Iso-mik® 10 mg

INSTRUCTIONS FOR MEDICAL USE OF THE MEDICINAL PRODUCT ISO-MIK® 10 MG (ISO-MIK 10 MG)

Composition:

Active substance: isosorbide dinitrate;

1 tablet contains isosorbide dinitrate 10 mg;

Excipients: potato starch; calcium stearate; sucrose; lactose monohydrate.

Pharmaceutical form.

Tablets.

Main physicochemical properties.

White or white with a creamy shade tablets, with a flat surface and bevelled edge.

Pharmacotherapeutic group.

Cardiovascular agents. Cardiological preparations. Vasodilators used in cardiology. Organic nitrates. Isosorbide dinitrate. ATC code C01DA08.

Pharmacological properties.

Pharmacodynamics.

Isosorbide dinitrate is one of the main antianginal agents within the group of organic nitrates, a peripheral vasodilator predominantly affecting venous vessels.

Like all organic nitrates, isosorbide dinitrate acts as a donor of nitric oxide (NO). NO induces relaxation of vascular smooth muscle (primarily in veins and systemic arteries) by stimulating guanylate cyclase and subsequently increasing intracellular levels of cyclic guanosine monophosphate (cGMP). This leads to activation of cGMP-dependent protein kinase and altered phosphorylation of various proteins in smooth muscle cells. As a result, dephosphorylation of myosin light chains occurs, reducing contractility.

The effect of isosorbide dinitrate is associated with reduced myocardial oxygen demand due to decreased preload (by dilating peripheral veins and reducing blood flow to the right atrium) and afterload (by reducing total peripheral vascular resistance), as well as due to a direct coronary vasodilating action. Isosorbide dinitrate promotes redistribution of coronary blood flow to areas with impaired perfusion. It increases exercise tolerance in patients with ischemic heart disease and angina pectoris.

The use of isosorbide dinitrate improves coronary perfusion without inducing a "coronary steal syndrome." It exhibits antihypertensive effects. In severe forms of heart failure, by reducing the tone of peripheral venous vessels, the drug decreases cardiac load, pressure in the pulmonary circulation vessels, and dyspnea.

Pharmacokinetics.

Oral bioavailability is 22% (due to the "first-pass" effect in the liver). Onset of action occurs within 15–40 minutes; peak effect develops within 1.5–2 hours. The overall duration of action is 4–6 hours or longer. The drug is metabolized in the liver. Elimination half-life is 4 hours and may be prolonged during repeated administration. It is excreted in urine almost entirely as metabolites.

Clinical Characteristics.

Indications.

• Prevention and treatment of angina attacks, including post-infarction angina.
• Treatment of chronic congestive heart failure – in combination with cardiac glycosides and diuretics.

Contraindications.

• Hypersensitivity to isosorbide dinitrate, other nitrates, or any component of the drug;
• Increased intracranial pressure (including in cases of head injury, hemorrhagic stroke) – since venodilation may lead to further increase;
• Severe arterial hypotension (systolic blood pressure below 90 mm Hg), hemorrhage, hypovolemia (isosorbide dinitrate, by reducing venous return, may provoke syncope);
• Acute circulatory failure (shock, vascular collapse);
• Cardiogenic shock (unless adequate end-diastolic pressure is maintained by appropriate measures);
• Angina caused by hypertrophic obstructive cardiomyopathy;
• Cardiac tamponade, aortic stenosis, mitral stenosis, constrictive pericarditis;
• Acute myocardial infarction;
• Primary pulmonary diseases (due to the risk of hypoxemia caused by redistribution of blood flow to areas of hyperventilation), toxic pulmonary edema, cor pulmonale;
• Severe anemia;
• Closed-angle glaucoma;
• Severe impairment of liver and/or kidney function, hyperthyroidism;
• Concomitant use with phosphodiesterase inhibitors (e.g., sildenafil, tadalafil, vardenafil).

Interaction with other medicinal products and other types of interactions.

Antihypertensive agents (e.g., β-adrenoblockers, angiotensin-converting enzyme inhibitors, calcium antagonists, vasodilators), phenothiazines, other nitrates/nitrites, quinidine, procainamide, cyclic antidepressants, monoamine oxidase inhibitors, narcotic analgesics – potentiation of the hypotensive effect of isosorbide dinitrate, possible development of orthostatic collapse.

Disopyramide – possible reduction in the effectiveness of isosorbide dinitrate.

Dihydroergotamine – concentration of dihydroergotamine in blood may increase, leading to enhanced hypertensive effect.

