Nitrates.

Generic

Active Ingredient Glyceryl Trinitrate: 400 micrograms/metered dose (One metered dose with 8.8mg solution contains 400 micrograms glyceryl trinitrate)

Sublingual spray.

Treatment of acute angina pectoris. Prevention of inducible angina (e.g. physical effort, emotional stress, exposure to cold).

Route 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 the 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 sprayed under the tongue within 2-3 minutes of the event starting.

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 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.

Glytrin Spray is not recommended for children.

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.

Tolerance to this drug and cross-tolerance to other nitrates may occur.

Glytrin 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 Glytrin in patients with volume depletion from diuretic therapy, severe hepatic or renal impairment and hypothyroidism.

Alcohol may potentiate the hypotensive effect. Vasodilators, antihypertensives, β- 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 Glytrin Spray, which can result in vasoconstiction since dihyroergotamine can antagonise the effects of glyceryl trinitrate. The concomitant administration of Glytrin 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.

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%)	Rare (0.01%<0.1%)
Nervous system disorders	Headache	Vertigo
Skin and subcutaneous tissue disorders		Facial Flushing
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
Skin and subcutaneous tissue disorders				Allergic skin reactions	Exfoliative dermatitis

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 Glytrin 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.

Sanofi-aventis

(P)

14 May 2009