Consumer medicine information

Nitrolingual Pumpspray

Glyceryl trinitrate

BRAND INFORMATION

Brand name

Nitrolingual Pumpspray

Active ingredient

Glyceryl trinitrate

Schedule

S3

 

Consumer medicine information (CMI) leaflet

Please read this leaflet carefully before you start using Nitrolingual Pumpspray.

What is in this leaflet

This leaflet answers some common questions about Nitrolingual Pumpspray. It does not contain all the available information.

It does not take the place of talking to your doctor or pharmacist.

All medicines have risks and benefits. Your doctor or pharmacist has weighed the risks of you using this medicine against the benefits they expect it will have for you.

If you have any concerns about using this medicine, ask your doctor or pharmacist.

Keep this leaflet with the medicine. You may need to read it again.

What Nitrolingual Pumpspray is used for

Nitrolingual Pumpspray is used to treat angina.

Nitrolingual Pumpspray may also be used to prevent angina if used 5-10 minutes before taking part in an activity which may provoke an attack of angina.

Angina is a pain or uncomfortable feeling in the chest, often spreading to the arms or the neck and sometimes to the shoulders and back. This may be caused by too little blood and oxygen getting to the heart.

The pain of angina is usually brought on by exercise or stress.

Nitrolingual Pumpspray belongs to a group of medicines called nitrates. It works by widening blood vessels, letting more blood and oxygen reach the heart.

Your doctor or pharmacist may have recommended Nitrolingual Pumpspray for another reason.

Ask your doctor or pharmacist if you have any questions about why Nitrolingual Pumpspray has been recommended for you.

There is no evidence to suggest that Nitrolingual Pumpspray is addictive.

Before you use it

When you must not use it

Do not use Nitrolingual Pumpspray if you are allergic to:

  • Glyceryl trinitrate (the active ingredient) or any of the other ingredients of Nitrolingual Pumpspray listed at the end of this leaflet
  • any medicine or food containing nitrates or nitrites

Symptoms of an allergic reaction may include:

  • asthma, wheezing or shortness of breath
  • swelling of the face, lips or tongue which may cause difficulty in swallowing or breathing
  • hives, itching or skin rash
  • fainting

Do not use phosphodiesterase inhibitors (e.g. Viagra®, Cialis®, Levitra® or others) if your doctor or pharmacist has asked you to use Nitrolingual Pumpspray.

Do not use soluble guanylate cyclase stimulators (such as Adempas®) if you are using Nitrolingual Pumpspray.

Do not use Nitrolingual Pumpspray after the expiry date (EXP) printed on the bottle and packaging. If you take this medicine after the expiry date has passed, it may not work (as well).

Do not use Nitrolingual Pumpspray if the packaging is torn or shows signs of tampering.

Do not use Nitrolingual Pumpspray to treat any other complaints unless your doctor or pharmacist has instructed you to do so.

If you are not sure whether you should start using Nitrolingual Pumpspray, contact your doctor or pharmacist.

Before you start to use it

Tell your doctor or pharmacist if:

  • you have any allergies to:
    - any other medicines
    - any other substances, such as foods, dyes or preservatives.
  • you have any medical conditions, including:
    - severe anaemia
    - low blood pressure (which can make you feel faint, weak or dizzy, especially when you stand up suddenly)
    - a recent heart attack or other serious heart disease
    - a recent head injury or stroke
    - an abnormality of haemoglobin (a pigment in your red blood cells which carries oxygen)
    - high blood pressure in the pulmonary artery.
    It may not be safe for you to use Nitrolingual Pumpspray if you have any of these medical conditions.
  • you are pregnant or intend to become pregnant.
  • you are breast-feeding or plan to breast-feed.

Do not use Nitrolingual Pumpspray if you are pregnant or breast-feeding unless you and your doctor or pharmacist have discussed the risks and benefits involved.

If you have not told your doctor or pharmacist about any of these things, tell them before you use Nitrolingual Pumpspray.

Taking other medicines

Tell your doctor if you are taking any other medicines, including any that you buy without a prescription from your pharmacy, supermarket or health food store.

