FROSAN [Enoxaparin] 80 mg/0.8 ml Solution for IV, S/C injections
FROSAN
instructions for medical use of the medicinal product
Tradename
Frosan, Фросан
International non-proprietary name
Enoxaparin,
Composition
One syringe contains:
active substance : enoxaparin sodium - 2000 IU / 0.2 ml (20 mg); 4000 IU/0.4 ml (40
mg); 6000 IU/0.6 ml (60 mg); 8000 IU/0.8 ml (80 mg)
excipient : water for injection
Dosage form
Solution for subcutaneous administration.
Pharmacotherapeutic group
Direct acting anticoagulant.
Pharmacological properties
Pharmacodynamics
Enoxaparin sodium is a low molecular weight heparin with high anti-Xa activity (100 IU/mg) and low anti-IIa or antithrombin activity (28 IU/mg). At doses required for various indications, enoxaparin sodium does not increase bleeding time. At prophylactic doses, enoxaparin sodium does not cause a marked change in activated partial thromboplastin time (APTT). It does not affect either platelet aggregation or fibrinogen binding to platelets.
Pharmacokinetics
Pharmacokinetic parameters were studied using the time of action of plasma anti-Xa activity, as well as anti-IIa activity in the recommended dose ranges. The absolute bioavailability of enoxaparin sodium after subcutaneous administration is close to 100%. The mean maximum plasma anti-Xa activity was observed between 3 and 5 hours after subcutaneous injection. The pharmacokinetics of enoxaparin sodium is likely to be linear over the recommended dose ranges. Even if a difference in steady state pharmacokinetic parameters between single and repeated administration has been reported, this difference is expected and is within the therapeutic ranges. The mean maximum plasma anti-IIa activity was observed between 3 and 4 hours after subcutaneous administration. Enoxaparin sodium is primarily metabolized in the liver. The half-life for anti-Xa activity is approximately 4 hours after a single dose and up to 7 hours after a second dose. The renal clearance of active metabolites is approximately 10% of the administered dose, and the total renal excretion is 40% of the dose. In the elderly, as kidney function declines with age, excretion may be reduced. In patients with severe renal insufficiency (creatinine clearance <30 ml/min), AUC increases markedly after repeated subcutaneous administration of 4000 anti-Xa IU 1 time per day.
Indications for use
Solution for injection containing 2000 IU anti-Xa/0.2 ml and 4000 IU anti-Xa/0.4 ml is indicated for the following cases:
• prevention of venous thrombosis and thromboembolism (especially during orthopedic and surgical operations);
• prevention of venous thrombosis and thromboembolism in patients on bed rest (CHF III or IV NYHA class, acute respiratory failure, acute infections or acute rheumatic diseases in combination with one of the risk factors for venous thrombosis: age over 75 years, cancer, thrombosis and history of thromboembolism, obesity, hormonal therapy, CHF, chronic respiratory failure).
Solution for injection containing 6000 IU anti-Xa/0.6 ml and 8000 IU anti-Xa/0.8 ml is indicated for:
• treatment of deep vein thrombosis, with and without pulmonary embolism;
• treatment of unstable angina and myocardial infarction without a Q wave on the ECG, when taken together with acetylsalicylic acid;
• prevention of hypercoagulability in the extracorporeal circulation system during hemodialysis.
Contraindications
The drug should not be used:
• with known hypersensitivity (allergy) to enoxaparin sodium, heparin or other low molecular weight heparins;
• with cerebral aneurysm or dissecting aortic aneurysm (with the exception of surgery);
• with hemorrhagic stroke (established or suspected) and at high risk of uncontrolled bleeding;
• in severe uncontrolled arterial hypertension;
• with severe enoxaparin- or heparin-induced thrombocytopenia (during the last months);
• in childhood (due to the lack of data on the safety and efficacy of the drug in this category of patients).
Dosage and administration
Frosan is administered by deep subcutaneous injection during prophylactic and therapeutic treatment and into the arterial circuit during a hemodialysis session. Subcutaneous injection is best done with the patient in the supine position. The drug is injected alternately into the left or right anterolateral and posterolateral parts of the anterior abdominal wall. When injecting, the needle should be inserted perpendicularly, and not at an angle, for its entire length into the thickness of the skin, sandwiched in the crease between the thumb and forefinger. The skin fold should be held until the end of the injection. After the injection, the injection site should not be rubbed.
Prevention of venous thrombosis and thromboembolism in surgical patients
In patients with an average risk of thromboembolism (for example, during abdominal operations), the recommended dose of enoxaparin sodium is 2000 IU / 0.2 ml or 4000 IU / 0.4 ml once a day. In general surgery, the first injection should be given 2 hours before surgery.
