nefazodone (Serzone, Nefazodone 5HT2, Serzone 5HT2)

Dosing and uses of Serzone, Nefazodone 5HT2 (nefazodone)

• Adult
• Pediatric

 

Adult dosage forms and strengths

tablet

• 50mg
• 100mg
• 150mg
• 200mg
• 250mg

 

Depression

Initial: 100 mg PO q12hr

Increase by 50-100 mg/dose at 1 week intervals

 

Geriatric

Initial: 50 mg PO q12hr (reduced clearance, increased side effects)

Increase by 50-100 mg/dose at 1 week intervals

Maintenance: 200-400 mg/day divided q12hr

 

Pediatric dosage forms and strengths

Safety & efficacy not established

 

Serzone, Nefazodone 5HT2 (nefazodone) adverse (side) effects

>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)

 

Warnings

Black box warnings

In short-term studies, antidepressants increased the risk of suicidal thinking and behavior in children, adolescents, and young adults (<24 yr of age) taking antidepressants for major depressive disorders and other psychiatric illnesses

This increase was not seen in patients aged >24 years; a slight decrease in suicidal thinking was seen in adults >65 years

In children and young adults, risks must be weighed against the benefits of taking antidepressants

Patients should be monitored closely for changes in behavior, clinical worsening, and suicidal tendencies; this should be done during initial 1-2 months of therapy and dosage adjustments

The patient’s family should communicate any abrupt changes in behavior to the healthcare provider

Worsening behavior and suicidal tendencies that are not part of the presenting symptoms may require discontinuation of therapy

This drug is not approved for use in pediatric patients

 

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 and lactation

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.

 

Pharmacology of Serzone, Nefazodone 5HT2 (nefazodone)

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