Consumer medicine information

Minitran Transdermal Delivery System

Glyceryl trinitrate

BRAND INFORMATION

Brand name

Minitran

Active ingredient

Glyceryl trinitrate

Schedule

S4

 

Consumer medicine information (CMI) leaflet

Please read this leaflet carefully before you start using Minitran Transdermal Delivery System.

SUMMARY CMI

Minitran™

Consumer Medicine Information (CMI) summary

The full CMI on the next page has more details. If you are worried about using this medicine, speak to your doctor or pharmacist.

1. Why am I using Minitran?

Minitran contains the active ingredient glyceryl trinitrate. Minitran is used to help prevent angina attacks (chest pain).

For more information, see Section 1. Why am I using Minitran? in the full CMI.

2. What should I know before I use Minitran?

Do not use if you have ever had an allergic reaction to Minitran or any of the ingredients listed at the end of the CMI, or other medicines or foods containing nitrates or nitrites.

Talk to your doctor if you have any other medical conditions, take any other medicines, or are pregnant or plan to become pregnant or are breastfeeding.

For more information, see Section 2. What should I know before I use Minitran? in the full CMI.

3. What if I am taking other medicines?

Some medicines may interfere with Minitran and affect how it works.

A list of these medicines is in Section 3. What if I am taking other medicines? in the full CMI.

4. How do I use Minitran?

Apply a new patch at the same time every day, usually in the morning. Remove the patch at bedtime.

More instructions can be found in Section 4. How do I use Minitran? in the full CMI.

5. What should I know while using Minitran?

Things you should do
  • Remind any doctor, dentist or pharmacist you visit that you are using Minitran.
  • Tell your doctor if you continue to have angina attacks or if they become more frequent.
  • If you become pregnant while using Minitran, tell your doctor immediately.
Things you should not do
  • Do not stop using this medicine suddenly as this may bring on angina attacks.
  • Do not use Minitran to relieve an attack of angina.
Driving or using machines
  • Be careful if you are driving or operating machinery until you know how Minitran affects you.

Minitran may lower your blood pressure and make you feel dizzy or lightheaded.

Drinking alcohol
  • Drinking alcohol while using Minitran is not recommended. Alcohol may increase the blood pressure lowering effects of Minitran.
Looking after your medicine
  • Store below 25°C in a cool dry place. Do not keep Minitran patches in the fridge.

For more information, see Section 5. What should I know while using Minitran? in the full CMI.

6. Are there any side effects?

Common side effects include headaches, reddening and itchiness of the skin after removing the patch, dizziness, light headedness, low blood pressure, hot flushes, nausea, and vomiting.

Serious side effects include allergic reaction, 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 headache. Seek immediate medical assistance if these side effects occur.

For more information, including what to do if you have any side effects, see Section 6. Are there any side effects? in the full CMI.



FULL CMI

Minitran™

Active ingredient(s): Glyceryl trinitrate


Consumer Medicine Information (CMI)

This leaflet provides important information about using Minitran. You should also speak to your doctor or pharmacist if you would like further information or if you have any concerns or questions about using Minitran.

Where to find information in this leaflet:

1. Why am I using Minitran?
2. What should I know before I use Minitran?
3. What if I am taking other medicines?
4. How do I use Minitran?
5. What should I know while using Minitran?
6. Are there any side effects?
7. Product details

1. Why am I using Minitran?

Minitran contains the active ingredient glyceryl trinitrate.

Minitran is an adhesive patch which is applied to the skin. It contains the active ingredient glyceryl trinitrate. Minitran is belongs to a group of medicines called nitrates. When a Minitran patch is placed on the skin, glyceryl trinitrate passes slowly through the skin and into the blood stream. The glyceryl trinitrate in Minitran enters your body in a controlled way, a little at a time. The glyceryl trinitrate causes the blood vessels to relax and increases the supply of blood and oxygen to the heart reducing the likeliness of having an angina attack.

Minitran is used to help prevent angina attacks (chest pain).

