Nefazodone

Oral
Depression

Debilitated patients: Initially, 50 mg bid, may increase gradually according to patient's response and tolerability.

May be taken with or without food.

Liver injury due to previous therapy with nefazodone; active liver disease or elevated baseline serum transaminases. Concomitant administration with carbamazepine, astemizole, cisapride, pimozide, terfenadine, triazolam. Concurrent use with or within 14 days of discontinuing MAOIs.

Patient with high risk of suicidality; history of mania or hypomania; decreased gastrointestinal motility, paralytic ileus, urinary retention, benign prostatic hyperplasia, xerostomia, visual problems; known CV or cerebrovascular disease that may be exacerbated by hypotension (e.g. previous MI, unstable heart disease, ischaemic stroke, angina), conditions predisposing to hypotension (e.g. dehydration, hypovolaemia, treatment with antihypertensive agents), at risk of seizure (e.g. history of seizure, head trauma, brain damage, alcoholism, concomitant use of drugs that may lower seizure threshold); anatomically narrow angles who have not had an iridectomy. Not indicated for treatment of bipolar depression. Avoid abrupt withdrawal. Discontinuation of use prior to elective surgery is recommended for as long as clinically feasible. Elderly and debilitated patients. Pregnancy and lactation.

Significant: Increased risk of suicidal thinking and behaviour; anticholinergic effects (e.g. xerostomia, constipation, urinary retention); bone fractures, mild pupillary dilation and other visual disturbances (e.g. blurred vision, scotoma, visual trails), orthostatic hypotension. Rarely, priapism, convulsions.
Cardiac disorders: Sinus bradycardia.
Gastrointestinal disorders: Nausea, dyspepsia, diarrhoea, vomiting.
General disorders and administration site conditions: Weakness, peripheral oedema.
Infections and infestations: Infection.
Metabolism and nutrition disorders: Increased appetite.
Nervous system disorders: Drowsiness, dizziness, headache, agitation, memory impairment, paraesthesia, ataxia.
Psychiatric disorders: Insomnia, confusion, abnormal dreams.
Respiratory, thoracic and mediastinal disorders: Pharyngitis, increased cough.
Skin and subcutaneous tissue disorders: Rash, pruritus.
Vascular disorders: Hypotension.
Potentially Fatal: Liver failure.

PO: C

This drug may cause CNS depression which may impair physical or mental abilities; if affected, do not drive or operate machinery.

Screen patients for bipolar disorder before starting treatment (including detailed psychiatric history). Obtain LFTs at baseline and periodically. Closely monitor for signs of clinical worsening, suicidal ideation, and unusual behavioural changes, especially at the start of therapy or when doses are increased or decreased.

Symptoms: Nausea, vomiting, somnolence, dizziness, and hypotension. Management: Supportive and symptomatic treatment. May perform gastric lavage with a large bore orogastric tube with appropriate airway protection, if necessary, soon after ingestion or in symptomatic patients. Administer activated charcoal. Ensure adequate airway, ventilation, and oxygenation; monitor vital signs and cardiac rhythm.

Increased serum concentrations of CYP3A4 substrates (e.g. alprazolam, buspirone, digoxin, simvastatin, atorvastatin, lovastatin, ciclosporin, tacrolimus).
Potentially Fatal: May result in serious reactions (e.g. serotonin syndrome) when given concomitantly with or within 14 days of discontinuing MAOI. May increase the serum concentrations of astemizole, cisapride, pimozide, or terfenadine, which may result in QT prolongation and, rarely, serious CV adverse events. Carbamazepine reduces nefazodone plasma concentrations, which may likely result in subtherapeutic levels. Significantly increases the serum concentration of triazolam.

Delayed absorption and decreased bioavailability with food.

Description: Nefazodone, a phenylpiperazine antidepressant, blocks the neuronal reuptake of serotonin and norepinephrine. It also blocks 5-HT₂ and α₁-receptors but has no significant affinity for α₂- and β-adrenergic, 5-HT_1A, benzodiazepine, dopaminergic, or cholinergic receptors.
Pharmacokinetics:
Absorption: Rapidly and well absorbed from the gastrointestinal tract. Bioavailability: Approx 20% (variable). Delayed and reduced absorption with food. Time to peak plasma concentration: Approx 1 hour.
Distribution: Widely distributed in body tissues (including the CNS). Enters breast milk (small amounts). Volume of distribution: 0.22-0.87 L/kg. Plasma protein binding: >99%.
Metabolism: Extensively metabolised in the liver via N-dealkylation and aliphatic and aromatic hydroxylation into at least 3 metabolites, namely, triazoledione, hydroxynefazodone (active), and m-chlorophenylpiperazine (active).
Excretion: Via urine (approx 55% as metabolites); faeces (approx 20-30%). Elimination half-life: 2-4 hours (nefazodone); 1.4-8 hours (active metabolites).

Source: National Center for Biotechnology Information. PubChem Compound Summary for CID 4449, Nefazodone. https://pubchem.ncbi.nlm.nih.gov/compound/Nefazodone. Accessed Feb. 23, 2022.

Store between 20-25°C.

Antidepressants

N06AX06 - nefazodone ; Belongs to the class of other antidepressants.

Anon. Nefazodone Hydrochloride. AHFS Clinical Drug Information [online]. Bethesda, MD. American Society of Health-System Pharmacists, Inc. https://www.ahfscdi.com. Accessed 11/01/2022.

Anon. Nefazodone. Lexicomp Online. Hudson, Ohio. Wolters Kluwer Clinical Drug Information, Inc. https://online.lexi.com. Accessed 11/01/2022.

Buckingham R (ed). Nefazodone. Martindale: The Complete Drug Reference [online]. London. Pharmaceutical Press. https://www.medicinescomplete.com. Accessed 11/01/2022.

Nefazodone Hydrochloride Tablet (Teva Pharmaceuticals USA, Inc.). DailyMed. Source: U.S. National Library of Medicine. https://dailymed.nlm.nih.gov/dailymed. Accessed 11/01/2022.