Glyceryl Trinitrate (GTN) 300 micrograms Tablets

Summary of Product Characteristics Updated 08-Sep-2017 | Martindale Pharma, an Ethypharm Group Company

1. Name of the medicinal product

GTN 300mcg

Glyceryl Trinitrate 300 micrograms Tablets

2. Qualitative and quantitative composition

Each tablet contains 300 micrograms Glyceryl Trinitrate equivalent to 0.3mg glyceryl trinitrate

Excipients with known effect

Contains lactose: 2.880mg

For the full list of excipients, see section 6.1.

3. Pharmaceutical form

Sublingual tablet

Plain White biconvex tablets 0.5mm diameter

4. Clinical particulars
4.1 Therapeutic indications

As a short-acting vasodilator

• Relief of angina pectoris

• Prophylaxis of angina pectoris

4.2 Posology and method of administration

Posology

Adults and the elderly

Treatment of acute attacks of Angina Pectoris

One tablet to be allowed to dissolve slowly under the tongue. The treatment may be repeated at five minute intervals. If pain persists for more than 15 minutes medical care should be sought.

Prophylaxis of Angina Pectoris

Glyceryl trinitrate, 0.3 mg (one tablet), may be used prior to activity which is likely to precipitate angina pectoris.

The patient should preferably rest in the sitting position because of the risk of symptomatic postural hypotension. This is particularly important for elderly people.

Children

Not recommended for children

Method of administration

For sublingual administration

4.3 Contraindications

• Hypersensitivity to the active substance, to other nitro compounds or to any of the excipients listed in section 6.1

• Glyceryl trinitrate is contraindicated in patients taking phosphodiesterase type 5 inhibitors such as sildenafil, tadalafil and vardenafil ( See section 4.5). These drugs have shown to significantly potentiate the hypotensive effects of nitrates

• Glyceryl trinitrate is contraindicated in angina caused by hypertrophic obstructive cardiomyopathy as it may exaggerate outflow obstruction.

• Glyceryl trinitrate should not be used in patients with possible increased intracranial pressure (e.g. cerebral haemorrhage or head trauma).

• Marked anaemia

• Closed angle glaucoma

4.4 Special warnings and precautions for use

Glyceryl trinitrate should be used with caution in patients in whom adequate preload is important for maintaining cardiac output (e.g. acute circulatory shock including hypovolemic shock or cardiogenic shock with inadequate diastolic filling pressures, severe mitral stenosis, pericardial tamponade, constrictive pericarditis, orthostatic dysfunction) because administration of a vasodilator in these patients may worsen clinical status.

Glyceryl trinitrate should be used with caution in patients with severe hypotension (systolic blood pressure below 90 mm Hg) and patients with cardiogenic shock, unless a sufficiently high left ventricular end diastolic pressure is assured by intra aortal counter pulsation or positive inotropic drugs.

Glyceryl trinitrate should be used with caution in patients with cerebrovascular disease since symptoms may be precipitated by hypotension.

Glyceryl trinitrate may worsen hypoxaemia in patients with lung disease or cor pulmonale. Arterial hypotension with bradycardia may occur in patients with myocardial infarction; this is thought to be reflexly mediated.

The use of glyceryl trinitrate could theoretically compromise myocardial blood supply in patients with left ventricular hypertrophy associated with aortic stenosis because of the detrimental effects of tachycardia and decreased aortic diastolic pressure.

Detailed haemodynamic studies in a small number of patients with valvular aortic stenosis with and without concomitant significant coronary artery disease studied in the supine position have not shown adverse effects with sublingual glyceryl trinitrate. However it seems prudent to be cautious in treating ambulant patients with the combination of angina and moderate to severe valvular aortic stenosis.

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

Sublingual tablets:

If angina symptoms have not resolved after a total of three doses, the patient should be instructed to seek prompt medical attention (see section 4.2).

These tablets contain lactose: 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

Consistent with its known effects on the nitric oxide/cyclic guanosine monophosphate (cGMP) pathway, phosphodiesterase type 5 inhibitors (e.g. sildenafil, vardenafil and tadalafil) have been shown to potentiate the hypotensive effects of nitrates, and coadministration with glyceryl trinitrate is therefore contraindicated (see section 4.3).

Treatment with other agents with hypotensive effects (e.g. vasodilators, antihypertensives, beta-blockers, calcium channel blockers and neuroleptics, tricyclic antidepressants and sapropterin) may potentiate the hypotensive effect of glyceryl trinitrate. In addition to these agents, the risk of hypotension and syncope with use of glyceryl trinitrate may be enhanced by alcohol.

N-acetylcysteine may potentiate the vasodilator effects of glyceryl trinitrate.

The possibility of tolerance to the effects of glyceryl trinitrate should be considered when used in conjunction with long-acting nitrate preparations. There is evidence that systemic nitrates may interfere with the anticoagulant effects of heparin. Early and frequent monitoring of anticoagulation is recommended when systemic nitrates and heparin are used in combination. There is a potential for drugs that cause dry mouth (eg anticholinergic, antimuscarinics, tricyclic antidepressants) to reduce the effectiveness of sublingual nitrates.

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 Fertility, pregnancy and lactation

Fertility

Animal studies did not indicate harmful effects with respect to fertility. However, the relevance of these animal findings to man is unknown.