2. What should I know before I use Minitran?

Warnings

Do not use Minitran if:

  • you are allergic to glyceryl trinitrate, or any of the ingredients listed at the end of this leaflet. Always check the ingredients to make sure you can use this medicine.
  • you are allergic to other medicines or foods containing nitrates or nitrites.
  • you have any of the following medical conditions:
    - severe anaemia (low iron levels in your blood or low red blood cell count)
    - an eye disease called closed angle glaucoma or raised pressure in the eye from any cause
    - increased pressure in the head from any cause (such as stroke, tumour, head injury)
    - disease in your heart valves or inflammation of your heart.
    - you are taking medicines for erectile dysfunction, such as sildenafil, vardenafil or tadalafil
    - you are taking medicines for treating high blood pressure in your lungs such as riociguat, sildenafil, or tadalafil. If you use these medicines together with Minitran, your blood pressure may fall to a dangerously low level.
    - you experience lightheadedness, dizziness or fainting when going from lying or sitting to standing up (postural hypotension).

Check with your doctor if you:

  • have allergies to any other medicines, foods, preservatives, or dyes.
  • have any other medical conditions including
    - low blood pressure
    - heart problems or blood vessel disorder other than angina
    - low oxygen levels in your blood.

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

During treatment, you may be at risk of developing certain side effects. It is important you understand these risks and how to monitor for them. See additional information under Section 6. Are there any side effects?

Pregnancy and breastfeeding

Check with your doctor if you are pregnant or intend to become pregnant.

The safety of Minitran in pregnancy has not been established.

Talk to your doctor if you are breastfeeding or intend to breastfeed.

It is unknown whether Minitran passes into breast milk.

Use in the Elderly

Severe low blood pressure, particularly when standing upright, may occur with even small doses of Minitran, particularly in the elderly. This may increase the risk of a fall.

Use in Children

Minitran is not recommended for use in children.

3. What if I am taking other medicines?

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

Some medicines may interfere with Minitran and affect how it works.

Medicines that may increase the effect of Minitran include:

  • other medicines for angina
  • medicines for high blood pressure or heart problems such as:
    - diuretics, also called water or fluid tablets
    - calcium channel blockers
    - beta blockers
    - ACE inhibitors
  • medicines used to treat depression called tricyclic antidepressants
  • medicines for mental disorders
  • dihydroergotamine, a medicine for migraine.

These medicines may increase the blood pressure lowering effects of Minitran, which may cause dizziness, lightheadness or fainting.

Do not use medicines for erectile dysfunction, such as sildenafil, vardenafil or tadalafil or medicines for treating high blood pressure in your lungs such as riociguat, sildenafil, or tadalafil at the same time as Minitran.

If you use these medicines together with Minitran, your blood pressure may fall to a dangerously low level.

Check with your doctor or pharmacist if you are not sure about what medicines, vitamins or supplements you are taking and if these affect Minitran.

4. How do I use Minitran?

How much to use

Your doctor will prescribe the correct dose for you.

Your doctor may start your treatment with one Minitran 5 patch every day and then change to a larger Minitran 10 or Minitran 15 patch if required.

When to use Minitran

Follow the instructions provided and use Minitran until your doctor tells you to stop.

Apply a new patch at the same time every day, usually in the morning.

Your doctor will likely ask you to take the patch off for 8 to 12 hours of every 24 hours (e.g., take the patch off at bedtime and put a new one on when you wake up in the morning).

This patch-free period helps maintain the effectiveness of the medicine.

Where to apply the Minitran patch

  • Apply the Minitran patch to the chest, shoulders, upper arm or back. Do not apply Minitran to the lower arm or lower leg.
  • Choose an area of skin that is clean, dry and free of irritation or cuts. The skin should be a non-hairy area so that the hair will not prevent direct contact of the patch with the skin. If hair is likely to interfere with adhesion of the patch, the area may be clipped but not shaved.
  • Use a different skin site each time you use a new Minitran patch. Wait several days before you use the same area again.

How to apply the Minitran patch

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 thoroughly.
  • After a shower or bath, wait a few minutes before applying the patch to make sure your skin is completely cool and dry.

Open the sachet that contains the patch:

  • Start at the notched corner.
  • Tear pouch along the dotted line.
  • Do not use scissors because you may accidentally cut the patch and the medicine may leak out.

Remove the protective liner from the sticky side of the patch:

  • Bend the patch so that the tab on the liner pops up.
  • Hold the tab to peel off the liner.
  • Apply sticky side of the patch to the upper arm or chest.
  • Remove and discard the other piece of liner.
  • Press patch firmly into place.

