Possible interaction of zopiclone and nefazodone.
OBJECTIVE
To describe a case in which concurrent treatment with nefazodone was associated with an elevation in the plasma concentration of zopiclone, possibly resulting in enhanced hypnosedative efficacy.


METHODS
An 86-year-old white woman was treated with nefazodone for depression. Zopiclone was also introduced for the management of insomnia, but she subsequently experienced morning drowsiness. The concentration of zopiclone in plasma was subsequently measured eight hours after administration on two occasions, during nefazodone therapy and after its withdrawal. After discontnuation of nefazodone, the plasma concentration of the S-enantiomer of zopiclone decreased from 107 to 16.9 ng/mL, while the R-enantiomer plasma concentration decreased from 20.6 to 1.45 ng/mL.


CONCLUSIONS
Nefazodone is a relatively potent inhibitor of CYP3A4, a hepatic isoenzyme thought to play a major role in the metabolic elimination of zopiclone. The substantial decrease in the plasma zopiclone concentrations observed after withdrawal of nefazodone likely reflects a drug interaction. Despite the normally short elimination half-life of zopiclone, the residual sedation initially observed in this case suggests that the interaction may have clinical significance.


CONCLUSIONS
The features observed in this case suggest the possibility of a drug-drug interaction between nefazodone and zopiclone. Further prospective investigation is required to elucidate the nature and magnitude of this effect.
Alderman
C P
CP
Quality Use of Medicines and Pharmacy Research Centre, University of South Australia, Daw Park. Chris.Alderman@rgh.sa.gov.au
Gebauer
M G
MG
Gilbert
A L
AL
Condon
J T
JT
D000368:Aged; D000369:Aged, 80 and over; D018687:Antidepressive Agents, Second-Generation / Q000009:adverse effects* / Q000627:therapeutic use; D053961:Azabicyclo Compounds; D003866:Depressive Disorder / Q000188:drug therapy; D003924:Diabetes Mellitus, Type 2 / Q000150:complications; D004347:Drug Interactions; D005260:Female; D006801:Humans; D006993:Hypnotics and Sedatives / Q000009:adverse effects* / Q000627:therapeutic use; D010879:Piperazines / Q000009:adverse effects* / Q000627:therapeutic use; D014230:Triazoles / Q000009:adverse effects* / Q000627:therapeutic use
D018687:Antidepressive Agents, Second-Generation; D053961:Azabicyclo Compounds; D006993:Hypnotics and Sedatives; D010879:Piperazines; D014230:Triazoles; C515050:zopiclone; C051752:nefazodone