Glyceryl trinitrate 400 micrograms/metered dose sublingual spray, suspension – Summary of Product Characteristics (SmPC) for healthcare professionals

1 NAME OF THE MEDICINAL PRODUCT

Glyceryl trinitrate 400 micrograms/metered dose sublingual spray, suspension

2 QUALITATIVE AND QUANTITATIVE COMPOSITION

Each metered dose contains 400 micrograms of glyceryl trinitrate.

Excipients with known effect: contains 9.2 mg of alcohol (ethanol) per metered dose (puff)

For the full list of excipients, see section 6.1

3 PHARMACEUTICAL FORM

Sublingual spray

Colourless or pale yellow, clear solution.

4 CLINICAL PARTICULARS

4.1 Therapeutic indications

For the treatment and prophylaxis of angina pectoris and the treatment of variant angina.

4.2 Posology and method of administration

Posology

Adults and elderly:

At the onset of an attack or prior to a precipitating event: one or two 400 microgram metered doses sprayed under the tongue. If symptoms do not resolve, this may be repeated at five minute intervals for a total of three doses. If symptoms have not resolved after a total of three doses, the patient should seek prompt medical attention.

For the prevention of exercise-induced angina or in other precipitating conditions: one or two 400 microgram metered doses sprayed under the tongue immediately prior to the event.

Paediatric population

No data are available on the use of glyceryl trinitrate in children.

Method of administration

The bottle should be held vertically with the valve head uppermost. The pump should be pressed 7 times for first activation. If the pump is new, or has not been used for 1 week or more, the first actuation should be released into the air. The spray orifice should then be placed as close to the mouth as possible with the spray nozzle facing towards it. The dose should be sprayed under the tongue and the mouth should be closed immediately after each dose. The spray should not be inhaled.

During application the patient should rest, ideally in the sitting position because of the risk of symptomatic postural hypotension. Hypotension and syncope can be a particular problem with the use of nitrates in the elderly.

4.3 Contraindications

• Hypersensitivity to the active substance, other nitrates or to any of the excipients listed in section 6.1.
• Acute circulatory shock including hypovolaemic shock.
• Cardiogenic shock, unless a sufficiently high left ventricular end diastolic pressure is assured by intraaortal counterpulsation or positive inotropic drugs.
• Severe hypotension (systolic blood pressure below 90 mmHg).
• Severe anaemia.
• Possible increased intracranial pressure (e.g. cerebral haemorrhage and head trauma).
• Severe mitral stenosis and angina caused by hypertrophic obstructive cardiomyopathy (as it may exaggerate outflow obstruction).
• Concomitant administration of phosphodiesterase inhibitors used for the treatment of erectile dysfunction or pulmonary arterial hypertension, e.g, sildenafil, vardenafil, tadalafil (see section 4.5).

4.4 Special warnings and precautions for use

Any lack of effect may be an indicator of early myocardial infarction.

As with all glyceryl trinitrate preparations, use in patients with incipient glaucoma should be avoided.

Glyceryl trinitrate should be used with caution in patients in whom adequate preload is important for maintaining cardiac output (e.g. 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 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.

This medicine contains 9.2 mg of alcohol (ethanol) in each dose. The amount in dose of this medicine is equivalent to less than 1 ml beer or 1 ml wine. The small amount of alcohol in this medicine will not have any noticeable effects.

4.5 Interaction with other medicinal products and other forms of interaction

Consistent with their 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. A severe and possibly dangerous fall in blood pressure may occur. This can result in collapse, unconsciousness and paradoxical myocardial ischaemia and may be fatal. Such use is therefore contraindicated (see section 4.3)

If a patient treated with these medicines for erectile dysfunction or pulmonary arterial hypertension needs a rapidly effective nitrate, the patient should be closely monitored.

Treatment with other agents with hypotensive effects (e.g. vasodilators, antihypertensives, diuretics, 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.

During the simultaneous use of dihydroergotamine (DHE), glyceryl trinitrate may lead to an increase in the DHE level and thus potentiate its hypertensive action.

4.6 Fertility, pregnancy and lactation

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.

Breastfeeding

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.

Fertility

Animal studies did not indicate harmful effects with respect to fertility. However, the relevance of these animal findings to man is unknown (see section 5.3).

4.7 Effects on ability to drive and use machines

Since hypotension, dizziness and syncope have been reported following treatment with glyceryl trinitrate, caution is recommended in patients performing skilled tasks, such as driving and operating machinery.

It is recommended that patients wait at least five minutes after using the spray before driving or operating machinery. If the patient feels faint, dizzy or unwell, the patient should wait until they feel better. This can occur in particular at the beginning of the treatment, with an increase of the dosage, when changing the medicinal product or when used in combination with alcohol.

4.8 Undesirable effects

Undesirable effects are listed below by system organ class and frequency. Frequencies are defined as follows: very common ≥ 1/10; common ≥ 1/100 and <1/10; uncommon ≥ 1/1000 and < 1/100; rare ≥ 1/10,000 and < 1/1000; very rare < 1/10,000; not known (frequency cannot be estimated fromthe available data).

* Particularly upon initiation of therapy and following an increase in dose. ** Symptoms which are known in conjunction with hypersensitivity reactions

Large doses 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 or search for MHRA Yellow Card in the Google Play or Apple App Store.

4.9 Overdose

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).

Flushing, severe headache, a feeling of suffocation, hypotension, fainting, restlessness, blurred vision, impairment of respiration, bradycardia and rarely, cyanosis and methaemoglobinaemia may occur. In a few patients there may be a reaction comparable to shock with nausea, vomiting, weakness, sweating and syncope.

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: Cardiac therapy, Organic nitrates, ATC code: C01D A02

Mechanism of action

Glyceryl trinitrate relieves angina pectoris by reduction of cardiac work and dilation of the coronary arteries. In this way, not only is there a lessening in arterial oxygen requirement but the amount of oxygenated blood reaching the ischaemic heart is increased.

5.2 Pharmacokinetic properties

The pharmacokinetics of glyceryl trinitrate are complex; venous plasma levels of the drug show wide and variable fluctuations and are not predictive of clinical effect. In a human pharmacodynamic study, pharmacological activity had commenced one minute after dosing and was obvious by two minutes.

5.3 Preclinical safety data

None stated.

6 PHARMACEUTICAL PARTICULARS

6.1 List of excipients

Triglycerides, medium-chain

Ethanol, anhydrous

Glycerol monocaprylocaprate

Peppermint oil

6.2 Incompatibilities

Not applicable.

6.3 Shelf life

36 months

6.4 Special precautions for storage

Store below 25 °C.

6.5 Nature and contents of container

Blue coated glass bottle is equipped with a metered dosing valve and a transparent protective cap, in a carton box. Each bottle is designed to deliver at least 180 or 200 doses.

6.6 Special precautions for disposal

Any unused medicinal product or waste material should be disposed of in accordance with local requirements

7 MARKETING AUTHORISATION HOLDER

EGIS Pharmaceuticals UK Ltd.

127 Shirland Road

London

W9 2EP

United Kingdom

8 MARKETING AUTHORISATION NUMBER(S)

PL 18190/0014

9 DATE OF FIRST AUTHORISATION/RENEWAL OF THE

AUTHORISATION

25/09/2026

10 DATE OF REVISION OF THE TEXT

25/09/2026