Some medicines may interfere with Nitrolingual Pumpspray. These include:

  • drugs which expand the blood vessels
  • drugs which lower blood pressure
  • drugs which help to reduce the amount of excess fluid in the body by increasing the amount of urine produced
  • drugs used to treat impaired sexual function
  • drugs used to treat high blood pressure in the pulmonary artery
  • some drugs for mental conditions
  • some drugs used to treat depression.
  • some drugs used to treat migraine headaches.
  • heparin, used to thin the blood.
  • adempas® used for pulmonary hypertension

These medicines may be affected by Nitrolingual Pumpspray or may affect how well it works.

You may need to take different amounts of your medicine or you may need to take different medicines.

Talk to your doctor or pharmacist about this.

If you have been prescribed a phosphodiesterase 5 inhibitor (e.g. Viagra®, Cialis®, Levitra® or others) for the treatment of erectile dysfunction or high blood pressure in the pulmonary artery and you experience an acute angina attack, immediately go to the emergency department at your nearest hospital.

Your doctor or pharmacist can advise further on the list of medicines to avoid while taking Nitrolingual Pumpspray.

Nitrolingual Pumpspray can be used with other medications which are used to prevent angina.

If your doctor or pharmacist transfers you from glyceryl trinitrate tablets to Nitrolingual Pumpspray you may receive a larger dose of the drug than usual, because Nitrolingual Pumpspray does not break down as quickly as glyceryl trinitrate tablets. As a result you may get more side effects.

Tell your doctor or pharmacist if you notice this. Your doctor or pharmacist can tell you what to do if you are taking any other medicines.

Use in Children

Nitrolingual Pumpspray is not recommended for use in children as there is no specific information about such use.

Always ask your doctor or pharmacist before giving medicines to children.

Use in Elderly

Elderly patients may be more sensitive to the effects or side effects of Nitrolingual Pumpspray.

If you are elderly you may need to watch carefully for signs of side effects.

How to use it

How much to use

Your doctor or pharmacist will tell you how much Nitrolingual Pumpspray to use.

Use the exact amount your doctor or pharmacist tells you to.

At the first sign of an angina attack, one metered dose should be sprayed under your tongue. If the pain persists after five minutes, administer a second metered dose.

DO NOT TAKE MORE THAN TWO DOSES DURING AN ANGINA ATTACK.

If this does NOT relieve the angina and the pain continues, then you should call an ambulance or the nearest hospital immediately.

When to use it

Your doctor or pharmacist will tell you how often you should use Nitrolingual Pumpspray.

Nitrolingual Pumpspray is NOT a medication which is taken regularly. It is used when you need to obtain relief from the pain of an acute attack of angina.

Nitrolingual Pumpspray may also be used 5 to 10 minutes before taking part in exercise or activities which may provoke an acute attack of angina.

The number of times that you can use Nitrolingual Pumpspray in any one day will depend on how severe your angina is, what other medicines you are taking and any other medical conditions you may have. You should discuss this with your doctor or pharmacist.

How to use it

Follow the instructions for using Nitrolingual Pumpspray to make sure that you receive the correct dose.

In order to completely fill the dosing chamber when using the spray for the first time, press the nozzle five times (quickly and completely), spraying into the air. This is called priming. If the product has not been used for one week, a priming of 1 spray is necessary. If the product has not been used for more than 4 months, a priming of 5 sprays is necessary.

The spray is then ready for use.

  1. Sit down and rest.
  2. Remove the plastic cover and hold the bottle upright with your forefinger on top of the grooved nozzle. There is no need to shake the bottle.
  3. Open your mouth and bring the bottle as close as possible, aiming it under your tongue.
  4. Press the nozzle firmly with your forefinger to release the spray under your tongue.
Do not inhale the spray.
  1. Release the nozzle and close your mouth. Avoid swallowing immediately after taking a dose.
  2. For a second dose repeat the above steps.
  3. Replace the plastic cover after use.

It is important to familiarise yourself with the position of the spray opening and nozzle for ease of use at night.

