1. Name Of The Medicinal Product
Corgard Tablets 40mg
Corgard Tablets 80mg
2. Qualitative And Quantitative Composition
The tablets contain Nadolol 40.0mg or 80.0mg.
3. Pharmaceutical Form
Pale blue round biconvex tablets.
4. Clinical Particulars
4.1 Therapeutic Indications
Corgard is indicated in the management of:
Angina Pectoris: For the long-term management of patients with angina pectoris by continuous medication.
Hypertension: For the long-term management of essential hypertension, either alone or in combination with other antihypertensive agents, especially thiazide-type diuretics.
Arrhythmias: For the treatment of cardiac tachyarrhythmias.
Migraine: For the prophylactic management of migraine headache. The efficacy of
Corgard in the treatment of a migraine attack that has already started has not been established, and Corgard is not indicated for such use.
Thyrotoxicosis: For the relief of the symptoms of hyperthyroidism and the pre-operative preparation of patients for surgery. Nadolol may be used in conjunction with conventional antithyroid therapy.
4.2 Posology And Method Of Administration
Adults:
Dosage should be titrated gradually with at least a week between increments to assess response; individuals show considerable variation in their response to beta-adrenergic blockade.
Corgard may be given in a once daily dosage without regard to meals. The dosage interval should be increased when creatinine clearance is below 50ml/min/1.73m2.
If Corgard is to be discontinued, reduce dosage over a period of at least two weeks (see warnings).
Angina pectoris: Initially 40mg once daily. This may be increased at weekly intervals until an adequate response is obtained or excessive bradycardia occurs. Most patients respond to 160mg or less daily. The value and safety of daily doses exceeding 240mg have not been established.
Hypertension: Initially 80mg once daily. This may be increased by a weekly increment of 80mg or less until an optimum response is obtained. Many patients respond to 80mg daily, and most patients respond to 240mg or less, daily, but higher doses have been required for a few patients. In some patients it is necessary to administer a diuretic, peripheral vasolidator and/or other antihypertensive agents in conjunction with nadolol in order to achieve satisfactory response.
Treatment of hypertension associated with phaeochromocytoma may require the addition of an alpha-blocking agent.
Cardiac tachyarrhythmias: Initially 40mg once daily. This may be increased if necessary to 160mg once daily. If bradycardia occurs dosage should be reduced to 40mg once daily.
Migraine: The initial dose of nadolol is 40mg once daily. Dosage may be gradually increased in 40mg increments until optimum migraine prophylaxis is achieved. The usual maintenance dose is 80 to 160mg administered once daily. After 4 to 6 weeks at the maximum dose if a satisfactory response is not obtained, therapy with nadolol should be withdrawn gradually.
Thyrotoxicosis: The dosage range is 80-160mg once daily. It has been found that most patients require a dose of 160mg once daily. Nadolol may be used together with conventional anti-thyroid treatment. For the preparation of patients for partial thyroidectomy, nadolol should be administered in conjunction with potassium iodide for a period of 10 days prior to operation. Nadolol should be administered on the morning of operation. Post-operatively, nadolol dosage should be slowly reduced and then withdrawn following clinical stability.
Children:
Safety and effectiveness in children have not been established.
Elderly:
In elderly patients a low initial dose should be used so that sensitivity to side-effects may be assessed.
Renal or hepatic impairment
As with all drugs patients with impaired renal or hepatic function should be monitored.
4.3 Contraindications
Like other drugs in this class, nadolol is contraindicated in bronchial asthma or a history of asthma; sinus bradycardia; 2nd and 3rd degree heart block; cardiogenic shock; right ventricular failure secondary to pulmonary hypertension; congestive heart failure.
4.4 Special Warnings And Precautions For Use
Exacerbation of angina and myocardial infarction have occurred after abrupt discontinuation of therapy with beta-adrenergic blocking agents in patients with angina pectoris or other evidence of coronary artery insufficiency. When discontinuing long-term treatment with nadolol, the dosage should be reduced gradually over a period of at least two weeks and the patient carefully monitored.
Beta-adrenergic blockade carries the potential hazard of precipitating cardiac failure. Should this occur and it is not controlled by digitalisation, nadolol should be withdrawn, consideration being given to the foregoing warning.
