Glyceryl Trinitrate Tablets BP 500 micrograms

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1. Name Of The Medicinal Product

GLYCERYL TRINITRATE TABLETS BP 500 micrograms

2. Qualitative And Quantitative Composition

Each tablet contains 500 micrograms Glyceryl Trinitrate BP.

3. Pharmaceutical Form

White uncoated tablets.

White, circular, biconvex uncoated tablets, impressed “C” on one face and the identifying letters “GF” on the reverse.

4. Clinical Particulars 4.1 Therapeutic Indications

As a short-acting vasodilator

Relief of angina pectoris

Prophylaxis of angina pectoris

Relief of acute spontaneous coronary artery spasm

4.2 Posology And Method Of Administration

Posology

1-2 tablets (0.5-1.0mg) should be placed under the tongue and allowed to dissolve slowly; this dose should be repeated as required. If pain persists after a total of 3 doses in 15minutes the patient should be advised to seek medical attention.

Dosage should be adjusted according to the response obtained by the individual patient and the severity of the anginal pain.

NB Tolerance may develop with daily use, but withdrawal for a week re-establishes the original sensitivity.

Method of Administration

For sublingual administration

4.3 Contraindications

Known hypersensitivity to nitrates and other ingredients in the tablets. Patients with rare hereditary problems of galactose intolerence, the Lapp lactase deficiency or glucose-galactose malabsorption should not take this medicine.

Marked anaemia, raised intercranial pressure including that caused by head trauma, cerebral haemorrhage, closed angle glaucoma, hypotensive conditions, hypovolaemia, obstructive hypertrophic cardiomyopathy, aortic stenosis, mitral stenosis, cardiac tamponade, obstructive heart failure and constrictive pericarditis.

Phosphodiesterase type-5 inhibitors (eg sildenafil, tadalafil, vardenafil) have been shown to potentiate the hypotensive effects of nitrates, and its co-administration with nitrates, and their co-administration with nitrates or nitric oxide donors is therefore contra-indicated.

4.4 Special Warnings And Precautions For Use

Caution is necessary in patients with severe hepatic or renal impairment, hypothyroidism, hypoxaemia, hypothermia or a recent history of myocardial infaraction and malnutrition.

4.5 Interaction With Other Medicinal Products And Other Forms Of Interaction

Some effects of glyceryl trinitrate are enhanced by alcohol. The hypotensive effects of nitrates are potentiated by concurrent administration of phosphodiestrase type-5 inhibitors (eg sildenafil, tadalafil, vardenafil).

Glyceryl trinitrate may potentiate the effects of anti-hypertensive drugs (such as vasodilators, beta-blockers, calcium-channel blockers, diuretics).

There is a potential for drugs that cause dry mouth (eg anticholinergic, antimuscarinics, tricyclic antidepressants) to reduce the effectiveness of sublingual nitrates.

There have been some reports that the anticoagulant effects of heparin may be reduced by the concurrent use of nitrates. The effects of heparin should be monitored and dose adjusted as necessary.

An enhanced hypotensive effect with sublingual apomorphine may occur as a result of concomitant administration with glyceryl trinitrate.

Ergot alkaloids may oppose the coronary vasodilatation of nitrates. Ergot alkaloids can precipitate angina and glyceryl trinitrate can reduce the first pass hepatic metabolism of dihydroergotamine.

4.6 Pregnancy And Lactation

There is no, or inadequate, evidence of safety of nitrates in human pregnancy or lactation; nitrates should not be administered in pregnancy or lactation unless considered essential.

4.7 Effects On Ability To Drive And Use Machines

As Glyceryl trinitrate can cause dizziness patients should make sure they are not affected before driving or operating machinery. This effect appears to be accentuated by alcohol.