IMPORTANT: The delivery tube must be immersed in the liquid. The contents of the bottle can only be sprayed as long as the opening at the bottom of the delivery tube is completely immersed in liquid.

What to expect

After one or two metered doses of Nitrolingual Pumpspray you should obtain relief from the pain of angina. If no relief is obtained and the pain continues you should call an ambulance or go to the nearest hospital immediately.

How long to use it

You may need to use Nitrolingual Pumpspray for as long as you continue to suffer from angina attacks.

If you take too much (overdose)

Immediately telephone your doctor, or the Poisons Information Centre (telephone 13 11 26) for advice, or go to Accident and Emergency at your nearest hospital, if you think you or anyone else may have used too much Nitrolingual Pumpspray. Do this even if there are no signs of discomfort or poisoning. You may need urgent medical attention. Keep these telephone numbers handy.

If you use too much Nitrolingual Pumpspray, you may suffer severe headaches. Your skin may become flushed or clammy, you may have trouble seeing or you may feel flushed, nauseous (sick), dizzy, lightheaded or faint. Your heart may also beat faster or slower than usual.

While you are using it

Things you must do

Use Nitrolingual Pumpspray exactly as your doctor or pharmacist has recommended. If you do not follow your doctor or pharmacist's instructions, you may not get relief from your angina attack.

Tell your doctor or pharmacist if you continue to have angina attacks or if they become more frequent while you are using Nitrolingual Pumpspray.

You may find it helpful to keep a written record of the number, causes, length and severity of your angina attacks, so you can tell your doctor or pharmacist at your next visit. This will help your doctor or pharmacist to choose the best possible treatment for your angina.

Tell your doctor or pharmacist immediately if you become pregnant while using Nitrolingual Pumpspray.

Tell all doctors, dentists and pharmacists who are treating you that you are using Nitrolingual Pumpspray, especially if you are being started on any new medicines.

Tell your doctor or pharmacist that you are taking Nitrolingual Pumpspray if you are about to be started on any new medicines.

Things you must not do

Do not use Nitrolingual Pumpspray to treat any other complaints unless your doctor or pharmacists tell you to.

Do not give this medicine to anyone else even if their symptoms seem similar to yours.

Do not suddenly stop using Nitrolingual Pumpspray if you have been using large amounts of the spray regularly. If you have been using large amounts of Nitrolingual Pumpspray regularly and stop using it suddenly, you may find that your attacks of angina become worse. If you want to stop using Nitrolingual Pumpspray ask your doctor or pharmacist how to stop using it gradually over a few weeks.

Things to be careful of

Be careful driving or operating machinery until you know how Nitrolingual Pumpspray affects you. Nitrolingual Pumpspray may cause dizziness and fainting in some patients, especially when you first start to use it. Make sure you know how you react to Nitrolingual Pumpspray before you drive a car, operate machinery or do anything else which could be dangerous.

Be careful when drinking alcohol while you are using Nitrolingual Pumpspray. If you drink alcohol while you are using Nitrolingual Pumpspray, your blood pressure may drop, making you feel dizzy or faint.

Be careful not to overdo physical activities when you first start using Nitrolingual Pumpspray. If you use Nitrolingual Pumpspray 5 to 10 minutes before exercise, you will probably feel better and more able to participate in physical activities. However, if you overdo physical activities you may still get an attack of angina.

Get up slowly when getting out of bed or standing up if you feel lightheaded, dizzy or faint. You may feel lightheaded or dizzy when you begin to use Nitrolingual Pumpspray or if the dose is increased. This is because your blood pressure is falling suddenly. Standing up slowly, especially when you get up from bed or chairs, will help your body get used to the change in position and blood pressure. If this problem gets worse or continues, talk to your doctor or pharmacist.

Side effects

Tell your doctor or pharmacist as soon as possible if you do not feel well while you are using Nitrolingual Pumpspray.

Nitrolingual Pumpspray helps most people with angina, but it may have unwanted side effects in some people.

All medicines have side effects. Sometimes they are serious, most of the time they are not. You may need medical treatment if you get some of the side effects.

Do not be alarmed by this list of possible side effects. You may not experience any of them.

