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CORGARD H.S. TABLETS; CORGARD TABLETS
CORGARD H.S. TABLETS
CORGARD TABLETS
SCHEDULING STATUS:
S3
PROPRIETARY NAME
(and dosage form)
CORGARD H.S. TABLETS
CORGARD TABLETS
COMPOSITION
CORGARD H.S. tablets contain 40mg of nadolol and CORGARD tablets contain 80mg of nadolol, chemically known as 2,3Cis-1,2,3,4-tetrahydro-5[2-hydroxy-3-(tert-butyl-amino) propoxy]-2,3-naphthalenediol.
PHARMACOLOGICAL CLASSIFICATION
Category A5.2 - Adrenolytics (Sympatholytics).
PHARMACOLOGICAL ACTION
Nadolol specifically competes with beta-adrenergic receptor agonists for available beta receptor sites. When access to beta receptor sites is blocked by nadolol, the chronotropic, inotropic and vasodilator responses to beta-adrenergic stimulation are decreased proportionally.
Absorption of nadolol after oral dosing is variable averaging about 30%.
Peak serum concentrations usually occur 3 to 4hours after administration of medication. Nadolol is not metabolized, and is excreted unchanged. The absorption of nadolol is not affected by food intake. The serum half-life of therapeutic doses of nadolol is relatively long and usually ranges from 20 to 24hours. Because nadolol is excreted predominantly in the urine its half life increases in the presence of renal impairment. Approximately 30% of the nadolol present in serum is reversibly bound to plasma protein.
Steady-state serum concentrations of nadolol are attained in six to nine days with once-daily dosage in persons with normal renal function. No consistent correlation between dose or plasma concentration and therapeutic effect has yet been established, and the observed dose-response range is wide. This may be because sympathetic tone varies widely between individuals. Because of the lack of any reliable test to estimate sympathetic tone, proper dosage requires titration. Corgard has low lipophilicity as determined by octanolwater partition coefficient (0,71). The extent to which it crosses the blood-brain barrier is limited.
By blocking catecholamine-induced increases in heart rate, velocity and extent of myocardial contraction, and blood pressure, nadolol generally reduces the oxygen requirement of the heart at any given level of effort.
Beta-adrenergic blocking agents, by virtue of their pharmacological activities, reduce both supine and erect blood pressures. Nadolol also decreases renin secretion by blockade of the beta receptors responsible for renin release from the kidneys; this may be one of its modes of action in reducing blood pressure.
Nadolol exerts an antiarrhythmic effect in doses associated with beta-adrenergic blockade, and this appears to be its principal antiarrhythmic mechanism of action. In addition, nadolol has been shown to reduce the rapid ventricular response which accompanies supraventricular tachyarrhythmias. Beta-adrenergic 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.
INDICATIONS
CORGARD is indicated for the management of:
Angina Pectoris
The initial treatment of angina pectoris due to coronary atherosclerosis involves weight control, rest, cessation of smoking, use of sublingual nitroglycerine and avoidance of precipitating circumstances. CORGARD is indicated specifically for the long term management of patients with angina pectoris who have not responded adequately to these conventional measures.
Hypertension
Beta-blocking agents are useful either alone or in conjunction with other hypertensive agents for the management of essential hypertension.
Note
They are not intended for the management of hypertensive crises but rather for the long term treatment of hypertension.
CONTRA-INDICATIONS
CORGARD is contra-indicated for patients with (1) Allergy to any of the components, (2) bronchial asthma, (3) chronic respiratory diseases, (4) allergic rhinitis during the pollen season, (5) sinus bradycardia and all degrees off heart block greater than 1st degree AV block, Heart Failure, Hepatic Failure, (6) cardiogenic shock, (7) bradycardia less than 50 per minute, (8) right ventricular failure secondary to pulmonary hypertension, (9) congestive heart failure (see WARNINGS), (10) patients receiving adrenergic augmenting psychotropic drugs (including MAO inhibitors), and during a two week withdrawal period from such drugs; (11) peripheral vascular disease and Raynaud's phenomenon; (12) heart failure; (13) Hepatic failure.
A patient's normal tachycardiac response to hypovolaemia or blood loss may be obscured during or after surgery. Particular caution should be taken in this regard.
WARNINGS
Important: Exacerbation of angina, hypertension and myocardial infarction have occurred after abrupt discontinuation of therapy with beta-adrenergic blocking agents in patients with angina pectoris or other evidence or coronary artery insufficiency. When discontinuing chronically administered CORGARD in such patients, the dosage should be gradually reduced over a period of at least two weeks and the patient should be carefully monitored. Patients should be advised to limit the extent of their physical activity during the period that the medicine is being discontinued. If angina markedly worsens or acute coronary insufficiency develops, re-institute CORGARD promptly at least temporarily. In addition, warn patients with angina pectoris against abrupt discontinuation of CORGARD. Because coronary artery disease is common and may be unrecognized , it may be prudent not to discontinue nadolol therapy abruptly even in patients under treatment for hypertension alone.
