Cutenox

Enoxaparin sodium.

Sterile, pyrogen-free, injectable solution contained in ready-to-use prefilled syringes.
Each Prefilled Syringe contains Enoxaparin sodium 20 mg, 40 mg, 60 mg, 80 mg; Water for Injection q.s. to 0.2 ml, 0.4 ml, 0.6 ml, 0.8 ml, respectively.
Excipients/Inactive Ingredients: Water for Injection.

Pharmaco-therapeutic class: Antithrombotic/Low molecular weight Heparin.
Pharmacology: Pharmacodynamics: Enoxaparin is a low molecular weight heparin with a high anti-Xa activity (100 I.U./mg), and with a low anti-IIa or anti thrombin activity (28 I.U./mg). At doses required for the various indications, enoxaparin does not increase bleeding time. At preventive doses, enoxaparin causes no notable modification of APTT. It neither influences platelet aggregation nor binding of fibrinogen to platelets.
Pharmacokinetics: The pharmacokinetic parameters have been studied in terms of the time course of plasma anti-Xa activity.
Bioavailability: After subcutaneous injection, enoxaparin is rapidly and completely absorbed. The bioavailability of enoxaparin is close to 95%.
Distribution: After subcutaneous injection, the maximum plasma activity is obtained 3 hours after the administration. The anti-Xa activity is located in the vascular space.
Biotransformation: Enoxaparin is primarily metabolized in the liver.
Elimination: The elimination half-life of anti-Xa activity is approximately 4.4 hours after administration of 40 mg of enoxaparin and 4 hours for an administration of 60 mg or 80 mg of enoxaparin.
Excretion: Enoxaparin is eliminated in the urine. In the elderly, the elimination is slightly decreased.

Prophylaxis of venous thromboembolism during surgical procedures, including cancer surgery.
Prophylaxis of deep vein thrombosis (DVT) in medical patients with severely restricted mobility during acute illness.
Treatment of established deep vein thrombosis with or without pulmonary embolism, without signs of clinical severity.
Prevention of thrombus formation in the extra-corporal circulation during hemodialysis.
Treatment of unstable angina/non-Q-wave myocardial infarction during the acute stage, in combination with aspirin.
Treatment of Acute ST-Segment Elevation Myocardial Infarction: For the treatment of acute STEMI in patients receiving thrombolysis and being managed medically or with percutaneous coronary intervention (PCI).
Additional therapeutic indications: Extended treatment of deep vein thrombosis (DVT) and pulmonary embolism (PE) and prevention of its recurrence in patients with cancer.

