Drug Interaction Report

MONITOR: Limited data suggest that furosemide and possibly other loop diuretics may potentiate the nephrotoxicity of some cephalosporins. The exact mechanism of interaction is unknown, although furosemide has been shown to increase the plasma concentrations and/or reduce the clearance of several cephalosporins such as cephaloridine and ceftazidime. Data from an early study identified an association between diuretic use and acute renal failure during cephaloridine treatment. Specifically, 9 out of 36 patients who developed acute renal failure while on cephaloridine were also receiving a diuretic (primarily furosemide). Other risk factors included shock, infection, excessive dosage of cephaloridine, and concomitant use of other potentially nephrotoxic drugs. Several case reports have also suggested an increased risk of nephrotoxicity with the combination of furosemide and cephaloridine or cephalothin, and one study found that administration of furosemide or ethacrynic acid increased both the incidence and extent of proximal renal tubular necrosis in cephaloridine-treated mice and rats. In contrast, a study conducted in patients with preexisting moderate renal impairment found no effect of furosemide on the serum half-life of cefoxitin, and glomerular filtration rate was not affected during concomitant administration of cefoxitin and furosemide.

MANAGEMENT: Although data are primarily limited to cephaloridine, which is no longer commercially marketed, caution may be advisable in patients receiving a loop diuretic in combination with other cephalosporins. Renal function should be monitored, particularly when high dosages are used or when these medications are administered in the elderly or patients with preexisting renal impairment.

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ADJUST DOSING INTERVAL: Oral products containing zinc such as mineral supplements and multivitamins may interfere with the gastrointestinal absorption of cephalexin, ceftibuten or cephradine. In one pharmacokinetic study (n=12), concurrent administration of zinc sulfate (250 mg, single oral dose) and cephalexin (500 mg, single oral dose) decreased cephalexin maximum concentration (Cmax) and systemic exposure (AUC; 0-inf) by 31.05% and 27.4%, respectively. However, in the same study, when zinc sulfate was administered 3 hours after the cephalexin dose, no significant alteration in cephalexin pharmacokinetics were observed.

MANAGEMENT: Oral medications or mineral supplements that contain zinc are recommended to be administered at least 3 hours after the cephalexin, ceftibuten or cephradine dose.

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