SUMMARY OF PRODUCT CHARACTERISTICS

1 NAME OF THE MEDICINAL PRODUCT

MONOMAX XL 60 mg Tablets

2    QUALITATIVE AND QUANTITATIVE COMPOSITION

Each prolonged release tablet contains 60mg of isosorbide mononitrate.

For the full list of excipients, see section 6.1.

3.    PHARMACEUTICAL FORM

Prolonged release tablets

White, oval convex tablets with a score line between” SL” and” 60 “, which are embossed on one side

4.1. Therapeutic indications

For the prophylactic treatment of angina pectoris

4.2 Posology and method of administration

Method of administration Oral use

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

Posology

Adults: Usual adult dose is one isosorbide mononitrate XL 60 mg tablet per day (taken in the morning). If necessary, the dosage may be increased to 120 mg once daily (i.e. 2 x 60mg tablets taken in the morning). The dosage can be titrated to minimise the possibility of headache by initiating treatment with 30mg (half a tablet), for the first two to four days.

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.

Contraindications

This product should not be given to patients with a known sensitivity to nitrates and a known hypersensitivity to the constituents of the tablets.

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 contraindicated. Isosorbide mononitrate is contraindicated in patients with constrictive cardiomyopathy and pericarditis, aortic stenosis, cardiac tamponade, mitral stenosis and severe anaemia

4.4    Special warnings and precautions for use

Isosorbide mononitrate XL 60 mg tablets 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, recent history of myocardial infarction, hypothyroidism, hypothermia, malnutrition, severe liver or renal disease.

Patients with rare hereditary problems of galactose intolerance, the Lapp lactase deficiency or glucose-galactose malabsorption 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.

Some of the effects of alcohol may be potentiated by this agent.

Vasodilators, antihypertensives and diuretics may potentiate the hypotension caused by nitrates particularly in the elderly.

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

There is no evidence of interaction with food.

4.6    Fertility, pregnancy and lactation

Since its safety and efficacy have not been established, this product should 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 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. These symptoms generally disappear during continued treatment. Pruritis has been reported rarely and myalgia, reported very rarely.

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.

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

5.    PHARMACOLOGICAL PROPERTIES

5.1    Pharmacodynamic properties

Anatomical Therapeutic Chemical (ATC ) code: C0lD A14; Vasodilators used in cardiac diseases, organic nitrates

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 dilate 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 bloodflow.

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 XL 60 mg tablets 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 tablets, 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 ^-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. Isosorbide mononitrate XL 60 mg tablets, when administered once daily in the morning, produces a plasma profile of high levels during the day and low levels during the night. Thus, no development of tolerance should be seen with Isosorbide mononitrate XL, when 60 mg or 120 mg is taken once daily in the morning.

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

Lactose monohydrate Hypromellose (E.464) Glyceryl palmitostearate Maize starch Magnesium stearate

6.2 Incompatibilities

Not applicable

6.3.    Shelf life

36 months

6.4.    Special precautions for storage

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

6.5 Nature and contents of container

The tablets are enclosed in blisters composed of 250 pm PVC film /25 pm aluminium foil.

The blisters are packed into folded printed cardboard cartons with a patient information leaflet. Packs contain 28 or 30 prolonged release tablets.

6.6. Special precautions for disposal and other handling

None

7.    MARKETING AUTHORISATION HOLDER

Chiesi Limited

Cheadle Royal Business Park

Highfield

Cheadle

SK8 3GY

United Kingdom

8.    MARKETING AUTHORISATION NUMBER(S)

PL 08829/0102

9. DATE OF FIRST AUTHORISATION / RENEWAL OF THE AUTHORISATION

24^th February 2000

10 DATE OF REVISION OF THE TEXT

29/04/2015