Consumer medicine information

Transiderm-Nitro

Glyceryl trinitrate

BRAND INFORMATION

Brand name

Transiderm-Nitro

Active ingredient

Glyceryl trinitrate

Schedule

S4

 

Consumer medicine information (CMI) leaflet

Please read this leaflet carefully before you start using Transiderm-Nitro.

What is in this leaflet

This leaflet answers some common questions about Transiderm-Nitro.

The information in this leaflet was last updated on the date listed on the final page. More recent information on the medicine may be available.

You should ensure that you speak to your pharmacist or doctor to obtain the most up to date information on the medicine. You can also download the most up to date leaflet from www.novartis.com.au. Those updates may contain important information about the medicine and its use of which you should be aware.

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 has weighed the risks of you using Transiderm-Nitro against the benefits they expect it will provide.

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

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

What Transiderm-Nitro is used for

Transiderm-Nitro is used to prevent angina. It is an adhesive patch that delivers a medicine called glyceryl trinitrate through the skin and into the bloodstream.

Transiderm-Nitro belongs to a group of medicines called nitrates. Nitrates work by widening blood vessels, letting more blood and oxygen reach the heart.

Ask your doctor if you have any questions about why this medicine has been prescribed for you. Your doctor may have prescribed it for another purpose.

There is not enough information to recommend this medicine for children.

Before you use Transiderm-Nitro

When you must not use it

Do not use Transiderm-Nitro if you are allergic to:

  • glyceryl trinitrate (the active ingredient) or any of the other ingredients of Transiderm-Nitro listed at the end of this leaflet
  • any other medicine or food containing nitrates or nitrites

Some of the symptoms of an allergic reaction may include shortness of breath, wheezing or difficulty breathing; swelling of the face, lips, tongue or other parts of the body; rash, itching or hives on the skin.

Do not use Transiderm-Nitro if you have any of the following medical conditions:

  • severe anaemia
  • glaucoma or raised pressure in the eye from any cause
  • increased pressure in the head from any cause (stroke, tumour, head injury)
  • disease in the valves of your heart or inflammation of your heart

If you are not sure whether any of the above medical conditions apply to you, your doctor can advise you.

Do not use Transiderm-Nitro if you are taking Viagra or Levitra, medicines used for impotence in men. If you use Viagra or Levitra together with Transiderm-Nitro, your blood pressure may fall to a dangerously low level.

Do not use Transiderm-Nitro after the expiry date printed on the pack or if the packaging is torn or shows signs of tampering. In that case, return it to your pharmacist.

Before you start to use it

Tell your doctor if you have any of the following medical conditions:

  • recent heart attack, stroke or head injury
  • heart problems or a blood vessel disorder other than angina
  • low blood pressure
  • problems with your lungs
  • problems with your liver

Your doctor may want to take special precautions if you have any of the above conditions.

Tell your doctor if you are pregnant or breast-feeding. This medicine may affect your baby if you use it while you are pregnant or breast-feeding. Your doctor can discuss with you the risks and benefits involved.

Tell your doctor if you are allergic to any other medicines, foods, dyes or preservatives. Your doctor will want to know if you are prone to allergies.

Taking other medicines

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

Some medicines and Transiderm-Nitro may interfere with each other.

These include:

  • Viagra or Levitra, medicines used for impotence in men
  • other medicines for angina
  • medicines for high blood pressure or heart problems
  • diuretic medicines, also called water or fluid tablets
  • some medicines used to treat depression called tricyclic antidepressants
  • medicines for mental disorders
  • dihydroergotamine, a medicine for migraine
  • acetylsalicylic acid (aspirin)
  • medicines used to treat inflammation called non-steroidal anti-inflammatory drugs (NSAIDs)

You may need to take different amounts of your medicines or to take different medicines while you are using Transiderm-Nitro. Your doctor and pharmacist have more information.

If you have not told your doctor about any of these things, tell him/her before you start using this medicine.

How to use Transiderm-Nitro

Follow all directions given to you by your doctor and pharmacist carefully. They may differ from the information contained in this leaflet.

