Enoxaparin STADA

Sterile pyrogen-free solution for Injection.
Each ml of the solution contains 100 mg/ml of enoxaparin sodium.
Solvent: Water for Injection.

Pharmacotherapeutic group: Antithrombotic agents; Heparin group. ATC code: B01AB05.
Pharmacology: Pharmacodynamics: Enoxaparin is a low-molecular-weight heparin in which the antithrombotic and anticoagulant activities of standard heparin have been dissociated. It is characterized by higher anti-Xa activity than anti-Ⅱa or antithrombin activity. For enoxaparin, the ratio between these two activities is 3.6. These anticoagulant activities are mediated through anti-thrombin III (ATIII) resulting in anti-thrombotic activities in humans.
Beyond its anti-Xa/IIa activity, further anti-thrombotic and anti-inflammatory properties of enoxaparin have been identified in healthy subjects and patients as well as in non-clinical models. These include ATIII-dependent inhibition of other coagulation factors like factor VIIa, induction of endogenous Tissue Factor Pathway Inhibitor (TFPI) release as well as a reduced release of von Willebrand factor (vWF) from the vascular endothelium into the blood circulation. These factors are known to contribute to the overall anti-thrombotic effect of enoxaparin.
At prophylactic doses, it does not significantly affect the aPTT.
At curative doses, a PTT can be prolonged by 1.5 to 2.2 times the control time at peak activity. This prolongation reflects the residual antithrombin activity.
Prophylactic treatment of venous thromboembolism in patients who are bedridden due to on acute medical disorder: A randomized, double-blind, placebo-controlled study (Medenox) was carried out to compare the safety and efficacy of enoxaparin 2,000 anti-Xa IU/0.2 ml (20 mg/0.2 ml) and enoxaparin 4,000 anti-Xa IU/0.4 ml in preventing venous thromboembolism. The study medication or placebo were administered once daily for 6 to 14 days to 1,102 patients who were bedridden due to an acute medical disorder occurring within the previous three days and who were at moderate risk of venous thromboembolism. The patients were over 40 years of age and had heart failure (NYHA class III or IV), acute respiratory failure revealing or complicating chronic respiratory insufficiency, an acute infectious or rheumatic disease associated with at least one thromboembolic risk factor (age >75 years, cancer, history of venous thromboembolism, obesity, varicose veins, hormone therapy, chronic heart or respiratory failure).
Medical patients at high risk of venous thromboembolism complications (acute phase of myocardial infarction, heart disease such as arrhythmia or valvular disease requiring anticoagulant therapy, intubated patients or patients who had experienced a stroke within the last three months) were not included in the study.
The primary efficacy criterion was the incidence of venous thromboembolic events on treatment day 10 (±4) defined as: deep vein thrombosis (DVT] documented systematically by venography (83.4% of evaluable patients) or by Doppler ultrasound (16.6% of evaluable patients) in patients with symptomatic DVT; non-fatal symptomatic pulmonary embolism confirmed by pulmonary angiography or spiral CT; fatal pulmonary embolism.
A significant decrease in the incidence of venous thromboembolic events was observed in the 866 evaluable patients on day 10 (±4), 16/291 (5.5%) in the enoxaparin 4,000 anti-Xa IU/0.4 ml (40 mg/0.4 ml) group versus 43/288 (14.9%) in the placebo group (p=0.0002). This was mainly due to the significant decrease in the incidence of total DVT (proximal and distal), i.e. 16/291 (5.5%) in the enoxaparin 4,000 anti-Xa IU/0.4 ml (40 mg/0.4 ml) group versus 41/288 (14.2%) in the placebo group (p=0.0004). Most DVTs were asymptomatic (only 6 were symptomatic). The observed benefit was maintained after 3 months.
Fifty-nine percent (59%) of patients in the enoxaparin 4,000 anti-Xa IU/0.4 ml (40 mg/0.4 ml) group regained autonomous mobility (>10 meters) during the treatment period.
Regarding safety, the incidence of hematomas or ecchymoses larger than 5 cm at the injection site was significantly higher in the enoxaparin 4,000 anti-Xa IU/0.4 ml/day (40 mg/day) group than in the placebo group.
This study showed no significant difference in efficacy between enoxaparin 2,000 anti-Xa IU/0.2 ml (20 mg/0.2 ml) and the placebo.
Treatment of acute ST-segment elevation myocardial infarction (STEMI), in combination with a thrombolytic agent in patients who are eligible or not for subsequent coronary angioplasty: In a large multicenter study, 20,479 patients with acute ST-segment elevation myocardial infarction having received fibrinolytic treatment were randomized to receive either: enoxaparin as an IV bolus injection of 3,000 anti-Xa IU (30 mg) immediately followed by a dose of 100 anti-Xa IU/kg (1 mg/kg) SC, then by an SC injection of 100 anti-Xa IU/kg (1 mg/kg) every 12 hours, or unfractionated heparin by the IV route as a bolus injection of 60 IU/kg (maximum 4,000 IU) followed by a continuous infusion at a dose adjusted to the activated partial thromboplastin time. The SC injections of enoxaparin were administered until discharge from hospital or for a maximum period of 8 days (in 75% of cases for at least 6 days). Half the patients receiving heparin were administered the drug for less than 48 hours (in 89.5% of cases 36 hours). All the patients were also treated with aspirin for at least 30 days. The enoxaparin dosage was adjusted for patients aged 75 years or more: 75 IU/kg as an SC injection every 12 hours, without an initial IV bolus injection.
During the study, 4,716 (23%) patients underwent coronary angioplasty under antithrombotic treatment using blinded study drugs. Patients did not receive an additional dose if the last SC injection of enoxaparin had been given less than 8 hours before balloon inflation, or, received an IV bolus injection of 30 anti-Xa IU/kg (0.3 mg/kg) if the last SC Injection of enoxaparin had been given more than 8 hours before balloon inflation.
Enoxaparin significantly reduced the incidence of primary end point events (composite end point consisting of myocardial infarction relapse and all-cause mortality within 30 days after inclusion: 9.9% in the enoxaparin group versus 12.0% in the unfractionated heparin group (relative risk reduction of 17%, p<0.001)). The incidence of myocardial infarction relapse was significantly lower in the enoxaparin group (3.4% versus 5%, p<0.001, relative risk reduction 31%). The incidence of deaths was lower in the enoxaparin group, with no statistically significant difference between the groups (6.9% versus 7.5%, p=0.11).
The benefit of enoxaparin in terms of the primary endpoint was consistent, irrespective of sub-group: age, sex, location of myocardial infarction, history of diabetes or myocardial infarction, type of thrombolytic administered and interval between the first clinical signs and treatment initiation.
Enoxaparin demonstrated a significant benefit versus unfractionated heparin in terms of the primary efficacy criterion, both in patients who had undergone coronary angioplasty within 30 days after inclusion (10.8% versus 13.9%, 23% reduction in relative risk) and in patients who did not have coronary angioplasty (9.7% versus 11.4%, 15% reduction in relative risk).