Noradrenaline, acetylcholine, histamine – weakening of their effects when used with nitrates, as isosorbide dinitrate may act as their physiological antagonist.

Heparin – possible reduction in its anticoagulant effect.

Hydralazine – improved cardiac output in heart failure when used in combination with isosorbide dinitrate.

Miotics – isosorbide dinitrate reduces their effectiveness.

Atropine and other drugs with M-cholinoblocking action (e.g., etacizin, etmozine) – possible reduction in the vasodilating effect of isosorbide dinitrate and increase in intraocular pressure.

Donors of sulfhydryl groups (captopril, acetylcysteine, unithiol) restore reduced sensitivity to the drug.

Phosphodiesterase inhibitors (sildenafil, tadalafil, vardenafil) – treatment of erectile dysfunction with these agents is contraindicated during use of isosorbide dinitrate, due to potential risk of uncontrolled arterial hypotension and life-threatening cardiovascular complications. If necessary, phosphodiesterase inhibitors should not be administered earlier than 72 hours after administration of nitrates.

Alcohol – severe disulfiram-like alcohol reactions may occur, including severe hypotension and collapse.

Sympathomimetic agents (adrenaline, ephedrine, noradrenaline, naphazoline, mesaton, isadrine) – possible reduction in antianginal effect of nitrates.

Sapropterin (tetrahydrobiopterin, BH4) – a cofactor of nitric oxide synthase. Medicinal products containing sapropterin should be used with caution in combination with any medicinal agents exerting vasodilatory action via nitric oxide metabolism or containing nitric oxide donors, including nitroglycerin (GTN), isosorbide dinitrate (ISDN), isosorbide mononitrate.

Special precautions for use.

The drug is not used to relieve angina attacks. To prevent reduction or loss of effect, prolonged use of high doses should be avoided. In case of nitrate tolerance, it is recommended to discontinue IZO-MIK® 10 MG for 24–48 hours or, after 3–6 weeks of regular use, to take a break of 3–5 days, replacing IZO-MIK® 10 MG with other antianginal medications during this period. Patients should be informed that the antianginal effect of isosorbide dinitrate is closely related to its dosing regimen; therefore, the prescribed dosing schedule must be strictly followed.

The drug should be prescribed with caution to patients prone to orthostatic reactions, those with hypothyroidism, hypothermia, malnutrition, and elderly patients due to age-related changes in liver, kidney, and heart function, concomitant diseases, and use of other medications.

During treatment, especially when gradually increasing the dose, monitoring of blood pressure and heart rate is required.

IZO-MIK® 10 MG should be discontinued gradually by reducing the dose.

To prevent arterial hypotension and "nitrate-induced" headache, treatment should be initiated with the lowest possible dose. Concomitant use of aspirin and/or acetaminophen may be considered to reduce isosorbide dinitrate-induced headache without negatively affecting the antianginal effect of isosorbide dinitrate.

Treatment with the drug may lead to orthostatic reactions, which are more likely to occur when alcohol or other vasodilators are used concomitantly. Patients should avoid alcohol consumption during treatment with IZO-MIK® 10 MG.

In patients with glucose-6-phosphate dehydrogenase deficiency, administration of isosorbide dinitrate may cause acute hemolysis (favism).

Isosorbide dinitrate may interfere with colorimetric determination of cholesterol levels.

Patients on maintenance therapy with the drug should be informed that they must not take medications containing phosphodiesterase inhibitors (e.g., sildenafil, tadalafil, vardenafil) due to the risk of developing uncontrolled hypotension.

In patients with closed-angle glaucoma, intraocular pressure may increase.

The drug contains lactose and therefore is contraindicated in patients with rare hereditary conditions such as galactose intolerance, lactase deficiency, or glucose-galactose malabsorption syndrome.

Use during pregnancy or breastfeeding.

There is insufficient data regarding the safety of isosorbide dinitrate use during pregnancy. Use of the drug is contraindicated during the first trimester of pregnancy. During the second and third trimesters, the drug should be used only if the potential benefit to the mother outweighs the potential risk to the fetus.

If use of the drug is necessary, breastfeeding should be discontinued.

Ability to affect reaction speed when driving or operating machinery.

Until individual response to the drug is established, patients should refrain from driving or operating machinery, considering that treatment may cause reduced ability to concentrate, slowed psychomotor reactions, dizziness, and visual disturbances.

Dosage and Administration.

The dosage and duration of therapy are determined individually by a physician. The drug is recommended to be taken on an empty stomach; however, to reduce the intensity of "nitrate" headache, the drug may be taken with food.

