Thenox

Each mL solution contains 10,000 anti-Xa IU equivalent to 100 mg enoxaparin sodium. One mg (0.01 mL) of enoxaparin sodium corresponds approximately to 100 anti-Xa IU.
Thenox 4,000 anti-Xa IU is equivalent to 40 mg in 0.4 mL.
Thenox 6,000 anti-Xa IU is equivalent to 60 mg in 0.6 mL.
Thenox 8,000 anti-Xa IU is equivalent to 80 mg in 0.8 mL.
Enoxaparin, a low molecular weight heparin prepared by alkaline degradation of unfractionated benzylated heparin, is anticoagulant. The average molecular weight of enoxaparin is approximately one-third that of heparin, 4500 Daltons.
Excipients/Inactive Ingredients: water for injection.

Pharmacotherapeutic group: Antithrombotic agent, heparin group. ATC code: B01AB05.
Pharmacology: Pharmacodynamics: Mechanism of action: Enoxaparin is a low molecular weight heparin having a small effect on the activated partial thromboplastin time (aPTT) and strongly inhibit factor Xa.
Pharmacodynamic effects: Onset of action: peak effect: Subcutaneous: anti-Xa and antithrombin (anti-IIa): 3 to 5 hours.
Duration: 40 mg dose: Anti-Xa activity: ~12 hours.
Pharmacokinetics: Enoxaparin is rapidly and almost completely absorbed after subcutaneous injection with a bioavailability of about 100%. Peak plasma activity occurs within 1 to 5 hours. The elimination half-life is about 4 to 5 hours but anti-Xa activity may persist for up to 24 hours after a 40 mg dose.
Elimination is prolonged in patients with renal impairment. Enoxaparin is metabolised in the liver and excreted in the urine, as unchanged drug and metabolites.

Thenox is a low-molecular weight heparin (LMWH). It is indicated for: Prophylaxis of post operative deep vein thrombosis (DVT) and/or pulmonary embolism (PE): Prophylaxis of DVT may lead to pulmonary embolism in patients undergoing general surgery including abdominal, hip or knee replacement, cancer surgery, who are at risk for thromboembolic complications.
Prophylaxis of deep vein thrombosis (DVT) in medical patients with an acute illness: Medically patients who are at risk for thromboembolic complications because of severely restricted mobility during acute illness such as acute heart failure, or NYHA Class III or IV, acute respiratory failure, severe lung diseases, acute/severe infections or acute rheumatic diseases.
Treatment of acute deep vein thrombosis (DVT) and/or pulmonary embolism (PE): Inpatient treatment of acute DVT with or without pulmonary embolism, when administered in conjunction with warfarin; for outpatient treatment of acute DVT without pulmonary embolism, when administered in conjunction with warfarin.
Prevention of thrombus formation (Clotting) in the extracorporeal circulation during hemodialysis.
Treatment of acute ST-segment elevation myocardial infarction (STEMI), in patients receiving thrombolysis and being managed medically or with percutaneous coronary intervention (PCI).
Prophylaxis and treatment of ischemic complications of unstable angina and non-ST elevation myocardial infarction (NSTEMI), when coadministered with aspirin and/or other therapy.

