GLYCERYL TRINITATE Sublingual tablets Ref.[7277] Active ingredients: Glyceryl trinitrate

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 mmHg) 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.

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.

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.

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.

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

Very Rare: Methaemoglobinaemia

Psychiatric disorder

Very Rare: Restlessness

Nervous system disorders

Very Common: Throbbing headache**

Common: Vertigo**, Dizziness, Drowsiness

Uncommon: Syncope

Very Rare: Cerebral ischaemia

Eye disorders

Frequency not known: Increased ocular pressure

Cardiac disorders

Common: Tachycardia

Rare: Enhanced angina, Pectoris symptoms, Bradycardia, Cyanosis

Frequency not known: Hypoxaemia, palpitation

Vascular disorders

Common: Orthostatic hypertension*

Uncommon: Facial flushing, Circulatory collapse

Gastrointestinal disorders

Uncommon: Nausea, Vomiting

Very Rare: Heartburn, Halitosis

Respiratory, thoracic and mediastinal disorders

Very Rare: Impairment of respiration

Skin and subcutaneous tissue disorders

Rare: Allergic skin reactions

Very Rare: Exfoliative dermatitis, Drug rash

General disorders and administration site complications

Common: Asthenia

Uncommon: Localised burning sensation, Tongue blisters

Frequency not known: Weakness

Investigations

Common: 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.

Not applicable.