Isosorbide Mononitrate Tablets 40mg

1. Name Of The Medicinal Product

ISOSORBIDE MONONITRATE TABLETS 40mg

2. Qualitative And Quantitative Composition

Each tablet contains 40mg Isosorbide mononitrate.

3. Pharmaceutical Form

White to off-white, uncoated tablets.

White to off-white, circular, biconvex uncoated tablets impressed “C” on one face and the identifying letters “IV”on the reverse.

4. Clinical Particulars

4.1 Therapeutic Indications

1) Prophylaxis of angina pectoris.

2) As an 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 (including elderly):

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 20mg 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).

Method of Administration

For oral administration.

4.3 Contraindications

Known hypersensitivity to isosorbide dinitrate or mononitrate; acute circulatory failure (shock, vascular collapse); angina caused by hypertrophic obstructive cardiomyopathy; very low blood pressure or low filling pressure; severe anaemia; cerebral haemorrhage; head trauma. 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. Alcohol should be avoided during treatment as reduction capacity may be reduced. Symptoms of circulatory collapse may arise after the first dose in patients with labile circulation and in patients already taking ACE inhibitors.

4.5 Interaction With Other Medicinal Products And Other Forms Of Interaction

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

Alcohol can accentuate cerebral ischaemia associated with postural hypotension.

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 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 used 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

None known.

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.

4.9 Overdose

Overdosage may lead to circulatory collapse. Gastric lavage may be performed if within four hours of ingestion, otherwise treatment is symptomatic. Hypotension may be treated by elevating the legs to promote venous return.

5. Pharmacological Properties

5.1 Pharmacodynamic Properties

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

Isosorbide 5-mononitrate is an active metabolite of isosorbide dinitrate and from an oral dose exerts qualitatively similar effects. However, unlike the dinitrate which is subject to considerable hepatic first-pass metabolism, it has virtually complete systemic availability from an oral dose hence it achieves predictable and sustained blood levels. Onset of pharmacological effects occur within 20 minutes of an oral dose and are maintained for more than 8 hours.

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

Not applicable.

6. Pharmaceutical Particulars

6.1 List Of Excipients

Also contains: crospovidone, lactose, magnesium stearate, maize starch, microcrystalline cellulose (E460), povidone.

6.2 Incompatibilities

None known.

6.3 Shelf Life

Shelf-life

Two 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, with polyfoam wad or cotton wool.

The product may also be supplied in blister packs in 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

Actavis UK Limited

(Trading style: Actavis)

Whiddon Valley

BARNSTAPLE

N Devon EX32 8NS

8. Marketing Authorisation Number(S)

PL 0142/0352

9. Date Of First Authorisation/Renewal Of The Authorisation

November 1994

Renewed: April 2000

10. Date Of Revision Of The Text

January 2009