Consumer medicine information

Imdur Durules

Isosorbide mononitrate

BRAND INFORMATION

Brand name

Imdur Durules

Active ingredient

Isosorbide mononitrate

Schedule

S4

 

Consumer medicine information (CMI) leaflet

Please read this leaflet carefully before you start using Imdur Durules.

What is in this leaflet

This leaflet answers some of the common questions people ask about IMDUR DURULES. It does not contain all the information that is known about IMDUR DURULES.

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

All medicines have risks and benefits. Your doctor has weighed the risks of you taking IMDUR DURULES against the benefits they expect it will 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 need to read it again.

What IMDUR DURULES are for

IMDUR DURULES are 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.

IMDUR DURULES belong to a group of medicines called nitrates.

IMDUR DURULES 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 IMDUR DURULES 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.

IMDUR DURULES are not addictive.

Before you use IMDUR DURULES

When you must not use it

Do not use IMDUR DURULES if you are allergic to it or food containing nitrates or nitrites or any ingredients listed at the end of the leaflet.

Do not use IMDUR DURULES if you have the following medical conditions:

  • Low blood pressure
  • Shock including those caused by low blood pressure or failing heart
  • Pericarditis (swelling around the heart)
  • Weakened muscle of the heart

You must not use IMDUR DURULES whilst taking sildenafil (Viagra*), vardenafil (Levitra=), tadalafil (Cialis+).

Do not use IMDUR DURULES 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 IMDUR DURULES from breast milk if you are breast feeding.

Do not give IMDUR DURULES to children. There is no specific information about use in children, so IMDUR DURULES 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 use it

You must tell your doctor if:

  1. you have any allergies to:
  • any medicine, foods, preservatives or dyes.

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

  1. you have any of these medical conditions:
  • 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 IMDUR DURULES if you have any of these conditions.

Do not use IMDUR DURULES to treat acute angina.

IMDUR DURULES must be taken once daily.

Do not stop taking it abruptly.

Taking other medicines

Tell your doctor if you are taking any other medicines, including:

  • sildenafil (Viagra*), vardenafil (Levitra=), tadalafil (Cialis+)
  • medicines that you buy without a prescription from a pharmacy, supermarket or health food shop.

These medicines may affect the way IMDUR DURULES 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 IMDUR DURULES.

Using IMDUR DURULES

How to take it

Take one IMDUR DURULE modified release tablet every day, at about the same time.

If your doctor tells you to take two 60mg IMDUR DURULES each day, take both modified release tablets at the same time.

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

Swallow IMDUR DURULES modified release tablets whole, with half a glass of water or other liquid e.g. fruit juice, milk. Do not chew or crush the tablets.

The 60mg modified release tablet can be broken in half if care is taken not to crumble them. IMDUR DURULES modified release tablets are designed to let the drug out over a number of hours. If they are crushed or chewed they won't work properly.

IMDUR DURULES modified release tablets are composed of a waxy substance that does not dissolve in the body. You may find the outer shell of the tablets in your bowel motions. The medication in them has already been absorbed by the body.

If you forget to take it

If you forget to take a dose, take it as soon as you remember, as long as it is not more than eight (8) hours late. If it is more than eight (8) hours after you should have taken IMDUR DURULES, wait until the right time the next day to take it.

Do not double the dose.

You may find that you will need to use the tablets or spray that your doctor has given you to use during angina attacks if you miss a dose of IMDUR DURULES.

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

Overdose

Telephone your doctor or the Poisons Information Centre (13 11 26), or go to casualty at your nearest hospital immediately if you think that you or anyone else may have taken too much IMDUR DURULES even if there are no signs of discomfort or poisoning.

If you take too many IMDUR DURULES modified release tablets you will have a pulsing headache. You may also feel excited, flushed, have cold sweats, nausea (feeling sick) and vomit.

While you are using IMDUR DURULES

Things you must do

Take IMDUR DURULES regularly once every day. If you don't you will be more likely to get attacks of angina.

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

Things you must not do

Do not use IMDUR DURULES 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.

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

Do not stop taking IMDUR DURULES unless you have discussed it with your doctor.

Do not use IMDUR DURULES for any other complaints unless your doctor tells you to.