In patients at high risk of thrombosis and thromboembolism (eg, in orthopedic surgery), the recommended dose of enoxaparin sodium is 4000 IU/0.4 ml once a day, starting 12 hours before surgery, or 3000 IU (30 mg) 2 once a day 12-24 hours after surgery. The duration of treatment with enoxaparin sodium is usually 7 to 10 days. Some patients may require longer treatment, and it should be continued as long as there is a risk of thrombosis and thromboembolism (in orthopedics, it is used at a dose of 4000 IU / 0.4 ml 1 time per day for 5 weeks).
Prevention of venous thrombosis and thromboembolism in therapeutic patients on bed rest
The recommended dose of enoxaparin sodium is 4000 IU/0.4 ml once a day for 6-14 days.
Treatment of deep vein thrombosis , with and without thromboembolism of the pulmonary artery
Enoxaparin sodium is administered at a dose of 150 IU/kg body weight (1.5 mg/kg) 1 time per day or 100 IU/kg (1 mg/kg) 2 times a day. For patients with complicated thromboembolic disorders, a dose of 100 IU / kg 2 times a day is recommended. The duration of treatment is 10 days. It is advisable to immediately start therapy with oral anticoagulants, while enoxaparin sodium therapy should be continued until a sufficient anticoagulant effect is achieved.
Treatment of unstable angina and non-Q wave myocardial infarction
The recommended dose of enoxaparin sodium is 100 IU/kg of body weight every 12 hours, while the appointment of acetylsalicylic acid at a dose of 100-325 mg 1 time per day. The average duration of therapy is 2-8 days (until the patient's clinical condition stabilizes).
Prevention of hypercoagulability in the extracorporeal circulation system during hemodialysis
The recommended dose of enoxaparin sodium is 100 IU/kg body weight. For patients at high risk of bleeding, the dose should be reduced to 50 IU/kg in dual vascular access or to 75 IU/kg in single vascular access. During hemodialysis, enoxaparin sodium should be injected into the arterial circuit at the start of the hemodialysis session. One dose is usually enough for a 4-hour session. However, if fibrin rings are detected during longer hemodialysis, an additional 50-100 IU / kg of body weight can be administered.
Special categories of patients
Elderly patients: no dose adjustment is required unless renal function is impaired.
In severe renal insufficiency, the dose is adjusted depending on the amount of creatinine clearance: with creatinine clearance less than 30 ml / min, the prophylactic dose is 2000 IU 1 time per day; therapeutic dose - 100 IU / kg of body weight 1 time per day. With mild to moderate renal insufficiency: dose adjustment is not required.
Special instructions and precautions
Do not enter in / m.
Low molecular weight heparins should not be used interchangeably as they differ in their manufacturing process, molecular weight, specific anti-Xa activity, units of action and dosage. It is necessary to strictly follow the specific instructions for the use of each drug.
Spinal/epidural anesthesia
When prescribing anticoagulant therapy during spinal / epidural anesthesia, particularly careful, constant monitoring of patients is necessary to detect any neurological symptoms (median back pain, impaired sensory and motor functions, including numbness or weakness in the lower extremities, dysfunction gastrointestinal tract and/or bladder). If symptoms characteristic of a brainstem hematoma are detected, urgent diagnosis and treatment are necessary, including, if necessary, spinal decompression.
Rare cases of spinal cord hematoma have been described in the treatment of enoxaparin sodium against the background of spinal/epidural anesthesia with the development of persistent paralysis. The risk of these phenomena is reduced when using the drug at a dose of up to 4000 IU. The risk increases with an increase in the dose of the drug, as well as with the use of penetrating epidural catheters after surgery or with the concomitant use of additional drugs that affect hemostasis (including NSAIDs). The risk also increases with traumatic or repeated lumbar puncture. During epidural or spinal anesthesia, insertion and removal of the catheter is best done when the anticoagulant effect of enoxaparin sodium is low: 10-12 hours after prophylactic doses of the drug or 24 hours after administration of higher doses (100 anti-Xa IU/kg of body weight). body 2 times a day or 150 anti-Xa IU / kg of body weight 1 time per day). Subsequent administration of the drug should be carried out no earlier than 2 hours after removal of the catheter.
