Medicinal products that could induce torsades de pointes

Due to the risk of hypokalaemia, hydrochlorothiazide should be administered with caution when associated with medicinal products that could induce torsades de pointes, in particular Class Ia and Class III antiarrhythmics and some antipsychotics.

Medicinal products affecting serum sodium level

The hyponatraemic effect of diuretics may be intensified by concomitant administration of drugs such as antidepressants, antipsychotics, antiepileptics, etc. Caution is advised in long-term administration of these drugs.

Digitalis glycosides

Thiazide-induced hypokalaemia or hypomagnesaemia may occur as undesirable effects favouring the onset of digitalis-induced cardiac arrhythmias (see section 4.4).

Calcium salts and vitamin D

Administration of thiazide diuretics, including hydrochlorothiazide, with vitamin D or with calcium salts may potentiate the rise in serum calcium. Concomitant use of thiazide type diuretics with calcium salts may cause hypercalcaemia in patients pre-disposed for hypercalcaemia (e.g. hyperparathyroidism, malignancy or vitamin-D-mediated conditions) by increasing tubular calcium reabsorption.

Antidiabetic agents (oral agents and insulin)

Thiazides may alter glucose tolerance. Dose adjustment of the antidiabetic medicinal product may be necessary.

Metformin should be used with caution because of the risk of lactic acidosis induced by possible functional renal failure linked to hydrochlorothiazide.

Beta blockers and diazoxide

Concomitant use of thiazide diuretics, including hydrochlorothiazide, with beta blockers may increase the risk of hyperglycaemia. Thiazide diuretics, including hydrochlorothiazide, may enhance the hyperglycaemic effect of diazoxide.

Medicinal products used in the treatment of gout (probenecid, sulfinpyrazone and allopurinol)

Dose adjustment of uricosuric medications may be necessary as hydrochlorothiazide may raise the level of serum uric acid. Increase of dosage of probenecid or sulfinpyrazone may be necessary. Co-administration of thiazide diuretics, including hydrochlorothiazide, may increase the incidence of hypersensitivity reactions to allopurinol.

Anticholinergic agents and other medicinal products affecting gastric motility

The bioavailability of thiazide-type diuretics may be increased by anticholinergic agents (e.g. atropine, biperiden), apparently due to a decrease in gastrointestinal motility and the stomach emptying rate. Conversely, it is anticipated that prokinetic drugs such as cisapride may decrease the bioavailability of thiazide-type diuretics.

Amantadine

Thiazides, including hydrochlorothiazide, may increase the risk of adverse effects caused by amantadine.

Ion exchange resins

Absorption of thiazide diuretics, including hydrochlorothiazide, is decreased by cholestyramine or colestipol. This could result in sub-therapeutic effects of thiazide diuretics. However, staggering the dosage of hydrochlorothiazide and resin such that hydrochlorothiazide is administered at least 4 h before or 4-6 h after the administration of resins would potentially minimise the interaction.