Consumer medicine information

Isomonit Sustained release tablets

Isosorbide mononitrate

BRAND INFORMATION

Brand name

Isomonit

Active ingredient

Isosorbide mononitrate

Schedule

S4

 

Consumer medicine information (CMI) leaflet

Please read this leaflet carefully before you start using Isomonit Sustained release tablets.

WHAT IS IN THIS LEAFLET

This leaflet answers some common questions about Isomonit.

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 risk of you taking Isomonit against the benefits it is expected to have for you.

If you have any concerns about taking this medicine, ask your doctor or pharmacist. Keep this leaflet with the medicine. You may want to read it again.

WHAT ISOMONIT IS USED FOR

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

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

Isomonit belong to a group of medicines called nitrates. It contains the active ingredient isosorbide mononitrate.

Isomonit work by relaxing the blood vessels, letting more blood and oxygen reach the heart.

Your doctor will have explained why you are being treated with Isomonit and told you what dose to take.

Follow all directions given to you by your doctor carefully.

They may differ from the information contained in this leaflet.

However, your doctor may prescribe this medicine for another use. Ask your doctor if you want more information.

Isomonit is not addictive.

BEFORE YOU TAKE ISOMONIT

When you must not take Isomonit

Do not take Isomonit if:

  • you are allergic to the active ingredient isosorbide mononitrate or food containing nitrates or nitrites or any of the inactive ingredients mentioned at the end of this leaflet under Product Description
  • you have hypotension (low blood pressure)
  • you are in a state of shock including shock caused by very low blood pressure due to a failing heart
  • you have a weakened muscle of the heart or pericarditis (swelling around the heart)
  • you are taking sildenafil, vardenafil, tadalafil
  • it is past its expiry date or the packaging appears to have been tampered with

Do not use Isomonit if you are pregnant or breast feeding unless your doctor says it is safe. Ask your doctor about the risks and benefits involved. We do not know if it is safe for you to take it while you are pregnant. It may affect your baby.

It is not known if your baby can take in Isomonit from breast milk if you are breast feeding.

Do not give Isomonit to children. There is no specific information about use in children, so Isomonit is not recommended for use in children. Always ask your doctor before giving medicines to children.

Do not use after the use by (expiry) date printed on the pack or if the packaging is torn or shows signs of tampering. If it has expired or is damaged, return it to your pharmacist for disposal.

If you are not sure whether you should take this medicine, talk to your doctor.

Before you start to take Isomonit

Tell your doctor if you have allergies to:

  • any other medicines, especially if they are in the same drug class as isosorbide mononitrate
  • any other substances, including foods, preservatives or dyes.

If you have an allergic reaction you may get a skin rash, hayfever, asthma or feel faint.

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

Tell your doctor if you have or have had any medical conditions, especially the following:

  • any illness affecting your liver or kidneys
  • low blood pressure (this can make you feel faint, weak or dizzy, especially when you stand up suddenly)
  • heart and blood vessel problems

It may not be safe for you to take Isomonit if you have any of these conditions.

Do not use Isomonit to treat acute angina.

Isomonit must be taken once daily.

Do not stop taking it abruptly.

Taking other medicines

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

In particular, tell your doctor if you take any of the following:

  • sildenafil (Viagra®), vardenafil (Levitra®), tadalafil (Cialis®)
  • N-acetylcysteine
  • captopril
  • calcium channel blockers
  • beta-blocker medicines.

These medicines may affect the way Isomonit work.

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

If you have not told your doctor about any of these things, tell them before you take any Isomonit.

HOW TO TAKE ISOMONIT

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

Take ONE (1) tablet taken once a day. If your doctor tells you to take TWO (2) tablets daily, both tablets should be taken at the same time.

Taking Isomonit at 24 hour intervals makes sure they keep working properly.

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

It is important that Isomonit is only taken once daily. This is so that there are some hours of the day where there are low levels of drug in the blood. This reduces the risk of the body getting used to the drug which could mean it wouldn't work so well.

If you forget to take your dose

If you miss a dose of Isomonit, take it as soon as you remember unless more than eight hours have passed. If more than eight hours have passed since the last dose was taken, do not take the missed dose but take the next dose at the normal time.

Do not take a double dose to make up for the dose you missed. 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. Isomonit tablets are not recommended and should not be taken for the treatment of acute angina attacks.

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

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

If you take too much

Immediately telephone your doctor or the Poisons Information Centre (telephone 13 11 26) for advice or go to Accident and Emergency at your nearest hospital, if you think that you or anyone else may have taken too much Isomonit.

