the morning by her significant other, after ingesting 30 nefazodone 100-mg tablets within the previous 5 hours. Nefazodone 100 mg bid was prescribed 4 weeks earlier. The patient's empty pill bottle and the date it was prescribed indicated that her reported amount was accurate. It is not known how much she had eaten prior to taking the medication. On arrival at the ED, her vital signs were BP 100/54 mm Hg taken on her right arm in a sitting position, T 37.2˚C, HR 97 beats/min, and RR 18 breaths/min. Physical examination revealed a woman with normal body weight. The patient opened her eyes to verbal command, but went to sleep if not stimulated. The rest of the examination, including a neurologic examination, was normal. She had neither previous suicide attempts nor alcohol or drug use other than tobacco. All blood was drawn approximately 20 minutes after her arrival in the ED, and the assays were performed in the hospital laboratory. Her blood chemistries, liver function analysis, and urinalysis were all negative. An electrocardiogram showed normal sinus rhythm. The serum nefazodone concentration was 5.5 µg/mL. A subtherapeutic amount of norpropoxyphene and propoxyphene were in her serum, and a urine toxicologic analysis demonstrated that phentermine and phenylpropanolamine were present, but concentrations were not determined.The patient was treated with two doses of charcoal, which she vomited along with multiple pill fragments. She was monitored in the ED for 3 hours and remained awake and alert. She was then transferred to the psychiatric unit for 6 days and was discharged in good condition on sertraline 100 mg/d. 2 The patient remained compliant as an outpatient.Discussion. Nefazodone is documented to be well tolerated, with a low incidence and severity of adverse affects. 3 To our knowledge, this is the first reported case of nefazodone overdose in the general population. During clinical trials, seven overdoses, ranging from 1000 to 11 200 mg, were reported prior to release of the drug (personal communication, James D Prazak, Manager of Professional Services, Bristol Myers-Squibb Co., July 17, 1996). One patient had a convulsion (cause not documented) after taking nefazodone 2000-3000 mg with methocarbamol and alcohol. The only other reported symptoms of overdose were nausea and somnolence.Nefazodone is absorbed rapidly, but has a low bioavailability of approximately 20%, and exhibits nonlinear kinetics. The clearance of the drug decreases as the dose increases. Its half life is 2-4 hours, and it reaches its peak plasma concentration (C max ) within 1 hour. 4 For a middle-age woman with a normal body weight, the C max after a single 300mg dose is 0.54 µg/mL. 5 Our patient took 10 times this dose, and after almost two half-life periods, she still had a blood concentration of 5.5 µg/mL of nefazodone. This is consistent with the nonlinear kinetics of this drug, and may indicate that at higher doses, the C max increases substantially. It may also indicate that other factors such as food intake or other pharmacolo...
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