Patients with a History of Cardiac Failure - Sympathetic stimulation may be a vital component supporting circulatory function in patients with congestive heart failure, and beta-blockade may worsen failure.
Although beta-blockers should be avoided in overt congestive heart failure, they can be cautiously used, if necessary, in patients with a history of heart failure who are well compensated, usually with digitalis and diuretics. Beta-adrenergic blocking agents do not abolish the inotropic action of digitalis on heart muscle.
Patients Without a History of Heart Failure - Continued depression of the myocardium with beta blockade over a period of time can, in some cases, lead to cardiac failure. At the first sign or symptom of impending heart failure, the patients should be fully digitalized and/or treated with diuretics, and the response observed closely. If cardiac failure continues despite adequate digitalization and diuresis, CORGARD should be withdrawn (gradually, if possible).
Major surgery
Because beta blockade impairs the ability of the heart to respond to flex stimuli. CORGARD should be withdrawn several days prior to surgery (excepting phaeochromocytoma). In the event of emergency surgery, the anaesthesiologist should be informed that the patient is on Nadolol therapy. The effects of CORGARD can be reversed by administration of beta receptor agonists such as isoproterenol or noradrenaline. However, such patients may be subject to protracted severe hypotension.
Bronchospasm, Chronic Bronchitis, Emphysema
CORGARD should not, in general be administered to patients with bronchospastic disease since it may block bronchodilation produced by endogenous or exogenous catecholamine stimulation of beta (2) receptors.
Diabetes and Hypoglycaemia
Beta-adrenergic blockade may prevent the appearance of premonitory signs and symptoms (pulse rate and pressure changes) of acute hypoglycaemia. This is especially important with labile diabetics. Beta blockade also reduces the release of insulin in response to hyperglycaemia; therefore, it may be necessary to adjust the dose of antidiabetic medication.
Response to Treatment for Anaphylactic Reaction - While taking beta-blockers, patients with a history of severe anaphylactic reaction to a variety of allergens may be more reactive to repeated challenge; either accidental, diagnostic or therapeutic. Such patients may be unresponsive to the usual doses of adrenaline used to treat allergic reactions.
Pregnancy
The safety of CORGARD in human pregnancy and lactation has not been established. Use of any drug in pregnancy or women of childbearing potential requires that the possible risk to mother and/or foetus be weighed against the expected therapeutic benefit.
Administration to pregnant mothers shortly before giving birth, or during labour may result in the new-born infants being born hypotonic, collapsed and hypoglycaemic. Nadolol is excreted in human milk.
Thyrotoxicosis Beta-adrenergic blockade may mask certain clinical signs of hyperthyroidism (e.g., tachycardia). Abrupt withdrawal of nadolol in thyroid patients can precipitate thyroid storm.
DOSAGE AND DIRECTIONS FOR USE
(Dosage must be individualised)
CORGARD can be administered any time in relation to meals without affecting absorption.
Angina Pectoris
Starting with 80mg once daily, dosage may be gradually increased by 80mg at weekly intervals until an adequate response is obtained or excessive bradycardia occurs.
Although individual patients may respond at various dosage levels, most patients will respond to 160mg or less per day. The value and safety of dosage in angina pectoris exceeding 240mg per day have not been established. If treatment is to be discontinued, reduce dosage gradually over a period of at least 2 weeks (see WARNINGS).
Hypertension
Starting with 80mg daily, the dosage may be gradually increased by 80mg increments until an optimum response is obtained. The effective dose varies from patients to patient; many patients respond to as little as 80mg daily and most patients respond to daily doses of 240mg or less. In some patients, it is necessary to administer a beta-adrenergic blocking agent in conjunction with a diuretic, vasodilator and/or other antihypertensive agents in order to achieve a satisfactory response.
CORGARD retention occurs in the presence of renal failure. Although non renal elimination does occur, dosage adjustments are necessary in this patient group.
The following dose intervals are recommended:
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Creatinine Clearance
(mL/min/1,72m2) |
Dosage Interval
(hours) |
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Less than 10 |
40 –60 |
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10 – 30 |
24 –48 |
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31 –50 |
24 –36 |
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More than 50 |
24 |
CORGARD can be removed from the general circulation by haemodialysis. Clearance of CORGARD by this procedure varies between 40 and 100mL per minute.
If a beta-blocker and clonidine are given concurrently, the clonidine should not be discontinued until several days after the withdrawal of the beta-blocker as severe rebound hypertension may occur.
SIDE-EFFECTS AND SPECIAL PRECAUTIONS
ADVERSE REACTION
Cardiovascular
Bradycardia. Symptoms of peripheral vascular insufficiency, usually of the Raynaud type. Severe peripheral vascular disease and even peripheral gangrene may be precipitated. Cardiac failure, hypotension, and rhythm/conduction disturbances. Single instances of first degree and third degree heart block have been reported. Intensification of AV block is a known effect of beta-blockers.
Central Nervous System
Dizziness or fatigue; paresthesias, sedation, and change in behaviour, sleeplessness, vivid dreams, nightmare, overt psychosis.
Respiratory
Bronchospasm.
