NATISPRAY 0,15 mg buccal powder spray bottle/200doses

Alcoholic solution of trinitrin at 4 percent................................................................................. 0,00458 ml

Quantity corresponding to trinitrin...................................................................................................0,15000 mg

For a dose of 0,05 ml.

Excipient(s) with notable effect: ethanol

Angina

• Curative treatment of angina attack.

• Very short-term (or pre-critical) preventive treatment of angina attack.

Dosage

Angina

• Curative treatment: in case of attack, the dosage is one spray to be renewed once or twice at an interval of 2 to 3 minutes, if the attack persists. If the dose must be renewed, the patient is advised to sit down and remain seated for about ten minutes after the second administration.

• Preventive treatment: one spray within the 2 or 3 minutes preceding a circumstance likely to trigger an angina attack (physical exertion, sudden exposure to cold, sexual intercourse or any other occasion of attack).

• In the following cases, preferably use the low dose:

• first treatment with a nitrate derivative,
• concomitant vasodilator and/or antihypertensive treatment,
• prescription to an elderly subject.

Method of administration

• Sublingual route.

• The spray must be applied under the tongue, as this is how the active product passes most rapidly into the blood.

Hypersensitivity to nitrated derivatives or to any of the excipients mentioned in the section Composition.

This medicine MUST NEVER BE USED:

• state of shock, severe hypotension,

• in combination with sildenafil (see section Interactions and Warnings and precautions):

• In any patient treated with a nitrate derivative, in whatever form, sildenafil must not be prescribed as long as the patient is under the effect of the nitrate derivative.
• In case of treatment with sildenafil, nitrate derivatives are contraindicated in whatever form. In particular, any coronary patient that, if during sexual activity they experience anginal pain, they must in no case take an immediate-acting nitrate derivative.
• Likewise, in a patient without coronary history presenting a first anginal episode following sexual activity, the possible intake of sildenafil should be sought by questioning (most often within the hour preceding sexual activity) and, if so, any nitrate treatment should be avoided.
• In general, according to the available data, the interval to be observed before administering a nitrate derivative to a patient exposed to sildenafil is not precisely known, but can be estimated at a minimum of 24 hours.

This medicine should GENERALLY NOT BE USED in cases of:

• obstructive cardiomyopathy,

• acute phase inferior-wall myocardial infarction with extension to the right ventricle, except in the presence of signs of left ventricular failure,

• intracranial hypertension,

• breastfeeding.

Warning

Association of nitrate derivatives with sildenafil

The combination of a nitrate derivative, whatever its nature or mode of administration, with sildenafil risks causing a significant and sudden drop in blood pressure, which may in particular lead to lipothymia, syncope or acute coronary accident (see sections Interactions and Contraindications).

Precautions for use

Vasodilator and antihypertensive substances, diuretics and alcohol may increase the hypotension caused by nitrate derivatives, especially in elderly subjects.

Contraindicated combinations

+ Sildenafil

Risk of significant hypotension (synergistic effect) which may worsen the state of myocardial ischaemia and in particular cause acute coronary accident.

Pregnancy

There are no reliable data on teratogenicity in animals.

In clinical practice, there are currently no sufficiently relevant data to assess a possible teratogenic or fetotoxic effect of trinitrin when administered during pregnancy.

Consequently, except in acute situations, the use of trinitrin is not recommended during pregnancy.

Breast-feeding

In the absence of data on passage into breast milk, breastfeeding is not recommended during the duration of treatment.

At the start of treatment, there is a risk of orthostatic hypotension, which may be accompanied by dizziness, presyncope, or, exceptionally, syncope.

• Dose-dependent headaches.

• Arterial hypotension, sometimes orthostatic, especially reported in elderly subjects or when combined with other vasodilators. These hypotensions may be associated with reflex tachycardia and be accompanied by dizziness, presyncope, or exceptionally syncope.

• Cutaneous vasodilation with erythema and hot flushes.

• Digestive disorders (nausea, vomiting).

• Rare burning sensations at the spray site.

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 reaction via the national reporting system: National Agency for the Safety of Medicines and Health Products (ANSM) and the network of Regional Centres of Pharmacovigilance - Website: https://signalement.social-sante.gouv.fr

In case of massive ingestion, most often accidental, nitrate derivatives may cause methemoglobinemia, warranting management in a specialised setting.

Pharmacotherapeutic class: VASODILATOR USED IN CARDIOLOGY/NITRATE DERIVATIVE ATC code: C01DA02

Nitrate derivatives are donors of nitric oxide (NO). NO, by stimulating the formation of cyclic GMP, leads to relaxation of vascular smooth muscle fibres.

The main actions of nitrated derivatives are as follows:

• predominant venous vasodilation responsible for a decrease in cardiac venous return, and therefore in cardiac preload;

• coronary vasodilation which, combined with a decrease in left ventricular telediastolic pressure linked to the decrease in venous return, results in a redistribution of coronary perfusion towards subendocardial zones, which are particularly vulnerable to ischaemia;

• an antispasmodic action at the coronary level;

• peripheral arteriolar vasodilation at high doses, resulting in a reduction of peripheral vascular resistance, and therefore of cardiac afterload.

These effects contribute at rest and during exertion to a decrease in myocardial oxygen demand (reduction of cardiac workload linked to pre- and afterload) and to an increase in oxygen supply (coronary vasodilation and redistribution), which are the basis for the indications of nitrate derivatives in angina.

In addition, the decrease in cardiac venous return, which is accompanied by a decrease in pulmonary capillary pressures, combined with the reduction of afterload at high doses of nitrate derivatives, underlies the indications of certain derivatives in left or global heart failure.

Absorption

Sublingual spraying of NATISPRAY ensures instant absorption of trinitrin. The maximum plasma concentration is reached in less than five minutes and decreases by 50 percent in 3 to 4 minutes.

Distribution

In plasma, trinitrin is present in free form and bound to proteins. It is distributed to the heart, adipose tissue and main organs. It is metabolized into dinitrated and mononitrated derivatives.

Elimination

Elimination of trinitrin and its metabolites occurs via the urinary route.

3 years.

No special precautions for storage.

Spray onto the buccal mucosa, under the tongue, without inhaling.

Hold the bottle vertically with the spray pump at the top. Place the spray nozzle as close as possible to the mouth.

Before first use, actuate the pump 5 times to prime it. A first priming spray may be necessary after a few hours without use.