Pregnancy

Animal studies did not indicate harmful effects with respect to pregnancy, embryofoetal development, parturition or postnatal development. However, the relevance of these animal findings to man is unknown. The administration of glyceryl trinitrate during pregnancy should only be considered if the expected benefit to the mother is greater than any possible risk to the foetus.

Lactation

It is unknown if glyceryl trinitrate or its metabolites are excreted in human milk. A risk to the suckling child cannot be excluded. A decision must be made whether to discontinue/abstain from breast-feeding or to discontinue/abstain from glyceryl trinitrate therapy taking into account the benefit of breast-feeding for the child and the benefit of therapy for the woman.

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

(≥ 1/10)

Common

(≥ 1/100 <1/10)

Uncommon

(≥ 1/1000 < 1/100)

Rare

(≥ 1/10,000 < 1/1000)

Very Rare

(< 1/10,00)

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

Blood and lymphatic system disorders

Methaemoglobinaemia

Psychiatric disorder

Restlessness

Nervous system disorders

Throbbing headache**

Vertigo**, Dizziness, Drowsiness

Syncope

Cerebral ischaemia

Eye disorders

Increased ocular pressure

Cardiac disorders

Tachycardia

Enhanced angina, Pectoris symptoms, Bradycardia, Cyanosis

Hypoxaemia, palpitation

Vascular disorders

Orthostatic hypertension*,

Facial flushing, Circulatory collapse

Gastrointestinal disorders

Nausea, Vomiting

Heartburn, Halitosis

Respiratory, thoracic and mediastinal disorders

Impairment of respiration

Skin and subcutaneous tissue disorders

Allergic skin reactions

Exfoliative dermatitis, Drug rash

General disorders and administration site complications

Asthenia

Localised burning sensation, Tongue blisters

Weakness

Investigations

Blood pressure decreased*

* Particularly upon initiation of therapy and following an increase in dose.

** Headache and dizziness, persisting after relief of angina may be minimised by removing the glyceryl trinitrate tablet before it has completely dissolved. Glyceryl trinitrate-induced hypotension may cause cerebral ischaemia.

Large dose of glyceryl trinitrate may cause vomiting, cyanosis, restlessness, methaemoglobinaemia and impairment of respiration.

During treatment with glyceryl trinitrate, temporary hypoxemia may occur due to a relative redistribution of the blood flow in hypoventilated alveolar areas.

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:

Signs and symptoms encountered with overdose are generally similar to those events reported during treatment use although the magnitude and/or severity of the reactions may be more pronounced (see section 4.8). At very high doses an increase in intracranial pressure with cerebral symptoms may occur. Additional gastrointestinal effects such as colicky pain and diarrhoea have also been reported. Treatment:

In the case of overdose, the patient's clinical status including vital signs and mental status should be assessed and supportive treatment of the cardiovascular and respiratory systems provided as clinically indicated or as recommended by the national poisons centre, where available. In the event of mild hypotension, passive elevation of the patient's legs and/or lowering of the head may be effective.

Arterial blood gas estimation should be performed and if there is acidosis or the patient is clinically cyanosed, then severe methaemoglobinaemia must be assumed. Oxygen therapy should be given with 1 to 2 mg/kg bodyweight of I.V. Methylene Blue over five minutes unless the patient is known to have G-6-PD deficiency.

5. Pharmacological properties
5.1 Pharmacodynamic properties

Pharmacotherapeutic Group: Organic nitrates

ATC code: C01D A02.

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 rapidly absorbed sublingually. Rapid metabolism occurs mainly in the liver and blood by glutathione - organic nitrate reductase to dinitrates which are less potent vasodilators than trinitrates.

Glyceryl trinitrate is also readily absorbed from the gastrointestinal tract, but owing to extensive first-pass metabolism in the liver its bioavailability is reduced (Half-life is 1 to 4 minutes.).

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

5.3 Preclinical safety data

None stated

6. Pharmaceutical particulars
6.1 List of excipients

Mannitol

Acacia

Lactose

Talc

Stearic Acid

Magnesium Stearate

6.2 Incompatibilities

Not applicable

6.3 Shelf life

Unopened: 24 months.

After first opening: Discard 8 weeks after first opening.

6.4 Special precautions for storage

Store in a dry place below 25°C. Protect from light.

6.5 Nature and contents of container

Amber glass bottle with aluminium wadded cap packed in a cardboard carton along with a patient leaflet.

Pack size: 100 tablets.

6.6 Special precautions for disposal and other handling

• After removing a tablet, close the cap tightly

• Do not transfer the tablets to another container

• Do not put any packing material into the bottle with the tablets

• 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 the pharmacist for disposal

7. Marketing authorisation holder

Macarthys Laboratories Ltd T/A Martindale Pharma

Bampton Road,

Harold Hill,

Romford,

RM3 8UG

8. Marketing authorisation number(s)

PL 01883/5958R

9. Date of first authorisation/renewal of the authorisation

Date of first authorization: 20th June 1990

10. Date of revision of the text

31/08/2017

Company Contact Details
Martindale Pharma, an Ethypharm Group Company
Address

Bampton Road, Harold Hill, Romford, Essex, RM3 8UG

Telephone

+44 (0)1277 266 600

Medical Information e-mail
WWW

http://www.martindalepharma.co.uk

Fax

+44 (0)1277 848 976

Customer Care direct line

+(0)800 137 627