Sidnofarm

INSTRUCTIONS FOR MEDICAL USE OF THE MEDICINAL PRODUCT SYDNOPHARM® (SYDNOPHARM)

Composition:

Active substance: molsidomine;

1 tablet contains molsidomine 2 mg;

Excipients: lactose monohydrate, mannitol (E 421), wheat starch, microcrystalline cellulose, hypromellose, colloidal anhydrous silicon dioxide, magnesium stearate, peppermint oil, Yellow West FCF (E 110).

Pharmaceutical form. Tablets.

Main physicochemical properties: round, biconvex tablets with a score line on one side, 8 mm in diameter, pale pink in colour with a minty odour.

Pharmacotherapeutic group.

Vasodilators used in the treatment of heart diseases. Molsidomine.

ATC code C01D X12.

Pharmacological Properties

Pharmacodynamics.

Molsidomine exerts venodilatory, antiaggregatory, analgesic, and prolonged antianginal effects. The venodilatory activity is due to the release of nitric oxide (NO) following a series of metabolic transformations, which stimulates soluble guanylate cyclase; thus, molsidomine is considered an NO donor. Accumulation of cyclic guanosine monophosphate (cGMP) leads to relaxation of vascular smooth muscle cells (primarily in veins). Reduction of preload, even without affecting myocardial contractility, helps restore the impaired balance between oxygen demand and supply in patients with coronary insufficiency. It dilates atherosclerotic but still responsive large epicardial coronary arteries and improves peripheral circulation.

Molsidomine increases tolerance to physical exertion and reduces symptoms of angiospasm. It inhibits the early phase of platelet aggregation and decreases the synthesis and release of serotonin, thromboxane, and other pro-aggregatory substances.

It reduces myocardial preload in patients with chronic heart failure, decreases pulmonary artery pressure, reduces left ventricular filling and myocardial wall tension, and stroke volume. The effect begins 20 minutes after administration, reaches its maximum within 0.5–1 hour, and lasts up to 6 hours. Unlike nitrate therapy, tolerance development with reduced efficacy during prolonged treatment is generally not observed with molsidomine.

Pharmacokinetics.

After oral administration, molsidomine is almost completely absorbed from the gastrointestinal tract. Bioavailability is 60–70%. Maximum plasma concentration (4.4 µg/mL) is achieved within 1 hour. Oral intake after food delays absorption but does not reduce it (maximum plasma concentration is reached 30–60 minutes later compared to administration on an empty stomach). The minimal effective plasma concentration of molsidomine is 3–5 ng/mL. It practically does not bind to plasma proteins. In the liver, it is metabolized to form the pharmacologically active compound SIN-1 (3-morpholinosydnonimine), which then forms the highly unstable intermediate SIN-1a (N-morpholino-N-aminosydnitronitrile), releasing NO and forming the pharmacologically inactive compound SIN-1c. Other metabolites are also formed during metabolism. Molsidomine is excreted primarily via the kidneys (90%, as metabolites) and 9% through the intestine. The elimination half-life ranges from 1 to 3.5 hours. It does not accumulate (including in patients with renal insufficiency).

In severe hepatic insufficiency (increase in bromsulphthalein test from 20% to 50%), delayed elimination and increased plasma concentration of molsidomine have been observed.

Clinical characteristics.

Indications.

Ischemic heart disease: prevention of attacks of stable and unstable angina (especially in elderly patients and in individuals with intolerance to nitrates).

As part of combination therapy for chronic heart failure.

Contraindications.

Hypersensitivity to the active substance or to any of the excipients, glaucoma (particularly closed-angle glaucoma), acute angina attack, acute myocardial infarction, acute circulatory failure including shock (including cardiogenic shock), vascular collapse, pronounced arterial hypotension (systolic blood pressure less than 100 mmHg), concomitant use of phosphodiesterase-5 (PDE5) inhibitors (sildenafil, vardenafil, tadalafil) due to high risk of developing arterial hypotension; toxic pulmonary edema, reduced central venous pressure; concomitant administration of nitric oxide donors in any form and stimulators of soluble guanylate cyclase (e.g., riociguat) is contraindicated due to the risk of hypotension.

Interaction with other medicinal products and other forms of interaction.

When used concomitantly with peripheral vasodilators, calcium channel blockers (CCBs), antihypertensive agents, and ethanol, the antihypertensive effect of the drug is enhanced. Sidnofarm may be used concomitantly with other antianginal drugs (e.g., added to dual or triple therapy with nitrates, CCBs, and β-blockers). Consumption of alcohol should be avoided during treatment with Sidnofarm.

Concomitant use with acetylsalicylic acid enhances its antiplatelet activity.

There is a high risk of developing arterial hypotension when used concomitantly with PDE5 inhibitors such as sildenafil, vardenafil, tadalafil. Combined use of Sidnofarm with PDE5 inhibitors is contraindicated.

Ergot alkaloids. There is a possibility of pharmacodynamic interaction between nitric oxide donors and ergot alkaloids, which may lead to antagonistic effects of the drugs. Concomitant use of nitric oxide donors and ergot alkaloids should be avoided.

Concomitant use of molsidomine and soluble guanylate cyclase stimulators (e.g., riociguat), which act as nitric oxide receptor stimulators, is contraindicated, as this combination may lead to an increased risk of hypotension.