If a patch falls off

If a patch does not stick or falls off, use a new patch on a different area of skin.

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

Do not re-use a patch once it has been removed from the skin.

You can bathe, shower and swim as normal when wearing a Minitran patch.

After removing a patch

Discard the patch in a manner that prevents accidental ingestion or application by curious children or pets. After normal use, there is still enough medicine in the patch to cause serious harm if they are accidentally eaten or applied.

If you forget to use Minitran

Minitran should be used regularly at the same time each day. If you miss applying your patch at the usual time, and 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 Minitran as you would normally.

If you forget to remove the patch at the scheduled time, just remove it as soon as possible and continue to follow your original schedule.

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

Do not use 2 patches to make up for the one that you missed.

This may increase the chance of you getting unwanted side effects.

If you use too much Minitran

If you think that you have used too much Minitran, you may need urgent medical attention.

You should immediately:

  • phone the Poisons Information Centre
    (by calling 13 11 26), or
  • contact your doctor, or
  • go to the Emergency Department at your nearest hospital.

You should do this even if there are no signs of discomfort or poisoning.

5. What should I know while using Minitran?

Things you should do

Call your doctor straight away if you become pregnant.

Your doctor can discuss with you the risks of using Minitran while you are pregnant.

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

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.

Get up slowly if you feel light-headed, dizzy, or faint when getting out of bed or standing up.

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 continues or gets worse, talk to your doctor.

If you experience skin reddening or itchiness when removing the patch

If this happens it usually only lasts a few hours. Making sure your skin is dry before you apply a patch and using a different area of skin each day can help prevent redness and irritation.

Remind any doctor, dentist or pharmacist you visit that you are using Minitran.

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

Things you should not do

Do not use Minitran to relieve an attack of angina.

Minitran will not relieve an attack of angina once it has started. Your doctor will have given you other tablets or spray to use if you get attacks of angina.

Do not stop using Minitran suddenly.

  • Stopping Minitran suddenly may bring on attacks of angina, especially if you have been using it for several weeks or more.
  • If your doctor asks you to stop using Minitran, your doctor will gradually reduce the dose over 4 to 6 weeks before you completely stop using it.

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

Driving or using machines

Be careful before you drive or use any machines or tools until you know how Minitran affects you.

Minitran may lower your blood pressure and make you feel dizzy or lightheaded, particularly when changing position suddenly.

Drinking alcohol

Tell your doctor if you drink alcohol.

Alcohol may enhance the blood pressure lowering effects of glyceryl trinitrate. This may lead to dizziness, lightheadedness, or fainting.

Looking after your medicine

Follow the instructions in the carton on how to take care of your medicine properly.

Store it in a cool dry place where the temperature stays below 25°C for example, do not store it:

  • in the bathroom or near a sink, or
  • in the car or on windowsills.

Do not keep Minitran patches in the fridge.

Keep Minitran patches where children cannot reach it.

Getting rid of any unwanted medicine

If you no longer need to use this medicine or it is out of date, take it to any pharmacy for safe disposal.

Do not use this medicine after the expiry date.

6. Are there any side effects?

All medicines can have side effects. If you do experience any side effects, most of them are minor and temporary. However, some side effects may need medical attention.

See the information below and, if you need to, ask your doctor or pharmacist if you have any further questions about side effects.

Less serious side effects

Less serious side effectsWhat to do
  • headache
  • reddening of the skin after the patch has been taken off, with or without itching
  • dizziness
  • light headedness
  • low blood pressure
  • hot flushes
  • nausea and vomiting.
Speak to your doctor if you have any of these less serious side effects and they worry you.

Serious side effects

Serious side effectsWhat to do
  • signs of an allergic reaction such as rash, itching or hives on the skin; swelling of the face, lips, tongue or other part 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 headache.
Call your doctor straight away, or go straight to the Emergency Department at your nearest hospital if you notice any of these serious side effects.

Tell your doctor or pharmacist if you notice anything else that may be making you feel unwell.

Other side effects not listed here may occur in some people.

Reporting side effects

After you have received medical advice for any side effects you experience, you can report side effects to the Therapeutic Goods Administration online at www.tga.gov.au/reporting-problems. By reporting side effects, you can help provide more information on the safety of this medicine.