Do not give your medicine to anyone else, even if they have the same condition as you.

Things to be careful of

You will probably feel better when you start taking IMDUR DURULES, 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 IMDUR DURULES affects you. IMDUR DURULES may cause dizziness and fainting in some patients, especially when you first start to take it. Make sure you know how you feel when you are taking IMDUR DURULES 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 IMDUR DURULES. If you drink alcohol while you are taking IMDUR DURULES, your blood pressure may drop, making you feel dizzy or faint.

Please talk to your doctor or pharmacist about these possibilities if you think they may bother you.

Side effects

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

IMDUR DURULES help 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 treatment if you get some of the side effects.

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

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

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

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

These are all mild side effects of IMDUR DURULES.

Tell your doctor if you notice anything else that is making you feel unwell. Some people may get other side effects while taking IMDUR DURULES.

After using it

Storage

Keep your IMDUR DURULES modified release tablets in the blister pack until it is time to take them. If you take IMDUR DURULES out of the blister pack it will not keep well.

Keep it in a cool dry place where the temperature stays below 30°C.

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

Do not leave it in the car on hot days. Heat and dampness can destroy some medicines.

Keep it where young 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

Ask your pharmacist what to do with any tablets you have left over if your doctor tells you to stop taking them, or you find that they have expired.

Product description

What IMDUR DURULES look like

IMDUR DURULES 60mg modified release tablets are yellow, oval tablets, scored on both sides, marked A/ID.

IMDUR DURULES 120mg modified release tablets are whitish, oval tablets marked A/IF.

Ingredients

Each IMDUR DURULE modified release tablet contains:

Isosorbide mononitrate 60mg or 120mg as the active ingredient;

plus,

Aluminium silicate

Paraffin special

Magnesium stearate

Hydroxypropylcellulose

Colloidal silica.

in blister packs of 30 modified release tablets.

The coating on each modified release tablet contains hydroxypropylmethylcellulose (E464), propylene glycol (E1520);

with colouring agents,

titanium dioxide (E171)

iron oxide yellow (E172).

Sponsor

Clinect Pty Ltd,
120-132 Atlantic Drive,
Keysborough, VIC 3173,
Australia
Free Call Australia: 1800 899 005

This leaflet was prepared 29 October 2018

Australian Registration Number (ARTG)

60mg 46390

120mg 62795

*Registered trademark of Pfizer

= Registered trademark of Bayer

+ Registered trademark of Eli Lilly

Published by MIMS January 2019

BRAND INFORMATION

Brand name

Imdur Durules

Active ingredient

Isosorbide mononitrate

Schedule

S4

 

1 Name of Medicine

Isosorbide mononitrate.

6.7 Physicochemical Properties

The chemical name is 1,4:3,6-Dianhydro-D-glucitol 5-nitrate. Molecular formula C6H9NO6; m.w. 191.14. Isosorbide mononitrate is a white to pale yellow crystalline powder and is freely soluble in water.

Chemical structure.

The chemical structure of isosorbide mononitrate is:

CAS number.

CAS 16051-77-7.

2 Qualitative and Quantitative Composition

Imdur Durules modified release tablets containing isosorbide mononitrate 60 mg or 120 mg. For the full list of excipients, see Section 6.1 List of Excipients.

3 Pharmaceutical Form

Imdur Durules (modified release tablets) 60 mg: Yellow, oval, biconvex tablets, scored on both sides, engraved A/ID.
Imdur Durules (modified release tablets) 120 mg: White to off-white, oval, biconvex tablets, engraved A/IF.

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 the 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 the 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 (NO). Organic nitrates are metabolised to NO 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 Imdur Durules 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 Imdur Durules has been shown not to be influenced by food intake.
After repeated once daily administration of Imdur Durules 60 mg, the maximum plasma level (about 3000 nmol/L) of isosorbide mononitrate is achieved at about 4 hours. The plasma concentration remains above 1400-1500 nmol/L for approximately 10 hours, dropping to under 500 nmol/L by the end of the dosage interval (24 hours after dose). This nitrate low period minimises the possibility of nitrate tolerance developing during prolonged treatment with Imdur Durules.