For oral administration in adults: 10–20 mg 3–4 times daily, 30 minutes before meals, without chewing, and with sufficient fluid. If the therapeutic effect is insufficient, the dose may be gradually increased up to the maximum dose of 120 mg per day.

In patients with congestive heart failure, hemodynamic monitoring is of great importance for determining individual dosage.

The interval between doses should be at least 4 hours.

Elderly patients: dosage may be reduced, especially in cases of impaired renal and/or hepatic function.

Children: There is no experience with use in children.

Overdose.

Symptoms: decreased arterial pressure, pallor, increased sweating, weak pulse filling, dizziness, headache, orthostatic hypotension, weakness, reflex tachycardia, hyperthermia, nausea, vomiting, diarrhea. Since nitrite ions are released during biotransformation of isosorbide dinitrate, development of methemoglobinemia with cyanosis, followed by tachypnea, anxiety, loss of consciousness, and cardiac arrest cannot be excluded.

With excessive doses, increased intracranial pressure may occur, leading to cerebral symptoms including seizures.

Treatment: in case of arterial hypotension, the patient should be placed in a horizontal position with elevated lower limbs. If arterial pressure does not normalize, circulating blood volume should be corrected; in severe cases, dopamine and sympathomimetics are indicated. Administration of epinephrine (adrenaline) is contraindicated. In cases of methemoglobinemia, depending on severity, antidotes may be used: vitamin C (1 g orally), methylene blue (up to 50 mL of 1% solution intravenously), toluidine blue (initially 2–4 mg/kg body weight intravenously, then depending on severity). Oxygen therapy, hemodialysis, and transfusion therapy may also be employed.

Adverse reactions.

Immune system disorders: allergic reactions such as fever, skin rashes, urticaria, pruritus, transient facial and trunk hyperemia; exfoliative dermatitis/Stevens-Johnson syndrome, angioedema (Quincke's edema); skin vasodilation with redness, sensation of warmth, diaphoresis, and flushing.

Gastrointestinal disorders: nausea, vomiting, burning sensation of the tongue, dry mouth, heartburn.

Nervous system disorders: dizziness, drowsiness, headache ("nitrate headache" at the beginning of treatment, which usually gradually decreases or disappears with continued use of the drug, but may be severe and persistent), general weakness, somnolence, blurred vision.

Cardiovascular disorders: tachycardia, arterial hypotension; rarely – cerebral ischemia and collapse; orthostatic hypotension with reflex tachycardia, palpitations, and symptoms of cerebral ischemia (including drowsiness, dizziness, weakness, blurred vision) – mostly at the beginning of treatment and when increasing the dose; peripheral edema – usually in patients with left ventricular insufficiency; exacerbation or increased frequency of angina attacks associated with decreased blood pressure, pallor of the skin; collapse associated with bradycardia, cardiac arrhythmias, and syncope. Alveolar hypoventilation leading to subsequent hypoxemia and risk of hypoxia/myocardial infarction in patients with ischemic heart disease.

Blood and lymphatic system disorders: hematological adverse effects, including methemoglobinemia, cases of hemolytic anemia induced by isosorbide dinitrate in patients with concomitant glucose-6-phosphate dehydrogenase deficiency.

Eye disorders: blurred vision, closed-angle glaucoma, cases of visual hallucinations, narrowing of visual fields.

Other: cases of development of tolerance to isosorbide dinitrate, as well as cross-tolerance to other nitrates, have been reported. Intracranial hemorrhage in the pituitary gland in patients with undiagnosed pituitary tumors. Prolonged use of high doses and/or shortened intervals between doses may lead to reduced or even complete loss of drug efficacy. Closed-angle glaucoma. Cases of visual hallucinations, narrowing of visual fields, significant increase in plasma renin and aldosterone levels associated with decreased glomerular filtration rate and osmotically free water clearance have been reported in patients with liver cirrhosis, especially with ascites.

Shelf life.

3 years.

Storage conditions.

Store at temperatures not exceeding 30 °C in the original packaging.

Keep out of reach of children.

Packaging.

50 tablets per bottle in a cardboard box.

Prescription status.

Prescription only.

Manufacturer.

LLC NPF "MIKROKHIM" (responsible for batch release, excluding batch control/testing).

Manufacturer's address and location of business activity.

5, Budyndustrії Str., Kyiv, 01013, Ukraine.

To report an adverse event related to the use of this medicinal product, please call +38(050) 309-83-54 (24/7).