Thrombocytopenia caused by the use of heparin
With a decrease in the number of platelets below the norm by 30-50%, as well as with the appearance of signs of internal bleeding (melena or detection of fresh blood in the feces, vomiting of blood, hypochromic anemia), enoxaparin sodium is canceled. With a history of thrombocytopenia induced by heparin in history, enoxaparin sodium is prescribed in exceptional cases due to the risk of immunoallergic thrombotic thrombocytopenia, which manifests itself 5-21 days after administration. The risk of heparin-induced thrombocytopenia may persist for several years.
Percutaneous coronary revascularization procedures
To reduce the risk of bleeding in the treatment of acute coronary syndrome, involving surgical invasive methods of treatment with a violation of the integrity of the vascular wall, the introduction of enoxaparin sodium should be carried out at least 6-8 hours before the manipulation or 6-8 hours after the manipulation.
Artificial heart valves
There are insufficient data on the efficacy and safety of the drug for the prevention of thromboembolic complications in patients with artificial heart valves.
Low weight
There has been an increase in the exposure of enoxaparin sodium during its prophylactic use in women weighing less than 45 kg and in men weighing less than 57 kg, which may lead to an increased risk of bleeding. Careful monitoring of the condition of such patients is recommended.
Obese patients
Obese patients have an increased risk of thrombosis and embolism. It is recommended to monitor the condition of patients for the development of symptoms and signs of thrombosis and embolism.
Laboratory samples
At doses used to prevent venous thrombosis and thromboembolism, enoxaparin sodium does not significantly affect bleeding time and general blood coagulation, as well as platelet aggregation or binding to fibrinogen. At higher doses, an increase in aPTT and activated clotting time may occur.
Influence on the ability to drive vehicles and mechanisms
Does not affect the management of vehicles and mechanisms that require increased concentration.
Use during pregnancy and during breastfeeding
There is no evidence that enoxaparin sodium crosses the placental barrier. However, it should only be used during pregnancy if absolutely necessary. Enoxaparin sodium is not recommended for use in pregnant women with prosthetic heart valves.
As a precautionary measure, nursing mothers taking enoxaparin sodium should be advised to avoid breastfeeding.
Interaction with other drugs
To avoid possible interactions with other medicines, inform your doctor about other medicines you are currently taking. It is recommended to interrupt the use of drugs that affect hemostasis before starting treatment with enoxaparin sodium, unless there are strict indications for this. Combination with vitamin K antagonists, antiplatelet agents (including acetylsalicylic acid and its derivatives, blockers of glycoprotein IIb / IIIa receptors), sulfinpyrazone, valproic acid, ketorolac and other NSAIDs is not recommended
(non-steroidal anti-inflammatory drugs), high molecular weight dextrans, clopidogrel, ticlopidine, glucocorticosteroids (systemic action), thrombolytics. As in the case of other low molecular weight heparins, if necessary, combined use with these drugs requires careful monitoring of the patient's condition and hemostasis.
Do not mix the drug in the same syringe with other drugs!
Side effect
Pinpoint hemorrhages (petechiae), ecchymosis, rarely - hemorrhagic syndrome (including retroperitoneal and intracranial bleeding, up to death), hyperemia and pain at the injection site, rarely - hematoma, the appearance of dense inflammatory nodes (resolve after a few days, discontinuation of treatment is not required); rarely - skin necrosis at the injection site, preceded by purpura or erythematous plaques (infiltrated and painful); asymptomatic thrombocytopenia (in the first days of treatment), rarely - immunoallergic thrombocytopenia (on days 5-21 of treatment) with the development
rebound thrombosis (heparin thrombotic thrombocytopenia), which can be complicated by organ infarction or limb ischemia; asymptomatic reversible increase in the activity of "liver" transaminases. Rarely - systemic and skin allergic reactions. Traumatic spinal/epidural anesthesia (increased with indwelling postoperative epidural catheter) Intraspinal hematoma (rare), which can lead to temporary or permanent paralysis.
If any of the side effects listed in the instructions get worse, or if you notice any other side effects not listed in the instructions, tell your doctor.
Overdose
Symptoms: bleeding.
Treatment: protamine sulfate (1 mg of protamine sulfate neutralizes the anti-IIa activity caused by 1 mg of enoxaparin sodium); high doses neutralize the anti-Xa activity of enoxaparin sodium by 60%.
Storage conditions
Store below 25º C. Do not freeze!
Keep out of the reach of children.
Best before date
2 years. Do not use after the expiry date stated on the package.
Holiday conditions
Released by prescription.
Release form
Single dose syringes 2000 IU/0.2 ml, 4000 IU/0.4 ml, 6000 IU/0.6 ml, 8000 IU/0.8 ml. 1 filled syringe is packed in PVC contour packaging sealed with aluminum foil. 2 PVC contour packs with instructions for use in a cardboard box.