Mononitrosid

INSTRUCTIONS FOR MEDICAL USE OF THE MEDICINAL PRODUCT MОNONITROSID (MONONITROSID)

Composition:

Active substance: isosorbide mononitrate;

One tablet contains 40 mg of diluted isosorbide mononitrate (calculated as 100% isosorbide mononitrate);

Excipients: lactose monohydrate, maize starch, calcium stearate.

Pharmaceutical form. Tablets.

Main physical and chemical properties: white-colored, flat cylindrical tablets with beveled edges and a score line.

Pharmacotherapeutic group. Drugs affecting the cardiovascular system. Vasodilators used in cardiology. Organic nitrates. Isosorbide mononitrate.

ATC Code C01D A14.

Pharmacological Properties

Pharmacodynamics

Isosorbide mononitrate is a metabolite of isosorbide dinitrate and induces vascular smooth muscle relaxation and vasodilation through the formation of nitric oxide. Isosorbide mononitrate simultaneously dilates peripheral veins and arteries, leading to increased venous capacitance, reduced venous return to the heart, and consequently decreased ventricular end-diastolic pressure and preload. Its effect on arterial vessels reduces systemic vascular resistance (afterload), thereby reducing the workload of the heart. The combined effect on preload and afterload decreases myocardial oxygen demand. Additionally, isosorbide mononitrate promotes redistribution of blood flow to subendocardial layers, particularly when coronary blood flow is partially impaired due to atherosclerotic plaques. Vasodilation induced by nitrates improves perfusion of the post-stenotic myocardial regions. Nitrates alleviate eccentric coronary stenosis and reduce venous spasms. Nitrates improve hemodynamics both at rest and during exertion in patients with congestive heart failure. As a result of reduced oxygen demand and enhanced oxygen supply, the extent of damaged myocardium is limited. Isosorbide mononitrate also affects other organs and systems: it relaxes bronchial smooth muscle and the smooth muscles of the gastrointestinal, biliary, and urinary tracts. The effect of the drug begins within 20 minutes and lasts up to 8 hours.

Isosorbide mononitrate slightly inhibits platelet aggregation and reduces intraplatelet thromboxane synthesis.

Pharmacokinetics

After oral administration, isosorbide mononitrate is completely absorbed. Maximum plasma concentration is reached within 1 hour after administration. The drug undergoes no significant biotransformation during the "first pass" through the liver and does not bind to plasma proteins. The elimination half-life of the drug is 4–5 hours. The pharmacokinetics of isosorbide mononitrate are not affected by the presence of cardiac, renal, or hepatic insufficiency.

Isosorbide mononitrate is metabolized in the liver to isosorbide and isosorbide-5-mononitrate-2-glucuronide. Both metabolites are pharmacologically inactive and are excreted by the kidneys. Only 2% of the drug is excreted unchanged in the urine.

Clinical characteristics.

Indications.

• Prevention of angina pectoris;
• congestive heart failure.

Contraindications.

• Hypersensitivity to the active substance or to any component of the medicinal product;
• acute circulatory failure, severe arterial hypotension (systolic pressure below 90 mm Hg) or hypovolemia, collapse; cardiogenic shock, unless adequate left ventricular end-diastolic pressure is maintained by intra-aortic counterpulsation or by drugs with positive inotropic effect;
• acute myocardial infarction with low left ventricular filling pressure;
• severe anemia;
• toxic pulmonary edema;
• recent head trauma or intracranial hemorrhage, increased intracranial pressure;
• glaucoma;
• hypersensitivity to nitrates;
• concomitant use with sildenafil and other phosphodiesterase inhibitors.

Interaction with other medicinal products and other forms of interaction.

Phosphodiesterase inhibitors (e.g., sildenafil), neuroleptics, vasodilators, and tricyclic antidepressants: potentiate the hypotensive effect of nitrates; therefore, they must not be used concomitantly with Mononitrosid.

Noradrenaline, acetylcholine, histamine: their effects are reduced when used concomitantly with nitrates.

Alcohol, opioid analgesics, vasodilating agents, and medicinal products that reduce blood pressure (such as beta-adrenoblockers, calcium antagonists, vasodilators): possible enhancement of their hypotensive effect.