If you do not understand the instructions on the label, ask your doctor or pharmacist for help.

How much to use

Your doctor may start your treatment with one Transiderm-Nitro 25 patch each day for several days and then change to the larger Transiderm-Nitro 50 patch. The usual dose for most people is one Transiderm-Nitro 50 patch each day, although some people may need more or less.

When to use it

You will normally apply a patch once each day, usually in the morning.

Your doctor will likely ask you to take the patch off for 8 to 12 hours out of every 24 hours (e.g. take it off at bedtime and put a new one on when you wake up in the morning). This "patch off" period may make the medicine more effective.

How to apply the patch

Follow these steps to apply a patch to your skin.

  1. Choose an area of skin:
  • The best place is your chest but you may use any area except below your knees or elbows.
  • Choose an area of skin that has no sores, cuts or rashes.
  • If the skin is very hairy, you can clip the hair (do not shave it) so that the patch sticks well and won't be hard to remove.
  • Use a different area of skin each day. Wait several days before using the same area again.
  1. Make sure the skin is clean, cool, dry and free from creams, lotions or oils:
  • You may need to wash the area with soap and water and dry it completely.
  • If your skin is very oily, you can use methylated spirits to clean it, then dry it completely.
  • After a shower or bath, wait a few minutes before applying the patch to make sure your skin is completely cool and dry.
  • You may use body lotion or bath oil after the patch has been applied.
  1. Open the sachet that contains the patch:
  • Tear open the sachet at the notch and remove the patch.
  • Do not use scissors because you may accidentally cut the patch and the medicine may leak out.
  • Any air bubbles on the patch are not important.
  1. Remove the protective liner from the sticky side of the patch:
  • Pick up the patch with the tab upwards and the white liner facing you.
  • Firmly bend the tab forward with your thumb.
  • Use both thumbs to peel off the protective liner, starting at the tab. Do not touch the sticky surface of the patch.
  • Throw the liner away.
  1. Apply the patch to the skin as soon as you have removed the liner:
  • Press the sticky side of the patch to the area of skin you have chosen so that the tan coloured side is showing.
  • Press the patch firmly in place with the palm of your hand for 10 to 20 seconds. The patch needs the pressure and heat of your hand to stick well.
  • Check that the patch has stuck by running your finger around the edge. Do not try to lift the edge of the patch to see if it has stuck.

How to remove the patch

  • Use the little tab to pull the patch away from your skin.
  • Fold the old patch in half with the sticky side inwards.
  • Throw the old patch away safely out of the reach of children. The patch still contains some leftover medicine that could harm a child.
  • Remove any stickiness from the skin with soap and water or methylated spirits.

If the patch falls off

  • Throw the patch away.
  • Apply a new patch to a different area of clean, dry skin.
  • Change the patch at the next time that you would normally change it.

Bathing, swimming, showering or exercising will usually not affect the patch if it has been correctly applied.

If the patch irritates your skin

  • Check that water has not gotten under the patch. If it has, remove the patch and apply a new one to a different area.
  • Try a less sensitive area, for example your upper arm.
  • Use a new area of skin for each patch. Do not use the same area of skin for at least a week.
  • You can use a mild cream on the sore area once the patch has been removed.

How long to use it

Use Transiderm-Nitro for as long as your doctor tells you to. Otherwise, you may not get relief from your attacks of angina. Try not to miss any doses and use the medicine even if you feel well.

Do not stop using Transiderm-Nitro suddenly. Stopping this medicine suddenly may bring on attacks of angina, especially if you have been using it for several weeks or more. If you want to stop using it, your doctor will tell you how to do it gradually (e.g. over 4 to 6 weeks) to avoid making your angina worse.

If you forget to use it

If it is almost time to apply your next patch, skip the one you missed and apply the next patch when you are meant to.

Otherwise, apply the patch as soon as you remember, respecting any prescribed patch-off period and then go back to using it as you would normally.