Common side effects:

Tell your doctor or pharmacist if you notice any of the following and they worry you:

  • headache
  • dizziness, weakness, feeling faint or lightheaded, especially when you stand up suddenly.

These are all mild side effects of Nitrolingual Pumpspray.

Less common side effects:

Tell your doctor or pharmacist immediately or go the casualty at your nearest hospital if you notice any of the following symptoms:

  • nausea (feeling sick)
  • vomiting
  • severe headache
  • severe dizziness or fainting
  • weak or unusually fast or slow heart beat
  • flushing of the face or neck
  • skin rash
  • weakness
  • blush colour of lips, nails or palms of hand.

These are all serious side effects. You may need urgent medical attention. Serious side effects are rare.

If any of the following happen, stop taking this medicine and tell your doctor immediately, or go to Accident and Emergency at your nearest hospital:

  • sudden signs of allergy such as rash, itching or hives on the skin, swelling of the face, lips, tongue or other parts of the body, shortness of breath, wheezing or trouble breathing
  • swelling of the face, lips, mouth, tongue or throat which may cause difficulty in swallowing or breathing

These are very serious side effects. If you have them, you may have had a serious allergic reaction to Nitrolingual. You may need urgent medical attention or hospitalisation.

Other side effects not listed above may also occur in some patients. Tell your doctor or pharmacist if you notice anything else that is making you feel unwell.

Ask your doctor or pharmacist if there is anything in this list you don't understand.

After using it

Storage

Keep Nitrolingual Pumpspray in a cool dry place where the temperature stays below 25°C.

Do not store Nitrolingual Pumpspray or any other medicine in the bathroom or near a sink or stove. Do not leave it in the car on hot days. Heat and dampness can destroy some medicines.

Keep Nitrolingual Pumpspray where children cannot reach it. A locked cupboard at least one-and-a-half metres above the ground is a good place to store medicines.

Disposal

Dispose of the bottle where children cannot reach it. There may be some solution left in the bottle which could harm them.

If your doctor tells you to stop using Nitrolingual Pumpspray, or the spray has passed its expiry date, ask your pharmacist what to do with any spray left over.

Do not open the empty container by force.

Do not spray into flames, onto red-hot surfaces or incinerate.

Product description

What it looks like

Nitrolingual Pumpspray is a metered dose pump spray. It delivers glyceryl trinitrate in the form of spray droplets. It is packaged in a plastic bottle which contains 13.9 mL of solution (200 doses).

Ingredients

Active Ingredient:

  • glyceryl trinitrate 400 micrograms per metered dose spray.

Inactive Ingredients:

  • fractionated coconut oil
  • glyceryl caprylate/caprate
  • ethanol
  • peppermint oil
  • Sodium (S) - lactate solution
  • (S) - Lactic acid
  • Water.

Manufacturer

Nitrolingual Pumpspray is made in Germany by G. Pohl Boskamp

Supplier

Nitrolingual Pumpspray is supplied in Australia by:

sanofi-aventis australia pty ltd
12-24 Talavera Road
Macquarie Park NSW 2113

This leaflet was revised October 2018

Australia Register Number: AUST R 308842

Nitrolingual® is the registered trademark of G. Pohl Boskamp GmbH & Co. KG.

Published by MIMS October 2019

BRAND INFORMATION

Brand name

Nitrolingual Pumpspray

Active ingredient

Glyceryl trinitrate

Schedule

S3

 

1 Name of Medicine

Glyceryl trinitrate.

6.7 Physicochemical Properties

Chemical structure.


CAS number.

55-63-0.

2 Qualitative and Quantitative Composition

Each metered dose of Nitrolingual Pumpspray delivers 400 microgram of glyceryl trinitrate per spray emission. This product delivers glyceryl trinitrate in the form of spray droplets beneath the tongue.
For full list of excipients, see Section 6.1 List of Excipients.

3 Pharmaceutical Form

Spray solution.

