Fraxiparine solution for subcutaneous injection of 9,500 anti-XaIU/ml (3800IU) 0.4ml syringes, 10pcs

Composition

1 syringe contains nadroparin calcium 3800 IU anti-Xa.

Pharmacological action

Fraxiparine-low molecular weight heparin (LMWH), obtained by depolymerization from standard heparin, is a glycoaminoglycan with an average molecular weight of 4,300 daltons.

It has a high ability to bind to the plasma protein antithrombin III (AT III). This binding leads to accelerated inhibition of factor Xa, which explains the high antithrombotic potential of nadroparin.

Other mechanisms that provide the antithrombotic effect of nadroparin include activation of a tissue factor conversion inhibitor (TFPI), activation of fibrinolysis through direct release of a tissue plasminogen activator from endothelial cells, and modification of the rheological properties of blood (reduced blood viscosity and increased permeability of platelet and granulocyte membranes).

Nadroparin calcium is characterized by a higher anti-Xa factor activity compared to anti-IIa factor or antithrombotic activity and has both immediate and prolonged antithrombotic activity.

Compared to unfractionated heparin, nadroparin has a lower effect on platelet function and aggregation, and little effect on primary hemostasis.

In prophylactic doses, nadroparin does not cause a marked decrease in APTT. With a course of treatment during the period of maximum activity, it is possible to increase the APTT to a value 1.4 times higher than the standard one. This prolongation reflects the residual antithrombotic effect of calcium nadroparin.

Indications

-Prevention of thromboembolic complications during surgical and orthopedic interventions in patients with a high risk of thrombosis (acute respiratory and / or heart failure in the ICU, unstable angina, myocardial infarction without a pathological Q wave on the ECG). – Treatment of thromboembolism. – Prevention of blood clotting during hemodialysis.

Use during pregnancy and lactation

Currently, there are only limited data on the penetration of nadroparin through the placental barrier in humans.

Therefore, the use of Fraxiparine during pregnancy is not recommended, unless the potential benefit to the mother outweighs the risk to the fetus.

Currently, there are only limited data on the excretion of nadroparin in breast milk.

In this regard, the use of nadroparin during lactation (breastfeeding) is not recommended.

No teratogenic effect of calcium nadroparin was found in experimental animal studies.

Contraindications

-Thrombocytopenia with a history of nadroparin use. – Signs of bleeding or an increased risk of bleeding associated with impaired hemostasis (with the exception of DIC-syndrome, not caused by heparin). – Organic diseases with a tendency to bleeding (for example, acute gastric or duodenal ulcers). – Injuries or surgeries on the brain, spinal cord, or eyes. – Intracranial hemorrhage. – Acute septic endocarditis. – Severe renal insufficiency (creatinine clearance less than 30 ml / min) in patients receiving Fraxiparine for the treatment of thromboembolism, unstable angina and non-Q-wave myocardial infarction. – Children and adolescents (under 18 years of age). – Hypersensitivity to nadroparin or any other components of the drug.

With caution should designate Fraxiparine in situations with a high risk of bleeding: when liver failure, renal failure, severe hypertension, if you have a history of peptic ulcers or other diseases with an increased risk of bleeding when blood circulation in the choroid and retina of the eye in the postoperative period after surgery on the brain and spinal cord, or eyes, in patients with body weight less than 40 kg, the duration of therapy beyond the recommended (10 days) in the case of non-compliance with the recommended treatment modalities (especially longevity and increasing doses for a course of application), in combination with drugs that increase the risk of bleeding.

Side effects

The most common side effect is the formation of a subcutaneous hematoma at the injection site. In some cases, there are dense nodules that do not mean encapsulation of heparin, which disappear after a few days.

High doses of Fraxiparine can cause bleeding of various localizations and mild thrombocytopenia (type I), which usually disappears during further therapy. There may be a temporary moderate increase in the level of liver enzymes (ALT, AST).

Skin necrosis and allergic reactions are rare. Several cases of anaphylactic reactions and immune thrombocytopenia (type II) combined with arterial and/or venous thrombosis or thromboembolism have been reported.

Interaction

Increased risk of hyperkalemia with concomitant use of Fraxiparine:  the risk of hyperkalemia increases with Fraxiparine in patients receiving potassium salts, potassium-sparing diuretics, ACE inhibitors, angiotensin II receptor antagonists, NSAIDs, heparins (low molecular weight or unfractionated), cyclosporine and tacrolimus, trimethoprim.