Always make sure you speak to your doctor or pharmacist before you decide to stop taking any of your medicines.

7. Product details

This medicine is only available with a doctor's prescription.

What Minitran contains

Active ingredient
(main ingredient)
Glyceryl trinitrate
Other ingredients
(inactive ingredients)
polymer 3273
ethyl oleate
glyceryl laurate

Do not take this medicine if you are allergic to any of these ingredients.

What Minitran looks like

Minitran is a patch made of thin, clear plastic covered by a layer of adhesive and the active ingredient, glyceryl trinitrate.

Minitran patches are oval shaped and are available in three sizes:

Minitran 5 is a 6.7 cm squared patch. It contains 18 mg glyceryl trinitrate and releases 5 mg of glyceryl trinitrate over 24 hours. The patch is marked "MINITRAN 5".

Registration number: AUST R 52028.

Minitran 10 is a 13.3 cm squared patch. It contains 36 mg glyceryl trinitrate and releases 10 mg of glyceryl trinitrate over 24 hours. The patch is marked "MINITRAN 10".

Registration number: AUST R 52029.

Minitran 15 is a 20 cm squared patch. It contains 54 mg glyceryl trinitrate and releases 15 mg of glyceryl trinitrate over 24 hours. The patch is marked "MINITRAN 15".

Registration number: AUST R 52030.

Each box of Minitran contains 30 patches.

Who distributes Minitran

iNova Pharmaceuticals (Australia) Pty Limited
ABN 13 617 871 539
Level 10, 12 Help Street
Chatswood NSW 2067
Tel: 1800 630 056

™ = Trademark

This leaflet was prepared in November 2022.

Published by MIMS December 2022

BRAND INFORMATION

Brand name

Minitran

Active ingredient

Glyceryl trinitrate

Schedule

S4

 

1 Name of Medicine

Glyceryl trinitrate.

2 Qualitative and Quantitative Composition

Minitran 5 has a surface area of 6.7 cm2 and contains 18 mg of glyceryl trinitrate (GTN). The amount of GTN released over 24 hours is 5 mg.
Minitran 10 has a surface area of 13.3 cm2 and contains 36 mg of glyceryl trinitrate. The amount of GTN released over 24 hours is 10 mg.
Minitran 15 has a surface area of 20.0 cm2 and contains 54 mg of glyceryl trinitrate. The amount of GTN released over 24 hours is 15 mg.
For the full list of excipients, see Section 6.1 List of Excipients.

3 Pharmaceutical Form

Drug delivery system, transdermal.

Minitran 5.

Thin, transparent oval patch 6.7 cm squared with "Minitran 5" printed on the patch in grey.

Minitran 10.

Thin, transparent oval patch 13.3 cm squared with "Minitran 10" printed on the patch in grey.

Minitran 15.

Thin, transparent oval patch 20.0 cm squared with "Minitran 15" printed on the patch in grey.
The Minitran Transdermal Delivery System is a unit designed to provide continuous controlled release of glyceryl trinitrate through intact skin to overcome the problems of the short half-life and extensive first pass metabolism of glyceryl trinitrate.
The rate of release of glyceryl trinitrate from Minitran is linearly dependent upon the area of the applied system; each cm2 of applied system delivers approximately 0.75 mg glyceryl trinitrate over 24 hours, which is equivalent to 0.03 mg/hour. (See Table 1.)
The remainder of the glyceryl trinitrate in the system serves as a reservoir and is not delivered in normal use.
The Minitran Transdermal Delivery System consists of a thin, transparent, low-density, polyethylene film covered by a hypoallergenic, medical grade, acrylate-based polymer adhesive containing glyceryl trinitrate.
Each patch is packaged in foil/polymer film laminate. Prior to use, a protective peel strip is removed from the adhesive surface.

4 Clinical Particulars

4.1 Therapeutic Indications

Prevention of chronic, stable angina pectoris due to coronary artery disease.

