Furosemide may enhance the nephrotoxicity of cephalosporin antibacterials such as cefalotin and can enhance the ototoxicity of aminoglycoside antibacterials and other ototoxic drugs.
Many of the interactions of furosemide are due to their effects on fluid and electrolyte balance. Diuretic-induced hypokalaemia may enhance the toxicity of digitalis glycosides and may also increase the risk of arrhythmias with drugs that prolong the QT interval, such as astemizole, terfenadine, halofantrine, pimozide, and sotalol. Furosemide may enhance the neuromuscular blocking action of competitive neuromuscular blockers, such as atracurium, probably by their hypokalaemic effect. The potassium-depleting effect of diuretics may be enhanced by corticosteroids, corticotropin, beta2 agonists such as salbutamol, carbenoxolone, amphotericin B, or reboxetine.
Diuretics may enhance the effect of other antihypertensives, particularly the first-dose hypotension that occurs with alpha blockers or ACE inhibitors. Orthostatic hypotension associated with diuretics may be enhanced by alcohol, barbiturates, or opioids. The antihypertensive effects of diuretics may be antagonised by drugs that cause fluid retention, such as corticosteriods, NSAIDs, or carbenoxolone; diuretics may enhance the nephrotoxicity of NSAIDs. Thiazides have been reported to diminish the response to pressors amines, such as noradrenaline, but the clinical significance of this effect is uncertain. Thiazides should not usually be used with lithium since the association may lead to toxic blood concentrations of lithium. Other drugs for which increased toxicity has been reported when given with thiazides include allopurinol and tetracyclines. Thiazides may alter the requirements for hypoglycaemics in diabetic patients.
Antibacterials: Severe hyponatraemia has been reported in patients taking trimethoprim with co-amilozide and hydrochlorothiazide.
Antiepileptics: There has been a report of symptomatic hyponatraemia associated with the use of hydrochlorothiazide of furosemide and carbamazepine.
Bile-acid binding resins: Gastrointestinal absorption of both chlorothiazide and hydrochlorothiazide has been reported to be reduced by colestipol and colestyramine. In a study in healthy subjects, colestyramine had the greatest effect on hydrochlorothiazide, decreasing absorption by 85% compared with a decrease of 43% with colestipol. Even when colestyramine was given 4 hours after hydrochlorothiazide reductions of absorption of at least 30 to 35% could be expected.
Calcium salts: The milk-alkali syndrome, characterized by hypercalcaemia, metabolic alkalosis, and renal failure, developed in a patient taking chlorothiazide and moderately large doses of calcium carbonate. Patients taking thiazides may be at increased risk of developing the syndrome because of their reduced ability to excrete excess calcium. Hypercalcaemia may also occur in patients taking thiazides with drugs that increase calcium levels.
Dopaminergics: For a report of increased amantadine toxicity associated with hydrochlorothiazide and triamterene.