Nitrates.

Isosorbide dinitrate

Each tablet contains isosorbide dinitrate 20 mg/40mg in a prolonged release formulation.

Prolonged release tablets. White with break score, marked IR 40/ IR 20 on the upper side and with SCHWARZ PHARMA on the reverse side.

For the prophylaxis and treatment of angina pectoris.

For oral administration.

Adults: One tablet to be taken once daily without chewing and with a sufficient amount of fluid. For patients with higher nitrate requirements the dose may be increased to one tablet twice daily; the second dose should be given 6 to 8 hours after the first.

The safety and efficacy of Isoket Retard has yet to be established

Clinical experience has not necessitated alternative advice for use in elderly patients.

This product should not be given to patients with a known sensitivity to nitrates (or any other ingredient in this product), very low blood pressure, acute myocardial infarction with low filling pressure, marked anaemia, head trauma, cerebral haemorrhage, acute circulatory failure, severe hypotension or hypovolaemia.

Phosphodiesterase inhibitors (e.g. Sildenafil) have been shown to potentiate the hypotensive effects of nitrates, and their co-administration with nitrates or nitric oxide donors is therefore contraindicated.

These tablets should be used with caution in patients who are suffering from hypothyroidism, hypothermia, malnutrition, severe liver disease or renal disease.

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

This product may give rise to symptoms of postural hypotension and sycope in some patients.

These tablets should be used with particular caution and under medical supervison in the following:

Hypertrophic obstructive cardiomyopathy (HOCM), constrictive pericarditis, cardiac tamponade, low cardiac filling pressures, aortic/mitral valve stenosis, and diseases associated with raised intracranial pressure.

Treatment with these tablets must not be interrupted or stopped to take phosphodiestearase inhibitor products due to the increased risk of inducing an attack of angina pectoris.

If these tablets are not taken as indicated with the appropriate dosing interval (see section 4.2) tolerance to the medication could develop.

Concurrent intake of drugs with blood pressure lowering properties e.g. beta-blockers, calcium antagonists, vasodilators etc. and/or alcohol may potentiate the hypotensive effect of the tablets. Symptoms of circulatory collapse can arise in patients already taking ACE inhibitors.

The hypotensive effect of nitrates is potentiated by concurrent administration of phosphodiesterase inhibitors (e.g. sildenafil). This might also occur with neuroleptics and tricyclic antidepressants.

Reports suggest that when administered concomitantly, nitrates may increase the blood level of dihydroergotamine and its hypertensive effect.

A very common (> 10% of patients) adverse reaction to these tablets is headache. The incidence of headache diminishes gradually with time and continued use,

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

Infrequently (i.e. in less than 1% of patients), nausea, vomiting, flush and allergic skin reaction (e.g. rash), which may be sometimes severe may infrequently occur. In isolated cases exfoliative dermatitis may occur. Very rarely, Stevens-Johnson-Syndrome or angiodema 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 on heartburn most likely due to a nitrate-induced sphincter relaxation have been recorded.

During treatment with these tablets, a temporary hypoxaemia may occur due to a relative redistribution of the blood flow in hypoventilated alveolar areas. Particularly in patients with coronary artery disease this may lead to a myocardial hypoxia.

UCB Pharma

(P)

21 May 2009