1 mg (0.01 ml) of enoxaparin corresponds approximately to 100 anti-Xa I.U.
For subcutaneous use, enoxaparin sodium injection should not be mixed with other injections or infusions.
Do not inject intramuscularly.
Subcutaneous administration technique: The prefilled syringes are ready-to-use. The air bubble from the syringe should not be expelled before the injection. The subcutaneous injection should preferably be made when the patient is lying down. Enoxaparin is administered in the subcutaneous cellular tissue of the anterolateral or posterolateral abdominal wall, alternately on the left and the right side. The injectable itself consists in introducing the needle perpendicularly and not tangentially, throughout its entire length into a fold of skin held between the thumb and index finger. The skin fold should be held throughout the injection. Do not rub the injection site after completion of the injection.
Prophylaxis of venous thromboembolism during surgical procedures, including cancer surgery: Enoxaparin sodium is given by subcutaneous injection; treatment is usually continued for 7 to 10 days or until the patient is ambulant.
Patients at low to moderate risk are given 20 mg (2000 units) once daily with the first dose about 2 hours pre-operatively.
In patients at high risk, such as those undergoing orthopedic surgery, the dose should be increased to 40 mg (4000 units) once daily with the initial dose given about 12 hours before the procedure. Alternatively, a dose of 30 mg (3000 units) may be given subcutaneously twice daily, starting within 12 to 24 hours after the operation. After hip replacement surgery, enoxaparin sodium may be continued in a dose of 40 mg (4000 units) once daily for a further 4-5 weeks.
For patients with a high venous thromboembolism (VTE) risk who undergo abdominal or pelvic surgery for cancer an extended thromboprophylaxis up to 4 weeks is recommended.
Prophylaxis of deep vein thrombosis (DVT) in medical patients with severely restricted mobility during acute illness: For the prophylaxis of deep vein thrombosis (DVT) in immobilised medical patients with acute medical conditions such as heart failure (NYHA class III or IV), acute respiratory failure, acute infections or acute rheumatic disease, the dose is 40 mg (4000 units) once daily for at least 6 days; treatment should be continued until the patient is fully ambulant up to a maximum of 14 days.
Treatment of established deep vein thrombosis with or without pulmonary embolism: The recommended dose is 1 mg/kg subcutaneously every 12 hours for 5 to 10 days. Afterward, the dosage is adjusted to 1.5 mg/kg subcutaneously once daily for up to 6 months. The benefit of anticoagulant therapy should be re-evaluated after 6 months of treatment.
Duration of therapy: 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.
In the extended treatment of deep vein thrombosis (DVT) and pulmonary embolism (PE) and prevention of its recurrence in patients with active cancer, physicians should carefully assess the individual thromboembolic and bleeding risks of the patient.
Prevention of thrombus formation in the extra-corporal circulation during hemodialysis: The recommended dose is 1 mg/kg. Enoxaparin should be introduced in the arterial line of the circuit at the beginning of the dialysis session. The effect of this dose is usually sufficient for a 4-hour session; in the event fibrin rings are found, a further dose of 0.5 to 1 mg/kg may be given. The dose should be reduced in patients at high risk of hemorrhage.
Treatment of unstable angina/non-Q-wave myocardial infarction during the acute stage, in combination with aspirin: A dose of 1 mg/kg should be given subcutaneously every 12 hours. The recommended treatment should be prescribed for a period of 2 to 8 days, until clinical stabilization of the patient. Enoxaparin should be administered concurrently with aspirin (100 to 325 mg daily per oral route).
Treatment of Acute ST-Segment Elevation Myocardial Infarction: In acute ST-elevation myocardial infarction the initial dose of enoxaparin is 30 mg (3000 units) intravenously, with a subcutaneous dose of 1 mg/kg given at the same time. Further dose of 1 mg/kg should be given subcutaneously every 12 hours for 8 days or until hospital discharge.
The first 2 subcutaneous doses should not exceed 100 mg (10000 units) each.
When administered in conjunction with a thrombolytic (fibrin-specific or non-fibrin specific), Enoxaparin Sodium should be given between 15 minutes before and 30 minutes after the start of fibrinolytic therapy.
Patients aged 75 years and older should be given subcutaneous doses only; the recommended dose is 0.75 mg/kg every 12 hours, with a maximum of 75 mg for each of first 2 doses.
Concomitant therapy: Unless contraindicated, all patients should receive aspirin (indefinitely).
For patients who undergo a percutaneous coronary intervention, an additional intravenous doses of 0.3 mg/kg should be given at the time of the procedure if the last subcutaneous dose was given more than 8 hours previously.
Special populations: Elderly: No dosage adjustment is necessary in preventive therapy. In curative therapy measurement of anti-Xa activity is recommended.
Children: Enoxaparin is not recommended for children.
Patients under 40 kg and over 100 kg weight: Particular clinical surveillance is necessary in order to adjust dosage if necessary. In all cases, strictly follow the Physician's prescription.
Renal impairment: Although no dose adjustment is recommended in patients with moderate (creatinine clearance 30 to 50 ml/min) and mild (creatinine clearance 50 to 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 as follows. (See table.)

Click on icon to see table/diagram/image

Action to be taken in case of overdose: Accidental overdosage after subcutaneous injection of massive doses of enoxaparin could lead to bleeding complications. Neutralization can be obtained by slowed intravenous injection of protamine sulfate (1 mg protamine sulfate can be use to neutralize the anticoagulant effect of about 1 mg enoxaparin). If more than 8 hours has elapsed since enoxaparin was administered, an infusion of 0.5 mg of protamine sulfate may be given for each 1 mg of enoxaparin sodium administered. If the activated partial thromboplastin time (aPTT) measured 2-4 hours after the first protamine infusion remains prolonged, a second dose of 0.5 mg of protamine sulfate may given for each 1 mg of enoxaparin sodium administered. Protamine administration may not be required if more than 12 hours has elapsed since administration of enoxaparin.

This medicine SHOULD NOT BE USED in the following situations: Hypersensitivity (allergy) to either enoxaparin, heparin or other low molecular weight heparins.
Major clotting disorders.
History of thrombocytopenia (in the past, marked fall in platelet count) with enoxaparin or with another heparin.
Active gastro-intestinal ulcer or organic lesion likely to bleed.
Acute infectious endocarditis (inflammation of the inner lining of the heart), except when affecting a mechanical valve replacement.
Hemorrhagic vascular cerebral stroke.
Uncontrolled arterial hypertension.

