Frauxiparin 9,500 anti-Xa IU/ml /7,600 IU anti-Xa /0.8 ml 0.8 ml syringes, 10 pcs.

Fraxiparin is a low molecular weight heparin (LMWH) obtained by depolymerization from standard heparin and is a glycosoaminoglycan with an average molecular weight of 4300 daltons. It exhibits a high ability to bind to the plasma protein antithrombin III (AT III). This binding leads to an accelerated inhibition of factor Xa, which explains the high antithrombotic potential of nadroparin.

The other mechanisms providing the antithrombotic effect of nadroparin include activation of tissue factor conversion inhibitor (TFPI), activation of fibrinolysis by direct release of tissue plasminogen activator from endothelial cells and modification of blood rheological properties (reduction of blood viscosity and increase of membrane permeability of platelets and granulocytes).

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

In comparison with unfractionated heparin, nadroparin has less effect on platelet function and aggregation and little effect on primary hemostasis.

In prophylactic doses nadroparin does not cause a pronounced decrease in the BHRT. With a course of treatment during the period of maximum activity it is possible to increase the ABTV to a value of 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 high risk of thrombosis (in acute respiratory and/or cardiac failure in the ICU, unstable angina, myocardial infarction without pathological Q tooth on ECG).
– Treatment of thromboemboli.
– Prevention of blood clotting during hemodialysis.

Active ingredient

Composition

1 dose of the infusion solution contains:

calcium nadroparin 7,600 IU anti-Xa in 1 syringe.

Associates:

Calcium hydroxide solution or diluted hydrochloric acid to pH 5.0-7.5,

water d/i to 0.8 ml.

How to take, the dosage

If injected by injection, the drug is preferably administered in the supine position, into the pelvic or posterolateral surface of the abdominal region, alternately on the right and left side. It is allowed to be injected into the thigh. To avoid loss of drug when using syringes, air bubbles should not be removed before injection.

The needle should be inserted perpendicularly, not at an angle, into the pinched skin fold formed between the thumb and forefinger. The fold should be maintained throughout the insertion period. The injection site should not be rubbed after injection.

For the prevention of thromboembolism in general surgical practice, the recommended dose of Fraxiparin is 0.3 ml (2850 anti-Ha ME) p/k. The drug is administered 2-4 hours before surgery, then once a day. Treatment is continued for at least 7 days or for the entire period of increased risk of thrombosis, before the patient is transferred to an outpatient regimen.

For prevention of thromboembolism during orthopedic surgeries Fraxiparin is administered by p/k in dose adjusted according to patient’s body weight at the rate of 38 anti-Ha IU/kg, which may be increased up to 50% on the 4th postoperative day. The initial dose is administered 12 hours before surgery, the 2nd dose 12 hours after the end of surgery. Then, Fraxiparin is continued once daily during the whole period of increased risk of thrombosis until the patient is transferred to an outpatient regimen. The minimum duration of therapy is 10 days.

In patients with high risk of thrombosis (with unstable angina, myocardial infarction without Q-wave) Fraxiparin is administered by p/c 2 times/day (every 12 hours). The duration of treatment is usually 6 days. In clinical trials, patients with unstable angina/ myocardial infarction without Q-wave, Fraxiparin was prescribed in combination with acetylsalicylic acid at a dose of 325 mg/day. The initial dose is administered as a single v/v bolus injection, subsequent doses are administered by p/v. The dose is set depending on body weight at a rate of 86 anti-Xa IU/kg.

In the treatment of thromboembolism, oral anticoagulants (if there are no contraindications) should be administered as early as possible. Therapy with Fraxiparin is not stopped until the target values of prothrombin time are achieved. The drug is administered by p/c 2 times / day (every 12 hours), the normal course length 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 circulation system during hemodialysis: The dose of Fraxiparin should be set for each patient individually, taking into account the technical conditions of dialysis. Fracyparin is injected 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 according to body weight, but sufficient for a 4-hour dialysis session.

In patients at increased risk of bleeding, half the recommended dose of the drug may be used. If the dialysis session lasts longer than 4 hours, additional small doses of Fraxiparin may be administered. For subsequent dialysis sessions the dose should be adjusted according to the observed effects. The patient should be monitored during the dialysis procedure for possible bleeding or signs of thrombosis in the dialysis system.

Dose adjustment is not required in elderly patients (except in patients with impaired renal function). It is recommended to monitor renal function parameters before starting treatment with Fraxiparin.

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: to treat thromboembolism or to prevent thromboembolism in patients with high risk of thrombosis (in unstable angina and myocardial infarction without Q wave) the dose should be reduced by 25%; in patients with severe renal insufficiency the drug is contraindicated.

Interaction

Risk of hyperkalemia with concomitant use of Fraxiparin: the risk of hyperkalemia is increased when using Fraxiparin in patients receiving potassium salts, potassium-saving diuretics, ACE inhibitors, angiotensin II receptor antagonists, NSAIDs, heparins (low-molecular or unfractionated), cyclosporine and tacrolimus, trimethoprim.

Potentiation of action when using fraxiparin: Fraxiparin may potentiate the effects of drugs that affect hemostasis, such as acetylsalicylic acid and other NSAIDs, vitamin K antagonists, fibrinolytics and dextran, platelet aggregation inhibitors (except acetylsalicylic acid as an analgesic and antipyretic medication, ie.i.e., in a dose greater than 500 mg; NSAIDs: abciximab, acetylsalicylic acid as an antiaggregant (i.e., in a dose of 50-300 mg) in cardiac and neurological indications, beraprost, clopidogrel, eptifibatide, iloprost, ticlopidine, tirofiban increase the risk of bleeding.

