Consumer medicine information

Isobide MR Tablets

Isosorbide mononitrate

BRAND INFORMATION

Brand name

Isobide MR

Active ingredient

Isosorbide mononitrate

Schedule

S4

 

Consumer medicine information (CMI) leaflet

Please read this leaflet carefully before you start using Isobide MR Tablets.

What is in this leaflet

This leaflet answers some common questions about Isobide MR.

It does not contain all of the available information. It does not take the place of talking to your doctor or pharmacist.

All medicines have benefits and risks. Your doctor has weighed the risks of you taking Isobide MR against the benefits they expect it will have for you.

If you have any concerns about taking this medicine, talk to your doctor or pharmacist.

Keep this leaflet with your medicine.

You may need to read it again.

What Isobide MR is used for

Isobide MR is used to prevent angina pectoris (heart pain). It is not recommended and should not be taken for the treatment of acute attacks.

Angina is a pain or uncomfortable feeling in the chest, often spreading to the arms or 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.

Isobide MR belongs to a group of medicines called nitrates. It works by widening blood vessels to improve the blood flow around the heart which means there is more oxygen being carried by the blood. This reduces the pain associated with angina.

Your doctor may have prescribed Isobide MR for another reason. Ask your doctor if you have any questions about why Isobide MR has been prescribes for you.

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

Before You Take Isobide MR

When you must not take it

Do not take Isobide MR if:

  1. you have an allergy to:
  • isosorbide mononitrate or any of the ingredients in Isobide MR listed at the end of this leaflet
  • any medicine or food containing nitrates or nitrites
Symptoms of an allergic reaction to these medicines 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
  1. you are taking any of the following phosphodiesterase type 5 inhibitors
  • Sildenafil
  • Tadalafil
  • Vardenafil
  1. You are pregnant, or intend to become pregnant
Isosorbide may affect your developing baby if you take it during pregnancy.
  1. You are breast feeding or intend to breast feed
Isosorbide passes into breast milk. The effect on the baby is unknown.

The use of Isobide MR during pregnancy or breast feeding should be discussed with your doctor.

Isobide MR should not be taken to stop an acute angina attack. They should be taken once daily.

Do not take Isobide MR if you are in a state of shock including shock caused by very low blood pressure due to a failing heart, have hypotension (low blood pressure), weakened muscle of the heart or pericarditis (swelling around the heart).

Do not take this medicine if the packaging is torn or shows signs of tampering.

Do not take if the expiry date (EXP) printed on the pack has passed. If you take this medicine after the expiry date has passed, it may not work as well.

If you are not sure whether you should start taking Isobide MR, contact your doctor.

Do not give Isosorbide to a child. The safety and effectiveness of Isosorbide has not been established in children.

Before you start to take it

Tell your doctor if:

  1. You have any allergies to any other medicines, foods, dyes or preservatives.
  2. You have or have had any medical conditions, especially the following:
  • Heart failure
  • Liver failure
  • Kidney failure
  1. You know you suffer from hypotension (low blood pressure) or blood vessel disease such as hardening of the arteries.

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 shop.

Some medicines may interfere with Isobide MR and may affect how well it works. You may need to take different amounts of your medicine, or you may need to take different medicines. Your doctor will advise you.

The combination of Isosorbide with Sildenafil (Viagra®), Tadalafil and Vardenafil may cause fainting or heart attacks.

The combination of N-acetylcysteine or captopril with Isosorbide may result in a prolonged anti-angina effect.

The combination of Isosorbide with a calcium channel blocker of the verapamil type may improve heart function. However, the combination of Isosorbide with any other calcium channel blocker may cause hypotension (low blood pressure) requiring dose adjustment of either medicine.

The combination of Isosorbide with betablocker medicines such as propranolol may cause hypotension (low blood pressure).

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

Your doctor and pharmacist may have more information on medicines to be careful with or avoid while taking Isobide MR.

How to take Isobide MR

How much to take

Your doctor will advise you on how many tablets you should take.

How to take it.

Take Isobide MR with half a glass of water. You must swallow the tablet whole.

Food does not affect the absorption of isosorbide so the tablets may be taken with or without food.

Follow all directions given to you by your doctor and pharmacist carefully.

These directions may differ from the information contained in this leaflet.

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

If you forget to take it

If you miss a dose of Isobide MR, take it as soon as you remember unless more than eight hours have passed.

If more than eight hours have passed since the time the dose should have been taken, do not take the missed dose but take the next dose at the normal time.