Sympathomimetics: may reduce the antianginal effect of nitrates.

Ergotamine derivatives (e.g., dihydroergotamine): nitrates may increase plasma levels and potentiate its hypertensive effect.

Heparin: enhanced anti-aggregatory effect.

Special precautions.

Do not use for the treatment of acute myocardial infarction or for relief of angina attacks.

The use of isosorbide mononitrate may lead to transient hypoxia and ischemia in patients with ischemic heart disease due to relative redistribution of blood flow into areas of alveolar hypoventilation.

Use with caution:

• in hypertrophic obstructive cardiomyopathy, constrictive pericarditis, cardiac tamponade, low cardiac filling pressure, aortic or mitral stenosis;
• in severe impairment of renal and/or hepatic function;
• in patients with hypothyroidism, hypothermia, or malnutrition;
• in elderly patients (as they may be more sensitive to the hypotensive effects of nitrates);
• in patients predisposed to arterial hypotension, orthostatic dysfunction (a decrease in systolic blood pressure by 10–25 mm Hg below 90 mm Hg upon changing body position), and during surgical procedures.

Failure to observe the recommended dosing intervals or prolonged use of high doses may lead to the development of nitrate tolerance due to depletion of tissue sulfhydryl group reserves. This can be avoided by following a dosing regimen that includes a nitrate-free interval. Additionally, administration of sulfhydryl groups into the body (e.g., using acetylcysteine, methionine, or captopril) may help prevent the development of tolerance.

Cross-tolerance with other nitrates may occur. To prevent diminished therapeutic effect or complete ineffectiveness of the drug, continuous long-term administration of high doses should be avoided.

After prolonged high-dose therapy, discontinuation of the drug should be gradual to prevent recurrence of angina symptoms.

Methemoglobinemia may develop with high-dose administration.

Isosorbide mononitrate may interfere with colorimetric determination of cholesterol levels.

Nitrate therapy may increase urinary concentrations of catecholamines (epinephrine/adrenaline/norepinephrine) and vanillylmandelic acid. Alcohol consumption should be avoided during treatment.

The product contains lactose and therefore should not be administered to patients with lactase deficiency, galactosemia, or glucose-galactose malabsorption syndrome.

Use during pregnancy or breastfeeding.

The drug affects fetal/infant hemodynamics and is therefore contraindicated during pregnancy and breastfeeding.

Ability to affect reaction speed when driving or operating machinery.

During treatment, reduced psychomotor reaction speed and dizziness may occur. This should be taken into account when driving or operating machinery.

Method of Administration and Dosage.

The drug is taken orally before meals, with sufficient amount of liquid.

The dose and frequency of administration are determined individually by a physician. To achieve maximum therapeutic effect, individual dosing of the drug is recommended, depending on the patient's condition, response to the drug, and tolerability.

Treatment should be initiated with low doses, which may be increased during therapy if necessary. The recommended dose is 40 mg (1 tablet) twice daily. To prevent the development of nitrate tolerance (regardless of the dosing regimen), a nitrate-free interval of 10–12 hours (usually at night) must be ensured. The second tablet should be taken no earlier than 8 hours after the first dose.

For the treatment of angina with frequent nocturnal attacks, the drug should be administered in the morning and immediately before bedtime.

Monitoring of hemodynamics is highly important for determining individual dosing.

Daily dose, depending on the severity of the disease, may reach 120 mg (maximum daily dose) administered in 3 doses.

Children.

The drug is not administered to children.

Overdose.

Symptoms: reduction of arterial pressure below 90 mm Hg, pallor, increased sweating, weak pulse, tachycardia, dizziness upon standing, headache, sensation of warmth or chills, hyperemia, feeling of fear, weakness, loss of consciousness, vertigo, orthostatic hypotension, cerebral symptoms, nausea, vomiting, diarrhea, methemoglobinemia, seizures, visual disturbances, increased intracranial pressure, cyanosis, dyspnea, tachypnea, shortness of breath, coma.

