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Logo SOTAZIDE tablets

SCHEDULING STATUS:
S3

PROPRIETARY NAME:
(dosage form)

SOTAZIDE tablets

COMPOSITION:
Each tablet contains 160 mg
sotalol hydrochloride with 25 mg hydrochlorothiazide.

PHARMACOLOGICAL CLASSIFICATION:
A 7.1.3: Vascular medicines –other hypotensives.

PHARMACOLOGICAL ACTION:
Sotazide is an antihypertensive which combines sotalol hydrochloride, a beta-adrenergic blocking agent and hydrochlorothiazide a diuretic/antihypertensive. The concomitant use of these agents frequently produces a more pronounced antihypertensive effect than if either is used alone.
The mechanism of action by which sotalol reduces arterial blood pressure in hypertensive patients has not been completely elucidated. However, the antihypertensive action is achieved without precipitating postural or exercise-induced hypotension. The effects of single daily doses on blood pressure last for at least 24 hours. Renin levels are decreased by sotalol.
Sotalol modifies the myocardial response to excessive sympathetic drive by reducing the availability of myocardial beta-receptor sites. The resulting competitive adrenergic blockade causes a reduction in heart rate (chronotropic effect) and a minor reduction in the force of contraction (inotropic effect). These changes reduce myocardial oxygen consumption and excitability.
Sotalol reduces the rate of pressure development in the left ventricle, the velocity of contraction, the resting heart rate and the increased heart rate and blood pressure induced by exercise. Sotalol also depresses AV conduction to a marked degree.
Sotalol exhibits an extended half-life of 10 - 15 hours. Sotalol does not cross the blood brain barrier in significant amounts.
Sotalol has a class II Vaughan-Williams antidysrhythmic action related to its sympatholytic activity. Sotalol has also been demonstrated both in animals and humans to prolong the action potential duration and the atrial and ventricular effective refractory periods (class III antidysrhythmic activity).

INDICATIONS:
SOTAZIDE is indicated for the management of hypertension.

CONTRA-INDICATIONS:
SOTAZIDE is contra-indicated in patients with bronchial asthma or obstructive lung disease, previous evidence of hypersensitivity to either sotalol hydrochlorothiazide or other sulphonamide-derived medicines, uncontrolled cardiac failure, cardiogenic shock, AV block (2nd and 3rd degree) and bradycardia less than 50 beats per minute, right ventricular failure secondary to pulmonary hypertension, anuria and renal failure, liver failure, peripheral vascular disease and Raynaud's phenomenon, anaesthesia that produces myocardial depression. SOTAZIDE is not indicated for the treatment of malignant hypertension and uncontrolled cardiac failure excluding that due to hypertrophic obstructive cardiomyopathy.
SOTAZIDE should not be given to patients after prolonged fasting or to those in a state of diabetic ketoacidosis or metabolic acidosis from any cause. Since SOTAZIDE is primarily renally excreted and dosages in patients with renal decompensation have not been determined, its use in the management of such patients is a relative contra-indication.

WARNINGS:
Cases of torsade de pointes (atypical ventricular tachycardia) have been reported during treatment with SOTAZIDE. Experience to date indicates that this can occur in hypokalaemic patients and in patients concomitantly treated with drugs which may cause torsade such as antidepressants and Class I antidysrhythmics. Thus, the patient's electrolyte balance, especially potassium levels, should always be checked and any abnormality corrected prior to initiation of SOTAZIDE therapy. It is also important to monitor the electrolyte balance frequently during SOTAZIDE treatment. Patients should be instructed to stop SOTAZIDE therapy during episodes of diarrhoea or when encountering conditions that may result in hypokalaemia. Institution of concurrent therapy with drugs known to prolong the QT interval and/or to be associated with atypical ventricular tachycardia especially quinidine, disopyramide and tricyclic antidepressants should be done under dose medical supervision.
SOTAZIDE should never be given to patients with phaeochromocytoma without concomitant alpha-adrenergic blocker therapy.
SOTAZIDE should be used with caution in patients with impaired hepatic function, liver disease or severe renal disease, since they are particularly sensitive to alterations of fluid and electrolyte balance.
Patients with cirrhosis of the liver are more liable to develop adverse reaction to oral diuretics. They often have pre-existing hypokalaemia due to aldosteronism and are intolerant of acute shifts in electrolyte balance.
Thiazides may precipitate azotaemia. Cumulative effects of the hydrochlorothiazide and sotalol components may develop in patients with impaired renal function.
The safety of SOTAZIDE in pregnancy and during lactation has not been established. The administration of a beta-blocker to pregnant mothers shortly before giving birth or during labour may result in the newborn infants being born hypotonic, collapsed and hypoglycaemic.

