Glyceryl Trinitrate Spray
SUMMARY OF PRODUCT CHARACTERISTICS
1 NAME OF THE MEDICINAL PRODUCT
Glyceryl trinitrate Spray
2. QUALITATIVE AND QUANTITATIVE COMPOSITION
Glyceryl trinitrate 400 micrograms/dose
3. PHARMACEUTICAL FORM
Sublingual spray
4. CLINICAL PARTICULARS
4.1. Therapeutic Indications
For the treatment and prophylaxis of angina pectoris.
4.2. Posology and Method of Administration
Adult:
At the onset of an attack: 1 or 2 sprays (400-800 micrograms). Dose should not exceed more than 3 sprays at any one time.
For prophylaxis: 1 - 2 sprays (400-800 micrograms) immediately prior to an angina inducing event.
The patient should be in the sitting position. The spray should be held upright and should not be inhaled. After spraying under the tongue the mouth should be closed immediately after each dose.
Elderly:
As Adult.
Children:
Not recommended.
4.3 Contraindications
• Known hypersensitivity to any component of the preparation.
• Acute circulatory failure (shock, collapse).
• Hypovolaemia
• Marked hypotension (systolic pressure below 90 mmHg).
• Cardiogenic shock (unless an appropriate left-ventricle end-diastolic pressure is ensured by intra-aortic balloon pump or by positive inotropic agents).
• Acute myocardial infarction with low filling pressure.
• Left heart failure with low filling pressure.
• Angina pectoris caused by hypertrophic, obstructive cardiomyopathy.
• Constrictive pericarditis.
• Pericardial tamponade.
• Aortic and mitral stenosis.
• Primary pulmonary hypertension (since hyperaemia of hypoventilated alveolar regions may lead to hypoxia). Coronary patients are especially at risk in this respect.
• Any condition with elevated intracranial pressure.
• Severe anaemia.
• Owing to its effect on the nitrogenmonoxide/cyclic guanosine monophosphate (cGMP) metabolic process, phosphodiesterase inhibitors (e.g. sildenafil, vardenafil, tadalafil) may potentiate the antihypertensive effects of nitrate preparations, therefore, their co- administration with nitrogenmonoxide-forming compounds and nitrates is contraindicated.
4.4 Special warnings and precautions for use
Special caution and close medical control is required in patients predisposed to postural hypotension.
The preparation should be administered carefully to patients with narrow angle glaucoma, or migraine.
There is a great interindividual variation as regards the sensitivity of the patients to nitrates. This should always be kept in mind when setting the dosage.
Any increase of the dose may lead to tolerance.
Glyceryl trinitrate increases the urinary excretion of catecholamines and VMA (vanillylmandelic acid).
The preparation contains alcohol. Its use may cause harm in liver disease, alcoholism, epilepsy, cerebral trauma and other CNS diseases, pregnancy and childhood. Glyceryl trinitrate may modify or intensify the effect of other agents.
Any lack of effect may be an indicator of early myocardial infarction.
4.5 Interaction with other medicinal products and other forms of interaction
Never co-administer with:
- Cyclic guanosine monophosphate-specific phosphodiesterase V inhibitors (PDE5) used for the treatment of erectile dysfunction (e.g. sildenafil, vardenafil, tadalafil) may increase the antihypertensive effects of Glyceryl Trinitrate Spray, therefore, their co-administration is contraindicated.
- Consumption of alcoholic beverages during the use of the preparation is strictly forbidden.
Carefully combine with:
- Other vasodilators and antihypertensive agents (beta-blockers, calcium-channel blockers, ACE inhibitors, Angiotensin-II receptor antagonists, alpha-blockers, diuretics, diazoxide, hydralazine, methyldopa, minoxidil, moxonidine); neuroleptics, anxiolytics, hypnotics, tricyclic antidepressants, baclofen, levodopa, MAOIs, aldesleukin, (they may augment the antihypertensive effect of glyceryl trinitrate);
- Dihydroergotamine (the serum level and the effect of dihydroergotamine may increase);
- Heparin (the efficacy of heparin may decrease).
