Glyceryl Trinitrate Spray 400 Micrograms Per Metered Dose Sublingual Spray
SUMMARY OF PRODUCT CHARACTERISTICS
1 NAME OF THE MEDICINAL PRODUCT
Glyceryl Trinitrate Spray 400 micrograms per metered dose sublingual spray
2 QUALITATIVE AND QUANTITATIVE COMPOSITION
Active ingredient: Glyceryl trinitrate: 400 micrograms per metered dose
This product contains small amounts of ethanol (alcohol) less than 100 mg per spray. For a full list of excipients, see Section 6.1.
3 PHARMACEUTICAL FORM
Metered dose sublingual spray solution.
4 CLINICAL PARTICULARS
4.1 Therapeutic indications
Treatment of acute angina pectoris.
Prevention of inducible angina (e.g. physical effort, emotional stress, exposure to cold).
Route of administration
Oromucosal (sublingual)
4.2 Posology and method of administration
Oromucosal dosage Adults including the elderly
At the onset of an attack, one or two metered doses (400 to 800 micrograms glyceryl trinitrate) to be sprayed under the tongue for the relief of anginal pain while breath is held. No more than three doses are recommended at any one time.
For the prevention of inducible angina (e.g. physical effort, emotional stress, exposure to cold), one or two 400 micrograms metered doses sprayed under the tongue within 2-3 minutes of the event starting.
Children
Glyceryl Trinitrate Spray is not recommended for children
Administration
During application the patient should rest, ideally in the sitting position. The canister should be held vertically with the valve head uppermost and the spray orifice as close to the mouth as possible. The dose should not be sprayed under the tongue and the mouth should be closed immediately after each dose. The spray should not be inhaled. Patients should be instructed to familiarise themselves with the position of the spray orifice, which can be identified by the finger rest on top of the valve, in order to facilitate orientation, for administration at night.
4.3 Contraindications
Hypersensitivity to nitrates or to any of the excipients. Severe hypotension (systolic blood pressure lower than 90mm Hg). Hypotensive shock, severe anaemia, constructive pericarditis, extreme bradycardia, Glucose-6-phosphate-dehydrogenase-deficiency, cerebral haemorrhage and brain trauma, aortic and/or mitral stenosis and angina caused by hypertrophic obstructive cardiomyopathy. Circulatory collapse, cardiogenic shock and toxic pulmonary oedema.
Concomitant use with phosphodiesterase inhibitors, such as Sildenafil, tadalafil, or vardenafil.
4.4 Special warnings and precautions for use
Tolerance to this drug and cross-tolerance to other nitrates may occur.
Glyceryl Trinitrate Spray should be administered with particular caution in:
• Pericardial tamponade
• Low filling pressures (e.g. acute myocardial infarction, left ventricular failure)
• Tendency to dysregulation of orthostatic blood pressure
• Diseases accompanied by an increase in intracranial pressure (so far further pressure increase has been observed solely in high doses of glyceryl trinitrate).
Alcohol should be avoided because of the hypotensive effect. Medical controls
of the intraocular pressure of glaucoma patients are advisable.
Particular caution should also be exercised when using Glyceryl Trinitrate Spray in patients with volume depletion from diuretic therapy, severe hepatic or renal impairment and hypothyroidism.
4.5 Interaction with other medicinal products and other forms of interaction
Alcohol may potentiate the hypotensive effect. Vasodilators, antihypertensives, B-blockers, calcium antagonists, neuroleptics, tricyclic antidepressant and diuretics can increase nitrate-induced hypotension.
The hypotensive effects of nitrates are potentiated by the concurrent administration of phosphodiesterase inhibitors, such as sildenafil, tadalafil, or vardenafil.
The bioavailability of dihydroergotamine may be increased by concomitant use of Glyceryl Trinitrate Spray, which can result in vasoconstriction since dihydroergotamine can antagonise the effect of glyceryl trinitrate. The concomitant administration of Glyceryl Trinitrate Spray and heparin can reduce the antithrombotic effect of heparin. Regular monitoring of coagulation parameters and adjustment of the heparin dose may be necessary.
In patients pre treated with organic nitrates a higher dose of glyceryl trinitrate may be necessary to achieve the desired haemodynamic effect.
4.6 Pregnancy and lactation
The safety of glyceryl trinitrate in human pregnancy, especially during the first trimester has not been established. It is not known whether glyceryl trinitrate is excreted into human breast milk. Glyceryl Trinitrate Spray should be used only after weighing the benefit for the mother against possible risks for the child. Nursing should be discontinued during treatment with this product.