RECOMMENDED DOSE: General dosing consideration: All patients should be evaluated for a bleeding disorder before administration, unless the medication is needed urgently.
Adult: Prophylaxis of post operative deep vein thrombosis (DVT) and/or pulmonary embolism (PE): Abdominal surgery: Usual dosage: 4,000 anti-Xa IU (40 mg) once daily by subcutaneous injection, with the initial dose given 2 hours prior to surgery.
Duration of therapy: 7 to 10 days; up to 12 days has been administered in clinical trials.
Hip or knee replacement surgery: Usual dosage: 3,000 anti-Xa IU (30 mg) subcutaneously every 12 hours. Initially given 12 to 24 hours prior to surgery, provided that hemostasis has been established.
Alternative dosage: For hip replacement surgery, 4,000 anti-Xa IU (40 mg) every 24 hours subcutaneously given initially 12 (±3) hours prior to surgery may be considered. Following the initial phase of thromboprophylaxis in hip replacement surgery, continued prophylaxis with enoxaparin 4,000 anti-Xa IU (40 mg) subcutaneously once daily for 3 weeks is recommended.
Duration of therapy: 7 to 10 days; up to 14 days has been administered and well tolerated in clinical trials.
Prophylaxis of deep vein thrombosis (DVT) in medical patients with an acute illness: Usual dosage: 4,000 anti-Xa IU (40 mg) subcutaneously once a day.
Duration of therapy: 6 to 11 days; up to 14 days has been administered and well tolerated in a controlled clinical trial.
Treatment of acute deep vein thrombosis (DVT) and/or pulmonary embolism (PE): Usual dosage: In inpatients treatment with acute DVT with or without PE, 1 mg/kg every 12 hours or 1.5 mg/kg every 24 hours subcutaneously at the same time every day.
In outpatient treatment of patients with acute DVT without PE, 1 mg/kg subcutaneously every 12 hours.
Duration of therapy: Therapy should be continued for a minimum of 5 days and until a therapeutic oral anticoagulant effect has been obtained as indicated by an international normalization ratio (INR) of 2 to 3. The average duration of therapy is 7 days; up to 17 days has been administered and well tolerated in controlled trials.
Concomitant therapy: Warfarin should be initiated when appropriate (usually within 72 hours of enoxaparin).
Prevention of thrombus formation (Clotting) in the extracorporeal circulation during hemodialysis: Usual dosage: 1 mg/kg (100 units/kg) into the arterial line of the circuit at the beginning of the dialysis session. A further dose of 0.5 to 1 mg/kg (50 to 100 units/kg) may be given if required, for example when fibrin rings are found.
The dose should be reduced in patients at high risk of hemorrhage.
Treatment of acute ST-segment elevation myocardial infarction (STEMI): Usual dosage: Single intravenous (IV) bolus of 30 mg plus a 1 mg/kg subcutaneous dose only, followed by 1 mg/kg dosing for the remaining dose subcutaneously every 12 hours.
When administered in conjunction with thrombolytic therapy (fibrin-specific or nonfibrin-specific), enoxaparin should be initiated between 15 minutes before and 30 minutes after the start of thrombolytic therapy.
Maximum dose: 100 mg for the first 2 doses. Only followed by 1 mg/kg dosing for the remaining dose.
Duration of therapy: The American College of Cardiology Foundation/American Heart Association (ACCF/AHA) guidelines recommend continuation for up to 8 days or until revascularization.
Concomitant therapy: Unless contraindicated, all patients should receive aspirin (indefinitely) and clopidogrel.
Percutaneous coronary intervention: If the last subcutaneous administration was given less than 8 hours before balloon inflation, no additional dosing is needed. If the last subcutaneous administration was given more than 8 hours before balloon inflation, an IV bolus of enoxaparin 0.3 mg/kg should be administered.
Prophylaxis of ischemic complications of unstable angina and non-ST elevation myocardial infarction (NSTEMI): Usual dosage: 1 mg/kg subcutaneously every 12 hours.
Duration of therapy: The ACCF/AHA guidelines recommend continuation for the duration of hospitalization (a minimum of at least 2 days) or up to 8 days generally for 2 - 8 days.
Concomitant therapy: Aspirin 100 to 325 mg orally once daily. ACCF/AHA guidelines recommend aspirin doses of 81 mg in preference to higher maintenance doses.
Treatment of ischemic complications of unstable angina and non-ST elevation myocardial infarction (NSTEMI): A dose of 100 anti-Xa IU/kg of enoxaparin is administered by subcutaneous injection twice daily at 12-hour intervals, in combination with aspirin (recommended doses: 75-325 mg orally, following a minimum loading dose of 160 mg). The recommended duration of treatment is about 2-8 days, until the patient is clinically stable.
Pediatric population: The efficacy of enoxaparin in pediatric population has not been established.
Elderly (75 years of age and older): For all therapeutics indication except STEMI, dose reduction is not required in the elderly patients, unless renal function is impaired (see "Renal impairment" as follows).
Acute STEMI - Do not use an initial IV bolus. Initiate dosing with 0.75 mg/kg subcutaneously every 12 hours (maximum, 75 mg for the first 2 doses only, followed by 0.75 mg/kg dosing for the remaining doses).
Hepatic impairment: Enoxaparin has not been studied in patients with hepatic impairment, no dosage adjustments provided. Caution should be used in these patients.
Renal impairment: No dosage adjustment is recommended in patients with mild (creatinine clearance 50 - 80 mL/min) or moderate (creatinine clearance 30 - 50 mL/min) renal impairment. However, dosage should be adjusted in patients with severe renal impairment (creatinine clearance less than 15 - 30 mL/min).
Dose should be adjusted as shown in the table as follows. (See table.)