4.8 Undesirable Effects

System Organ Class

Very Common

(

Common

(

Uncommon

(

Rare

(

Very Rare

(< 1/10,00)

Frequency not known (cannot be estimated from the available data)

Nervous system disorders

Throbbing headache

Vertigo

       

Eye disorders

         

Increased ocular pressure

Cardiac disorders

     

Tachycardia, bradycardia

 

Syncope, hypoxaemia

Vascular disorders

 

Dizziness

 

Postural hypotension

   

Gastrointestinal disorders

 

Nausea

     

vomiting

Skin and subcutaneous tissue disorders

 

Facial flushing

 

Allergic skin reactions

Exfoliative dermatitis

 

General disorders and administration site complications

 

Weakness

Localised burning sensation

      4.9 Overdose

Toxic effects of glyceryl trinitrate include vomiting, restlessness, hypotension, syncope, cyanosis and methaemoglobinaemia; impairment of respiration, hypoxia, bradycardia and psychosis may ensue.

Overdosage should be treated with gastric lavage, followed by charcoal administration if necessary in case that nitrates were ingested, attention to any respiratory and circulatory symptoms. Oxygen may prove additionally useful.

Effects of hypotension may be minimised by treating the patient in the recumbent position with the head lowered or raised legs. Methaemoglobinaemia may be treated with methylene blue intravenously 1-4mg/kg body-weight. The circulation may be maintained with infusions of plasma or suitable electrolyte solutions.

5. Pharmacological Properties 5.1 Pharmacodynamic Properties

ATC Code: CO1D AO2 Organic nitrates

Glyceryl trinitrate is a vasodilator and is used for angina of effort. Vasodilation is achieved by the releasing of free redical nitric oxide which activates guanylate cyclase and increases synthesis of guanosine 3? and 5?-monophosphate with resultant effects on the phosphorylation of proteins in smooth muscle. If taken in excess, its vasodilatory effect can cause headache.

5.2 Pharmacokinetic Properties

Glyceryl trinitrate is readily absorbed from the oral mucosa, but rapidly metabolised so that it only has a fleeting duration of action.

Glyceryl trinitrate is also readily absorbed from the gastrointestinal tract, but owing to extensive first-pass metabolism in the liver its bioavailability is reduced (short plasma half-life).

Glyceryl trinitrate is metabolised by hydrolysis to dinitrates and the mononitrate, which is the main urinary metabolite.

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

The tablets also contain: lactose, stearic acid, magnesium stearate, colloidal silicon dioxide, mannitol, acacia.

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

Discard 8 weeks after first opening.

6.4 Special Precautions For Storage

Store below 25°C in a dry place.

Protect from light.

6.5 Nature And Contents Of Container

The product is supplied in amber glass bottles with screw caps lined with aluminium foil.

Pack sizes: 56s, 60s, 84s, 90s, 100s, 112s, 120s, 168s, 180s, 200s, 1000s

Product may also be supplied in bulk packs, for reassembly purposes only, in amber glass containers with screw caps lined with aluminium foil, filled with aluminium foil as a cushioning material.

Maximum size of bulk packs: 5,000

6.6 Special Precautions For Disposal And Other Handling

• Your Glyceryl Trinitrate tablets will be presented in a glass airtight container with a foil-lined cap. Keep them in this.

• After use reclose the bottle cap tightly.

• Do not put cotton wool, other drugs, or anything else in the bottle with the tablets.

• Store the tablets below 25oC in a dry place, protected from light. If you need to carry them with you DO NOT carry them close to your body, rather in a purse, wallet or handbag.

If you do not use the tablets within 8 weeks of first opening the bottle, obtain a fresh supply and return the old tablets to your pharmacist. (A fresh tablet should produce a slight burning sensation when placed under the tongue; if this does not occur, obtain a fresh supply). In any event do not use the tablets after the expiry date shown.

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 0142/6296 R

9. Date Of First Authorisation/Renewal Of The Authorisation

February 1986

January 1994, June 1999

10. Date Of Revision Of The Text

16/04/2010

Glyceryl Trinitrate Tablets BP 500 micrograms

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