5 Pharmacological Properties

5.1 Pharmacodynamic Properties

Pharmacotherapeutic group: Vasodilators used in cardiac diseases, organic nitrates.
ATC code: C01DA02.
Glyceryl trinitrate, an organic nitrate, is a vasodilator which has effects on both arteries and veins. The chemical name for glyceryl trinitrate is 1,2,3 propanetriol trinitrate (C3H5N3O9) and the compound has a molecular weight of 227.09.

Mechanism of action.

The principal pharmacological action of glyceryl trinitrate is relaxation of vascular smooth muscle, producing a vasodilator effect on both peripheral arteries and veins, with more prominent effects on the latter. Dilation of the postcapillary vessels, including large veins, promotes peripheral pooling of blood and decreases venous return to the heart, thereby reducing left ventricular end diastolic pressure (preload). Arteriolar relaxation reduces systemic vascular resistance and arterial pressure (afterload).
The smaller ventricular radius and reduced systolic wall tension lower the myocardial energy and O2 requirements. The reduction in cardiac filling pressures promotes perfusion of subendocardial wall layers threatened by ischemia.
On a molecular level, nitrates most likely act via formation of nitric oxide (NO) and cyclic guanosyl monophosphate (cGMP), which is thought to mediate relaxation.
Therapeutic doses of glyceryl trinitrate may reduce systolic, diastolic and mean arterial blood pressure. Effective coronary perfusion pressure is usually maintained, but can be compromised if blood pressure falls excessively or increased heart rate decreases diastolic filling time.
Elevated central venous and pulmonary capillary wedge pressures, pulmonary vascular resistance and systemic vascular resistance are also reduced by glyceryl trinitrate therapy. Heart rate is usually slightly increased, presumably a reflex response to the fall in blood pressure. Cardiac index may be increased, decreased, or unchanged. Patients with elevated left ventricular filling pressure and systemic vascular resistance values in conjunction with a depressed cardiac index are likely to experience an improvement in cardiac index. On the other hand, when filling pressures and cardiac index are normal, cardiac index may be slightly reduced.

Clinical trials.

No data available.

5.2 Pharmacokinetic Properties

Absorption.

When administered sublingually, glyceryl trinitrate is rapidly absorbed from the mucosa of the mouth and reaches the vascular system, bypassing the liver. The systemic availability is subject to strong individual variations and is on average approximately 39%.

Metabolism.

Glyceryl trinitrate is metabolized in the liver as well as in many other cells, including the erythrocytes, with cleavage of one or more nitrate groups. A liver reductase enzyme has primary importance in the formation of the glycerol nitrate metabolites and inorganic nitrate. Two active major metabolites, 1,2, and 1,3-dinitroglycerols, the products of hydrolysis, although less potent as vasodilators, have longer plasma half-lives than the parent compound. The dinitrates are further metabolized to mononitrates (considered biologically inactive with respect to cardiovascular effects) and ultimately glycerol and carbon dioxide.
After sublingual administration, a wide range of intraindividual and interindividual variations are observed for the plasma concentration. In a study involving 21 healthy male subjects, a sublingual double dose totalling 800 microgram resulted in the following pharmacokinetic parameter values: Cmax was 1.0 nanogram/mL, tmax was 7.5 minutes and the plasma half-life was 5.5 minutes.
Plasma protein binding is approximately 60%.

Excretion.

Glyceryl trinitrate and its metabolites are principally renally eliminated and less than 1% is excreted unchanged.

5.3 Preclinical Safety Data

No data available.

4 Clinical Particulars

4.1 Therapeutic Indications

Treatment of acute angina pectoris.
As well as relieving the pain of an acute attack, Nitrolingual Pumpspray may be used prophylactically five to ten minutes prior to engaging in activities which may precipitate an acute attack.

