Noxadium 4000/Noxadium 6000

Noxadium 4000: Clear colourless liquid.
Each 0.4 mL solution contains: Enoxaparin Sodium 4000 IU Anti-Factor Xa (equivalent to 40 mg).
Noxadium 6000: Clear colourless solution.
Each 0.6 mL solution contains: Enoxaparin Sodium 6000 IU Anti-Factor Xa (equivalent to 60 mg).

Pharmacotherapeutic group: Antithrombotic agent, heparin group.
Pharmacology: Pharmacodynamics: Noxadium 4000: Pharmacodynamic effects: Enoxaparin is a LMWH with a mean molecular weight of approximately 4,500 daltons, in which the antithrombotic and anticoagulant activities of standard heparin have been dissociated. The drug substance is the sodium salt. In the in vitro purified system, enoxaparin sodium has a high anti-Xa activity (approximately 100 IU/mg) and low anti-IIa or anti thrombin activity (approximately 28 IU/mg), with a ratio of 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 antithrombotic 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 antithrombotic effect of enoxaparin sodium. When used as prophylactic treatment, enoxaparin sodium does not significantly affect the aPTT.
When used as curative treatment, aPTT can be prolonged by 1.5-2.2 times the control time at peak activity.
Pharmacokinetics: Absorption and Distribution: Maximum anti-Factor Xa and anti-thrombin (anti-Factor) activities occur 3 to 5 hours after SC injection of Enoxaparin. Mean peak anti-Factor Xa activity was 0.16 IU/mL (1.58 pg/mL) and 0.38 IU/mL (3.83 pg/mL) after the 20 mg and 40 mg clinically tested SC doses, respectively. Mean (n=46) peak anti-Factor Xa activity was 1.1 IU/mL at steady state in patients with unstable angina receiving 1 mg/kg SC every 12 hours for 14 days. Mean absolute bioavailability of Enoxaparin, after 1.5 mg/kg given SC, based on anti-Factor Xa activity is approximately 100% in healthy volunteers.
Enoxaparin pharmacokinetics appears to be linear over the recommended dosage ranges. After repeated subcutaneous administration of 40 mg once daily and 1.5 mg/kg once daily regimens in healthy volunteers, the steady-state is reached on day 2 with an average exposure ratio about 15% higher than after a single dose. Steady-state Enoxaparin activity levels are well predicted by single-dose pharmacokinetics. After repeated subcutaneous administration of the 1 mg/kg twice daily regimen, the steady state is reached from 4 with mean exposure about 65% higher than after a single dose and mean peak and trough levels of about 1.2 and 0.52 IU/mL, respectively. Based on Enoxaparin sodium pharmacokinetics, this difference in steady state is expected and within the therapeutic range.

Prophylaxis of Deep Vein Thrombosis.
Treatment of Acute Deep Vein Thrombosis.
Prophylaxis of Ischaemic Complications of Unstable Angina and Non-Q-Wave Myocardial Infarction.
Treatment of Acute ST-Segment Elevation Myocardial Infarction (STEMI).

All patients should be evaluated for a bleeding disorder before administration of Enoxaparin, unless the medication is needed urgently, or as prescribed by the physician.
Abdominal surgery: In patients undergoing abdominal surgery who are at risk for thromboembolic complications, the recommended dose of Enoxaparin is 40 mg once a day administered by SC injection with the initial dose given 2 hours prior to surgery. The usual duration of administration is 7 to 10 days; up to 12 days administration has been well tolerated in clinical trials.
Hip or Knee Replacement surgery: In patients undergoing hip or knee replacement surgery, the recommended surgery dose of enoxaparin is 30 mg every 12 hours administered by SC injection. Provided that hemostasis has been established, the initial dose should be given 12 to 24 hours after surgery.
For hip replacement surgery, a dose of 40 mg once a day SC is given initially 12 hours prior to surgery may be considered. The initial phase of thromboprophylaxis in hip replacement surgery patients, continued prophylaxis with Enoxaparin 40 mg once a day administered by SC injection for 3 weeks is recommended. The usual duration of administration is 7 to 10 days; up to 14 days administration has been well tolerated in clinical trials.
Medical Patients During Acute illness: In medical patients at risk for thromboembolic complications due to severely restricted mobility during acute illness, the recommended dose of Enoxaparin is 40 mg once a day administered by SC injection. The usual duration of administration is 6 to 11 days up to 14 days of Enoxaparin has been well tolerated in the controlled clinical trial.
Administration: Enoxaparin is a clear, colorless to pale yellow sterile solution, and as with other parenteral drug products, should be inspected visually for particulate matter and discoloration prior to administration.
Enoxaparin is administered by SC injection. It must not be administered by intramuscular injection. Enoxaparin is intended for use under the guidance of a physician. Patients may self-inject only if their physician determines that it is appropriate and with medical follow-up, as necessary. Proper training in subcutaneous injection technique (with or without the assistance of an injection device) should be provided.
Subcutaneous Injection Technique: Patients should be lying down and enoxaparin administered by deep SC injection. To avoid the loss of drug do not expel the air bubble from the syringe before the injection. Administration should be alternated between the left and right anterolateral and left and right posterolateral abdominal wall. The whole length of the needle should be introduced into a skin fold held between the thumb and forefinger; the skin fold should be held throughout the injection. To minimize bruising, do not rub the injection site after completion of the injection.

