SUMMARY OF PRODUCT CHARACTERISTICS

1 NAME OF THE MEDICINAL PRODUCT

Isosorbide Mononitrate 10 mg Tablets

2 QUALITATIVE AND QUANTITATIVE COMPOSITION

Isosorbide-5-mononitrate-lactose trituration 90%, 11.10 mg equivalent to isosorbide-5-mononitrate, 10.00 mg.

(The lactose complies with Ph.Eur.).

3 PHARMACEUTICAL FORM

Tablets

White, upperside flat with bevelled edge and score engraving (E/10), underside rounded.

4 CLINICAL PARTICULARS

4.1 Therapeutic indications

For the prophylaxis of angina pectoris

4.2 Posology and method of administration

For oral administration Adults

One tablet to be taken asymmetrically (to allow a nitrate low period) two or three times a day. For patients not already receiving prophylactic nitrate therapy it is recommended that the initial dose be one tablet of Isosorbide Mononitrate 10 mg Tablets twice a day.

The dosage may be increased up to 120 mg per day.

The lowest effective dose should be used.

Elderly

There is no evidence to suggest that an adjustment of the dosage is necessary.

Children

The safety and efficacy of Isosorbide Mononitrate 10 mg Tablets has yet to be established in children.

Treatment with Isosorbide Mononitrate Tablets, as with any other nitrate, should not be stopped suddenly. Both the dosage and frequency should be tapered gradually (see section 4.4).

4.3    Contraindications

Isosorbide Mononitrate 10 mg Tablets should not be used in cases of acute myocardial infarction with low filling pressure, acute circulatory failure (shock, vascular collapse), or very low blood pressure, hypertrophic obstructive cardiomyopathy (HOCM), constrictive pericarditis, cardiac tamponade, low cardiac filling pressures, aortic/mitral valve stenosis and diseases associated with a raised intra-cranial pressure e.g. following a head trauma and including cerebral haemorrhage.

This product should not be given to patients with a known sensitivity to isosorbide mononitrate, the listed ingredients or other nitrates.

Isosorbide Mononitrate 10 mg Tablets should not be used in patients with marked anaemia, severe hypotension, closed angle glaucoma or hypovolaemia.

Phosphodiesterase type-5 inhibitors (e.g. sildenafil, tadalafil and vardenafil) have been shown to potentiate the hypotensive effects of nitrates, and their co-administration with nitrates or nitric oxide donors is therefore contraindicated (see section 4.5).

4.4    Special warnings and precautions for use

Isosorbide Mononitrate 10 mg Tablets should be used with caution in patients who have a recent history of myocardial infarction, or who are suffering from hypothyroidism, hypothermia, malnutrition and severe liver or renal disease.

Symptoms of circulatory collapse may arise after first dose, particularly in patients with labile circulation.

This product may give rise to postural hypotension and syncope in some patients. Severe postural hypotension with light-headedness and dizziness is frequently observed after the consumption of alcohol.

Hypotension induced by nitrates may be accompanied by paradoxical bradycardia and increased angina.

Isosorbide Mononitrate Tablets contain lactose and therefore should not be used in patients with rare hereditary problems of galactose intolerance, the Lapp lactase deficiency or glucose-galactose malabsorption.

In the event of an acute angina attack, a sublingual treatment such as a GTN spray or tablet should be used instead of Isosorbide Mononitrate Tablets.

If the tablets are not taken as indicated (see section 4.2.) tolerance to the medication could develop. The lowest effective dose should be used.

Treatment with Isosorbide Mononitrate Tablets, as with any other nitrate, should not be stopped suddenly. Both the dosage and frequency should be tapered gradually (see section 4.2)

4.5    Interaction with other medicinal products and other forms of interaction

Concurrent administration of drugs with blood pressure lowering properties, e.g. beta-blockers, calcium channel blockers, vasodilators, alprostadil, aldesleukin, angiotensin II receptor antagonists etc and/or alcohol may potentiate the hypotensive effect of Isosorbide Mononitrate Tablets. This may also occur with neuroleptics and tricyclic antidepressants.

Any blood pressure lowering effect of Isosorbide Mononitrate Tablets will be increased if used together with phosphodiesterase type-5 inhibitors which are used for erectile dysfunction (see special warnings and contraindications). This might lead to life threatening cardiovascular complications. Patients who are on Isosorbide Mononitrate Tablets therapy therefore must not use phosphodiesterase type-5 inhibitors

Reports suggest that concomitant administration of Isosorbide Mononitrate Tablets may increase the blood level of dihydroergotamine and its hypertensive effect.

4.6    Fertility, pregnancy and lactation

No data have been reported which would indicate the possibility of adverse effects resulting from the use of isosorbide mononitrate in pregnancy. Safety in pregnancy, however, has not been established. It is not known whether nitrates are excreted in human milk and therefore caution should be exercised when administered to nursing women.

Isosorbide mononitrate should only be used in pregnancy and during lactation if, in the opinion of the physician, the possible benefits of treatment outweigh the hazards.