Do this even if there are no signs of discomfort or poisoning. You may need urgent medical attention.

The most common symptom of overdose is a pulsing headache. You may also feel excited, flushed, have cold sweats, nausea (feeling sick) and vomit.

WHILE YOU ARE TAKING ISOMONIT

Things you must do

Always follow your doctor's instructions carefully.

Tell your doctor if you become pregnant while taking Isomonit.

If you are about to start taking a new medicine, tell your doctor and pharmacist that you are taking Isomonit.

Tell your doctor if you continue to get angina attacks, or they become more frequent while you are taking Isomonit.

Things you must not do

Do not stop taking Isomonit without your doctor's permission. It is important not to stop taking this medicine abruptly.

Do not use Isomonit to treat any other complaint unless your doctor says so.

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

Do not take medicines known as phosphodiesterase type 5 inhibitor used to treat impotence (or erectile dysfunction) whilst on Isomonit.

Do not take Isomonit to relieve acute attacks of angina. Your doctor will have given you other tablets or a spray to use when you get attacks of angina.

Things to be careful of

You will probably feel better when you start taking Isomonit, but be careful not to overdo physical activities straight away. You will need time to improve your physical fitness.

Be careful driving or operating machinery until you know how Isomonit affects you. Isomonit may cause tiredness or dizziness especially when you first start to take it. Make sure you know how you feel when you are taking Isomonit before you drive a car, operate machinery, or do anything else that could be dangerous if you are dizzy.

Be careful when drinking alcohol while you are using Isomonit. If you drink alcohol, 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 Isomonit.

This medicine helps most people with angina, but it may have unwanted side 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 attention if you get some of the side effects.

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

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

Isomonit often causes adverse effects in the early stages of treatment.

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

  • headache
  • feeling faint
  • dizziness
  • fatigue
  • muscle tenderness or weakness, not caused by exercise.

Headache is the most common side effect while taking Isomonit. It can occur at the beginning of treatment, but usually goes away after a few days.

These are all mild side effects of Isomonit.

Tell your doctor if you notice any other effects while taking this medicine.

Other side effects not listed above may also occur in some people.

AFTER TAKING ISOMONIT

Storage

Keep Isomonit in the original packaging until it is time to take them. If you take Isomonit out of the blister pack, it will not keep well.

Store below 25°C in a dry place, out of the reach of children.

Protect from light and moisture.

Do not store Isomonit or any other medicine in the bathroom or near a sink. Do not leave it on a window sill or in the car. Heat and dampness can destroy some medicines.

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

Disposal

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

PRODUCT DESCRIPTION

What Isomonit looks like

Isomonit modified release tablets are oval tablets with a cream coloured film coating and half scored on both sides. They are available in packs of 30 tablets.

Ingredients

Active Ingredient

Isomonit tablets contain isosorbide mononitrate as the active ingredient.

Inactive Ingredients

As well as the active ingredient, Isomonit also contains some inactive ingredients. These are stearic acid, carnauba wax, hypromellose, lactose monohydrate, magnesium stearate, purified talc, titanium dioxide, purified siliceous earth, macrogol 4000, iron oxide yellow CI77492.

Supplier

Sandoz Pty Ltd
ABN 60 075 449 553
54 Waterloo Road
Macquarie Park, NSW 2113
Australia
Tel: 1800 726 369

This leaflet was revised in February 2019.

Australian Register Number

Isomonit 60 mg modified release tablets (blister): AUST R 75241

Published by MIMS March 2019

BRAND INFORMATION

Brand name

Isomonit

Active ingredient

Isosorbide mononitrate

Schedule

S4

 

1 Name of Medicine

Isosorbide mononitrate.

2 Qualitative and Quantitative Composition

Each Isomonit modified release tablet contains 60 mg isosorbide mononitrate.

Excipient with known effect.

Lactose monohydrate.
For the full list of excipients, see Section 6.1 List of Excipients.

3 Pharmaceutical Form

Isomonit modified release tablets are oval tablets with a cream coloured film coating and half scored on both sides.

4 Clinical Particulars

4.1 Therapeutic Indications

Isomonit is indicated for prophylactic treatment of angina pectoris.
Isomonit is 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

Dosage.

One 60 mg Isomonit tablet once daily. The dose may be increased to 120 mg once daily.
Isomonit should not be administered twice daily.
Isomonit should not be chewed or crushed, and should be swallowed whole with half a glass of fluid.
There is insufficient evidence to show that one halved tablet of Isomonit 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.