- Patients with a history of previous nitrate treatment (with e.g. isosorbide-dinitrate, isosorbide-mononitrate) may require higher glyceryl trinitrate doses.
4.6. Pregnancy and Lactation
There are no specific data available on the use of glyceryl trinitrate in human pregnancy. Since angina is uncommon in pregnancy it is unlikely that the need for glyceryl trinitrate would arise. In all cases, the benefit of treatment to the patient must be balanced against any possible hazard to the foetus. There is no information regarding excretion of glyceryl trinitrate in breast milk.
4.7. Effects on Ability to Drive and Use Machines
Glyceryl trinitrate Spray should not impair ability to drive or use machines, however, patients should be advised not to drive etc. if they feel unwell or faint after using the spray.
Undesirable effects
4.8
Headache due to vasodilatation may occur at the beginning of the treatment. Occasionally, the first dose, or the first elevated dose may cause a blood pressure drop and/or postural hypotension with reflex tachycardia, dizziness and weakness.
Application may cause a mild, transient burning sensation in the mouth.
Rarely nausea, vomiting, heartburn, flushing and allergic skin reactions or in some cases hypersensitivity reactions and exfoliative dermatitis may appear. Sporadically, in cases with extreme blood pressure reduction, the treatment may aggravate the symptoms of angina pectoris (paradoxical nitrate reaction).
Sometimes collapse occurs with bradyarrhythmia and syncope.
4.9. Overdose
Symptoms - flushing, severe headache, a feeling of suffocation, hypotension, fainting. Rarely cyanosis and methaemoglobinaemia. In a few patients a reaction comparable to shock with nausea, vomiting, weakness, sweating and syncope.
Emergency procedures - recovery often occurs without special treatment. Elevate legs to promote venous return.
Antidote - treat methaemoglobinaemia with intravenous methylene blue. Treat symptomatically for serious respiratory and circulatory effects.
5. PHARMACOLOGICAL PROPERTIES 5.1. Pharmacodynamic Properties
Glyceryl trinitrate relaxes smooth muscle and reduces blood pressure. Its antianginal effects are believed to depend on reducing myocardial oxygen demand by means of peripheral vasodilation.
5.2. Pharmacokinetic Properties
The onset of action following sublingual administration is within 2 minutes. Duration of action is about 30 minutes.
5.3.
Pre-clinical Safety Data
No animal toxicological studies have been performed using Glyceryl trinitrate Spray. Animal studies using inorganic nitrates have shown toxic effects due to excessive pharmacodynamic action (e.g. hypovolaemia, shock, and circulatory collapse) or due to the effects of methaemoglobinaemia. These effects have always occurred at doses proportional to doses in the toxic range in humans.
Studies in pregnant animals have shown similar toxic effects but no evidence of a direct teratogenic effect.
6. PHARMACEUTICAL PARTICULARS
6.1. List of Excipients
Propylene glycol BP
Ethanol (96%) v/v BP
6.2. Incompatibilities
None known.
6.3. Shelf-Life
Opened and unopened: 36 months.
6.4. Special Precautions for Storage
Do not store above 25°C. Protect from sunlight and do not expose to temperatures above 50°C. Do not pierce or burn after use. Do not spray on to a naked flame or any incandescent material.
6.5. Nature and Contents of Container
Aluminium canister with a metered dosing valve and nozzle. Plastic protective cap. Each 180 dose canister contains 10 gram of solution. Each canister contains 200 doses canister contains 11 gram of solution.
6.6. Instructions for Use, Handling and Disposal
None stated.
7. MARKETING AUTHORISATION HOLDER
EGIS Pharmaceuticals UK Ltd 127 Shirland Road London W9 2EP
United Kingdom
8. MARKETING AUTHORISATION NUMBER(S)
PL 18190/0013
9 DATE OF FIRST AUTHORISATION/RENEWAL OF THE AUTHORISATION
02/03/2009
10 DATE OF REVISION OF THE TEXT
24/11/2010