Source: Medicines & Healthcare Products Regulatory Agency (GB) Revision Year: 2018 Publisher: G. Pohl-Boskamp GmbH & CO KG., Kieler Strasse 11, 25551 Hohenlockstedt, Germany
Hypersensitivity to the active substance, other nitrates or to any of the excipients listed in 6.1. Acute circulatory shock including hypovolaemic shock. Cardiogenic shock, unless a sufficiently high left ventricular enddiastolic pressure is assured by intra-aortal 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).
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.
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 contra-indicated (section 4.3)
If a patient treated with these drugs for erectile dysfunction or pulmonary arterial hypertension needs a rapidly effective nitrate, he/she 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, glyceryl trinitrate may lead to an increase in the DHE level and thus potentiate its hypertensive action.
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).
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.
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.
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.
Undesirable effects are listed below by system organ class and frequency. Frequencies are defined as follows: very common ≥1/10 (≥10%); common ≥1/100 and <1/10 (≥1% and <10%); uncommon ≥1/1000 and <1/100 (≥0.1% and <1%); rare ≥1/10,000 and <1/1000 (≥0.01% and <0.1%); very rare <1/10,000 (<0.01%); not known (cannot be estimated from the available data).
Very rare: Methaemoglobinaemia
Very rare: Restlessness
Very common: Headache
Common: Dizziness, Drowsiness
Uncommon: Syncope
Very rare: Cerebral ischaemias
Common: Tachycardia
Uncommon: Enhanced angina pectoris symptoms, Bradycardia, Cyanosis
Common: Orthostatic hypotension*, Facial flushing
Uncommon: Circulatory collapse
Uncommon: Nausea, Vomiting
Not known: Tongue swelling**, Tongue blistering
Very Rare: Impairment of respiration
Rare: Allergic skin reactions
Uncommon: Allergic dermatitis**
Very rare: Exfoliative dermatitis, Drug rash
Common: Asthenia
Common: Blood pressure decreased*
* 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 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.uk/yellowcard or search for MHRA Yellow Card in the Google Play or Apple App Store.
Not known.
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