Nefazodone Loratadine

Barbey JT. Loratadine/nefazodone interaction. Clin Pharmacol TherQ.OOT) 71, 403. 

Drugs that can increase carbamazepine serum levels include cimetidine, danazol, diltiazem, erythromycin, felbamate, clarithromycin, fluoxetine, isoniazid, niacinamide, propoxyphene, ketaconazole, itraconazole, verapamil, valproate, troleandomycin, loratadine, nicotinamide, tricyclic antidepressants, SSRIs, nefazodone, protease inhibitors. 

Drugs that inhibit CYP3A4 inhibit the clearance of terfenadine, an antihistamine that can prolong the QTC interval. This can cause potentially dangerous interactions. In a double-blind, placebo-controlled study of the effect of nefazodone (600 mg/day for 1 week) on the pharmacokinetics of terfenadine (120 mg/day for 14 days) and another antihistamine, loratadine (20 mg/day for 14 days), in 67 healthy volunteers, nefazodone significantly reduced the clearance of terfenadine and prolonged the mean QTC interval (27). In addition, nefazodone produced a similar but smaller decrease in the clearance of loratadine and combined treatment also significantly increased the QTC interval. This effect of nefazodone on... 

Abernethy DR, Barbey JT, Franc J, Brown KS, Feirrera I, Ford N, Salazar DE. Loratadine and terfenadine interaction with nefazodone both antihistamines are associated with QTc prolongation. Clin Pharmacol Ther 2001 69(3) 96-103. 

Nefazodone is a phenylpiperazine antidepressant that is predominantly metabolized by CYP3A. In a randomized, double-blind, double-dummy, parallel-group, multiple-dose study in healthy men and women who were given loratadine 20 mg od or nefazodone 300 mg every 12 hours, the plasma loratadine concentrations were significantly increased by co-administration of nefazodone (7). The mean QT interval was unchanged by loratadine alone, but was markedly prolonged with co-administration of nefazodone, and the extent of prolongation correlated with the plasma loratadine concentration. 

Nefazodone inhibits the metabolism of terfenadine and thereby prolongs the QT interval. This combination should be avoided. There is also some evidence that the combination of nefazodone and loratadine increases the QT interval, although to a lesser extent than terfenadine. In vitro evidence suggests nefazodone will also inhibit the metabolism of astemizole. 

A randomised, placebo-controlled study in healthy subjects found that when they were given nefazodone 300 mg twice daily with loratadine 20 mg once daily, the loratadine AUC was increased by 39%. Similarly, the QTc interval was increased by 21.6 milliseconds by the combination, which was about half the increase seen with terfenadine 60 mg twice daily given with the same dose of nefazodone. Neither nefazodone, loratadine nor terfenadine alone prolonged the QTc interval. The findings for loratadine in this study were unexpected, since this antihistamine was considered to have no clinically relevant effect on the QT interval (but see also Table 15.2 , (p.583)). The use of the Bazett formula to calculate QTc has... 

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