Sydnopharm (Tablets) Instructions for Use

Marketing Authorization Holder

Sopharma, JSC (Bulgaria)

ATC Code

C01DX12 (Molsidomine)

Active Substance

Molsidomine (Rec.INN registered by WHO)

Dosage Form

Sydnopharm

Tablets 2 mg: 30 pcs.

Dosage Form, Packaging, and Composition

Tablets are light pink in color, round, biconvex, with a score line, and with a minty odor.

Excipients: lactose monohydrate – 60 mg, mannitol – 40 mg, wheat starch – 26.99 mg, microcrystalline cellulose – 21.4 mg, hypromellose – 5 mg, colloidal anhydrous silicon dioxide – 2 mg, magnesium stearate – 1.6 mg, peppermint leaf oil – 1 mg, dye sunset yellow (E110) – 0.01 mg.

10 pcs. – blisters (3) – cardboard packs.

Clinical-Pharmacological Group

Peripheral vasodilator. Anti-anginal drug

Pharmacotherapeutic Group

Drugs for the treatment of heart diseases; vasodilators for the treatment of heart diseases; other vasodilators for the treatment of heart diseases

Pharmacological Action

Peripheral vasodilator, antianginal agent from the sydnonimine group. It dilates peripheral venous vessels and has antiplatelet, analgesic, and antianginal effects. The venodilating activity is due to the release of nitric oxide (NO) after a series of metabolic transformations, which stimulates soluble guanylate cyclase; therefore, Molsidomine is considered a NO donor. As a result, cGMP accumulates, which promotes relaxation of the smooth muscles of the vascular wall (to a greater extent in veins). Reducing preload, even without a direct effect on myocardial contractility, leads to the restoration of the impaired ratio between myocardial oxygen demand and its supply in coronary artery disease (oxygen demand is reduced by 26%). It relieves spasm of the coronary arteries and improves collateral circulation.

It increases exercise tolerance and reduces the number of angina attacks during physical exertion. It suppresses the early phase of platelet aggregation and reduces the release and synthesis of serotonin, thromboxane, and other proaggregants.

In patients with chronic heart failure, by reducing preload, it helps to reduce the size of the heart chambers. It reduces pressure in the pulmonary artery, decreases left ventricular filling and myocardial wall tension, and stroke volume.

The action begins 20 minutes after oral administration, reaches a maximum in 0.5-1 hour, and lasts up to 6 hours. The development of tolerance with a decrease in effectiveness during long-term therapy is not typical (unlike nitrates).

Pharmacokinetics

Absorption and Distribution

After oral administration, it is almost completely absorbed from the gastrointestinal tract. Bioavailability is 60-70%. C_max is 4.4 µg/ml and is reached in 1 hour. When taken orally after a meal, absorption, although slowed down, is not reduced (C_max in blood plasma is reached 30-60 minutes later than when taken on an empty stomach). The minimum effective concentration of molsidomine in blood plasma is 3-5 ng/ml. It practically does not bind to plasma proteins. It does not accumulate.

Metabolism and Excretion

It is metabolized in the liver to form a pharmacologically active compound SIN-1 (3-morpholino-sydnonimine), from which a very unstable substance SIN-1a (N-morpholino-N-aminoisosinitrile) is formed, releasing NO to form a pharmacologically inactive compound SIN-1c. Other metabolites are also formed during metabolism. It is excreted 90% by the kidneys (in the form of metabolites), 9% through the intestines. T_1/2 is 0.85-2.35 hours.

Pharmacokinetics in Special Clinical Cases

In severe hepatic insufficiency (increase in bromsulfalein test to 20-50%), a slowdown in excretion and an increase in the concentration of molsidomine in blood plasma were noted.

It does not accumulate (including in patients with renal failure).

Indications

• Prevention of angina attacks.

ICD codes

Dosage Regimen

The dosage regimen and duration of therapy are set individually by the physician based on clinical response and tolerability.

For the prevention of angina attacks, initiate therapy with an initial dose of 1-2 mg taken orally two to three times daily.

Administer tablets before meals to ensure optimal absorption, as food intake can delay the onset of action.

If the therapeutic effect is insufficient after several days, titrate the dose upward by increasing the frequency of administration to a maximum of three times per day.

Do not exceed the maximum daily dose of 6 mg.

Monitor blood pressure closely, especially after the first dose and during any dose escalation, due to the risk of hypotension.

In elderly patients and those with hepatic impairment or a tendency to arterial hypotension, initiate therapy at the lower end of the dosage range and adjust with caution.

This medication is for prophylactic use only; it is not indicated for the acute relief of an angina attack.

Adverse Reactions

From the cardiovascular system frequently – decreased blood pressure, collapse (with initially elevated blood pressure, the degree of its decrease is greater than with initially normal or low blood pressure); facial redness, tachycardia.

From the central nervous system headache (usually minor, disappears during further treatment), slowing of the speed of psychomotor reactions (to a greater extent at the beginning of treatment), dizziness.

From the digestive system nausea, loss of appetite, diarrhea.

Allergic reactions skin rash, itching, bronchospasm; rarely – anaphylactic shock.

Contraindications

• Acute myocardial infarction occurring with arterial hypotension;
• Severe arterial hypotension (systolic blood pressure below 100 mm Hg);
• Collapse;
• Cardiogenic shock;
• Low left ventricular filling pressure;
• Toxic pulmonary edema;
• Simultaneous use of sildenafil;
• Pregnancy;
• Lactation period;
• Childhood and adolescence under 18 years (efficacy and safety have not been established);
• Hypersensitivity to molsidomine.

With caution

Patients after a hemorrhagic stroke, with increased intracranial pressure, with a tendency to arterial hypotension, elderly persons, patients with glaucoma (especially closed-angle), with cerebrovascular disorders.

Use in Pregnancy and Lactation

Use is contraindicated during pregnancy and breastfeeding.

Use in Hepatic Impairment

Elderly patients with impaired liver and kidney function and arterial hypotension require dose adjustment.

Use in Renal Impairment

Elderly patients with impaired liver and kidney function and arterial hypotension require dose adjustment.

Pediatric Use

Contraindication: childhood and adolescence under 18 years (efficacy and safety have not been established).

Geriatric Use

Elderly patients with impaired liver and kidney function and arterial hypotension require dose adjustment.

Special Precautions

Molsidomine is not used to relieve an angina attack.

The first dose of molsidomine should be prescribed with caution and under blood pressure control, as intense headaches and an excessive decrease in blood pressure with loss of consciousness are possible.

Elderly patients with impaired liver and kidney function and arterial hypotension require dose adjustment.

Alcohol consumption should be avoided during treatment.

Influence on the ability to drive vehicles and operate machinery

During treatment (especially at the beginning of therapy), it is necessary to refrain from driving vehicles and engaging in other potentially hazardous activities that require increased attention and speed of psychomotor reactions.

Drug Interactions

Concomitant use of molsidomine with vasodilators, antihypertensive agents, and ethanol increases the severity of the hypotensive effect.

When used concomitantly with acetylsalicylic acid, its antiplatelet effect is enhanced.

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.