Overview
Serzone is a controversial, oral anti-depressant drug recently taken off the market in the United States – and less recently pulled in other countries - after causing liver failure and death in some patients.

Also known by its generic name, nefazodone, Serzone has been prescribed for those suffering moderate to severe depression. It was originally marketed as an alternative to other anti-depressants because it did not create the sexual side effects commonly associated with such drugs.

Structure, Appearance
Serzone’s chemical structure is unrelated to selective serotonin reuptake inhibitors, tricyclics, tetracyclics, or monoamine oxidase inhibitors (MAOI). The molecular formula is C25H32ClN5O2 • HCl. Nefazodone hydrochloride is a nonhygroscopic, white crystalline solid. It is freely soluble in chloroform, soluble in propylene glycol, and slightly soluble in polyethylene glycol and water.
Serzone is supplied as hexagonal tablets containing 50 mg, 100 mg, 150 mg, 200 mg, or 250 mg of nefazodone hydrochloride and the following inactive ingredients: microcrystalline cellulose, povidone, sodium starch glycolate, colloidal silicon dioxide, magnesium stearate, and iron oxides (red and/or yellow) as colorants.

How It Works
The mechanism of action of nefazodone, as with other antidepressants, is unknown. Preclinical studies have shown that nefazodone inhibits neuronal uptake of serotonin and norepinephrine. That is, Serzone prevents the brain from taking in hormones that affect, among other things, a person’s mood.

How It is Processed
Nefazodone hydrochloride is rapidly and completely absorbed but is subject to extensive metabolism, so that its absolute bioavailability is low, about 20%, and variable. Peak plasma concentrations occur at about one hour and the half-life of nefazodone is 2–4 hours. Nefazodone is widely distributed in body tissues, including the central nervous system (CNS).

Precautions & Drug Interactions
While nefazodone did not alter the in vitro protein binding, it is UNKNOWN whether displacement of either nefazodone or these drugs occurs in the womb. There was a 5% decrease in the protein binding of Haloperidol.

In a multiple-dose study of patients with liver cirrhosis, the AUC values for nefazodone and HO-NEF at steady state were approximately 25% greater than those observed in normal volunteers.

WARNING
Cases of life-threatening hepatic failure have been reported in patients treated with SERZONE. The reported rate in the United States is about 1 case of liver failure resulting in death or transplant per 250,000 – 300,000 patient-years of SERZONE treatment.

The total patient-years is a summation of each patient’s duration of exposure expressed in years. For example, 1 patient-year is equal to 2 patients each treated for 6 months, 3 patients each treatedfor 4 months, etc.

Ordinarily, treatment with SERZONE should not be initiated in individuals with active liver disease or with elevated baseline serum transaminases. There is no evidence that pre-existing liver disease increases the likelihood of developing liver failure, however, baseline abnormalities can complicate patient monitoring.

Patients should be advised to be alert for signs and symptoms of liver dysfunction (jaundice, anorexia, gastrointestinal complaints, malaise, etc.) and to report them to their doctor immediately if they occur. SERZONE should be discontinued if clinical signs or symptoms suggest liver failure. Patients who develop evidence of hepatocellular injurysuch as increased serum AST or serum ALT levels ≥3 times the upper limit of NORMAL, while on SERZONE should be withdrawn from the drug. These patients should be presumed to be at increased risk for liver injury if SERZONE is reintroduced. Accordingly, such patients should not be considered for re-treatment.