Isosorbide Mononitrate Tablets 40mg
Out of date information, search anotherSUMMARY OF PRODUCT CHARACTERISTICS
1 NAME OF THE MEDICINAL PRODUCT
ISOSORBIDE MONONITRATE TABLETS 40 mg
2 QUALITATIVE AND QUANTITATIVE COMPOSITION
Isosorbide mononitrate 40.0 mg For excipients, see Section 6.1.
3 PHARMACEUTICAL FORM
Tablets
White round tablets, scored on one side with an embossment "ISMN 40".
4. CLINICAL PARTICULARS
4.1 Therapeutic indications
Isosorbide mononitrate is indicated for the prophylaxis of angina pectoris.
4.2 Posology and method of administration
For oral administration, it is recommended that the tablets should be swallowed whole with a little fluid after meals.
Dosage should be reduced in patients with renal or hepatic impairment.
Adults
One tablet to be taken asymmetrically (to allow a nitrate low period) two or three times a day. Patients already accustomed to prophylactic nitrate therapy may normally be transferred directly to a therapeutic dose of isosorbide mononitrate. For patients not already receiving prophylactic nitrate therapy it is recommended that the initial dose be one tablet of Isosorbide Mononitrate Tablets 20mg twice a day.
The maintenance dose in individual patients is usually between 20- 120 mg daily.
The lowest effective dose should be used.
Elderly
Dosage requirements may be reduced especially when hepatic or renal function is impaired. Also, particular care should be taken due to susceptibility to hypotension.
Children
The safety and efficacy of Isosorbide Mononitrate Tablets 10 mg has yet to be established in children.
Treatment with Isosorbide Mononitrate Tablets, as with any other nitrates, should not be stopped suddenly. Both the dosage and frequency should be tapered gradually (see section 4.4)
4.3 Contraindications
Isosorbide Mononitrate Tablets 10 mg should not be used in cases of acute myocardial infarction with low filling pressures, acute circulatory failure (shock, vascular collapse), or very low blood pressure, hypertrophic obstructive cardiomyopathy (HOCM), constrictive pericarditis, cardiac tamponade, low cardiac filling pressures, aortic/mitral valve stenosis and diseases associated with a raised intra-cranial pressure e.g. following a head trauma and including cerebral haemorrhage.
This product should not be given to patients with a known hypersensitivity to isosorbide dinitrate or mononitrate, to other nitrates or to any of the excipients.
Isosorbide Mononitrate Tablets 10 mg should not be used in patients with marked anaemia, sever hypotension, closed angle glaucoma or hypovolaemia.
Phosphodiesterase Type 5 Inhibitors (e.g. sildenafil, tadalafil, vardenafil) have been shown to potentiate the hypotensive effects of nitrates and their co-administration with nitrates or nitric oxide donors is therefore contraindicated (see section 4.5).
4.4 Special warnings and precautions for use
Isosorbide Mononitrate Tablets 10 mg should be used with caution in patients who have a recent history of myocardial infarction, or who are suffering from closed-angle glaucoma, hypothyroidism, hypothermia, malnutrition and sever liver or renal disease.
Symptoms of circulatory collapse may arise after first dose in patients with labile circulation and in patients already taking ACE inhibitors.
This product may give rise to postural hypotension and syncope in some patients. Severe postural hypotension with light headedness and dizziness is frequently observed after the consumption of alcohol, therefore alcohol should be avoided during treatment. Hypotension induced by nitrates may be accompanied by paradoxical bradycardia and increased angina.
In the event of an acute angina attack, sublingual treatment such as a GTN spray or tablet should be used instead of isosorbide mononitrate tablets.
Isosorbide Mononitrate Tablets contain sucrose and lactose and therefore should not be used in patients with rare hereditary problems of fructose intolerance or galactose intolerance, the Lapp lactase deficiency, sucrase-isomaltase insufficiency or glucose-galactose malabsorption.
If the tablets are not taken as indicated (see section 4.2) tolerance to the medication and cross-tolerance to other nitrates may occur. The lowest effective dose should be used.
Treatment with isosorbide mononitrate tablets, as with any other nitrate, should not be stopped suddenly. Both the dosage and frequency should be tapered gradually (see section 4.2).
4.5 Interaction with other medicinal products and other forms of interaction
Isosorbide mononitrate can act as a physiological antagonist to noradrenaline, acetylcholine, histamine and other agents.
Concurrent administration of drugs with blood pressure lowering properties, e.g, beta-blockers, calcium channel blockers, vasodilators, alprostadil, aldesleukin, angiotensin II receptor antagonist, ACE inhibitors etc may potentiate the hypotensive effect of Isosorbide Mononitrate Tablets. This may also occur with neuroleptics and tricyclic antidepressants.
Alcohol can accentuate cerebral ischaemia associated with postural hypotension.
Any blood pressure lowering effect of Isosorbide Mononitrate Tablets will be increased if used together with phosphodiesterase type 5 inhibitors (eg sildenafil, tadalafil and verdenafil) which are used for erectile dysfunction (see special warnings and contraindications). This might lead to life threatening cardiovascular complications. Patients who are on Isosorbide Mononitrate Tablets therapy therefore must not use phosphodiesterase type-5 inhibitors.
Reports suggest that concomitant administration of Isosorbide Mononitrate Tablets may increase the blood level of dihydroergotamine and its hypertensive effect.
4.6 Fertility, pregnancy and lactation
No data have been reported which would indicate the possibility of adverse effects resulting from the use of isosorbide mononitrate in pregnancy. Safety in pregnancy, however, has not been established. It is not known whether nitrates are excreted in human milk and therefore caution should be exercised when administered to nursing women.