Do not inject intramuscularly.
Low molecular weight heparins should not be used interchangeably since they differ in their molecular weights, specific anti-Xa activities and dosage. Very careful attention and compliance with the specific mode of use of each product are absolutely essential.
Enoxaparin is to be used with extreme caution in patients with history of heparin-induced thrombocytopenia.
Spinal/Epidural anesthesia: As with other anticoagulants, there have been cases of neuraxial hematomas reported with the concurrent use of enoxaparin sodium and spinal/epidural anesthesia. These may result in long-term or permanent paralysis. The risk of these events is higher with use of post-operative indwelling epidural catheters or with concomitant use of drugs affecting hemostasis such as NSAIDs, platelet inhibitors or other anticoagulant (see Interactions). The risk also appears to be increased by traumatic or repeated neuraxial punctures. When scheduling or using epidural or spinal anesthesia/analgesia with enoxaparin, placement and removal of the catheter is best performed prior to enoxaparin administration. Otherwise it should occur when anticoagulant activity of enoxaparin is low. If an indwelling catheter remains in place for greater than 24 hours after surgery, the timing of catheter removal is extremely important: it should be removed 24 hours after the most recent dose of enoxaparin sodium. The subsequent enoxaparin sodium dose should be given no sooner than 2 hours after catheter removal. Extreme vigilance and frequent monitoring of the patient's neurological status is required.
If signs of neuraxial hematoma are suspected urgent diagnosis and treatment including spinal cord decompression are necessary.
This drug should only be taken under medical supervision.
Never suddenly discontinue treatment without consulting the Physician.

Enoxaparin injection procedure should be seriously observed. Monitoring of platelet count level is necessary regardless of the therapeutic indication and the dosage administered. It is recommended that the platelet count be measured before the initiation of the treatment and regularly thereafter during treatment. If a significant decrease of the platelet count (30 to 50% of the initial count) is observed, the treatment should be discontinued. Enoxaparin should be used with caution in case of renal or hepatic insufficiency, history of peptic ulcer or any organic lesion likely to bleed, hemorrhagic vascular cerebral stroke, uncontrolled severe arterial hypertension, diabetic retinopathy; shortly after neuro or ophthalmologic surgery and in case of spinal/epidural anesthesia (see Warnings).
In patients with cancer with a platelet count below 80 g/L (80,000 platelet count/mm³), anticoagulation treatment can only be considered on a case-by-case basis and careful monitoring is recommended. In case of doubt the patient must consult a Physician or Pharmacist for advice.

In case of pregnancy or lactation the patient always have to ask the Physician or Pharmacist for advice before the beginning of the treatment. As a precautionary measure, enoxaparin should not be used during pregnancy whereas lactation is not contraindicated.

Like any active product, this drug may induce undesirable effects to a greater or lesser degree.
Hemorrhage (bleeding): This may occur during treatment with any anticoagulant; the Physician should be informed immediately.
Bluish marks at injection sites.
Localized or general allergic reactions.
Thrombocytopenia (abnormally low platelet count level): Physician should be informed immediately.
Rare incidences of severe skin rash at injection sites: Consult a Physician.
Risk of osteoporosis (bone demineralization leading to bone fragility) if treatment is administered over several months.
Increased blood level of certain enzymes (transaminases).
Cause of neuraxial hematomas with the concurrent use of enoxaparin and spinal/epidural anesthesia or spinal puncture which may have resulted in varying degrees of neurologic injuries including long term or permanent paralysis have been reported (see Warnings).
Do not hesitate to ask a Physician or Pharmacist for advice and to report any undesirable effect not mentioned in this monograph.

In order to avoid possible interactions with other drugs the patient must inform the Physician or Pharmacist about any other current treatment. Not recommended combinations (substances increasing the risk of hemorrhage): acetylsalicylic acid (and derivatives) at analgesic and antipyretic doses. Non steroidal anti-inflammatory drugs (general route), ticlopidine, dextran 40 (parenteral use). Combinations to be used with caution: oral anticoagulant, thrombolytic drugs, acetylsalicylic acid at anticoagulant platelet dose (in the treatment of unstable angina and non-Q-wave myocardial infarction), glucocorticoids (general route).

Store below 30°C. Do not freeze. Keep inside packaging until use.

Anticoagulants, Antiplatelets & Fibrinolytics (Thrombolytics)

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

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