Potentiation of action when using Fraxiparine:  Fraxiparine can potentiate the effect of drugs that affect hemostasis, such as acetylsalicylic acid and other NSAIDs, vitamin K antagonists, fibrinolytics and dextran, platelet aggregation inhibitors (except for acetylsalicylic acid as an analgesic and antipyretic drugs, i. e. in a dose of more than 500 mg; NSAIDs): abciximab, acetylsalicylic acid as an antiplatelet agent (i. e. at a dose of 50-300 mg) for cardiological and neurological indications, beraprost, clopidogrel, eptifibatide, iloprost, ticlopidine, tirofiban increase the risk of bleeding.

How to take, course of use and dosage

When subcutaneous use of the drug is preferably administered in the supine position of the patient, in the subcutaneous tissue of the anterolateral or posterolateral surface of the abdominal region, alternately on the right and left sides. It can be inserted into the hip. To avoid losing the drug when using syringes, do not remove air bubbles before injection.

The needle should be inserted perpendicular, rather than at an angle, into the pinched skin fold formed between the thumb and index finger. The fold should be maintained throughout the entire period of drug use. Do not rub the injection site after the injection.

For the prevention of thromboembolism in general surgical practice, the recommended dose of Fraxiparine is 0.3 ml (2850 anti-Xa ME) subcutaneously. The drug is administered 2-4 hours before the operation, then-1 time/day. Treatment is continued for at least 7 days or for the entire period of increased risk of thrombosis, until the patient is transferred to outpatient mode.

To prevent thromboembolism during orthopedic operations, Fraxiparine is administered subcutaneously at a dose set depending on the patient’s body weight at the rate of 38 anti-Xa IU/kg, which can be increased to 50% on the 4th postoperative day. The initial dose is given 12 hours before surgery, and the second dose is given 12 hours after surgery. Further, Fraxiparine is continued to be used 1 time / day for the entire period of increased risk of thrombosis until the patient is transferred to outpatient mode.

The minimum duration of therapy is 10 days.

Patients at high risk of thrombosis (unstable angina, non-Q-wave myocardial infarction) Fraxiparine is prescribed subcutaneously 2 times a day (every 12 hours). The duration of treatment is usually 6 days. In clinical trials, Fraxiparine was administered in combination with acetylsalicylic acid at a dose of 325 mg/day in patients with unstable angina/non-Q-wave myocardial infarction. The initial dose is administered as a single intravenous bolus injection, subsequent doses are administered subcutaneously. The dose is set depending on body weight at the rate of 86 anti-Xa IU/kg.

In the treatment of thromboembolism, oral anticoagulants (if there are no contraindications) should be prescribed as early as possible. Fraxiparine therapy is not stopped until the target values of the prothrombin time indicator are reached. The drug is prescribed subcutaneously 2 times a day (every 12 hours), the usual course duration is 10 days. The dose depends on the patient’s body weight at the rate of 86 anti-Xa IU/kg of body weight. Prevention of blood clotting in the extracorporeal circulatory system during hemodialysis:  the dose of Fraxiparine should be set for each patient individually, taking into account the technical conditions of dialysis. Fraxiparine is administered once into the arterial line of the dialysis loop at the beginning of each session. For patients without an increased risk of bleeding, the recommended initial doses are set depending on body weight, but sufficient for a 4-hour dialysis session.

In patients with an increased risk of bleeding, half the recommended dose of the drug can be used. If the dialysis session lasts longer than 4 hours, additional small doses of Fraxiparine may be administered. When performing subsequent dialysis sessions, the dose should be selected depending on the observed effects. The patient should be monitored during the dialysis procedure for possible bleeding or signs of thrombosis in the dialysis system.

No dose adjustment is required in elderly patients (with the exception of patients with impaired renal function). Before starting treatment with Fraxiparine, it is recommended to monitor the indicators of renal function.

In patients with mild to moderate renal insufficiency (creatinine clearance ≥ 30 ml / min and less than 60 ml / min): to prevent thrombosis, no dose reduction is required; in patients with severe renal insufficiency (creatinine clearance less than 30 ml / min), the dose should be reduced by 25%.

In patients with mild to moderate renal insufficiency: for the treatment of thromboembolism or for the prevention of thromboembolism in patients at high risk of thrombosis (unstable angina and non-Q-wave myocardial infarction), the dose should be reduced by 25%, and the drug is contraindicated in patients with severe renal insufficiency.

Overdose

Symptoms: the main sign of overdose is bleeding; it is necessary to monitor the number of platelets and other parameters of the blood coagulation system.

Treatment: minor bleeding does not require special therapy (usually it is enough to reduce the dose or delay the subsequent use). Protamine sulfate has a pronounced neutralizing effect against the anticoagulant effects of heparin, but in some cases the anti-Xa activity may partially recover.

