This information is intended for use by health professionals

1. Name of the medicinal product

ISOSORBIDE MONONITRATE TABLETS 20mg

2. Qualitative and quantitative composition

Each tablet contains 20mg Isosorbide mononitrate.

3. Pharmaceutical form

White to off-white uncoated tablets.

White to off-white, circular, flat bevelled-edge uncoated tablets impressed “C” on one face and the identifying letters “IS” on either side of a central division line on the reverse.

4. Clinical particulars
4.1 Therapeutic indications

1) Prophylaxis of angina pectoris.

2) Adjunctive treatment in the management of severe acute or chronic congestive cardiac failure not responding to cardiac glycosides and/or diuretics.

4.2 Posology and method of administration

Posology

It is recommended that the tablets should be swallowed whole with a little fluid after meals.

Dosage should be reduced in patients with renal or hepatic impairment.

Adults:

Angina: Usually 20mg, two or three times daily. Patients already accustomed to prophylactic nitrate therapy may normally be transferred directly to a therapeutic dose of isosorbide mononitrate. For patients not already receiving prophylactic nitrate therapy, it is recommended that the initial dosage should be one tablet twice daily.

The maintenance dose in individual patients is usually between 20-120mg daily.

Congestive cardiac failure: In severe congestive cardiac failure doses of 20mg, two or three times daily may be employed depending on individual requirements. The optimum dosage is best determined by continuous haemodynamic monitoring. The use of isosorbide mononitrate tablets in severe congestive cardiac failure should be regarded as an adjunctive therapy to more conventional treatment (eg cardiac glycosides, diuretics).

Elderly: Dosage requirements may be reduced especially when hepatic or renal function is impaired. Also, particular care should be taken due to susceptibility to hypotension.

Children: Safety and efficacy has not been established.

Method of Administration

For oral administration.

4.3 Contraindications

Known hypersensitivity to isosorbide dinitrate or mononitrate and other nitrates; acute circulatory failure (shock, vascular collapse); angina caused by hypertrophic obstructive cardiomyopathy; acute myocardial infarction with very low blood pressure or low filling pressure; severe anaemia; severe hypotension or cerebral haemorrhage; head trauma; marked anaemia or hypotension. Phosphodiesterase type-5 inhibitors (eg sildenafil, tadalafil, vardenafil) have been shown to potentiate the hypotensive effects of nitrates, and its co-administration with nitrates or nitric oxide donors is therefore contra-indicated.

4.4 Special warnings and precautions for use

Tolerance and cross-tolerance to other nitrates may occur. Isosorbide mononitrate should be used with caution in patients with closed-angle glaucoma; hypothyroidism; hypothermia; malnutrition; severe liver or renal disease. Symptoms of circulatory collapse may arise after the first dose in patients with labile circulation and in patients already taking ACE inhibitors but these symptoms can largely be avoided if the treatment is started with a low dose.

This product contains lactose. Patients with galactose intolerance, Lapp lactase deficiency or glucose-galactose, which are very rare hereditary problems, should not take this medicine.

4.5 Interaction with other medicinal products and other forms of interaction

Isosorbide dinitrate can act as a physiological antagonist to norepinephrine (noradrenaline), acetylcholine, histamine and other agents.

Alcohol can accentuate cerebral ischaemia associated with postural hypotension and therefore should be avoided during treatment with isosorbide mononitrate.

Beta-blocking drugs have a different pharmacological action in angina and may have a complimentary effect when co-administered with isosorbide mononitrate.

The hypotensive effects of nitrates are potentiated by concurrent administration of ACE inhibitors.

The hypotensive effects of nitrates are potentiated by concurrent administration of phosphodiesterase type-5 inhibitors (eg sildenafil, tadalafil and vardenafil).

4.6 Pregnancy and lactation

There is inadequate evidence of safety of the drug in the human pregnancy but nitrates have been widely use in the treatment of angina for many years without apparent ill consequence; animal studies have shown no hazard. Nevertheless, it is not advisable to use this drug during pregnancy or lactation.