4.3 Contraindications

Known hypersensitivity to nitrates or to any of the components in Isomonit, shock (including cardiogenic shock), hypotension, obstructive hypertrophic cardiomyopathy, 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.

Isomonit 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 isosorbide mononitrate modified release tablets are administered. It is therefore important that isosorbide mononitrate 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.
Caution should also be observed if isosorbide mononitrate modified release tablets are administered to patients with: severe cerebral arteriosclerosis, pronounced mitral stenosis, hypotension.

Acute angina.

Isosorbide mononitrate modified release tablets are not indicated for the relief of acute attacks of angina.

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.

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 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 (IR) 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 IR 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 isosorbide mononitrate 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 (see Section 4.4 Special Warnings and Precautions for Use).

Paediatric use.

Due to lack of data, the use of isosorbide mononitrate 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.

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.

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.

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)

Adverse effects associated with the vascular activity of the drug are common and as expected with all nitrate preparations. They occur mainly in the early stages of treatment. Headache predominates (up to 30%), but the incidence reduces rapidly as treatment continues. Only 2-3% of patients withdrew during clinical trials due to this adverse effect.
Hypotension (4%) with symptoms such as dizziness and nausea have been reported. These symptoms generally disappear during long-term treatment.
The following adverse reactions have been reported in studies with isosorbide mononitrate:

Cardiovascular.

Hypotension (4-5%), tachycardia.

Central nervous system.

Headache, vertigo, fainting.

Gastrointestinal.

Poor appetite (2.5%), nausea (1%), vomiting, diarrhoea, heartburn.

Skin.

Rash, pruritus.
Tiredness, sleep disturbances (6%), and gastro-intestinal disturbances (6%) have been reported during clinical trials with isosorbide mononitrate but at a frequency no greater than for placebo.
The following adverse events have been observed in the post-marketing period (definitions of frequency: common 1 - 9.9%; uncommon 0.1 - 0.9%; rare 0.01 - 0.09%; very rare < 0.01%).

Central nervous system.

Common: dizziness.

Musculoskeletal.

Very rare: myalgia.

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 Poison Information Centre on 131126 (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 post-stenotic 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

Absorption.

Administration of isosorbide mononitrate 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. Drug particles close to the tablet surface are released relatively rapidly, but those incorporated more deeply are released more slowly. The absorption of isosorbide mononitrate modified release tablet has been shown not to be influenced by food intake.
After repeated once daily administration of isosorbide mononitrate 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 isosorbide mononitrate modified release tablets.
The release mechanism in Isomonit comprises active drug distributed within a hydrophobic cellulose matrix with release occurring by diffusion.

Distribution.

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.

Metabolism and excretion.

Isosorbide mononitrate has an elimination half-life of around 5 hours. Isosorbide mononitrate modified release tablets provide a sustained release presentation of isosorbide mononitrate, with approximately 85% bioavailability.
Elimination takes place predominantly by denitrification and conjugation in the liver. The metabolites are excreted mainly via the kidneys, with only about 2% of the dose being excreted intact.

Special populations.

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 isosorbide mononitrate 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 Isomonit 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 sustained release tablets than with whole tablets.
Pharmacokinetic studies suggest that absorption of isosorbide mononitrate modified release tablet is slower in some patients with acute myocardial infarction compared to healthy volunteers. At steady state absorption of isosorbide mononitrate modified release tablet is similar in patients with acute myocardial infarction and in healthy volunteers. The steady state elimination half-life is longer in patients with acute myocardial infarction compared to healthy volunteers (see Section 4.4 Special Warnings and Precautions for Use, Acute myocardial infarction and congestive cardiac failure).

5.3 Preclinical Safety Data

Genotoxicity.

No data available.

Carcinogenicity.

No data available.

6 Pharmaceutical Particulars

6.1 List of Excipients

Hypromellose, carnauba wax, stearic acid, lactose monohydrate, purified siliceous earth, 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.
For information on interactions with other medicines and other forms of interactions, see Section 4.5 Interactions with Other Medicines and Other Forms of Interactions.

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. Protect from light and moisture.

6.5 Nature and Contents of Container

Isomonit modified release tablets are available in PVC/PVDC/Al blister packs 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

Isosorbide mononitrate is a white to pale yellow, crystalline, odourless powder that is freely soluble in water.
The chemical name of isosorbide mononitrate is 1,4:3,6-dianhydro-D-glucitol 5-nitrate. Its empirical formula is C6H9NO6 (MW: 191.14).

Chemical structure.

Its chemical structure is:

CAS number.

16051-77-7.

7 Medicine Schedule (Poisons Standard)

S4.

Summary Table of Changes