Beta-blocking impairs the ability of the heart to respond to stress. It has been the usual practice to recommend withdrawal of beta-blockers several days prior to surgery. However, this may render the patient's blood pressure unstable and difficult to control during anaesthesia and the anaesthetist may wish to advise on discontinuation of therapy. In no circumstances should beta-blockers be discontinued prior to surgery in patients with phaeochromocytoma or thyrotoxicosis. In the event of emergency surgery, the effects of nadolol may be reversed by isoprenaline or noradrenaline. However, such patients may be subject to protracted severe hypotension. General anaesthetics which can cause myocardial depression, such as cyclopropane, trichloroethylene, chloroform and ether, should be avoided if nadolol is continued during surgery.
Nadolol should be administered with caution to patients with chronic obstructive airways disease. Discontinue therapy if condition relapses.
Care should be exercised in the administration of nadolol to diabetic patients since early signs of acute hypoglycaemia may be masked. It may also be necessary to adjust the dosage of hypoglycaemic drugs, or insulin doses.
There have been reports of skin rashes (including a psoriasiform type) and/or ocular changes (conjunctivitis and `dry eye') associated with the use of beta-adrenergic blocking drugs. The reported incidence is small and in most cases the symptoms have cleared when the treatment was withdrawn. Discontinuance of the drug should be considered if any such reaction is not otherwise explicable. Cessation of the therapy with a beta-adrenergic blocker should be gradual.
Beta-blocking may mask certain signs (e.g. tachycardia) of hyperthyroidism. Patients suspected of developing thyrotoxicosis should be managed carefully to avoid abrupt withdrawal of beta-blockade which might precipitate a thyroid storm.
Precautions
Occasionally, beta-blockade with drugs such as nadolol may produce hypotension and/or marked bradycardia, resulting in vertigo, syncope or orthostatic hypotension.
Nadolol should be used with caution in patients with impaired renal or hepatic function.
Administration in renal failure:
In patients with decreased renal function, dosage adjustment is necessary. The recommended dosage intervals are:
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4.5 Interaction With Other Medicinal Products And Other Forms Of Interaction
General anaesthetics: Those which cause myocardial depression such as chloroform, cyclopropane, trichloroethylene and ether should be avoided as the patient may be subject to protracted severe hypotension.
Myocardial Depressants: Myocardial depressants such as lignocaine and procainamide may subject the patient to protracted severe hypotension.
Adrenoceptor Stimulants: Beta-adrenoceptor stimulants such as isoprenaline and verapamil, or alpha-adrenoceptor stimulants such as noradrenaline and adrenaline, will reverse the hypotensive effects and increase vasoconstrictor activity.
Catecholamine Depleting Drugs: e.g. Reserpine. Excessive reduction in sympathetic drive to the heart might occur. Close observation is advised.
Antihypertensives: e.g. Neurone-blocking drugs, vasodilators, diuretics. Additive hypotensive effect.
Clonidine: If Corgard and clonidine are given concurrently, clonidine should not be discontinued until several days after Corgard withdrawal.
Hypoglycaemics, Insulin: Possible dosage adjustment, see warnings.
Monoamine oxidase inhibitors: Administration of nadolol during and within 2 weeks of administration of adrenergic augmenting psychotropic drugs such as monoamine oxidase inhibitors, should be avoided, although the clinical significance is undetermined.
4.6 Pregnancy And Lactation
The safety of nadolol in pregnancy has not been established and animal studies have shown some foetotoxicity. Use of any drug in pregnancy or by women of childbearing potential requires that the possible risk to mother and/or foetus be weighed against the expected therapeutic benefit.
Nadolol is excreted in human milk; therefore nursing mothers should only receive nadolol if deemed essential.
4.7 Effects On Ability To Drive And Use Machines
None known.
4.8 Undesirable Effects
Most patients tolerate nadolol well. Side-effects resemble those reported with other beta-blocking drugs and rarely require withdrawal of treatment. Those reported infrequently include gastro-intestinal effects, bradycardia, fatigue, light-headedness, cold extremities, insomnia, paraesthesia, dryness of the mouth and alopecia. Cardiac insufficiency, hypotension and AV block have occurred on rare occasions.
