SUMMARY OF PRODUCT CHARACTERISTICS

1    NAME OF THE MEDICINAL PRODUCT

MONOMAX SR 60

2 QUALITATIVE AND QUANTITATIVE COMPOSITION

Each modified-release capsule contains 40mg of isosorbide mononitrate.

For the full list of excipients, see section 6.1.

3. PHARMACEUTICAL FORM

Modified-release capsule

Each size 2 capsule contains off-white to yellowish microgranules. The capsule shell has an opaque, white cap and body. "ISMN SR" is axially printed on the cap and "40" is axially printed on the body in black ink.

4.1. Therapeutic indications

For the prophylactic treatment of angina pectoris.

4.2 Posology and method of administration

Method of administration For oral use

Capsules may be taken with or without food, and should be swallowed whole and not chewed.

Posology

Adults: One capsule to be taken in the morning. This may be increased to 120mg if required. The product must not be given in divided doses, as a daily nitrate free period is required in order to prevent the development of tolerance.

Paediatric population: Safety and efficacy in children have not been established.

Older people: There is no evidence of a need for routine dosage adjustment in older people, but special care may be needed in those with increased susceptibility to hypotension or marked hepatic or renal insufficiency.

4.3 Contraindications

Hypersensitivity to the active substance or to any of the excipients listed in section 6.1. This product should not be given to patients with a known sensitivity to nitrates.

Relative contraindications to the use of isosorbide mononitrate are severe cerebral vascular insufficiency and hypotension.

Sildenafil has been shown to potentiate the hypotensive effects of nitrates, and its coadministration with nitrates or nitric oxide donors is therefore contra-indicated.

This product is contraindicated in patients with constrictive pericarditis, pericardial tamponade, restrictive cardiomyopathy and marked anaemia

4.4 Special warnings and precautions for use

Isosorbide mononitrate SR 40 mg capsules are not indicated for relief of acute angina attacks; in the event of an acute attack, sublingual or buccal glyceryl trinitrate tablets / sprays should be used.

Isosorbide mononitrate should be used with caution in patients who are predisposed to closed angle glaucoma.

Isosorbide mononitrate should be used with caution in patients suffering from head trauma, cerebral haemorrhage, hypothyroidism, hypothermia, malnutrition, severe liver or renal disease.

Isosorbide mononitrate may give rise to symptoms of postural hypotension and syncope, particularly following the first dose and at higher doses.

Isosorbide mononitrate should be used with caution in patients with aortic or mitral stenosis. It is not suitable for treating angina associated with hypertrophic cardiomyopathy.

Patients with rare hereditary problems of fructose or galactose intolerance, the Lapp lactase deficiency, glucose-galactose malabsorption or sucrase- isomaltase insufficiency should not take this medicine.

4.5 Interaction with other medicinal products and other forms of interaction

Only limited information is available on the possible interaction between isosorbide mononitrate and other drugs.

Vasodilators (including neuroleptics and tricyclic antidepressants), antihypertensives and diuretics may potentiate the hypotension caused by nitrates particularly inolder people.

The hypotensive effects of nitrates are potentiated by concurrent administration of sildenafil.

Monomax / Angeze SR capsules should not be taken at the same time as alcohol. In vitro data suggests that in combination with Monomax / Angeze SR capsules, alcohol may increase the rate of in vivo release of the product from the prolonged release preparation. Alcohol may increase dose-dependent effects and lead to potential adverse pharmacodynamic interactions. Alcohol use could therefore increase the rate and seriousness of isosorbide 5-mononitrate adverse drug reactions such as vasodilatory related events.

There is no evidence of interaction with food.

4.6    Fertility, pregnancy and lactation

There is inadequate evidence of safety of the drug in human pregnancy, although animal studies have shown no evidence of teratogenicity. This product should therefore not be used during pregnancy or lactation unless considered essential by the physician.

4.7    Effects on ability to drive and use machines

Since postural hypotension with symptoms such as dizziness has been reported, patients should be advised to be careful when driving or operating machinery if they suffer from these symptoms.

4.8    Undesirable effects

Most of the adverse reactions are pharmacodynamically mediated and dose dependent. Side effects including flushing, postural hypotension, pruritis and dry skin rashes may occur occasionally. Headache may occur at the onset of treatment but may be minimised by commencing with low doses of 30mg and gradually increasing the dose. Hypotension, with symptoms such as dizziness and nausea, has occasionally been reported.

Using the recommended dosage schedules there is no evidence of development of nitrate tolerance.

