SERZONE
Clinical safety rating: caution
Comprehensive clinical and safety monograph for SERZONE (SERZONE).
Serzone (nefazodone) is a serotonin antagonist and reuptake inhibitor (SARI). It blocks postsynaptic 5-HT2 receptors and inhibits serotonin and norepinephrine reuptake, leading to increased serotonergic and noradrenergic neurotransmission.
| Metabolism | Primarily metabolized by CYP3A4 isoenzyme; major metabolites include hydroxynefazodone, mCPP, and triazole dione. |
| Excretion | Primarily hepatic metabolism; <1% excreted unchanged renally; metabolites excreted in urine (approximately 85%) and feces (approximately 15%). |
| Half-life | Terminal elimination half-life is 18-22 hours for nefazodone; steady-state achieved in 3-5 days. |
| Protein binding | 99% bound to albumin and alpha-1-acid glycoprotein. |
| Volume of Distribution | Vd is approximately 50-70 L (0.7-1.0 L/kg), indicating extensive tissue distribution. |
| Bioavailability | Oral bioavailability is about 20% due to extensive first-pass metabolism; variable with food (increases absorption). |
| Onset of Action | Oral: 1-2 weeks for therapeutic antidepressant effect; full benefit may require 4-6 weeks. |
| Duration of Action | Duration of action is approximately 24 hours with once-daily dosing; clinical effects persist with continued use. |
Initial 100 mg orally twice daily; titrate to 200-300 mg twice daily. Maximum 600 mg/day.
| Dosage form | TABLET |
| Renal impairment | No specific guidelines; use with caution in severe renal impairment (CrCl <30 mL/min). |
| Liver impairment | Contraindicated in Child-Pugh Class C; reduce dose by 50% in Child-Pugh A/B. |
| Pediatric use | Not approved; safety and efficacy not established. |
| Geriatric use | Start at 100 mg once daily; increase slowly to 200-300 mg daily in divided doses. |
| 1st trimester | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
Clinical note
Comprehensive clinical and safety monograph for SERZONE (SERZONE).
| Breastfeeding | Nefazodone and its metabolites are excreted into breast milk. Infant plasma levels are low to undetectable. M/P ratio not well characterized. Consider risk of infant sedation and decreased feeding; use caution, especially with preterm neonates. |
| Teratogenic Risk | First trimester: Data limited; animal studies show no consistent teratogenicity but some developmental toxicity at high doses. Second and third trimesters: Risk of neonatal adaptation syndrome (irritability, respiratory distress) with late-third trimester exposure; also associated with persistent pulmonary hypertension of the newborn (PPHN). Avoid unless benefit outweighs risk. |
■ FDA Black Box Warning
WARNING: LIVER TOXICITY. Serzone can cause severe, life-threatening hepatotoxicity, including hepatic failure requiring liver transplantation or resulting in death. Elevations of liver enzymes to 3 or more times the upper limit of normal have been reported. Serzone should not be used in patients with active liver disease or elevated baseline serum transaminases. Patients should be monitored for signs of liver dysfunction, and treatment should be discontinued if liver injury is suspected.
| Serious Effects |
Absolute: Active liver disease or elevated baseline serum transaminases. Concomitant use with MAOIs (or within 14 days of discontinuation). Concomitant use with terfenadine, astemizole, cisapride, pimozide, or carbamazepine (due to CYP3A4 inhibition). Hypersensitivity to nefazodone or any excipients.
| Precautions | Hepatotoxicity: Risk of severe liver injury; discontinue if signs of hepatic dysfunction. Suicidal thoughts/behaviors: Monitor for worsening depression or suicidality, especially in young adults. Serotonin syndrome: Risk when used with other serotonergic drugs. Activation of mania/hypomania in bipolar disorder. Priapism: Rare but requires immediate medical attention. Orthostatic hypotension: Caution in patients with cardiovascular disease or dehydration. Seizures: Use cautiously in patients with seizure disorders. Drug interactions: Inhibits CYP3A4; avoid use with terfenadine, astemizole, cisapride, pimozide, and carbamazepine. |
Loading safety data…
| Fetal Monitoring | Monitor maternal blood pressure, liver function (risk of hepatotoxicity), and signs of serotonin syndrome. Fetal monitoring for growth and well-being; neonatal monitoring for adaptation syndrome and PPHN after delivery. |
| Fertility Effects | No definitive human data. Animal studies suggest possible luteal phase shortening and implantation interference at high doses; may affect fertility in women. Use with caution in women attempting conception. |