4.3 Contraindications

Nitrolingual Pumpspray should not be used in the event of the following.
Known sensitivity to any of the ingredients in the product (see Section 2 Qualitative and Quantitative Composition).
Idiosyncratic reaction to organic nitrates.
Acute circulatory failure (shock, circulatory collapse).
Obstructive myocardial failure (aortic or mitral stenosis, compressive pericarditis, obstructive cardiomyopathy).
Acute inferior myocardial infarction with right ventricular involvement (see Section 4.4 Special Warnings and Precautions for Use).
Constrictive pericarditis and pericardial tamponade.
Uncorrected hypovolaemia.
Pronounced hypotension (systolic blood pressure below 90 mmHg).
Cardiogenic shock.
Primary pulmonary hypertension, since hypoxaemia may occur due to a possible increase in blood flow to hypoventilated alveolar regions (pulmonary "shunt" formation). This applies especially to patients with coronary artery disease.
Increased intracranial pressure (e.g. head trauma or cerebral haemorrhage).
Severe anaemia, arterial hypoxaemia.
Concomitant use of phosphodiesterase 5 inhibitors (e.g. sildenafil, vardenafil, tadalafil): due to a considerable increase in the hypotensive effect and the resulting severe side effects (e.g. syncope, myocardial infarction), certain drugs (phosphodiesterase 5 inhibitors) for the treatment of erectile dysfunction or pulmonary arterial hypertension may not be given additionally to an existing therapy with nitric oxide donors (e.g. Nitrolingual Pumpspray).
Concomitant use of nitrates in any form, with soluble guanylate cyclase stimulators, due to an increased risk of hypotension (see Section 4.5 Interactions with Other Medicines and Other Forms of Interactions).

4.4 Special Warnings and Precautions for Use

Use with caution in the following circumstances.

The use of any form of glyceryl trinitrate during the early days of acute myocardial infarction requires particular attention to haemodynamic monitoring and clinical status. A reduction in systolic blood pressure below 90 mmHg should be avoided.
Hypotension and reflex tachycardia may occur (see Section 4.8 Adverse Effects (Undesirable Effects)) and cause increased myocardial oxygen demand. These conditions may lead to cardiac arrhythmias such as ventricular fibrillation (sometimes fatal) mainly in patients with acute inferior myocardial infarction with right ventricular involvement (see Section 4.3 Contraindications).
Especially careful monitoring is necessary in aortic and/or mitral stenosis, and patients with congestive heart failure.
As Nitrolingual Pumpspray is more stable than glyceryl trinitrate tablets, it is possible that some patients transferred to the spray will receive a larger dose of the drug than usual. This may increase possible side effects, e.g. headache (see Section 4.8 Adverse Effects (Undesirable Effects)).
Severe hypotension, particularly with upright posture, may occur even with small doses of glyceryl trinitrate. The drug, therefore, should be used with caution in subjects who may have volume depletion from diuretic therapy or in patients who have low systolic blood pressure. Paradoxical bradycardia and increased angina pectoris may accompany glyceryl trinitrate induced hypotension. Nitrate therapy may aggravate the angina caused by hypertrophic cardiomyopathy.
In cases where cyanosis should develop during high dose treatment, work up must include search for methaemoglobinaemia (requiring specific treatment).
Headaches or symptoms of hypotension, such as weakness or dizziness, particularly when arising suddenly from a recumbent position, may be due to overdosage. When they occur, the dose or frequency of application should be reduced.

Tolerance.

Tolerance to this drug and cross tolerance to other nitrates and nitrites may occur. Tolerance to the vascular and antianginal effects of nitrates has been demonstrated in clinical trials, experience through occupational exposure, and in isolated tissue experiments in the laboratory.
Intermittent therapy, such as with Nitrolingual Pumpspray, will reduce the likelihood of tolerance developing to glyceryl trinitrate.

Withdrawal.

Various clinical trials in angina patients indicate that withdrawal of glyceryl trinitrate may cause rebound of haemodynamic effect and a more ready provocation of anginal attack. Sudden discontinuation should be avoided (see Section 4.8 Adverse Effects (Undesirable Effects)).

Hypoxaemia.

Arterial oxygen tension decreases after administration of glyceryl trinitrate in normal subjects and in patients with coronary artery disease.
Caution should be observed in patients with severe ischaemic heart disease as a decrease in available oxygen may oppose its antianginal effect.

Methaemoglobinaemia.

