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Pharmacologic class: Phenylpiperazine
Therapeutic class: Antidepressant
Pregnancy risk category C
FDA Box 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.
Potentiates effects of norepinephrine and serotonin by blocking synaptic reuptake in nerve cells and disrupting alpha1-adrenergic receptors
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.
• Elderly patients
• 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
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).
• 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.
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
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
• 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).
• 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.