Isosprbide Mononitrate-Teva (Tablets) Instructions for Use

Marketing Authorization Holder

Teva Pharmaceutical Industries, Ltd. (Israel)

Manufactured By

Merckle, GmbH (Germany)

ATC Code

C01DA14 (Isosorbide mononitrate)

Active Substance

Isosorbide mononitrate (Rec.INN registered by WHO)

Dosage Form

Isosprbide Mononitrate-Teva

Tablets 40 mg: 20, 30, 50 or 100 pcs.

Dosage Form, Packaging, and Composition

10 pcs. – blisters (2) – carton packs.
10 pcs. – blisters (3) – carton packs.
10 pcs. – blisters (5) – carton packs.
10 pcs. – blisters (10) – carton packs.

Clinical-Pharmacological Group

Peripheral vasodilator. Anti-anginal drug

Pharmacotherapeutic Group

Vasodilating agent – nitrate

Pharmacological Action

Peripheral vasodilator with a predominant effect on venous vessels, antianginal agent. It reduces the myocardial oxygen demand by reducing preload (dilation of peripheral veins and decreased blood flow to the right atrium) and afterload (decrease in total peripheral vascular resistance), and also has a direct coronary vasodilating effect.

It promotes the redistribution of coronary blood flow to areas with reduced blood supply. It increases exercise tolerance in patients with coronary artery disease and angina pectoris. In heart failure, it promotes myocardial unloading by reducing preload. It reduces pressure in the pulmonary circulation.

Pharmacokinetics

After oral administration, isosorbide-5-mononitrate is rapidly and completely absorbed from the gastrointestinal tract. Bioavailability is 90-100%. Plasma concentration is directly proportional to the dose.

Isosorbide-5-mononitrate is almost completely biotransformed in the liver to form inactive metabolites.

It is excreted by the kidneys mainly in the form of metabolites, 2% unchanged. T_1/2 is 4-5 hours.

Indications

Coronary artery disease: prevention of angina attacks, including after myocardial infarction.

Chronic heart failure – as additional symptomatic therapy in combination with cardiac glycosides and/or diuretics when they are insufficiently effective.

ICD codes

Dosage Regimen

Administer orally. Swallow the tablet whole with a sufficient amount of liquid.

Initiate therapy with a low dose to minimize the risk of headache and hypotension. Titrate the dose gradually based on clinical response and tolerability.

For the prophylaxis of angina pectoris, the typical initial dose is 20 mg (half a 40 mg tablet) once or twice daily. Increase the dose to the standard maintenance dose of 40 mg once or twice daily as tolerated.

To prevent the development of tolerance, implement a dosing schedule that provides a daily nitrate-free interval. Administer the first dose in the morning and the second dose, if applicable, 7 hours later to ensure a drug-free period of approximately 17 hours.

For patients with chronic heart failure used as adjunctive therapy, the dosing regimen is similar. The maximum single dose should not exceed 40 mg.

In elderly patients and those with hepatic or renal impairment, use with caution and consider initiating treatment at the lower end of the dosing range.

Do not abruptly discontinue treatment; gradually reduce the dose to prevent withdrawal syndrome.

Adverse Reactions

From the cardiovascular system: frequent – tachycardia, orthostatic hypotension; infrequent – “paradoxical” increase in angina attacks; collapse (sometimes accompanied by bradyarrhythmia and syncope); frequency unknown – pronounced decrease in blood pressure.

From the nervous system: very frequent – “nitrate” headache; frequent – drowsiness, dizziness; rare – cerebral ischemia.

From the digestive system: infrequent – nausea, vomiting; very rare – heartburn.

From the skin and subcutaneous tissues: infrequent – skin allergic reactions (including rash), facial flushing; very rare – angioedema, Stevens-Johnson syndrome; frequency unknown – exfoliative dermatitis.

General disorders: frequent – asthenia, development of tolerance (including cross-tolerance to other nitrates). To prevent the development of tolerance, continuous use of high doses of isosorbide mononitrate should be avoided.

Long-term use of isosorbide mononitrate can cause transient hypoxemia due to relative redistribution of blood flow to hypoventilated alveolar areas (in patients with coronary artery disease – can lead to myocardial ischemia).

Contraindications

Hypersensitivity to isosorbide dinitrate, other nitrates; acute circulatory disorders (shock, collapse); cardiogenic shock (unless measures are taken to maintain end-diastolic pressure); hypertrophic obstructive cardiomyopathy; constrictive pericarditis; cardiac tamponade; severe arterial hypotension (systolic blood pressure below 90 mm Hg); severe hypovolemia; severe anemia; severe aortic and subaortic stenosis, severe mitral stenosis; cerebral hemorrhage; simultaneous use of PDE5 inhibitors (including sildenafil, vardenafil, tadalafil); simultaneous use with the soluble guanylate cyclase stimulator riociguat; age under 18 years (efficacy and safety not established).

With caution low left ventricular filling pressure, including in acute myocardial infarction, impaired left ventricular function; aortic and/or mitral stenosis; diseases accompanied by increased intracranial pressure; closed-angle glaucoma; tendency to orthostatic disorders of vascular regulation, severe renal and/or hepatic insufficiency, hypothyroidism, inadequate and malnutrition; pregnancy, period of breastfeeding.

Use in Pregnancy and Lactation

Use during pregnancy and lactation (breastfeeding) is possible in cases where the expected benefit of therapy for the mother outweighs the potential risk to the fetus or child.

If use during lactation is necessary, the issue of discontinuing breastfeeding should be considered.

Use in Hepatic Impairment

Should be used with caution in patients with severe hepatic insufficiency.

Use in Renal Impairment

Should be used with caution in patients with severe renal insufficiency.

Pediatric Use

Contraindicated for use in children and adolescents under 18 years of age.

Special Precautions

Not used for relief of angina attacks. Use with caution in increased intracranial pressure.

During therapy, monitoring of blood pressure and heart rate is necessary.

During the use of isosorbide mononitrate, alcohol consumption should be avoided.

Effect on the ability to drive vehicles and mechanisms

During treatment, it is not recommended to drive vehicles and engage in other potentially hazardous activities that require quick psychomotor reactions.

Drug Interactions

With simultaneous use with adsorbents, astringents and coating agents, the absorption of isosorbide mononitrate is reduced.

With simultaneous use with anticholinergic agents, memory and attention disorders are possible in elderly patients.

With simultaneous use of vasodilators, calcium channel blockers, tricyclic antidepressants, ethanol, an increase in the hypotensive effect is possible.

With simultaneous use with antihypertensive drugs, beta-blockers, antipsychotics, PDE inhibitors (including sildenafil, vardenafil, tadalafil), an increase in the hypotensive effect is possible.

With simultaneous use with dihydroergotamine, an increase in the concentration and enhancement of the effect of dihydroergotamine is possible.

With simultaneous use with norepinephrine, the therapeutic effect of norepinephrine is reduced.

Simultaneous use of isosorbide mononitrate with riociguat, a soluble guanylate cyclase stimulator, is contraindicated, as it may cause hypotension.

Storage Conditions

Store at 2°C (36°F) to 25°C (77°F). Keep in original packaging, protected from light. Keep out of reach of children.

Dispensing Status

Rx Only

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.