came first. An optimal duration of treatment is not known, but it is likely to be longer than 8 days. For patients managed with percutaneous coronary intervention (PCI) : If the last Enoxaparin Sodium Injection SC administration was given less than 8 hours before balloon inflation, no additional dosing is needed. If the last Enoxaparin Sodium Injection SC administration was given more than 8 hours before balloon inflation, an IV bolus of 0.3 mg/kg of Enoxaparin Sodium Injection should be administered.

Renal impairment : Although no dose adjustment is recommended in patients with moderate (creatinine clearance 30–50 mL/min) and mild (creatinine clearance 50–80 mL/min) renal impairment, all such patients should be observed carefully for signs and symptoms of bleeding. The recommended prophylaxis and treatment dosage regimens for patients with severe renal impairment (creatinine clearance < 30 mL/min) are described in the table below

For treatment of acute ST-segment elevation myocardial infarction in geriatric patients ≥75 years of age, do not use an initial intravenous bolus. Initiate dosing with 0.75 mg/kg subcutaneously every 12 hours (maximum 75 mg for the first two doses only, followed by 0.75 mg/kg dosing for the remaining doses). No dose adjustment is necessary for other indications in geriatric patients unless kidney function is impaired.

In clinical studies, haemorrhages, thrombocytopenia and thrombocytosis were the most commonly reported reactions Other adverse reactions observed in clinical studies and reported in post-marketing experience (* indicates reactions from post-marketing experience) are detailed below. Frequencies are defined as follows : very common (≥ 1/10); common (≥ 1/100 to < 1/10); uncommon (≥ 1/1000 to < 1/100); rare (≥ 1/10,000 to <1/1,000); and very rare (< 1/10,000) or not known (cannot be estimated from available data). Within each system organ class, adverse reactions are presented in order of decreasing seriousness.

Blood and the lymphatic system disorders

• Common : Haemorrhage, haemorrhagic anaemia*, thrombocytopenia, thrombocytosis
• Rare : Eosinophilia*, cases of immuno-allergic thrombocytopenia with thrombosis; in some of them thrombosis was complicated by organ infarction or limb ischaemia (see section 4.4).

Immune system disorders

• Common : Allergic reaction
• Rare : Anaphylactic/Anaphylactoid reactions including shock*

Nervous system disorders

• Common : Headache*

Vascular disorders

• Rare : Spinal haematoma* (or neuraxial haematoma). These reactions have resulted in varying degrees of neurologic injuries including long-term or permanent paralysis (see section 4.4).

Hepato-biliary disorders

• Very common : Hepatic enzyme increases (mainly transaminases > 3 times the upper limit of normality)
• Uncommon : Hepatocellular liver injury *
• Rare : Cholestatic liver injury*

Skin and subcutaneous tissue disorders

• Common : Urticaria, pruritus, erythema
• Uncommon : Bullous dermatitis
• Rare : Alopecia, cutaneous vasculitis*, skin necrosis* usually occurring at the injection site (these phenomena have been usually preceded by purpura or erythematous plaques, infiltrated and painful).
• Injection site nodules* (inflammatory nodules, which were not cystic enclosure of Enoxaparin). They resolve after a few days and should not cause treatment discontinuation.

Musculoskeletal, connective tissue and bone disorders

• Rare : Osteoporosis* following long term therapy (greater than 3 months)

General disorders and administration site conditions

• Common : Injection site haematoma, injection site pain, other injection site reaction (such as oedema, haemorrhage, hypersensitivity, inflammation, mass, pain, or reaction)
• Uncommon : Local irritation, skin necrosis at injection site

Investigations

• Rare : Hyperkalaemia

Description of selected adverse reactions

Haemorrhages

These included major haemorrhages, reported at most in 4.2% of the patients (surgical patients). Some of these cases have been fatal. In surgical patients, haemorrhage complications were considered major : (1) if the haemorrhage caused a significant clinical event, or (2) if accompanied by haemoglobin decrease ≥ 2 g/dL or transfusion of 2 or more units of blood products. Retroperitoneal and intracranial haemorrhages were always considered major. As with other anticoagulants, haemorrhage may occur in the presence of associated risk factors such as : organic lesions liable to bleed, invasive procedures or the concomitant use of medications affecting haemostasis.

