INDICATIONS     CONTRA-INDICATIONS     DOSAGE     SIDE-EFFECTS     PREGNANCY     OVERDOSE     IDENTIFICATION     PATIENT INFORMATION

Logo ALDAZIDE® Tablets
SCHEDULING STATUS:
S3

PROPRIETARY NAME
(and dosage form):

ALDAZIDE® Tablets

COMPOSITION:
Each tablet contains spironolactone 25 mg plus isobutylhydrochlorothiazide 2,5 mg.

PHARMACOLOGICAL CLASSIFICATION:
A18.1 Diuretics.

PHARMACOLOGICAL ACTION:
Spironolactone promotes diuresis in patients with oedema or ascites. Spironolactone acts in the distal portion of the renal tubule by competitive inhibition of aldosterone, a sodium retaining, potassium-excreting hormone. Isobutylhydrochlorothiazide promotes sodium and water excretion by inhibiting sodium and chloride reabsorption in the kidney tubule.
The combination of spironolactone and isobutylhydrochlorothiazide provides an effective treatment for many patients who would not respond to either drug alone. The combination results in an additive diuretic effect since both drugs will increase sodium and water excretion by acting in different parts of the renal tubule.

INDICATIONS:
Essential hypertension, oedema and ascites of congestive heart failure, cirrhosis of the liver, the nephrotic syndrome, idiopathic oedema.

CONTRA-INDICATIONS:
ALDAZIDE is contra-indicated in patients with acute renal insufficiency, significant renal compromise, Addison’s disease, significant hypercalcaemia, hyperkalaemia, or hypersensitivity to spironolactone, thiazide diuretics or to other sulfonamide-derived medicines.
Safety in pregnancy has not been established.
Lactation.
Thiazide as well as canrenone, the principal metabolite of spironolactone, is excreted in breast milk.

DOSAGE AND DIRECTIONS FOR USE:
The average daily dose is 2-4 tablets. For oedema it is recommended that therapy be started with four tablets a day. After the disappearance of oedema, the dose can be reduced according to the patient’s needs. If adequate diuresis does not occur after three days of treatment, the dose can be increased up to 8 tablets daily. For hypertension, the initial dose of four tablets a day should be continued for at least two weeks, since the response to ALDAZIDE may be delayed. The dose can then be adjusted according to the patient’s needs.

SIDE-EFFECTS AND SPECIAL PRECAUTIONS:
Side-effects:
Gynaecomastia may develop in association with the use of ALDAZIDE. Development of gynaecomastia is related to both dose and duration of therapy. Gynaecomastia is usually reversible when ALDAZIDE is discontinued, although in rare instances some breast enlargement may persist.
The following adverse events have been reported:
Gastro-intestinal disorders: abdominal pain, vomiting, nausea, diarrhoea, gastro-intestinal disturbance.
Body as a whole: asthenia, fever, anaphylactoid reaction, malaise.
Skin and appendages: rash, pruritis, dermatitis, photosensitivity.
Nervous system disorders: dizziness, headache, paraesthesia.
Psychiatric disorders: impotence.
Neoplasm: breast neoplasm, including malignancy.
Metabolic and nutritional disorders: electrolyte disturbances.
Reproductive disorders: breast disorders, menstrual disorders.
Haematological disorders: thrombocytopenia.
Other adverse reactions reported with the use of ALDAZIDE include pancreatitis and cholestatic jaundice.

Special precautions:
The concurrent administration of other potassium-sparing diuretics, routine use of potassium supplements or a diet rich in potassium is not recommended as this may induce hyperkalaemia.
Periodic estimation of serum electrolytes is desirable due to the possibility of hypokalaemia or hyperkalaemia, hyperchloraemic alkalosis, hyponatraemia and possible transient blood urea elevation, especially in the elderly and/or patients with pre-existing impaired renal or hepatic function.
Reversible hyperchloraemic metabolic acidosis, usually in association with hypokalaemia, has been reported in some patients with decompensated hepatic cirrhosis, even when renal function is normal. Caution should be used in treating patients with acute or severe liver impairments, since vigorous diuretic therapy may precipitate hepatic encephalopathy.
Hyponatraemia may be induced, especially when ALDAZIDE is combined with other diuretics. Thiazides may raise the concentration of blood uric acid. Dosage adjustment of antigout medications may be necessary.
In diabetic and prediabetic patients, thiazides may increase blood glucose concentrations. Dosage adjustments of insulin or hypoglycaemic medications may be required. Increases in cholesterol and triglyceride levels may be associated with thiazide therapy. Sulfonamide derivatives, including thiazides, have been reported to exacerbate or activate systemic erythematosus.

Interaction with other medicaments and other forms of interaction:
Severe hyperkalaemia has been reported in patients who have had potassium-sparing diuretics administered, including spironolactone and ACE inhibitors.
Spironolactone potentiates the effects of other diuretics and antihypertensive agents given concomitantly.
The dose of such drugs may need to be reduced when ALDAZIDE is added to the treatment regimen. Spironolactone and thiazides may reduce vascular responsiveness to norepinephrine.
Caution should be exercised in the management of patients subjected to anaesthesia while they are being treated with ALDAZIDE. Spironolactone has been shown to increase the half-life of digoxin. Cholestyramine and colestipol reduce the absorption of thiazides and may lower its diuretic effect. Thiazide diuretics decreases lithium renal clearance and increase the risk of toxicity. Lithium dose adjustment may be required.
Thiazides may also increase responsiveness to skeletal muscle relaxants (e.g. tubocurarine). Nonsteroidal anti-inflammatory drugs may attentuate the natriuretic efficacy of diuretics due to the inhibition of intrarenal synthesis of prostaglandins.
Aspirin attentuates the diuretic effect of spironolactone by blocking secretion of canrenone, a spironolactone metabolite, in the renal tubule.
Indomethacin and mefenamic acid have been shown to inhibit the excretion of canrenone. Spironolactone enhances the metabolism of antipyrine.
Spironolactone can interfere with assays for plasma digoxin concentrations.

Effects on ability to drive and use machines:
Somnolence and dizziness have been reported in some patients. Caution is advised when driving or operating machinery until the response to initial treatment has been determined.

KNOWN SYMPTOMS OF OVERDOSAGE AND PARTICULARS OF ITS TREATMENT:
Acute overdose may be manifested by nausea, vomiting, drowsiness, mental confusion, maculopapular or erythematous rash, dizziness or diarrhoea. Electrolyte imbalance and dehydration may occur. If digitalis has been administered, hypokalaemia may accentuate cardiac arrhythmias.
Treatment of overdose should be symptomatic and directed at fluid and electrolyte replacement. In the case of recent ingestion, gastric lavage should be carried out.

IDENTIFICATION:
White, round, biconvex, film-coated tablets, diameter 8,7 mm, engraved SEARLE/116 on one side, plain on the other, with a characteristic peppermint odour.

PRESENTATION:
ALDAZIDE is supplied in blisters of 60 tablets.

STORAGE INSTRUCTIONS:
ALDAZIDE should be stored in a cool dry place below 30°C.
Keep out of reach of children.

REFERENCE NUMBER:
H1945 (Act 101/1965).

NAME AND BUSINESS ADDRESS OF THE APPLICANT:
Pharmacia South Africa (Pty) Ltd
Alphen West G
George Street
Midrand
1685

DATE OF PUBLICATION OF THIS PACKAGE INSERT:
28 February 1997

New addition to this site: January 2005
Source: Pharmaceutical Industry

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