Matsitentan-29F (Tablets) Instructions for Use

Marketing Authorization Holder

February 29, LLC (Russia)

Manufactured By

Pharmproekt, JSC (Russia)

ATC Code

C02KX04 (Macitentan)

Active Substance

Macitentan (Rec.INN registered by WHO)

Dosage Form

Macitentan-29F

Film-coated tablets 10 mg: 28 pcs.

Dosage Form, Packaging, and Composition

Film-coated tablets white or almost white, biconvex, round.

Excipients: lactose monohydrate, microcrystalline cellulose PH102, croscarmellose sodium, povidone K30, sodium stearyl fumarate, polysorbate 80, partially hydrolyzed polyvinyl alcohol, talc, titanium dioxide, glyceryl monocaprylocaprate, sodium lauryl sulfate.

28 pcs. – polyethylene jars (1) – cardboard packs with an insert.

Clinical-Pharmacological Group

Non-selective antagonist of endothelin receptors type ET_A and ET_B. Vasodilator

Pharmacotherapeutic Group

Antihypertensive agents; other antihypertensive agents; antihypertensive agents for the treatment of pulmonary arterial hypertension

Pharmacological Action

Antagonist of endothelin-1 (ET) receptors of types A and B (ET_A and ET_B), vasodilator.

Endothelin-1 is a mediator of various effects, including vasoconstriction, induction of fibrosis, cell proliferation, hypertrophy, and inflammation.

Macitentan is highly active and persistently blocks endothelin-1 receptors on pulmonary artery smooth muscle cells, thereby preventing endothelin-mediated activation of secondary messenger systems, the action of which leads to vasoconstriction and proliferation of smooth muscle cells.

Indications

For the long-term treatment of pulmonary arterial hypertension (WHO functional class II-III) as monotherapy or as part of combination therapy in adult patients with primary (idiopathic and hereditary) pulmonary arterial hypertension; with pulmonary arterial hypertension and compensated congenital uncomplicated heart disease; with pulmonary arterial hypertension and connective tissue diseases.

ICD codes

Dosage Regimen

Take orally.

Administer once daily.

Take every day at the same time to maintain consistent plasma concentrations.

The recommended dosage is 10 mg.

Dose adjustment is not required for patients aged 65 years and older.

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

Can be taken regardless of meals; food does not affect absorption.

Do not discontinue therapy without consulting your physician.

Regular monitoring of hemoglobin and hematocrit is required due to the risk of anemia.

Conduct liver function tests (ALT, AST) prior to initiation and during treatment.

Use with caution in patients with moderate hepatic impairment (Child-Pugh 7-9).

Contraindicated in patients with severe hepatic impairment (Child-Pugh ≥10).

Contraindicated in patients with severe renal impairment (CrCl <30 mL/min).

Adverse Reactions

From the hematopoietic system anemia, leukopenia, thrombocytopenia.

From the nervous system headache.

From the cardiovascular system pronounced decrease in blood pressure.

From the respiratory system nasal congestion, nasopharyngitis, pharyngitis, bronchitis.

From the digestive system increased activity of hepatic transaminases (ALT/AST).

Allergic reactions: hypersensitivity reactions (e.g., angioedema, skin itching, rash).

Other peripheral edema/fluid retention, influenza-like syndrome, urinary tract infection.

Contraindications

Severe hepatic impairment (10 points and above on the Child-Pugh scale), both in the case of diagnosed liver cirrhosis and without it; baseline increase in ALT and/or AST hepatic transaminase activity more than 3 times the upper limit of normal; severe renal impairment (CrCl <30 ml/min), including when dialysis is required; pregnancy, breastfeeding period; use of the drug in women of childbearing potential not using reliable methods of contraception; age under 18 years (limited clinical experience); hypersensitivity to macitentan.

Use in Pregnancy and Lactation

Contraindicated for use during pregnancy and during lactation; breastfeeding must be discontinued.

Use in Hepatic Impairment

Should be used with caution in patients with moderate hepatic impairment (7-9 points on the Child-Pugh scale).

Use in Renal Impairment

Contraindicated for use in patients with severe renal impairment (CrCl <30 ml/min), including when dialysis is required.

Pediatric Use

The use of macitentan in children and adolescents under 18 years of age is contraindicated (limited clinical experience).

Geriatric Use

Dosage adjustment is not required in patients aged 65 years and older.

Should be used with caution in patients over 75 years of age.

Special Precautions

With caution: severe anemia before starting treatment; pulmonary arterial hypertension (PAH) WHO FC I (insufficient clinical data); PAH associated with HIV infection, or induced by drugs or toxins (clinical data are limited); age over 75 years (limited experience of use); moderate hepatic impairment (7-9 points on the Child-Pugh scale): when used concomitantly with potent CYP3A4 inhibitors (e.g., itraconazole, ketoconazole, voriconazole, clarithromycin, telithromycin, nefazodone, ritonavir and saquinavir); when used concomitantly with potent CYP3A4 inducers (e.g., rifampicin, St. John’s wort, carbamazepine, phenytoin).

Drug Interactions

Warfarin – the pharmacodynamic effect of warfarin was not altered. Warfarin did not affect the pharmacokinetics of macitentan and its active metabolite.

Sildenafil – did not affect the pharmacokinetics of macitentan, did not cause a decrease in exposure to the active metabolite of macitentan.

Ketoconazole – concomitant use of ketoconazole, a potent inhibitor of the CYP3A4 isoenzyme, at a dose of 400 mg once/day was accompanied by a twofold increase in macitentan plasma exposure. The exposure to the active metabolite of macitentan decreased by 26%. Caution should be exercised when using macitentan concomitantly with potent inhibitors of the CYP3A4 isoenzyme.

Cyclosporine A – concomitant use did not affect the blood concentrations of macitentan and its active metabolite to a clinically significant extent.

Rifampicin – a decrease in the effectiveness of macitentan is possible. Concomitant use of macitentan with potent inducers of the CYP3A4 isoenzyme (e.g., rifampicin, St. John’s wort, carbamazepine, phenytoin) should be avoided.

Hormonal contraceptives – Macitentan does not affect the pharmacokinetics of CYP3A4 substrates. A decrease in the effectiveness of hormonal contraceptives is not expected.

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.