Drug information of Nefazodone

Nefazodone

Drug group:

Nefazodone, an antidepressant synthetically derived phenylpiperazine, is used to treat major depression.

Mechanism of effect

Within the serotonergic system, nefazodone acts as an antagonist at type 2 serotonin (5-HT2) post-synaptic receptors and, like fluoxetine-type antidepressants, inhibits pre-synaptic serotonin (5-HT) reuptake. These mechanisms increase the amount of serotonin available to interact with 5-HT receptors. Within the noradrenergic system, nefazodone inhibits norepinephrine uptake minimally. Nefazodone also antagonizes alpha(1)-adrenergic receptors, producing sedation, muscle relaxation, and a variety of cardiovascular effects. Nefazodone's affinity for benzodiazepine, cholinergic, dopaminergic, histaminic, and beta or alpha(2)-adrenergic receptors is not significant.

Pharmacodynamic

Although it is structurally similar to trazodone, nefazodone has a mechanism of action different from other antidepressants and, hence, lacks the risk for major cardiovascular toxicity seen with tricyclics and insomnia and inhibition of REM sleep seen with the selective serotonin reuptake inhibitors.

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

Drug indications

depression

Dosage

Adult

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

Safety & efficacy not established

Drug contraindications

Breast feeding

Interactions

Ergotamine-C , Irinotecan , Buspirone , Daunorubicin , Deflazacort , Sibutramine , Cisapride , Methylergonovin , Midazolam , Carbamazepine , eplerenone , fentanyl , Cyclobenzaprine , Ranolazine , Buprenorphine , Tapentadol , Remifentanil , rasagiline , propoxyphene , Procarbazine , Pimozide , Tranylcypromine , Dihydroergotamine , Simvastatin , Lovastatin , Regorafenib , Terfenadine , Alfuzosin , Flibanserin , Eliglustat , lurasidone , astemizole , Phenelzine , isocarboxazid , safinamide , Lomitapide , dronedarone , Axitinib , Almotriptan , eletriptan , Ivabradine , Prednisolone , Dolasetron , Palonosetron , Sufentanil , Alfentanil , Quinine , Mefloquine , Ivacaftor , brigatinib , Abiraterone , Lorcaserin , nasal Mometasone , Dutasteride , Copanlisib , Etravirine , Dabrafenib , Estropipate , Acalabrutinib , Cabazitaxel , Desvenlafaxine , Maraviroc , Halofantrine , Darifenacin , Nintedanib , Dexfenfluramine , Nicardipine , Nisoldipine , Fesoterodine , Pazopanib , Palbociclib , Isradipine , Ixazomib , Pimavanserin , Tasimelteon , trabectedine , Duvelisib , Sonidegib , Avanafil , Estazolam , Edoxaban , Entrectinib , Levomilnacipran , ELBASVIR/GRAZOPREVIR , Larotrectinib , gilteritinib , glasdegib , Abemaciclib , Nitrendipine , 5-hydroxytryptophan , Suvorexant , Ruxolitinib , riociguat , tolvaptan , bazedoxifene/conjugated estrogens , Gefitinib , Dasatinib , Remdesivir , Cannabidiol , lasmiditan , vemurafenib , Vernakalant , voxelotor , Avapritinib , Remoxipride , Capmatinib , Nesiritide

Alerts

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

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

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

Points of recommendation

  • Avoid driving and doing other tasks or actions that call for you to be alert until you see how nefazodone affects you.
  • To lower the chance of feeling dizzy or passing out, rise slowly if you have been sitting or lying down. Be careful going up and down stairs.
  • It may take several weeks to see the full effects.
  • Avoid drinking alcohol while taking nefazodone.
  • Talk with your doctor before you use other drugs and natural products that slow your actions.
  • Some people may have a higher chance of eye problems with nefazodone. Your doctor may want you to have an eye exam to see if you have a higher chance of these eye problems. Call your doctor right away if you have eye pain, change in eyesight, or swelling or redness in or around the eye.
  • This medicine may affect how much of some other drugs are in your body. If you are taking other drugs, talk with your doctor. You may need to have your blood work checked more closely while taking nefazodone with your other drugs.
  • Tell your doctor if you are pregnant or plan on getting pregnant. You will need to talk about the benefits and risks of using nefazodone while you are pregnant.
  • Tell your doctor if you are breast-feeding. You will need to talk about any risks to your baby.
  • May take several weeks to achieve full response
  • Take with or without food.
  • To gain the most benefit, do not miss doses.
  • Keep taking nefazodone as you have been told by your doctor or other health care provider, even if you feel well.
  • Skip the missed dose and go back to your normal time.
  • Do not take 2 doses at the same time or extra doses.

Pregnancy level

C

Related drugs

Trazodone


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