nefazodone hydrochloride
Serzone

Available forms
Available by prescription only
Tablets: 50 mg, 100 mg, 150 mg, 200 mg, 250 mg

Indications and dosages
 Depression. Adults: Initially, 200 mg daily P.O. divided into two doses. Dosage increased in 100- to 200-mg increments daily at intervals of no less than 1 week, p.r.n. Usual dosage range, 300 to 600 mg daily.
≡ Dosage adjustment. For adults age 65 and older, initial dosage is 50 mg P.O. b.i.d. Increase slowly as needed. Usual dosage is 200 to 400 mg daily.

Pharmacodynamics
Antidepressive action: Action of drug isn’t precisely defined. It inhibits neuronal uptake of serotonin and norepinephrine. It also occupies central 5-hydroxytryptamine₂ (serotonin) and alpha₁-adrenergic receptors where it acts as an antagonist.

Pharmacokinetics
Absorption: Rapidly and completely absorbed but, because of extensive metabolism, its absolute bioavailability is only about 20%. Food delays absorption and reduces bioavailability.
Distribution: More than 99% is bound to plasma proteins.
Metabolism: Extensively metabolized by n-dealkylation and aliphatic and aromatic hydroxylation.
Excretion: Excreted in urine. Half-life of drug is 2 to 4 hours.

Contraindications and precautions
Contraindicated in patients hypersensitive to drug or other phenylpiperazine antidepressants. Don’t use within 14 days of MAO inhibitor therapy or with pimozide. Also contraindicated in patients who were withdrawn from nefazodone because of liver injury.
  Use cautiously in patients with CV or cerebrovascular disease that could be worsened by hypotension (such as history of MI, angina, or CVA) or conditions that would predispose patient to hypotension (such as dehydration, hypovolemia, or antihypertensive treatment). Use cautiously in patients with a history of seizures or mania.

Interactions
Drug-drug. Alprazolam, triazolam: Potentiates effects of these drugs. Avoid use together. If needed, dosages of alprazolam and triazolam may need to be reduced greatly.
CNS active drugs: May alter CNS activity. Use together cautiously.
Digoxin: Increases digoxin levels. Use together cautiously, and monitor digoxin levels.
Highly plasma protein-bound drugs: May increase risk and severity of adverse reactions. Monitor patient closely.
MAO inhibitors: May cause severe excitation, hyperpyrexia, seizures, delirium, or coma. Avoid use together.
Pimozide: May cause decreased pimozide metabolism, leading to increased levels and cardiotoxicity. Avoid use together.
Drug-herb. St. John’s wort: Increases sedative and hypnotic effects. Discourage use together.

Adverse reactions
CNS: headache, somnolence, dizziness, asthenia, insomnia, light-headedness, confusion, memory impairment, paresthesia, abnormal dreams, decreased concentration, ataxia, incoordination, psychomotor retardation, tremor, hypertonia, fever.
CV: orthostatic hypotension, vasodilation, hypotension, peripheral edema.
EENT: blurred vision, abnormal vision, pharyngitis, tinnitus, visual field defect.
GI: dry mouth, nausea, constipation, dyspepsia, diarrhea, increased appetite, vomiting, thirst, taste perversion.
GU: urinary frequency, urinary tract infection, urine retention, vaginitis.
Metabolic: hyponatremia.
Musculoskeletal: neck rigidity, arthralgia.
Respiratory: cough.
Skin: pruritus, rash.
Other: infection, flu syndrome, chills, breast pain.

Effects on lab test results
• May decrease sodium levels.

Overdose and treatment
Overdose may cause nausea, vomiting, and somnolence. Other drug-related adverse reactions may occur.
 Provide symptomatic and supportive treatment for hypotension or excessive sedation. Use gastric lavage if needed.

Special considerations
• Allow at least 1 week after stopping drug before giving patient an MAO inhibitor. Also, allow at least 14 days after stopping an MAO inhibitor before starting nefazodone.
• Drug therapy may precipitate mania or hypomania in patients with bipolar or other affective disorders.
• Monitor patient for suicidal tendencies. Give a minimum supply of drug.
• Don’t initiate therapy in patients with active liver disease or with elevated baseline serum transaminases. There is no evidence that preexisting liver disease increases the likelihood of developing liver failure; however, baseline abnormalities can complicate patient monitoring.
• Discontinue drug if signs and symptoms of liver dysfunction occur, such as serum AST or ALT levels that are three or more times the upper limit of normal. Don’t restart therapy.
 ALERT Don’t confuse Serzone (nefazodone) with Seroquel (quetiapine).
Breast-feeding patients
• It isn’t known if nefazodone appears in breast milk. Use cautiously in breast-feeding women.
Pediatric patients
• Safety and efficacy in children younger than age 18 haven’t been established.
Geriatric patients
• Because of increased systemic exposure to nefazodone, begin treatment at half the usual dose, but increase dose over the same dosage range as in younger patients.
• Observe usual precautions in elderly patients who have ongoing medical illnesses or are receiving other drugs.

Patient education
• Warn patient not to engage in potentially hazardous activities until CNS effects are known.
• Instruct men to stop drug immediately and seek medical attention if they have prolonged or inappropriate erections.
• Instruct women to report planned, suspected, or known pregnancy during therapy.
• Instruct patient not to drink alcoholic beverages during therapy.
• Tell patient to report rash, hives, or other related allergic reactions.
• Teach patient the signs and symptoms of liver dysfunction, including jaundice, anorexia, GI complaints, and malaise. Tell patient to report these adverse events immediately.
• Inform patient that several weeks of therapy may be needed to obtain the full antidepressant effect. Once improvement occurs, advise patient not to discontinue drug until directed.

Reactions may be common, uncommon, life-threatening, or COMMON AND LIFE THREATENING.
◆ Canada only
◇ Unlabeled clinical use