nefazodone hydrochloride

nefazodone hydrochloride

[nĕfa′zodōn]

an antidepressant drug.

indication It is prescribed in the treatment of mental depression in adults.

contraindications It should not be given to patients with an allergy to nefazodone hydrochloride or similar antidepressants, patients in the recovery phase of acute myocardial infarction, or patients also using monoamine oxidase inhibitors, pimozide, or carbamazepine. Caution is advised in prescribing it for patients with concurrent use of triazolam or alprazolam, a history of drug abuse, cardiovascular disease, low blood pressure, seizures, benign prostatic hyperplasia, constipation, or suicidal ideation.

adverse effects It has rarely caused life-threatening liver failure, so it should be discontinued immediately if there are signs of hepatic toxicity. The side effects most often reported include dry mouth, impaired vision, eye pain, flulike symptoms, ringing in the ears, swollen limbs, and muscle pain.

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nefazodone hydrochloride

Pharmacologic class: Phenylpiperazine

Therapeutic class: Antidepressant

Pregnancy risk category C

FDA Boxed Warning

• Drug may increase risk of suicidal thinking and behavior in children and adolescents with major depressive disorder and other psychiatric disorders. Risk must be balanced with clinical need, as depression itself increases suicide risk. With patient of any age, observe closely for clinical worsening, suicidality, and unusual behavior changes when therapy begins. Advise family and caregivers to observe patient closely and communicate with prescriber as needed.
• Drug isn't approved for use in pediatric patients.

Action

Potentiates effects of norepinephrine and serotonin by blocking synaptic reuptake in nerve cells and disrupting alpha₁-adrenergic receptors

Availability

Tablets: 50 mg, 100 mg, 150 mg, 200 mg, 250 mg

⊘Indications and dosages

➣ Major depression

Adults: Initially, 100 mg P.O. b.i.d. May increase weekly up to 600 mg/day in two divided doses.

Dosage adjustment

• Elderly patients

Contraindications

• Hypersensitivity to drug, its components, or other phenylpiperazines
• Active hepatic disease, baseline transaminase elevation, or previous drug withdrawal necessitated by hepatic damage
• MAO inhibitor use within past 14 days
• Concurrent cisapride (not available in U.S.), pimozide, carbamazepine, or triazolam therapy

Precautions

Use cautiously in:
• cardiovascular or cerebrovascular disease
• history of suicide attempt, drug abuse, or mania
• elderly patients
• pregnant or breastfeeding patients
• children younger than age 18 (safety not established).

Administration

• Give with food or milk if GI upset occurs.
• Know that tablets may be crushed.
☞ Don't give concurrently with cisapride, pimozide, carbamazepine, or triazolam.
☞ Don't give within 14 days of MAO inhibitors.

Route	Onset	Peak	Duration
P.O.	Days-wks	Few wks	Unknown

Adverse reactions

CNS: dizziness, asthenia, agitation, light-headedness, insomnia, drowsiness, confusion, weakness, headache, impaired memory, poor concentration, paresthesia, psychomotor retardation, tremor, suicidal behavior or ideation (especially in child or adolescent)

CV: hypotension, orthostatic hypotension, peripheral edema

EENT: abnormal or blurred vision, eye pain, tinnitus, pharyngitis

GI: nausea, vomiting, diarrhea, constipation, dyspepsia, dry mouth

GU: urinary frequency or retention, urinary tract infection

Hepatic: hepatotoxicity, hepatic failure

Respiratory: increased cough

Skin: rash, pruritus

Other: increased appetite, thirst, infection, chills, fever, flulike symptoms

Interactions

Drug-drug. Alprazolam, triazolam: increased blood level and effects of these drugs

Antihypertensives, nitrates: additive hypotension

Carbamazepine, cisapride, pimozide: increased nefazodone blood level, leading to toxicity

CNS depressants (including antihistamines, opioids, sedative-hypnotics): additive CNS depression

Digoxin: increased digoxin blood level

HMG-CoA reductase inhibitors: increased risk of myopathy

MAO inhibitors: potentially fatal reactions (hyperpyrexia, excitation, seizures, delirium, coma)

Drug-diagnostic tests. CBC, cholesterol, glucose, hematocrit: decreased levels

Hepatic enzymes: increased levels

Drug-herbs. Chamomile, hops, kava, skullcap, valerian: increased CNS depression

S-adenosylmethionine (SAM-e), St. John's wort: increased risk of adverse serotonergic effects, including serotonin syndrome

Drug-behaviors. Acute alcohol ingestion: additive hypotension

Alcohol use: increased CNS depression

Patient monitoring

• Monitor vital signs with patient lying down, sitting, and standing. Notify prescriber if blood pressure drops 20 mm Hg.
• Assess CBC.
☞ Monitor liver function tests frequently. Notify prescriber of abnormal results.
• Closely monitor neurologic status.
• Evaluate patient for withdrawal symptoms (which may occur if therapy stops abruptly).
☞ Monitor closely for increasing depression and suicidal ideation (especially in child or adolescent).

Patient teaching

• Advise patient to take with food or milk to minimize GI upset.
• Tell patient to crush drug if he can't swallow it whole.
• Inform patient that therapeutic response may take up to 4 weeks. Encourage him to keep taking drug as prescribed.
☞ Tell patient drug may cause adverse CNS effects. Advise him to report significant mood changes (especially depression or suicidal thoughts). Caution parent to report these problems in child or adolescent.
☞ Instruct patient to immediately report unusual tiredness, yellowing of skin or eyes, nausea, or anorexia.
• Instruct patient to rise slowly and carefully, to avoid dizziness from temporary blood pressure drop.
• Tell patient to avoid alcohol and to consult prescriber before taking herbs.
☞ Instruct patient not to stop taking drug abruptly. Dosage must be tapered.
• As appropriate, review all other significant and life-threatening adverse reactions and interactions, especially those related to the drugs, tests, herbs, and behaviors mentioned above.