Molsidomine

Pharmacological properties

Molsidomine is a derivative of sydnonimine. the active metabolite of Molsidomine is linsidomin (sin 1a) - a compound that reduces the tone of the smooth muscles of the walls of blood vessels and has an antianginal effect. relaxation of smooth muscles contributes to an increase in the volume of veins and the vascular bed, which leads to a decrease in venous return, due to which the filling pressure of both ventricles decreases. this reduces the load on the heart and improves hemodynamic conditions in the coronary circulation. the expansion of arterial vessels leads to a decrease in peripheral resistance, due to which the load on the heart and myocardial tension are reduced and, as a result, the myocardial oxygen demand is reduced. in addition, Molsidomine reduces the severity of spasm of the coronary arteries and expands their large branches. the antiplatelet effect of Molsidomine is of clinical importance in the treatment of coronary heart disease. unlike nitrates, Molsidomine does not cause tachyphylaxis.

Pharmacokinetics After oral administration, Molsidomine is absorbed in the digestive tract by about 90%. The onset of action is observed approximately 20 minutes after administration, the duration of action after a single dose is 4-6 hours. C_max in the blood is reached after about 30-60 minutes. Bioavailability is about 65%, the degree of binding to plasma proteins is 11%. Molsidomine is metabolized in the liver by an enzymatic route to the active metabolite - sydnonimine 1 (SIN-1), which is non-enzymatically transformed into N-morpholino-N-aminoacetonitrile (SIN 1A) - linsidomine.

It is not known whether Molsidomine and its metabolites pass into breast milk.

Molsidomine is excreted mainly with urine - 90–95% (2% unchanged) and feces - 3-4%. The total clearance is 40–80 l / h, and SIN-1 - 170 l / h. T_½ is 1.6 hours, increasing in case of severe liver failure (with cirrhosis of the liver is about 13.1 hours). T_½ Linsidomine metabolite is 1–2 hours and increases to 7.5 hours in severe liver failure. The drug does not accumulate in the body.

Indications

IHD: prevention of angina attacks (with intolerance or lack of effectiveness of nitrates).

Chronic heart failure (as part of combination therapy).

Application

The dose and frequency of administration of the drug are set individually for each patient, depending on the degree of manifestation and phase of activity of the disease.

In case of spontaneous angina attacks, the last dose of Molsidomine is best taken before bedtime.

The dose of the drug should be increased gradually, to prevent adverse reactions in the form of persistent headache in some patients.

The drug can be used regardless of food intake.

Usually, 1–2 mg is prescribed 3-4 times a day (3–8 mg of Molsidomine per day).

If necessary, the dose can be increased to 4 mg 3-4 times a day (12-16 mg of Molsidomine per day).

Contraindications

Hypersensitivity to the drug.

Glaucoma, especially angle-closure.

The acute stage of myocardial infarction, especially with a decrease in blood pressure.

Cardiogenic shock.

Arterial hypotension.

The combined use of Molsidomine and sildenafil.

Side effects

The following side effects are observed.

From the cardiovascular system: lowering blood pressure, orthostatic hypotension, collapse.

From the side of the central nervous system: headache that occurs at the beginning of treatment and disappears with its continuation; dizziness, fatigue, general weakness.

From the gastrointestinal tract: anorexia, nausea, vomiting.

From the skin: hyperemia of the face; allergic reactions, including skin rashes.

From the respiratory system: bronchospasm.

special instructions

Cautions and special measures when applied. Molsidomine, as a rule, does not cause a significant decrease in hell, however, caution should be exercised in patients with arterial hypotension, elderly people with reduced BCC, and patients receiving treatment with other vasodilators.

Patients after hemorrhagic stroke, with impaired cerebral circulation and increased intracranial pressure, patients after recent myocardial infarction, patients with a tendency to hypotensive reactions require special attention during treatment with the drug.

With prolonged use of nitrates to prevent the development of tolerance to them, it is recommended to include Molsidomine in the treatment regimen.

Patients with hepatic or renal failure should use lower doses with a gradual increase in them until the desired therapeutic effect is obtained. In general, in the treatment of patients with impaired renal function, the dose of Molsidomine is not recommended. But, taking into account that 90–95% of the metabolites of Molsidomine is excreted by the kidneys, it is possible to reduce the dose or increase the intervals between doses of the drug, taking into account the individual response of the patients.

Due to the fact that the drug contains lactose, it cannot be used in the treatment of patients with a rare form of congenital galactose intolerance, with Lapp lactase deficiency or glucose-galactose malabsorption syndrome.

Use during pregnancy and lactation. In animal studies, no teratogenic effect of the drug was detected. However, due to the lack of convincing data on the safety of the drug, the use of Molsicor in the treatment of pregnant women is contraindicated.

During breastfeeding, the use of the drug is contraindicated.

Children. Do not use the drug in children.

The ability to influence the reaction rate when driving vehicles and working with other mechanisms. Given the adverse reactions of the drug (dizziness) and the possible negative effect on the concentration of attention in people who drive or work with other mechanisms, the drug can be prescribed with caution only after a thorough assessment of the possible risk.

Interactions

With the simultaneous use of Molsidomine with peripheral vasodilators, calcium ion antagonists, antihypertensive drugs, the hypotensive effect is potentiated.

With the simultaneous use of Molsidomine with acetylsalicylic acid, the antiplatelet effect is potentiated.

The combined use of Molsidomine and iloprost leads to a significant inhibition of platelet aggregation, therefore, if necessary, such a combination of drugs should conduct appropriate studies to assess the blood picture and platelet aggregation.

During treatment with the drug, sildenafil should not be used because of the possibility of developing irreversible arterial hypotension with dangerous consequences.

The simultaneous use of Molsidomine and sildenafil is contraindicated because of the possibility of an unpredictable sharp decrease in blood pressure with fainting and even collapse, therefore, before prescribing Molsidomine, the doctor should inform the patient about the impossibility of simultaneous therapy with these drugs. If necessary, the administration of Molsidomine after completion of sildenafil therapy can be started no earlier than 24 hours after taking the latter.

The reason for this interaction is the mechanism of action of sildenafil and Molsidomine. Sildenafil inhibits the activity of PDE-5, which is responsible for the metabolic breakdown of cyclic guazine monophosphate (cGMP). At the same time, as a result of the transformation of Molsidomine, cGMP is activated and blood vessels expand. Thus, an increase in the concentration of cGMP in connection with the simultaneous administration of sildenafil and Molsidomine leads to a sharp decrease in blood pressure.

The drug can be used simultaneously with β-adrenergic blockers and calcium antagonists.

Alcohol enhances the effect of the drug, so the use of alcohol during treatment with the drug is prohibited.

Overdose

Symptoms of an overdose are severe headache, hypotension, tachycardia. in case of taking a dose significantly higher than the usual single dose, if no more than 1 hour has passed, the stomach should be washed. if necessary, carry out symptomatic treatment.

Treatment: forced diuresis. There is no data on the effectiveness of dialysis in case of overdose.

Storage conditions

In the original packaging at a temperature not exceeding 25 ° C in a dark place and out of the reach of children.