1. NAME OF THE MEDICINAL PRODUCT

Isosorbide Mononitrate Extended-Release Tablets USP 30mg Taj Pharma
Isosorbide Mononitrate Extended-Release Tablets USP 60mg Taj Pharma

  1. QUALITATIVE AND QUANTITATIVE COMPOSITIONa) Each Extended-Release Tablet contains:
    Isosorbide Mononitrate USP             30mg
    Excipients                                             q.s.

    b) Each Extended-Release Tablet contains:
    Isosorbide Mononitrate USP              60mg
    Excipients                                              q.s.

For the full list of excipients, see section 6.1.

  1. PHARMACEUTICAL FORM

Extended-release film-coated tablet

  1. CLINICAL PARTICULARS

4.1 Therapeutic indications

Prophylactic treatment of angina pectoris.

4.2 Posology and method of administration

Posology

Adults

Isosorbide Mononitrate Extended Release Tablets USP 30mg/60mg (one tablet) once daily given in the morning. The dose may be increased to 120mg (two tablets) daily, both to be taken once daily in the morning. The dose can be titrated to minimise the possibility of headache, by initiating treatment with 30mg (half a tablet) for the first 2-4 days.

Paediatric population

The safety and efficacy of Isosorbide Mononitrate Extended Release Tablets USP in children has not yet been established.

Older people

No evidence of a need for routine dosage adjustment in older people has been found, but special care may be needed in those with increased susceptibility to hypotension or marked hepatic or renal insufficiency.

The core of the tablet is insoluble in the digestive juices but disintegrates into small particles when all active substance has been released. Very occasionally the matrix may pass through the gastrointestinal tract without disintegrating and be found visible in the stool, but all active substance has been released.

Method of administration

Isosorbide Mononitrate Extended Release Tablets USP Tablets must not be chewed or crushed. They should be swallowed whole with half a glass of water.

4.3 Contraindications

Hypersensitivity to the active substance or to any of the excipients listed in section 6.1. Constrictive cardiomyopathy and pericarditis, aortic stenosis, cardiac tamponade, mitral stenosis and severe anaemia.

Patients treated with Isosorbide Mononitrate Extended Release Tablets USP must not be given Phosphodiesterase Type 5 Inhibitors (e.g. sildenafil).

Severe cerebrovascular insufficiency or hypotension are relative contraindications to the use of Isosorbide Mononitrate Extended Release Tablets USP.

4.4 Special warnings and precautions for use

Isosorbide Mononitrate Extended Release Tablets USP is not indicated for relief of acute angina attacks; in the event of an acute attack, sublingual or buccal glyceryl trinitrate tablets should be used.

4.5 Interaction with other medicinal products and other forms of interaction

Concomitant administration of Isosorbide Mononitrate Extended Release Tablets USP and Phosphodiesterase Type 5 Inhibitors can potentiate the vasodilatory effect of Isosorbide Mononitrate Extended Release Tablets USP with the potential result of serious side effects such as syncope or myocardial infarction. Therefore, Isosorbide Mononitrate Extended Release Tablets USP and Phosphodiesterase Type 5 Inhibitors (e.g. sildenafil) must not be given concomitantly.

4.6 Fertility, pregnancy and lactation

The safety and efficacy of Isosorbide Mononitrate Extended Release Tablets USP during pregnancy or lactation has not been established.

4.7 Effects on ability to drive and use machines

Patients may develop dizziness when first using Isosorbide Mononitrate Extended Release Tablets USP. Patients should be advised to determine how they react to Isosorbide Mononitrate Extended Release Tablets USP before they drive or operate machinery.

4.8 Undesirable effects

Most of the adverse reactions are pharmacodynamically mediated and dose dependent. Headache may occur when treatment is initiated, but usually disappears after 1-2 weeks of treatment. The dose can be titrated to minimise the possibility of headache, by initiating treatment with 30mg. Hypotension, with symptoms such as dizziness and nausea with syncope in isolated cases, has occasionally been reported. These symptoms generally disappear during continued treatment.

The following definitions of frequencies are used: Very Common (≥1/10), Common (≥1/100 to <1/10), Uncommon (≥1/1,000 to <1/100), Rare (≥1/10,000 to <1/1,000) and Very Rare (<1/10,000).

Adverse drug reactions by frequency and system organ class (SOC)

System Organ ClassFrequencyReaction
Nervous system disordersCommonHeadache, dizziness
RareFainting
Cardiac and vascular disordersCommonHypotension, tachycardia
Gastrointestinal disordersCommonNausea
UncommonVomiting, diarrhoea
Skin and subcutaneous tissue disordersRareRash, pruritus
Musculoskeletal and connective tissue disordersVery rareMyalgia

Reporting of suspected adverse reactions

Reporting suspected adverse reactions after authorisation of the medicinal product is important. It allows continued monitoring of the benefit/risk balance of the medicinal product.

