Parnaparin Natriya Velpharm (Solution) Instructions for Use

Marketing Authorization Holder

Velpharm-M, LLC (Russia)

Manufactured By

Velpharm, LLC (Russia)

ATC Code

B01AB07 (Parnaparin)

Active Substance

Parnaparin sodium (Rec.INN registered by WHO)

Dosage Forms

	Parnaparin sodium Velpharm	Solution for subcutaneous injection 3200 anti-Xa IU/0.3 ml
		Solution for subcutaneous injection 4250 anti-Xa IU/0.4 ml

Dosage Form, Packaging, and Composition

Solution for subcutaneous injection

0.3 ml – ampoules – cardboard packs – By prescription
0.3 ml – ampoules (2 pcs.) – cardboard packs – By prescription
0.3 ml – ampoules (3 pcs.) – cardboard packs – By prescription
0.3 ml – ampoules (4 pcs.) – cardboard packs – By prescription
0.3 ml – ampoules (5 pcs.) – cardboard packs – By prescription
0.3 ml – ampoules (6 pcs.) – cardboard packs – By prescription
0.3 ml – syringes – cardboard packs – By prescription
0.3 ml – syringes (2 pcs.) – cardboard packs – By prescription
0.3 ml – syringes (3 pcs.) – cardboard packs – By prescription
0.3 ml – syringes (4 pcs.) – cardboard packs – By prescription
0.3 ml – syringes (5 pcs.) – cardboard packs – By prescription
0.3 ml – syringes (6 pcs.) – cardboard packs – By prescription

Solution for subcutaneous injection

0.4 ml – ampoules – cardboard packs – By prescription
0.4 ml – ampoules (2 pcs.) – cardboard packs – By prescription
0.4 ml – ampoules (3 pcs.) – cardboard packs – By prescription
0.4 ml – ampoules (4 pcs.) – cardboard packs – By prescription
0.4 ml – ampoules (5 pcs.) – cardboard packs – By prescription
0.4 ml – ampoules (6 pcs.) – cardboard packs – By prescription
0.4 ml – syringes – cardboard packs – By prescription
0.4 ml – syringes (2 pcs.) – cardboard packs – By prescription
0.4 ml – syringes (3 pcs.) – cardboard packs – By prescription
0.4 ml – syringes (4 pcs.) – cardboard packs – By prescription
0.4 ml – syringes (5 pcs.) – cardboard packs – By prescription
0.4 ml – syringes (6 pcs.) – cardboard packs – By prescription

Pharmacotherapeutic Group

Antithrombotic agents; heparin group

Pharmacological Action

Parnaparin sodium is a direct-acting anticoagulant. It is a low molecular weight glycosaminoglycan with a molecular weight ranging from 4000 to 6000 Da (average molecular weight about 5000 Da), which is obtained during the depolymerization of heparin isolated from the porcine small intestinal mucosa.

Parnaparin sodium has an antithrombotic effect. In vitro and in vivo, it significantly inhibits factor Xa, has a slight effect on factor IIa and on aPTT. The antithrombotic activity (anti-Xa) of the drug exceeds the anticoagulant activity (anti-IIa). The ratio of anti-Xa/anti-IIa activity ranges from 1.5 to 3 (compared to heparin, for which this ratio is 1). Parnaparin sodium does not have a proaggregant platelet effect.

Pharmacokinetics

The pharmacokinetics of parnaparin sodium is linear in the dose range from 3200 anti-Xa IU to 12,800 anti-Xa IU. The bioavailability, assessed by anti-Xa activity, is close to 100%.

After a single subcutaneous injection, the maximum anti-Xa activity in plasma is reached after 2-3 hours. Then a decrease in activity is observed, which is still detectable 12 hours after administration. With repeated administration, a steady state is reached on day 3 when using the drug at a dose of 3200 anti-Xa IU 2 times/day and on day 4 when using a dose of 6400 anti-Xa IU 1 time/day.

AUC has a linear dependence on the dose. With subcutaneous administration, the pharmacokinetic profile of anti-Xa activity is more favorable compared to the profile with intravenous administration, as it is characterized by a smoother curve with fewer peaks and a slower decline in activity.

In the liver, Parnaparin sodium is metabolized to inactive compounds and excreted from the body by the kidneys. The T_1/2 is about 6 hours.