4.7    Effects on ability to drive and use machines

Dizziness, tiredness or blurred vision might occur at the start of treatment. The patient should therefore be advised that if affected, they should not drive or operate machinery. This effect may be increased by alcohol.

4.8 Undesirable effects

A very common (>10% of patients) adverse reaction to Isosorbide Mononitrate Tablets is throbbingheadache. The incidence of headache diminishes gradually with time and continued use.

At the start of therapy or when the dosage is increased, hypotension and/or light headedness in the upright position are commonly observed (i.e. in 1 - 10% of patients). These symptoms may be associated with dizziness, drowsiness, reflex tachychardia and a feeling of weakness.

Infrequently (i.e. in less than 1% of patients) nausea, vomiting, flushing and allergic skin reaction (e.g. rash) may occur sometimes severely. In single cases exfoliative dermatitis may occur.

Severe hypotensive responses have been reported for organic nitrates and include nausea, vomiting, restlessness pallor and excessive perspiration. Uncommonly collapse may occur (sometimes accompanied by bradyarrhythmia and syncope). Uncommonly severe hypotension may lead to enhanced angina symptoms.

A few reports of heartburn most likely due to a nitrate induced sphincter relaxation have been recorded.

Tachycardia and paroxysmal bradycardia have been reported.

Reporting of suspected adverse reactions

Reporting suspected adverse reactions after authorisation of the medicinal products is important. It allows continued monitoring of the benefit/risk balance of the medicinal product. Healthcare professionals are asked to report any suspected adverse reactions via the Yellow Card Scheme at: www.mhra.gov .uk/yellowcard.

4.9 Overdose

Symptoms and signs:

Headache, hypotension, nausea, vomiting, sweating, tachycardia, vertigo, restlessness, warm flushed skin, blurred vision and syncope. A rise in intracranial pressure with confusion and neurological deficits can sometimes occur. Methaemoglobinaemia (cyanosis, hypoxaemia, restlessness, respiratory depression, convulsions, cardiac arrhythmias, circulatory failure, raised intracranial pressure) occurs rarely.

Management:

Consider oral activated charcoal if ingestion of a potentially toxic amount has occurred within 1 hour. Observe for at least 12 hours after the overdose. Monitor blood pressure and pulse. Correct hypotension by raising the foot of the bed and/or by expanding the intravascular volume. Other measures as indicated by the patient’s clinical condition. If severe hypotension persists despite the above measures consider use of inotropes

If methaemoglobinaemia (symptoms or > 30% methaemoglobin), IV administration of methylene blue 1-2 mg/kg body weight. If therapy fails with second dose after 1 hour or contraindicated, consider red blood cell concentrates or exchange transfusion. In case of cerebral convulsions, diazepam or clonazepam IV, or if therapy fails, phenobarbital, phenytoin or propofol anaesthesia.

5.1 Pharmacodynamic properties

ATC Code: CO1D A14 Vasodilator used in cardiac diseases

Isosorbide mononitrate is an organic nitrate which, in common with other cardioactive nitrates, is a vasodilator. It produces decreased left and right ventricular end-diastolic pressures to a greater extent than the decrease in systemic arterial pressure, thereby reducing afterload and especially the preload of the heart.

Isosorbide mononitrate influences the oxygen supply to ischaemic myocardium by causing the redistribution of blood flow along collateral channels and from epicardial to endocardial regions by selective dilation of large epicardial vessels.

It reduces the requirement of the myocardium for oxygen by increasing venous capacitance, causing a pooling of blood in peripheral veins, thereby reducing ventricular volume and heart wall distension.

5.2 Pharmacokinetic properties

lsosorbide-5-mononitrate is rapidly absorbed and peak plasma levels occur approx. 1 hour following oral dosing.

lsosorbide-5-mononitrate is completely bioavailable after oral doses and is not subject to pre-systemic elimination processes.

lsosorbide-5-mononitrate is eliminated from the plasma with a half-life of about 5.1 hours. It is metabolised to lsosorbide-5-MN-2-glucoronide, which has a half-life of approximately 2.5 hours. As well as being excreted unchanged in the urine.

After multiple oral dosing plasma concentrations are similar to those that can be predicted from single dose kinetic parameters.

5.3 Preclinical safety data

Preclinical data reveal no special hazard for humans based on conventional studies of single and repeated dose toxicity, genotoxicity, oncogenicity and toxicity to reproduction.

6.1 List of excipients

Lactose monohydrate

Microcrystalline cellulose Potato starch Purified talc

Colloidal silicon dioxide Aluminium stearate.

6.2 Incompatibilities

None Known

6.3 Shelf life

5 years

6.4 Special precautions for storage

None

6.5 Nature and contents of container

Cartons of blister strips of PP/aluminium or of PP/PP.

Aluminium foil thickness l6pm or 20pm.

Pack sizes: 14, 50, 56, 60, 84 and 90 tablets.

6.6 Special precautions for disposal

None