Click on icon to see table/diagram/image

MODE OF ADMINISTRATION: Enoxaparin should not be administered by intramuscular (IM) injection. It should be administered by subcutaneous (SC) or intravenous (IV) injection only.
Thenox, in prefilled syringe, are for single, one-time use only.
Subcutaneous injection: Patients should be lying down and enoxaparin should be 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 30 and 40 mg prefilled syringes.
Administration should be alternated between the left and the 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 until the injection is complete. Do not rub the injection site after completion of the injection to minimize bruising.
IV bolus injection: Enoxaparin should be administered through an IV line. It should not be mixed or coadministered with other injection or infusion. To avoid the possible mixture with other drugs, the IV access chosen should be flushed with a sufficient amount of saline or dextrose solution prior to and following the IV bolus administration to clear the port of the drug.
Admixture compatibility: For subcutaneous use, enoxaparin should not be mixed or coadministered with other injections or infusions. For IV use (i.e. for treatment of acute STEMI), enoxaparin can be mixed with normal saline solution (0.9%) or dextrose 5% in water.

OVERDOSE AND TREATMENT: As with other anticoagulants, bleeding may occur at any site during enoxaparin therapy. An unexpected decrease in hematocrit or blood pressure may indicate hemorrhage and should prompt evaluation to determine a bleeding site. To largely neutralize the effects of enoxaparin following overdosage, the dose of protamine sulfate is determined by the administered dose of the low molecular weight heparin, the time elapsed since the drug was given and blood coagulation studies.
The dose of protamine sulfate to be given should be equal to that of the administered enoxaparin sodium dose if enoxaparin was administered in the previous 8 hours (i.e., 1 mg of protamine sulfate should be given to neutralize 1 mg of enoxaparin sodium).
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 be 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. However, even after higher dosages of protamine sulfate, the aPTT may remain more prolonged than would be the case following treatment of overdosage of conventional heparin since anti-Xa activity is never completely neutralized. A maximum of about 60% of anti-Xa activity is neutralized with protamine sulfate administration of overdosage of enoxaparin.

Enoxaparin is contraindicated in patients with: Known hypersensitivity to enoxaparin, heparin, pork products or any other ingredient in formulation.
Active major bleeding and conditions or diseases involving a high risk of hemorrhage including: major blood clotting disorders; active gastric or duodenal ulcer; hemorrhagic cerebrovascular accident (except if there are systemic emboli); injuries to and operations on the brain, spinal cord, eyes and ears.
Current heparin induced thrombocytopenia (HIT) or HIT with thrombosis due to high cross-reactivity to heparin-platelet factor-4 antibody. Or thrombocytopenia associated with positive in vitro test for antiplatelet antibodies in the presence of the drug.