Treatment: symptomatic. Discontinue the drug. Intravenous administration of physiological saline and plasma is recommended. If drug intake occurred recently, gastric lavage and administration of enterosorbents (activated charcoal) are recommended for drug elimination. In case of arterial hypotension, the patient should be placed on a horizontal surface with low head elevation (legs should be elevated).

In severe cases, dopamine and sympathomimetics are administered. In case of methemoglobinemia development, ascorbic acid 1 g orally, 1% methylene blue intravenously, toluidine blue 2–4 mg/kg body weight intravenously, artificial ventilation of lungs are prescribed; if necessary, blood transfusion is performed. Hemodialysis is indicated.

Adverse Reactions.

Nervous system: headache, which gradually decreases over several days but may be severe and persistent, inattention, dizziness, drowsiness and weakness, motor restlessness, syncope.

Cardiovascular system: arterial (including orthostatic) hypotension, collapse with cardiac arrhythmia and bradycardia, worsening of angina symptoms, bradyarrhythmia, reflex tachycardia, transient hypoxemia due to myocardial hypoxia in patients with ischemic heart disease.

Gastrointestinal tract: nausea, vomiting, diarrhea, dyspepsia.

Skin and subcutaneous tissue: skin allergic reactions (including rash, pruritus, exfoliative dermatitis), dilation of skin vessels with redness, pallor and increased sweating.

Immune system: hypersensitivity reactions may occur in patients with individual intolerance to any component of the drug.

Other: facial flushing, tinnitus, asthenia.

Cases of development of tolerance to the drug, including cross-tolerance to other organic nitrates, have been observed. To prevent weakening of the drug's effect or complete inefficacy, continuous administration of high doses over a prolonged period should be avoided.

Shelf life. 4 years.

Storage conditions. In the original packaging at a temperature not exceeding 25 °C. Keep out of reach of children.

Packaging. 10 tablets per blister, 3 or 4 blisters per carton.

Prescription status. By prescription only.

Manufacturer. Public Joint-Stock Company "Scientific and Production Center "Borshchahivskyy Chemical and Pharmaceutical Plant".

Limited Liability Company "Agrofarm".

Manufacturer’s location and address of its business activity.

Ukraine, 03134, Kyiv, Miru St., 17.

Ukraine, 08200, Kyiv Oblast, Irpin, Centralna St., 113-A.

INSTRUCTION

for medical use of the medicinal product

MONONITROSID

(MONONITROSID)

Composition:

Active substance: isosorbide mononitrate;

1 tablet contains 40 mg of isosorbide mononitrate diluted (equivalent to 100% isosorbide mononitrate);

Excipients: lactose monohydrate, corn starch, calcium stearate.

Pharmaceutical form. Tablets.

Main physicochemical properties: white, flat cylindrical tablets with beveled edges and a score line.

Pharmacotherapeutic group. Drugs affecting the cardiovascular system. Vasodilators used in cardiology. Organic nitrates. Isosorbide mononitrate. ATC code C01DA14.

Pharmacological properties.

Pharmacodynamics.

Isosorbide mononitrate is a metabolite of isosorbide dinitrate. It causes relaxation of vascular smooth muscle and vasodilation due to nitric oxide formation. Isosorbide mononitrate simultaneously dilates peripheral veins and arteries, leading to increased venous capacitance, reduced venous return to the heart, and consequently decreased ventricular end-diastolic pressure and preload. Its effect on arterial vessels reduces systemic vascular resistance (afterload), thereby easing cardiac workload. The combined effect on preload and afterload reduces myocardial oxygen demand. Additionally, isosorbide mononitrate promotes redistribution of blood flow to subendocardial layers, especially when coronary blood flow is partially reduced due to atherosclerotic plaques. Nitrate-induced dilation improves perfusion of post-stenotic myocardial segments. Nitrates eliminate eccentric coronary stenosis and reduce venous spasm. Nitrates improve hemodynamics both at rest and during exertion in patients with congestive heart failure. By reducing oxygen demand and increasing oxygen supply, the extent of damaged myocardium is limited. Isosorbide mononitrate also affects other organs and systems: it relaxes bronchial smooth muscle, and smooth muscles of the gastrointestinal, biliary, and urinary tracts. The drug's effect begins within 20 minutes and lasts up to 8 hours.