Special precautions for use

Do not use for the treatment of acute attacks of angina pectoris!

Molsidomine usually does not cause significant reduction in arterial blood pressure; however, caution should be exercised when administering it to patients with arterial hypotension or at increased risk of arterial hypotension, elderly patients with reduced circulating blood volume, and patients receiving treatment with other vasodilators. Close monitoring is required, and dosage should be adjusted according to the patient's condition.

During treatment with Sidnofarm, it should be borne in mind that resting arterial pressure (AP), particularly systolic AP, may decrease. In such cases, initially high blood pressure responds more significantly than normotensive or hypotensive pressure.

Use with caution in patients with hypertrophic obstructive cardiomyopathy, constrictive (stricturing) pericarditis, pericardial tamponade, reduced ventricular pressure, aortic stenosis or mitral stenosis, acute myocardial infarction, or impaired left ventricular function (left ventricular insufficiency).

Since 90–95% of molsidomine metabolites are excreted by the kidneys, dosage reduction or increased intervals between doses may be necessary, depending on the individual patient's response to the drug. Patients with hepatic or renal insufficiency should receive lower doses, gradually increasing them until the desired therapeutic effect is achieved. In cases of pronounced liver dysfunction (increase in bromsulphthalein test by 20–50%), plasma concentration of molsidomine increases and elimination half-life is prolonged, necessitating dosage adjustment.

Particular attention during treatment with the drug is required for patients after hemorrhagic stroke, those with impaired cerebral circulation and elevated intracranial pressure; patients with recent myocardial infarction, glaucoma, or predisposition to hypotensive reactions, or those with existing arterial hypotension. Sidnofarm should be administered only under strict medical supervision with continuous hemodynamic monitoring.

When nitrates are used long-term, molsidomine is recommended to be included in the treatment regimen to prevent the development of nitrate tolerance.

Elderly patients with hepatic or renal functional impairment should be prescribed lower doses of the drug.

The product contains 0.06 g of lactose monohydrate. The medicinal product should not be administered to patients with rare hereditary problems of galactose intolerance, Lapp lactase deficiency, or glucose-galactose malabsorption.

Wheat starch may contain gluten, but only in insignificant amounts, and is therefore considered safe for individuals with celiac disease.

Colourant E 110 may cause allergic reactions.

Use during pregnancy or breastfeeding

The use of the drug during pregnancy is contraindicated.

The medicinal product should not be used during breastfeeding. If treatment is necessary, breastfeeding should be discontinued.

Ability to influence reaction rate when driving vehicles or operating machinery

Due to the drug's adverse effects (dizziness) and possible negative impact on attention and concentration, the drug should be administered with caution to individuals who drive vehicles or operate machinery, following careful assessment of the potential risk.

Dosage and Administration.

The medicinal product should be taken orally during or after a meal, with plenty of fluid.

For the prevention of angina attacks, administer 1–2 mg (½–1 tablet) 4–6 times daily during the first and second days of therapy. Afterwards, the dose may be increased if necessary to 2–4 mg 2–3 times daily.

The dosage regimen is individual and depends on the type and stage of the disease, as well as the severity of clinical symptoms. The usual daily dose is 2–4 mg (1–2 tablets), divided into 2 equal doses. Occasionally, the dose may be increased up to 6–8 mg (3–4 tablets), which should be divided into 3–4 doses.

Maximum daily dose – 12 mg.

Duration of treatment depends on the course of the disease and is determined by the physician.

Children.

The use of this medicinal product in children is contraindicated.

Overdose.

Symptoms: bradycardia, weakness, drowsiness, severe headache, dizziness and arterial hypotension, tachycardia accompanied by nausea and vomiting; in severe cases – collapse.

Treatment: measures aimed at rapid elimination of the drug from the body (gastric lavage, forced diuresis) and symptomatic therapy should be applied.

There is no data on the effectiveness of dialysis in cases of overdose.

Side effects.

Central nervous system: headache (usually mild, disappears during further treatment), dizziness, increased fatigue, slowed psychomotor and motor reaction speed (in most cases at the beginning of treatment), weakness.

Gastrointestinal tract: nausea, loss of appetite, diarrhea, vomiting.

Cardiovascular system: thrombocytopenia, circulatory failure, pronounced decrease in arterial pressure, orthostatic hypotension, rarely progressing to collapse or shock, tachycardia, facial skin redness. In such cases, dose reduction or discontinuation of the drug may be required.

Immune system: hypersensitivity reactions, including allergic reactions, pruritus, rashes, bronchospasm, asthma, anaphylactic shock.

Skin and subcutaneous tissues: urticaria.

Shelf life.

3 years.

Storage conditions.

Keep out of reach of children.

Store at a temperature not exceeding 25 °C in the original packaging to protect from light.

Packaging.

10 tablets in a blister pack made of PVC film and aluminum foil. 3 blisters per cardboard box.

Prescription status.

Prescription only.

Manufacturers.

JSC "Sofarma".

JSC "Vitamins".

Manufacturers' addresses and locations of their business activities.

JSC "Sofarma"
Iliensko Shose str., 16, Sofia, 1220, Bulgaria.

JSC "Vitamins"
31 Uspenska str., Uman, Cherkasy region, 20300, Ukraine.