Do not use a double dose to make up for the one that you missed. This may increase the chance of you getting an unwanted side effect.

If you have trouble remembering when to use your medicine, ask your pharmacist for some hints.

If you use too much (overdose)

Remove the patch. Immediately telephone your doctor or Poisons Information Centre (telephone 13 11 26), or go to Accident and Emergency at your nearest hospital, if you think that you or anyone else may have used too much Transiderm-Nitro. Do this even if there are no signs of discomfort or poisoning. Keep telephone numbers for these places handy.

Some of the symptoms of an overdose may include fast heartbeat, dizziness, light-headedness or fainting, especially when you get up quickly from a sitting or lying position. This is because your blood pressure is too low.

While you are using Transiderm-Nitro

Things you must do

Tell your doctor if you continue to have angina attacks or if they become more frequent or severe while you are using Transiderm-Nitro. Keep a record of the number of attacks, when they happen and the possible cause (for example, during exercise or during the period when the patch is off). This helps your doctor give you the best possible treatment.

If you become pregnant while taking Transiderm-Nitro, tell your doctor immediately. You doctor can discuss with you the risks of using it while you are pregnant.

If you are about to be started on any new medicine, remind your doctor and pharmacist that you are using Transiderm-Nitro.

Tell any other doctor, dentist or pharmacist who treats you that you are using Transiderm-Nitro.

Things you must not do

Do not use Transiderm-Nitro to relieve an attack of angina. This medicine will not relieve an attack of angina once it has started. Your doctor will have given you other tablets or spray to use when you get attacks of angina.

Do not give this medicine to anyone else, even if their condition seems similar to yours.

Do not take it to treat any other complaints unless your doctor tells you to.

Things to be careful of

If you are using more than one patch, be careful to remember where you placed it and when you put it on. Some people using Transiderm Nitro will be using other medicines that are also patches. Sometimes keeping track of these patches can be confusing. Be sure to pay particular attention to where you put each patch and what time each patch should be removed.

Be careful driving, operating machinery or doing jobs that require you to be alert until you know how Transiderm-Nitro affects you. This medicine may cause dizziness, fainting or blurred vision in some people, especially when you first start to use it or if the dose is increased.

Be careful when drinking alcohol while you are using Transiderm-Nitro. Your blood pressure may drop, making you feel dizzy or faint.

If this medicine makes you feel light-headed, dizzy or faint, be careful when getting up from a sitting or lying position. You can usually prevent these symptoms by getting up slowly and flexing leg muscles and toes to get the blood flowing. When getting out of bed, dangle your legs over the side for a minute or two before standing up. Use extra care when exercising, driving or standing for long periods, especially in hot weather.

Be careful not to overdo physical activities when you start using Transiderm-Nitro. You may feel better when you start using it, but you will need time to improve your physical fitness.

Side effects

Tell your doctor or pharmacist as soon as possible if you do not feel well while you are using Transiderm-Nitro.

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

If you are over 65 years old, you should be especially careful and report any side effects promptly to your doctor. As people grow older, they are more likely to get side effects from medicines.

Do not be alarmed by these lists of possible side effects. You may not experience any of them.

Ask your doctor or pharmacist to answer any questions you may have.

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

  • headache, which usually goes away after taking a mild pain reliever such as paracetamol
  • dizziness or lightheadedness, sometimes accompanied by a fast heart beat, especially when getting up suddenly
  • itching or burning under the patch
  • reddening of the skin after the patch has been taken off
  • flushing of the face
  • nausea (feeling sick) or vomiting
  • palpitations: abnormal feeling of heart beat.

Tell your doctor immediately or go to Accident and Emergency at your nearest hospital if you notice any of the following:

  • 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 troubled breathing
  • severe redness, swelling or blisters under the patch
  • chest pains that are not relieved by taking your usual medicine for treating an angina attack
  • severe dizziness or fainting
  • severe or persistent headache

Tell your doctor if you notice anything else that is making you feel unwell. Some people may have other side effects not yet known or mentioned in this leaflet.

