Iso-mik® 20 mg

INSTRUCTION FOR MEDICAL USE OF THE MEDICINAL PRODUCT ISO-MIK® 20 MG (ISO-MIK 20 MG)

Composition:

Active substance: isosorbide dinitrate;

One tablet contains 20 mg of isosorbide dinitrate;

Excipients: potato starch; calcium stearate; lactose monohydrate.

Pharmaceutical form.

Tablets.

Main physicochemical properties.

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

Pharmacotherapeutic group.

Medicinal products affecting the cardiovascular system. 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 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 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, leading to 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 due to its direct coronary vasodilating action. Isosorbide dinitrate promotes redistribution of coronary blood flow to areas with impaired perfusion. It improves exercise tolerance in patients with ischemic heart disease and angina pectoris.

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

Pharmacokinetics.

Bioavailability after oral administration 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, and the 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 almost entirely in the urine as metabolites.

Clinical characteristics.

Indications.

• Prophylaxis and treatment of angina pectoris attacks, including postinfarction 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 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 pectoris caused by hypertrophic obstructive cardiomyopathy;
• cardiac tamponade, aortic stenosis, mitral sten0sis, constrictive pericarditis;
• acute myocardial infarction;
• primary pulmonary diseases (due to risk of hypoxemia caused by blood flow redistribution 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, tricyclic antidepressants, monoamine oxidase inhibitors, narcotic analgesics – potentiation of the hypotensive effect of isosorbide dinitrate, possible development of orthostatic collapse.

Disopyramide – possible reduction in 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, since isosorbide dinitrate may act as their physiological antagonist.

Heparin – possible reduction of 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-cholinolytic action (e.g. etacizine, etmozine) – possible reduction of vasodilating 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) – 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 be taken no 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, naftyzinum, mesaton, isadrine) – possible reduction of 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 causing vasodilation 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 IZOMIK® 20 MG for 24–48 hours or, after 3–6 weeks of regular use, to take a 3–5 day break, replacing IZOMIK® 20 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 schedule, and therefore the prescribed dosing regimen 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.

IZOMIK® 20 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. Aspirin and/or acetaminophen may be used to reduce isosorbide dinitrate-induced headache without negatively affecting the antianginal effect of isosorbide dinitrate.

Treatment with the drug may lead to the development of orthostatic reactions, which occur more frequently when alcohol or other vasodilators are used concomitantly. Alcohol consumption should be avoided during treatment with IZOMIK® 20 MG.

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

Isosorbide dinitrate may interfere with the results of colorimetric cholesterol determination.

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 its use 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 on 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 of pregnancy, the drug should be used only with careful consideration 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 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 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, the recommended dosage is 10–20 mg taken orally 3–4 times daily, 30 minutes before meals. The tablets should be swallowed whole with sufficient amount of liquid, without chewing. If the 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 the individual dosage.

The interval between doses should be at least 4 hours.

Elderly patients: The dose may be reduced, especially in the presence of renal and/or hepatic impairment.

Children.

There is no experience with use in children.

Overdose.

Symptoms: decreased arterial blood pressure, pallor, excessive sweating, weak pulse, dizziness, headache, orthostatic hypotension, weakness, reflex tachycardia, hyperthermia, nausea, vomiting, diarrhea. Since nitrite ions are released during the biotransformation of isosorbide dinitrate, development of methemoglobinemia cannot be excluded, which may lead 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, administration of dopamine and sympathomimetics is indicated. Epinephrine (adrenaline) is contraindicated. In cases of methemoglobinemia, depending on the severity, antidotes may be used: vitamin C (1 g orally), methylene blue (up to 50 ml of a 1% solution intravenously), or toluidine blue (initially 2–4 mg/kg body weight intravenously, then dosage adjusted according to 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; 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/disappears with continued use of the drug, but may be severe and persistent), general weakness, drowsiness, 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/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 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 the visual field.

Other: cases of development of tolerance to isosorbide dinitrate, as well as cross-tolerance to other nitrates, have been reported. Hypophyseal hemorrhage in patients with undiagnosed pituitary tumors. Prolonged use of high doses and/or shortening the interval between doses may lead to reduced or even complete loss of drug efficacy. Closed-angle glaucoma. Cases of visual hallucinations, narrowing of the 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 temperatures not exceeding 30 °C in the original packaging.

Keep out of reach of children.

Packaging.

50 tablets in a bottle in a cardboard box.

Prescription status.

Prescription only.

Manufacturer.

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

Manufacturer's address and location of business activity.

