Nefazodone interaction with other drugs

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. 

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

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a BZD and another drug known to induce seizures may possibly increase seizure risk, especially if the BZD is abruptly withdrawn.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... 

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. 

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. 

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