After using Transiderm-Nitro

Storage

  • Keep your medicine in the original container until it is time to use it.
  • Store it in a cool dry place but not in the freezer. Store below 30°C. Do not store Transiderm-Nitro or any other medicine in the bathroom or near a sink.
  • Do not leave it in the car or on window sills.

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

Disposal

  • Fold used patches in half with the sticky side inwards.
  • Dispose of the patches where children cannot reach them.

Used patches still contain some glyceryl trinitrate that could harm a child.

If your doctor tells you to stop using Transiderm-Nitro or the expiry date has passed, ask your pharmacist what to do with any medicine that is left over.

Product description

What it looks like

Transiderm-Nitro 25 is a tan coloured oval patch marked CG DOD; 30 patches per carton.

Transiderm-Nitro 50 is a tan coloured oblong patch marked CG DPD; 30 patches per carton.

Transiderm-Nitro patches are made up of five layers:

  • a waterproof tan coloured backing film
  • a drug reservoir containing glyceryl trinitrate
  • a membrane which controls the release of glyceryl trinitrate into the skin
  • an adhesive (sticky) layer
  • a white to off-white protective liner which is removed before using the patch.

Ingredients

Transiderm-Nitro 25 patches contain 25 mg glyceryl trinitrate and have a contact surface of 10 square cm. that releases approximately 5 mg glyceryl trinitrate in 24 hours.

Transiderm-Nitro 50 patches contain 50 mg glyceryl trinitrate and have a contact surface of 20 square cm. that releases approximately 10 mg glyceryl trinitrate in 24 hours.

The patches also contain:

  • lactose
  • dimethicone
  • silica colloidal anhydrous
  • ethylene va copolymer
  • silicon medical adhesive

Sponsor

Transiderm-Nitro is supplied in Australia by:

NOVARTIS Pharmaceuticals Australia Pty Limited
ABN 18 004 244 160
54 Waterloo Road
North Ryde NSW 2113
Telephone 1 800 671 203

®= Registered Trademark

This leaflet was prepared in July 2019.

Australian Registration Number.

Transiderm-Nitro 25 AUST R 17107

Transiderm-Nitro 50 AUST R 17105

(CMI tdn300719c based on PI tdn300719i)

Published by MIMS October 2019

BRAND INFORMATION

Brand name

Transiderm-Nitro

Active ingredient

Glyceryl trinitrate

Schedule

S4

 

1 Name of Medicine

Glyceryl trinitrate.

2 Qualitative and Quantitative Composition

Transiderm-Nitro is a transdermal therapeutic system for application to intact skin.
Transiderm-Nitro is a flat self-contained multilayer unit designed to provide continuous controlled release of glyceryl trinitrate through a semipermeable membrane for the recommended application period. In cases where the permeability of the skin is excessive, drug release is limited by the release membrane.
Transiderm-Nitro is composed of four layers. Proceeding from the visible outer surface towards the inner surface which adheres to the skin, these layers are:
1) an impermeable tan-coloured backing film;
2) a drug reservoir containing glyceryl trinitrate;
3) a semi-permeable release membrane that controls the release of glyceryl trinitrate to the skin;
4) a layer of silicone adhesive;
5) a white to off-white coloured protective liner which is removed prior to use.
The following two systems are available (see Table 1).
For the full list of excipients, see Section 6.1 List of Excipients.

3 Pharmaceutical Form

Transdermal drug delivery system (patch).
Transiderm-Nitro 25 contains glyceryl trinitrate 25 mg and has a release rate of 0.2 mg/hour. The tan coloured backing film is marked with the letters "CG DOD".
Transiderm-Nitro 50 contains glyceryl trinitrate 50 mg and has a release rate of 0.4 mg/hour. The tan coloured backing film is marked with the letters "CG DPD".

4 Clinical Particulars

4.1 Therapeutic Indications

Transiderm-Nitro is indicated for the prevention of chronic stable angina pectoris due to coronary artery disease.

4.2 Dose and Method of Administration

Dosing regimen.

