Enoxaparin Sodium Injection BP
Composition of Enoxaparin 20
Each 0.2 ml pre-filled Syringe Contains
Enoxaparin Sodium BP 20 mg (2000 IU)
Water for injections BP q.s to 0.2m1
Indications Enoxaparin 20
Enoxaparin Injection is indicated for the prophylaxis of deep vein Thrombosis, which may lead to pulmonary embolism: in patients undergoing abdominal surgery who are at risk for thromboembolic complications;
in patients undergoing hip replacement surgery, during and following hospitalization;
in patients undergoing Thee replacement surgery;
in medical patients who are at riskforthromboembolic complications due to severely restricted mobikly during acute illness. -Enoxaparin Injection is indicated forthe prophylaxis of ischemic complications of unstable angina and non-(1-wave myocardial infarction, when concurrently administered with aspirin.
- Enoxaparin Injection is indicated for: the inpatient treatment of acute deep vein thrombosis with or without pulmonary embolism, when administered in conjunction with warfarin sodium; the outpatient treatment of acute deep vein thrombosis without pulmonary embolism when administered in conjunction with warfarin sodium.
Mechanism of Action
Enoxaparin binds to and accelerates the activity of antithrombin III. By activating antithrombin III, enoxaparin preferentially potentiates the inhibition of coagulation factors Xa and Ila. The anticoagulant effect of enoxaparin can be directly correlated to its ability to inhibit factor Xa. FactorXa catalyzes the conversion of prothrombin to thrombin, so enoxaparinis inhibition of this process results in decreased thrombin and ultimately the prevention of fibrin clotformation.
Pharmacokinetic
Absorption
Bloavallability
Mean absolute bioavailability of 92% when given sub-0 (based on anti-Factork activity).
Onset
Maximum anti-Factork and anti-thrombin (anti-Factor lia) activities occur 3-5 hours after administration.
Duration
Substantial anti-FactorX,activily persists in plasma for about 12 hours following administration (40 mg once daily).
Protein binding
BO% bound-albumin
Metabolism
Undergoes desulfation and polymerization viathe liver
Distribution
Extent
About 6 L (based on anti-Factor), activity).
Not known whether enoxaparin is distributed into milk.
Does not appearto cross placenta.
Elimination
Elimination Route
Enoxaparin sodium is primarily metabolized in the liver by desuffalion and/or depolymerization to lower molecular weight species with much reduced biological potency. Renal clearance of active fragments represents about 10% of the administered dose and total renal excretion of active and non-active fragments 40% of the dose.
Half-life 4.5 hours (based on anti-Factor), activity).
Contraindications The use of Enoxaparin Sodium injection BP should be avoided in the following cases:
Hypersensitivity to either enonparin sodium, heparin or its derivatives including other Low
Molecular Weight Heparin;
Active bleeding or serious blood coagulation disorder;
History or presence of thrombocytopenia following administration of enoxaparin or other heparin
through a type II immunologic mechanism
Active gestroduodenel ulcer;
Cerebrovascular episodes (unless there are systemic embolisms).
Acute bacterial endocarditis.
Adverse Effects
Haemorrhage
During enoxaparin sodium therapy, bleeding may occur in the presence of associated risk factors such as: organic lesions liable to bleed, invasive procedures orthe use of medications affecting haemostasis
The origin of the bleeding should be investigated and appropriate treatment instituted. Major haemorrhage including retropernoneal and intracranial bleeding has been reported. Some of these cases have been lethal. Them have been reports of neurmial haematomas with the concurrent use of enoxaparin sodium and spinaVepidural anaesthesia or spinal puncture. These events have resulted in varying degrees of neurologic injuries including long-term or permanent paralysis.
Thrombocylopenia
Mild, transient, asymptomatic thrombocytopenia (type I) has been reported dining the first days of therapy. Rare cases of immuno-allergic thrombocytopenia with orwithout thrombosis have been reported .
Local reactions
Pain, hematoma, and mild local irritation may follow the subcutaneous injection of enoxaparin sodium. Rarely, hard inflammatory nodules, which are not cystic enclosures of enoxaparin sodium, have been observed at the injection site. They resolve after a few days and should not cause treatment discontinuation. Exceptional cases of sib necrosis at the injection site have been reported with heparin and Low Molecular Weight Heparin. These phenomena are usually preceded by purpura or erythematous plaques, infiltrated and painful. Treatment must be discontinued.
Others
Very rare cases of hypersensitivity cutaneous vasculitis have been reported.