4.2 Dose and Method of Administration

The response to nitrates differs between individuals and the minimum effective dose should be prescribed in each case. It is, therefore, recommended that treatment is started with one Minitran 5 patch per day, with upward dosage titration when necessary.
Attenuation of effect has occurred in some patients being treated with sustained release nitrate preparations. To avoid the development of tolerance (loss of effect) with continuous application and on the basis of current clinical studies, it is recommended that Minitran should be applied daily with a patch free interval of 8-12 hours (usually at night).
Each Minitran patch is contained in a sealed pouch. The adhesive layer is covered by a protective film which should be removed before application. The Minitran patch should be applied to a clean, dry, healthy area of skin on the upper arm or chest and should not be applied to the distal parts of the extremities. Subsequent patches should not be applied to the same area of skin until several days have elapsed. Minitran patches adhere easily to the skin and also stay in place whilst bathing or during physical exercise.
No specific information on use in the elderly is available.

4.3 Contraindications

Minitran is contraindicated in cases of:
known hypersensitivity to organic nitrates or to the stated excipients including adhesive in the patch;
severe anaemia;
increased intra-ocular and intracranial pressure; and
marked arterial hypotension or shock.
It is also contraindicated in acute myocardial insufficiency due to obstruction as in aortic or mitral stenosis or constrictive pericarditis.
Do not use Minitran in patients who are taking phosphodiesterase inhibitors (such as sildenafil, tadalafil, or vardenafil) for erectile dysfunction or pulmonary hypertension because concomitant use may amplify the vasodilatory effects of Minitran resulting in severe hypotension.
Do not use Minitran in patients who are taking the soluble guanylate cyclase stimulator riociguat. Concomitant use can cause hypotension.

4.4 Special Warnings and Precautions for Use

Amplification of the vasodilatory effects of Minitran patch by phosphodiesterase inhibitors, e.g. sildenafil can result in severe hypotension.
Severe hypotension, particularly with upright posture, may occur with even small doses of glyceryl trinitrate, particularly in the elderly. Minitran should therefore be used with caution in elderly patients who may be volume depleted, are on multiple medications, or who, for whatever reason, are already hypotensive. Hypotension induced by glyceryl nitrate may be accompanied by paradoxical bradycardia and increased angina pectoris.
Minitran is not indicated for the treatment of acute angina attacks requiring rapid relief. The benefits of transdermal glyceryl trinitrate in patients with acute myocardial infarction or congestive heart failure have not been established. If one elects to use glyceryl trinitrate in these conditions, careful clinical or haemodynamic monitoring must be used to avoid the hazards of hypotension and tachycardia.
Minitran should be removed before attempting cardioversion or defibrillation. A cardiovertor/defibrillator should not be discharged through a paddle electrode that overlies a Minitran patch due to the risk of burns to the patient and damage to the paddle.
Minitran should be used with caution in patients with hypoxaemia or ventilation perfusion imbalance, as a decrease in available oxygen may diminish the anti-anginal effect of Minitran. Nitrate therapy, including Minitran, may aggravate the angina caused by hypertrophic cardiomyopathy, particularly in the elderly.
The appearance of tolerance (the decline in, or loss of efficacy) to the preparation and of cross tolerance with other nitrates may occur with repeated or continuous administration of long-acting nitrates, including Minitran and other transdermal systems. This can be prevented by keeping plasma glyceryl trinitrate levels low for a certain period of the dosing interval and for this reason intermittent therapy is preferable (see Section 4.2 Dose and Method of Administration).
As all nitrate vasodilators can induce withdrawal reactions, abrupt withdrawal of Minitran should be avoided. It is advisable to gradually reduce the dosage over a period of 4 to 6 weeks to prevent a potential withdrawal reaction.
The use of products for topical application, especially if prolonged, may give rise to sensitisation phenomena, in which case treatment should be suspended and suitable therapeutic measures adopted.

Use in the elderly.

Elderly patients may be more susceptible to hypotension and may be at greater risk of falling at the therapeutic doses of glyceryl trinitrate.

Paediatric use.

The safety and efficacy of Minitran in children have yet to be established and, therefore, recommendations for its use cannot be made.