The incidence of major bleeding at 30 days was significantly higher (p<0.0001) in the enoxaparin group (2.1%) versus the heparin group (1.4%). There was a higher incidence of gastrointestinal bleeding in the enoxaparin group (0.5%) versus the heparin group (0.1%), while the incidence of intracranial bleeding was similar in both groups (0.8% with enoxaparin versus 0.7% with heparin).
The analysis of the composite criteria measuring overall clinical benefit showed statistically significant superiority (p<0.0001) for enoxaparin versus unfractionated heparin: a relative risk reduction of 14% in favor of enoxaparin (11.0% versus 12.8%) for the composite criteria consisting of death, myocardial infarction relapse, or major bleeding (TIMI criteria) at 30 days, and of 17% (10.1% versus 12.2%) for the composite criteria consisting of death, myocardial infarction relapse or intracranial bleeding at 30 days.
The beneficial effect of enoxaparin on the primary end point observed during the first 30 days was maintained over a 12-month follow-up period.
Pharmacokinetics: The pharmacokinetic parameters of enoxaparin have been evaluated based on the time course of plasma anti-Xa and anti-IIa activity at the recommended doses (validated amidolytic methods) following single and repeated subcutaneous administration, and following single intravenous injection.
Bioavailability: Subcutaneously administered enoxaparin is rapidly and almost completely absorbed (nearly 100%). Peak plasma activity is observed between 3 and 4 hours after administration. This peak activity (expressed as anti-Xa IU) is 0.18±0.04 (after 20 mg/0.2 ml), 0.43±0.11 (after 4,000 anti-Xa IU (40 mg/0.4 ml)) in prophylactic treatment.
An IV bolus injection of 30 mg followed by 1 mg/kg by the SC route every 12 hours leads to a first peak in anti-Factor Xa levels of 1.16 IU/ml (n=16) and a mean exposure corresponding to 88% of the steady state level. Steady state is reached as of the second day of treatment.
Enoxaparin pharmacokinetics appear to be linear over the recommended dose ranges. Intra-patient and inter-patient variability is low. After repeated subcutaneous administration of 40 mg once daily in healthy volunteers, the steady state is reached on day 2 with mean enoxaparin activity of approximately 15% higher than that obtained after a single dose. Steady-state enoxaparin activity levels are well predicted by single dose pharmacokinetics. After repeated subcutaneous administration of 1 mg/kg b.i.d., the steady state is reached between day 3 and 4 with mean exposure about 65% higher than after a single dose, and with maximum and minimum anti-Xa activity of about 1.2 and 0.52 anti-Xa IU/ml, respectively. Based on enoxaparin sodium pharmacokinetics, this difference in steady state is expected and is within the therapeutic range. Plasma anti-IIa activity after subcutaneous administration is about 10-fold lower than anti-Xa activity. The mean maximum anti-IIa activity is observed approximately 3 to 4 hours following subcutaneous injection, and reaches 0.13 anti-IIa IU/ml following repeated administration of a 1 mg/kg (100 anti-Xa IU/kg) dose b.i.d.
No pharmacokinetic interaction has been observed between enoxaparin and the thrombolytic agent when co-administered.
Distribution: The volume of distribution of enoxaparin anti-Xa activity is about 5 liters and is close to the blood volume.
Metabolism: Enoxaparin is metabolized mainly in the liver (desulfation, depolymerization).
Elimination: Following subcutaneous injection, the apparent anti-Xa activity elimination half-life is higher for low-molecular-weight heparins than for unfractionated heparins. Enoxaparin exhibits a monophasic elimination pattern with a half-life of about 4 hours after a single subcutaneous dose to about 7 hours after repeated dosing.
With low-molecular-weight heparin, plasma decay occurs more quickly for anti-IIa activity than for anti-Xa activity. Enoxaparin and its metabolites are eliminated via the renal route (nonsaturable mechanism) and by the biliary route. Renal clearance of fragments with anti-Xa activity accounts for about 10% of the administered dose, and total renal excretion of active and non-active compounds for 40% of the dose.
High-risk populations: Elderly patients: As kidney function is physiologically impaired in this population, elimination is slower. This does not affect doses or the administration schedule in prophylactic treatment as long as the renal function of these patients remains within acceptable limits, i.e. only slightly impaired.
It is essential to systematically assess renal function in elderly patients over 75 years of age using the Cockcroft formula before initiating treatment with LMWH (see Precautions for use under Precautions).
Patients with mild to moderate renal failure (i.e. creatinine clearance >30 ml/min): In certain cases, it may be useful to monitor the circulating anti factor Xa activity to prevent overdose when enoxaparin is used as curative treatment (see Precautions).
A linear relationship between anti-Xa plasma clearance and creatinine clearance at steady-state has been observed, which indicates decreased clearance of enoxaparin sodium in patients with reduced renal function. Anti-Xa exposure represented by AUC, at steady-state, is marginally increased in mild (creatinine clearance 50-80 ml/min) and moderate (creatinine clearance 30-50 ml/min) renal impairment after repeated subcutaneous 40 mg once daily doses. In patients with severe renal impairment (creatinine clearance <30 ml/min), the AUC at steady state is significantly increased on average by 65% after repeated subcutaneous 40 mg once daily doses (see Precautions).
Hemodialysis: Low molecular weight heparin is injected in the arterial line of the dialysis circuit at sufficient doses to avoid coagulation in the circuit.
The pharmacokinetic parameters remain, in principle, unchanged except in cases of overdose or where the drug passes into the general circulation, causing high anti-Xa activity related to terminal renal insufficiency.
Toxicology: Preclinical safety data: No long-term studies in animals have been performed to evaluate the carcinogenic potential of enoxaparin.
Enoxaparin was not mutagenic in in vitro tests, including the Ames test, mouse lymphoma cell forward mutation test, and human lymphocyte chromosomal aberration test, and the in vivo rat bone marrow chromosomal aberration test.
Enoxaparin was found to have no effect on fertility or reproductive performance of male and female rats at SC doses up to 20 mg/kg/day. Teratology studies have been conducted in pregnant rats and rabbits at SC doses of enoxaparin up to 30 mg/kg/day. There was no evidence of teratogenic effects or fetotoxicity due to enoxaparin.
Besides the anticoagulant effects of enoxaparin, there was no evidence of adverse effects at 15 mg/kg/day in the 13-week subcutaneous toxicity studies both in rats and dogs and at 10 mg/kg/day in the 26-week subcutaneous and intravenous toxicity studies both in rats, and monkeys.

