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DEMADEX (TORSEMIDE): DRUG INTERACTIONS

In patients with essential hypertension, Torsemide (Demadex) has been administered together with beta-blockers, ACE inhibitors, and calcium-channel blockers. In patients with congestive heart failure, Demadex has been administered together with digitalis glycosides, ACE inhibitors, and organic nitrates. None of these combined uses was associated with new or unexpected adverse events.

Torsemide does not affect the protein binding of glyburide or of warfarin, the anticoagulant effect of phenprocoumon (a related coumarin derivative), or the pharmacokinetics of digoxin or carvedilol (a vasodilator/be ta-blocker). In healthy subjects, coadministration of Demadex was associated with significant reduction in the renal clearance of spironolactone, with corresponding increases in the AUC. However, clinical experience indicates that dosage adjustment of eitheragent is not required.

Because Torsemide (Demadex) tablets and salicylates compete for secretion by renal tubules, patients receiving high doses of salicylates may experience salicylate toxicity when Demadex is concomitantly administered. Also, although possible interactions between torsemide and nonsteroidal anti-inflammatory agents (including aspirin) have not been studied, coadministration of these agents with another loop diuretic (furosemide) has occasionally been associated with renal dysfunction.

The natriuretic effect of Demadex (like that of many other diuretics) is partially inhibited by the concomitant administration of indomethacin. This effect has been demonstrated for Demadex (Torsemide/Torasemide) under conditions of dietary sodium restriction (50 mEq/day) but not in the presence of normal sodium intake (150 mEq/day).

The pharmacokinetic profile and diuretic activity of torsemide are not altered by cimetidine or spironolactone. Coadministration of digoxin is reported to increase the area under the curve for torsemide by 50%, but dose adjustment of Demadex is not necessary.

Concomitant use of torsemide and cholestyramine has not been studied in humans but, in a study in animals, coadministration of cholestyramine decreased the absorption of orally administered torsemide. If Demadex (Torsemide/Torasemide) tablets and cholestyramine are used concomitantly, simultaneous administration is not recommended.

Coadministration of probenecid reduces secretion of Demadex into the proximal tubule and thereby decreases the diuretic activity of Torsemide/Torasemide (Demadex).

Other diuretics are known to reduce the renal clearance of lithium, inducing a high risk of lithium toxicity, so coadministration of lithium and diuretics should be undertaken with great caution, if at all. Coadministration of lithium and Demadex has not been studied.

Other diuretics have been reported to increase the ototoxic potential of aminoglycoside antibiotics and of ethacrynic acid, especially in the presence of impaired renal function. These potential interactions with Torsemide/Torasemide (Demadex) tablets have not been studied.

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