Drug interactions nefazodone

Coadministration with cisapride, pimozide, or carbamazepine (see Warnings and Drug Interactions) patients who were withdrawn from nefazodone because of evidence of liver injury (see Warning box. Warnings) hypersensitivity to nefazodone or other phenylpiperazine antidepressants. 

The use of two or more agents concurrently has the potential for possibly deleterious drug interactions. Thus, as noted in subsequent chapters, the addition or elimination of an agent may significantly alter the activity of the concurrent drug treatment (e.g., carbamazepine lowering haloperidol plasma levels nefazodone increasing the levels of triazolam). 

Two open label studies have been done with nefazodone (. 367, 368). As discussed earlier, the value of such open label studies is dubious. Moreover, this strategy is limited by the divided dose schedule recommended for the immediate release formulation of nefazodone, the need for dose adjustment, and the potential for complicated drug-drug interactions, particularly when switching from fluoxetine to nefazodone. 

Because most antidepressants require oxidative metabolism as a necessary step in their elimination, they can be the target of a pharmacokinetic drug-drug interaction, as well as the cause. The CYP enzymes mediating the biotransformation of the various antidepressants are also shown in Table 7-30. CYP 1A2 and 3A3/4 are induced by anticonvulsants such as barbiturates and carbamazepine. As expected, coadministration of these anticonvulsants has been shown to lower plasma levels of TCAs and would be predicted to have the same effect on nefazodone, sertraline, and venlafaxine. 

The substantial fall in plasma zopiclone concentration after withdrawal of nefazodone probably reflected a drug interaction due to inhibition of CYP3A4 by nefazodone (38). Despite the normally short half-life of zopiclone, the residual sedation initially observed in this case suggests that the interaction had clinical significance. 

Wright DH, Lake KD, Bruhn PS, Emery RW Jr. Nefazodone and cyclosporine drug-drug interaction. J Heart Lung Transplant 1999 18(9) 913-5. 

The substantial fall in plasma zopiclone concentration after withdrawal of nefazodone probably reflected a drug interaction due to inhibition of CYP3A4 by... 

Nefazodone is highly (>99%) protein bound, which may cause clinical drug interactions with other medications that are highly protein bound. 

Dockens RC, Greene DS, Barbhaiya RH Assessment of phaimacokinetic and phaimacody-namic drug interactions between nefazodone and digoxin in healthy male volunteers J Clin Pharmacol 996) 36,160-7. 

The manufacturers of trazodone say that in vitro drug metabolism studies suggest that there is a potential for drug interactions when trazodone is given with a potent CYP3A4 inhibitor such as nefazodone. There may be substantial increases in trazodone levels, with the potential for adverse effects, and a lower dose oftrazodone should be considered. The UK manufacturer suggests avoidance of the combination where possible. ... 

Potential interaction with drugs that inhibit or are metabolized by cytochrome P-450 (3A4 and 2D6) isozymes Caution is indicated in the combined use of nefazodone with any drugs known to be metabolized by the 3A4 isozyme (in particular, cisapride or pimozide). 

Drug/Food interactions Food delays absorption of nefazodone and decreases the bioavailability by about 20%. 

NA /D, abd pain, bleeding, fevCT, T QT Interactions t Effects W7 atazanavir, clarithromycin, CT5rthromycin, indinavir, itraconazole, ketoconazole, nefazodone, nelfi-navir, ritonavir, saquinavir, telithromycin X effects W7 antacids, carbamazqjine, dexamethasone, phenobarbital, phenytoin, rifampicin, St. John s wort EMS Drug contains lactose, may cause D/abd discomfort in pts w/ lactose intolerance OD Sxs unknown symptomatic and supportive... 

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