Fraxiparin ® injection solution is used for the following indications:
prevention of thromboembolic complications, namely: in patients with acute diseases (such as acute heart failure, respiratory failure, severe infections or rheumatic diseases) and reduced physical activity who are at high risk of thromboembolic complications; venous thromboembolic disease in surgical interventions accompanied by moderate and high risk of complications; prevention of blood clotting in the extracorporeal circulation circuit during hemodialysis (sessions that usually last ≤ 4 hours); treatment of deep vein thrombosis; treatment of unstable angina and acute myocardial infarction (AMI) without a pathological Q wave on the ECG in combination with acetylsalicylic acid.
Composition
The active substance is nadroparin calcium (1 ml of solution contains 9500 anti-Xa nadroparin calcium; 1 pre-filled syringe (0.4 ml) contains 3800 anti-Xa nadroparin calcium).
Excipients: calcium hydroxide solution (or diluted hydrochloric acid), water for injections.
Contraindication
Nadroparin is contraindicated in the following cases:
Hypersensitivity to nadroparin or any of the excipients; severe heparin-induced thrombocytopenia type II caused by unfractionated heparin or low molecular weight heparin in history, as well as nadroparin-induced thrombocytopenia in history; bleeding episodes or bleeding tendency associated with hemostasis disorders (disseminated intravascular coagulation may be an exception to this rule if not associated with heparin treatment); organic lesions with a risk of bleeding (e.g. active ulcer); acute hemorrhagic stroke; lack of data in severe renal impairment (defined creatinine clearance <30 ml/minute according to the Cockcroft formula) in therapeutic doses for the treatment of deep vein thrombosis, thromboembolic events, unstable angina and myocardial infarction without pathological Q wave, except for use in hemodialysis; epidural or spinal anesthesia is contraindicated if LMWH is used to treat; acute infective endocarditis (except for certain embolic cardiopathies); the drug is contraindicated in pediatric patients (up to 18 years of age).
In therapeutic doses, this drug is not recommended at all in the following cases:
acute periods of major acute ischemic stroke with or without impaired consciousness; if acute ischemic stroke is of embolic origin, it is necessary to wait 72 hours before using the drug; however, the effectiveness of LMWH in therapeutic doses has not yet been established regardless of the cause, extent of the lesion and clinical severity of ischemic stroke; the use of nadroparin is generally not recommended for patients with mild or moderate renal impairment; however, if its use is considered necessary in these cases, it should be considered: if the doctor considers it appropriate to reduce the dose for patients with mild to moderate renal impairment, taking into account individual risk factors for bleeding and thromboembolic complications (creatinine clearance ≥ 30 ml / minute and < 50 ml / minute), the dose should be reduced by 25-33%; dose reduction is not required for patients with mild renal impairment (creatinine clearance ≥ 50 ml / minute).
Also, this drug in therapeutic doses is not recommended at all for any patients, regardless of age, in combination with the following medications:
acetylsalicylic acid in doses used for pain relief, fever reduction and inflammation; nonsteroidal anti-inflammatory drugs (NSAIDs) (systemic administration); dextran 40 (parenteral administration).
In prophylactic doses, nadroparin is generally not recommended in the following cases:
severe renal impairment (creatinine clearance of about 30 ml/minute according to the Cockcroft formula); however, if its use is considered necessary in this situation, and also if, taking into account individual risk factors for bleeding or thromboembolic complications, a dose reduction is considered adequate by the personal physician, the dose should be reduced by 25-33%; intracerebral hemorrhage - within the first 24 hours.
Also, this drug in prophylactic doses is not recommended at all for patients over 65 years of age in combination with the following medications:
acetylsalicylic acid in doses used for pain relief, fever reduction and inflammation; NSAIDs (systemic administration); dextran 40 (parenteral administration).
Method of application
For subcutaneous use (except hemodialysis). This dosage form is intended for adults. Do not use for injection.