A missed dose may lead to an angina attack that in turn may need medication, prescribed by your doctor, capable of treating an acute attack such as use of immediate release tablets or spray administered under the tongue. Isobide MR is not recommended and should not be taken for the treatment of acute angina attacks.

Do not take a double dose to make up for the dose you missed.

If you are not sure what to do, ask your doctor or pharmacist.

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 the nearest hospital, if you think you or anyone else may have taken too much Isobide MR. Do this even if there are no signs of discomfort or poisoning.

You may need urgent medical attention.

If you take too much Isobide MR, the most common symptom is a pulsing headache. More serious symptoms are excitation, flushing, cold sweats, nausea, vomiting, vertigo, increased heart beat and a fall in blood pressure.

While you are taking Isobide MR

Things you must do

Use Isobide MR exactly as your doctor has prescribed.

If you do not follow your doctor's instructions, you may not get relief from your attacks of angina.

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

Tell all doctors, dentists and pharmacists who are treating you that you are taking Isobide MR.

Things you must not do

Do not use it to treat any other complaints unless your doctor says to.

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

Things to be careful of

Be careful driving or operating machinery until you know how Isobide MR affects you. Isobide MR may cause tiredness, dizziness or lightheadedness in some people, especially after the first dose. Make sure you know how you react to Isobide MR before you drive a car, operate machinery or do anything else that could be dangerous.

Be careful not to overdo physical activities when you first start using Isobide MR.

You may feel better when you start taking it, but you will need time to improve your physical fitness.

Get up slowly when getting out of bed or standing up if you feel light-headed, dizzy or faint. You may feel light-headed or dizzy when you begin to take Isosorbide 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. The problem usually goes away after the first few days.

If this problem gets worse or continues, talk to your doctor.

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

Side Effects

Tell your doctor or pharmacist as soon as possible if you do not feel well while you are taking Isobide MR.

Isobide MR helps most people with angina, but it may have unwanted effects in a few people.

All medicines can 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.

Ask your doctor or pharmacist any questions you may have.

Isobide MR often causes adverse effects in the early stages of treatment.

More common reactions
Headache is the main adverse reaction which is quite common when you start taking Isobide MR. The incidence of headaches usually reduces as treatment is continued. Other symptoms such as dizziness, nausea, tiredness, and disturbed sleep may also occur. Again, these side effects reduce over time if Isobide MR is continued.

Less common reactions
Other side effects which have been reported are poor appetite, vomiting, diarrhoea and heartburn.

These may be serious side effects. You may need urgent medical attention or hospitalisation. These side effects are rare.

Some people may experience other side effects while taking Isobide MR.

These side effects are not listed above. Tell your doctor if you notice anything else that is making you feel unwell.

After taking Isobide MR

Storage

Keep Isobide MR 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.

Keep your tablets in the packaging until it is time to take them. If you take the tablets out of the pack they may not keep well.

Keep your tablets in a cool dry place. Isobide MR should be stored below 25 degrees C.

Do not store Isobide MR or any other medicine in the bathroom or near a sink.

Do not leave in the car or on window sills. Heat and dampness can destroy some medicines.

Disposal

If your doctor tells you to stop taking Isobide MR, or your tablets have passed their expiry date, ask your pharmacist what to do with any that are left over.

Product description

What it looks like

Isobide MR 60 mg tablets are oval tablets with a cream coloured film coating and half scored on both sides.

They are presented in blister (AUST R 184066) or bottle (AUST R 184067)* packs of 30 tablets.

*not marketed

Ingredients

Active Ingredient:
Isobide MR tablets contain 60 mg isosorbide mononitrate.

Other Ingredients:
Also contains stearic acid, carnauba wax, hypromellose, lactose monohydrate, magnesium stearate, purified talc, titanium dioxide, colloidal anhydrous silica, macrogol 4000, iron oxide yellow.

Please read this leaflet carefully before you start taking Isobide MR. You may wish to keep it to read again.

Name and Address of the Sponsor

Arrotex Pharmaceuticals Pty Ltd
15-17 Chapel St
Cremorne 3121 VIC
Australia

www.arrotex.com.au

Date of Preparation

October 2022

Published by MIMS November 2022

BRAND INFORMATION

Brand name

Isobide MR

Active ingredient

Isosorbide mononitrate

Schedule

S4

 

1 Name of Medicine

Isosorbide mononitrate.

2 Qualitative and Quantitative Composition

Isobide MR 60 mg tablets contain 60 mg isosorbide mononitrate.
Isosorbide mononitrate is a white to pale yellow, crystalline, odourless powder that is freely soluble in water.
For the full list of excipients, see Section 6.1 List of Excipients.

