Nefazodone

Mechanism-of-action classes: Adrenergic alpha1-Antagonists; Monoamine Oxidase Inhibitors; Norepinephrine Uptake Inhibitors; Serotonin Uptake Inhibitors.

• Nefazodone hydrochloride tablets are indicated for the treatment of depression. When deciding among the alternative treatments available for this condition, the prescriber should consider the risk of hepatic failure associated with nefazodone hydrochloride treatment (see WARNINGS ).

• Coadministration of terfenadine, astemizole, cisapride, pimozide, or carbamazepine with nefazodone hydrochloride is contraindicated (see WARNINGS and PRECAUTIONS ). Nefazodone hydrochloride tablets are contraindicated in patients who were withdrawn from nefazodone because of evidence of liver injury (see BOXED WARNING ).contraindicated

When deciding among the alternative treatments available for depression, the prescriber should consider the risk of hepatic failure associated with nefazodone hydrochloride treatment (see WARNINGS ). Initial Treatment The recommended starting dose for nefazodone hydrochloride tablets USP is 200 mg/day, administered in two divided doses (BID). In the controlled clinical trials establishing the antidepressant efficacy of nefazodone, the effective dose range was generally 300 to 600 mg/day. Consequently, most patients, depending on tolerability and the need for further clinical effect, should have their dose increased. Dose increases should occur in increments of 100 mg/day to 200 mg/day, again on a BID schedule, at intervals of no less than 1 week. As with all antidepressants, several weeks on treatment may be required to obtain a full antidepressant response. Dosage for Elderly or Debilitated Patients The recommended initial dose for elderly or debilitated patients is 100 mg/day, administered in two divided doses (BID). These patients often have reduced nefazodone clearance and/or increased sensitivity to the side effects of CNS-active drugs. It may also be appropriate to modify the rate of subsequent dose titration. As steady-state plasma levels do not change with age, the final target dose based on a careful assessment of the patient’s clinical response may be similar in healthy younger and older patients.

Clinical Worsening and Suicide Risk Patients with major depressive disorder (MDD), both adult and pediatric, may experience worsening of their depression and/or the emergence of suicidal ideation and behavior (suicidality) or unusual changes in behavior, whether or not they are taking antidepressant medications, and this risk may persist until significant remission occurs. Suicide is a known risk of depression and certain other psychiatric disorders, and these disorders themselves are the strongest predictors of suicide. There has been a long-standing concern, however, that antidepressants may have a role in inducing worsening of depression and the emergence of suicidality in certain patients during the early phases of treatment. Pooled analyses of short-term placebo-controlled trials of antidepressant drugs (SSRIs and others) showed that these drugs increase the risk of suicidal thinking and behavior (suicidality) in children, adolescents, and young adults (ages 18 to 24) with major depressive disorder (MDD) and other psychiatric disorders. Short-term studies did not show an increase in the risk of suicidality with antidepressants compared to placebo in adults beyond age 24; there was a reduction with antidepressants compared to placebo in adults aged 65 and older. The pooled analyses of placebo-controlled trials in children and adolescents with MDD, obsessive compulsive disorder (OCD), or other psychiatric disorders included a total of 24 short-term trials of 9 antidepressant drugs in over 4400 patients.

Associated with Discontinuation of Treatment Approximately 16% of the 3496 patients who received nefazodone in worldwide premarketing clinical trials discontinued treatment due to an adverse experience. The more common (≥ 1%) events in clinical trials associated with discontinuation and considered to be drug related (i.e., those events associated with dropout at a rate approximately twice or greater for nefazodone compared to placebo) included: nausea (3.5%), dizziness (1.9%), insomnia (1.5%), asthenia (1.3%), and agitation (1.2%). Incidence in Controlled Trials Commonly Observed Adverse Events in Controlled Clinical Trials The most commonly observed adverse events associated with the use of nefazodone (incidence of 5% or greater) and not seen at an equivalent incidence among placebo-treated patients (i.e., significantly higher incidence for nefazodone compared to placebo, p ≤ 0.05), derived from the table below, were: somnolence, dry mouth, nausea, dizziness, constipation, asthenia, lightheadedness, blurred vision, confusion, and abnormal vision. Adverse Events Occurring at an Incidence of 1% or More Among Nefazodone-Treated Patients The table that follows enumerates adverse events that occurred at an incidence of 1% or more, and were more frequent than in the placebo group, among nefazodone-treated patients who participated in short-term (6 to 8 week) placebo-controlled trials in which patients were dosed with nefazodone to ranges of 300 to 600 mg/day.

Pregnancy Teratogenic Effects Pregnancy category C Reproduction studies have been performed in pregnant rabbits and rats at daily doses up to 200 and 300 mg/kg, respectively (approximately 6 and 5 times, respectively, the maximum human daily dose on a mg/m 2 basis). No malformations were observed in the offspring as a result of nefazodone treatment. However, increased early pup mortality was seen in rats at a dose approximately five times the maximum human dose, and decreased pup weights were seen at this and lower doses, when dosing began during pregnancy and continued until weaning. The cause of these deaths is not known. The no-effect dose for rat pup mortality was 1.3 times the human dose on a mg/m 2 basis. There are no adequate and well-controlled studies in pregnant women. Nefazodone should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus.

