 ISORDIL® SUBLINGUAL Tablets 5 mg
ISORDIL® Tablets 10 mg
ISORDIL® Tablets 30 mg
ISORDIL® TEMBIDS® Tablets 40 mg
SCHEDULING STATUS:
S3
PROPRIETARY NAME
(and dosage form):
ISORDIL® SUBLINGUAL Tablets 5 mg
ISORDIL® Tablets 10 mg
ISORDIL® Tablets 30 mg
ISORDIL® TEMBIDS® Tablets 40 mg
COMPOSITION:
ISORDIL SUBLINGUAL 5 mg tablet contains 5 mg Isosorbide dinitrate.
ISORDIL 10 mg tablet contains 10 mg Isosorbide dinitrate.
ISORDIL 30 mg tablet contains 30 mg Isosorbide dinitrate.
ISORDIL TEMBIDS tablet contains 40 mg Isosorbide dinitrate.
ISORDIL 30 mg and 40 mg tablets contain TARTRAZINE.
PHARMACOLOGICAL CLASSIFICATION:
A.7.1.4 Vasodilators - coronary and other medicines used in angina pectoris.
PHARMACOLOGICAL ACTION:
ISORDIL is a dilator of arterial and venous smooth muscle. It relaxes smooth muscle including vascular muscle, lowers peripheral arterial blood pressure, decreases venous return and decreases left ventricular filling pressure.
INDICATIONS:
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i) |
Angina pectoris:
ISORDIL Sublingual tablets: For treatment of angina pectoris and for prophylaxis in situations likely to provoke an angina attack i.e., physical or emotional stress.
ISORDIL Oral tablets: For prophylaxis of angina pectoris due to coronary artery disease. The oral tablets are not indicated for the treatment of acute anginal attack, since the onset of this product is not sufficiently rapid to abort acute attack.
ISORDIL Tembids tablets. For prophylaxis of angina pectoris due to coronary artery disease. The Tembids tablets are not indicated for the treatment of acute anginal attack, since the onset of this product is not sufficiently rapid to abort such an attack. |
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ii) |
Congestive Heart Failure:
Sublingual and oral ISORDIL is also recommended in acute and chronic congestive heart failure including that which maybe associated with myocardial infarction.
At present, based on currently available literature, such therapy should be considered only as adjunct to the more conventional modes of treatment such as diuretics, and angiotensin converting enzyme (ACE) inhibitors.
Only in cases refractory to conventional therapy should ISORDIL be used alone or concomitantly with other vasodilators. ISORDIL is particularly effective in patients with increased left ventricular end diastolic pressure (LVEDP) and normal or approximately normal cardiac output, in whom pulmonary congestion (oedema) is the leading problem. |
CONTRA-INDICATIONS:
Contra-indicated in patients hypersensitive to isosorbide dinitrate.
ISORDIL should not be used in patients with severe anaemia, recent head trauma or cerebral haemorrhage, severe renal or hepatic impairment, or in patients with increased intracranial pressure.
Safety in pregnancy and lactation has not been established.
Safety and effectiveness in paediatric patients have not been establised.
WARNINGS:
Tolerance may develop with daily use but gradual withdrawal restores the original sensitivity.
ISORDIL 30 mg and 40 mg tablets contain F D & C Yellow No. 5 (Tartrazine) which may cause allergic type reactions (including Bronchial Asthma) in certain susceptible individuals. Although the overall incidence of Tartrazine sensitivity in the general population is currently thought to be low, it is frequently seen in patients who also have aspirin sensitivity.
Amplification of the vasodilatory effects of Isordil by sildenafil can result in severe hypotension.
DOSAGE AND DIRECTIONS FOR USE:
Angina Pectoris:
ISORDIL 5 mg SUBLINGUAL Tablets:
The basic dosage is one-half to two tablets (2,5-10 mg) every 2 to 3 hours, used sublingually for treatment of an angina pectoris attack, (including angina decubitus) or prophylactically in situations likely to provoke such attacks.
The sublingual tablets may also be taken orally in doses of 5-10 mg for the prevention of angina pectoris or to supplement the oral dosage forms. The sublingual tablets may also be taken orally in patients requiring dosage adjustment because of headache during the early stages of therapy.
ISORDIL oral dosage forms (10 mg; 30 mg and TEMBIDS tablets) should preferably be taken with a glass of water on an empty stomach (either 1 hour before or 2 hours after a meal) for faster absorption.
ISORDIL oral dosage forms (10 mg; 30 mg and TEMBIDS tablets) are not intended for relief of acute symptoms of angina pectoris.
ISORDIL 10 mg tablets are administered orally. The dosage range is 5 mg (half tablet) to 20 mg three times a day, according to the patients' need.