Enoxaparin STADA is a low-molecular-weight heparin (LMWH). (See Table 1.)

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Administration: SUBCUTANEOUS ROUTE (except for haemodialysis indication for solution for injection containing 4,000 anti-Xa IU/0.4 ml (40 mg/0.4 ml) and except for patients with acute ST-segment elevation myocardial infarction, in whom IV bolus administration is required for solution for injection containing 6,000 anti-Xa IU/0.6 ml (60 mg/0.6 ml).
These presentations are suitable for adults.
This drug is not to be injected via the intramuscular route.
One milliliter of solution for injection is equivalent to approximately 10,000 anti-Xa IU (100 mg/ml) of enoxaparin.
Subcutaneous injection technique: Injection should be made preferably when the patient is lying down. Enoxaparin STADA is administered by deep subcutaneous injection. Do not expel the air bubble from the syringe before the injection to avoid the loss of drug when using the 40 mg pre-filled syringes. The administration should be alternated between the left and right anterolateral or posterolateral abdominal wall.
The whole length of the needle should be introduced vertically into a skin fold gently held between the thumb and index finger. The skin fold should not be released until the injection is complete. Do not rub the injection site after administration (see Instruction for Use under Patient Counselling Information).
Intravenous (bolus) injection technique for the treatment of acute ST-segment elevation myocardial infarction only: Enoxaparin sodium should be administered through an intravenous line. It should not be mixed or co-administered with other medications. To avoid the possible mixture of enoxaparin sodium with other drugs, the intravenous access chosen should be flushed with a sufficient amount of saline or dextrose solution prior to and following the intravenous bolus administration of enoxaparin sodium to clear the port of drug. Enoxaparin sodium may be safely administered with normal saline solution (0.9%) or 5% dextrose in water.
Initial 3,000 anti-Xa IU (30 mg) bolus: For the initial 3,000 anti-Xa IU (30 mg) bolus, using an enoxaparin sodium graduated prefilled syringe, expel the excessive volume to retain only 3,000 anti-Xa IU/0.3 ml (30 mg/0.3 ml) in the syringe. The 3,000 anti-Xa IU (30 mg) dose can be directly injected into the intravenous line.
Additional bolus for patients treated by coronary angioplasty when last SC administration was given more than 8 hours before balloon inflation: For patients undergoing subsequent coronary angioplasty, an additional IV bolus of 30 anti-Xa IU/kg (0.3 mg/kg) is to be administered if last SC administration was given more than 8 hours before balloon inflation (see Treatment of acute ST-segment elevation myocardial infarction in combination with a thrombolytic agent in patients eligible or not for subsequent coronary angioplasty as follows).
In order to assure the accuracy of the small volume to be injected, it is recommended to dilute the drug to 300 anti-Xa IU/ml (3 mg/ml).
To obtain a 300 anti-Xa IU/ml (3 mg/ml) solution, using a 6,000 anti-Xa IU (60 mg) enoxaparin sodium prefilled syringe, it is recommended to use a 50 ml infusion bag (i.e. using either normal saline solution (0.9%) or 5% dextrose in water) as follows: Withdraw 30 ml from the infusion bag with a syringe and discard the liquid. Inject the complete contents of the 6,000 anti-Xa IU (60 mg) enoxaparin sodium prefilled syringe into the 20 ml remaining in the bag. Gently mix the contents of the bag. Withdraw the required volume of diluted solution with a syringe for administration into the intravenous line.
After dilution is completed, the volume to be injected can be calculated using the following formula [Volume of diluted solution (ml) = Patient weight (kg) x 0.1] or using the table as follows. It is recommended to prepare the dilution immediately before use. (See Table 2.)