Metabolism

Nefazodone 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 to 4 hours.

Human Experience In premarketing clinical studies, there were seven reports of nefazodone overdose alone or in combination with other pharmacological agents. The amount of nefazodone ingested ranged from 1000 mg to 11,200 mg. Commonly reported symptoms from overdose of nefazodone included nausea, vomiting, and somnolence. One nonstudy participant took 2000 to 3000 mg of nefazodone with methocarbamol and alcohol; this person reportedly experienced a convulsion (type not documented). None of these patients died. In postmarketing experience, overdose with nefazodone alone and in combination with alcohol and/or other substances has been reported. Commonly reported symptoms were similar to those reported from overdose in premarketing experience. While there have been rare reports of fatalities in patients taking overdoses of nefazodone, predominantly in combination with alcohol and/or other substances, no causal relationship to nefazodone has been established. Overdosage Management Treatment should consist of those general measures employed in the management of overdosage with any antidepressant. Ensure an adequate airway, oxygenation, and ventilation.

• Sep 16, 2003ANDAANDA076037Teva

1. 1Depression1815%
2. 2Drug Ineffective1714%
3. 3Product Availability Issue1613%
4. 4Insomnia1512%
5. 5Feeling Abnormal1311%
6. 6Illness1311%
7. 7Withdrawal Syndrome129.9%
8. 8Drug Hypersensitivity119.1%
9. 9Anxiety108.3%
10. 10Nausea108.3%
11. 11Drug Interaction97.4%
12. 12Wrong Technique In Product Usage Process86.6%
13. 13Adverse Event75.8%
14. 14Headache75.8%
15. 15Weight Decreased65.0%

The 6 most recently updated of 6 ClinicalTrials.gov registrations naming Nefazodone as an intervention. Registration is not evidence of efficacy or safety — reference crosswalk only.

• Comparative Effectiveness Research Trial for Antidepressant Incomplete and Non-responders With TRD
  Completed · Phase 4 · Interventional · 278 enrolled · Massachusetts General Hospital
  NCT02977299updated 2022-04-27
• Effectiveness of Nefazodone and Bupropion in Treating Marijuana Dependent Individuals
  Completed · Phase 2 · Interventional · 132 enrolled · National Institute on Drug Abuse (NIDA)
  NCT00249509updated 2017-01-16
• Effect of Nefazodone on Relapse in Females With Cocaine Abuse - 10
  Completed · Phase 3 · Interventional · 0 enrolled · National Institute on Drug Abuse (NIDA)
  NCT00000293updated 2017-01-12
• Effects of Nefazodone on Treatment of Female Cocaine Abusers - 3
  Completed · Phase 2 · Interventional · 0 enrolled · National Institute on Drug Abuse (NIDA)
  NCT00000286updated 2017-01-12
• Nefazodone in the Treatment of Cocaine Dependence and Depression - 4
  Completed · Phase 2 · Interventional · 69 enrolled · Boston Medical Center
  NCT00015210updated 2015-07-30
• Nefazodone in the Treatment of Social Phobia
  Completed · Phase 4 · Interventional · 24 enrolled · Emory University
  NCT00231348updated 2013-11-13

Frequently asked questions

How does Nefazodone work?

Mechanism-of-action classes: Adrenergic alpha1-Antagonists; Monoamine Oxidase Inhibitors; Norepinephrine Uptake Inhibitors; Serotonin Uptake Inhibitors.

What is Nefazodone used for?

According to FDA labeling, Nefazodone carries indications including: Nefazodone hydrochloride tablets are indicated for the treatment of depression. When deciding among the alternative treatments available for this condition, the prescriber should consider the risk of hepatic failure associated with nefazodone hydrochloride treatment (see WARNINGS ).. This is a reference summary of labeled uses, not medical advice or a treatment recommendation.

What class of drug is Nefazodone?

Nefazodone is classified as Other antidepressants, Serotonin Reuptake Inhibitor, Adrenergic alpha1-Antagonists, Monoamine Oxidase Inhibitors, Norepinephrine Uptake Inhibitors, Serotonin Uptake Inhibitors, Increased Central Nervous System Norepinephrine Activity, Increased Central Nervous System Serotonin Activity.

What are the contraindications for Nefazodone?

Nefazodone labeling lists contraindications including: Coadministration of terfenadine, astemizole, cisapride, pimozide, or carbamazepine with nefazodone hydrochloride is contraindicated (see WARNINGS and PRECAUTIONS ). Nefazodone hydrochloride tablets are contraindicated in patients who were withdrawn from nefazodone because of evidence of liver injury (see BOXED WARNING ).. Always consult the full prescribing information and a clinician.