SUMMARY OF PRODUCT CHARACTERISTICS

1    NAME OF THE MEDICINAL PRODUCT

Elantan LA25

2    QUALITATIVE AND QUANTITATIVE COMPOSITION

Isosorbide mononitrate 25mg

For excipients, see 6.1.

3 PHARMACEUTICAL FORM

Prolonged release capsules

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 capsule to be taken in the morning.

For patients with higher nitrate requirements the dose may be increased to two capsules taken simultaneously. The lowest effective dose should be used.

Elderly

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

Children

The safety and efficacy of these capsules has yet to be established in children.

Attenuation of effect has occurred in some patients being treated with prolonged release preparations. In such patients intermittent therapy may be more appropriate (see section 4.4).

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

4.3 Contraindications

The capsules 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 a cerebral haemorrhage.

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

Elantan LA should not be used in patients with marked anaemia, closed angle glaucoma, severe hypotension or hypovolaemia.

Phosphodiesterase type 5 inhibitors (eg 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

The capsules should be used with caution in patients who have a recent history of myocardial infarction or who are suffering from hypothyroidism, hypothermia, malnutrition, 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 symptoms of 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.

Elantan LA capsules 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 Elantan LA capsules.

If these capsules are not taken as indicated (see section 4.2.) tolerance to the medication could develop. In some patients being treated with prolonged release preparations, attenuation of effect is observed. In such patients, intermittent therapy may be more appropriate. The lowest effective dose should be used.

Treatment of Elantan LA, 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 Elantan LA. This may also occur with neuroleptics and tricyclic antidepressants.

Any blood pressure lowering effect of Elantan LA 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 Elantan LA therapy therefore must not use phosphodiesterase type 5 inhibitors.

Reports suggest that concomitant administration of Elantan LA may increase the blood level of dihydroergotamine and its hypertensive effect.

4.6 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 outweigh the possible hazards.

4.7 Effects on ability to drive and use machines

Dizziness, tiredness or blurred vision may 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 Elantan is throbbing headache. 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 (ie in less than 1% of patients) nausea, vomiting, flushing and allergic skin reaction (eg 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.

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 the 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    PHARMACOLOGICAL PROPERTIES

5.1    Pharmacodynamic properties

ATC Code: C01D A 14 - Vasodilator used in cardiac disease.

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

Isosorbide mononitrate is a vasodilator, which is rapidly absorbed following oral administration. These capsules have a bioavailability of 84 (+/- 7) % when compared to the immediate release isosorbide mononitrate tablets. There is no effect of food on bioavailability.

The capsules contain pellets which are formulated to release 30% of the dose immediately whilst 70% of the dose is released slowly.

Time to peak plasma levels (Tmax) is 5 (+/-3) hrs, with a half life (TL2) of 5.02 (+/-0.68) hrs.

Isosorbide mononitrate is extensively metabolised to nitric oxide (NO - which is the active agent) and isosorbide (inactive). In patients with cirrhotic disease or cardiac failure or renal failure, pharmacokinetic parameters were similar to those obtained in healthy volunteers.

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 PHARMACEUTICAL PARTICULARS

6.1    List of excipients

Lactose monohydrate Purified talc Ethyl cellulose Macrogol 20000 Hydroxypropyl cellulose Sucrose Corn starch

Gelatin

Titanium dioxide Iron oxide red (E172) Iron oxide black (E172)

6.2 Incompatibilities

None Known.

6.3 Shelf life

5 years.

6.4    Special precautions for storage

Do not store above 30°C.

6.5    Nature and contents of container

Cartons of blister strips of PVC and aluminium or of PP and aluminium. Aluminium foil thickness 20pm or 16pm.

Pack size: 28 capsules.

6.6 Special precautions for disposal

None.

7    MARKETING AUTHORISATION HOLDER

UCB Pharma Limited

208 Bath Road

Slough

Berkshire

SL1 3WE

United Kingdom

8    MARKETING AUTHORISATION NUMBER(S)

PL 00039/0741

9    DATE OF FIRST AUTHORISATION/RENEWAL OF THE

AUTHORISATION

07/09/2007

10 DATE OF REVISION OF THE TEXT

13/03/2013