Pharmacokinetically induced benzodiazepine withdrawal.

Pharmacokinetic interactions between medications can have clinically significant effects. Concern usually arises when a medication is added to a continuing regimen, though discontinuation of a medication can also have an impact. A case is presented of a patient who experienced benzodiazepine withdrawal symptoms on discontinuation of nefazodone, an antidepressant that inhibits the cytochrome P450 3A4 isoenzyme. Plasma levels of alprazolam, a substrate for the 3A4 isozyme, fell rapidly when nefazodone was discontinued, presumably because of renewed 3A4 isoenzyme activity. The management of the patient's withdrawal symptoms is described.