Isosorbide mononitrate slightly inhibits platelet aggregation and reduces intraplatelet thromboxane synthesis.

Pharmacokinetics.

After oral administration, isosorbide mononitrate is completely absorbed. Maximum plasma concentration is reached within 1 hour after intake. During the "first pass" through the liver, isosorbide mononitrate undergoes no biotransformation and does not bind to plasma proteins. Elimination half-life is 4–5 hours. The pharmacokinetics of isosorbide mononitrate are not affected by cardiac, renal, or hepatic insufficiency.

Isosorbide mononitrate is metabolized in the liver to isosorbide and isosorbide-5-mononitrate-2-glucuronide. Both metabolites are pharmacologically inactive and excreted by the kidneys. Only 2% of the drug is excreted unchanged in urine.

Clinical characteristics.

Indications.

• Prevention of angina pectoris;
• congestive heart failure.

Contraindications.

• Hypersensitivity to the active substance or any component of the drug;
• acute circulatory failure, severe arterial hypotension (systolic blood pressure below 90 mm Hg) or hypovolemia, collapse; cardiogenic shock, unless adequate left ventricular end-diastolic pressure is maintained by intra-aortic counterpulsation or positive inotropic agents;
• acute myocardial infarction with low left ventricular filling pressure;
• severe anemia;
• toxic pulmonary edema;
• recent traumatic brain injury or intracranial hemorrhage, increased intracranial pressure;
• glaucoma;
• hypersensitivity to nitrates;
• concomitant use with sildenafil and other phosphodiesterase inhibitors.

Interaction with other medicinal products and other types of interactions.

Phosphodiesterase inhibitors (e.g., sildenafil), neuroleptics, vasodilators, and tricyclic antidepressants: potentiate the hypotensive effect of nitrates; therefore, they must not be used concomitantly with Mononitrosid.

Noradrenaline, acetylcholine, histamine: their effects are reduced when used simultaneously with nitrates.

Alcohol, opioid analgesics, vasodilating agents, and drugs that lower blood pressure (such as beta-blockers, calcium antagonists, vasodilators): possible enhancement of their hypotensive effects.

Sympathomimetics: may reduce the antianginal effect of nitrates.

Dihydroergotamine: nitrates may increase its plasma levels and enhance its hypertensive effect.

Heparin: enhances antiplatelet effect.

Special precautions.

Do not use for treatment of acute myocardial infarction or for relief of angina attacks.

Administration of isosorbide mononitrate may cause transient hypoxia and ischemia in patients with ischemic heart disease due to relative redistribution of blood flow to areas of alveolar hypoventilation.

Use with caution:

• in hypertrophic obstructive cardiomyopathy, constrictive pericarditis, cardiac tamponade, low cardiac filling pressure, aortic or mitral stenosis;
• in severe renal and/or hepatic impairment;
• in patients with hypothyroidism, hypothermia, or malnutrition;
• in elderly patients (as they may be more sensitive to the hypotensive effects of nitrates);
• in patients prone to arterial hypotension, orthostatic dysfunction (systolic blood pressure drop of 10–25 mm Hg below 90 mm Hg upon changing body position), or undergoing surgical procedures.

Failure to observe the recommended interval between doses or prolonged use of high doses may lead to nitrate tolerance due to depletion of tissue sulfhydryl groups. This can be avoided by following a regimen with a nitrate-free interval.

To prevent tolerance development, sulfhydryl group supplementation (e.g., with acetylcysteine, methionine, or captopril) may also be used.

Cross-tolerance to other nitrates may occur. To prevent diminished response or complete inefficacy of the drug, continuous administration of high doses over a prolonged period should be avoided.

After prolonged high-dose therapy, the drug should be discontinued gradually to prevent recurrence of angina symptoms.

Methemoglobinemia may occur with high-dose administration.

Isosorbide mononitrate may interfere with colorimetric cholesterol assays.

Under the influence of nitrates, urinary concentrations of catecholamines (epinephrine/adrenaline/norepinephrine) and vanillylmandelic acid may increase. Alcohol should be avoided during treatment.

