Drug information of Nefazodone
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.
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.
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%)
Enzymes inhibited: CYP3A4
Initial: 100 mg PO q12hr
Increase by 50-100 mg/dose at 1 week intervals
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
Safety & efficacy not established
Drug contraindicationsBreast feeding
Side effectsInfection , Insomnia , Headache , nausea , dry mouth , dizziness , Blurred vision , Bradycardia , vertigo , asthenia , decreased libido , increased appetite , difficulty urinating , Restlessness , lightheadedness , Ataxia , Digestive complaints
InteractionsErgotamine-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
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.