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  • Clexane
    / Sanofi


    Active Ingredient
    Enoxaparin (as sodium) 100 mg/ml

    Status in Israel
    RX

    Presentation and Status in Health Basket

    Presentation Basket Yarpa Pharmasoft

    Pre-filled Syringe (solution for injection)

    2 X 20 mg / 0.2 ml

    partial basket chart 84286 3989

    Pre-filled Syringe (solution for injection)

    2 X 40 mg / 0.4 ml

    partial basket chart 84287 3990

    Pre-filled Syringe (solution for injection)

    2 X 60 mg / 0.6 ml

    partial basket chart 84288 3991

    Pre-filled Syringe (solution for injection)

    2 X 80 mg / 0.8 ml

    partial basket chart 84289 3992

    Pre-filled Syringe (solution for injection)

    2 X 100 mg / 1 ml

    partial basket chart 84290 3993

    Dosage

    SUBCUTANEOUS ROUTE (except for patients undergoing hemodialysis and in patients with acute ST-segment elevation myocardial infarction, in whom IV bolus administration is required). This presentation is suitable for adults. This drug is not to be injected via the intramuscular route. • Clexane 100mg/ml – One milliliter of solution for injection is equivalent to approximately 10000 anti-Xa IU of enoxaparin. • Clexane Forte 150mg/ml – One milliliter of solution for injection is equivalent to approximately 15000 anti-Xa IU of enoxaparin. Subcutaneous injection technique: The prefilled syringe is ready for immediate use; no air should be expelled before administering the injection. Enoxaparin should be administered by injection into the subcutaneous tissue, preferably with the patient supine. Administration should be alternated between the left and right anterolateral and posterolateral abdominal walls. The whole length of the needle should be inserted perpendicularly, not from the side, into a skin fold held between the thumb and forefinger. This skin fold should be held throughout the injection. General recommendation Regular monitoring of the platelet count is essential throughout the treatment due to the risk of heparin-induced thrombocytopenia (HIT).
    Dosage per indication Prophylactic treatment of venous thromboembolic disease in surgery As a general rule, these recommendations apply to surgical procedures carried out under general anesthesia. For spinal and epidural anesthesia techniques, the benefit of a pre-operative injection of enoxaparin should be weighed against the theoretically increased risk of spinal hematoma.
    Administration schedule One injection daily. Dose The dose must be determined based on the individual risk related to the patient and the type of surgery. o Surgery involving moderate thrombogenic risk: In surgery involving moderate thrombogenic risk and in patients who are not at high risk of thromboembolism, effective prevention is achieved by daily injection of 20mg (2000 anti-Xa IU, 0.2 ml). The studied dosage regimen involves administration of the first injection 2 hours before surgery. o Surgery involving high thrombogenic risk. Hip and knee surgery: The dosage is 40mg (4000 anti-Xa IU , 0.4 ml) injected once daily. The studied dosage regimen involves either administration of the first injection of 40mg (4000 anti-Xa IU) (total dose) twelve hours before surgery, or a first injection of 20mg (2000 anti-Xa IU) (half dose) 2 hours before surgery. Other situations: When there appears to be an increased risk of venous thromboembolism due to the type of surgery (particularly cancer surgery) and/or due to the patient (particularly history of venous thromboembolism), administering a prophylactic dose identical to that for high-risk orthopedic surgery, such as hip or knee surgery, can be considered. • Duration of treatment Treatment with LMWH should be maintained, along with the usual methods of elastic support of the legs, until the patient is fully and actively ambulatory: o in general surgery, the duration of LMWH treatment must be less than 10 days unless there is a patient-specific risk of venous thromboembolism; o the therapeutic benefit of prophylactic treatment consisting of an injection of 40mg (4000 anti-Xa IU)/day of enoxaparin for 4 to 5 weeks after hip surgery has been established; o if the patient is still at risk of venous thromboembolism after the recommended treatment duration, continuing prophylactic therapy must be considered, particularly by administration of oral anticoagulants; However, the clinical benefit of long-term treatment with low-molecular-weight heparins or oral anticoagulants has not yet been evaluated. Prevention of clotting in the 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 1mg (100 anti-Xa IU)/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 may be adjusted subsequently given high inter- and intra-individual variability. The maximum recommended dose is 1mg (100 anti-Xa IU)/kg. 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 0.5mg (50 anti-Xa IU)/kg (double vascular access) or 0.75mg (75 anti-Xa IU)/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 Enoxaparin sodium can be administered subcutaneously either as a single injection of 1.5mg/kg or as twice daily injections of 1 mg/kg. • Dose The dose per injection is 1mg (100 anti-Xa IU)/kg twice daily or 1.5mg (150 anti-Xa IU)/kg as a single injection. • 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 . Oral anticoagulant treatment should therefore be initiated as soon as possible. Curative treatment of unstable angina/non-Q-wave myocardial infarction A dose of 1mg (100 anti-Xa IU)/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 30mg(3000 anti-Xa IU) followed by an SC injection of 1mg (100 anti-Xa IU) /kg within 15 minutes, then every 12 hours (a maximum of 100mg (10000 anti-Xa IU) for each of the first two SC doses only, followed by 1 mg/kg SC dosing for the remaining doses). For dosage in patients ≥75 years of age, see Dosage and Administration: Renal Impairment and Elderly. 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 0.3mg (30 anti-Xa IU)/kg 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 3mg (300 IU)/ml (i.e. 0.3 ml of enoxaparin diluted in 10 ml).
    See prescribing information for full details.