The response to nitrate preparations varies from patient to patient; the lowest effective dose should be prescribed.
Therapy should be initiated with the application of one Transiderm-Nitro 25 every 24 hours. According to the clinical response, the daily dose may be titrated upwards as follows:
one Transiderm-Nitro 50 (normal maintenance dose);
one Transiderm-Nitro 25 + one Transiderm-Nitro 50;
two Transiderm-Nitro 50.

Tolerance.

Development of tolerance or attenuation of therapeutic effects commonly occurs with prolonged or frequent administration of long-term nitrates, including Transiderm-Nitro or other transdermal systems. A patch-off period of 8-12 hours, usually at night, every 24 hours is recommended to overcome tolerance. Clinical trials have shown that in the majority of patients intermittent therapy is more effective than continuous administration. Continuous application of Transiderm-Nitro may be appropriate for patients in whom long-term clinical responsiveness can be judged reliably.

Application.

The Transiderm-Nitro system should be applied to intact, clean dry skin which is free of hair (clipping may be necessary). The system must be changed daily to minimise skin irritation and the application site should be changed regularly to prevent local irritation. A number of days should elapse before using the same site again. Suitable application sites include the chest, inner side of the upper arm or shoulders. Transiderm-Nitro should not be applied to the distal parts of the extremities.

4.3 Contraindications

Transiderm-Nitro should not be prescribed to patients:
who are hypersensitive or intolerant to organic nitrate compounds;
who are known or suspected to be hypersensitive to components of the patch;
have acute circulatory failure associated with marked hypotension (shock, states of collapse);
have marked anaemia;
have conditions associated with elevated intracranial pressure;
have increased intraocular pressure e.g. glaucoma;
have myocardial insufficiency due to obstruction (e.g. in the presence of aortic or mitral stenosis or of constrictive pericarditis).
Concomitant use of Transiderm-Nitro and phosphodiesterase type 5 (PDE5) inhibitors such as sildenafil (Viagra) is contraindicated because PDE5 inhibitors may amplify the vasodilatory effects of Transiderm-Nitro, resulting in severe hypotension.

4.4 Special Warnings and Precautions for Use

Defibrillation/ diathermy.

The Transiderm-Nitro patch contains an aluminium layer. Therefore the patch must be removed before applying magnetic or electrical fields to the body during procedures such as magnetic resonance imaging (MRI), or attempting cardioversion or DC defibrillation, as well as before applying diathermy treatment.

Myocardial infarction/ acute heart failure.

In cases of recent myocardial infarction or acute heart failure, treatment with Transiderm-Nitro should be carried out cautiously under strict medical surveillance and/or haemodynamic monitoring.

Hypoxaemia.

Glyceryl trinitrate should not be used in patients with arterial hypoxaemia due to severe anaemia, because in such patients the biotransformation of the drug is reduced (see Section 5.2 Pharmacokinetic Properties; Section 4.3 Contraindications). Similarly, caution is called for in patients with hypoxaemia and a ventilation/ perfusion imbalance due to lung disease, ischaemic heart failure or cerebral ischaemia. Patients with angina pectoris, myocardial infarction, or cerebral ischaemia frequently suffer from abnormalities of the small airways (especially alveolar hypoxia). Under these circumstances vasoconstriction occurs within the lung to shift perfusion from areas of alveolar hypoxia to better ventilated regions of the lung. As a potent vasodilator, glyceryl trinitrate could reverse this protective vasoconstriction and thus result in increased perfusion of poorly ventilated areas, worsening of the ventilation/ perfusion imbalance, and a further decrease in the arterial partial pressure of oxygen.

Abrupt withdrawal.

Abrupt withdrawal of the drug following chronic use may be associated with withdrawal reactions including an increase in the frequency of anginal attacks. The withdrawal may also exacerbate Raynaud's phenomenon in susceptible patients.
As with other nitrate preparations, when transferring the patient on long-term therapy to another form of medication, glyceryl trinitrate should be gradually withdrawn over a period of 4 to 6 weeks and overlapping treatment started.

