SUMMARY OF PRODUCT CHARACTERISTICS

1    NAME OF THE MEDICINAL PRODUCT

Glyceryl Trinitrate Pump Spray 400 micrograms per metered dose

2    QUALITATIVE AND QUANTITATIVE    COMPOSITION

Active Ingredient: Glyceryl Trinitrate: 400 micrograms per metered dose.

This product contains small amounts of ethanol (alcohol) less than 100mg per spray. For full list of excipients, see section 6.1.

3    PHARMACEUTICAL FORM

Metered dose oromucosal (sublingual) spray solution.

Pump spray.

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:

Before using the pump spray for the first time, the patient should press the spray button three times to fill the pumping chamber. If the patient has not used the spray for a few days, the spray should be pumped 1 or 2 times before use.

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 microgram metered doses to be sprayed under the tongue within 2-3 minutes of the event starting.

Children

Glyceryl Trinitrate Pump Spray is not recommended for children

Administration

During application the patient should rest, ideally in the sitting position. The bottle 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 the top of the actuator, 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, 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 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 Pump 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 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 and medical controls of the intraocular pressure of glaucoma-patients are advisable. Particular caution should also be exercised when using Glyceryl Trinitrate Pump 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 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 bioavailability of dihydroergotamine may be increased by concomitant use of Glyceryl Trinitrate Pump Spray, which can result in vasoconstriction since dihydroergotamine can antagonise the effects of glyceryl trinitrate. The concomitant administration of Glyceryl Trinitrate Pump Spray 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 pre-treated with organic nitrates a higher dose of glyceryl trinitrate may be necessary to achieve the desired haemodynamic effect.

4.6 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. Glyceryl Trinitrate Pump 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 Pump Spray.

4.8 Undesirable effects

The following adverse reactions have been reported:

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				Tacycardia, Bradycardia

Rarely collapse states with bradycardia and syncope, a severe fall in blood pressure accompanied by an enhancement of the anginal symptoms may occur.

Use of Glyceryl Trinitrate Pump Spray 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 avoided.

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.

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: C0IDA02

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 principle mechanism of metabolism involves denitration.

5.3 Preclinical safety data

Preclinical date reveal no special hazard for human based conventional studies of safety pharmacology, repeated dose toxicity, genotoxicity, carcinogenic potential, or toxicity to reproduction.

6 PHARMACEUTICAL PARTICULARS

6.1 List of excipients

Alcohol (ethanol), medium chain triglyceride.

6.2 Incompatibilities

Not applicable.

6.3 Shelf life

3 years.

6.4 Special precautions for storage

Glyceryl Trinitrate Pump Spray should be stored below 25°C and not close to direct sources of heat.

The spray should not be used near naked flames.

6.5 Nature and contents of container

Glass bottles encased in red transparent PVC with metering valve and spray nozzle covered with a polypropylene cap.

Each Glyceryl Trinitrate Pump Spray will deliver 200 metered doses of 0.4 mg glyceryl trinitrate.

6.6    Special precautions for disposal

Glyceryl Trinitrate Pump Spray 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 Pump Spray near a naked flame.

Any unused product or waste material should be disposed of in accordance with local requirements.

7    MARKETING AUTHORISATION HOLDER

Ayrton Saunders Ltd.,

9 Arkwright Road

Astmoor Industrial Estate

Runcorn

Cheshire

WA7 1NU,

UK.

8    MARKETING AUTHORISATION NUMBER(S)

PL 16431/0024

9    DATE OF FIRST AUTHORISATION/RENEWAL OF THE AUTHORISATION

09/04/2014

10    DATE OF REVISION OF THE TEXT

06/08/2014