Methaemoglobinaemia has been reported in association with high doses of glyceryl trinitrate therapy. This may be clinically significant, especially in the presence of methaemoglobin reductase deficiencies or in congenital methaemoglobin variants.
Case reports of clinically significant methaemoglobinaemia are rare at conventional doses of organic nitrates. The formation of methaemoglobin is dose related and in the case of genetic abnormalities of haemoglobin that favour methaemoglobin formation, even conventional doses of organic nitrates could produce harmful concentrations of methaemoglobin.

Paediatric use.

The safety and effectiveness of glyceryl trinitrate in children have not been established.

Use in the elderly.

No data available.

Effects on laboratory tests.

No data available.

4.5 Interactions with Other Medicines and Other Forms of Interactions

Nitroglycerin should be used with care in combination with other medicines with blood pressure lowering effect. Concomitant intake of vasodilators, antihypertensive drugs, diuretic substances, β-blockers, calcium channel blockers, hypotensive medicines (e.g. antipsychotics or tricyclic antidepressants) or alcohol may potentiate the antihypertensive effect of Nitrolingual Pumpspray.
Concomitant intake of nitric oxide donors (e.g. Nitrolingual Pumpspray) and certain drugs (phosphodiesterase 5 inhibitors) for the treatment of erectile dysfunction or pulmonary arterial hypertension enhances the hypotensive effect. Therefore, the concomitant administration of nitric oxide donors, e.g. the active ingredient of Nitrolingual Pumpspray, and these drugs is contraindicated (see Section 4.3 Contraindications). If a patient treated with these drugs needs a rapidly effective nitrate (e.g. in case of an acute angina pectoris attack) he/ she must be hospitalised immediately.
Agonists of soluble guanylate (sGC), which is the receptor for nitric oxide (NO), must not be used concomitantly with nitrates (see Section 4.3 Contraindications).
In patients previously treated with organic nitrates (e.g. isosorbide dinitrate, isosorbide-5-mononitrate) it may become necessary to increase the glyceryl trinitrate dose to achieve the desired haemodynamic effect.
If used concomitantly with dihydroergotamine (DHE), Nitrolingual Pumpspray may increase the DHE level and consequently enhance its hypertensive effect. Concomitant use of nitrates and ergot alkaloids should be avoided.
Concomitant administration of heparin and glyceryl trinitrate weakens the effect of heparin.
Glyceryl trinitrate may also potentiate the anticholinergic effects of tricyclic antidepressants.

4.6 Fertility, Pregnancy and Lactation

(Category B2)
The safety of glyceryl trinitrate administered to women who are or who may become pregnant has not been established. Therefore, Nitrolingual Pumpspray should not be given to pregnant women unless, in the judgement of the physician, the expected benefit outweighs any potential risk.
It is not known whether glyceryl trinitrate is excreted in human milk. Safety in breastfeeding women has not been established. Breastfeeding is therefore inadvisable for the duration of the treatment unless, in the judgement of the physician, the probable clinical benefits outweigh the possible risk to the child.

Effects of fertility.

No data available.

4.8 Adverse Effects (Undesirable Effects)

Adverse reactions to Nitrolingual Pumpspray, particularly headache and hypotension, are generally dose related. Headache is the most commonly reported side effect, but usually subsides with continued use. It may be severe and persistent.
Uncommon cases of hypotension, sometimes severe, and/or orthostatic hypotension, possibly associated with reflex tachycardia or paradoxical reflex bradycardia, have been reported when glyceryl trinitrate was used for the first time or the dose was increased. This may be accompanied by a reflex increase in heart rate, somnolence, dizziness and weakness especially on standing. In rare cases with a large drop in blood pressure angina pectoris symptoms may be intensified (paradoxical nitrate reaction). Less often states of collapse may occur, occasionally accompanied by bradyarrhythmias. Rarely nausea, vomiting, transient flushing, allergic skin reactions may occur.
Anaphylactic reactions, angioedema, lip and tongue swelling, urticaria have been reported.
Uncommon cases of asthenia have been reported.
Abrupt withdrawal may precipitate angina. Withdrawal may also exacerbate Raynaud's phenomenon in susceptible patients.

Reporting suspected adverse effects.