ISORDIL 30 mg tablets are administered orally, and, are indicated for patients requiring a higher dosage range to prevent or abort an anginal attack. It allows the physician to titrate the ISORDIL dosage, and to provide greater patient response, with greater convenience. The recommended daily dosage range is up to 120 mg a day. Thus, a regimen of 10 to 30 mg four times a day may be administered to provide prolonged and dependable prophylaxis against anginal attacks. Increases in dosage should be gradual to avoid side-effects. However, doses as high as 360 mg per day have been used in extreme cases without undue side-effects.
ISORDIL TEMBIDS Tablets 40 mg: These sustained action tablets are administered orally every 6 to 12 hours according to need. They are indicated for sustained prophylaxis against angina pectoris attacks including nocturnal angina. Although the latter condition is relatively infrequent, it is nonetheless angina, i.e. pain of coronary artery disease.
The medicine is gradually released over a 6-hour period to provide 8-10 hours of sustained effect. Although experiencing a reduction in the number of anginal attacks while under TEMBIDS therapy, patients may still have an attack under stressful conditions. In such cases, the therapy should be supplemented with sublingual ISORDIL tablets or nitroglycerin.
ISORDIL TEMBIDS SHOULD NOT BE CHEWED.
Congestive Heart Failure:
In acute and chronic congestive heart failure, both sublingual and oral forms of ISORDIL may be applied at a dosage level determined by the supervising physician, usually not exceeding 5-15 mg every two to three hours sublingually, or in oral doses of 30-160 mg daily, in divided doses. Oral doses up to 240 mg daily may be required.
The selection of sublingual or oral ISORDIL should be made on the basis of duration of action rather than the magnitude of response, since this is the major difference observed for these dosage forms. In order to obtain full therapeutic effect it is important that the dosage of sublingual and oral forms of ISORDIL be individualized in accordance with each patient's needs, clinical response and haemodynamic monitoring.
Every dosing regimen for ISORDIL must provide a daily dose-free interval to minimize the development of tolerance. With ISORDIL Sublingual tablets and Oral tablets, it appears that one daily dose-free interval must be at least 14 hours long. The necessary dose-free interval for ISORDIL TEMBIDS tablets has not been clearly identified, but is presumably somewhat longer.
ISORDIL therapy should begin with the lowest effective dose and further adjusted as necessary, based on the patient’s pathophysiologic state. The initial dose depends on the assessment of the severity of the degree of heart failure.
For treatment of acute congestive heart failure, the sublingual form of ISORDIL is preferable.
For treatment of chronic congestive heart failure, the rapid acting sublingual form of ISORDIL should be administered initially to stabilize the patient’s symptoms or to determine the magnitude of haemodynamic response, followed by the oral form for maintenance.
ISORDIL TEMBIDS are not recommended in the treatment of congestive heart failure because effects are difficult to terminate if excessive hypotension or tachycardia develop, although the dosage form may be acceptable once the patient is stabilised.
SIDE-EFFECTS AND SPECIAL PRECAUTIONS:
Cutaneous vasodilation with facial flushing, tachycardia, oedema and coldness of the skin.
Rarely cyanosis and methaemoglobinaemia may occur. Impairment of respiration and bradycardia may ensue.
Headache, which usually decreases after a few days, is common but may be severe and persistent. Headaches may often be controlled by decreasing the dose.
Transient episodes of dizziness and weakness as well as other signs of cerebral ischaemia associated with postural hypotension, and syncope may occasionally develop. Cresendo angina and rebound hypertension have also been reported but are uncommon.
Patients with normal or low pulmonary capillary wedge pressure may be unusually sensitive to hypotensive effects.
An occasional individual exhibits a marked sensitivity to the hypotensive effects of nitrate, and severe responses (laryngeal oedema, blurred vision, dryness of the mouth, nausea, vomiting, weakness, restlessness, pallor, perspiration and collapse) can occur even with the usual therapeutic dose. Alcohol antihypertensives or other hypotension producing medication, opioid analgesics or vasodilators may enhance this effect. Dosage adjustments may be necessary.
Drug rash and/or exfoliative dermatitis may occasionally occur.
A slight increase and decrease in intra-ocular pressure has been found in patients with closed angle glaucoma.
Precautions:
Haemolysis may occur in glucose-6-dehydrogenase deficient patients.
Tolerance can develop with long term use of this medicine, as a function of its dosage and frequency of administration. Cross tolerance to other nitrites and nitrates may occur. Isosorbide dinitrate should be dispensed and kept in the original container with the lid closed in order to maintain its half-life potency.
Use of ISORDIL TEMBIDS should be avoided in patients with gastrointestinal hypermotility or malabsorption syndrome because they may not dissolve and may be excreted intact.
Severe hypotension, particularly with upright posture, may occur with even small doses of isosorbide dinitrate. This medicine should therefore be used with caution in patients who may be volume depleted or who, for whatever reason, are already hypotensive.
Hypotension induced by isosorbide dinitrate may be accompanied by paradoxical bradycardia and increased angina pectoris.