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General recommendation: Regular monitoring of the platelet count is essential throughout the treatment due to the risk of heparin-induced thrombocytopenia (HIT) (see Precautions).
General: Prophylactic treatment of venous thromboembolic disease in surgery: Duration and dose of Enoxaparin STADA therapy are based upon patient risk. The thromboembolic risk for individual patient can be estimated using validated risk stratification models.
In patients with a moderate risk of thrombo-embolism, the recommended dose of enoxaparin sodium is 40 mg once daily by subcutaneous injection. In general surgery, the first injection should be given 2 hours before the surgical procedure.
Enoxaparin sodium treatment is usually prescribed for an average period of 7 to 10 days. A longer treatment duration may be appropriate in some patients and enoxaparin sodium should be continued for as long as there is a risk of venous thromboembolism and until the patient is ambulatory.
In patients with a high risk of thrombo-embolism the recommended dose of enoxaparin sodium given by subcutaneous injection, is 40 mg once daily, initiated 12 hours prior to surgery or 30 mg twice daily, initiated 12 to 24 hours after surgery.
For patients who undergo major orthopedic surgery with a high venous thromboembolism risk, a thromboprophylaxis up to 5 weeks is recommended.
For patients who undergo cancer surgery with a high venous thromboembolism risk, a thromboprophylaxis up to 4 weeks is recommended.
For special recommendations concerning dosing intervals for Spinal/Epidural Anesthesia and Percutaneous coronary revascularisation procedures (see Warnings).
Prophylactic treatment of deep vein thrombosis in acute medical conditions: Dosage: The dosage is 40 mg or 4,000 anti-Xa IU/0.4 ml injected subcutaneously once daily.
Duration of treatment: Therapeutic benefit has been established for a treatment duration of between 6 to 14 days.
To date, no efficacy and safety data are available concerning prophylaxis for more than 14 days. If the risk of venous thromboembolism persists, prolonged prophylactic treatment, particularly with oral anticoagulants, must be considered.
Prevention of clotting in extracorporeal: circulation/hemodialysis: Injection by the intravascular route (in the arterial line of the dialysis circuit).
In patients undergoing repeated hemodialysis sessions, prevention of clotting in the extrarenal purification system is obtained by injecting an initial dose of 100 anti-Xa IU/kg (1 mg/kg) in the arterial line of the dialysis circuit at the beginning of the session.
This dose, administered as a single intravascular bolus injection, is only suitable for hemodialysis sessions of 4 hours or less. It can be adjusted subsequently as a result of high inter- and intra-individual variability. However, if fibrin rings are found, for example after a longer than normal session, a further dose of 0.5 to 1 mg/kg may be given. The maximum recommended dose is 100 anti-Xa IU/kg (1 mg).
In hemodialysis patients at high risk of hemorrhage (particularly pre- and post-operative dialysis) or with active hemorrhage, dialysis sessions may be carried out using a dose of 50 anti-Xa IU/kg (0.5 mg/kg) (double vascular access) or 75 anti-Xa IU/kg (7.5 mg/kg) (single vascular access).
Curative treatment of deep vein thrombosis (DVT), with or without pulmonary embolism, without signs of clinical severity: Any suspected deep vein thrombosis should be quickly confirmed by the appropriate examinations.
Administration schedule and Dose: Enoxaparin STADA can be administered subcutaneously either as a single daily injection of 150 anti-Xa IU/Kg (1.5 mg/kg) or as twice daily injections of 100 anti-Xa IU/kg (1 mg/kg).
In patient with complicated thromboembolic disorders, a dose of 100 anti-Xa (1 mg) twice daily is recommended.
LMWH dosage has not been evaluated in terms of bodyweight in patients weighing more than 100 kg or less than 40 kg. The efficacy of LMWH treatment may be slightly lower in patients weighing more than 100 kg, and the risk of hemorrhage may be higher in patients weighing less than 40 kg. Specific clinical monitoring must be carried out in these patients.
DVT treatment duration: Treatment with low-molecular-weight heparin should be quickly replaced by oral anticoagulant therapy, unless contraindicated. Treatment duration with LMWH should not exceed 10 days, including the time needed to reach the required oral anticoagulant effect, except when this is difficult to achieve (see Precautions for use: Laboratory tests: Platelet monitoring under Precautions). Oral anticoagulant treatment should therefore be initiated as soon as possible.
Curative treatment of unstable angina/non-Q-wave myocardial infarction: A dose of 100 anti-Xa IU/kg (1 mg/kg) of enoxaparin is administered by subcutaneous injection twice daily at 12-hour intervals, in combination with aspirin (recommended doses: 75 to 325 mg orally, following a minimum loading dose of 160 mg). The recommended duration of treatment is about 2 to 8 days, until the patient is clinically stable.
Treatment of acute ST-segment elevation myocardial infarction in combination with a thrombolytic agent in patients eligible or not for subsequent coronary angioplasty: An initial IV bolus injection of 3,000 anti-Xa IU (30 mg) followed by an SC injection of 1 mg/kg within 15 minutes, then every 12 hours (a maximum of 10,000 anti-Xa (100 mg) for each of the first two SC doses followed by 1 mg/kg SC dosing for the remaining doses).
The first dose of enoxaparin should be administered at any time between 15 minutes before and 30 minutes after the start of thrombolytic treatment (whether fibrin-specific or not).
The recommended duration of treatment is 8 days, or until the patient is discharged from hospital if the hospitalization period is less than 8 days.
Concomitant treatment: administration of aspirin must be instituted as soon as possible after symptoms appear, and maintained at a dosage of between 75 mg and 325 mg daily for at least 30 days, unless otherwise indicated.
Patients treated by coronary angioplasty: If the last SC injection of enoxaparin was performed less than 8 hours before balloon inflation, no additional administration is necessary; if the last SC injection was performed more than 8 hours before balloon inflation, an IV bolus of 30 anti-Xa IU/kg (0.3 mg) of enoxaparin must be administered. In order to improve the accuracy of the volumes to be injected, it is recommended to dilute the drug to 300 IU/ml (3 mg/ml) (see Intravenous (bolus) injection technique for the treatment of acute ST-segment elevation myocardial infarction only as previously mentioned).
In patients aged 75 and over, treated for acute ST-segment elevation myocardial infarction, the initial IV bolus injection should not be administered. An SC dose of 75 anti-Xa IU/kg (7.5 mg/kg) every 12 hours should be administered (maximum of 7,500 anti-Xa IU (75 mg) for each of the first two injections only, followed by 0.75 mg/kg SC dosing for remaining doses).

Signs and Symptoms: Accidental overdosage with enoxaparin sodium after intravenous, extracorporeal or subcutaneous administration may lead to hemorrhagic complications. Following oral administration of even large doses, it is unlikely that enoxaparin sodium will be absorbed.
Management: Antidote and treatment: In case of hemorrhage, certain patients can be treated with protamine sulfate, taking the following factors into account: its efficacy is far lower than that reported in overdoses with unfractionated heparin; due to its undesirable effects (particularly anaphylactic shock), the benefit/risk ratio of protamine sulfate should be carefully weighed beforehand.
Neutralization is performed by slow intravenous injection of protamine (sulfate or hydrochloride). The protamine dose required depends on: the heparin dose injected (100 anti-heparin units of protamine neutralizes the activity of 1 mg (100 anti-Xa IU) of low molecular-weight heparin), if enoxaparin sodium was administered within the last 8 hours; the time since the heparin injection; an infusion of 50 anti-heparin units of protamine per 1 mg (100 anti-Xa IU) of enoxaparin sodium may be administered if enoxaparin sodium was given more than 8 hours previously, or if a second dose of protamine seems necessary; if the injection of enoxaparin sodium was given more than 12 hours previously, it is not necessary to administer protamine.
These recommendations concern patients with normal renal function receiving repeated doses.
Nevertheless, the anti-Xa activity cannot be completely neutralized (maximum about 60%). Furthermore, the neutralization may be transient due to the absorption pharmacokinetics of low-molecular-weight heparin, which may require dividing the total calculated dose of protamine into several injections (2 to 4) given over 24 hours.
In principle, no serious consequences are likely after ingestion of low-molecular weight heparin, even in massive quantities (no cases reported), due to the very low gastric and intestinal absorption of the drug.

Whatever the dose (curative or prophylactic), this medicinal product must not be used in the following situations: Hypersensitivity to enoxaparin sodium, heparin or its derivatives, including the other LMWHs; Bleeding or tendency to bleed related to impaired hemostasis (a possible exception to this contraindication may be disseminated intravascular coagulation, when not related to heparin treatment (see Precautions for use under Precautions); Organic lesion likely to bleed; Clinically significant active major bleeding and conditions with a high risk of uncontrolled hemorrhage, including recent hemorrhagic stroke; History of immune mediated heparin-induced thrombocytopenia (HIT) within the past 100 days or in the presence of circulating antibodies (see Precautions).
This medicinal product must not be used at curative doses in the following situations: Intracerebral hemorrhage; Spinal or epidural anesthesia must never be performed in patients under curative LMWH treatment.