Gastrointestinal
Nausea, diarrhoea, abdominal discomfort, constipation, vomiting, indigestion, anorexia, bloating, and flatulence.
Other
Rash; pruritus; headache; dry mouth, eyes, or skin; impotence or decreased libido; facial swelling; weight gain; slurred speech; cough; nasal stuffiness; sweating; tinnitus; blurred vision, light headedness, cold extremities, hypoglycaemia, skeletal muscle weakness. Reversible alopecia has been reported infrequently.
Patients with phaeochromocytoma usually require treatment with an alpha-adrenergic blocker.
Given for prolonged periods, laboratory parameters should be observed at intervals. The drug should be used with caution in patients with impaired renal or hepatic function.
Discontinuation of therapy should be gradual and patients should be advised to limit the extent of their physical activity during the period that the medicine is being discontinued.
Caution should be exercised when transferring a patient from clonidine. The withdrawal of clonidine may result in the release of large amounts of cathecholamines which may give rise to a hypertensive crisis. If beta-blockers are administered in those circumstances, the unopposed alpha-receptor stimulation may potentiate this effect.
INTERACTIONS
Anesthetics:
Beta blockers may exaggerate the hypotension induced by general anesthetics (see WARNINGS, Major Surgery).
Antidiabetic drugs (oral agents and insulin):
Hypoglycemia or hyperglycemia; adjust dosage of antidiabetic drug accordingly (see WARNINGS, Diabetes and Hypoglycemia).
Antimuscarinic agents:
May counteract the bradycardia caused by beta blockers.
Calcium-channel blockers:
Calcium channel blockers generally potentiate the pharmacologic effects of beta blockers. Patients taking both agents should be carefully monitored for adverse cardiovascular events.
Catecholamine-depleting drugs (e.g., reserpine):
Additive effects; monitor closely for evidence of hypotension and/or excessive bradycardia (e.g., vertigo, syncope, postural hypotension)
Other antiarrhythmic agents:
Additive or antagonistic effects may occur.
Other antihypertensive agents/diuretics:
Carefully determine additive effects.
Lidocaine, IV:
Significant reduction of lidocaine clearance can occur when beta blockers are administered concurrently.
MAO Inhibitors:
Isolated cases of bradycardia have occurred during concurrent use of beta blockers and MAOI's.
Non-steroidal anti-inflammatory agents:
The antihypertensive effects of beta blockers may be reduced during concurrent administration of indomethacin and possibly other NSAIDs.
Phenothiazines and other antipsychotic agents:
Additive antihypertensive effects have occurred with other beta blockers when they were given concurrently with phenothiazines or haliperidol.
Vasoconstrictor agents
Effects can be additive, e.g., with ergot alkaloids.
Paediatric Use:
Safety and effectiveness in children have not been established.
Elderly:
Some reduction in dosage may also be appropriate for the elderly since decreased kidney function is a physiological consequence of ageing.
SPECIAL PRECAUTIONS
The normal dose should be reduced in elderly patients, or in patients suffering from renal dysfunction; in the perioperative period it is generally unwise to reduce the dosage to which the patient is accustomed, as there may be danger of aggravation of angina pectoris or of hypertension.
KNOWN SYMPTOMS OF OVERDOSAGE AND PARTICULARS OF ITS TREATMENT
In addition to gastric lavage, the following measures should be employed, as appropriate. In determining the duration of corrective therapy, take note of the long duration of the effect of nadolol.
Excessive Bradycardia
Administer atropine (0.25 to 1.0mg). If there is no response to vagal blockade, administer isoproterenol cautiously.
Cardiac Failure:
Administer a digitalis glycoside and diuretic. It has been reported that glucagon may also be useful in this situation.
Hypotension:
If fluid administration is ineffective, administer vasopressors such as dopamine, dobutamine, levarterenol or isoproterenol. There is some pharmacological evidence that levarterenol (norepinephrine) is the medicine of choice.
Bronchospasm:
Administer a beta agonist agent and/or a theophylline derivative.
Nadolol can be removed from the general circulation by hemodialysis.
IDENTIFICATION
CORGARD H.S. tablets are white round, biconvex, with "SQUIBB 207" embossed on one side.
CORGARD tablets are white round, biconvex, with “Corgard 80”embossed on the one side and “Squibb”on the other side with a part bisect bar.
PRESENTATION
Bottles of 30 tablets.
STORAGE INSTRUCTIONS
Store at room temperature not exceeding 25°C.
Protect from moisture and excessive heat and store in a tightly closed container.
KEEP OUT OF REACH OF CHILDREN
REGISTRATION NUMBER
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CORGARD H.S. |
K/5.2/183 |
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CORGARD |
K/5.2/184 |
NAME AND BUSINESS ADDRESS OF APPLICANT
Bristol-Myers Squibb (Pty) Ltd*
47 Van Buuren Road
BEDFORDVIEW
2008
DATE OF PUBLICATION OF THIS PACKAGE INSERT
March 1996
* Authorised user of the TM CORGARD
Updated on this site: February 2003
Source: Pharmaceutical Industry
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