    Indications

    Solution for injection at 20 mg and 40 mg: Prophylactic treatment of thrombo-embolic disorders of venous origin and in particular in orthopedic surgery or in general surgery. Prevention of thrombus formation in the extra-corporeal circulation during hemodialysis. Solution for injection at 40 mg: Prophylactic treatment of deep vein thrombosis (DVT) in patients who are bedridden due to an acute medicdbal disorder: Heart failure (NYHA class III or IV ); acute respiratory failure; episode of acute infection or acute rheumatic disorder combined with at least one other venous thromboembolic risk factor.Solution for injection at 60 mg, 80 mg and 100 mg: Treatment of deep vein thrombosis (DVT). Treatment of unstable angina and non-Q-wave myocardial infarction, administered concurrently with aspirin. Treatment of pulmonary embolism. Treatment of acute ST-segment elevation myocardial infarction, in combination with a thrombolytic agent in patients eligible or not for subsequent coronary angioplasty.Forte solution for injection at 120 mg and 150 mg: Treatment of deep vein thrombosis (DVT) once daily. Treatment of pulmonary embolism once daily. Multidose vials at 100 mg/ml: Treatment of acute ST-segment elevation myocardial infarction, in combination with a thrombolytic agent in patients eligible or not for subsequent coronary angioplasty.


    Contra-Indications

    Regardless of the dose (curative or preventive), this medicinal product MUST NOT BE USED in the following situations:  Hypersensitivity to enoxaparin, heparin or its derivatives, including the other LMWHs History of serious type II heparin-induced thrombocytopenia (HIT), whether caused by unfractionated or low-  molecular-weight heparin  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 Organic lesion likely to bleed  Clinically significant active bleeding  For the Multi Dose Vial presentation: Premature and full-term neonates, due to the benzyl alcohol content.
    See prescribing information for full details.


    Special Precautions

    General: 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.
    For the Multi Dose Vial presentation: As this medicinal product contains 15 mg/ml benzyl alcohol, it may cause toxic or anaphylactoid reactions in infants and children under 3 years of age.
    The administration of medications containing benzyl alcohol to newborns or premature neonates has been associated with a fatal “Gasping Syndrome” (symptoms include a striking onset of gasping syndrome, hypotension, bradycardia, and cardio-vascular collapse). As benzyl alcohol may cross the placenta, solution for injection should be used with caution in pregnancy. See prescribing information for full details.
    Special precautions for disposal and handling: Dispose of the product safely as instructed by your healthcare professional. For prefilled syringes with a safety system: Clexane/Clexane Forte is a solution for injection in prefilled syringes with an automatic safety system intended to prevent accidental needle sticks after injection. Instructions on how to use the device are provided in the Package Leaflet.


