Chemical formula: C₁₄H₁₁ClN₂O₄S Molecular mass: 338.766 g/mol PubChem compound: 2732
Chlortalidone interacts in the following cases:
Concomitant administration of certain non-steroidal anti-inflammatory drugs (e.g. indometacin) may reduce the diuretic and antihypertensive activity of chlortalidone; there have been isolated reports of a deterioration in renal function in predisposed patients.
The bioavailability of thiazide-type diuretics may be increased by anticholinergic agents (eg atropine, biperiden), apparently due to a decrease in gastrointestinal motility and stomach-emptying rate.
The hypokalaemic effect of diuretics may be potentiated by corticosteroids, ACTH, β2–agonists, amphotericin and carbenoxolone.
Chlortalidone should be used with caution in patients with impaired hepatic function or progressive liver disease since minor changes in the fluid and electrolyte balance due to thiazide diuretics may precipitate hepatic coma, especially in patients with liver cirrhosis.
It may prove necessary to adjust the dosage of insulin and oral anti-diabetic agents.
Thiazide-induced hypokalaemia or hypomagnesaemia may favour the occurrence of digitalis-induced cardiac arrhythmias.
The antihypertensive effect of ACE inhibitors is potentiated by agents that increase plasma renin activity (diuretics). It is recommended that the diuretic be reduced in dosage or withdrawn for 2 to 3 days and/or that the ACE inhibitor therapy be started with a low initial dose of the ACE inhibitor. Patients should be monitored for several hours after the first dose.
Diuretics potentiate the action of curare derivatives and antihypertensive drugs (e.g. guanethidine, methyldopa, β-blockers, vasodilators, calcium antagonists and ACE inhibitors).
Concurrent administration of thiazide diuretics may increase the incidence of hypersensitivity reactions to allopurinol, increase the risk of adverse effects caused by amantadine, enhance the hyperglycaemic effect of diazoxide, and reduce renal excretion of cytotoxic agents (e.g. cyclophosphamide, methotrexate) and potentiate their myelosuppressive effects.
Absorption of thiazide diuretics is impaired in the presence of anionic exchange resins such as colestyramine. A decrease in the pharmacological effect may be expected.
Concomitant treatment with ciclosporin may increase the risk of hyperuricaemia and gout-type complications.
The pharmacological effects of both calcium salts and vitamin D may be increased to clinically significant levels if given with thiazide diuretics. The resultant hypercalcaemia is usually transient but may be persistent and symptomatic (weakness, fatigue, anorexia) in patients with hyperparathyroidism.
Treatment with thiazide diuretics has been associated with electrolyte disturbances such as hypokalaemia, hypomagnesaemia, hyperglycaemia and hyponatraemia. Since the excretion of electrolytes is increased, a very strict low-salt diet should be avoided.
Hypokalaemia can sensitise the heart or exaggerate its response to the toxic effects of digitalis.
Like all thiazide diuretics, kaluresis induced by chlortalidone is dose dependent and varies in extent from one subject to another. With 25 to 50mg/day, the decrease in serum potassium concentrations averages 0.5mmol/l. Periodic serum electrolyte determinations should be carried out, particularly in digitalised patients.
If necessary, chlortalidone may be combined with oral potassium supplements or a potassium-sparing diuretic (eg triamterene).
If hypokalaemia is accompanied by clinical signs (eg muscular weakness, paresis and ECG alteration), chlortalidone should be discontinued.
Combined treatment consisting of chlortalidone and a potassium salt or a potassium-sparing diuretic should be avoided in patients also receiving ACE inhibitors.
Monitoring of serum electrolytes is particularly indicated in the elderly, in patients with ascites due to liver cirrhosis, and in patients with oedema due to nephrotic syndrome. There have been isolated reports of hyponatraemia with neurological symptoms (eg nausea, debility, progressive disorientation and apathy) following thiazide treatment.
For nephrotic syndrome, chlortalidone should be used only under close control in normokalaemic patients with no signs of volume depletion.
Diuretics are best avoided for the management of oedema or hypertension in pregnancy as their use may be associated with hypovolaemia, increased blood viscosity and reduced placental perfusion. There have been reports of foetal bone marrow depression, thrombocytopenia, and foetal and neonatal jaundice associated with the use of thiazide diuretics.
Chlortalidone passes into the breast milk; mothers taking chlortalidone should refrain from breast-feeding their infants.
Patients should be warned of the potential hazards of driving or operating machinery if they experience side effects such as dizziness.
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