4.9 Overdose

Symptoms

Pulsing headache. More serious symptoms are excitation, flushing, cold perspiration, nausea, vomiting, vertigo, syncope, tachycardia and a fall in blood pressure.

Management

Induction of emesis, activated charcoal. In case of pronounced hypotension the patient should first be placed in the supine position with legs raised. If necessary fluids should be administered intravenously.

  1. PHARMACOLOGICAL PROPERTIES

5.1 Pharmacodynamic properties

Pharmacotherapeutic group: Vasodilators used in cardiovascular disease (organic nitrates).

The principal pharmacological action of isosorbide mononitrate, an active metabolite of isosorbide dinitrate, is relaxation of vascular smooth muscle, producing vasodilation of both arteries and veins with the latter effect predominating. The effect of the treatment is dependent on the dose. Low plasma concentrations lead to venous dilatation, resulting in peripheral pooling of blood, decreased venous return and reduction in left ventricular end-diastolic pressure (preload). High plasma concentrations also dilate the arteries reducing systemic vascular resistance and arterial pressure leading to a reduction in cardiac afterload. Isosorbide mononitrate may also have a direct dilatory effect on the coronary arteries. By reducing the end diastolic pressure and volume, the preparation lowers the intramural pressure, thereby leading to an improvement in the subendocardial blood flow.

The net effect when administering isosorbide mononitrate is therefore a reduced workload of the heart and an improved oxygen supply/demand balance in the myocardium.

5.2 Pharmacokinetic properties

Isosorbide mononitrate is completely absorbed and is not subject to first pass metabolism by the liver. This reduces the intra- and inter-individual variations in plasma levels and leads to predictable and reproducible clinical effects.

The elimination half-life of isosorbide mononitrate is around 5 hours. The plasma protein binding is less than 5%. The volume of distribution for isosorbide mononitrate is about 0.6 l/kg and total clearance around 115 ml/minute. Elimination is primarily by denitration and conjugation in the liver. The metabolites are excreted mainly via the kidneys. Only about 2% of the dose given is excreted intact via the kidneys.

Impaired liver or kidney function have no major influence on the pharmacokinetic properties.

Isosorbide Mononitrate Extended Release Tablets USP is an extended release formulation (Durules). The active substance is released independently of pH, over a 10-hour period. Compared to ordinary tablets the absorption phase is prolonged and the duration of effect is extended.

The extent of bioavailability of Isosorbide Mononitrate Extended Release Tablets USP is about 90% compared to immediate release tablets. Absorption is not significantly affected by food intake and there is no accumulation during steady state. Isosorbide Mononitrate Extended Release Tablets USP exhibits dose proportional kinetics up to 120mg. After repeated peroral administration with 30mg/60mg once daily, maximal plasma concentration (around 3000 nmol/l) is achieved after around 4 hours. The plasma concentration then gradually falls to under 500 nmol/l at the end of the dosage interval (24 hours after dose intake). The tablets are divisible.

In placebo-controlled studies, Isosorbide Mononitrate Extended Release Tablets USP once daily has been shown to effectively control angina pectoris both in terms of exercise capacity and symptoms, and also in reducing signs of myocardial ischaemia. The duration of the effect is at least 12 hours, at this point the plasma concentration is at the same level as at around 1 hour after dose intake (around 1300 nmol/l).

Isosorbide Mononitrate Extended Release Tablets USP is effective as monotherapy as well as in combination with chronic β-blocker therapy.

The clinical effects of nitrates may be attenuated during repeated administration owing to high and/or even plasma levels. This can be avoided by allowing low plasma levels for a certain period of the dosage interval. Isosorbide Mononitrate Extended Release Tablets USP, when administered once daily in the morning, produces a plasma profile of high levels during the day and low levels during the night. With Isosorbide Mononitrate Extended Release Tablets USP 30mg/60mg or 120mg once daily no development of tolerance with respect to antianginal effect has been observed. Rebound phenomenon between doses as described with intermittent nitrate patch therapy has not been seen with Isosorbide Mononitrate Extended Release Tablets USP.

5.3 Preclinical safety data

The accessible data indicate that isosorbide mononitrate has expected pharmacodynamic properties of an organic nitrate ester, has simple pharmacokinetic properties, and is devoid of toxic, mutagenic or oncogenic effects.