General: Low Molecular Weight Heparins should not be used interchangeably since they differ in their manufacturing process, molecular weights, specific anti-Xa activities, units and dosage.
Although the concentrations of the various low-molecular-weight heparins are all expressed in anti-Xa international units (IU), their efficacy is not only related to their anti-Xa activity. It would be dangerous to replace one LMWH dosage regimen by another as each regimen has been validated by specific clinical studies. Particular care is therefore required and the specific instructions for use of each drug must be followed.
Spinal/epidural anesthesia in patients given prevent treatment with LMWH: There have been rare reports of spinal hematomas following administration of LMWH during spinal/epidural anesthesia, resulting in long-term or permanent paralysis.
The risk of intra-spinal hematomas appears to be higher in epidural anesthesia with a catheter than in spinal anesthesia. The risk also appears to be increased by traumatic or repeated neuraxial puncture or in patients with a history of spinal surgery or spinal deformity.
The occurrence of these rare events may be increased by prolonged post-operative use of epidural catheters.
To reduce the potential risk of bleeding associated with the concurrent use of enoxaparin sodium and epidural or spinal anesthesia/analgesia, the pharmacokinetic profile of the drug should be considered (see Pharmacology: Pharmacokinetics under Actions). Placement and removal of the catheter is best performed when the anticoagulant effect of enoxaparin is low; however, the exact timing to reach a sufficiently low anticoagulant effect in each patient is not known.
If pre-operative LMWH treatment is required (long term bedridden patients, trauma) and if the benefit of local/regional spinal anesthesia has been carefully weighed, patients who received a pre-operative injection of LMWH can be anesthetized provided that an interval of at least 12 hours is respected between the heparin injection and the spinal anesthesia. Close neurological monitoring is recommended due to the risk of intraspinal hematoma.
In almost all patients, prophylactic treatment with LMWH can be initiated within 6 to 8 hours after the anesthesia or removal of the catheter, under neurological monitoring.
Placement or removal of a catheter should be delayed for at least 12 hours after administration of lower doses (20 mg once daily, 30 mg once or twice daily or 40 mg once daily) of enoxaparin, 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. Anti-Xa levels are still detectable at these time points, and these delays are not a guarantee that neuraxial haematoma will be avoided. 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 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. For patients with creatinine clearance <30 ml/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 (30 mg once daily) and at least 48 hours for the higher dose (1 mg/kg/day).
Extra caution should be exercised during co-administration with other drugs which affect hemostasis (specifically non-steroidal anti-inflammatory drugs, aspirin).
Should the physician decide to administer anticoagulation in the context of epidural/spinal anesthesia 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. Patients should be in structured to inform their physician immediately if they experience any of the previously mentioned signs or symptoms. If signs or symptoms of spinal haematoma are suspected, urgent diagnosis and treatment including spinal cord decompression should be initiated.
Risk of heparin-induced thrombocytopenia (HIT): Use of enoxaparin sodium in patients with a history of immune mediated HIT within the past 100 days or in the presence of circulating antibodies is contraindicated. Circulating antibodies may persist several years. Enoxaparin sodium is to be used with extreme caution in patients with a history (more than 100 days) of heparin-induced thrombocytopenia without circulating antibodies. The decision to use enoxaparin sodium in such a case must be made only after a careful benefit risk assessment and after non-heparin alternative treatments are considered.
Solution for injection containing 6000 anti-Xa IU (60 mg) Coronary angioplasty revascularization procedure: To minimize the risk of hemorrhage during coronary angioplasty for unstable angina, non-Q-wave myocardial infarction and acute ST-segment elevation myocardial infarction, it is recommended that the advised intervals between enoxaparin injections be strictly complied with. It is important to perform hemostasis at the vascular puncture site following coronary angioplasty. If an occlusion device is used, the introducer can be removed immediately. If manual compression is performed, the introducer must be removed 6 hours after the last SC/IV injection of enoxaparin. If enoxaparin treatment is continued, the following injection must be performed at the earliest 6 to 8 hours after removal of the introducer. The puncture site must be monitored to detect any signs of bleeding or hematoma.
Prophylactic treatment in acute medical conditions: In patients with an acute infection or acute rheumatic disorder, prophylactic treatment is only justified if the disorder is associated with at least one of the following venous thromboembolic risk factors: age >75 years; cancer; history of venous thromboembolism; obesity; hormone therapy; heart failure; chronic respiratory failure.
In medical prophylaxis, there is very limited clinical experience in elderly patients over 80 years of age whose bodyweight is below 40 kg.
Use in Pregnancy: Pregnant women with Mechanical prosthetic heart valves: The use of Enoxaparin Injection for thromboprophylaxis in pregnant women with mechanical prosthetic heart valves has not been adequately studied. During a clinical study in pregnant women with mechanical prosthetic heart valves receiving 1 mg/kg enoxaparin twice daily to reduce the risk of thromboembolic events, two of eight women developed thrombosis which led to an obstructed valve with fatal outcome for both the woman and the fetus. In addition, other isolated post-marketing cases of thrombosis have been reported in pregnant women with mechanical prosthetic heart valves who received thromboembolic prophylaxis with enoxaparin. Therefore, the risk of thromboembolic events in this population might be higher (see Precautions for use: Mechanical prosthetic heart valves under Precautions).
Use in children: As no relevant data are available, use of LMWH is not recommended in children.