Acute anginal attack.

Transiderm-Nitro is not suitable for the treatment of acute attacks of angina pectoris. To arrest such attacks, the additional use of rapid-acting nitrate preparations is indicated.

Tolerance to sublingual glyceryl trinitrate.

As tolerance to glyceryl trinitrate patches develops (see Section 4.2 Dose and Method of Administration), the effect of sublingual glyceryl trinitrate on exercise tolerance may be partially diminished. This should also be borne in mind when sublingual glyceryl trinitrate tablets are used to treat acute anginal attacks.

Increased angina.

In some controlled clinical trials of glyceryl trinitrate patch therapy in which a nitrate-free interval was used, a minority of patients experienced an increase in the frequency of angina attacks occurring during the patch-off period. If such symptoms do develop in a patient, the use of concomitant anti-anginal therapy (e.g. beta blockers, calcium channel antagonists) is desirable.

Hypertrophic cardiomyopathy.

Nitrate therapy may aggravate the angina caused by hypertrophic cardiomyopathy.

Hypotension.

Severe hypotension, particularly with upright posture, may occur with even small doses of glyceryl trinitrate. This drug should, therefore, be used with caution in patients who may be volume depleted or who, for whatever reason, are already hypotensive. Hypotension induced by glyceryl trinitrate may be accompanied by paradoxical bradycardia and increased angina pectoris.
Symptoms of hypotension, particularly of the orthostatic type, such as faintness, weakness or dizziness, may be due to overdosage. When these symptoms occur, the dosage should be reduced or the product discontinued.

Use in elderly.

No data available.

Paediatric use.

There are insufficient data on the use of Transiderm-Nitro in children, therefore, it is not recommended in this patient population.

Effects on laboratory tests.

No data available.

4.5 Interactions with Other Medicines and Other Forms of Interactions

Concomitant use of alcohol may enhance the vascular effects of glyceryl trinitrate. Concomitant treatment with other vasodilators or antihypertensives (e.g. PDE5 inhibitors such as sildenafil (Viagra), calcium antagonists, beta-blockers, ACE-inhibitors, diuretics), tricyclic antidepressants, major tranquillisers and dihydroergotamine may potentiate the blood pressure lowering effects of glyceryl trinitrate, therefore, adjustment of dosage may be required in these circumstances.
There is a possibility that the ingestion of acetylsalicylic acid and non-steroidal anti-inflammatory drugs might diminish the therapeutic response to Transiderm-Nitro.

4.6 Fertility, Pregnancy and Lactation

Effects on fertility.

No data available.
(Category B2)
The safety of Transiderm-Nitro in pregnancy has not been established. Therefore, Transiderm-Nitro should not be administered to women who are or who may become pregnant unless, in the judgement of the physician, the probable clinical benefits outweigh the possible risks.
No information is available on the secretion of glyceryl trinitrate in breast milk, therefore, Transiderm-Nitro is not recommended in nursing mothers unless in the judgement of the physician, the probable clinical benefits outweigh the possible risks.

4.7 Effects on Ability to Drive and Use Machines

Transiderm-Nitro, especially at the start of treatment, may impair the patient's reactions either when driving a vehicle or operating machinery (see Section 4.8 Adverse Effects (Undesirable Effects), Cardiovascular disorders, Nervous system disorders).

4.8 Adverse Effects (Undesirable Effects)

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.
The adverse effects listed by MedDRA system organ class (SOC). Within each system organ class the adverse drug reactions are ranked by frequency, with the most frequent first. Within each frequency grouping, adverse drug reactions are ranked in order of decreasing seriousness. In addition, the corresponding frequency category, using the following convention (CIOMS III: very common: ≥ 1/10; common: ≥ 1/100 and < 1/10; uncommon: ≥ 1/1,000 and < 1/100; rare: ≥ 1/10,000 and < 1/1,000; very rare: < 1/10,000, including isolated reports.

Nervous system disorders.

Very common: headache. Rare: dizziness.