Nitrate therapy may aggravate the angina caused by hypertonic cardiomyopathy.
In the treatment of heart failure, weather acute or chronic, pulmonary capillary pressure should not be allowed to fall below 15 mm Hg or systolic blood pressure below physiological range in normal or hypertensive patients. In patients with hypotension in the range of 90-100 mm Hg of systolic pressure there should be no fall at all. In sensitive patients, ISORDIL in high doses may cause paradoxical side-effects which may increase ischaemia and may even lead to extension of myocardial damage and advanced congestive heart failure.
Nitrate therapy should be discontinued it methaemoglobinaemia occurs, if blurred vision or dry mouth continues or is severe. When this medicine is to be discontinued following high dose or long term administration, dosage should be reduced gradually to prevent possible withdrawal rebound angina.
Geriatrics: The relationship of age to the effects of nitrates has not been studied in geriatrics. However elderly patients may be more sensitive to the hypotensive effects of nitrates and are more likely to have age related renal function impairment, which may require caution in patients receiving nitrates.
Paediatrics : Safety and effectiveness in paediatric patients has not been established.
Interactions:
The effects of norepinephrine, acetylcholine, histamine and many other agents maybe decreased when used concurrently with nitrates.
Concurrent use of sympathomimetics may reduce the anti-anginal effects of nitrates.
Alcohol, antihypertensives or other hypotension producing medication, opioid analgesics or vasodilators may intensify the orthostatic hypotensive effects of nitrates. Dosage adjustment may be necessary.
The effectiveness of sublingual isosorbide dinitrate may be reduced when concomitantly administered with disopyramide due to diminished salivary secretions caused by antimuscarinic action of disopyramide, which may inhibit the dissolution of the sublingual tablets.
Amplification of the vasodilatory effects of Isordil by sildenafil can result in severe hypotension. The time course and dose dependence of this interaction has not been studied. Appropriate supportive care has not been studied, but it seems reasonable to treat this as a nitrate overdose, with elevation of the extremities and with central volume expansion.
Laboratory/Physiology values:
Serum cholesterol determination by the Zlatkis-Zak colour reaction method may be falsely decreased.
Methaemoglobin concentration in blood may be increased by excessive doses of nitrate.
KNOWN SYMPTOMS OF OVERDOSAGE AND PARTICULARS OF ITS TREATMENT:
Symptoms: The ill effects of isosorbide dinitrate overdose are generally the results of isosorbide dinitrate's capacity to induce vasodilation, venous pooling, reduced cardiac output, and hypotension. These haemodynamic changes may have protean manifestations, including increased intracranial pressure, with any or all of persistent throbbing headache, confusion and moderate fever; vertigo; palpitations; visual disturbances; nausea and vomiting (possibly with colic and even bloody diarrhoea); syncope (especially in the upright posture); air hunger and dyspnoea, later followed by reduced ventilatory effort; diaphoresis; with the skin either flushed or cold and clammy; heart block and bradycardia; paralysis; coma; seizures; and death.
Treatment: In general, treatment should be symptomatic and supportive.
IDENTIFICATION:
ISORDIL SUBLINGUAL 5 mg tablets are small, round pink tablets.
ISORDIL 10 mg tablets are round, white scored tablets.
ISORDIL 30 mg tablets are round, yellow scored tablets.
ISORDIL TEMBIDS 40 are round, greenish-yellow, bevel edged, sustained action tablets.
PRESENTATION:
ISORDIL SUBLINGUAL 5 mg tablet: supplied in containers of 50 tablets.
ISORDIL 10 mg tablet: supplied in containers of 50 and 500 tablets.
ISORDIL 30 mg tablet: supplied in containers of 50 tablets.
ISORDIL TEMBIDS 40 mg: supplied in containers of 30 and 100 tablets and in amber glass bottles containing 500 tablets.
STORAGE INSTRUCTIONS:
Store in a cool (below 25°C), dry place.
Isosorbide dinitrate should be dispensed and kept in the original container with the lid closed in order to maintain its half-life potency.
KEEP OUT OF REACH OF CHILDREN.
REFERENCE NUMBERS:
ISORDIL 5 mg: H0602 (Act 101/1965);
ISORDIL 10 mg: H0603 (Act 101/1965);
ISORDIL 40 mg: H0604 (Act 101/1965).
REGISTRATION NUMBER:
ISORDIL 30 mg: L/7.1.4/27
NAME AND BUSINESS ADDRESS OF THE APPLICANT:
AKROMED PRODUCTS (PTY) LTD
Building 12,
Healthcare Park
Woodlands Drive
Woodmead
Sandton 2148
DATE OF PUBLICATION OF THIS PACKAGE INSERT:
8 January 1990
Trademark and product under licence from WYETH-AYERST LABORATORIES, U.S.A.
308457 030433 Harry's Printers K30314 G03
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