This medicinal product is generally not advisable at curative doses in the following cases: Acute extensive ischemic stroke, with or without impaired consciousness.
If the stroke is caused by embolism, enoxaparin must not be administered for 72 hours following the event. The efficacy of curative doses of LMWH has however not yet been established, regardless of the cause, extent or clinical severity of cerebral infarction.
Acute infectious endocarditis (except for some emboligenic cardiac conditions).
Mild to moderate kidney failure (creatinine clearance between 30 and 60 ml/min).
In addition, in subjects of any age, curative doses of this medicinal product are generally not advisable when combined with the following (see Interactions): Acetylsalicylic acid at analgesic, antipyretic and anti-inflammatory doses; NSAIDs (systemic use); Dextran 40 (parenteral use).
This medicinal product is generally not advisable at prophylactic doses in the following cases: In patients with severe renal failure (creatinine clearance of approximately 30 ml/min as per the Cockcroft formula) (see Precautions for use: Renal function as follows); During the first 24 hours following intracerebral hemorrhage.
In addition, in subjects over 65 years of age, prophylactic doses of this medicinal product are generally not advisable when combined with the following (see Interactions): Acetylsalicylic acid at analgesic, antipyretic and anti-inflammatory doses; NSAIDs (systemic use); Dextran 40 (parenteral use).
Precautions for use: Do not administer by the intramuscular route; Hemorrhage.
The recommended dosage regimens must be respected (dosage and duration of treatment). Failure to comply with these recommendations can lead to hemorrhage, particularly in high-risk patients (the elderly, patients with renal failure, etc.).
As with other anticoagulants, bleeding may occur at any site (see Adverse Reactions).
If bleeding occurs, the origin of the hemorrhage should be investigated and appropriate treatment instituted.
Serious hemorrhagic events have been reported in the following situation: elderly subjects, particularly due to age-related renal impairment; patients with renal failure; bodyweight below 40 kg; treatment lasting longer than the recommended mean duration of ten days; non-compliance with treatment recommendations (particularly treatment duration and dose adjustment based on bodyweight in curative treatment); co-administration with drugs increasing the risk of hemorrhage (see Interactions).
Enoxaparin sodium, as with any other anticoagulant therapy, should be used with caution in conditions with increased potential for bleeding.
In any event, special monitoring is essential in the elderly and/or patients with renal failure, as well as during treatment prolonged beyond ten days.
Elderly patients (especially patients eighty years of age and older) may be at an increased risk for bleeding complications with the therapeutic dosage ranges. Careful clinical monitoring is advised.
Assay of anti-Xa activity may in certain cases be useful in detecting drug accumulation (see Laboratory tests as follows).
Mechanical prosthetic heart valves: The use of Enoxaparin Injection in the prevention of thromboembolic events in patients with mechanical prosthetic heart valves has not been specifically investigated. However, some isolated cases of thrombosis have been reported in patients with this device who received enoxaparin as prophylactic treatment of thromboembolic events. Confounding factors, including underlying disease and insufficient clinical data, limit the evaluation of these cases. Some of these cases were pregnant women in whom thrombosis led to maternal and fetal death. Pregnant women with prosthetic heart valves may be at higher risk for thrombo-embolism (see Use in Pregnancy: Pregnant women with Mechanical prosthetic heart valves under Warnings).
Renal function: In patients with renal impairment, there is an increase in exposure of enoxaparin sodium which increases the risk of bleeding. Since 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. 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, careful clinical monitoring is advised.
Before low-molecular-weight heparin treatment is initiated, it is essential to evaluate renal function, particularly in subjects 75 years or older, by determining creatinine clearance (Cl_cr), using the Cockcroft formula and based on a recent bodyweight measurement: In male patients: Cl_cr = (140-age) x weight/(0.814 x serum creatinine) where age is expressed in years, weight in kg and serum creatinine in μmol/l.
This formula must be adjusted for female patients by multiplying the result by 0.85.
When serum creatinine is expressed in mg/ml, the value should be multiplied by a factor of 8.8.
The following dosage adjustments are recommended for therapeutic dosage ranges: See Table 3.

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The following dosage adjustments are recommended foe prophylactic dosage ranges: See Table 4.

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Hepatic impairment: In the absence of clinical studies, caution should be used in hepatically impaired patients.
Low weight: 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), which may lead to a higher risk of bleeding. Therefore, careful clinical monitoring is advised in these patients.
Obese Patients: Obese patients are at higher risk for thromboembolism. The safety and efficacy of prophylactic doses in obese patients (BMI >30 kg/m²) 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.
Laboratory tests: Platelet monitoring: Heparin-induced thrombocytopenia (HIT): There is a risk of serious, occasionally thrombogenic, heparin-induced thrombocytopenia (reported with unfractionated heparin and less often with LMWH) of immunologic origin, called type II HIT (see Adverse Reactions).
As a result of this risk, platelet counts must be performed regardless of the therapeutic indication and the dose administered.
Platelet counts must be performed before administration or at the latest within 24 hours of initiating treatment, then twice a week during the usual treatment duration.
Should long-term treatment prove necessary in certain specific cases i.e. hip surgery, second and third trimesters of high-risk pregnancy (see Use in Pregnancy & Lactation), the schedule for platelet counts is twice a week during the first month of treatment (highest risk period) and then once a week until treatment discontinuation.
HIT should be suspected when the platelet count is below 100,000/mm³ and/or when there is a drop of 30% to 50% between two successive platelet counts. HIT mainly develops 5 to 21 days after heparin treatment is instituted (with a peak incidence after about 10 days).
This complication can however occur much earlier in patients with a history of heparin-induced thrombocytopenia, and isolated cases have been reported after 21 days. This type of patient history must therefore be systematically investigated by means of an in-depth interview before starting treatment. Furthermore, the risk of recurrence when reinstituting heparin may remain for several years or even indefinitely (see Contraindications).
In all cases, the occurrence of HIT constitutes an emergency situation and requires a specialist opinion.
Any significant drop in the platelet count (30% to 50% versus baseline) is a warning sign even before values reach a critical level. Should a decrease in platelets be observed, the following must be performed in all cases: an immediate platelet counts for verification; discontinuation of heparin treatment, if the drop is confirmed or even increased based on these results and when no other obvious cause is identified. A sample must be taken using a citrate tube in order to perform in vitro platelet aggregation and immunological tests. However, under these conditions the immediate measures to be taken are not based on in vitro platelet aggregation or immunological test results as only a few specialized laboratories perform these tests routinely and the results are available at best after several hours. These tests are however necessary to assist in diagnosis of the complication as the risk of thrombosis is very high if heparin treatment is continued; prevention or treatment of HIT-related thrombotic complications.
If continued anticoagulant therapy appears to be essential, heparin must be replaced by an antithrombotic agent of a different group such as sodium danaparoid or hirudin, prescribed at curative or preventive doses on a case-by-case basis.
Replacement by oral anticoagulants can only take place after the platelet count has reverted to normal due to the risk of exacerbation of thrombosis by oral anticoagulants.
Replacement of heparin by oral anticoagulants: Clinical monitoring and laboratory tests (prothrombin time expressed as the INR) must be intensified to monitor the effect of oral anticoagulants.
As there is an interval before the oral anticoagulant reaches its maximum effect, heparin therapy should be continued at a constant dose for as long as necessary in order to maintain INR within the desired therapeutic range, for the indication in two successive tests.
Monitoring of anti-factor Xa activity: As most of the clinical studies which demonstrated the efficacy of LMWH were conducted using a dose based on bodyweight without specific laboratory monitoring, the usefulness of laboratory tests for assessing the efficacy of LMWH treatment has not been established. However, laboratory tests, i.e. monitoring of anti-Xa activity may be useful in managing the risk of bleeding in certain clinical conditions often associated with a risk of overdose.
These situations mainly involve the curative indications of LMWH, due to the doses administered, in patients with: mild to moderate renal failure (creatinine clearance of approximately 30 ml/min to 60 ml/min calculated using the Cockcroft formula). As LMWH is primarily eliminated by the renal route, unlike standard unfractionated heparin, any renal failure can result in relative overdose. Severe renal failure is a contraindication to the use of LMWH at curative doses (see Contraindications); extreme high or low bodyweight (thinness or even cachexia, obesity); unexplained bleeding.
In contrast, laboratory monitoring is not recommended at prophylactic doses if the LMWH treatment complies with the therapeutic recommendations (particularly treatment duration), nor during hemodialysis.
To detect possible heparin accumulation following repeated administration, it is recommended, if necessary, to collect a blood sample at peak activity (based on available data), i.e. approximately 4 hours after the third injection when the drug is given as 2 subcutaneous injections per day.
Repeating anti-Xa activity assays to determine blood heparin levels, for example every 2 to 3 days, should be decided on a case-by-case basis, depending on the results of the preceding assay, and a possible LMWH dose adjustment should be considered.
The anti-Xa activity observed varies for each LMWH and each dosage regimen.
For information, based on available data, the mean value (± standard deviation) observed 4 hours after the 7th injection of enoxaparin given at a dose of 1 mg/kg/injection b.i.d. was 1.20±0.17 anti-Xa IU/ml.
This mean value was observed during clinical trials for anti-Xa activity assays carried out by a chromogenic method (amidolytic).
Activated partial thromboplastin time (aPTT): Some LMWHs moderately increase aPTT. As no clinical relevance has been established, monitoring of treatment using this test is of no use.
Situations involving particular risk: Monitoring of treatment should be intensified in the following cases: hepatic insufficiency; history of gastro-intestinal ulcers or any other organic lesion likely to bleed; Chorioretinal vascular disease; post-operatively, following cerebral or spinal cord surgery; lumbar puncture: this should only be considered taking into account the risk of intra-spinal bleeding and should be postponed whenever possible; concomitant use of medicinal products affecting hemostasis (see Interactions).
Effects on ability to drive and use machine: Enoxaparin sodium has no effect on the ability to drive and operate machines.

