Dilasidom^® (Tablets) Instructions for Use

ATC Code

C01DX12 (Molsidomine)

Active Substance

Molsidomine (Rec.INN registered by WHO)

Clinical-Pharmacological Group

Peripheral vasodilator. Anti-anginal drug

Pharmacotherapeutic Group

Vasodilating agent

Pharmacological Action

An anti-anginal drug from the sydnonimine group. The active metabolite of molsidomine is linsidomine (SIN-1A), a compound that reduces the tone of the smooth muscles of the vascular walls and has an antiplatelet effect.

Relaxation of smooth muscles is facilitated, among other things, by an increase in venous volume, which increases the capacity of the vascular bed and reduces venous return, leading to a decrease in the filling pressure of both ventricles. This in turn reduces the load on the heart and improves hemodynamic conditions in the coronary circulation.

Dilation of large coronary arteries causes a decrease in systemic vascular resistance (SVR), reduces the load on the heart and reduces myocardial wall tension, which leads to a decrease in myocardial oxygen demand. Furthermore, Molsidomine reduces spasm of the coronary arteries and dilates the large branches of these arteries.

The antiplatelet effect of molsidomine has clinical significance in the therapy of coronary artery disease (CAD). Unlike nitrates, Molsidomine does not cause tachycardia.

The action of molsidomine begins approximately 20 minutes after oral administration, the maximum effect is achieved in 30-60 minutes, and the duration of action is from 4 to 6 hours.

Pharmacokinetics

Absorption and Distribution

After oral administration, Molsidomine is absorbed from the gastrointestinal tract by approximately 90%. Bioavailability is about 65%.

It is 11% bound to plasma proteins. It is not known whether Molsidomine or its metabolites are excreted in breast milk.

Molsidomine does not accumulate in the body.

Metabolism

Molsidomine is biotransformed in the liver by an enzymatic pathway to form the active metabolite sydnonimine-1 (SIN-1), from which SIN-1A (N-morpholino-N-aminoisosinitrile) – linsidomine – is formed non-enzymatically.

Excretion

Molsidomine is excreted primarily by the kidneys (90-95%, including 2% unchanged) and through the intestines (3-4%). The total clearance of molsidomine is 40-80 L/h, and that of SIN-1 is 170 L/h. The T_1/2 of molsidomine is 1.6 hours, and that of linsidomine is from 1 to 2 hours.

Pharmacokinetics in Special Clinical Cases

In severe hepatic insufficiency, the T_1/2 of molsidomine increases, for example, in liver cirrhosis it is about 13.1 hours. The T_1/2 of linsidomine also increases to approximately 7.5 hours.

Indications

• Prevention of angina attacks;
• Chronic heart failure (in combination with cardiac glycosides, diuretics).

ICD codes

Dosage Regimen

Tablets

For the prevention of angina attacks, Dilasidom^® is prescribed at 2-4 mg 1-2 times/day. If necessary, the dose can be increased to 12-16 mg/day (1 tablet of 4 mg 3-4 times/day).

In elderly patients, in patients with hepatic or renal insufficiency, and also in patients with low blood pressure, the dose of the drug must be reduced.

The tablets should be taken at regular intervals with a sufficient amount of liquid (about 1/2 glass). The drug can be taken regardless of meals.

Adverse Reactions

From the cardiovascular system pronounced decrease in blood pressure, sometimes up to collapse, orthostatic hypotension.

From the central nervous system at the beginning of treatment, sometimes – headache, in rare cases – dizziness; slowing of the speed of mental and motor reactions (to a greater extent at the beginning of treatment).

From the digestive system nausea.

Allergic reactions: facial flushing, itching, bronchospasm; very rarely – skin rash, development of anaphylactic shock.

Contraindications

• Shock, collapse;
• Severe arterial hypotension (systolic blood pressure below 100 mm Hg);
• Decreased central venous pressure;
• Low left ventricular filling pressure;
• Acute stage of myocardial infarction;
• Concomitant use of PDE5 inhibitors, including sildenafil, tadalafil, vardenafil (due to the high risk of arterial hypotension);
• Pregnancy;
• Breastfeeding period;
• Age under 18 years (efficacy and safety have not been established);
• Hypersensitivity to molsidomine.

The drug should be prescribed with caution in glaucoma (especially angle-closure glaucoma), cerebrovascular accident, increased intracranial pressure, patients prone to arterial hypotension, elderly patients, after acute myocardial infarction, in renal and/or hepatic insufficiency.

Use in Pregnancy and Lactation

The use of Dilasidom^® is contraindicated during pregnancy (especially in the first trimester) and during lactation.

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

Use in Hepatic Impairment

In hepatic insufficiency, the dose of the drug must be reduced.

Use in Renal Impairment

In renal insufficiency, the dose of the drug must be reduced.

Pediatric Use

Contraindication: age under 18 years (efficacy and safety have not been established);

Geriatric Use

The drug should be prescribed with caution to elderly patients.

Special Precautions

The first dose of the drug should be taken under blood pressure monitoring.

Dilasidom^® is not applicable for stopping angina attacks!

In patients with a high risk of developing a hypotensive reaction, an individual approach to dosing the drug should be taken.

In the acute phase of myocardial infarction, Dilasidom^® can be used only after hemodynamic parameters have stabilized.

In renal insufficiency, the plasma concentration of molsidomine does not change.

The drug can be combined with other antianginal agents.

In case of impaired liver function, only with its pronounced decrease (increase in bromsulphalein test to 20-50%), the plasma concentration of molsidomine and the half-life increase, which may require correction of the drug dose.

Taking into account the lactose content, the drug should not be used in patients with rare hereditary forms of galactose intolerance, the Lapp lactase deficiency, or glucose-galactose malabsorption syndrome.

During treatment, the intake of ethanol (alcohol) should be avoided.

Effect on the ability to drive vehicles and mechanisms

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 concentration and speed of psychomotor reactions.

Overdose

Symptoms severe headache, pronounced decrease in blood pressure, tachycardia.

Treatment if less than an hour has passed since taking a dose of the drug that is many times higher than the usual single dose, gastric lavage should be considered. Furthermore, symptomatic treatment should be initiated.

Drug Interactions

With the simultaneous administration of molsidomine with peripheral vasodilators, slow calcium channel blockers, antihypertensive agents, and ethanol, the hypotensive effect is enhanced.

With the simultaneous use of molsidomine with acetylsalicylic acid, the antiplatelet activity is enhanced.

There is a high risk of developing arterial hypotension with the simultaneous use of phosphodiesterase type 5 inhibitors, such as sildenafil, tadalafil, vardenafil. The concomitant use of PDE5 inhibitors with molsidomine is contraindicated.

Storage Conditions

List B. The drug should be stored in a dry, light-protected place, out of the reach of children, at a temperature between 15°C (59°F) and 25°C (77°F).

Shelf Life

The shelf life is 3 years.

Dispensing Status

The drug is dispensed by prescription.

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.