Increased Risk of Hemorrhage

1. Cases of epidural or spinal hemorrhage and subsequent hematomas have been reported with the use of Enoxaparin Sodium Injection and epidural or spinal anesthesia/analgesia or spinal puncture procedures, resulting in long-term or permanent paralysis. The risk of these events is higher with the use of postoperative indwelling epidural catheters, with the concomitant use of additional drugs affecting hemostasis such as NSAIDs, with traumatic or repeated epidural or spinal puncture, or in patients with a history of spinal surgery or spinal deformity.
2. Placement or removal of an epidural catheter or lumbar puncture is best performed when the anticoagulant effect of Enoxaparin is low. Placement or removal of a catheter should be delayed for at least 12 hours after administration of lower doses (30 mg once or twice daily or 40 mg once daily) of Enoxaparin Sodium Injection, and at least 24 hours after the administration of higher doses (0.75 mg/kg twice daily, 1 mg/kg twice daily, or 1.5 mg/kg once daily) of Enoxaparin Sodium Injection.
3. Patients receiving the 0.75 mg/kg twice daily dose or the 1 mg/kg twice daily dose should not receive the second Enoxaparin dose in the twice daily regimen to allow a longer delay before catheter placement or removal. Likewise, although a specific recommendation for timing of a subsequent Enoxaparin Sodium Injection dose after catheter removal cannot be made, consider delaying this next dose for at least four hours, based on a benefit-risk assessment considering both the risk for thrombosis and the risk for bleeding in the context of the procedure and patient risk factors.
4. For patients with creatinine clearance <30mL/minute, additional considerations are necessary because elimination of Enoxaparin is more prolonged; consider doubling the timing of removal of a catheter, at least 24 hours for the lower prescribed dose of Enoxaparin Sodium Injection (30 mg once daily) and at least 48 hours for the higher dose (1 mg/kg/day).
5. Should the physician decide to administer anticoagulation in the context of epidural or spinal anesthesia/analgesia or lumbar puncture, frequent monitoring must be exercised to detect any signs and symptoms of neurological impairment such as midline back pain, sensory and motor deficits (numbness or weakness in lower limbs), bowel and/or bladder dysfunction
6. Instruct patients to report immediately if they experience any of the above signs or symptoms. If signs or symptoms of spinal hematoma are suspected, initiate urgent diagnosis and treatment including consideration for spinal cord decompression even though such treatment may not prevent or reverse neurological sequelae.
7. Enoxaparin Sodium injection should be used with extreme caution in conditions with increased risk of hemorrhage, such as bacterial endocarditis, congenital or acquired bleeding disorders, active ulcerative and angiodysplastic gastrointestinal disease, hemorrhagic stroke, or shortly after brain, spinal, or ophthalmological surgery, or in patients treated concomitantly with platelet inhibitors. Major hemorrhages including retroperitoneal and intracranial bleeding have been repor ted. Some of these cases have been fatal. Bleeding can occur at any site during therapy with Enoxaparin Sodium injection. An unexplained fall in hematocrit or blood pressure should lead to a search for a bleeding site.

Percutaneous Coronary Revascularization Procedures

To minimize the risk of bleeding following the vascular instrumentation during the treatment of unstable angina, non-Q-wave myocardial infarction, and acute ST-segment elevation myocardial infarction, adhere precisely to the intervals recommended between Enoxaparin Sodium injection doses. It is important to achieve hemostasis at the puncture site after PCI. In case a closure device is used, the sheath can be removed immediately. If a manual compression method is used, sheath should be removed 6 hours after the last IV/SC Enoxaparin Sodium injection. If the treatment with Enoxaparin Sodium is to be continued, the next scheduled dose should be given no sooner than 6 to 8 hours after sheath removal. The site of the procedure should be observed for signs of bleeding or hematoma formation.