Indications

Deep vein thrombosis; post-thrombophlebitic syndrome; chronic venous insufficiency; acute superficial thrombophlebitis; varicophlebitis; prevention of deep vein thrombosis during general surgical and orthopedic operations, as well as in patients with a high risk of developing deep vein thrombosis.

ICD codes

Dosage Regimen

Administer subcutaneously into the abdominal area, into the thickness of the skin fold.

Ensure the single dose is 3200-6400 anti-Xa IU.

For prevention of deep vein thrombosis in general surgery, use 3200 anti-Xa IU once daily.

Initiate the first dose 2 hours before surgery.

Continue the regimen for at least 7 days or until the patient is fully ambulatory.

For prevention of deep vein thrombosis in orthopedic surgery, use 4250 anti-Xa IU once daily.

Initiate the first dose 12 hours preoperatively or 12 hours postoperatively.

Continue treatment for at least 10 days.

For treatment of established deep vein thrombosis, use 6400 anti-Xa IU twice daily.

Alternatively, use 4250 anti-Xa IU every 12 hours for initial treatment.

Adjust the frequency of administration and duration based on the clinical situation.

Set the total duration of therapy individually, according to the patient’s thrombotic risk.

For patients with a high risk of thrombosis, consider extended prophylaxis.

Do not administer intramuscularly or intravenously.

Rotate injection sites to minimize local reactions.

Monitor platelet counts regularly during therapy.

Discontinue immediately if thrombocytopenia is suspected.

Adverse Reactions

From the blood coagulation system: sometimes – thrombocytopenia; In isolated cases, spinal or epidural hematoma occurs, associated with the prophylactic use of the drug during spinal, epidural and lumbar puncture. The hematoma causes neurological disorders of varying severity, including persistent or irreversible paralysis.

Local reactions: sometimes – hematoma and skin necrosis at the injection site. Skin necrosis may be preceded by purpura or erythematous painful lesions with or without general symptoms.

Other: sometimes – allergic reactions; possibly – increased activity of liver transaminases.

Contraindications

Regional anesthesia in patients receiving Parnaparin sodium for therapeutic purposes; conditions or diseases complicated by bleeding, as well as an increased risk of bleeding or predisposition to bleeding in hemostasis disorders (except for consumption coagulopathy not caused by heparin), gastric and duodenal ulcer and erosive-ulcerative lesions of the gastrointestinal tract during exacerbation, angiodysplasia, chorioretinopathy, hemorrhagic stroke; thrombocytopenia induced by parnaparin sodium, including in the anamnesis; acute bacterial endocarditis (except for prosthetic endocarditis); severe uncontrolled arterial hypertension (BP >180/100 mm Hg); severe traumatic brain injury (in the postoperative period); simultaneous use with salicylates and other NSAIDs, antiplatelet drugs (clopidogrel, dipyridamole), sulfinpyrazone and the combination of ticlopidine with parnaparin in high doses; children and adolescents under 18 years of age; hypersensitivity to parnaparin, to heparin and pork products.

Use in Pregnancy and Lactation

There is no convincing data on the penetration through the placental barrier and excretion of parnaparin in breast milk.

Since the risk of toxic effects of parnaparin sodium on the fetus cannot be completely ruled out, use during pregnancy is possible only in case of extreme necessity and under direct medical supervision.

If it is necessary to use during lactation, breastfeeding should be discontinued.

In experimental studies on animals, no teratogenic or embryotoxic effects of parnaparin sodium were detected.

Special Precautions

Use with caution in patients with renal and hepatic insufficiency; mild and moderate arterial hypertension; gastric and duodenal ulcer and erosive-ulcerative lesions of the gastrointestinal tract in the anamnesis; other diseases/conditions in the anamnesis that may be complicated by bleeding; with thrombocytopenia caused by other low molecular weight heparins, including in the anamnesis; with chorioretinopathy in the anamnesis; with diseases of the brain and spinal cord in the postoperative period; simultaneously with indirect anticoagulants, systemic corticosteroids, dextran (for parenteral use).

Parnaparin sodium, like other low molecular weight heparins, can cause thrombocytopenia. Heparin-induced thrombocytopenia usually develops 4-10 days after the start of treatment or earlier in repeated cases. In 10-20% of patients, early mild thrombocytopenia (platelets >100,000/µl) occurs, which may persist or regress with continued treatment. As a result of the formation of antibodies to the heparin/platelet factor 4 complex, a more severe immune form, type II heparin-induced thrombocytopenia, may develop in some cases, followed by thrombosis and thromboembolism of the arteries of the brain, lungs, and lower extremities, often with a fatal outcome.