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 five hours. Imdur Durules 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, Imdur Durules 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 beta-blocker therapy.
It is known that the clinical effects may be attenuated during repeated administration with nitrates in high doses and/or during frequent administration. However, the pharmacokinetic characteristics of Imdur Durules produce a nitrate low period following once daily dosage. No development of tolerance with respect to antianginal effect has been detected when Imdur Durules are given at a dose of one or two tablets (60 mg or 120 mg) once daily. The drug is not recommended for twice daily administration.
Pharmacokinetic studies suggest that absorption of Imdur Durules is slower in some patients with acute myocardial infarction compared to healthy volunteers. At steady state absorption of Imdur Durules 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 & congestive cardiac failure).

5.3 Preclinical Safety Data

Genotoxicity.

No data available.

Carcinogenicity.

No data available.

4 Clinical Particulars

4.1 Therapeutic Indications

Imdur Durules are indicated for prophylactic treatment of angina pectoris.
Imdur Durules are not recommended for the management of acute attacks of angina pectoris (see Section 4.4 Special Warnings and Precautions for Use).

4.3 Contraindications

Known hypersensitivity to nitrates or to any of the components in Imdur Durules.
Shock (including cardiogenic shock), hypotension, obstructive hypertrophic cardiomyopathy and pericarditis.
Phosphodiesterase type 5 inhibitors (e.g. sildenafil, tadalafil and vardenafil) must not be given concomitantly with Imdur Durules.

4.4 Special Warnings and Precautions for Use

Please 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 Imdur Durules are administered. It is therefore important that Imdur Durules 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 Imdur Durules are administered to patients with severe cerebral arteriosclerosis, pronounced mitral stenosis, hypotension.

Acute angina.

Imdur Durules 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 Imdur Durules, such withdrawal is not recommended because of the possibility of severe exacerbation of anginal symptoms.

Use in renal impairment.

The elimination of isosorbide mononitrate following administration of an immediate release (IR) tablet has been investigated in patients with severe renal impairment, but not using the modified release Durule. 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 Imdur Durule presentation in patients with severe renal impairment, the possibility of accumulation should be borne in mind when administering Imdur Durules to such patients, in whom a reduced dosage may be appropriate.

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).

Paediatric use.

Due to lack of data, the use of Imdur Durules cannot be recommended in children.

Use in the elderly.

No dose reduction is necessary in the elderly unless they have severe renal impairment (see Section 4.4 Special Warnings and Precautions for Use).

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 undertaken 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 breast feeding is not recommended.

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 Imdur Durules 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 reactions.

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 https://www.tga.gov.au/reporting-problems.

4.2 Dose and Method of Administration

One 60 mg Imdur Durule once daily. The dose may be increased to 120 mg once daily.
Imdur Durules should not be administered twice daily.
If headache occurs, the initial dose may be reduced to half a 60 mg tablet daily until the headache disappears. Patients with severe renal impairment may require dosage reduction to half a tablet given once daily.
Imdur Durules should not be chewed or crushed, and should be swallowed whole with half a glass of fluid. If care is taken to avoid crushing or chewing the tablet, half doses of the 60 mg tablet may be administered without affecting the modified release properties of Imdur Durules. The 120 mg tablet is not scored and should not be administered in half doses.

4.7 Effects on Ability to Drive and Use Machines

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

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.

Management.

Administer activated charcoal. In patients with severe hypotension, first place in the 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).

7 Medicine Schedule (Poisons Standard)

S4.

6 Pharmaceutical Particulars

6.1 List of Excipients

Imdur Durules contain the active drug embedded in a porous inert matrix consisting of paraffin-synthetic, aluminium sodium silicate, magnesium stearate, hydroxypropylcellulose and silica - colloidal anhydrous. In addition the tablet coating contains hypromellose, macrogol, titanium dioxide, hydrogen peroxide, paraffin-synthetic and water-purified.

6.2 Incompatibilities

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

6.3 Shelf Life

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

6.4 Special Precautions for Storage

Store below 30°C.

6.5 Nature and Contents of Container

Imdur Durules 60 mg: blister packs of 7^, 10^, 15^, 30.
Imdur Durules 120 mg: blister packs of 7^, 30.
^ Currently 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.

Summary Table of Changes