4.7 Effects on ability to drive and use machines
The ability to react may be diminished because of the side effects or interactions due to the nitrates. This effect is potentiated by alcohol consumption. Therefore, driving and / or using machines should be avoided during treatment with Glyceryl Trinitrate Spray.
4.8
Undesirable effects
|
System Organ Class |
Very Common ( 10%) |
Common ( 1% < 10%) |
Uncommon ( 0.1% < 1%) |
Rare ( 0.01%< 0.1%) |
Very Rare ( 0.001%< 0.01%) |
|
Nervous System Disorders |
Headache |
Vertigo | |||
|
Skin and Subcutaneous Tissue Disorders |
Facial flushing |
Allergic skin reactions |
Exfoliative dermatitis | ||
|
Vascular Disorders |
Dizziness |
Postural hypotension | |||
|
General Disorders and Administration Site Conditions |
Weakness |
Burning sensation Stinging sensation Tongue blistering | |||
|
Gastrointestinal Disorders |
Nausea | ||||
|
Cardiac Disorders |
Tachycardia Bradycardia |
Rarely collapse states with bradycardia ad syncope, a severe fall in blood pressure accompanied by an enhancement of the anginal symptoms, or exfoliative dermatitis may occur. Tolerance development and the occurrence of crossed tolerance of other nitro compounds have been found in chronic, continuous treatment using high doses. To avoid a decrease in efficacy or a loss of efficacy, high continuous doses should be avoided.
Use of Glyceryl Trinitrate Spray may give rise to transient hypoaemia and in patients with coronary heart disease, ischemia as a result of a relative redistribution of the bloodstream, which is to hypoventilated alveolar areas.
4.9 Overdose
Signs and symptoms
Flushing, severe headache, vertigo, tachycardia, a feeling of suffocation, hypotension, fainting 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.
Treatment
Recovery often occurs without special treatment. Hypotension may be corrected by elevation of the legs to promote venous return. Methaemoglobinaemia should be treated by intravenous methylthioninium chloride and / or toluidine blue. Symptomatic treatment should be given for respiratory and circulatory defects in more serious cases.
5 PHARMACOLOGICAL PROPERTIES
5.1 Pharmacodynamic properties
ATC-Code: CO1DAO2
Glyceryl trinitrate acts on vascular smooth muscles to produce arterial and venous vasodilatation. The vasodilatation results in a reduction of venous return and an improvement in myocardial perfusion with the result of a reduction in the work performed by the heart and hence reduced oxygen demand.
5.2 Pharmacokinetic properties
Glyceryl trinitrate is rapidly absorbed through the buccal and sublingual mucosa, and in man, peak concentrations in plasma are observed within four minutes of sublingual administration.
The absolute bioavailability after sublingual administration is approximately 39%. After sublingual administration the plasma levels have shown a wide range of intra and inter individual variability.
The compound is extensively metabolised by liver enzymes and has a plasma half-life of 1 - 3 minutes. The principal mechanism of metabolism involves denitration.
5.3 Preclinical safety data
Preclinical data reveal no special hazard for humans based on conventional studies of safety pharmacology, repeated dose toxicity, genotoxicity, carcinogenic potential, or toxicity to reproduction.
PHARMACEUTICAL PARTICULARS
6
6.1 List of excipients
Peppermint Oil
Propellant 1,1,1,2-tetrafluoroethane (HFC 134A) Ethanol
6.2 Incompatibilities
Not applicable
6.3 Shelf life
Two years
6.4 Special precautions for storage
Store below 25°C.
Do not refrigerate or freeze.
The canister contains a pressurised liquid. Do not expose to temperatures higher than 50°C. Do not pierce canister.
6.5 Nature and contents of container
Internally lacquered monobloc aluminium pressurised container, sealed with a metered spray valve.
The product is presented in either a 75 or 200 dose pack with one metered dose spray. Each metered dose contains 400 micrograms of Glyceryl Trinitrate
6.6 Special precautions for disposal
Glyceryl trinitrate spray is an aerosol spray and contains a pressurised liquid. Do not expose to temperature higher than 50°C, and do not pierce the canister, even when empty. It should not be sprayed at a naked flame or any incandescent material. Patients, especially those who smoke, should be warned not to use Glyceryl Trinitrate Spray near a naked flame.
7 MARKETING AUTHORISATION HOLDER
Ayrton Saunders Ltd 9 Arkwright Road
Astmoor Industrial Estate
Runcorn
Cheshire
WA7 1NU
United Kingdom
8 MARKETING AUTHORISATION NUMBER(S)
PL16431/0023
9 DATE OF FIRST AUTHORISATION/RENEWAL OF THE AUTHORISATION
11/09/2007
10 DATE OF REVISION OF THE TEXT
13/06/2011