The use of protamine sulfate is necessary only in severe cases. It should be noted that 0.6 ml of protamine sulfate neutralizes about 950 anti-XaIU nadroparin. The dose of protamine sulfate is calculated taking into account the time elapsed after the use of heparin, with a possible reduction in the dose of the antidote.

Special instructions

Particular attention should be paid to the specific instructions for use for each drug belonging to the class of low-molecular-weight heparins, since they may use different dosage units (units or mg). Because of this, it is unacceptable to alternate Fraxiparine with other LMWH during long-term treatment. It is also necessary to pay attention to which drug is used – Fraxiparine or Fraxiparine Forte, because this affects the dosage regimen. Graduated syringes are designed to select the dose depending on the patient’s body weight.

Fraxiparine is not intended for intravenous use. Since there is a possibility of developing thrombocytopenia (heparin-induced thrombocytopenia) when using heparins, platelet levels should be monitored during the entire course of treatment with Fraxiparine. Rare cases of thrombocytopenia, sometimes severe, have been reported, which may be associated with arterial or venous thrombosis, which is important to consider in the following cases: with thrombocytopenia; with a significant decrease in the level of platelets (by 30-50% compared to normal indicators); with negative dynamics from thrombosis, for which the patient is receiving treatment; with DIC-syndrome. In these cases, treatment with Fraxiparine should be discontinued. Thrombocytopenia is immuno-allergic in nature and usually occurs between the 5th and 21st days of therapy, but may occur earlier if the patient has a history of heparin-induced thrombocytopenia.

In the presence of a history of heparin-induced thrombocytopenia (against the background of the use of conventional or low-molecular-weight heparins), Fraxiparine can be prescribed if necessary. However, in this situation, strict clinical monitoring and at least daily measurement of the platelet count is indicated. If thrombocytopenia occurs, Fraxiparine should be discontinued immediately. If thrombocytopenia occurs against the background of heparins (conventional or low-molecular-weight), then the possibility of prescribing anticoagulants of other groups should be considered. If other drugs are not available, another low-molecular-weight heparin may be used. At the same time, the number of platelets in the blood should be monitored daily. If signs of initial thrombocytopenia continue to occur after drug replacement, treatment should be discontinued as soon as possible.

It should be remembered that the control of platelet aggregation based on in vitro tests is of limited importance in the diagnosis of heparin-induced thrombocytopenia. In elderly patients, renal function should be evaluated before starting Fraxiparine therapy. Heparins can inhibit the secretion of aldosterone, which can lead to hyperkalemia, especially in patients with elevated blood potassium levels or in patients at risk of developing hyperkalemia (with diabetes mellitus, chronic renal failure, metabolic acidosis, or with concomitant use of drugs that can cause hyperkalemia, during long-term therapy). In patients with an increased risk of hyperkalemia, blood potassium levels should be monitored.

The risk of spinal/epidural hematomas is increased in individuals with installed epidural catheters or with concomitant use of other medications that affect hemostasis (NSAIDs, antiplatelet agents, other anticoagulants). The risk is also likely to increase with traumatic or repeated epidural or spinal punctures. The question of the combined use of neuroaxial blockade and anticoagulants should be decided individually, after evaluating the effectiveness/risk ratio. In patients who are already receiving anticoagulants, the need for spinal or epidural anesthesia should be justified. In patients who are planning elective surgery with spinal or epidural anesthesia, the need for the introduction of anticoagulants should be justified.

If the patient is undergoing a lumbar puncture or spinal or epidural anesthesia, a sufficient time interval should be observed between the introduction of Fraxiparine and the introduction or removal of the spinal/epidural catheter or needle. The patient should be closely monitored for signs and symptoms of neurological disorders. If violations in the neurological status of the patient are detected, urgent appropriate therapy is required.

In the prevention or treatment of venous thromboembolism, as well as in the prevention of blood clotting in the extracorporeal circulatory system during hemodialysis, the combined use of Fraxiparine with such drugs as acetylsalicylic acid, other salicylates, NSAIDs and antiplatelet agents is not recommended, as this may increase the risk of bleeding.

Fraxiparine should be used with caution in patients receiving oral anticoagulants, systemic corticosteroids, and dextrans. When prescribing oral anticoagulants to patients receiving Fraxiparine, its use should be continued until the prothrombin time indicator stabilizes to the required value.

Form of production

Solution for subcutaneous use.

Storage conditions

The drug should be stored out of the reach of children, away from heating devices at a temperature not exceeding 30°C; do not freeze.

Shelf

life is 3 years.

Active ingredient

Calcium Nadroparin

Conditions of release from pharmacies

By prescription

Dosage form

solution for injection

Purpose

For adults as prescribed by a doctor, for pregnant women as prescribed by a doctor

Indications

Angina, Myocardial infarction, Thrombosis prevention