No

Antidepressant, Serotonin Reuptake Inhibitor/Antagonist

Treatment of depression

C

Hypersensitivity to nefazodone or related compounds (phenylpiperazines); concurrent use or use of monoamine oxidase inhibitors within previous 14 days; use in a patient during the acute recovery phase of MI; concurrent use with terfenadine, astemizole, or cisapride; concurrent therapy with triazolam is generally contraindicated (dosage must be reduced by 75%, which often may not be possible with available dosage forms).

Nefazodone should not be initiated within 1 week of discontinuing a MAOI. May cause sedation, resulting in impaired performance of tasks requiring alertness (ie, operating machinery or driving). Sedative effects may be additive with other CNS depressants. Does not potentiate ethanol but use is not advised. In particular, triazolobenzodiazepines (alprazolam and triazolam) should be avoided, since the metabolism of these drugs may be impaired. The degree of sedation is low relative to other antidepressants. May worsen psychosis in some patients or precipitate a shift to mania or hypomania in patients with bipolar disease. May increase the risks associated with electroconvulsive therapy. This agent should be discontinued, when possible, prior to elective surgery. Therapy should not be abruptly discontinued in patients receiving high doses for prolonged periods. Rare reports of priapism have occurred. The incidence of sexual dysfunction with nefazodone is generally lower than with SSRIs.

Use caution in patients with depression, particularly if suicidal risk may be present. Use caution in patients with a previous seizure disorder or condition predisposing to seizures such as brain damage, alcoholism, or concurrent therapy with other drugs which lower the seizure threshold. Use with caution in patients with hepatic or renal dysfunction and in elderly patients. Use with caution in patients with a history of cardiovascular disease (including previous MI, stroke, tachycardia, or conduction abnormalities). However, the risk of conduction abnormalities with this agent is very low relative to other antidepressants.

>10%:

Central nervous system: Headache, drowsiness, insomnia, agitation, dizziness

Gastrointestinal: Xerostomia, nausea, constipation

Neuromuscular & skeletal: Weakness

1% to 10%:

Cardiovascular: Postural hypotension

Central nervous system: Lightheadedness, confusion, memory impairment, abnormal dreams, decreased concentration, ataxia

Dermatologic: Pruritus, rash

Gastrointestinal: Vomiting, dyspepsia, diarrhea, increased appetite, thirst, taste perversion

Neuromuscular & skeletal: Arthralgia, paresthesia, tremor

Ocular: Blurred vision, abnormal vision, visual field defect

Respiratory: Cough

Otic: Tinnitus

Miscellaneous: Flu syndrome

Symptoms of overdose include drowsiness, vomiting, hypotension, tachycardia, incontinence, coma

Following initiation of essential overdose management, toxic symptoms should be treated. Ventricular arrhythmias often respond to lidocaine 1.5 mg/kg bolus followed by 2 mg/minute infusion with concurrent systemic alkalinization (sodium bicarbonate 0.5-2 mEq/kg I.V.). Seizures usually respond to diazepam I.V. boluses (5-10 mg for adults up to 30 mg or 0.25-0.4 mg/kg/dose for children up to 10 mg/dose). If seizures are unresponsive or recur, phenytoin or phenobarbital may be required. Hypotension is best treated by I.V. fluids and by placing the patient in the Trendelenburg position.

CYP3A3/4 enzyme substrate; CYP3A3/4 enzyme inhibitor

Nefazodone likely increases cisapride serum concentrations via CYP3A4 inhibition; this combination may lead to cardiac arrhythmias and should be avoided

Combined use of nefazodone with an SSRI may produce serotonin syndrome

Nefazodone inhibits the metabolism of triazolam (decrease dose by 75%) and alprazolam (decrease dose by 50%)

Pimozide's serum concentration may be increased. Concurrent use is contraindicated.

Inhibits neuronal reuptake of serotonin and norepinephrine; also blocks 5HT₂ and alpha₁ receptors; has no significant affinity for alpha₂, beta-adrenergic, 5-HT1A, cholinergic, dopaminergic, or benzodiazepine receptors

Onset of effect: Therapeutic effects take at least 2 weeks to appear

Metabolism: In the liver to 3 active metabolites; triazoledione, hydroxynefazodone and m-chlorophenylpiperazine (mCPP)

Half-life: 2-4 hours (parent compound), active metabolites persist longer

Time to peak serum concentration: 30 minutes, prolonged in presence of food

Elimination: Primarily as metabolites in urine and secondarily in feces

Oral: Adults: 200 mg/day, administered in two divided doses initially, with a range of 300-600 mg/day in two divided doses thereafter

Alcohol: Additive CNS effect, avoid use

Therapeutic plasma levels have not yet been defined

No information available to require special precautions

>10% of patients experience significant dry mouth which will disappear with cessation of drug therapy

Take exactly as directed (do not increase dose or frequency); may take 2-3 weeks to achieve desired results; may cause physical and/or psychological dependence. Avoid excessive alcohol, caffeine, and other prescription or OTC medications not approved by prescriber. Maintain adequate hydration (2-3 L/day of fluids unless instructed to restrict fluid intake). You may experience drowsiness, dizziness, or lightheadedness (use caution when driving or engaging in tasks requiring alertness until response to drug is known); nausea or vomiting (small frequent meals, frequent mouth care, chewing gum, or sucking lozenges may help); or orthostatic hypotension (use caution when climbing stairs or changing position from lying or sitting to standing). Report persistent insomnia or excessive daytime sedation; muscle cramping, tremors, weakness, or change in gait; chest pain, palpitations, or rapid heartbeat; vision changes or eye pain; difficulty breathing or breathlessness; abdominal pain or blood in stool; or worsening of condition. Pregnancy/breast-feeding precautions: Inform prescriber if you are or intend to be pregnant. Breast-feeding is not recommended.

Dosing after meals may decrease lightheadedness and postural hypotension, but may also decrease absorption and therefore effectiveness; use side rails on bed if administered to the elderly; observe patient's activity and compare with admission level; assist with ambulation; sitting and standing blood pressure and pulse

Tablet, as hydrochloride: 50 mg, 100 mg, 150 mg, 200 mg, 250 mg

Fontaine R, Ontiveros A, Elie R, et al, "A Double-Blind Comparison of Nefazodone, Imipramine, and Placebo in Major Depression," J Clin Psychiatry, 1994, 55(6):234-41.

Rickels K, Schweizer E, Clary C, et al, "Nefazodone and Imipramine in Major Depression: A Placebo-Controlled Trial," Br J Psychiatry, 1994, 164(6):802-5.

Shea JP, Shulka UA, Rittman KA, "Single Dose Pharmacokinetics of Nefazodone in Elderly Subjects, Renally Impaired Patients, and Patients With Hepatic Cirrhosis in Comparison to Healthy Volunteers," Clin Pharmacol Ther, 1988, 43:146.