The drug contains lactose and therefore must not be administered to patients with lactase deficiency, galactosemia, or glucose-galactose malabsorption syndrome.

Use during pregnancy or breastfeeding.

The drug affects fetal/infant hemodynamics and is therefore contraindicated during pregnancy and breastfeeding.

Ability to influence reaction rate when driving or operating machinery.

During treatment, psychomotor reaction speed may decrease, and dizziness may occur; this should be considered when driving or operating machinery.

Administration and dosage.

The drug is taken orally before meals, with sufficient liquid.

Dosage and frequency are determined individually by a physician. To achieve maximum therapeutic effect, individualized dosing based on patient condition, response to the drug, and tolerability is recommended.

Treatment should begin with low doses, which may be increased as needed during therapy. Recommended dose: 40 mg (1 tablet) twice daily. To prevent nitrate tolerance (regardless of dosing regimen), a 10–12 hour nitrate-free interval (usually at night) must be ensured. The second tablet should be taken no sooner than 8 hours after the first.

In patients with frequent nocturnal angina attacks, the drug should be administered in the morning and immediately before bedtime.

Hemodynamic monitoring is important for individual dose determination.

Daily dose may reach up to 120 mg (maximum daily dose) in three divided doses, depending on disease severity.

Children.

The drug is not used in children.

Overdose.

Symptoms: blood pressure reduction below 90 mm Hg, pallor, excessive sweating, weak pulse, tachycardia, dizziness upon standing, headache, sensation of heat or chills, flushing, anxiety, weakness, loss of consciousness, vertigo, orthostatic hypotension, cerebral symptoms, nausea, vomiting, diarrhea, methemoglobinemia, seizures, visual disturbances, increased intracranial pressure, cyanosis, dyspnea, tachypnea, shortness of breath, coma.

Treatment: symptomatic. Discontinue the drug. Intravenous administration of physiological saline and plasma is recommended. If ingestion was recent, gastric lavage and administration of enterosorbents (activated charcoal) are advised. In case of arterial hypotension, place the patient on a horizontal surface with feet elevated (Trendelenburg position).

In severe cases, dopamine and sympathomimetics are administered. In case of methemoglobinemia, administer ascorbic acid 1 g orally, 1% methylene blue intravenously, toluidine blue 2–4 mg/kg body weight intravenously, artificial ventilation of the lungs; if necessary, perform blood transfusion. Hemodialysis is indicated.

Adverse reactions.

Nervous system: headache, which gradually decreases over several days but may be severe and persistent, inattention, dizziness, drowsiness and weakness, motor restlessness, syncope.

Cardiovascular system: arterial (including orthostatic) hypotension, collapse with cardiac arrhythmia and bradycardia, worsening of angina symptoms, bradyarrhythmia, reflex tachycardia, transient hypoxemia due to myocardial hypoxia in patients with ischemic heart disease.

Gastrointestinal tract: nausea, vomiting, diarrhea, dyspepsia.

Skin and subcutaneous tissue: skin allergic reactions (including rash, pruritus, exfoliative dermatitis), dilation of skin vessels with redness, pallor and increased sweating.

Immune system: hypersensitivity reactions may occur in patients with individual intolerance to any component of the drug.

Other: facial flushing, tinnitus, asthenia.

Cases of development of tolerance to the drug, including cross-tolerance to other organic nitrates, have been observed. To prevent weakening of the drug's effect or complete inefficacy, continuous administration of high doses over a prolonged period should be avoided.

Shelf life. 4 years.

Storage conditions. In the original packaging at a temperature not exceeding 25 °C. Keep out of reach of children.

Packaging. 10 tablets per blister, 3 or 4 blisters per carton.

Prescription status. By prescription only.

Manufacturer. Public Joint-Stock Company "Scientific and Production Center "Borshchahivskyy Chemical and Pharmaceutical Plant".

Limited Liability Company "Agrofarm".

Manufacturer’s location and address of its business activity.

Ukraine, 03134, Kyiv, Miru St., 17.

Ukraine, 08200, Kyiv Oblast, Irpin, Centralna St., 113-A.