Hydrochlorothiazide

Hydrochlorothiazide antagonizes the action of lidocaine, mexiletine and tocainide when hypokalaemia is present.

Due to the risk of hypokalaemia, caution should be used when hydrochlorothiazide is co-administered with medicines associated with torsades de pointes, e.g. anti-dysrhythmics, antipsychotics and other medicines known to induce Torsades de pointes.

In some patients, the administration of NSAIDs can reduce the diuretic, natriuretic and antihypertensive effects of loop, potassium-sparing and thiazide diuretics. Therefore, when hydrochlorothiazide and NSAIDs are used concomitantly, the patient should be observed closely to determine if the desired effect of the diuretic is obtained.

Co-administration may potentiate orthostatic hypotension.

Hydrochlorothiazide should be given with caution in renal function impairment since it can further reduce renal function.

In patients with renal disease, hydrochlorothiazide may precipitate azotaemia and oliguria. Cumulative effects of the medicine may develop in patients with impaired renal function. If progressive renal impairment becomes evident, as indicated by rising non-protein nitrogen, careful reappraisal of therapy is necessary, with consideration given to discontinuing diuretic therapy.

Increased serum calcium levels due to decreased excretion may occur when administered concurrently with hydrochlorothiazide.

Hydrochlorothiazide may enhance the toxicity of digitalis glycosides by depleting serum-potassium concentrations.

Hydrochlorothiazide has been reported to diminish the response to pressor amines, such as noradrenaline, but the clinical significance of this effect is uncertain.

May have an additive effect. Discontinuation of diuretic therapy 2 to 3 days before the initiation of treatment with an ACE inhibitor may reduce the likelihood of first dose-hypotension. The antihypertensive effect of the drug may be enhanced in the post-sympathectomy patient.

Hydrochlorothiazide may enhance the neuromuscular blocking action of competitive muscle relaxants, such as tubocurarine.

Hydrochlorothiazide may enhance the neuromuscular blocking action of competitive muscle relaxants, such as tubocurarine.

Concomitant use of carbamazepine and hydrochlorothiazide has been associated with a risk of symptomatic hyponatremia. Electrolytes should be monitored during co-administration. If possible, a different class of diuretic should be used.

The presence of anionic exchange resins may delay or decrease absorption of hydrochlorothiazide. Sulphonamide diuretics should be taken at least one hour before or four to six hours after these medicines.

Single doses of either cholestyramine or colestipol resins bind hydrochlorothiazide and reduce its absorption from the gastrointestinal tract by up to 85% and 43% respectively.

Hydrochlorothiazide should be discontinued before carrying out tests for parathyroid function.

Hydrochlorothiazide may cause diagnostic interference of the bentiromide test. Hydrochlorothiazide may decrease serum Protein Bound Iodine (PBI) levels without signs of thyroid disturbance.

Sensitivity reactions may occur in patients with a history of bronchial asthma.

The antihypertensive effects of the medicine may be enhanced in the post-sympathectomy patient.

Hydrochlorothiazide may cause hyperglycaemia and aggravate or unmask diabetes mellitus. Blood-glucose concentrations should be monitored in patients taking antidiabetic medicines, including insulin and oral hypoglycaemic medicines, since requirements may change.

Oral and parenteral antidiabetic drugs: May require adjustment of dosage with concurrent use.

There is limited experience with hydrochlorothiazide during pregnancy, especially during the first trimester. Animal studies are insufficient.

Hydrochlorothiazide crosses the placenta. Based on the pharmacological mechanism of action of hydrochlorothiazide its use during the second and third trimester may compromise foeto-placental perfusion and may cause foetal and neonatal effects like icterus, disturbance of electrolyte balance and thrombocytopenia.

Hydrochlorothiazide should not be used for gestational oedema, gestational hypertension or preeclampsia due to the risk of decreased plasma volume and placental hypoperfusion, without a beneficial effect on the course of the disease.

Hydrochlorothiazide should not be used for essential hypertension in pregnant women except in rare situations where no other treatment could be used.

Hydrochlorothiazide is excreted in human milk in small amounts. Thiazides in high doses causing intense diuresis can inhibit the milk production. The use of hydrochlorothiazide during breast feeding is not recommended. If hydrochlorothiazide is used during breast feeding, doses should be kept as low as possible.

Hydrochlorothiazide has moderate influence on the ability to drive and use machines. Since adverse reactions such as dizziness, drowsiness and visual disturbance have been reported in patients receiving hydrochlorothiazide, patients should not drive, use machinery or perform any tasks that require concentration, until they are certain that hydrochlorothiazide does not adversely affect their ability to do so.

a) Summary of the safety profile

b) Description of selected adverse reactions

Eye disorders

Cases of choroidal effusion with visual field defect have been reported after the use of thiazide and thiazide-like diuretics.

Metabolism and nutrition disorders

Electrolyte imbalances, hypochloraemic alkalosis, hyponatraemia (may occur in patients with severe heart failure who are very oedematous, particularly with large doses in conjunction with restricted salt in the diet), and hypokalaemia (intensifies the effect of digitalis on cardiac muscle and administration of digitalis or its glycosides may have to be temporarily suspended and patients with cirrhosis of the liver are particularly at risk), metabolic disturbances especially at high doses, hyperglycaemia in diabetic and other susceptible patients, hyperuricaemia and precipitate attacks of gout in some patients, hypomagnesaemia, anorexia.

Vascular disorders

Postural hypotension (aggravated by barbiturates, alcohol, narcotics or antihypertensive medicines), necrotising angiitis (vasculitis, cutaneous vasculitis).