4.9 Overdose
Excessive bradycardia should be treated initially with atropine. If there is no response, isoprenaline may be administered with caution.
Cardiac failure should be managed by digitalisation and diuretics. Glucagon has also been reported to be useful.
Hypotension may be managed with vasopressors such as adrenaline.
Bronchospasm may be counteracted by isoprenaline and aminophylline.
5. Pharmacological Properties
5.1 Pharmacodynamic Properties
Nadolol is a beta-adrenergic receptor blocking agent with a prolonged activity, permitting once-daily dosage in angina, hypertension, cardiac arrhythmias, the prophylaxis of migraine, and the relief of hyperthyroid symptoms.
Nadolol is not metabolised. It has no membrane stabilising or intrinsic sympathomimetic activity, and its only effect on the autonomic nervous system is one of beta-adrenergic blockade. Nadolol is nonselective.
Receptor blockade by nadolol results in protection from excessive inappropriate sympathetic activity. Nadolol reduces the number and severity of attacks of angina pectoris by blocking response to catecholamine stimulation and thus lowers the oxygen requirement of the heart at any given level of effort.
Nadolol reduces both supine and erect blood pressure. Like other beta-blockers nadolol exerts an antiarrhythmic action. Nadolol has been shown to reduce the rapid ventricular response which accompanies atrial fibrillation/flutter by slowing conduction through the A-V node. Beta-blockade is of particular value in arrhythmias caused by increased levels of, or sensitivity of the heart to, circulating catecholamines, e.g. arrhythmias associated with phaeochromocytoma, thyrotoxicosis, or exercise. Nadolol is effective in reducing ventricular premature beats in selected patients.
Nadolol exerts an effect in the prophylaxis of migraine by a mechanism which may involve prevention of vasoconstriction in the area served by the internal carotid artery and prevention of excessive adrenergic vasodilation in the external carotid artery.
Nadolol alleviates the symptoms of thyrotoxicosis and provides symptomatic control before and during thyroid surgery.
Beta-blocking agents have been shown in large scale studies to reduce mortality by preventing reinfarction and sudden death in patients surviving their first myocardial infarction.
5.2 Pharmacokinetic Properties
About 30 percent of an oral dose of Corgard is absorbed. Peak serum concentrations usually occur in 3 to 4 hours after drug administration. The presence of food in the gastrointestinal tract does not affect the rate or extent of Corgard absorption. Approximately 30 percent of the Corgard present in serum is reversibly bound to plasma protein. Unlike most available beta-blocking agents, Corgard is not metabolised, and is excreted unchanged principally by the kidneys. The serum half-life of therapeutic doses of Corgard is relatively long, ranging from 20 to 24 hours (permitting once daily dosage). A significant correlation between minimum steady-state serum concentrations of Corgard and total oral daily dose has been demonstrated in hypertensive patients; however, the observed dose-response range is wide and proper dosage requires individual titration.
5.3 Preclinical Safety Data
None stated..
6. Pharmaceutical Particulars
6.1 List Of Excipients
The tablets also contain citric acid anhydrous, polyvidone, corn starch, microcrystalline cellulose, magnesium stearate, indigo carmine (E132) and indigo carmine aluminium lake.
6.2 Incompatibilities
Not applicable.
6.3 Shelf Life
48 months.
6.4 Special Precautions For Storage
Store below 25OC.
6.5 Nature And Contents Of Container
Blisters in cartons containing 28 tablets.
6.6 Special Precautions For Disposal And Other Handling
None stated.
7. Marketing Authorisation Holder
Sanofi-Synthelabo
PO Box 597
Guildford
Surrey
8. Marketing Authorisation Number(S)
Corgard tablets 40mg: PL 11723/0099
Corgard tablets 80mg: PL 11723/0100
9. Date Of First Authorisation/Renewal Of The Authorisation
Corgard tablets 40mg: 24 November 1995
Corgard tablets 80mg: 24 November 1995
10. Date Of Revision Of The Text
Corgard tablets 40mg: November 2001
Corgard tablets 80mg: November 2001
Legal Category POM
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