Each ALDAZIDE tablet contains 25 mg spironolactone and 2.5mg isobutyl-hydrochlorothiazide (thiabutazide)
The treatment of essential hypertension; oedematous conditions, including congestive heart failure, cirrhosis of the liver (with or without ascites), the nephrotic syndrome; idiopathic oedema; in the treatment of diuretic-induced hypokalaemia when other measures are considered inappropriate or inadequate. Treatment of patients with congestive heart failure taking digitalis when other therapies are considered Inadequate or inappropriate.
Aldosterone may be an aetiologic factor in some cases involving malignant effusions and beneficial results have been reported with the use of spironolactone-thiazide combinations.
Acute renal insufficiency, significant impairment of renal function, anuria, hyperkalaemia, or sensitivity to spironolactone, thiazide diuretics or to other sulfonamide-derived drugs.
The concomitant administration of potassium supplements or of other potassium-sparing agents is not recommended as it may induce hyperkalaemia. Sulfonamide derivatives, including thiazides, have been reported to exacerbate or activate systemic lupus erythematosus.
Periodic estimation of serum electrolytes is desirable due to the possibility of hyperkalaemia, hyponatraemia and possible transient BUN elevation, especially in patients with pre-existing impaired renal function, in whom the risk/benefit ratio should always be weighed. Caution should be used in treating patients with acute or severe hepatic failure especially patients with lower effective plasma volume.
There may also be an increased potential to precipitate hepatic coma in such patients.
Both spironolactone and hydrochlorothiazide reduce the vascular responsiveness to nor adrenaline. Therefore, caution should be exercised in the management of patients subjected to regional or general anaesthesia while they are being treated with ALDAZIDE.
As carbenoxolone may cause sodium retention and thus decrease the effectiveness of ALDAZIDE, concurrent use of the two agents should be avoided.
Reversible hyperchloraemic metabolic acidosis, usually in association with hyperkalaemia, has been reported to occur in some patients with decompensated hepatic cirrhosis, even in the presence of normal renal function.
Spironolactone has been shown to increase the half-life of digoxin. This may result in increased serum digoxin levels and subsequent digitalis toxicity. It may be necessary to reduce the maintenance and digitalization doses when spironolactone is administered and the patient should be carefully monitored to avoid over-or under-digitalization.
Several reports of possible interference with digoxin radio-immunoassays by spironolactone, or its metabolites have appeared in the literature. Neither the extent nor the potential clinical significance of its interference (which may be assay-specific) has been fully established.
Usage in Pregnancy
Spironolactone or Its metabolites may, and thiazides do, cross the placental barrier. Therefore, the use of ALDAZIDE in pregnant women requires that the anticipated benefit be weighed against possible hazards to the mother and foetus.
Thiazides, as well as canrenone, a metabolite of spironolactone, appear in breast milk. If use of the drug is deemed essential, an alternative method of infant feeding should be instituted.
Spironolactone has been shown to be a tumorigen in chronic toxicity studies performed in rats, with its proliferative effects manifested on endocrine organs and the liver. In one study using 25, 75, and 250 times the usual daily human dose (2mg/kg), there was a statistically significant dose-related increase in benign adenomas of the thyroid and testes in female rats, there was a statistically significant increase in malignant mammary tumours at the mid-dose only. In male rats, there was a dose related increase in proliferative changes in the liver. At the highest dosage level (500mg/kg), the range of effects included hepatocytomegaly, hyperplastic nodules, and hepatocellular carcinoma; the last was not statistically significant at a value of p = 0.05.
Spironolactone is metabolized to a minor extent to canrenone.
Canrenone and canrenoic acid are the major metabolites of potassium canrenoate.
A dose-related (above 20mg/kg/day) incidence of myelocytic leukaemia was observed in rats fed dally doses of potassium canrenoate (Soldactone) for a period of one year. In one long term (two year) oral carcinogenicity study of potassium canrenoate in the rat, myelocytic leukaemia and hepatic, thyroid, testicular and mammary tumours were observed.
Potassium canrenoate did not produce a mutagenic effect in tests using bacteria or yeast. It did produce a positive mutagenic effect in several in vitro tests in mammalian cells following metabolic activation. In an in vivo mammalian system potassium canrenoate was not mutagenic. An increased incidence of leukaemia was not observed in chronic rat toxicity studies conducted with spironolactone at doses up to 500 mg/kg/day.
Gynaecomastia may develop in association with the use of spironolactone, and physicians should be alert to its possible onset. The development of gynaecomastia appears to be related to both dosage level and duration of therapy and is normally reversible when ALDAZIDE is discontinued. In rare instances some breast enlargement may persist.
Other adverse effects associated with the use of spironolactone are infrequent and include: gastrointestinal symptoms including cramping and diarrhoea, drowsiness, lethargy, headache, maculopapular or erythematous cutaneous eruptions, urticaria, mental confusion, drug fever, ataxia, inability to achieve or maintain erection, irregular menses or amenorrhoea, and post-menopausal bleeding. A few cases of agranulocytosis have been reported in patients taking spironolactone.
Adverse reactions reported in association with the use of thiazides include: gastrointestinal symptoms (anorexia, nausea, vomiting, diarrhoea, abdominal cramps), purpura, thrombocytopenia, leukopenia, agranulocytosis, dermatologic symptoms, (cutaneous eruptions, pruritus, erythema multiforme), paraesthesia, acute pancreatitis, jaundice, dizziness, vertigo, headache, xanthopsia, photosensitivity, necrotizing angitis, aplastic anaemia, orthostatic hypotension, muscle spasm, weakness, and restlessness. Thiazides have been reported to decrease glucose tolerance and to induce hyperuricaemia.
Adverse reactions are usually reversible upon discontinuation of ALDAZIDE.
DOSAGE AND ADMINISTRATION
For essential hypertension
Two to four tablets daily of ALDAZIDE in divided doses will be adequate for most patients provided treatment Is continued for two weeks or longer. The dosage of other antihypertensive drugs should first be decreased by at least 50% when ALDAZIDE is added to the regimen, and then adjusted as necessary. If desired, the daily dose may be given as a single dally dose.
For oedematous conditions
A daily dosage of four tablets of ALDAZIDE in divided doses will be adequate for most patients provided treatment is continued for two weeks or longer. However, dosage may range between one and eight tablets daily. If desired, the dally dose may be given as a single daily dose.
For oedema in children, the usual daily maintenance dose of ALDAZIDE should be that which provides 1.65 to 3.3mg of spironolactone per kilogram of body weight.
Tablets (8.7mm diameter), round, biconvex, ivory, peppermint flavoured, uncoated, stamped SEARLE, each containing 25mg spironolactone and 2.5mg isobutyl-hydrochlorothiazide.
Packs containing 100 tablets. Reg.No. DL 2013005
Manufactured in Indonesia under licence by
PT SOHO INDUSTRI PHARMASI, Jakarta
Division of Monsanto Australia Limited