INSTRUCTION

for medical use of the medicinal product

ISO-MIK® 10 MG

(ISO-MIK 10 MG)

Composition:

Active substance: isosorbide dinitrate;

1 tablet contains isosorbide dinitrate 10 mg;

Excipients: potato starch; calcium stearate; sucrose; lactose monohydrate.

Pharmaceutical form.

Tablets.

Main physico-chemical properties.

White or almost white tablets with a creamy shade, flat surface, beveled edges.

Pharmacotherapeutic group.

Medicinal products affecting the cardiovascular system. Cardiological preparations. Vasodilators used in cardiology. Organic nitrates. Isosorbide dinitrate. ATC code C01D A08.

Pharmacological Properties.

Pharmacodynamics.

Isosorbide dinitrate is one of the main antianginal agents from the group of organic nitrates and a peripheral vasodilator that primarily affects venous vessels.

Like all organic nitrates, isosorbide dinitrate acts as a donor of nitric oxide (NO). NO causes relaxation of vascular smooth muscles (mainly veins and systemic arteries) by stimulating guanylate cyclase and subsequent increase in intracellular cyclic guanosine monophosphate (cGMP) concentration. This activates cGMP-dependent protein kinase and alters phosphorylation of various proteins in smooth muscle cells. This leads to dephosphorylation of myosin light chains and reduced contractility.

The effect of isosorbide dinitrate is associated with reduced myocardial oxygen demand due to decreased preload (by dilating peripheral veins and reducing blood flow to the right atrium) and afterload (by reducing total peripheral vascular resistance), as well as direct coronary vasodilating action. Isosorbide dinitrate promotes redistribution of coronary blood flow to areas with impaired perfusion. It increases exercise tolerance in patients with ischemic heart disease and angina.

The use of isosorbide dinitrate improves coronary perfusion without development of the "coronary steal syndrome." It exhibits antihypertensive effects. In severe forms of heart failure, due to reduced tone of peripheral venous vessels, the drug reduces cardiac load, pressure in pulmonary circulation vessels, and dyspnea.

Pharmacokinetics.

Bioavailability after oral administration is 22% (first-pass effect in the liver). Onset of action occurs within 15–40 minutes; maximum effect develops within 1.5–2 hours. Total duration of action is 4–6 hours or longer. The drug is metabolized in the liver. Elimination half-life is 4 hours and may be prolonged during repeated administration. It is excreted in urine almost entirely as metabolites.

Clinical characteristics.

Indications.

• Prevention and treatment of angina attacks, including post-infarction angina.
• Treatment of chronic congestive heart failure – in combination with cardiac glycosides and diuretics.

Contraindications.

• Hypersensitivity to isosorbide dinitrate, other nitrates, or any component of the drug;
• Increased intracranial pressure (including in cases of head injury, hemorrhagic stroke) – since venodilation may lead to further increase in pressure;
• Severe arterial hypotension (systolic blood pressure below 90 mm Hg), hemorrhage, hypovolemia (isosorbide dinitrate, by reducing venous return, may provoke syncope);
• Acute circulatory failure (shock, vascular collapse);
• Cardiogenic shock (unless adequate end-diastolic pressure is maintained by appropriate measures);
• Angina caused by hypertrophic obstructive cardiomyopathy;
• Cardiac tamponade, aortic stenosis, mitral stenosis, constrictive pericarditis;
• Acute myocardial infarction;
• Primary pulmonary diseases (due to risk of hypoxemia caused by redistribution of blood flow to areas of hyperventilation), toxic pulmonary edema, cor pulmonale;
• Severe anemia;
• Closed-angle glaucoma;
• Severe impairment of liver and/or kidney function, hyperthyroidism;
• Concomitant use with phosphodiesterase inhibitors (e.g., sildenafil, tadalafil, vardenafil).

Interaction with other medicinal products and other forms of interaction.

Antihypertensive agents (e.g., β-blockers, angiotensin-converting enzyme inhibitors, calcium antagonists, vasodilators), phenothiazines, other nitrates/nitrites, quinidine, procainamide, tricyclic antidepressants, monoamine oxidase inhibitors, opioid analgesics – potentiation of the hypotensive effect of isosorbide dinitrate, possible development of orthostatic collapse.

Disopyramide – possible reduction in the effectiveness of isosorbide dinitrate.

Dihydroergotamine – concentration of dihydroergotamine in blood may increase, leading to enhanced hypertensive effect.

