nefazodone (Rx)

>10%

Headache (31-35%)

Somnolence (21-25%)

Nausea (21-25%)

Xerostomia (21-25%)

Dizziness (15-20%)

Asthenia (11-15%)

Constipation (11-15%)

Insomnia (11-15%)

1-10%

Infection (6-10%)

Dyspepsia (6-10%)

Lightheadedness (6-10%)

Confusion (6-10%)

Blurred vision (6-10%)

Abnormal vision (6-10%)

Increased appetite (1-5%)

Memory loss (1-5%)

Paresthesia (1-5%)

Vasodilation (1-5%)

Decreased concentration (1-5%)

Ataxia (1-5%)

Decreased libido (1-5%)

Breast pain (1-5%)

Decreased hematocrit (1-5%)

Agitation with discontinuation (1-5%)

Orthostatic hypotension (2.6%)

Bradycardia (1.5%)

Frequency Not Defined

Hypomania

Mania

Seizure

Suicidal thoughts

Suicide

Worsening depression

Liver failure (rare, 1 in 250,000-300,000)

Contraindications

Co-administration with terfenadine (discontinued), astemizole (discontinued), cisapride, pimozide, carbamazepine

Concurrent administration with alprazolam or triazolam (reduce dose by 50% and 75%, respectively)

Hypersensitivity to nefazadone or other phenylpiperazine antidepressants

Co-administration with MAO inhibitors or within 14 days of administration

Avoid during breast-feeding

Cautions

Clinical worsening & suicide ideation may occur despite medication in adolescents & young adults (18-24 yo)

May take several weeks to achieve full response

May cause anticholinergic effects

Use caution in patients experiencing xerostomia, visual problems, paralytic ileus, BPH, urinary retention, or decreased motility

Hepatic failure associated with nefazodone use

Sedation may occur; may impair physical or mental abilities

Orthostatic hypotension may occur

Discontinue MAOI 14 d before nefazodone

Discontinue nefazodone 7 d before starting an MAOI

Discontinued in Canada following severe adverse hepatic events

Pregnancy Category: C

Lactation: unknown; use with caution

Pregnancy Categories

A: Generally acceptable. Controlled studies in pregnant women show no evidence of fetal risk.

B: May be acceptable. Either animal studies show no risk but human studies not available or animal studies showed minor risks and human studies done and showed no risk.

C: Use with caution if benefits outweigh risks. Animal studies show risk and human studies not available or neither animal nor human studies done.

D: Use in LIFE-THREATENING emergencies when no safer drug available. Positive evidence of human fetal risk.

X: Do not use in pregnancy. Risks involved outweigh potential benefits. Safer alternatives exist.

NA: Information not available.

Mechanism of Action

Antidepressant structurally unrelated to SSRI, tricyclics, tetracyclics, or MAO inhibitors but inhibits neuronal reuptake of serotonin & norepinephrine; it is also a 5-HT2 and alpha1 receptor antagonist

Pharmacokinetics

Half-life elimination: 2-4 hrs

Peak Plasma Time: 1 hr

Bioavailability: 20% (decreased by food)

Protein Bound: >99%

Vd: 0.22-0.87 L/kg

Metabolism: hepatic P450 enzyme CYP3A4

Metabolites: hydroxynefazodone (HO-NEF), metachlorphenylpiperazine (mCPP)

Excretion: Urine (55%); feces (20-30%)

Dialyzable: No

Enzymes inhibited: CYP3A4