Combinations that are not recommended: Lithium: Increased plasma lithium with signs of overdosage, as with a salt-free diet (decreased urinary lithium excretion). However, if the use of diuretics is necessary, careful monitoring of plasma lithium and dose adjustment are required.
Combinations requiring precautions for use: Torsades de pointes-inducing drugs such as but not limited to: class Ia antiarrhythmics (e.g quinidine, hydroquinidine, disopyramide); class III antiarrhythmics (e.g amiodarone, sotalol, dofetilide, ibutilide, bretylium); some antipsychotics: phenothiazines (e.g chlorpromazine, cyamemazine, levomepromazine, thioridazine, trifluoperazine); benzamides (e.g amisulpride, sulpiride, sultopride, tiapride); butyrophenones (e.g droperidol, haloperidol); other antipsychotic (e.g pimozide); other substances (e.g bepridil, cisapride, diphemanil, erythromycin IV, halofantrine, mizolastine, pentamidine, sparfloxacin, moxifloxacin, vincamine IV, methadone, astemizole, terfenadine).
Increased risk of ventricular arrhythmias, particularly torsades de pointes (hypokalaemia is a risk factor).
Monitor for hypokalaemia and correct, if required, before introducing this combination. Clinical, plasma electrolytes and ECG monitoring.
Use substances which do not have the disadvantage of causing torsades de pointes in the presence of hypokalaemia.
N.S.A.I.Ds. (systemic route) including COX-2 selective inhibitors, high dose salicylic acid (≥ 3 g/day): Possible reduction in the antihypertensive effect of indapamide.
Risk of acute renal failure in dehydrated patients (decreased glomerular filtration). Hydrate the patient; monitor renal function at the start of treatment.
Angiotensin converting enzyme (A.C.E.) inhibitors: Risk of sudden hypotension and/or acute renal failure when treatment with an A.C.E. inhibitor is initiated in the presence of preexisting sodium depletion (particularly in patients with renal artery stenosis).
In hypertension, when prior diuretic treatment may have caused sodium depletion, it is necessary: either to stop the diuretic 3 days before starting treatment with the A.C.E. inhibitor, and restart a hypokalaemic diuretic if necessary; or give low initial doses of the A.C.E. inhibitor and increase the dose gradually.
In congestive heart failure, start with a very low dose of A.C.E. inhibitor, possibly after a reduction in the dose of the concomitant hypokalaemic diuretic.
In all cases, monitor renal function (plasma creatinine) during the first weeks of treatment with an A.C.E. inhibitor.
Other compounds causing hypokalaemia: amphotericin B (IV), gluco- and mineralo-corticoids (systemic route), tetracosactide, stimulant laxatives: Increased risk of hypokalaemia (additive effect).
Monitoring of plasma potassium and correction if required. Must be particularly borne in mind in case of concomitant digitalis treatment. Use non-stimulant laxatives.
Baclofen: Increased antihypertensive effect.
Hydrate the patient; monitor renal function at the start of treatment.
Digitalis preparations: Hypokalaemia and/or hypomagnesaemia predispose to the toxic effects of digitalis.
Monitoring of plasma potassium, magnesium and ECG and, if necessary, adjust the treatment.
Combinations requiring special care: Allopurinol: Concomitant treatment with indapamide may increase the incidence of hypersensitivity reactions to allopurinol.
Combinations to be taken into consideration: Potassium-sparing diuretics (amiloride, spironolactone, triamterene): Whilst rational combinations are useful in some patients, hypokalaemia or hyperkalaemia (particularly in patients with renal failure or diabetes) may still occur. Plasma potassium and ECG should be monitored and, if necessary, treatment reviewed.
Metformin: Increased risk of metformin induced lactic acidosis due to the possibility of functional renal failure associated with diuretics and more particularly with loop diuretics. Do not use metformin when plasma creatinine exceeds 15 mg/l (135 μmol/l) in men and 12 mg/l (110 μmol/l) in women.
Iodinated contrast media: In the presence of dehydration caused by diuretics, increased risk of acute renal failure, in particular when large doses of iodinated contrast media are used.
Rehydration before administration of the iodinated compound.
Imipramine-like antidepressants, neuroleptics: Antihypertensive effect and increased risk of orthostatic hypotension increased (additive effect).
Calcium (salts): Risk of hypercalcaemia resulting from decreased urinary elimination of calcium.
Ciclosporin, tacrolimus: Risk of increased plasma creatinine without any change in circulating ciclosporin levels, even in the absence of water/sodium depletion.
Corticosteroids, tetracosactide (systemic route): Decreased antihypertensive effect (water/sodium retention due to corticosteroids).