  1. PHARMACEUTICAL PARTICULARS

6.1 List of excipients

Aluminium silicate, Paraffin special, Hydroxypropylcellulose LF, Magnesium stearate, Colloidal anhydrous silica, Hypromellose 6cps, Macrogol, Titanium dioxide, Iron oxide yellow

6.2 Incompatibilities

Not applicable for extended release products.

6.3 Shelf life

Glass bottle: 3 years

Blister pack: 3 years

6.4 Special precautions for storage

Do not store above 30°C.

6.5 Nature and contents of container

Amber glass bottles with a LD-polyethylene cap in a pack of 100 tablets.

Press-through package of thermoformed PVC, in packs of 7, 14, 28 and 98 tablets.

Not all pack sizes may be marketed.

6.6 Special precautions for disposal and other handling

Do not crush or chew tablets. The tablets should be taken with half a glass of water.

  1. MANUFACTURED IN INDIA BY:

TAJ PHARMACEUTICALS LTD.
Mumbai, India
Unit No. 214.Old Bake House,
Maharashtra chambers of  Commerce Lane,
Fort, Mumbai – 400001
at:Gujarat, INDIA.
Customer Service and Product Inquiries:
1-800-TRY-FIRST (1-800-222-434 & 1-800-222-825)
Monday through Saturday 9:00 a.m. to 7:00 p.m. EST
E-mail: tajgroup@tajpharma.com

ISOSORBIDE MONONITRATE EXTENDED-RELEASE TABLETS USP

Package leaflet: Information for the user

Isosorbide Mononitrate

Read all of this leaflet carefully before you start taking this medicine because it contains important information for you.

  • Keep this leaflet. You may need to read it again.
  • If you have any further questions, ask your doctor or pharmacist.
  • This medicine has been prescribed for you only. Do not pass it on to others. It may harm them, even if their signs of illness are the same as yours.
  • If you get any side effects, talk to your doctor or pharmacist. This includes any possible side effects not listed in this leaflet. See section 4.

WHAT IS IN THIS LEAFLET

  1. What Isosorbide Mononitrate is and what it is used for
  2. What you need to know before you take Isosorbide Mononitrate
  3. How to take Isosorbide Mononitrate
  4. Possible side effects
  5. How to store Isosorbide Mononitrate
  6. Contents of the pack and other information

 

  1. WHAT ISOSORBIDE MONONITRATE IS AND WHAT IT IS USED FOR

Isosorbide Mononitrate contains a medicine called isosorbide mononitrate. This belongs to a group of medicines called ‘nitrates’.

  • It is used to prevent chest pain (angina).
  • It works by making the blood vessels relax and widen. This makes it easier for the heart to pump blood around the body.

The tablets are made so that they release the medicine slowly over a number of hours.

  1. WHAT YOU NEED TO KNOW BEFORE YOU TAKE ISOSORBIDE MONONITRATE DO NOT TAKE ISOSORBIDE MONONITRATE:
  • If you are allergic to isosorbide mononitrate or any of the other ingredients of this medicine (listed in section 6).
  • If you have ever had a stroke.
  • If you have very low blood pressure.
  • If you have severe anaemia.
  • If you have a heart problem called ‘cardiomyopathy’ or ‘pericarditis’ or you have narrow heart valves.
  • If you are taking sildenafil or similar medicines called Phosphodiesterase Type 5 Inhibitors, (used for male impotence). See the section “Other medicines and Isosorbide Mononitrate”.

Do not take Isosorbide Mononitrate if any of the above apply to you. If you are not sure, talk to your doctor or pharmacist before taking Isosorbide Mononitrate.

Warnings and precautions

Talk to your doctor or pharmacist before taking Isosorbide Mononitrate if:

  • You have ever had any serious damage to your heart, such as a heart attack or operation.

If any of the above apply to you, or you are not sure, talk to your doctor or pharmacist before taking Isosorbide Mononitrate.

Other medicines and Isosorbide Mononitrate

Tell your doctor or pharmacist if you are taking, have recently taken or might take any other medicines. This includes medicines that you buy without a prescription and herbal medicines. This is because Isosorbide Mononitrate can affect the way some medicines work and some medicines can have an effect on Isosorbide Mononitrate.

Do not take Isosorbide Mononitrate if you are taking the following medicines:

  • Sildenafil or similar medicines called Phosphodiesterase Type 5 Inhibitors, (used for male impotence).

Do not take Isosorbide Mononitrate if any of the above apply to you. If you are not sure, talk to your doctor or pharmacist before taking Isosorbide Mononitrate.