3 Pharmaceutical Form

Tablets 60 mg. A cream, film-coated oval tablet of 13 mm length scored on both sides.

4 Clinical Particulars

4.1 Therapeutic Indications

Prophylactic treatment of angina pectoris. Isobide MR 60 mg Modified release tablets are not recommended for the management of acute attacks of angina pectoris (see Section 4.4 Special Warnings and Precautions for Use).

4.2 Dose and Method of Administration

One (1) tablet once daily. That dose may be increased to two (2) tablets daily, both tablets taken at the same time. Isobide MR 60 mg Modified release tablets should not be administered twice daily.
There is insufficient evidence to show that one halved tablet of Isobide MR delivers exactly half the dose of one full tablet, or whether the rate of release is the same. In-vitro dissolution testing showed that dissolution was slightly faster with halved isosorbide mononitrate modified release tablets than with whole tablets.
Isobide MR 60 mg Modified release tablets should not be chewed or crushed, and should be swallowed whole with half a glass of fluid.

4.3 Contraindications

Known hypersensitivity to nitrates or to any of the components in Isobide MR 60 mg Modified release tablets, shock (including cardiogenic shock), hypotension, obstructive hypertrophic cardiomyopathy and pericarditis.
Phosphodiesterase type 5 inhibitors (e.g. sildenafil, tadalafil and vardenafil) are contraindicated and must not be given to patients already receiving isosorbide mononitrate therapy. Concomitant administration of isosorbide mononitrate and Phosphodiesterase type 5 inhibitors can potentiate the vasodilatory effect of isosorbide mononitrate with the potential result of serious side effects such as syncope or myocardial infarction.

Acute angina.

Isobide MR 60 mg Modified release tablets are not indicated for the relief of acute attacks of angina.

4.4 Special Warnings and Precautions for Use

Note.

There is a risk of developing tolerance to haemodynamic and antianginal effects if higher doses (more than 120 mg/day) and/or more frequent doses (e.g. twice daily) of Isobide MR 60 mg Modified release tablets are administered. It is therefore important that Isobide MR 60 mg Modified release tablets are administered once a day in order to ensure that intervals with low nitrate concentrations are achieved each day, reducing the risk of the development of tolerance.

Acute myocardial infarction and congestive cardiac failure.

The benefits of isosorbide mononitrate in patients with acute myocardial infarction or congestive cardiac failure have not been established. Because the effects of isosorbide mononitrate are difficult to terminate rapidly, the medicine is not recommended in these settings. If isosorbide mononitrate is used in these conditions, careful clinical and haemodynamic monitoring is necessary to avoid the hazards of hypotension and tachycardia.

Hypotension.

Severe hypotension, particularly with upright posture, may occur with even small doses of isosorbide mononitrate. Hypotension and lightheadedness on standing may be more frequent in patients who have consumed alcohol. The drug should be used with caution in patients who may be volume depleted or who, for whatever reason, are already hypotensive. Hypotension induced by isosorbide mononitrate may be accompanied by paradoxical bradycardia and increased angina pectoris.

Industrial workers.

Tolerance develops in industrial workers who have had long-term exposure to high doses of organic nitrates. Chest pain, acute myocardial infarction, and even sudden death have occurred during temporary withdrawal of nitrates from these workers, demonstrating the existence of true physical dependence.

Check the following before use.

Caution should be observed if Isobide MR 60 mg Modified release tablets are administered to patients with: severe cerebral arteriosclerosis, pronounced mitral stenosis, hypertrophic cardiomyopathy, hypotension or cardiogenic shock.

Abrupt withdrawal.

Although no clear cut rebound phenomena were seen upon abrupt withdrawal of isosorbide mononitrate modified release tablets, such withdrawal is not recommended because of the possibility of severe exacerbation of anginal symptoms.

Use with caution in the following circumstances.

Use in hepatic impairment.

Isosorbide mononitrate has been shown to cause a significant decrease in portal pressure in patients with cirrhosis and portal hypertension during long-term therapy (see Section 4.5 Interactions with Other Medicines and Other Forms of Interactions, Propranolol).

Use in renal impairment.

The elimination of isosorbide mononitrate following administration of an immediate release tablet has been investigated in patients with severe renal impairment, but not using the modified release tablet. Renal impairment makes no therapeutically important difference to the pharmacokinetics of isosorbide mononitrate administered as an immediate release tablet, although two single dose studies did indicate a prolonged half-life in these patients with severe renal impairment. One of these studies also showed a higher plasma concentration. In view of the lack of data regarding the use of the tablet presentation in patients with severe renal impairment, the possibility of accumulation should be borne in mind when administering Isobide MR 60 mg Modified release tablets to such patients, in whom a reduced dosage may be appropriate.