Parnaparin sodium should be used with particular caution in patients with a history of thrombocytopenia caused by heparin or another low molecular weight heparin; their platelet count should be measured daily. With thrombocytopenia <100,000/µl, with the occurrence and progression of thrombosis, Parnaparin sodium must be discontinued and the patient switched to alternative anticoagulant therapy. Switching to oral anticoagulant therapy in such cases is not recommended, as it may lead to the progression of thrombosis.

If heparin-induced thrombocytopenia is suspected, in vitro platelet aggregation tests are not of great diagnostic value; consultation with specialists is necessary.

Performing spinal or epidural anesthesia, spinal-epidural analgesia, or lumbar puncture against the background of prophylactic use of parnaparin sodium, as well as other low molecular weight heparins, may be complicated by spinal or epidural hematoma with the development of persistent or irreversible paralysis. The risk of these complications increases with the use of epidural catheters, with the simultaneous use of NSAIDs, antiplatelet drugs or anticoagulants, with trauma or repeated spinal punctures, the presence of initial hemostasis disorders or in elderly patients. If it is necessary to perform anesthesia/analgesia of this type against the background of prophylactic use of parnaparin sodium, the presence of these risk factors should be carefully checked before such interventions.

Particular attention should be paid to patients who received Parnaparin sodium before or after epidural or spinal anesthesia, checking for neurological symptoms such as back pain, sensory and motor disorders (numbness or weakness in the lower extremities), impaired bowel or bladder function. Patients should be informed of the need to immediately consult a doctor if these symptoms occur. If an epidural or spinal hematoma is suspected, immediate diagnosis and treatment are required, including spinal cord decompression.

Low molecular weight heparins differ from each other in molecular weight and specific activity, doses, so it is not recommended to alternate the use of parnaparin sodium with other low molecular weight heparins during treatment.

If skin necrosis develops, treatment with parnaparin sodium should be discontinued.

Drug Interactions

With simultaneous use with acetylsalicylic acid, other salicylates, NSAIDs, the risk of bleeding increases due to the antiplatelet effect and the damaging effect on the gastrointestinal mucosa of these drugs.

With simultaneous use with ticlopidine, the risk of bleeding increases due to the antiplatelet effect. Concomitant use with parnaparin sodium in high doses is contraindicated. When used together with parnaparin sodium in low prophylactic doses, careful clinical monitoring and control of coagulation parameters are necessary.

When used together with other antiplatelet drugs (for example, clopidogrel, dipyridamole), the risk of bleeding is increased.

The risk of bleeding is increased with simultaneous use with sulfinpyrazone.

With simultaneous use with oral anticoagulants, an enhancement of the anticoagulant effect is possible. When replacing parnaparin sodium with oral anticoagulants, careful monitoring of the patient is necessary. To assess the effect of these drugs on hemostasis, a blood test should be performed before prescribing parnaparin sodium.

The risk of bleeding is increased with the use of corticosteroids in high doses for more than 10 days due to damage to the gastrointestinal mucosa and a direct effect on the vascular wall. The use of parnaparin sodium simultaneously with corticosteroids must be justified and this therapy should be carried out under medical supervision.

With simultaneous use with dextran (for parenteral use), the risk of bleeding increases due to the antiplatelet effect. With such a combination, a dose adjustment of parnaparin sodium is necessary so that the decrease in blood coagulation parameters does not exceed 1.5 times.

The effect of parnaparin sodium is reduced with simultaneous use with ascorbic acid, antihistamines, cardiac glycosides, penicillin (for intravenous administration), tetracycline, phenothiazine derivatives.

Parnaparin sodium is an acidic polysaccharide that forms insoluble complexes with bases. For this reason, the solution of parnaparin sodium is incompatible with solutions of vitamin K, B vitamins, hydrocortisone, hyaluronidase, calcium gluconate, quaternary ammonium bases, chloramphenicol, tetracycline and aminoglycosides.

Storage Conditions

Store at 2°C (36°F) to 25°C (77°F). Keep in original packaging, protected from light. Keep out of reach of children.

Dispensing Status

Rx Only

Important Safety Information

This information is for educational purposes only and does not replace professional medical advice. Always consult your doctor before use. Dosage and side effects may vary. Use only as prescribed.