Active substance(s): GLYCERYL TRINITRATE
NAME OF THE MEDICINAL PRODUCT
Glytrin, 400 micrograms per metered dose, Sublingual Spray
QUALITATIVE AND QUANTITATIVE COMPOSITION
Glyceryl Trinitrate: 400 micrograms/metered dose
Excipients with known effect:
This product contains small amounts of ethanol (alcohol) less than 100mg per spray.
For the full list of excipients, see Section 6.1
Metered dose oromucosal (sublingual) spray solution.
Small aerosol canister
Treatment of acute angina pectoris
Prevention of inducible angina (e.g. physical effort, emotional stress, exposure
Route of Administration
Posology and method of administration
Before using Glytrin for the first time, the patient should check that the spray is
working by pressing the pump button a few times until it produces a fine mist of
liquid. The patient should practice aiming the spray onto a tissue or similar item so
that they will be able to aim it correctly under the tongue when they need to use it. If
the patient does not need to use Glytrin very often, the spray should be checked
regularly to see that it still works properly.
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
For the prevention of inducible angina (e.g. physical effort, emotional
stress, exposure to cold), one or two 400 microgram metered doses sprayed
under the tongue within 2 – 3 minutes of the event starting.
Glytrin is not recommended for
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 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.
Hypersensitivity to the active substance or to any of the excipients listed in section
Severe hypotension (systolic blood pressure lower than 90mm Hg).
Hypotensive shock, severe anaemia, constrictive pericarditis, extreme bradycardia,
Glucose-6-phosphate-Dehydrogenase-deficiency, cerebral haemorrhage and brain
trauma, aortic and/or mitral stenosis and angina caused by hypertrophic obstructive
Circulatory collapse, cardiogenic shock and toxic pulmonary oedema.
Concomitant use with phosphodiesterase inhibitors such as Sildenafil, Tadalafil or
Concomitant use with the soluble guanylate cyclase stimulator riociguat (see
Special warnings and precautions for use
Tolerance to this drug and cross-tolerance to other nitrates may occur.
Glytrin should be administered with particular caution in:
Low filling pressures (e.g. acute myocardial infarction, left ventricular
Tendancy to dysregulation of orthostatic blood pressure
Diseases accompanied by an increase in intracranial pressure (so far
further pressure has been observed solely in high doses of glyceryl
trinitrate). Alcohol should be avoided because of the hypotensive effect
and medical controls of the intraocular pressure of glaucoma patients are
advisable. Particular caution should also be exercised when using Glytrin
in patients with volume depletion from diuretic therapy, severe hepatic or
renal impairment and hypothyroidism.
Interaction with other medicinal products and other forms of interaction
Alcohol may potentiate the hypotensive effect.
Vasodilators, antihypertensives, ß-blockers, calcium antagonists, neuroleptics,
tricyclic antidepressants 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 use of a soluble guanylate cyclase stimulator such as riociguat is
contraindicated (see section 4.3) since concomitant use can cause hypotension.
The bioavailability of dihydroergotamine may be increased by concomitant use of
Glytrin, which can result in vasoconstriction since dihydroergotamine can antagonise
the effects of glyceryl trinitrate.
The concomitant administration of Glytrin and heparin can reduce the antithrombotic
effect of heparin. Regular monitoring of coagulation parameters and adjustments of
the heparin dose may be necessary.
In patients pretreated with organic nitrates a higher dose of glyceryl trinitrate may be
necessary to achieve the desired haemodynamic effect.
Fertility, 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. Glytrin should
only be used after weighing the benefit for the mother against possible risks for the child.
Nursing should be discontinued during treatment with this product.
Preclinical data reveal no special hazard for humans based on conventional studies of
toxicity to reproduction (see section 5.3).
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 Glytrin.
The following adverse reactions have been reported:
(≥1/100 to <
(≥ 1,000 to < (≥1/10,000
to < 1,000)
*symptoms which are known in conjunction with hypersensitivity reactions
Use of Glytrin may give rise to transient hypoxaemia and, in patients with coronary
heart disease, ischaemia as a result of a relative redistribution of the bloodstream,
which is to hypoventilated alveolar areas.
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
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.
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.
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.
Pharmacotherapeutic group: Vasodilators used in cardiac diseases,
Glyceryl trinitrate acts on vascular smooth muscles to produce arterial and venous
vasodilation. The vasodilation 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.
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 principle mechanism of metabolism involves
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.
List of Excipients
Propellant HFC 134A (1,1,1.2 Tetrafluoroethane)
Special precautions for storage
Do not store above 25°C. Do not refrigerate or freeze.
Nature and Content of Containers
Internally lacquered monobloc aluminium pressurised container sealed with a
metered spray valve.
The product is presented in packs with one metered dose spray.
One metered dose spray (= one aluminium container) contains 1760.0mg of
solution (according to 11400.0mg of solution and propellant) providing 200
single metered doses.
Special precautions for disposal
Glytrin 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 Glytrin near
a naked flame.
MARKETING AUTHORISATION HOLDER
Ayrton Saunders Ltd
9 Arkwright Road
Astmoor Industrial Estate
MARKETING AUTHORISTATION HOLDER
DATE OF FIRST AUTHORISATION/RENEWAL OF THE
DATE OF REVISION OF THE TEXT