Cardiac disorders.

Rare: tachycardia.

Vascular disorders.

Rare: orthostatic hypotension, flushing.

Gastrointestinal disorders.

Very common: nausea, vomiting.

Skin and subcutaneous tissue disorders.

Common: dermatitis contact.

General disorders and administration site conditions.

Common: application site erythema, pruritus, burning, irritation.

Investigations.

Heart rate increase.
Like other nitrate preparations, Transiderm-Nitro may frequently give rise to headache, which is due to cerebral vasodilatation and is dose-dependent. Such headaches often regress after a few days despite the maintenance of therapy. The possibility of persistent headaches during intermittent therapy should be considered. When they present as a problem, they should be treated with mild analgesics. In cases where the headaches are unresponsive to treatment, the dosage of glyceryl trinitrate should be reduced or use of the product discontinued.
Upon removal of the patch, any slight reddening of the skin will usually disappear within a few hours. The application site should be changed regularly to prevent local irritation.
A slight reflex-induced increase in heart rate can be avoided by resorting, if necessary, to combined treatment with a beta-blocker.
The following adverse drug reactions have been derived from post-marketing experience with Nitroderm TTS via spontaneous case reports and literature cases. Because these reactions are reported voluntarily from a population of uncertain size, it is not possible to reliably estimate their frequency which is therefore categorized as not known. Within each system organ class, adverse drug reactions are presented in order of decreasing seriousness.

Cardiac disorders.

Palpitation.

Skin and subcutaneous tissue disorders.

Rash generalized.

4.9 Overdose

For information on the management of overdose, contact the Poisons Information Centre on 13 11 26 (Australia).
High doses of glyceryl trinitrate may lead to severe hypotension and reflex tachycardia or to collapse and syncope. Methaemoglobinaemia has also been reported following accidental overdosage of glyceryl trinitrate.
However, with Transiderm-Nitro, the release membrane will reduce the likelihood of overdosage occurring. The nitrate effect of Transiderm-Nitro can be rapidly terminated simply by removing the system(s). Hypotension or any signs of collapse that may occur can be treated by elevating the patient's legs and, if necessary, bandaging them.

5 Pharmacological Properties

5.1 Pharmacodynamic Properties

Pharmacotherapeutic group, ATC code.

Vasodilators used in cardiac diseases, ATC code: C01DA02.

Mechanism of action.

Glyceryl trinitrate relaxes smooth muscle throughout the body. In the vascular system it acts chiefly on the systemic veins and the large coronary arteries, with more predominant effects on the former.
In angina pectoris a fundamental mechanism of action of glyceryl trinitrate is primarily based on an increase in venous capacitance (venous pooling) leading to a decreased return of blood to the heart. Due to this phenomenon, left-ventricular end-diastolic pressure (preload) and hence filling volume diminishes, resulting in a decreased myocardial oxygen requirement at rest and especially during exercise, with an improvement in exercise capacity in patients with angina pectoris.
In the coronary arterial circulation, glyceryl trinitrate dilates both extramural conductance and small resistance vessels. The drug appears to cause a redistribution of coronary blood flow to the ischaemic subendocardium by selectively dilating large epicardial vessels. It is also capable of dilating atherosclerotic stenoses where the atheroma is eccentrically located.
Glyceryl trinitrate also exerts a dose-dependent dilating effect on the arteriolar vascular bed, as a result of which systemic vascular resistance (afterload) and left-ventricular systolic wall tension decrease, leading to a reduction in myocardial oxygen consumption.

Clinical trials.