Pregnancy: There is no evidence from animal studies that enoxaparin has teratogenic effects.
To date, substances responsible for malformation in humans have proved to be teratogenic in animals during well-conducted studies in two species.
As there are no adequate and well-controlled studies in pregnant women and because animal studies are not always predictive of human response, this drug should be used during pregnancy only if the physician has established a clear need.
Prophylactic treatment during the first trimester: There are currently not enough relevant clinical data concerning possible teratogenic or fetotoxic effects of enoxaparin when the drug is administered preventively during the first trimester. As a precautionary measure, enoxaparin prophylaxis should not be administered during the first trimester.
If epidural anesthesia is planned, preventive heparin treatment should be interrupted whenever possible within 12 hours before anesthesia at the latest.
Prophylactic treatment during the second and third trimesters: Administration of prophylactic doses of enoxaparin to women during the second and third trimesters in a limited number of pregnancies has apparently not resulted in any particular teratogenic or fetotoxic effects. However, additional studies are needed to evaluate the effects of exposure under these conditions. Therefore, enoxaparin prophylaxis during the second and third trimesters should only be administered if necessary.
If epidural anesthesia is planned, preventive heparin treatment should be interrupted whenever possible within 12 hours before anesthesia at the latest.
Curative treatment: Current clinical data are insufficiently relevant to determine a possible malformative or fetotoxic effect of enoxaparin administered at curative doses throughout pregnancy.
The use of curative doses of enoxaparin is therefore not recommended throughout pregnancy as a precaution. Spinal or epidural anesthesia must never be performed during curative treatment with LMWH.
Lactation: Since gastro-intestinal absorption by neonates is unlikely in principle, treatment with enoxaparin is not contraindicated in breast-feeding women. As a precaution, lactating mothers receiving enoxaparin sodium should be advised to avoid breast-feeding.

Enoxaparin has been evaluated in more than 15,000 patients who received enoxaparin in clinical trials. These included 1,776 for prophylaxis of deep vein thrombosis following orthopedic or abdominal surgery in patients at risk for thromboembolic complications, 1,169 for prophylaxis of deep vein thrombosis in acutely ill medical patients with severely restricted mobility, 559 for treatment of deep vein thrombosis with or without pulmonary embolism, 1,578 for treatment of unstable angina and non-Q-wave myocardial infarction and 10,176 for treatment of acute ST-elevation myocardial infarction. Enoxaparin sodium regimen administered during these clinical trials varies depending on indications. The enoxaparin sodium dose was 40 mg SC once daily for prophylaxis of deep vein thrombosis following surgery or in acutely ill medical patients with severely restricted mobility. In treatment of deep vein thrombosis (DVT) with or without pulmonary embolism (PE), patients receiving enoxaparin were treated with either a 1 mg/kg SC dose every 12 hours or a 1.5 mg/kg SC dose once a day. In the clinical studies for treatment of unstable angina and non-Q-wave myocardial infarction, doses were 1 mg/kg SC every 12 hours and in the clinical study for treatment of acute ST-segment elevation myocardial infarction enoxaparin sodium regimen were a 30 mg IV bolus followed by 1 mg/kg SC every 12 hours.
The adverse reactions observed in these clinical studies and reported in post-marketing experience are detailed as follows.
Frequencies are defined as follows: very common (1/10); common (1/100 to <1/10); uncommon (1/1,000 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). Post-marketing adverse reactions are designated with a frequency "not known".
Haemorrhages: In clinical studies, haemorrhages were the most commonly reported reaction. These included major haemorrhages, reported at most in 4.2% of the patients (surgical patients). Some of these cases have been fatal. 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 (see Precautions and Interactions). (See Table 5.)

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Thrombocytopenia and thrombocytosis: See Table 6.

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Other clinically relevant adverse reactions: These reactions are presented as follows, whatever the indications, by system organ class, frequency grouping and decreasing order of seriousness. (See Table 7.)