DOSAGE AND DIRECTIONS FOR USE:
Usual dose:
Mild to moderate hypertension –one SOTAZIDE tablet daily.
The individual optimal dosage should be determined from blood pressure readings and pulse rates taken at 1 to 4 weekly intervals until blood pressure control is achieved. If SOTAZIDE and clonidine are given concurrently, the clonidine should not be discontinued until several days after the withdrawal of SOTAZIDE as severe rebound hypertension may occur.

SIDE-EFFECTS AND SPECIAL PRECAUTIONS:
Dizziness, dyspnoea, tiredness, light-headedness, headache, fever, excessive bradycardia and/or hypotension have been observed.
A reduction in dosage may alleviate symptoms of weakness and dizziness if blood pressure continues to fall after a month or two on the maintenance dose. Bronchoconstriction may occur in patients suffering from asthma, bronchitis and other chronic pulmonary diseases when SOTAZIDE is administered.

Congestive cardiac failure and marked bradycardia may occur. If excessive bradycardia (and/or hypotension) occurs, atropine 0,5 to 2,0 mg should be given intravenously, immediately followed, if necessary by a beta-receptor stimulating agent such as isoprenaline, 5 µg/minute intravenously up to 25 µg initially. Patients experiencing this effect on initial administration of SOTAZIDE should be removed from therapy.

SOTAZIDE should not be given to patients with cardiac decompensation unless incipient or established heart failure is controlled with digitalis and/or diuretics. At the first sign of impending cardiac failure or the progression of failure, conventional management must be instituted. Careful control of dosages and of the individual patient’s response (and notably pulse rate) is essential in this situation.

Note:
Reduced dosages should be used in elderly patients and in patients with renal decompensation as adverse reactions are more common in such patients.

Treatment with SOTAZIDE may be associated with exacerbation of peripheral vascular disease, or with the development of Raynaud's phenomenon (due to unopposed arteriolar alpha-sympathetic tone), sexual impotence, hypoglycaemia, skeletal muscle weakness and gastro-intestinal disturbances. Severe peripheral vascular disease and even peripheral gangrene may be precipitated.

A variety of neuropsychiatric disorders may occur, ranging from vague fatigue and malaise, sleeplessness, vivid dreams and nightmares, to overt psychosis. In the peri-operative period it is generally unwise to reduce the dosage of beta-blocker therapy to which the patient is accustomed, as there may be danger of aggravation of angina pectoris or of hypertension during the surgical period. A patient’s normal tachycardia response to hypovolaemia or blood loss may be obscured during or after surgery by beta-blocker therapy. Particular caution should be taken in this regard.

Abrupt discontinuation of treatment with SOTAZIDE in hypertensive patients with angina pectoris induces severe and continuous angina in some cases. Should such a reaction occur, SOTAZIDE treatment should be withdrawn gradually by reducing the dosage over a period of weeks. Patients should be advised to limit the extent of their physical activity during the period that the medicine is being discontinued.

With SOTAZIDE, negative inotropism beta-II-blockade and depression of AV conduction is dose-dependent.
Patients should be kept under close medical supervision when concurrent therapy is instituted with medicines known to prolong the QT interval and/or to be associated with a typical ventricular tachycardia, especially quinidine, disopyramide and tricyclic antidepressants. As ventricular tachycardia can be associated with syncope, patients who faint should have an electrocardiogram.