5 Budynstustriyi St., Kyiv, 01013, Ukraine.

Report any adverse events associated with the use of this medicinal product at +38 (050) 309-83-54 (24/7).

INSTRUCTION

for medical use of the medicinal product

ISO-MIK® 20 MG

(ISO-MIK 20 MG)

Composition:

Active ingredient: isosorbide dinitrate;

1 tablet contains 20 mg of isosorbide dinitrate;

Excipients: potato starch; calcium stearate; lactose monohydrate.

Pharmaceutical form.

Tablets.

Main physicochemical properties.

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

Pharmacotherapeutic group.

Medicinal products affecting the cardiovascular system. 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 and acts as a peripheral vasodilator primarily affecting venous vessels.

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

The therapeutic 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 through direct coronary vasodilation. Isosorbide dinitrate promotes redistribution of coronary blood flow to areas with impaired perfusion. It improves exercise tolerance in patients with ischemic heart disease and angina pectoris.

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

Pharmacokinetics

Oral bioavailability is approximately 22% (due to the "first-pass" effect in the liver). Onset of action occurs within 15–40 minutes, peak effect develops at 1.5–2 hours, and the total duration of action is 4–6 hours or longer. The drug is metabolized in the liver. Elimination half-life is about 4 hours and may be prolonged with repeated administration. It is excreted almost entirely in the urine 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 cranio-cerebral trauma, hemorrhagic stroke) – since venodilation may lead to its 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 risk of developing 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-blockers, angiotensin-converting enzyme inhibitors, calcium antagonists, vasodilators), phenothiazines, other nitrates/nitrites, quinidine, procainamide, tricyclic 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 enhancement of its hypertensive effect.

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

Heparin – possible reduction of its anticoagulant effect.

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

Myotic agents – isosorbide dinitrate reduces their effectiveness.

Atropine and other drugs with M-cholinolytic action (e.g., etacizine, 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) – 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 be administered no earlier than 72 hours after administration of nitrates.

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

Sympathomimetic agents (epinephrine, ephedrine, norepinephrine, 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 intended for the relief of acute angina attacks. To prevent reduction or loss of effect, prolonged use of high doses should be avoided. In the case of "nitrate" tolerance, it is recommended to discontinue ISO-MIK® 20 MG for 24–48 hours, or after 3–6 weeks of regular use, to make a 3–5 day break, replacing ISO-MIK® 20 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 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 with gradual dose escalation, monitoring of blood pressure and heart rate is required.

ISO-MIK® 20 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 efficacy of isosorbide dinitrate.

Treatment with the drug may lead to orthostatic reactions, which occur more frequently when alcohol or other vasodilators are used concomitantly. Consumption of alcohol should be avoided during treatment with ISO-MIK® 20 MG.

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

Isosorbide dinitrate may interfere with the results of colorimetric cholesterol determination.

Patients receiving maintenance therapy with this 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.

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 expected 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-induced" headache, the drug may be taken with food.

For adults, administer orally 10–20 mg 3–4 times daily, 30 minutes before meals. The tablets should be swallowed whole with sufficient amount of liquid. 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: the dose 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 blood pressure, pallor, increased sweating, weak pulse filling, dizziness, headache, orthostatic hypotension, weakness, reflex tachycardia, hyperthermia, nausea, vomiting, diarrhea. Since nitrite ions are released during the 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 lower limbs. If blood pressure does not normalize, circulating blood volume should be corrected. In severe cases, administration of dopamine and sympathomimetics is indicated. Epinephrine (adrenaline) is contraindicated. In cases of methemoglobinemia, antidotes may be used depending on severity: 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 may also be applied.

Side effects.

Immune system disorders: allergic reactions such as fever, skin rashes, urticaria, itching, transient facial and trunk hyperemia; exfoliative dermatitis/Stevens-Johnson syndrome, angioedema; vasodilation of the skin with redness, sensation of warmth, diaphoresis, 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/disappears with continued use of the drug, but may be severe and persistent), general weakness, drowsiness, 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; worsening 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 with subsequent hypoxemia and risk of developing 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 field.

Other: cases of development of tolerance to isosorbide dinitrate, as well as cross-tolerance to other nitrates, have been reported. Hypophyseal hemorrhage 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 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 in a bottle in a cardboard box.

Prescription status.

Prescription only.

Manufacturer.

LLC "MIKROKHEM" ("MIKROKHEM" Pharmaceutical Company) (production unit (all stages of the manufacturing process)).

Manufacturer's address and location of business activity.

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

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