Generic Name

Nefazodone Hydrochloride

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Classification

FDA Approved Indications

• Major depressive disorder

Mechanism of Action

Nefazodone inhibits the reuptake of serotonin and norepinephrine, and antagonizes certain serotonin receptors, leading to increased serotonergic neurotransmission and antidepressant effects.

Dosage and Administration

Adult: Initial dose: 200 mg two to three times daily. Dose may be increased gradually as needed and tolerated, typically up to 300-600 mg per day in divided doses.

Pediatric: Not approved for pediatric use.

Geriatric: Start at lower dose; monitor closely due to increased sensitivity and potential for adverse effects.

Renal Impairment: Use with caution; dosage adjustments may be necessary.

Hepatic Impairment: Contraindicated in severe hepatic impairment; caution in mild to moderate impairment.

Pharmacokinetics

Absorption: Well-absorbed with oral administration.

Distribution: Extensively distributed; protein binding approximately 99%.

Metabolism: Primarily via hepatic CYP3A4.

Excretion: Metabolites excreted mainly via feces, with some renal excretion.

Half Life: Approximately 2-6 hours; active metabolites may prolong the effect.

Contraindications

• History of hepatic impairment or active liver disease.
• Concurrent use of other serotonergic drugs due to risk of serotonin syndrome.

Precautions

• Hepatic monitoring recommended; may cause hepatotoxicity.
• Use with caution in patients with underlying cardiac disease, seizure history, or those taking other CNS depressants.
• Pregnancy/lactation: Use only if clearly needed; advise on potential risks.

Adverse Reactions - Common

• Dizziness (Frequent)
• Sedation (Frequent)
• Dry mouth (Common)
• Nausea (Common)

Adverse Reactions - Serious

• Hepatotoxicity/liver failure (Rare but serious)
• Serotonin syndrome (Rare)
• Orthostatic hypotension (Uncommon)

Drug-Drug Interactions

• CYP3A4 inhibitors or inducers (e.g., ketoconazole, rifampin) which can alter nefazodone levels.
• Other serotonergic drugs (e.g., SSRIs, MAOIs) increasing serotonin syndrome risk.

Drug-Food Interactions

N/A

Drug-Herb Interactions

N/A

Nursing Implications

Patient/Family Teaching

• Do not use alcohol or other CNS depressants concurrently.
• Report any signs of liver problems (jaundice, dark urine, abdominal pain).
• Be aware of symptoms of serotonin syndrome (confusion, hallucinations, rapid heartbeat, changes in blood pressure, fever, loss of coordination).

Special Considerations

Black Box Warnings:

• Hepatotoxicity leading to severe, sometimes fatal, liver injury. Regular monitoring of liver function is mandatory.

Genetic Factors: None established specific to nefazodone.

Lab Test Interference: None reported.

Overdose Management

Signs/Symptoms: Drowsiness, blood pressure changes, nausea, vomiting, and in severe cases, coma or hepatotoxicity.

Treatment: Supportive care, activated charcoal if ingestion is recent, monitor liver function, and provide symptomatic treatment. There's no specific antidote.

Storage and Handling

Storage: Store at room temperature away from moisture, light, and heat.

Stability: Stable under standard conditions for the duration of the expiration date. Discard if expired or contaminated.