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Post marketing experience: The following adverse reactions have been identified during post-approval use of enoxaparin. The adverse reactions are derived from spontaneous reports and therefore, the frequency is "not known" (cannot be estimated from the available data).
Immune System Disorders: Anaphylactic/anaphylactoid reaction including shock.
Nervous System Disorders: Headache.
Vascular Disorders: Cases of spinal haematoma (or neuraxial haematoma) have been reported with the concurrent use of enoxaparin as well as spinal/epidural anesthesia or spinal puncture. These reactions have resulted in varying degrees of neurologic injuries including long-term or permanent paralysis (see Spinal/epidural anesthesia in patients given prevent treatment with LMWH under Warnings).
Blood and Lymphatic System Disorders: Haemorrhagic anemia; Cases of immune-allergic thrombocytopenia with thrombosis; in some of them thrombosis was complicated by organ infarction or limb ischaemia (see Precautions for use: Laboratory tests: Platelet monitoring under Precautions); Eosinophilia.
Skin and subcutaneous disorders: Cutaneous vasculitis, skin necrosis usually occurring at the injection site (these phenomena have been usually preceded by purpura or erythematous plaques, infiltrated and painful). Treatment with enoxaparin sodium must be discontinued; Injection site nodules (inflammatory nodules, which were not cystic enclosure of enoxaparin). They resolve after a few days and should not cause treatment discontinuation; Alopecia.
Hepatobiliary disorders: Hepatocellular liver injury; Cholestatic liver injury.
Musculoskeletal and connective tissue disorders: Osteoporosis following long-term therapy (greater than 3 months).

Certain drugs or therapeutic classes may promote the occurrence of hyperkalemia: potassium salts, potassium-sparing diuretics, conversion enzyme inhibitors, angiotensin II inhibitors, non-steroidal anti-inflammatory drugs, heparins (low-molecular-weight or unfractionated heparin), ciclosporin and tacrolimus, trimethoprim.
Occurrence of hyperkalemia may depend on possible related risk factors. This risk is potentiated when the previously mentioned drugs are co-administered.
It is recommended that agents which affect hemostasis should be discontinued prior to enoxaparin therapy unless strictly indicated. These agents include medications such as: Systemic salicylates, acetylsalicylic acid, and NSAIDs including ketorolac; Dextran 40, ticlopidine and clopidogrel; Systemic glucocorticoids; Thrombolytic and anticoagulants; Other anti-platelet agents including glycoprotein IIb/IIIa antagonists.
If the combination is indicated, enoxaparin sodium should be used with careful clinical and laboratory monitoring when appropriate.
Preventive forms (Elderly patients-over 65 years of age) & curative forms: Inadvisable combinations: Acetylsalicylic acid at analgesic, antipyretic and anti-inflammatory doses (and, by extrapolation, other salicylates): Increased risk of bleeding (salicylate-induced platelet function inhibition and gastroduodenal mucosal damage).
Use a non-salicylate antipyretic analgesic (such as paracetamol).
NSAIDs (systemic use): Increased risk of bleeding (NSAID-induced platelet function inhibition and gastroduodenal mucosal damage).
If co-administration cannot be avoided, close clinical monitoring is required.
Dextran 40 (parenteral use): Increased risk of bleeding (inhibition of platelet function by dextran 40).
Combinations requiring precautions for use: Oral anticoagulants: Potentiation of the anticoagulant effect.
When heparin is replaced by an oral anticoagulant, clinical monitoring must be intensified.
Combinations to take into consideration: Platelet aggregation inhibitors (other than acetylsalicylic acid at analgesic, anti-pyretic and anti-inflammatory doses; NSAIDs): abciximab, acetylsalicylic acid at antiaggregant doses in cardiological and neurological indications, beraprost, clopidogrel, eptifibatide, iloprost, ticlopidine, tirofiban. Increased risk of bleeding.
Preventive forms (Patients under 65 years of age): Combinations to take into consideration: Combined use of drugs which variably affect hemostasis potentiate the risk of bleeding. Therefore, regardless of the age of the patients, co-administration of LMWH at preventive doses with the following drugs must be taken into consideration by means of continued clinical monitoring and possible laboratory tests: oral anticoagulants, platelet aggregation inhibitors (abciximab, NSAIDS, acetylsalicylic acid at any dose, clopidogrel, eptifibatide, iloprost, ticlopidine, tirofiban) and thrombolytic agents.

Incompatibilities: Subcutaneous injection: Do not admix with other products.
Intravenous (Bolus) Injection (for acute STEMI indication only): Enoxaparin sodium may be safely administered with normal saline solution (0.9%) or 5% dextrose in water.

Do not store above 30°C. Do not freeze pre-filled syringes.
Shelf-life: 36 months.

Instructions for Use: Pre-filled syringe with safety device: Subcutaneous injection technique: In case of self-injection, your healthcare professional will show you how to administer your injections before you are released from hospital. It is essential that you follow these instructions exactly. If you have questions, be sure you ask your healthcare professional to provide the explanations you require.
Proper subcutaneous (under the skin) injection is essential to prevent pain and bruising at the injection site.
To avoid accidental needle sticks after injection, the prefilled syringes are fitted with an automatic safety device.
Prepare the site for injection: The recommended site for injection is into the fat of the lower abdomen. This should be at least 5 centimeters away from your belly button and out towards your sides.
Prior to injection, wash your hands. Cleanse (do not rub) the selected site for injection with an alcohol swab. Select a different site of lower abdomen for each injection.
Prepare the syringe before the injection: Check the syringe if not damaged and the medicine in it is a clear solution without particle. If not, use another syringe.
For prophylactic dosages (40 mg): Take the protective cap off the needle.
A drop may appear at the tip of the needle. If this occurs, remove the drop before injection by tapping on the syringe, with the needle pointing down.
The prefilled syringe is ready to use.
Do not expel any air from the syringe before administering the injection.
For therapeutic dosages (60 mg): Take the protective cap off the needle.
Adjust the close to be injected (if necessary): The amount of medicine to be injected must be adjusted depending on the patient 's body weight; therefore, any excess medicine must be expelled before injection. Hold the syringe pointing down (to keep the air bubble in the syringe) and expel the excess medicine into an appropriate container.
NOTE: If the excess medicine is not expelled before injection, the safety device will not be activated at the end of injection.
When there is no need to adjust the dose, the prefilled syringe is ready to use. Do not expel any air from the syringe before administering the injection.
A drop may appear at the tip of the needle. If this occurs, remove the drop before injection by tapping on the syringe, with the needle pointing down.
Administer the injection (all dosages: 40 and 60 mg): While lying down or sitting in a comfortable position, grasp a skin fold between your thumb and index finger.
Hold the needle at a right angle to the skin fold and inject into the skin fold. This skin fold should be held throughout the injection. Complete the injection using all of the medicine in the syringe.
Once the plunger is fully pressed down the safety device is activated automatically. This protects the used needle.
Note: The plunger has to be pressed down all the way for the safety device to be activated.
Immediately dispose of the syringe in the nearest sharps container.
For other information contact your physician.

Anticoagulants, Antiplatelets & Fibrinolytics (Thrombolytics)

B01AB05 - enoxaparin ; Belongs to the class of heparin group. Used in the treatment of thrombosis.

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