Do not remove the air bubble from the syringe before injection. Nadroparin is administered by subcutaneous injection, preferably with the patient in the supine position. The drug is injected into the subcutaneous tissue of the anterolateral and posterolateral abdominal walls, alternately on the right and left. The needle should be fully inserted perpendicularly, and not at any other angle, into the skin fold pinched between the thumb and forefinger of the operator. The skin fold should be held during the injection. Since there is a risk of developing GIT, platelet counts should be monitored throughout the course of treatment.
Prevention of venous thromboembolic disease during surgical interventions
In general, these recommendations apply to the timing of surgical interventions performed under general anesthesia. In the case of spinal and epidural anesthesia, the feasibility of preoperative administration should be assessed, taking into account the theoretical increased risk of spinal hematoma. Specific recommendations should be followed regarding the time intervals between the administration of nadroparin and the performance of spinal/epidural anesthesia or lumbar puncture.
The frequency of administration is one injection per day.
The dose administered depends on the individual risk associated with each patient and the type of surgery.
Surgery with moderate risk of thrombosis. During surgery with moderate risk of thrombosis and in patients not at high risk of thromboembolism, effective prophylaxis of thromboembolic disease is provided by daily administration of 2850 anti-Xa (0.3 ml). The treatment regimen studied included the first injection 2 hours before the intervention.
Surgical operations that are accompanied by a high risk of thrombosis. Operations on the hip or knee joints: the dose of nadroparin is selected depending on the patient's body weight. It is administered once a day for:
38 anti-Xa/kg: preoperative, i.e. 12 hours before surgery; postoperative, 12 hours after the end of surgery, and then once a day for the first three days after surgery; 57 anti-Xa/kg starting on the 4th day after surgery.
Other situations. If there is an increased risk of thromboembolic complications associated with the type of surgical intervention (especially in oncology operations) and/or with the patient himself (especially with a history of thromboembolic disease), a sufficient dose of nadroparin is 2850 IU (0.3 ml).
Duration of treatment. Treatment with LMWH in combination with conventional elastic compression techniques of the lower extremities should be continued until the patient is able to actively and fully move:
In general surgery, the duration of LMWH treatment should not exceed 10 days, except in individual cases of high patient-related risk of venous thromboembolic complications; if the risk of venous thromboembolic complications persists after the recommended duration of treatment, continued prophylactic therapy with oral anticoagulants should be considered.
However, the clinical benefit of long-term treatment with LMWH or VKA has not yet been studied.
Prevention of venous thromboembolic disease in patients with acute illnesses
Nadroparin is administered subcutaneously once daily. The dose should be adjusted according to the patient's body weight. Treatment should be continued throughout the entire period of thromboembolic risk.
Dose administered once daily:
body weight <70 kg - 0.4 ml; body weight> 70 kg - 0.6 ml.
The dose may be reduced to 0.3 ml (2800 anti-Xa) for elderly patients.
Prevention of blood clotting in the extracorporeal circulation circuit / during hemodialysis
Intravascular administration (into the arterial line of the dialysis circuit). In patients who regularly undergo hemodialysis, to prevent the formation of blood clots in the extrarenal blood purification circuit, the drug is administered into the arterial line of the dialysis circuit at a dose of 65 IU/kg at the beginning of the session.
This dose, administered as a single intravascular bolus, is intended only for dialysis sessions lasting 4 hours or less and should be adjusted accordingly to account for the significant inter-patient variability and individual patient effects.
General dosage recommendations depending on the patient's body weight (volume of the drug "Fraxiparin ®" per session):
<51 kg - 0.3 ml; 51-70 kg - 0.4 ml; > 70 kg - 0.5 ml.
The dose should then be adjusted according to the individual needs of each patient and the technical conditions of dialysis. In patients at risk of bleeding, dialysis sessions may be accompanied by the use of only half the dose.
Treatment of deep vein thrombosis (DVT)
If DVT is suspected, the diagnosis should be confirmed promptly by appropriate investigations.
The frequency of administration is two injections per day (i.e. every 12 hours).