Isosorbide mononitrate should only be used in pregnancy and during lactation if, in the opinion of the physician, the possible benefits of treatment outweigh the hazards.
4.7 Effects on ability to drive and use machines
Dizziness, tiredness or blurred vision might occur at the start of treatment. The patients should therefore be advised that if affected, they should not drive or operate machinery. This effect may be increased by alcohol.
4.8 Undesirable effects
A very common (>10% of patients) adverse reaction to Isosorbide Mononitrate Tablets is throbbing headache. The incidence of headache diminishes gradually or disappears after 1-3 weeks and optimum dosage of isosorbide mononitrate may be achieved.
At the start of therapy or when the dosage is increased, hypotension and/or light headedness in the upright position are commonly observed (i.e in 1-10% of patients). These symptoms may be associated with cutaneous vasodilatation with flushing, dizziness, drowsiness, reflex tachycardia and occasionally unexplained bradycardia and a feeling of weakness.
Infrequently (i.e. in less than 1% of patients) nausea, vomiting, flushing and allergic skin reaction (e.g. rash) may occur sometimes severely. In single cases exfoliative dermatitis may occur.
Severe hypotensive responses have been reported for organic nitrates and include nausea, vomiting, restlessness, pallor and excessive perspiration. Uncommonly collapse may occur (sometimes accompanied by bradyarrhythmia and syncope). Uncommonly severe hypotension may lead to enhanced angina symptoms.
A few reports of heartburn most likely due to a nitrate induced sphincter relaxation have been recorded.
Tachycardia and paroxysmal bradycardia have been reported.
Nitrate-induced pituitary apoplexy has been reported in patients with undiagnosed pituitary tumours.
4.9 Overdose
Symptoms and signs:
Pulsing headache, hypotension, nausea, vomiting, flushing, cold perspiration, sweating, tachycardia, vertigo, restlessness, excitation, warm flushed skin, blurred vision and syncope. A rise in intracranial pressure with confusion and neurological deficits can sometimes occur. Methaemoglobinaemia (cyanosis, hypoxaemia, restlessness, respiratory depression, convulsions, cardiac arrhythmias, circulatory failure, raised intracranial pressure) occurs rarely.
Management:
Induction of emesis, consider oral activated charcoal if ingestion of a potentially toxic amount has occurred within 1 hour. Observe for at least 12 hours after the overdose. Monitor blood pressure and pulse. Correct hypotension by raising the foot of the bed and/or by expanding the intravascular volume. Other measures as indicated by the patient's clinical condition. If severe hypotension persists despite the above measures consider use of inotropes or intravenous administration of fluid.
If methaemoglobinaemia (symptoms or > 30% methaemoglobin), IV administration of methylene blue 1-2 mg/kg body weight. If therapy fails with second dose after 1 hour or contraindicated, consider red blood cell concentrates or exchange transfusion. In case of cerebral convulsions, diazepam or clonazepam IV, or if therapy fails, phenobarbital, phenytoin or propofol anaesthesia.
5 PHARMACOLOGICAL PROPERTIES
5.1 Pharmacodynamic properties
ATC Code: C01D A14 Vasodilators used in cardiovascular diseases.
Isosorbide mononitrate is an organic nitrate which, in common with other cardioactive nitrates, is a vasodilator. It produces decreased left and right ventricular end-diastolic pressures to a greater extent than the decrease in systemic arterial pressure, thereby reducing afterload and especially the preload of the heart.
Isosorbide mononitrate influences the oxygen supply to ischaemic myocardium by causing the redistribution of blood flow along collateral channels and from epicardial to endocardial regions by selective dilation of large epicardial vessels.
It reduces the requirement of the myocardium for oxygen by increasing venous capacitance, causing a pooling of blood in peripheral veins, thereby reducing ventricular volume and heart wall distension.
5.2 Pharmacokinetic properties
Isosorbide-5-mononitrate is rapidly absorbed and peak plasma levels occur approx. 1 hour following oral dosing.
Isosorbide-5-mononitrate is completely bioavailable after oral doses and is not subjected to pre-systemic elimination processes.Isosorbide-5-mononitrate is eliminated from the plasma with half-life of about 5.1 hours. It is metabolized to Isosorbide-5MN-2-glucoronide, which has a half-life of approximately 2.5 hours. As well as being excreted unchanged in the urine.
After multiple oral dosing plasma concentrations are similar to those that can be predicted from single dose kinetic parameters.
5.3 Preclinical safety data
Not applicable.
Pharmaceutical Particulars
6.
6.1 List of excipients
Lactose, Compressible sugar, Sodium starch glycollate, Colloidal anhydrous silica, Magnesium stearate.
6.2 Incompatibilities
Not applicable.
6.3 Shelf life
4 years
6.4 Special precautions for storage
Store in a dry place, below 25 °C.
6.5 Nature and contents of container
Aluminium foil/UPVC blister packs: 28, 50, 56, 60 or 100 tablets.
Recloseable polyethylene jars: 100, 500 tablets.
6.6 Special precautions for disposal
No specific statement.
7 MARKETING AUTHORISATION HOLDER
Dexcel®-Pharma Ltd.
7 Sopwith Way Drayton Fields, Daventry Northamptonshire NN11 8PB UK
PL 14017/0012
9 DATE OF FIRST AUTHORISATION/RENEWAL OF THE
AUTHORISATION
09/02/2005
10 DATE OF REVISION OF THE TEXT
12/11/2013