Warnings and Precautions of Enoxaparin 20:
Warnings
Neurologic Effects
Epidural or spinal hematomas and neurologic injury, including long-term or permanent paralysis, associated with concurrent use of low molecular weight heparin and neuraxial (spinaVepidural) anesthesia or spinal puncture procedures. Frequent monitoring for signs of neurologic impairment recommended.
Hematologic Effects
Use with extreme caution in patients with an increased risk of hemorrhage. Such patients include those with bacterial endocardilis, congenital or acquired bleeding disorders, active ulceration and angiodysplastic GI disease, hemorrhagic stroke, or recent brain, spinal, or ophthalmologic surgery. Increased risk for hemorrhage in patients treated concomitantly with platelet inhibitors. Carefully monitor patients with low body weight or renal impairment for signs and symptoms of bleeding. As with other anticoagulants, bleeding may occur at any site during therapy. Major (sometimes fatal) hemorrhages, including retroperitoneal and intracranial bleeding, have been reported. Search for bleeding site if an unexplained fall in hematocrit or blood pressure occurs. ti enoxaparin overdosage occurs, protamine sulfate may be administered. Because fatal reactions resembling anaphylaxis have been reported with protamine sulfate administration, use only when resuscitation techniques and treatment for anaphylactic shock are readily available. Valve thrombosis that was potentially fatal and/or required surgical intervention reported during prophylaxis in some patients (including pregnant women) with mechanical prosthetic heart valves. Women with mechanical prosthetic heartvalves are at higher riskfor thromboembolism during pregnancy. If enoxaparin is used, monitor ad-factor X, concentrations frequently and adjust dosage appropriatelyto maintain antifactork concentrations at approximately 1-1.2 units/mL.
Precautions
Hematologic Effects
Periodic CBCs, including platelet counts, and stool occult blood tests are recommended. If abnormal coagulation parameters or bleeding should occur, monitor anti-factorXa levels. If thromboembolic events occur despite prophylaxis, institute appropriate therapy.
Pregnancy and Lactation
Pregnancy
Animal studies have not shown any evidence of foetotoxicily or teratogenicily. In the pregnant rat, the transfer of ‘S-enoxaparin across the maternal placenta to the foetus is minimal.
In humans, there is no evidence that enoxaparin crosses the placental barrier during the second trimester of prognancy. There is no information available concerning the first and the thirdtrimesters.
As there are no adequately powered 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.
Pregnant women with mechanical prosthetic heart valves
The use of enoxaparin for thromboprophylmris in pregnant women with mechanical prosthetic heart valves has not been adequately studied. Ina clinical study of pregnant women with mechanical prosthetic heart valves given enoxaparin (1 mg/kg bid) to reduce the risk of thromboembolism, 2 of 8 women developed clots resulting in blockage of the valve and leading to maternal and foetal death. There have been isolated postmarketing reports of valve thrombosis in pregnant women with mechanical prosthetic heart valves while receiving enoxaparin forthromboprophylaids. Pregnant women with mechanical prosthetic heartvalves may be at higher risk forthromboembolism. Enoxaparin sodium is not recommended for use in pregnant women with prosthetic heart valves (see section 4.4 Special warnings and precautions tor use: Prosthetic heart valves).
Lactation In lactating rats, the concentration teS-enoxaparin arks labelled metabolites in milk is very low.
kis not known whether unchanged enoxaparin is excreted in human breast milk. The oral absorption of enoxaparin is unlikely. However, as a precaution, lactating mothers receiving enoxaparin should be advised to avoid breast-feeding.
Interactions
it is recommended that agents which affect haemostasis should be discontinued prior to enoxaparin therapy unless their use is essential, such as: systemic salicylates, acetylsalicylic acid, NSAIDs including ketorolac, dextran, and clopidogrel, systemic glucocorticoids, thrombolytics and anticoagulants. If the combination cannot be avoided, enoxaparin should be used with careful clinical and laboratory monitoring.
Dosage and Administration of Enoxaparin 20
Prophylaxis of deep vein thrombosis
In patients with a moderate risk of thromboembolism (&g. abdominal surgery), the recommended dose of enoxaparin sodium is 2000 anti—Xa IU (20 mg) or 4000 anti-Xa IU (40 mg) or 6000 anti-Xa IU (60 mg) once daily by subcutaneous injection. In general surgery, the first injection should be given 2 hours before the surgical procedure.