Dose administered. A single dose is 85 IU anti-Xa/kg. Weight-based dosing of LMWH has been studied in patients weighing more than 100 kg or less than 40 kg. In patients weighing more than 100 kg, the effectiveness of LMWH treatment may be reduced, and in patients weighing less than 40 kg, the risk of bleeding is increased. Special clinical supervision is required.
General dosage recommendations based on patient body weight are 0.1 ml/10 kg every 12 hours.
Duration of treatment for DVT. When treating with LMWH, oral anticoagulant therapy should be started as early as possible, unless contraindicated. The duration of treatment with LMWH should not exceed 10 days, including the stabilization period when switching to VKA, unless stabilization is difficult. Therefore, oral anticoagulant therapy should be started as early as possible.
Treatment of unstable angina/non-Q wave myocardial infarction
Nadroparin is administered subcutaneously 2 times a day (every 12 hours) in a single dose of 86 IU anti-Xa/kg in combination with aspirin (recommended dosage: 75-325 mg orally after a minimum loading dose of 160 mg).
The initial dose should be administered as a bolus injection followed by subcutaneous administration of 86 anti-Xa/kg. Subsequent doses should be administered subcutaneously.
The recommended duration of treatment is approximately 6 days until the patient is clinically stabilized, with the dose calculation based on the patient's body weight.
If thrombolytic therapy is necessary in the absence of clinical data on the simultaneous administration of nadroparin and thrombolytics, it is recommended to interrupt treatment with nadroparin and treat the patient according to the usual regimen.
Application features
Pregnant women
Animal studies have not shown any teratogenic or fetotoxic effects of nadroparin. As a precautionary measure, prophylactic doses of nadroparin should not be used during the first trimester of pregnancy, and therapeutic doses should not be used throughout the entire pregnancy. The use of nadroparin in prophylactic doses in the second and third trimesters of pregnancy should not be considered unless the therapeutic benefit outweighs the potential risk. If epidural anesthesia is planned, prophylactic heparin should be temporarily discontinued, if possible, at least 12 hours before anesthesia.
Data on the excretion of nadroparin into breast milk are limited. However, absorption of nadroparin in the gastrointestinal tract of the newborn is theoretically unlikely, therefore treatment with nadroparin is not contraindicated during breastfeeding.
There are no clinical studies on the effects of nadroparin on fertility.
Children
Fraxiparin ® is not recommended for the treatment of children, as there is insufficient data on the safety and efficacy of the drug to determine the dosage for this group of patients.
Overdose
Accidental overdose with subcutaneous administration of large doses of LMWH may lead to hemorrhagic complications. It is necessary to determine the platelet count and other coagulation parameters. Minor bleeding very rarely requires specific treatment, usually it is enough to reduce or delay the next dose of nadroparin. In case of severe bleeding, the use of protamine sulfate is sometimes indicated.
However, it is not possible to completely neutralize anti-Xa activity. In addition, due to the kinetics of LMWH absorption, such neutralization may be temporary, so it is necessary to divide the full calculated dose of protamine into several injections (2 to 4) administered over a 24-hour period.
Ingestion, even in large doses, of LMWH (such cases have not been registered) theoretically does not lead to serious consequences, since the absorption of the drug at the gastric and intestinal levels is very low.
Side effects
Blood and lymphatic system: very often (≥ 1/10) - bleeding of various localizations, occurring mainly with:
concomitant risk factors: organic lesions with a tendency to bleeding, certain drug combinations, age, impaired renal function, insufficient body weight; non-compliance with therapeutic parameters, which include the duration of treatment and dose adjustment according to body weight.
Hepatobiliary system: often (≥ 1/100 and <1/10) - increased levels of hepatic transaminases, usually reversible.
Interaction
Do not mix with other drugs.
Storage conditions
Store in the original packaging at a temperature not exceeding 30 °C, out of the reach of children. Do not refrigerate. Do not freeze.
Shelf life - 3 years.