    Side Effects

    The adverse reactions observed in clinical studies and reported in 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); 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 patients1). Some of these cases have been fatal. As with other anticoagulants, haemorrhage may occur during enoxaparin therapy in the presence of associated risk factors such as: organic lesions liable to bleed, invasive procedures or the concomitant use of medications affecting haemostasis.The origin of the bleeding should be investigated and appropriate treatment instituted.Post marketing experience The following adverse reactions have been identified during post-approval use. 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 sodium as well as spinal/epidural anaesthesia or spinal puncture. These reactions have resulted in varying degrees of neurologic injuries including long-term or permanent paralysis.(For full details see prescribing information).
    Blood and Lymphatic System Disorders – Haemorrhagic anemia – Cases of immuno-allergic thrombocytopenia with thrombosis; in some of them thrombosis was complicated by organ infarction or limb ischaemia – 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.
    Hepatobilary disorders – Hepatocellular liver injury – Cholestatic liver injury.
    Musculoskeletal and connective tissue disorders – Osteoporosis following long-term therapy (greater than 3 months) • Valve thrombosis in patients with prosthetic heart valves have been reported rarely, usually associated with inadequate dosing. Heparin products can cause hypoaldosteronism which may result in an increase in plasma potassium. Rarely, clinically significant hyperkalaemia may occur particularly in patients with chronic renal failure and diabetes mellitus.
    See prescribing information for full details.


    Drug interactions

    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 above-mentioned drugs are co-administere.
    See prescribing information for full details.


    Pregnancy and Lactation

    Pregnancy: There is no evidence from animal studies that enoxaparin has teratogenic effects. In the absence of any teratogenic effect in animals, no such effect is expected in man. To date, substances responsible for malformation in humans have proved to be teratogenic in animals during well-conducted studies in two species. Prophylactic treatment during the first trimester and curative treatment There are currently not enough relevant clinical data to evaluate possible teratogenic or fetotoxic effects of enoxaparain when the drug is administered prophylactically during the first trimester or at curative doses throughout pregnancy. Consequently, as a precautionary measure, enoxaparin should preferably not be administered prophylactically during the first trimester, nor at curative doses throughout pregnancy. If epidural anesthesia is planned, prophylactic heparin treatment should be interrupted whenever possible at the latest within 12 hours before anesthesia. Epidural or spinal anesthesia should never be performed during curative treatment with LMWH. Prophylactic treatment during the second and third trimesters To date, there seems to be no evidence from clinical use of enoxaparin in a limited number of pregnancies during the second and third trimesters, that the drug administered at prophylactic doses has any particular teratogenic or fetotoxic effects. However, additional studies are needed to evaluate the effects of exposure under these conditions. Therefore, prophylactic enoxaparin treatment during the second and third trimesters should only be considered if necessary. If epidural anesthesia is planned, prophylactic heparin treatment should be interrupted whenever possible at the latest within 12 hours before anesthesia.
    Lactation: Since gastro-intestinal absorption by neonates is unlikely in principle, treatment with enoxaparin is not contraindicated in breast-feeding women.


    Overdose

    Accidental overdose following subcutaneous administration of massive doses of low-molecular-weight heparin may result in hemorrhagic complications. 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 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 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. 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. Accidental overdose following subcutaneous administration of massive doses of low- molecular-weight heparin may result in hemorrhagic complications. 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 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 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. 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.
    See prescribing information for full details.


    Manufacturer
    Sanofi Winthrop Industrie, France
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