Dimolegin (Tablets) Instructions for Use

Marketing Authorization Holder

Avexima Diol, LLC (Russia)

Manufactured By

Pharmazashchita SPC, FSUE FMBA of Russia (Russia)

ATC Code

B01AF (Direct factor Xa inhibitors)

Dosage Form

Dimolegin

Enteric-coated film-coated tablets, 10 mg: 60 or 100 pcs.

Dosage Form, Packaging, and Composition

Enteric-coated film-coated tablets white or almost white, biconvex, round in shape.

Excipients: ProSolv SMCC 90 HD (Prosolv^® SMCC 90 HD) [microcrystalline cellulose, colloidal silicon dioxide] – 79.5 mg, magnesium stearate – 0.5 mg.

Coating composition methacrylic acid – ethyl acrylate copolymer – 6.08 mg (60.8%), talc – 1.52 mg (15.2%), titanium dioxide – 1.216 mg (12.16%), triethyl citrate – 1.064 mg (10.64%), colloidal silicon dioxide – 0.12 mg (1.2%) or an identical ready-made film coating – 10 mg.

10 pcs. – blister packs (6) – cardboard packs.
10 pcs. – blister packs (10) – cardboard packs.

Clinical-Pharmacological Group

Anticoagulant – direct factor Xa inhibitor

Pharmacotherapeutic Group

Direct factor Xa inhibitors

Pharmacological Action

A highly selective direct inhibitor of the coagulation factor Xa protein.

The activation of factor X to form factor Xa via the intrinsic and extrinsic coagulation pathways plays a central role in the coagulation cascade. Factor Xa is a component of the forming prothrombinase complex, the action of which leads to the conversion of prothrombin to thrombin. As a result, these reactions lead to the formation of a fibrin thrombus, consisting of platelets entangled with fibrin strands. Factor Xa molecules catalyze the formation of a large amount of thrombin and enhance the blood clotting process by activating platelets and a number of coagulation factors. Selective factor Xa inhibitors, which include this agent, prevent the formation of thrombin and blood clots.

Pharmacokinetics

The active substance after oral administration slowly enters the systemic circulation (T_max 3.5 h). It penetrates into blood cells. T_max of the active substance in blood cells is reached in 3.7 h (approximately simultaneously with plasma). When entering the blood, it predominantly accumulates in blood cells, as the C_max and AUC values in blood cells – 26.07 ng/ml and 554 ng×h/ml are higher than in plasma – 19.37 ng/ml and 245.2 ng×h/ml.

It is metabolized with the formation of a hydroxy derivative form. Conjugates with glucuronic acid were not detected. T_1/2 from blood plasma is long – 61.7±19.8 h, T_1/2 from blood cells – 76.2±35.3 h. There is no data on excretion with milk. It is excreted mainly by the kidneys with urine. Sufficiently high concentrations of the active substance in the urine are detected within 48 hours after administration. The active substance is detected unchanged in the feces.

Indications

For the prevention of thrombotic complications as part of complex therapy in adult patients diagnosed with a new coronavirus infection (COVID-19) of moderate severity.

ICD codes

Dosage Regimen

Administer orally once daily. Take the recommended dose of 60 mg at the same time each day, preferably in the morning with food or on an empty stomach.

Swallow the tablet whole with water; do not crush, split, or chew the enteric-coated tablet.

The standard duration of treatment is up to 30 days as part of a complex therapy for COVID-19. Do not exceed this treatment period without specific medical instruction.

If a dose is missed, take it as soon as remembered on the same day. If remembered on the next day, skip the missed dose and resume the normal schedule; do not double the dose to compensate.

Discontinue therapy immediately and seek medical attention if signs of clinically significant bleeding occur.

No dosage adjustment is required for elderly patients or those with mild to moderate renal impairment. The drug is contraindicated in patients with severe renal impairment (CrCl <30 ml/min).

Adverse Reactions

Hemorrhagic complications – there is an increased risk of occult or overt bleeding from any organs and tissues, which can lead to post-hemorrhagic anemia. The risk of bleeding may increase in patients with uncontrolled arterial hypertension and/or when used concomitantly with drugs that affect hemostasis. Signs, symptoms, and severity may vary depending on the location, intensity, or duration of bleeding. Hemorrhagic complications can manifest as weakness, pallor, dizziness, headache, or unexplained swelling, shortness of breath, shock, the development of which cannot be explained by other causes. Due to anemia, symptoms of myocardial ischemia may develop, such as chest pain and angina. When using anticoagulants, secondary complications in relation to severe bleeding may develop, such as compartment syndrome and renal failure due to hypoperfusion.

