Nefazodone drug interactions with

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

Coadministration with cisapride, pimozide, or carbamazepine (see Warnings and Drug Interactions) patients who were withdrawn from nefazodone because of evidence of liver injury (see Warning box.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

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). 

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. 

With the important exception of additive effects when combined with other CNS depressants, including alcohol, BZDs interact with very few drugs. Disulfiram (see the section The Alcoholic Patient in Chapter 14) and cimetidine may increase BZD blood levels, and diazepam may increase blood levels of digoxin and phenytoin. Antacids may reduce the clinical effects of clorazepate by hindering its biotransformation to desmethyidiazepam. Coadministration of a BZD and another drug known to induce seizures may possibly increase seizure risk, especially if the BZD is abruptly withdrawn. Furthermore, as noted earlier, important interactions have been reported among nefazodone, erythromycin, troleandomycin, and other macrolide antibiotics, as well as itraconazole. In each case, metabolism is inhibited, and triazolam levels can increase significantly. 

Drugs that participate in major CYP3A4 interactions with macrohdes are listed in Table 4. Other drugs that may be affected include alprazolam (138), the water-soluble artemisinin analogue artehnic acid (139), gallopamil (140), lovastatin (141), nefazodone (142), and risperidone... 

Clinically important, potentially hazardous interactions with citalopram, dihydroergotamine, ergot-containing drugs, escitalopram, fluoxetine, fluvoxamine, isocarboxazid, MAO inhibitors, methysergide, naratriptan, nefazodone, paroxetine, phenelzine, rizatriptan, sertraline, sibutramine, St John s wort, tranylcypromine, venlafaxine, zolmitriptan... 

The interactions of nefazodone with alprazolam, midazolam, triazolam and zopiclone are established and clinically important. The practical consequences are that the effects of alprazolam, midazolam and triazolam are expected to be increased but the extent is uncertain. Be alert for any evidence of any psychomotor impairment, drowsiness etc. and reduce the benzodiazepine dosage if necessary. More study is needed. Lorazepam does not interact with nefazodone. There seems to be no direct information about other benzodiazepines and related drugs. 

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 interactions through the cytochrome P450 CYP 2D6 and CYP 3A4 enz)unes can be noted from Tables 19.2a and 19.2b. The combination of drugs that are substrates of the same enzyme creates potential for competitive inhibition of their metabolism with unexpected elevation of plasma concentration. Similarly, potent inhibitors, e.g. fluoxetine and paroxetine (CYP 2D6), fluoxetine and nefazodone (CYP 3A4) and fluvoxamine (CYP 1A2), may cause adverse effects by reducing metabolic breakdown of co-prescribed drugs that are used in standard doses. Antidepressants are commonly prescribed with antipsychotics in a depressive... 

The use of cisapride and its benefit to harm balance in children has been reviewed (25). Overall it is well tolerated. The most common adverse effects are diarrhea, abdominal cramps, borborygmi, and colic. Serious adverse events are rare and include isolated cases of extrapyramidal reactions, seizures in epileptic patients, cholestasis, QT interval prolongation and ventricular dysrhythmias, anorexia, and enuresis. Interactions of cisapride with other drugs are similar to those reported in adults. Co-administration of drugs that inhibit CYP3A4, such as imidazoles, macrolide antibiotics, the antidepressant nefazodone, and protease inhibitors such as ritonavir, are contraindicated. Furthermore, co-administration of anticholinergic drugs can compromise the beneficial effects of cisapride. 

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