Use in the elderly.

No dose reduction is necessary in elderly patients unless they have severe renal impairment.

Paediatric use.

Due to lack of data, the use of Isobide MR 60 mg Modified release tablets cannot be recommended in children.

Effects on laboratory tests.

No data available.

4.5 Interactions with Other Medicines and Other Forms of Interactions

Phosphodiesterase type 5 inhibitors.

Concomitant administration of isosorbide mononitrate and Phosphodiesterase type 5 inhibitors can potentiate the vasodilatory effect of isosorbide mononitrate with the potential result of serious side effects such as syncope or myocardial infarction. Therefore, Phosphodiesterase type 5 inhibitors (e.g. sildenafil, tadalafil and vardenafil) should not be given to patients already receiving isosorbide mononitrate therapy.

Sulfhydryl containing compounds.

The metabolism of organic nitrates to nitric oxide is dependent on the presence of sulfhydryl groups in the muscle. The combination of oral N-acetylcysteine and a single dose of modified release isosorbide mononitrate 60 mg significantly prolonged the total exercise time in patients with angina pectoris and angiographically proven significant coronary artery disease, when compared with isosorbide mononitrate alone. Concomitant administration of other exogenous sources of sulfhydryl groups such as methionine and captopril may produce a similar interaction.

Phenylalkylamine calcium antagonists.

The addition of a calcium channel blocker of the verapamil type, such as gallopamil 75 mg, has been shown to further improve left ventricular functional parameters when given in combination with isosorbide mononitrate in a modified release formulation.

Propranolol.

The addition of isosorbide mononitrate to propranolol treatment in patients with cirrhosis and portal hypertension caused a marked fall in portal pressure, a reduction in hepatic blood flow, cardiac output and mean arterial blood pressure, but no additional change in azygos blood flow. The additional effect of isosorbide mononitrate was especially evident in patients whose portal pressure was not reduced by propranolol.

Calcium antagonists (general).

Marked symptomatic orthostatic hypotension has been reported when calcium antagonists and organic nitrates were used in combination. Dose adjustments of either class of agent may be necessary.

4.6 Fertility, Pregnancy and Lactation

Effects on fertility.

No data available.
(Category B2)
The safety of isosorbide mononitrate in pregnancy has not been established. In the absence of Segment I and III studies with isosorbide mononitrate, the drug should only be administered to pregnant women if, in the opinion of the physician, the clinical benefits outweigh the potential risks.
 At present there is no documentation about the passage of isosorbide mononitrate into breast milk, therefore its use in women who are breastfeeding is not recommended.

4.7 Effects on Ability to Drive and Use Machines

Patients may develop dizziness when first using isosorbide mononitrate. Patients should be advised to determine how they react before they drive or operate machinery.

4.8 Adverse Effects (Undesirable Effects)

The adverse effects which follow have been reported in studies with isosorbide mononitrate.

Very common.

Headache (up to 30%) necessitating withdrawal of 2 - 3% of patients.

Common.

Tiredness, sleep disturbances (6%) and gastrointestinal disturbances (6%) have been reported during clinical trials with isosorbide mononitrate modified release tablets, but at a frequency no greater than for placebo. Hypotension (4 to 5%), poor appetite (2.5%), nausea (1%).
Adverse effects associated with the clinical use of the drug are as expected with all nitrate preparations. They occur mainly in the early stages of treatment.

Very common.

Headache predominates (up to 30%), but the incidence reduces rapidly as treatment continues.

Common.

Hypotension (4%) with symptoms such as dizziness and nausea have been reported. These symptoms generally disappear during long-term treatment.
Other reactions that have been reported with isosorbide mononitrate modified release tablets include: tachycardia, vomiting, diarrhoea, vertigo and heartburn.

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

Symptoms.

The most common symptom of overdose is a pulsing headache. More serious symptoms are excitation, flushing, cold sweats, nausea, vomiting, vertigo, syncope, tachycardia and a fall in blood pressure.

Treatment.

Administer activated charcoal. In patients with severe hypotension, place patient in supine position with the legs raised. If necessary, further symptomatic treatment should be given, including intravenous fluid administration.
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.