Reporting of suspected adverse reactions

Reporting suspected adverse reactions after authorisation of the medicinal product 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

A pulsating headache is the commonest.

More serious symptoms are excitation, flushing, cold perspiration, nausea, vomiting, vertigo, syncope, tachycardia and a fall in blood pressure.

Management

Induce emesis. Use activated charcoal.

Treatment should be symptomatic with appropriate measures to support the circulation. The main symptom is likely to be hypotension.

If pronounced hypotension, place the patient in the supine position with legs raised. If necessary, intravenous fluids should be administered.

5.1 Pharmacodynamic properties

The principal pharmacological action of isosorbide mononitrate, an active metabolite of isosorbide dinitrate, is relaxation of vascular smooth muscle, producing vasodilation of both arteries and veins with the venous effect predominating. The effect of the treatment is dependent on the dose. Low plasma concentrations lead to venous dilation, resulting in peripheral pooling of blood, decreased venous return and reduction in left ventricular end-diastolic pressure (preload). High plasma concentration also dilates the arteries, reducing systemic vascular resistance and arterial pressure and thus a reduction in cardiac after-load. Isosorbide mononitrate may also dilate the coronary arteries directly. By reducing the end-diastolic pressure and volume, the preparation lowers the intramural pressure, this in turn leading to an improvement in subendocardial blood flow.

The net effect, when administering isosorbide mononitrate, is therefore a reduced workload on the heart and an improved oxygen supply/demand balance in the myocardium.

5.2 Pharmacokinetic properties

In man, isosorbide mononitrate is absorbed completely and rapidly following oral administration.

Isosorbide mononitrate is not subject to the "hepatic first-pass" effect, and provides a low degree of inter-individual variation of blood levels, leading to predictable and reproducible clinical effects.

Isosorbide mononitrate SR 40mg capsules have all the pharmacokinetic characteristics of a true modified-release dosage form. Compared with an immediate-release dosage form, the peak plasma concentration obtained is lower and occurs later, while the apparent elimination half-life is unchanged. Thus compared to ordinary capsules, the absorption phase is prolonged and the duration of effect is extended.

Isosorbide mononitrate is effective in monotherapy as well as in combination with long term S-blocker therapy.

The clinical effects of nitrates may be reduced following repeated administration due to too high and / or constant plasma levels. This can be avoided by allowing low plasma levels for a certain period between doses.

The slow continuous diffusion of the active ingredient from the modified-release microgranules makes it possible, at steady state, to maintain plasma concentrations above the putative effective level of 100ng/ml for a period of about 16 hours for the 40mg capsules and 20 hours for the 60mg capsules.

Thus, no development of tolerance should be seen with isosorbide mononitrate SR capsules when they are taken in accordance with the recommended dosage regime.

5.3 Preclinical safety data

Isosorbide mononitrate produces very few toxic effects and is less toxic than isosorbide dinitrate. After chronic administration at high doses (60mg/kg), signs of toxicity have been detected in canine liver and kidneys. Tests conducted have shown no evidence of a teratogenic or mutagenic potential.

6.1.    List of excipients

For Microgranules :

Maize starch Sucrose

For Microgranule Coating:

Lactose monohydrate Bleached dewaxed shellac,

Dewaxed shellac,

Copolymer of methacrylic acid and methyl methacrylate (1:1), Copolymer of ethyl acrylate, methyl methacrylate and trimethylammonioethyl methacrylate chloride (1:2:0.1),

Talc

For Capsule Shell:

Gelatin

Titanium dioxide (E.171)

Printing Ink:

Iron oxide (E.172)

6.2.    Incompatibilities

Not applicable

6.3. Shelf life

24 months

6.4. Special precautions for storage

Do not store above 25°C. Store in the original package.

6.5. Nature and contents of container

The capsules are enclosed in blisters composed of 250pm PVC film/20pm aluminium foil.

The blisters are packed into folded printed cardboard cartons with a patient information leaflet. Packs contain 8 (sample packs only), 28, 30, 56 or 60 modified-release capsules.

6.6. Special precautions for disposal and other handling

Not applicable

7.    MARKETING AUTHORISATION HOLDER

Chiesi Limited

Cheadle Royal Business Park

Highfield

Cheadle

SK8 3GY

United Kingdom

8.    MARKETING AUTHORISATION NUMBER(S)

PL 08829/0030

9    DATE OF FIRST AUTHORISATION/RENEWAL OF THE

AUTHORISATION

01/08/2001

10 DATE OF REVISION OF THE TEXT

07/05/2015