Composition:

Each film coated tablet of ISOMAK contains:

10 or 20 mg of isosorbide mononitrate.

Clinical pharmacology:

Isosorbide mononitrate is the major active metabolite of isosorbide dinitrate (ISDN), and most of the clinical activity of the dinitrate is attributable to the mononitrate.

Mechanism of action:

The principle pharmacological action of Isosorbide mononitrate (ISMN) and all organic nitrates in general is relaxation of vascular smooth muscles, producing dilatation of peripheral arteries and veins, especially the latter and dilatation of coronary arteries.

Pharmacokinetics and metabolism:

Maximum serum concentrations of ISMN are achieved in 30 to 60 minutes, with an absolute bioavalability of nearly 100%. ISMN is primarily metabolized in the liver, but unlike oral ISDN, it is not subject to first-pass metabolism.

Indications:

– Prevention and long-term treatment of angina pectoris.

– Treatment of severe heart failure.

– High pressure in the pulmonary circulation (pulmonary hypertension).

Contraindications:

• ISOMAK must not be used in case of:

Hypersensitivity to nitro-compounds, acute circulatory failure, cardiogenic shock, if sufficiently high left ventricular, enddiastolic pressure is not guaranteed by intraaortal, concomitant intake of sildenafil (Viagra), very low blood pressure (systolic blood pressure below 90 mm Hg).

• Isosorbide mononitrate should only be administered with caution in case of:

Disorder of the heart muscle with narrowing of the inner part of the heart (hypertrophic obstructive cardiomyopathy), constrictive pericarditis, low filling pressures e.g. in case of acute myocardial infarction, impaired function of the left ventricle (left heart failure). A drop in systolic blood pressure below 90 mm Hg should be avoided, narrowing of the aortic, tendency to disturbances of the circulatory regulation caused by low blood pressure (orthostatic disturbances of circulatory regulation), diseases associated with increased pressure in the cranial cavity (intracranial pressure) (so far, a further pressure increase has only been observed after high-dose i.v. application of glyceryl trinitrate).

ISOMAK is not appropriate for the treatment of sudden cardiac pain (e.g. acute anginal attack, acute myocardial infarction).

• Pregnancy and lactation:

For safety reasons Isosorbide mononitrate should only be administered during pregnancy and lactation if explicitly prescribed by the physician as experience with the use in pregnant and nursing women is not sufficient. Animal experiments showed no evidence of embryotoxic effects.

Precautionary measures and Warnings:

What should be observed while taking part in road traffic, operating machinery, and performing works without safe hold:

Even when used according to instructions, this drug may change the reactivity to such an extent as to impair the ability to take part in road traffic, operate machinery or perform works without safe hold. This applies especially at the start of treatment, dosage increase, and chang of drug. It is particularly true in combination with alcohol.

Drug interactions:

Antihypertensives, ß-blockers, calcium antagonists, neuroleptics or tricyclic antidepressants, sildenafil (Viagra, drug for the treatment of erectile dysfunction), and alcohol may potentiate the blood pressure lowering effect of ISOMAK.

Co-administration of dihydroergotamine may result increased DHE levels.

Dosage & Administration:

The recommended starting dose is 10 mg tablet twice daily. For most patients, after several days the dose can be increased to 20 mg tablets twice daily according to the need of patient and his clinical response.

Over-dosage:

Marked decrease in blood pressure (hypotension) with reflex increase in pulse rate, debility, dizziness, and drowsiness as well as headache, flush, nausea, vomiting, and diarrhea may occur.

Side effects:

Headache may frequently occur at the start of treatment. It usually diminishes after a few days as therapy is continued.

First use or dosage increase may occasionally result in blood pressure fall and/or disturbances of the circulatory regulation when changing the position.

Collapse conditions, occasionally with cardiac irregularity with slowness of the heart beat (bradycardiac arrhythmia) and syncopes (sudden loss of consciousness) are rarely observed.

Storage:

Store at temperature below 25^°c.

How supplied:

3 Blisters contain 30 film coated tablets of ISOMAK.