Some well-controlled clinical trials using exercise tolerance testing have shown maintenance of effectiveness when patches are worn continuously, however, the majority of such controlled trials have shown the development of tolerance (i.e. attenuation of effect as measured by exercise testing) within the first day. As might be expected on pharmacological grounds, tolerance is also observed with high transdermal doses greater than 4 mg/hour.
Efficacy of organic nitrates is restored after a nitrate-free interval. The shortest drug-free interval sufficient to restore response has not been defined. Intervals of 8 to 12 hours are known to be sufficient to restore response. When administered according to an intermittent regimen, doses of Transiderm-Nitro which deliver 0.4-0.8 mg/hr (20-40 cm2) have resulted in increased exercise capacity for 8 to 12 hours.
Controlled clinical trial data suggest that the intermittent use of nitrates may be associated with a decrease in exercise tolerance compared with placebo during the last part of the nitrate-free interval. The clinical relevance of this observation is unknown; however, the possibility of increased angina in the nitrate-free interval should be considered (see Section 4.4 Special Warnings and Precautions for Use).

5.2 Pharmacokinetic Properties

Transiderm-Nitro.

Absorption.

Following the single application of Transiderm-Nitro, the plasma concentration of glyceryl trinitrate reaches a plateau within 2 hours which is maintained for the recommended application period. This steady-state concentration of glyceryl trinitrate shows a linear dependence on the size of the system's contact surface with the skin.
Replacement of the system during the steady-state phase does not cause a significant fluctuation in plasma concentrations. Removal of the system from the skin causes plasma concentrations of glyceryl trinitrate to fall to below detectable levels within one hour. After repeated application of Transiderm-Nitro no accumulation occurs.

Glyceryl trinitrate.

Metabolism.

The volume of distribution of glyceryl trinitrate is about 3 L/kg and glyceryl trinitrate is cleared from this volume at extremely rapid rates, with a resulting serum half-life of about 3 minutes. The observed clearance rates (close to 1 L/kg/min) greatly exceed hepatic blood flow. Glyceryl trinitrate is rapidly metabolised by a glutathione-dependent organic nitrate reductase in the liver. In addition, and probably more importantly, studies with human erythrocytes in vitro have shown that the erythrocyte is also a site of biotransformation of glyceryl trinitrate by a sulphhydryl-dependent enzymatic process and by an interaction with reduced haemoglobin. The amount of reduced haemoglobin in human erythrocytes seems to play a major role in their metabolic activity, and caution should therefore be exercised in cases of anaemia. In in vitro studies it has been found that extrahepatic vascular tissues (femoral vein, inferior vena cava, aorta) likewise play an important role in glyceryl trinitrate metabolism, a finding which is consistent with the large systemic clearance seen with nitrates. It has also been shown in vitro that the biotransformation of glyceryl trinitrate occurs concurrently with vascular smooth muscle relaxation; this observation is consistent with the hypothesis that glyceryl trinitrate biotransformation is involved in the mechanism of glyceryl trinitrate-induced vasodilatation.

5.3 Preclinical Safety Data

Genotoxicity.

No data available.

Carcinogenicity.

No data available.

6 Pharmaceutical Particulars

6.1 List of Excipients

Lactose, dimethicone, silica colloidal anhydrous, ethylene va copolymer and silicon medical adhesive.

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 30°C.

6.5 Nature and Contents of Container

Transiderm-Nitro 25 contains glyceryl trinitrate 25 mg and has a release rate of 0.2 mg/hour. The tan coloured backing film is marked with the letters "CG DOD".
Transiderm-Nitro 50 contains glyceryl trinitrate 50 mg and has a release rate of 0.4 mg/hour. The tan coloured backing film is marked with the letters "CG DPD".
All systems are supplied in cartons containing 10 or 30 individually pouched units.

6.6 Special Precautions for Disposal

In Australia, any unused medicine or waste material should be disposed of by taking to your local pharmacy.
Patients should be warned not to cut the patches and to dispose of them carefully as they still contain glyceryl trinitrate after use. Transiderm-Nitro should be kept out of the reach of children both before and after use.

6.7 Physicochemical Properties

Glyceryl trinitrate is an organic nitrate derivative with the chemical name 1,2,3-propanetriol trinitrate.

Chemical structure.


CAS number.

The CAS registry number for glyceryl trinitrate is 55-63-0.

7 Medicine Schedule (Poisons Standard)

Schedule 4 - Prescription Only Medicine.

Summary Table of Changes