In patients with a high risk of thromboembolism (e.g. orthopedic surgery), the recommended dose of enoxaparin sodium given by subcutaneous injection, is 4000 anti-Xa IU (40 mg) once daily, initiated 12 hours prior to surgery or 3000 anti-Xa IU (30 mg) twice daily, initiated 12 to 24 hours after surgery. Enoxaparin sodium treatment should be prescribed for as long as There is a risk of thromboembolism, usually until the patient is discharged from the clinic or hospital (an average period of 7 to 10 days after the surgery). Continued therapy with 4000 anti-XAILI (40 mg) once daily for 3 weeks following the intlial therapy has been proven to be beneficial in orthopaedic surgery. Under normal conditions
of use, enoxaparin sodium does not alter the general blood coagulation tests and therefore, it is pointless to monitor the progress of the treatment with these tests. For special recommendations concerning dosing intervals for “spinaVepidural anesthesia” and “percutaneous coronary revascularisation procedures”
Prophylaxis of venous thromboembolism in medical (non-surgical) patients :
The recommended dose of enoxaparin sodium is 2000 anti-Xa IU (20 mg) or 4000 anti-Xa IU (40 mg) or 6000 ardi-Xa IU (60 mg) once daily by subcutaneous injection. Treatment with enmaparin sodium is prescribed for a minimum of 6 days and continued until the return to full ambulation, for a maximum of 14 days.
Treatment of deep vein thrombosis with or without pulmonary embolism:
For the treatment of deep vein thrombosis with or without pulmonary embolism, 100 anti-Xa !Mg It mg/kg) of body weight of enoxaparin sodium are administered twice daily (every 12 hours), subcutaneously. In patients with no thromboembolic risk followed also by no symptoms of pulmonary embolism 150 anti-Xa IUrirg (1.5 mg/kg) Enoxaparin Sodium injection BP should be given once daily.
Enoxaparin sodium treatment is usually prescribed for an average period of 10 days. Oral anticoagulant therapy should be initiated when appropriate and enoxaparin sodium treatment should be continued until a therapeutic marnicoagulant effect has been achieved (International Normalisation Ratio 2 to 3).
Treatment of unstable angina and non-Q-wave myocardial Infarction
The recommended dose of enoxaparin sodium is 100 anti-Xa IU/kg (1 mg/kg) every 12 hours by subcutaneous injection, administered concurrently with oral aspirin (100 to 325 mg once daily).
Treatment with enoxaparin sodium in these patients should be prescribed fora minimum of 2 days and continued until clinical stabilization. The usual duration °treatment is 2 to 8 days.
Prevention of extra corporeal thrombus during haemodialysis
In patients who undergo repeated sessions of haemodialysis, the prevention of thrombosis is the extra corporeal circulation during haemodialysis is achieved by the administration of one dose of 100 anti-Xa IU/kg (1 mg/kg) into the arterial line of the circuit of the haemodialysis atthe beginning of the session.
The effect of this dose is usually sufficient for a 4-hour session of haemodialysis; however, if fibrin rings are found, for example after a longer than normal session, a further dose of 50 to 100 anti-Xa IU/kg (0.5 to 1 mg/kg) may be given. For patients with a high risk of haemorrhage, the recommended dose should be reduced to 50 anti-Xa IU/kg (0.5 mg/kg) (for double vascular access) or 75 anti-Xa IU/kg (0.75 mg/kg) (for single vascular access).
Method of administration
The pre-filled disposable syringe is ready for immediate use. Enoxeparin Sodium is administered by deep subcutaneous injection.
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 atter administration.
When using ampoules orvials of enoxaparin sodium, the volume to be injected should be measured precisely with a graduated syringe fitted with an appropriate needle for subcutaneous injection.
Symptoms and Treatment of Overdosage
it enoxaparin overdosage occurs, protamine sulfate may be administered. Because fatal reactions resembling anaphylaxis have been reported with protamine sulfate administration, use only when resuscitation techniques and treatment for anaphylactic shock are readily available.
ff athromboembolic event occurs despite enoxaparin prophylaxis, discontinue the drug and initiate appropriate therapy.
Cases of heparin-induced thrombocytopenia with thrombosis reported, including complications such as organ infarction, limb ischemia, or death.
Use with extreme caution in patients with a history of heparin-induced thrombocytopenia. Monitor thrombocytopenia of any degree closely.
If platelet count falls to <100,000/md, discontinue therapy. ]
Presentation
Enoxaparin Sodium Injection BP (20 mg/0.2 ml):
Boxthat contains 2 pre-filled syringes of 0.2 ml in blister packaging
Shelf Life : 24 months
Storage : Store below 25 °C. Do not allow to freeze.
Marketed by:
PYXUS PHARMACEUTICALS PVT. LTD.