Pregnancy, breast-feeding and fertility

If you are pregnant or breast-feeding, think you may be pregnant or are planning to have a baby, ask your doctor or pharmacist for advice before taking this medicine.

Driving and using machines

You may feel dizzy after taking Isosorbide Mononitrate. If this happens, do not drive or use any tools or machines.

  1. HOW TO TAKE ISOSORBIDE MONONITRATE

Always take this medicine exactly as your doctor or pharmacist has told you. Check with your doctor or pharmacist if you are not sure.

Taking this medicine

  • Swallow the tablets whole or broken in half (if this is easier to swallow).
  • Take the tablets with half a glass of water.
  • Do not crush or chew the tablets.

How much to take

  • The recommended dose is one or two tablets a day.
  • Take the medicine in the morning.
  • Your doctor may ask you to start on a low dose so that you are less likely to have a reaction to starting Isosorbide Mononitrate.
  • The blister strips are marked with the days of the week. If you are taking two tablets a day, make sure you take one tablet from each strip marked with the same day of the week.

You must not take Isosorbide Mononitrate for a sudden attack of angina. If you have a sudden attack, take a glyceryl trinitrate tablet (follow the instructions given on the label).

Very occasionally, some people see the remains of the tablet in their bowel motions. This is quite normal and does not mean that the medicine has not been released.

Use in children

Do not give these tablets to children.

If you take more Isosorbide Mononitrate than you should

If you take more Isosorbide Mononitrate than you should, talk to a doctor or go to a hospital straight away. Take the medicine pack with you so the tablets can be identified.

If you forget to take Isosorbide Mononitrate

  • If you forget a dose, take it as soon as you remember it. However, if it is nearly time for the next dose, skip the missed dose.
  • Do not take a double dose to make up for a forgotten dose.

If you have any further questions on the use of this medicine, ask your doctor or pharmacist.

  1. POSSIBLE SIDE EFFECTS

Like all medicines, this medicine can cause side effects, although not everybody gets them. The following side effects may happen with this medicine:

  • Feeling sick (nausea).
  • Feeling dizzy.

The above problems usually disappear with time. Other possible side effects:

Common (may affect up to 1 in 10 people)

  • Low blood pressure. This may make you feel faint or dizzy.
  • Faster heartbeat
  • Headache
  • Feeling dizzy
  • Feeling sick (nausea).

Uncommon (may affect up to 1 in 100 people)

  • Being sick (vomiting)
  • Diarrhoea

Rare (may affect up to 1 in 1,000 people)

  • Fainting
  • Rash
  • Itchy skin

Very rare (may affect up to 1 in 10,000 people)

  • Pain in muscles

Reporting of side effects

If you get any side effects, talk to your doctor or pharmacist. This includes any possible side effects not listed in this leaflet.

  1. HOW TO STORE ISOSORBIDE MONONITRATE
  • Keep this medicine out of the sight and reach of children.
  • Do not store above 30°C.
  • Do not use this medicine after the expiry date which is stated on the carton. The expiry date refers to the last day of that month.
  • Do not throw away any medicines via wastewater or household waste. Ask your pharmacist how to throw away medicines you no longer use. These measures will help protect the environment.
  1. CONTENTS OF THE PACK AND OTHER INFORMATION WHAT ISOSORBIDE MONONITRATE CONTAINSa) Each Extended Release Tablet contains:
    Isosorbide Mononitrate USP      30mg
    Excipients                                             q.s.b) Each Extended Release Tablet contains:
    Isosorbide Mononitrate                60mg
    Excipients                                              q.s.

The other ingredients are aluminium silicate, paraffin special, hydroxypropyl cellulose, magnesium stearate, colloidal anhydrous silica, hypromellose, macrogol, titanium dioxide and iron oxide.

What Isosorbide Mononitrate looks like and contents of the pack

Isosorbide Mononitrate Tablets 60 mg are yellow, and come in blister strips containing 7 tablets, which have the days of the week shown. A pack may contain either 7, 14, 28 or 98 tablets as multiples of the 7 tablet blister strip.

Isosorbide Mononitrate Tablets 60 mg may also come in glass bottles of 100 tablets.

  1. MANUFACTURED IN INDIA BY:

TAJ PHARMACEUTICALS LTD.
Mumbai, India
Unit No. 214.Old Bake House,
Maharashtra chambers of  Commerce Lane,
Fort, Mumbai – 400001
at:Gujarat, INDIA.
Customer Service and Product Inquiries:
1-800-TRY-FIRST (1-800-222-434 & 1-800-222-825)
Monday through Saturday 9:00 a.m. to 7:00 p.m. EST
E-mail: tajgroup@tajpharma.com