Noradrenaline, acetylcholine, histamine – reduced effects when used with nitrates, as isosorbide dinitrate may act as their physiological antagonist.

Heparin – possible reduction in anticoagulant effect.

Hydralazine – improved cardiac output in heart failure when used in combination with isosorbide dinitrate.

Miotics – isosorbide dinitrate reduces their effectiveness.

Atropine and other drugs with M-cholinolytic action (e.g., etacizin, etmozine) – possible reduction in vasodilatory effect of isosorbide dinitrate and increase in intraocular pressure.

Sulfhydryl group donors (captopril, acetylcysteine, unithiol) restore reduced sensitivity to the drug.

Phosphodiesterase inhibitors (sildenafil, tadalafil, vardenafil) – concomitant use of phosphodiesterase inhibitors for erectile dysfunction is contraindicated during treatment with isosorbide dinitrate due to potential risk of uncontrolled arterial hypotension and life-threatening cardiovascular complications. If necessary, phosphodiesterase inhibitors should be administered no earlier than 72 hours after nitrate administration.

Alcohol – possible severe disulfiram-like alcohol reactions, including severe hypotension and collapse.

Sympathomimetic agents (adrenaline, ephedrine, noradrenaline, naphazoline, mesaton, isadrine) – possible reduction in antianginal effect of nitrates.

Sapropterin (tetrahydrobiopterin, BH4) – a cofactor of nitric oxide synthase. Medicinal products containing sapropterin should be used with caution in combination with any drugs exerting vasodilatory effects via nitric oxide metabolism or containing nitric oxide donors, including nitroglycerin (GTN), isosorbide dinitrate (ISDN), isosorbide mononitrate.

Special precautions for use.

The drug is not used to relieve acute angina attacks. To prevent reduction or loss of effect, prolonged use of high doses should be avoided. In case of nitrate tolerance, it is recommended to discontinue IZO-MIK® 10 MG for 24–48 hours or, after 3–6 weeks of regular use, to take a break for 3–5 days, replacing IZO-MIK® 10 MG during this period with other antianginal medications. Patients should be informed that the antianginal effect of isosorbide dinitrate is closely related to its dosing regimen, and therefore the prescribed dosing schedule must be strictly followed.

The drug should be prescribed with caution to patients predisposed to orthostatic reactions, patients with hypothyroidism, hypothermia, malnutrition, as well as elderly patients due to age-related changes in liver, kidney, and heart function, concomitant diseases, and use of other medications.

During treatment, especially when gradually increasing the dose, monitoring of blood pressure and heart rate is required.

IZO-MIK® 10 MG should be discontinued by gradual dose reduction.

To prevent arterial hypotension and nitrate-induced headache, treatment should be initiated with the lowest possible dose. Concomitant use of aspirin and/or acetaminophen may be considered to reduce isosorbide dinitrate-induced headache without negatively affecting the antianginal effect of isosorbide dinitrate.

Treatment with the drug may cause orthostatic reactions, which occur more frequently when alcohol or other vasodilators are used concomitantly. Consumption of alcohol should be avoided during treatment with IZO-MIK® 10 MG.

In patients with glucose-6-phosphate dehydrogenase deficiency, administration of isosorbide dinitrate may lead to acute hemolysis (favism).

Isosorbide dinitrate may interfere with colorimetric determination of cholesterol levels.

Patients receiving maintenance therapy with the drug should be informed that they must not take medications containing phosphodiesterase inhibitors (e.g., sildenafil, tadalafil, vardenafil) due to the risk of developing uncontrolled hypotension.

In patients with closed-angle glaucoma, an increase in intraocular pressure may occur.

The drug contains lactose and therefore is contraindicated in patients with rare hereditary conditions such as galactose intolerance, lactase deficiency, or glucose-galactose malabsorption syndrome.

Use during pregnancy or breastfeeding.

Data regarding the safety of isosorbide dinitrate use during pregnancy are insufficient. Use of the drug is contraindicated during the first trimester of pregnancy. During the second and third trimesters, the drug should be used only after careful assessment of the benefit-risk ratio to the mother and potential risk to the fetus.

If use of the drug is necessary, breastfeeding should be discontinued.

Ability to influence reaction speed when driving or operating machinery.

Until individual response to the drug is established, patients should refrain from driving or operating machinery, considering that treatment may lead to reduced concentration, slowed psychomotor reactions, dizziness, and visual disturbances.

Dosage and Administration

The dosage and duration of therapy are determined individually by a physician. The drug is recommended to be taken on an empty stomach; however, to reduce the intensity of "nitrate-induced" headache, the drug may be taken with food.