General warning: Do not administer intramuscularly. Not to be used interchangeably (unit to unit) with heparin or any other low molecular weight heparins. Due to the different in molecular weight, anti-Xa activity, etc.
Epidural or Spinal anesthesia or lumbar puncture: Neuraxial anesthesia or spinal puncture may result in epidural or spinal hematomas and subsequently long-term or permanent paralysis. Factors that can increase the risk of developing epidural or spinal hematomas include use of indwelling epidural catheters: concomitant use of other drug that affect hematostasis, such as NSAIDs, platelet inhibitors and anticoagulants. A history of traumatic or repeated epidural or spinal punctures and a history of spinal deformity or spinal surgery.
Clinicians should carefully consider in: The benefit and risk before neuraxial intervention in patients anticoagulated or to be anticoagulated for thromboprophylaxis.
The timing of spinal catheter placement and removal in relation to anticoagulant use, considering both the dosage and pharmacokinetic properties of the anticoagulant. Insertion or removal of epidural catheter or lumbar puncture is best performed when the anticoagulant effect of enoxaparin is minimal. In patients receiving low dosage of enoxaparin sodium (30 mg once or twice daily or 40 mg once daily), insertion or removal of a spinal catheter should be delayed for at least 12 hours after a dose of enoxaparin. In patients receiving higher dosage of enoxaparin sodium (0.75 mg/kg twice daily, 1 mg/kg twice daily or 1.5 mg/kg once daily), a delay of at least 24 hours is recommended between the enoxaparin dose and catheter placement/removal.
Monitoring frequently for sign and symptoms of neurological impairment. If neurological compromise is noted, urgent treatment is necessary.
Clinicians should adhere precisely to the recommended dosing interval for enoxaparin. Recommendations for the timing of sheath removal is based on the method of post-PCI arterial closure. If the closure device is used, the sheath may be removed immediately. If manual compression is used, the sheath should be removed 6 hours after the last dose of enoxaparin. If the treatment with enoxaparin is to be continued, the next scheduled dose should be given no sooner than 6-8 hours after sheath removal.
Hemorrhage: Enoxaparin should be used with extreme caution in patients with an increased risk of hemorrhage (e.g., congenital or acquired bleeding disorders; active ulceration and angiodysplastic GI disease; hemorrhagic stroke; recent brain, spinal or ophthalmic surgery; uncontrolled arterial hypertension; history of recent GI ulceration; diabetic retinopathy).
History of Heparin-induced thrombocytopenia (HIT): Enoxaparin should be used with extreme caution or avoid in patients with a history of HIT, especially if administered within 100 days of HIT episode.
Thrombocytopenia of any degree should be monitored closely, and enoxaparin should be discontinued if platelet count fall below 100,000/mm³. For patients with HIT with or without thrombosis, nonheparin anticoagulants such as lepirudin or argatroban are recommended; continued use of a low molecular weight heparin is contraindicated.
Patients with mechanical prosthetic heart valves: The use of enoxaparin for prophylaxis of thromboembolism in patients with mechanical prosthetic heart valves has not been adequately studied and a clinical consensus regarding optimal therapy remains to be established.
Pregnant women with mechanical prosthetic heart valves may be at higher risk for thromboembolism. If enoxaparin is used in pregnant women with mechanical prosthetic heart valves, frequent monitoring of peak and trough anti-factor Xa concentrations and adjustment of enoxaparin sodium dosage may be necessary.
The ACC/AHA suggest that the dosage of a low molecular weight heparin should be adjusted to maintain anti-factor Xa levels of 0.7-1.2 units/mL 4 hours after administration in pregnant women with mechanical prosthetic heart valves and that a low molecular weight heparin should not be used in such women unless anti-factor Xa levels are monitored 4-6 hours after administration of the drug.
Sensitivity reactions: Hypersensitivity reactions, including anaphylactoid reactions, pruritus, urticaria, vesiculobullous and rare cases of hypersensitivity cutaneous vesiculitis have occurred.

General precaution: Periodic complete blood cell counts, including platelet counts and stool occult blood tests are recommended during use of enoxaparin.
Routine monitoring of anti-Xa levels is not required but has been utilized in patients with obesity, and/or renal insufficiency. Anti-Xa level monitoring is recommended in pregnant women receiving enoxaparin for the prevention of thromboembolism with mechanical heart valves or receiving therapeutic dose of enoxaparin.
Specific populations: Low body weight: Increased exposure to enoxaparin has been observed in patients with low body weight (less than 45 kg in women or less than 57 kg in men); which may lead to a higher risk of bleeding. Therefore, such patients should be carefully monitored for signs and symptoms of bleeding.
Obese Patients: Obese patients are at higher risk for thromboembolism. Safety and efficacy of thromboprophylactic dosages of enoxaparin in patients with a body mass index (BMI) greater than 30 kg/m² have not been established and there is no consensus on how dosage should be adjusted in such patients. These patients should be closely monitored for signs and symptoms of thromboembolism.
Traceability: Enoxaparin is a biological product similar to other biological products. It is recommended for healthcare professionals record the trade name and batch number of the administered product in patients file to improve the product traceability.
EFFECTS ON ABILITY TO DRIVE AND USE MACHINE: Enoxaparin has no or negligible influence on the ability to drive and use machines.
Renal impairment: Using enoxaparin with caution in patients with renal impairment since elimination of the drug may be delayed. Patients with renal impairment should be carefully monitored for signs and symptoms of bleeding. In addition, anti-Xa levels may be used to monitor the anticoagulant effect of enoxaparin in patients with substantial renal impairment.
Hepatic impairment: Enoxaparin has not been studied in patients with hepatic impairment. Caution should be used in these patients.
Use in Children: Safety and efficacy not established in children younger than 18 years of age.
Use in the Elderly: No substantial differences in efficacy relative to younger adults. In elderly patients, a high incidence of bleeding complications has been observed following administration of enoxaparin sodium at a dosage of 1.5 mg/kg once daily or 1 mg/kg every 12 hours, and the risk of bleeding complications increases with age.