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 use of Minitran and other vasodilatory agents, calcium antagonists, β-blockers, ACE inhibitors, neuroleptics, diuretics, antihypertensives, tricyclic antidepressants, sildenafil and alcohol may enhance the blood pressure lowering effects of glyceryl trinitrate.
Use of Minitran with phosphodiesterase inhibitors is contraindicated (see Section 4.3 Contraindications). Concomitant use of Minitran with riociguat, a soluble guanylate cyclase inhibitor, is contraindicated (see Section 4.3 Contraindications).
There is a risk of coronary artery constriction with concurrent administration of dihydroergotamine.

4.6 Fertility, Pregnancy and Lactation

Effects on fertility.

Lower doses of glyceryl trinitrate did not affect fertility in rats but doses up to 230 mg/kg/day caused moderate to severe testicular degeneration and/or atrophy with severe to complete aspermatogenesis.
(Category B2)
The safety of Minitran in pregnancy has not been established. As with all drugs, Minitran should not be prescribed during pregnancy, particularly during the first trimester, unless there are compelling reasons for doing so. If Minitran is in regular use and pregnancy occurs, the physician should be notified immediately.
It is not known whether glyceryl trinitrate passes into the breast milk. The benefits for the mother must be weighed against the risks to the child.

4.7 Effects on Ability to Drive and Use Machines

No specific studies have been conducted to assess the direct effect of Minitran on the ability to drive and use machines. However, adverse effects of Minitran include dizziness and fainting which could affect the ability to drive or use machines. See Section 4.8 Adverse Effects (Undesirable Effects).

4.8 Adverse Effects (Undesirable Effects)

Adverse reactions to glyceryl trinitrate are generally dose-related and almost all of these reactions are the result of its vasodilatory activity. Headache is the most frequently encountered adverse reaction, particularly when high doses are used. This usually regresses after a few days despite the continuation of therapy. However, if headache is persistent, it may be necessary to reduce the dose or interrupt treatment.
Reddening of the skin, with or without itching or a slight erythematous reaction, sometimes develops and generally disappears a few hours after removal of the patch without adopting other measures. The site of application should be altered daily to avoid local irritation.

Common (≥ 1%).

Central nervous system.

Headache.

Cardiovascular.

Hypotension (postural), dizziness, lightheadedness, hot flushes.

Dermatological.

Application site reaction (redness).

Gastrointestinal.

Nausea, vomiting.

Uncommon (≥ 0.1% to < 1%).

Cardiovascular.

Palpitations, tachycardia, angina aggravated, fainting.

Rare (< 0.1%).

Cardiovascular.

Rebound hypertension.

Haematological.

Methaemoglobinaemia.

Hypersensitivity.

Anaphylaxis, allergic contact dermatitis.

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.

4.9 Overdose

High doses of glyceryl trinitrate may induce rapid reduction in arterial pressure, causing collapse. Due to the controlled release of glyceryl trinitrate from Minitran, overdosage is likely to be rare. In cases of suspected overdosage, the Minitran patch should be removed and any reduction in arterial blood pressure and symptoms of collapse should be treated by appropriate measures.

Haemodynamic effects.

The adverse effects of glyceryl trinitrate overdose are generally the results of vasodilation, venous pooling, reduced cardiac output and hypotension. These haemodynamic changes may have protean manifestations, including increased intra-cranial pressure with any or all of the following: persistent throbbing headache, confusion and moderate fever; vertigo; palpitations; visual disturbances; nausea and vomiting (possibly with colic and even bloody diarrhoea); syncope (especially in the upright posture); air hunger and dyspnoea, later followed by reduced ventilatory effort; diaphoresis, with the skin either flushed or cold and clammy; heart block and bradycardia; paralysis; coma; seizures and death.
Because the hypotension associated with glyceryl trinitrate overdose is the result of venodilation and arterial hypovolaemia, prudent therapy should be directed towards an increase in central fluid volume. Passive elevation of the patient's legs may be sufficient, but intravenous infusion of normal saline or a similar fluid may also be necessary. The use of adrenaline or other arterial vasoconstrictors in this setting is likely to do more harm than good. In patients with renal disease or congestive heart failure, therapy resulting in central volume expansion is not without hazard. Treatment of glyceryl trinitrate overdose in these patients may be subtle and difficult and invasive monitoring may be required.

Methaemoglobinaemia.