Use of Enoxaparin Sodium Injection with Concomitant Medical Conditions

Enoxaparin Sodium injection should be used with care in patients with a bleeding diathesis, uncontrolled arterial hypertension or a history of recent gastrointestinal ulceration, diabetic retinopathy, renal dysfunction and hemorrhage

History of Heparin-Induced Thrombocytopenia

Enoxaparin Sodium injection should be used with extreme caution in patients with a history of heparin induced thrombocytopenia.

Thrombocytopenia

Thrombocytopenia can occur with the administration of Enoxaparin Sodium injection. Thrombocytopenia of any degree should be monitored closely. If the platelet count falls below 100,000/mm3, Enoxaparin Sodium injection should be discontinued. Cases of heparin-induced thrombocytopenia with thrombosis have also been observed in clinical practice. Some of these cases were complicated by organ infarction, limb ischemia, or death

Interchangeability with Other Heparins

Enoxaparin Sodium injection cannot be used interchangeably (unit for unit) with heparin or other low molecular weight heparins as they differ in manufacturing process, molecular weight distribution, anti- Xa and anti-IIa activities, units, and dosage. Each of these medicines has its own instructions for use.

Pregnant Women with Mechanical Prosthetic Heart Valves

The use of Enoxaparin Sodium injection for thromboprophylaxis in pregnant women with mechanical prosthetic heart valves has not been adequately studied. There also have been isolated postmarketing reports of valve thrombosis in pregnant women with mechanical prosthetic heart valves while receiving Enoxaparin for thromboprophylaxis. Women with mechanical prosthetic heart valves may be at higher risk for thromboembolism during pregnancy, and, when pregnant, have a higher rate of fetal loss from stillbirth, spontaneous abortion and premature delivery. Therefore, frequent monitoring of peak and trough anti- Factor Xa levels, and adjusting of dosage may be needed.

Laboratory Tests

Periodic complete blood counts, including platelet count, and stool occult blood tests are recommended during the course of treatment with Enoxaparin Sodium injection. When administered at recommended prophylaxis doses, routine coagulation tests such as Prothrombin Time (PT) and Activated Partial Thromboplastin Time (aPTT) are relatively insensitive measures of Enoxaparin Sodium injection activity and, therefore, unsuitable for monitoring. Anti-Factor Xa may be used to monitor the anticoagulant effect of Enoxaparin Sodium injection in patients with significant renal impairment. If during Enoxaparin Sodium injection therapy abnormal coagulation parameters or bleeding should occur, anti-Factor Xa levels may be used to monitor the anticoagulant effects of Enoxaparin Sodium injection.

Pregnancy

Pregnancy Category B

All pregnancies have a background risk of birth defect, loss, or other adverse outcome regardless of drug exposure. The fetal risk summary below describes the potential of Enoxaparin Sodium injection to increase the risk of developmental abnormalities above the background risk.

Fetal Risk Summary

Enoxaparin Sodium Injection does not cross the placenta, and is not expected to result in fetal exposure to the drug. Human data suggest that Enoxaparin Sodium Injection does not increase the risk of major developmental abnormalities. Based on animal data, Enoxaparin is not predicted to increase the risk of major developmental abnormalities.

Nursing Mothers

It is not known whether Enoxaparin Sodium injection is excreted in human milk. Because many drugs are excreted in human milk and because of the potential for serious adverse reactions in nursing infants from Enoxaparin Sodium injection, a decision should be made whether to discontinue nursing or discontinue Enoxaparin Sodium injection, taking into account the importance of Enoxaparin Sodium injection to the mother and the known benefits of nursing.