Pregnancy: There are no adequate and well-controlled studies of enoxaparin in pregnant women. However, available data in humans and animals indicate that enoxaparin does not cross the placenta and has not shown evidence of teratogenicity or fetotoxicity.
Breast-feeding: It is not known whether enoxaparin is distributed into milk; because many drugs are distributed into human milk and because of the potential for serious adverse reactions to enoxaparin in nursing infants, a decision should be made whether to discontinue nursing or the drug, taking into account the importance of the drug to the woman.
Fertility: No clinical data of enoxaparin sodium in fertility.

As with all anticoagulants, bleeding is the major adverse effect of enoxaparin. Hemorrhage may occur at virtually any site. Risk is dependent on multiple variables. At the recommended doses, single injections of enoxaparin do not significantly influence platelet aggregation or affect global clotting time (i.e. PT or aPTT).
1%-10%: Central nervous system: confusion (2%), pain.
Gastrointestinal: nausea (3%), diarrhea (2%).
Hematologic & oncologic: Major hemorrhage (<1% to 4%; includes cases of intracranial, retroperitoneal or intraocular hemorrhage; incidence varies with indication/population), thrombocytopenia (moderate 1%; severe 0.1%), anemia (<2%), bruise.
Hepatic: increased serum ALT (6%), increased serum AST (6%).
Local: Hematoma at injection site (9%), irritation at injection site, bruising at injection site, erythema at injection site, pain at injection site.
Renal: Hematuria (≤2%).
Miscellaneous: Fever (5% to 8%).
<1%, post-marketing and/or case report: Alopecia, anaphylaxis, anaphylactoid reaction, eczematous rash (plaques), eosinophilia, epidural hematoma (spinal; after neuraxial anesthesia or spinal puncture; risk may be increased with indwelling epidural catheter or concomitant use of other drugs affecting hemostasis), headache, hepatic injury (hepatocellular and cholestatic), hyperkalemia, hyperlipidemia (very rare), hypersensitivity angiitis, hypersensitivity reaction, hypertriglyceridemia, intracranial hemorrhage (up to 0.8%), osteoporosis (following long-term therapy), pruritic erythematous rash (patches), pruritus, purpura, retroperitoneal hemorrhage, severe anemia (hemorrhagic), shock, skin necrosis, thrombocythemia, thrombocytopenia, thrombosis (prosthetic valve [in pregnant females] or associated with enoxaparin-induced thrombocytopenia; can cause limb ischemia or organ infarction), urticaria, vesiculobullous rash.

Drugs Affecting Hemostasis: Potential pharmacodynamic interaction (increased risk of bleeding) when enoxaparin is used with drugs inhibiting coagulation (e.g., anticoagulants, platelet aggregation inhibitors [e.g., salicylates or other nonsteroidal anti-inflammatory agents, dipyridamole, sulfinpyrazone]). Such drugs should be discontinued prior to initiating enoxaparin therapy since concomitant use of enoxaparin with these agents may increase the risk of hemorrhage. If concomitant use of enoxaparin and drugs that affect hemostasis is considered essential, careful clinical and laboratory monitoring is advised.

Store below 25°C. Do not freeze.
SHELF-LIFE: 36 months.

Anticoagulants, Antiplatelets & Fibrinolytics (Thrombolytics)

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

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