Special Instructions

Particular attention should be paid to the specific instructions for use for each drug in the low molecular weight heparin class, since they may use different dosing units (units or mg). For this reason, it is unacceptable to alternate Fracyparin with other LMWHs during long-term treatment. It is also necessary to pay attention to whether Fracyparin or Fracyparin Forte is used, as this affects the dosing regimen. Graduated syringes are intended for selection of the dose depending on the patient’s body weight.

Fraxiparin is not intended for intravenous administration. As there is a possibility of thrombocytopenia (heparin-induced thrombocytopenia) when using heparin, it is necessary to monitor the thrombocyte level during the whole course of treatment with Fraxiparin. Rare cases of thrombocytopenia, sometimes severe, which may be associated with arterial or venous thrombosis have been reported, which is important to consider in the following cases: thrombocytopenia; a significant decrease in platelet levels (30-50% compared with normal values); negative dynamics from the thrombosis for which the patient is receiving treatment; DIC. In these cases, treatment with Fraxiparin should be discontinued. Thrombocytopenia is of immune-allergic 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 conventional or low molecular weight heparins), Fraxiparin may be prescribed if necessary. However, in this situation, strict clinical monitoring and at least daily measurement of platelet counts are indicated. If thrombocytopenia occurs, the use of Fraxiparin should be discontinued immediately. If thrombocytopenia occurs with heparins (normal or low molecular weight), other anticoagulants should be considered. If other drugs are not available, another low molecular weight heparin may be used. The blood platelet count should be monitored daily. If signs of initial thrombocytopenia continue to be observed after replacement of the drug, treatment should be discontinued as soon as possible.

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

The risk of spinal/epidural hematomas is increased in persons with epidural catheters in place or with concomitant use of other drugs that affect hemostasis (NSAIDs, antiaggregants, other anticoagulants). The risk probably also increases with traumatic or repeated epidural or spinal punctures. The combined use of neuroaxial blockade and anticoagulants should be decided on a case-by-case basis, after an assessment of the efficacy/risk ratio.

In patients already receiving anticoagulants, the need for spinal or epidural anesthesia must be justified. In patients who are scheduled for elective surgery with spinal or epidural anesthesia, the need for anticoagulants must be justified. If the patient undergoes a lumbar puncture or spinal or epidural anesthesia, a sufficient time interval between the administration of Fraxiparin and the insertion or removal of the spinal/epidural catheter or needle should be observed. The patient should be closely monitored for signs and symptoms of neurological abnormalities. If abnormalities in the patient’s neurological status are detected, urgent appropriate therapy is required.

During prevention or treatment of venous thromboembolism as well as during prevention of blood clotting in extracorporeal circulation system during hemodialysis it is not recommended to use Fraxiparin together with such drugs as acetylsalicylic acid, other salicylates, NSAIDs and antiaggregants because this may increase the risk of bleeding.
Fraxiparin should be used with caution in patients receiving oral anticoagulants, GCS for systemic use and dextrans.

If oral anticoagulants are administered to patients receiving Fraxiparin, its use should be continued until prothrombin time stabilizes to the required value.

Contraindications

– Thrombocytopenia with a history of nadroparin use.
– Signs of bleeding or increased risk of bleeding associated with impaired hemostasis (except for DIC syndrome not caused by heparin).
– Organic diseases with a tendency to bleeding (e.g., acute gastric or duodenal ulcer).
– Trauma or surgical interventions on the brain, spinal cord or eyes.
– Intracranial hemorrhage.
– Acute septic endocarditis.
– Severe renal failure (CKR less than 30 ml/min) in patients receiving Fraxiparin for treatment of thromboembolism, unstable angina and myocardial infarction without Q-wave.
– Child and adolescent age (under 18 years).
– Hypersensitivity to nadroparin or any other components of the drug.

Fraxiparin should be administered with caution in situations associated with an increased risk of bleeding: In hepatic failure, renal failure, severe arterial hypertension, a history of peptic ulcers or other conditions with an increased risk of bleeding, impaired blood flow in the vasculature and retina, in the postoperative period after operations on the brain and spinal cord or eyes, in patients with a body weight less than 40 kg, with a duration of therapy longer than recommended (10 days), if the recommended treatment conditions are not followed (especially increasing the duration and to

Side effects

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

High doses of Fraxiparin may provoke bleeding of various localizations and mild thrombocytopenia (type I), which usually disappears during further therapy. Temporary moderate increase of liver enzymes (ALT, AST) is possible.

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.

Overdose

Symptoms: the main sign of overdose is bleeding; the platelet count and other parameters of the clotting system should be monitored.

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

The use of protamine sulfate is necessary only in severe cases. Note that 0.6 ml of protamine sulfate neutralizes about 950 anti-Xa ME of nadroparin. The dose of protamine sulfate is calculated taking into account the time elapsed after heparin administration, with possible reduction of the antidote dose.

Pregnancy use

There are currently only limited data on penetration of nadroparin through the placental barrier in humans.

Hence, the use of Fracyparin in pregnancy is not recommended unless the potential benefit to the mother exceeds the risk to the fetus.

There are currently only limited data on the excretion of nadroparin with breast milk.

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

There have been no teratogenic effects of calcium nadroparin in experimental studies on animals.