4.7 Effects on ability to drive and use machines

Isosorbide mononitrate may, owing to side effects (e.g. dizziness), affect the ability to drive and use machines to a slight or moderate extent. This action is potentiated by intake of alcohol.

4.8 Undesirable effects

Side-effects which are common to all nitrates in the treatment of angina pectoris include cutaneous vasodilatation with flushing, tachycardia and occasionally unexplained bradycardia. Transient episodes of dizziness and weakness, and other signs of cerebral ischaemia associated with postural hypotension may occur. Nitrate headache may be relieved by simple analgesics. In the majority of patients, headache diminishes or disappears after 1-3 weeks and optimum dosage of isosorbide mononitrate may be achieved.

Dry rash and/or exfoliative dermatitis may occasionally occur.

Nitrate-induced pituitary apoplexy has been reported in patients with undiagnosed pituitary tumours.

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; website: www.mhra.gov.uk/yellowcard or search for MHRA Yellow Card in the Google Play or Apple App Store.

4.9 Overdose

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

Treatment: Induction of emesis, activated charcoal. In case of pronounced hypotension the patient should first be placed in the supine position with legs raised. If necessary intravenous administration of fluid.

5. Pharmacological properties
5.1 Pharmacodynamic properties

Isosorbide mononitrate is an active metabolite of the vasodilator isosorbide dinitrate.

5.2 Pharmacokinetic properties

Isosorbide mononitrate is readily absorbed from the gastrointestinal tract following oral administration. Peak plasma levels are reached in about 1 hour. Unlike isosorbide dinitrate, it does not undergo first-pass hepatic metabolism and bioavailability is nearly 100%. Isosorbide mononitrate is metabolised to inactive metabolites, including isosorbide and isosorbide glucuronide. Only 2% of isosorbide mononitrate is excreted unchanged in the urine. An elimination half-life of about 4-5 hours has been reported.

5.3 Preclinical safety data

There are no pre-clinical data of relevance to the prescriber which are additional to that already included in other sections of the SPC.

6. Pharmaceutical particulars
6.1 List of excipients

Also contains: lactose, magnesium stearate, maize starch, polyvidone.

6.2 Incompatibilities

None known.

6.3 Shelf life

Shelf-life

Three years from the date of manufacture.

Shelf-life after dilution/reconstitution

Not applicable.

Shelf-life after first opening

Not applicable.

6.4 Special precautions for storage

Store below 25°C in a dry place.

6.5 Nature and contents of container

The product containers are rigid injection moulded polypropylene or injection blow-moulded polyethylene containers with polyfoam wad and snap-on polyethylene lids; in case any supply difficulties should arise the alternative is amber glass containers with screw caps and polyfoam wad or cotton wool.

An alternative closure for polyethylene containers is a polypropylene, twist on, push down and twist off child-resistant, tamper-evident lid.

The product may also be supplied in blister packs and cartons:

a) Carton: Printed carton manufactured from white folding box board.

b) Blister pack: (i) 250µm white rigid PVC. (ii) Surface printed 20µm hard temper aluminium foil with 5-7g/M2 PVC and PVdC compatible heat seal lacquer on the reverse side.

Pack sizes: 28s, 30s, 56s, 60s, 84s, 90s, 100s, 112s, 1000s

Product may also be supplied in bulk packs, for reassembly purposes only, in polybags contained in tins, skillets or polybuckets filled with suitable cushioning material. Bulk packs are included for temporary storage of the finished product before final packaging into the proposed marketing containers.

Maximum size of bulk packs: 50,000.

6.6 Special precautions for disposal and other handling

Not applicable.

Administrative Data

7. Marketing authorisation holder

Accord-UK Ltd

(Trading style: Accord)

Whiddon Valley

Barnstaple

Devon

EX32 8NS

8. Marketing authorisation number(s)

PL 0142/0379

9. Date of first authorisation/renewal of the authorisation

March 1994.

Renewed: March 1999

10. Date of revision of the text

05.07.2019