Isosorbide mononitrate is an active metabolite of isosorbide dinitrate and exerts qualitatively similar effects. Isosorbide mononitrate reduces the workload of the heart by producing venous and arterial dilatation. By reducing the end diastolic pressure and volume, isosorbide mononitrate lowers intramural pressure, hence leading to an improvement in the subendocardial blood flow. The net effect when administering isosorbide mononitrate is therefore a reduced workload for the heart and an improvement in the oxygen supply/demand balance of myocardium.
Nitrates are highly effective in the prophylaxis of symptomatic and asymptomatic myocardial ischaemia. Nitrates dilate coronary arteries not only in pre- and poststenotic vessels, but also in eccentric lesions. The natural initiator of vascular relaxation is thought to be endothelium derived relaxing factor (EDRF), which has both the clinical and biological characteristics of nitric oxide. Organic nitrates are metabolised to nitric oxide in the muscle cell via a sulfhydryl dependent mechanism. They are therefore thought to be the physiological substitute for EDRF.

Clinical trials.

No data available.

5.2 Pharmacokinetic Properties

Isosorbide mononitrate has an elimination half-life of around 5 hours. Isobide MR 60 mg Modified release tablets provide a modified release presentation of isosorbide mononitrate, with approximately 85% bioavailability. The release mechanism in Isobide MR comprises active drug distributed within a hydrophobic cellulose matrix with release occurring by diffusion. Drug particles close to the tablet surface are released relatively rapidly, but those incorporated more deeply are released more slowly. Administration of Isobide MR 60 mg Modified release tablets results in a gradual, non-pH dependent release of the active substance, which is completed after approximately 10 hours. Compared to ordinary tablets, the absorption phase is prolonged and the duration of effect is extended. The absorption of Isobide MR 60 mg Modified release tablets has been shown not to be influenced by food intake.
After repeated once daily administration of Isobide MR 60 mg Modified release tablets, the maximum plasma level (about 3,000 nanomol/L) of isosorbide mononitrate is achieved at about 4 hours. The plasma concentration remains above 1,400 to 1,500 nanomol/L for approximately 10 hours, dropping to under 500 nanomol/L by the end of the dosage interval (24 hours after dose). This nitrate low period minimises the possibility of nitrate tolerances developing during prolonged treatment with Isobide MR 60 mg Modified release tablets.
Isosorbide mononitrate is less than 5% plasma protein bound. The distribution volume of isosorbide mononitrate is about 0.6 L/kg, indicating that it is mainly distributed into total body water. Elimination takes place predominantly by hydrolysis of the nitrate and conjugation in the liver. The metabolites are excreted mainly via the kidneys, with only about 2% of the dose being excreted intact.
In placebo controlled studies, isosorbide mononitrate modified release tablets have been shown to significantly increase exercise capacity in patients with angina pectoris taking no other chronic treatment, as well as in patients taking concomitant β-blocker therapy.
It is known that the clinical effects may be attenuated during repeated administration with nitrates in high doses and/or frequent administration. However, the pharmacokinetic characteristics of Isobide MR 60 mg Modified release tablets produce a nitrate low period following once daily dosage. No development of tolerance with respect to antianginal effect has been detected when isosorbide mononitrate modified release tablets are given at a dose of one or two tablets (60 or 120 mg) once daily. The drug is not recommended for twice daily administration.
There is insufficient evidence to show that one halved tablet of Isobide MR delivers exactly half the dose of one full tablet, or whether the rate of release is the same. In-vitro dissolution testing showed that dissolution was slightly faster with halved isosorbide mononitrate modified release tablets than with whole tablets.

5.3 Preclinical Safety Data

Genotoxicity.

No data available.

Carcinogenicity.

No data available.

6 Pharmaceutical Particulars

6.1 List of Excipients

Other ingredients are hypromellose, carnauba wax, stearic acid, lactose monohydrate, colloidal anhydrous silica, magnesium stearate, purified talc, titanium dioxide, iron oxide yellow and macrogol 4000.

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

Protect from light and moisture.

Blisters.

Store below 25°C.

6.5 Nature and Contents of Container

Available in PVDC/PVC/Al blisters of 30 tablets.

6.6 Special Precautions for Disposal

In Australia, any unused medicine or waste material should be disposed of in accordance with local requirements.

6.7 Physicochemical Properties

Chemical structure.


Chemical name: 1,4:3,6-dianhydro-D-glucitol 5-nitrate.
Molecular Formula: C6H9NO6.
Molecular Weight: 191.14.

CAS number.

[16051-77-7].

7 Medicine Schedule (Poisons Standard)

Schedule 4 (Prescription only Medicine).

Summary Table of Changes