Pediatric Use

Safety and effectiveness of Enoxaparin Sodium injection in pediatric patients have not been established.

Geriatric Use

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

The incidence of bleeding complications was higher in geriatric patients as compared to younger patients when Enoxaparin Sodium injection was administered at doses of 1.5 mg/kg once a day or 1 mg/kg every 12 hours. The risk of Enoxaparin Sodium injection-associated bleeding increased with age. Serious adverse events increased with age for patients receiving Enoxaparin Sodium injection. Careful attention to dosing intervals and concomitant medications (especially antiplatelet medications) is advised. Enoxaparin Sodium injection 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

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 IV bolus prior to the normal dosage regimen and had their SC dose adjusted to 0.75 mg/kg every 12 hours. The incidence of bleeding complications was higher in patients ≥65 years of age as compared to younger patients (<65 years).

Renal Impairment

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 moderate (creatinine clearance 30–50 mL/min) and mild (creatinine clearance 50–80 mL/min) renal impairment. In patients with renal failure, treatment with Enoxaparin has been associated with the development of hyperkalemia.

Hepatic Impairment

The impact of hepatic impairment on Enoxaparin's exposure and antithrombotic effect has not been investigated. Caution should be exercised when administering Enoxaparin to patients with hepatic impairment.

Low-Weight Patients

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). All such patients should be observed carefully for signs and symptoms of bleeding.

Obese Patients

Obese patients are at higher risk for thromboembolism. The safety and efficacy of prophylactic doses of Enoxaparin Sodium Injection in obese patients (BMI >30 kg/m ) has not been fully determined and there is no consensus for dose adjustment. These patients should be observed carefully for signs and symptoms of thromboembolism.

Whenever possible, agents which may enhance the risk of hemorrhage should be discontinued prior to initiation of Enoxaparin Sodium injection therapy. These agents include medications such as : anticoagulants, platelet inhibitors including acetylsalicylic acid, salicylates, NSAIDs (including ketorolac tromethamine), dipyridamole, or sulfinpyrazone. If co-administration is essential, conduct close clinical and laboratory monitoring

Accidental overdosage following administration of Enoxaparin Sodium injection may lead to hemorrhagic complications. Injected Enoxaparin Sodium injection may be largely neutralized by the slow IV injection of protamine sulfate (1% solution). The dose of protamine sulfate should be equal to the dose of Enoxaparin Sodium injection injected : 1 mg protamine sulfate should be administered to neutralize 1 mg Enoxaparin Sodium injection, if Enoxaparin Sodium was administered in the previous 8 hours. An infusion of 0.5 mg protamine per 1 mg of Enoxaparin Sodium may be administered if Enoxaparin Sodium was administered greater than 8 hours previous to the protamine administration, or if it has been determined that a second dose of protamine is required. The second infusion of 0.5 mg protamine sulfate per 1 mg of Enoxaparin Sodium injection may be administered if the aPTT measured 2 to 4 hours after the first infusion remains prolonged. If at least 12 hours have elapsed since the last Enoxaparin Sodium injection, protamine administration may not be required; however, even with higher doses of protamine, the aPTT may remain more prolonged than following administration of heparin. In all cases, the anti-Factor Xa activity is never completely neutralized (maximum about 60%). Particular care should be taken to avoid overdosage with protamine sulfate. Administration of protamine sulfate can cause severe hypotensive and anaphylactoid reactions. Because fatal reactions, often resembling anaphylaxis, have been reported with protamine sulfate, it should be given only when resuscitation techniques and treatment of anaphylactic shock are readily available.

Store below 25°C. Do not freeze

Keep out of reach of children

Shelf-life 

Refer on the pack

Presentation :

ENOXARIN 40 : A pre-filled syringe of 40 mg / 0.4 ml.

ENOXARIN 60 : A pre-filled syringe of 60 mg / 0.6 ml.