Isosorbide Dinitrate Tablets BP 20mg

1. Name Of The Medicinal Product

ISOSORBIDE DINITRATE TABLETS BP 20mg

2. Qualitative And Quantitative Composition

Each tablet contains 20mg Isosorbide Dinitrate PhEur.

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 code “IU” and “20” on either side of a central division line on the reverse.

4. Clinical Particulars

4.1 Therapeutic Indications

1) Prophylaxis and treatment of angina pectoris.

2) As an adjunctive treatment in the management of severe acute or chronic congestive cardiac failure.

4.2 Posology And Method Of Administration

Posology

Adults

• Angina: 30-120mg daily in divided doses according to individual requirements. Dosage should be gradually increased to minimise the possibility of nitrate headache and/or tolerance.

• Congestive cardiac failure: In severe congestive cardiac failure doses of 40-160mg daily in divided doses may be employed depending on individual requirements. The optimum dosage is best determined by continuous haemodynamic monitoring. The use of isosorbide dinitrate tablets in severe congestive cardiac failure should be regarded as an adjunctive therapy to more conventional treatment (eg cardiac glycosides, diuretics).

The maximum daily dose should not exceed 240mg in divided doses.

Elderly

• Dosage may be reduced in the elderly especially where there is impairment of renal or hepatic function.

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 (Isosorbide dinitrate by lowering venous return may precipitate syncope and should be avoided in patients with haemorrhage or those who are volume depleted); severe anaemia. Cardiac tamponade, aortic stenosis, constrictive pericarditis, mitral stenosis. Inferior Myocardial Infaraction with right ventricular involvement, raised intra-cranial pressure (as venodilatation may further increase raised intra-cranial pressure). Cor pulmonale. Phosphodiesterase inhibitors (eg sildenafil, tadalafil, vardenafil) has been shown to potentiate the hypotensive effects of nitrates, and their co-administration with nitrates or nitric oxide donors is therefore contra-indicated. Hypersensitivity to any of the excipients.

4.4 Special Warnings And Precautions For Use

Tolerance and cross-tolerance to other nitrates may occur. Use with caution in patients with closed-angle glaucoma (increased intra-ocular pressure).

Alcohol should be avoided during treatment as reduction capacity may be reduced. Isosorbide dinitrate may act as a physiological antagonist to acetylcholine, histamine and noradrenaline (norepinephrine).

There is a possibiity of precipitating haemolysis in patients with G6PD deficiency (Favism).

There is a risk of precipitating intra-cardiac conduction abnormalities when isosorbide dinitrate is used in patients with seriously damaged myocardia.

Severe hepatic or renal impairment, hypothyroidism, malnutrition or hypothermia, head trauma, cerebral haemorrhage.

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

Isosorbide dinitrate can act as a physiological antagonist to noradrenaline (norepinephrine), acetylcholine, histamine and other agents. The hypotensive effects of nitrates are potentiated by concurrent administration of phosphodiesterase inhibitors (eg sildenafil, tadalafil and vardenafil).

Othostatic hypotension may occur with the combined use of calcium channel blockers, anti-hypertensive agents, phenothiazines and tricyclic anti-depressants. Use of alcohol may produce severe hypotension and collapse.

4.6 Pregnancy And Lactation

There are no data reported indicating the possibility of adverse effects during the human pregnancy, however, the tablets should not be administered during pregnancy or lactation unless considered to be essential.

4.7 Effects On Ability To Drive And Use Machines

None known.

4.8 Undesirable Effects

The following frequencies are used:

Very common:

Common:

Uncommon:

Rare:

Very rare: < 0,01 %, including isolated cases

Very common:

• Headache (“Nitrate headache”) at the beginning of treatment, which in most cases improve/resolve after some days of continued treatment.

• Cutaneous vasodilation including flushing.

Common:

• Decrease in blood pressure and/or orthostatic hypotension with reflex tachycardia and symptoms/signs of cerebral ischaemia (including drowsiness and dizziness and weakness) with first time use and when the dose is increased.

• Peripheral oedema in patients treated for left ventricular failure.

Uncommon:

• Nausea and vomiting

• Allergic skin reactions

• Marked decreases in blood pressure with an aggravation of symptomatic angina pectoris

• Collapse associated with bradycardia and cardiac rhythm disturbances

Very rare: < 0,01 %, including isolated cases

• Exfoliative dermatitis/Stevens-Johnson Syndrome or angioedema

• Alveolar hypoventilation with consequent hypoxaemia and the risk of developing a myocardial infarction in patients with coronary heart disease

• Angle closure glaucoma

• Pituitary apoplexy in patients with undiagnosed pituitary tumours.

Development of tolerance and also with cross tolerance against other nitrates have been described. In order to avoid weakening or even loss of effect high continuous doses should be avoided.

Enhancement of the dose and/or change in the dose interval may lead to reduction or even loss of effect.

4.9 Overdose

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 and giving intravenous fluids.

5. Pharmacological Properties

5.1 Pharmacodynamic Properties

Isosorbide dinitrate is a vasodilator.

5.2 Pharmacokinetic Properties

Isosorbide dinitrate is readiliy absorbed from the oral mucosa and also following oral administration. It undergoes extensive first pass metabolism, mainly in the liver.

The major metabolites are Isosorbide 2-mononitrate and Isosorbide 5-mononitrate which both possess vasodilatory activity and may contribute to the activity of the parent compound.

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: magnesium stearate, maize starch, lactose, 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 or polyethylene ullage filler 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.

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, 50s, 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 0142/0322

9. Date Of First Authorisation/Renewal Of The Authorisation

April 1993

10. Date Of Revision Of The Text

16/06/2009