Zopiclone nefazodone

An 86-year-old white woman taking nefazodone for depression started to take zopiclone for insomnia, but subsequently had morning drowsiness (37). The plasma concentration of zopiclone was measured 8 hours after administration on two occasions, during and after nefazodone therapy. After withdrawal of nefazodone, the plasma concentration of the -enantiomer of zopiclone fell from 107 to 17 ng/ml, while the plasma concentration of the i -enantiomer fell from 21 to 1.5 ng/ml. 

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. 

Alderman CP, Gebauer MG, Gilbert AL, Condon JT. Possible interaction of zopiclone and nefazodone. Ann Pharmacother 2001 35(U) 1378-80. 

Nefazodone competes for hepatic oxidative pathways that metabolize most benzodiazepines, as well as zolpidem, zopiclone, and buspirone (SEDA-22, 39) (SEDA-22, 41). 

Omeprazole, like cimetidine, can impair benzodiazepine metabolism and lead to adverse effects (SEDA-18, 43). Other drugs, including antibiotics (erythromycin, chloramphenicol, isoniazid), antifungal drugs (ketoconazole, itraconazole, and analogues), some SSRIs (fluoxetine, paroxetine), other antidepressants (nefazodone), protease inhibitors (saquinavir), opioids (fentanyl), calcium channel blockers (diltiazem, verapamil), and disulfiram also compete for hepatic oxidative pathways that metabolize most benzodiazepines, as well as zolpidem, zopiclone, and buspirone (SEDA-22,39) (SEDA-22,41). 

An 86-year-old white woman taking nefazodone for depression started to take zopiclone for insomnia, but... 

Increased depressive effects when taken with other CNS depressants > Theoretically, inhibitors of CYP450 3A4, such as nefazodone and fluvoxamine, could increase plasma levels of zopiclone... 

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

Nefazodone increases the plasma levels and effects of alprazolam, midazolam, triazolam and zopiclone, but not lorazepam. 

Nefazodone appears to inhibit the oxidative metabolism of alprazolam, midazolam, triazolam and zopiclone by the cytochrome P450 isoenzyme CYP3A4 so that they accumulate in the body. Lorazepam is unaffected because it is primarily excreted as a conjugate. 

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. 

---