For adults, administer orally 10–20 mg 3–4 times daily, 30 minutes before meals, without chewing, with sufficient amount of liquid. If therapeutic response is inadequate, the dose may be gradually increased up to the maximum dose of 120 mg per day.

In patients with congestive heart failure, hemodynamic monitoring is of great importance for determining individual dosage.

The interval between doses should be at least 4 hours.

Elderly patients: dosage may be reduced, especially in cases of impaired renal and/or hepatic function.

Children: Experience with use in children is lacking.

Overdose.

Symptoms: decreased arterial pressure, pallor, increased sweating, weak pulse filling, dizziness, headache, orthostatic hypotension, weakness, reflex tachycardia, hyperthermia, nausea, vomiting, diarrhea. Since nitrite ions are released during biotransformation of isosorbide dinitrate, development of methemoglobinemia cannot be excluded, leading to cyanosis, subsequent tachypnea, sense of anxiety, loss of consciousness, and cardiac arrest.

With excessive doses, increased intracranial pressure may occur, resulting in cerebral symptoms, including seizures.

Treatment: In case of arterial hypotension, the patient should be placed in a horizontal position with elevated legs. If blood pressure does not normalize, circulating blood volume should be corrected; in severe cases, dopamine and sympathomimetics are indicated. Epinephrine (adrenaline) is contraindicated. In case of methemoglobinemia, depending on severity, antidotes may be used: vitamin C (1 g orally), methylene blue (up to 50 ml of 1% solution intravenously), toluidine blue (initially 2–4 mg/kg body weight intravenously, then according to severity). Oxygen therapy, hemodialysis, and transfusion therapy are also applied.

Adverse reactions.

Immune system disorders: allergic reactions such as fever, skin rashes, urticaria, pruritus, transient facial and trunk hyperemia; exfoliative dermatitis/Stevens-Johnson syndrome, angioedema (Quincke's edema); vasodilation of the skin with redness, sensation of warmth, diaphoresis, and flushing.

Gastrointestinal disorders: nausea, vomiting, sensation of mild burning of the tongue, dry mouth, heartburn.

Nervous system disorders: dizziness, drowsiness, headache ("nitrate headache" at the beginning of treatment, which usually gradually decreases or disappears with continued use of the drug, but may be severe and persistent), general weakness, drowsiness, blurred vision.

Cardiovascular system disorders: tachycardia, arterial hypotension; rarely – cerebral ischemia and collapse; orthostatic hypotension with reflex tachycardia, palpitations, and symptoms of cerebral ischemia (including drowsiness, dizziness, weakness, blurred vision) – mostly at the beginning of treatment and when increasing the dose; peripheral edema – usually in patients with left ventricular insufficiency; exacerbation or increased frequency of angina attacks associated with lowering of blood pressure, pallor of the skin; collapse associated with bradycardia, cardiac rhythm disturbances, and syncope. Alveolar hypoventilation leading to subsequent hypoxemia and risk of hypoxia/myocardial infarction in patients with ischemic heart disease.

Blood and lymphatic system disorders: hematological adverse effects, including methemoglobinemia; cases of hemolytic anemia induced by isosorbide dinitrate in patients with concomitant glucose-6-phosphate dehydrogenase deficiency.

Eye disorders: blurred vision, closed-angle glaucoma, visual hallucinations, narrowing of visual field.

Other: cases of development of tolerance to isosorbide dinitrate, as well as cross-tolerance to other nitrates, have been reported. Hemorrhage into the pituitary gland in patients with undiagnosed pituitary tumor. Prolonged use of high doses and/or shortening of the interval between doses may lead to reduced or even complete loss of drug efficacy. Closed-angle glaucoma. Cases of visual hallucinations, narrowing of visual field, significant increase in plasma renin and aldosterone levels associated with decreased glomerular filtration rate and osmotically free water clearance have been reported in patients with liver cirrhosis, especially with ascites.

Shelf life.

3 years.

Storage conditions.

Store at a temperature not exceeding 30 °C in the original packaging.

Keep out of reach of children.

Packaging.

50 tablets per bottle in a cardboard box.

Prescription status.

Prescription only.

Manufacturer.

LLC NVP "MIKROKHIM" (production unit (all stages of the manufacturing process)).

Manufacturer's address and location of business activity.

33 Lenin St., Rubizhne, Luhansk Oblast, 93000, Ukraine.

To report an adverse reaction during the use of this medicinal product, please call +38(050) 309-83-54 (24/7).