Other important drug interactions may occur when beta-blocking agents are administered in conjunction with digitalis (potentially dangerous bradycardia and heart block may result), anti-diabetic agents including insulin and the oral hypoglycaemic agents, psychotropic medicines including phenothiazines and, MAO-inhibitors (which potentiate the action of beta-blocker) and during the two-week withdrawal period from such medicines, calcium antagonists (may have a negative inotropic action on the heart) and antidysrhythmic agents such as procainamide, lignocaine and verapamil.
Such drug interactions can have life-threatening consequences.

Caution should be exercised when transferring a patient from clonidine. The withdrawal of clonidine may result in the release of large amounts of catecholamines which may give rise to a hypertensive crises. If SOTAZIDE is administered in these circumstances the unopposed alpha-receptor stimulation may aggravate the hypertensive effect.

Headache, restlessness, jaundice, pancreatitis, xanthopsia, hyperglycaemia, hypokalaemia, glycosuria and hyperuricaemia have been reported with the use of hydrochlorothiazide, as have photosensitivity, fever, respiratory distress and anaphylactic reactions. Depression of the formed elements of the blood and necrotizing angiitis have also been reported with the use of the thiazides.

Decreased serum-bound iodine without symptoms of thyroid disturbance has occurred with thiazides.

Hypercalcaemia and hypophosphataemia have accompanied pathological changes in the parathyroids of a few hypersensitive patients receiving thiazides over prolonged periods.
Gout may be precipitated or hyperuricaemia may occur with the administration of thiazides.

Patients should have regular examinations to detect the possible development of hepatic dysfunction, blood dyscrasias or idiosyncratic reactions.

All patients receiving SOTAZIDE therapy should be checked periodically for clinical signs of fluid or electrolyte imbalance, hyponatraemia, hypochloraemic alkalosis, hypomagnesaemia and hypokalaemia. Hypokalaemia can sensitize or exaggerate the response of the heart to the toxic effects (dysrhythmogenicity) of cardiac glycosides and other antidysrhythmic agents.

If any serum electrolyte imbalance is present, this should be corrected before initiation of SOTAZIDE therapy.

Safety during long-term administration has not been established.

KNOWN SYMPTOMS OF OVERDOSAGE AND PARTICULARS OF ITS TREATMENT:
Overdosage with beta-blockers may produce bradycardia and severe hypotension. In addition to bradycardia and hypotension which are typical findings in SOTAZIDE poisoning, overdoses with sotalol have resulted in a prolongation of the QT interval in the electrocardiogram and in ventricular tachydysrhythmias. For this reason close monitoring of the electrocardiogram in patients with suspected SOTAZIDE intoxication is recommended. Furthermore, every effort should be made to correct promptly metabolic and electrolyte imbalances which are very likely to result from an excessive amount of hydrochlorothiazide and might contribute to the initiation of ventricular dysrhythmias.

Bradycardia associated with severe hypotension should be treated with intravenous atropine. If necessary, this should be followed up by a slow intravenous infusion of isoprenaline.

Bronchospasm and heart failure may be produced in certain individuals. Bronchospasm should be treated by intravenous aminophylline, and heart failure with digitalis and diuretics.

IDENTIFICATION:
Pale blue, capsule-shaped, biconvex tablet, transversely scored on one side.

PRESENTATION:
Plastic securitainers of 30 and 100 tablets.

STORAGE INSTRUCTIONS:
Store in a cool (below 25°C) dry place.
KEEP OUT OF REACH OF CHILDREN.

REGISTRATION NUMBER:
K/7.1.3/321

NAME AND BUSINESS ADDRESS OF APPLICANT:
Bristol-Myers Squibb (Pty) Ltd
AMR Park, 1 Concorde Road East,
Bedfordview, 2008

DATE OF PUBLICATION OF THIS PACKAGE INSERT:
August 1989

List No. 5457

8/91 Com Code 29-0043

* Authorised user of the TM SOTAZIDE

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