From the blood and lymphatic system infrequently – thrombocytosis.

From the heart often – bradycardia (without QT_c interval prolongation).

From the skin and subcutaneous tissues infrequently – urticaria, subcutaneous hematoma.

From the kidneys and urinary tract infrequently – hematuria.

Contraindications

Hypersensitivity to the active substance; clinically significant active bleeding (intracranial hemorrhage, gastrointestinal bleeding); concomitant therapy with fibrinolytics and other anticoagulants (unfractionated heparin, low molecular weight heparins, heparin derivatives, vitamin K antagonists, oral anticoagulants, direct thrombin inhibitors); anemia (no experience of use); thrombocytopenia (no experience of use); congenital thrombophilias (antithrombin III deficiency, protein C deficiency, protein S deficiency, Leiden mutation of coagulation factor V, increased level of coagulation factor VIII, prothrombin G20210A mutation); other blood clotting disorders and contraindications to the prescription of anticoagulants; liver diseases with impaired function (except for non-alcoholic steatohepatitis with normal activity of liver transaminases) and biliary tract (no experience of use); severe renal failure (CrCl <30 ml/min); diseases of the digestive organs that may impair the absorption of the drug (Crohn’s disease, ulcerative colitis, irritable bowel syndrome); pregnancy; breastfeeding period; children under 18 years of age.

With caution should be used in patients with an increased risk of bleeding (with congenital or acquired bleeding tendency, uncontrolled severe arterial hypertension, gastric and duodenal ulcer in the acute stage, recently suffered gastric and duodenal ulcer, vascular retinopathy, bronchiectasis or history of pulmonary bleeding, erosive gastritis with an increased risk of bleeding, presence of malignant tumors with a high risk of bleeding, recent head or spinal cord injury, recent surgery on the brain, spinal cord or eyes, recent intracranial hemorrhage, diagnosed or suspected esophageal varices, vascular aneurysm or pathology of the vessels of the brain or spinal cord); in patients with mild to moderate renal impairment; in patients receiving simultaneously drugs that affect hemostasis (NSAIDs, antiplatelet agents, dextran, corticosteroids, SSRIs and SNRIs).

Use in Pregnancy and Lactation

Contraindicated for use during pregnancy and breastfeeding. Women of childbearing potential should use effective methods of contraception during treatment with this agent.

Use in Hepatic Impairment

Contraindicated for use in patients with severe liver dysfunction.

Use in Renal Impairment

Contraindicated for use in patients with severe renal failure (CrCl <30 ml/min).

Pediatric Use

Contraindicated for use in children and adolescents under 18 years of age.

Special Precautions

There is no experience of continuous use of this agent for more than 30 days and repeated use after its discontinuation.

During therapy, careful monitoring of patients for the development of bleeding is necessary; in case of their development, therapy should be discontinued. Monitoring of blood coagulation parameters is not required. However, if INR or aPTT increases more than 3.5 times above the upper limit of normal, this agent should be immediately discontinued.

When performing spinal or epidural anesthesia or diagnostic puncture of these areas in patients receiving antithrombotic agents for the prevention of thromboembolism, there is a risk of developing epidural or spinal hematomas, which, in turn, can cause persistent or irreversible paralysis. This risk may be further increased with the use of an indwelling epidural catheter in the postoperative period or with the parallel use of other drugs that affect hemostasis. Installed epidural or subarachnoid catheters should be removed at least 5 hours before the administration of the 1st dose of the drugs. A similar increase in risk may be noted when performing traumatic or repeated punctures of the epidural or subarachnoid space. Frequent monitoring of patients for the development of manifestations of neurological dysfunction (in particular, numbness or weakness of the lower extremities, impaired bowel or bladder function) is necessary. If such disorders develop, emergency examination and treatment should be performed. Before performing interventions on the epidural or subarachnoid spaces in patients receiving anticoagulants, including for the prevention of thrombosis, an assessment of the ratio of potential benefits and risks is necessary.

Drug Interactions

Use with caution simultaneously with drugs that affect hemostasis (NSAIDs, acetylsalicylic acid, clopidogrel, prasugrel, ticlopidine, dextran, glucocorticosteroids, SSRIs, SNRIs), because in this case, the anticoagulant effect is enhanced and the risk of hemorrhagic complications increases. Simultaneous use with fibrinolytics and other anticoagulants is contraindicated.

Caution should be exercised when co-administering drugs that are substrates of CYP2C9 (losartan, diclofenac, ibuprofen, naproxen), drugs of the azole group (including ketoconazole, fluconazole), as well as other drugs – inhibitors of CYP3A4.

Storage Conditions

Store at 2°C (36°F) to 30°C (86°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.