Accidental overdosage following administration of Enoxaparin may lead to hemorrhagic complications. Injected enoxaparin may be largely neutralized by the slow I.V. injection of protamine sulfate (1% solution). The dose of protamine sulfate should be administered to neutralize 1 mg Enoxaparin If Enoxaparin Sodium was administered in the protamine administration, or if it has been determined that a second dose of protamine is required. The second infusion of 0.5 mg protamine sulfate per 1 mg of Enoxaparin may be administered if the aPTT measured 2 to 4 hours after the first infusion remains prolonged.
After 12 hours of the enoxaparin sodium injection, protamine administration may not be required. However, even with higher doses of protamine, the aPTT may remain more prolonged than under normal condition found following administration of heparin. In all cases, the anti-Factor Xa activity is never completely neutralized (maximum about 60%).

Enoxaparin is contraindicated in patients with active major bleeding, in patients with thrombocytopenia associated with a positive in vitro test for antiplatelet antibody in the presence of Enoxaparin Sodium, or in patients with hypersensitivity to Enoxaparin Sodium. Patients with known hypersensitivity.

General: Enoxaparin should not be mixed with other injections for infusion.
Enoxaparin should be used with care in patients with a bleeding diathesis, uncontrolled arterial hypertension or a history of recent gastrointestinal ulceration, diabetic retinopathy, and hemorrhage. Enoxaparin should be used with care in elderly patients who may show delayed elimination of enoxaparin.
If thromboembolic events occur despite enoxaparin prophylaxis, appropriate therapy should be initiated.

Pregnancy: In humans, there is no evidence that enoxaparin crosses the placental barrier during the second and third trimester of pregnancy. There is no information available concerning the first trimester.
Animal studies have not shown any evidence of foetotoxicity or teratogenicity. Animal data have shown that enoxaparin passage through the placenta is minimal.
Enoxaparin sodium should be used during pregnancy only if the physician has established a clear need. Pregnant women receiving enoxaparin sodium should be carefully monitored for evidence of bleeding or excessive anticoagulation and should be warned of the haemorrhagic risk. Overall, the data suggest that there is no evidence for an increased risk of haemorrhage, thrombocytopenia or osteoporosis with respect to the risk observed in non-pregnant women, other than that observed in pregnant women with prosthetic heart valves.
If an epidural anaesthesia is planned, it is recommended to withdraw enoxaparin sodium treatment before.
Breastfeeding: It is not known whether unchanged enoxaparin is excreted in human breast milk. In lactating rats, the passage of enoxaparin or its metabolites in milk is very low. The oral absorption of enoxaparin sodium is unlikely. Enoxaparin can be used during breastfeeding.
Fertility: There are no clinical data for enoxaparin sodium in fertility. Animal studies did not show any effect on fertility.

Hemorrhage: The incidence of major hemorrhagic complication during Enoxaparin treatment has been low.
Thrombocytopenia: Mild to moderate thrombocytopenia can occur with the administration of Enoxaparin. Cases of heparin-induced thrombocytopenia with thrombosis have also been observed in clinical practices. Some of these cases were complicated by organ infarction, limb ischemia, or death.
Since Aminotransferase determinations are important in the differential diagnosis of myocardial infarction, liver disease, and pulmonary emboli, elevations that might be caused by drugs like Enoxaparin should be interpreted with caution.
Local Reaction: Mild local irritation, pain, hematoma, ecchymosis, and erythema may follow SC Enoxaparin than in patients treated with I.V. heparin.
Adverse events in Enoxaparin treated patients with unstable angina or Non-Q-wave myocardial infection: Non major hemorrhagic, primarily injection site ecchymoses and hematomas were more frequently reported in patients treated with I.V. heparin.

Unless really needed, agents which may enhance the risk of hemorrhage should be discontinued prior to initiation of Enoxaparin therapy. These agents include medications such as: anticoagulants, platelet inhibitors including acetylsalicylic acid, salicylates, NSAIDS (including ketorolac, tromethamine), dipyridamole, or sulfinpyrazone. If co-administration, conduct close clinical and laboratory monitoring.
Heparin-induced thrombocytopenia: Enoxaparin should be used with extreme caution in patients with a history of heparin-induced thrombocytopenia.
Hemorrhage: Enoxaparin, like other anticoagulants, should be used with extreme caution in conditions with increased risk of hemorrhage, such as bacterial endocarditis, congenital or acquired bleeding disorders, active ulcerative and angiodysplastic gastrointestinal disease, hemorrhagic stroke, or shortly after brain, spinal, or ophthalmological surgery, or in patients treated concomitantly with platelet inhibitors. Cases of epidural or spinal hematomas have been reported with the associated use of Enoxaparin and spinal/epidural anesthesia or spinal puncture resulting in long-term or permanent paralysis. The risk of these events is higher with the use of post-operative indwelling epidural catheters or by the concomitant use of additional drugs affecting homeostasis such as NSAIDS.
Major hemorrhages including retroperitoneal and intracranial bleeding have been reported. Some of these cases have been fatal.
Bleeding can occur at any site during therapy with Enoxaparin. An unexplained fall in hematocrit or blood pressure should lead to a search for a bleeding site.
Low-weight patients: An increase in exposure of Enoxaparin with sodium with prophylactic dosages (non-weight adjusted) has been observed in low weight (<45 kg) and low-weight men (<57 kg), which may lead to a higher risk of bleeding. Therefore, careful clinical monitoring is advised. Patients should be observed carefully for signs and symptoms of bleeding.
Use in Pregnancy: Enoxaparin is not predicated to increase the risk of development and abnormalities.
Enoxaparin does not cross the placenta, based on human and animal studies, and shows no evidence of teratogenic effects of fetoxicity.
Since there are no adequate and well-controlled studies in pregnant women, Enoxaparin should be used during pregnancy only if clearly needed. Pregnant women should be apprised of the potential hazard to the fetus and the mother if Enoxaparin is administered during pregnancy.

Store at temperatures not exceeding 30°C.

Anticoagulants, Antiplatelets & Fibrinolytics (Thrombolytics)

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

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