Reporting suspected adverse reactions after registration 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 at www.tga.gov.au/reporting-problems (Australia) or https://nzphvc.otago.ac.nz/reporting/ (New Zealand).

4.2 Dose and Method of Administration

The spray should not be inhaled.
At the onset of an attack, initially one metered dose (400 microgram) should be sprayed under the tongue, followed by a second metered dose if pain relief has not occurred within 5 minutes. No more than two metered doses are recommended. If chest pain persists, seek prompt attention.
For the prevention of exercise induced angina or in other precipitating conditions: one or two 400 microgram metered doses sprayed under the tongue immediately prior to the event.
The maximum number of doses of Nitrolingual Pumpspray used per day should be determined by the prescribing physician after consideration of the severity of angina, concurrent medication and patient's full medical history.
Nitrolingual Pumpspray should be primed before using it for the first time by pressing the nozzle five times.
If Nitrolingual Pumpspray has not been used for 7 days a priming of 1 spray will be necessary. If the product has not been used for more than 4 months it will need to be primed several times (max 5) until an even spray is obtained.
During administration the patient should rest in the sitting position. The bottle should be kept vertical with the nozzle head uppermost. Hold the opening in the nozzle head as close to the open mouth as possible. Close the mouth immediately after each dose.
Patients should be instructed to familiarise themselves with the position of the spray opening for ease of use at night.

4.7 Effects on Ability to Drive and Use Machines

Especially during treatment start, nitroglycerin may induce symptoms related to orthostatic hypotension such as dizziness which can possibly impact the ability to drive or use machines.

4.9 Overdose

Symptoms.

The clinical picture depends on the extent of overdosage and is characterized mainly by the following symptoms.
Drop in blood pressure with orthostatic regulatory disturbances, reflex tachycardia, persistent throbbing headaches, weakness, dizziness, somnolence, visual disturbances, flushing and perspiring skin (later becoming cold and cyanotic), nausea and vomiting (possibly with colic or bloody diarrhoea) may occur. Methaemoglobinemia has been reported in association with high doses of nitroglycerin therapy (see Section 4.4 Special Warnings and Precautions for Use). This is possibly clinically significant, especially in the context of methaemoglobin reductase deficiencies or in congenital methaemoglobin variants.

Treatment.

Keep the patient recumbent and comfortably warm. Hypotension and reflex tachycardia caused by overdosage can be treated by elevating the legs. Since the duration of the haemodynamic effects following overdosage with glyceryl trinitrate is quite short (because of its short half-life), additional measures are usually not required.
Administer oxygen and artificial ventilation if necessary.
In cases of severe overdose apply the general guidelines for treating overdose and/or shock therapy. For pronounced hypotension and/or shock, volume expansion should be performed.
If further therapy is indicated, administration of an intravenous alpha adrenergic agonist (e.g. metaraminol) should be considered.

Warning.

Adrenaline is ineffective in reversing the severe hypotensive events associated with overdose. It and related compounds are contraindicated in this situation.
For general advice on overdose management, contact the Poisons Information Centre, telephone number 13 11 26 (Australia) or the National Poisons Centre, 0800 POISON or 0800 764 766 (New Zealand).

7 Medicine Schedule (Poisons Standard)

S3.

6 Pharmaceutical Particulars

6.1 List of Excipients

Nitrolingual Pumpspray contains the following excipients: fractionated coconut oil, glyceryl caprylate/ caprate, ethanol, peppermint oil, sodium (s)-lactate solution, (S)-Lactic acid and water.

6.2 Incompatibilities

Incompatibilities were either not assessed or not identified as part of the registration of this medicine.

6.3 Shelf Life

In Australia, information on the shelf life can be found on the public summary of the Australian Register of Therapeutic Goods (ARTG). The expiry date can be found on the packaging.

6.4 Special Precautions for Storage

Store below 25°C.

6.5 Nature and Contents of Container

Metered dose pump spray containing 5.5 mL of solution (60 doses)* or 13.9 mL of solution (200 doses).
*Not marketed in Australia.

6.6 Special Precautions for Disposal

In Australia, any unused medicine or waste material should be disposed of by taking to your local pharmacy.

Summary Table of Changes