Nitrate ions liberated during metabolism of glyceryl trinitrate can oxidise haemoglobin into methaemoglobin. Assuming that nitrate moieties of glyceryl trinitrate are quantitatively applied to the oxidation of haemoglobin, patients without cytochrome b5 reductase activity would require about 1 mg/kg of glyceryl trinitrate before manifesting clinically significant (≥ 10%) methaemoglobinaemia. Patients with normal reductase function would require even larger doses of glyceryl trinitrate before manifesting clinically significant methaemoglobinaemia. Continuous glyceryl trinitrate infusion at 3.1 to 4.0 mg/hour for 2-4 weeks in 36 patients resulted in an average methaemoglobin level of 0.2%, which was comparable to the level observed in patients receiving placebo. Nevertheless, there are case reports of significant methaemoglobinaemia in association with moderate overdoses of organic nitrates in patients who were thought not to be susceptible.
Methaemoglobin levels are available from most clinical laboratories. The diagnosis should be carried out in patients who exhibit signs of impaired oxygen delivery despite adequate cardiac output and adequate arterial pO2. Classically, methaemoglobinaemic blood is described as chocolate brown without colour change on exposure to air. When methaemoglobinaemia is diagnosed, the treatment of choice is methylene blue, 1 to 2 mg/kg intravenously.
For information on the management of overdose, contact the Poisons Information Centre on 13 11 26 (Australia).

5 Pharmacological Properties

5.1 Pharmacodynamic Properties

Mechanism of action.

The principal pharmacological action of glyceryl trinitrate is relaxation of the vascular smooth muscle and consequent dilation of peripheral arteries and veins, especially the latter. Dilation of the veins promotes peripheral pooling of blood and decreases venous return to the heart, thereby reducing left ventricular end-diastolic pressure and pulmonary capillary wedge pressure (preload). Arteriolar relaxation reduces systemic vascular resistance, systolic arterial pressure and mean arterial pressure (afterload). Dilation of the coronary arteries also occurs, which is of importance in the treatment of coronary spasm.

Clinical trials.

No data available.

5.2 Pharmacokinetic Properties

When a Minitran Transdermal Delivery System is applied to the skin, glyceryl trinitrate is absorbed continuously through the skin into the systemic circulation, maintaining constant blood levels. In healthy volunteers, steady-state plasma concentrations of glyceryl trinitrate are reached by about two hours after application of a patch and are maintained for the duration of wearing the patch. Upon removal of the patch, the plasma concentration declines, with a half-life of about an hour.

5.3 Preclinical Safety Data

Genotoxicity.

No genotoxicity studies were undertaken with glyceryl trinitrate.

Carcinogenicity.

Studies in animals have not been performed with Minitran patches to evaluate the carcinogenic and mutagenic potential. Glyceryl trinitrate, the active component of the Minitran patch, given in the diet to rats at doses up to 1% caused an increase in the incidence of hepatic cholangiofibrosis, hepatocellular carcinomas and/or neoplastic nodules and Leydig cell tumours in the testis.
The Minitran patch contains an acrylate-based polymer adhesive. One of the unpolymerised acrylate monomers has been characterised as a carcinogen in animals and has been shown to have genotoxic potential in animals and in vitro which appears more pronounced in germ cells as compared to somatic cells. However, the risk of the very low levels of unpolymerised monomer causing tumours in humans following dermal application of the Minitran patch is very minimal.

6 Pharmaceutical Particulars

6.1 List of Excipients

Ethyl oleate, Glyceryl laurate, Polymer 3273 (PI 2372).

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. Do not refrigerate.

6.5 Nature and Contents of Container

Minitran 5.

Plastic laminate/Al Sachet. Quantity per carton: 1's#, 3's#, 30's;

Minitran 10.

Plastic laminate/Al Sachet. Quantity per carton: 1's#, 3's#, 30's;

Minitran 15.

Plastic laminate/Al Sachet. Quantity per carton: 1's#, 3's#, 30's.
#Not marketed.

6.6 Special Precautions for Disposal

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

6.7 Physicochemical Properties

Glyceryl trinitrate (GTN) is a 1,2,3-propanetriol trinitrate, an organic nitrate.
It has a molecular weight of 227.09. GTN is also known as nitroglycerin.

Chemical structure.

Its structural formula is:

CAS number.

55-63-0.

7 Medicine Schedule (Poisons Standard)

S4.

Summary Table of Changes