nefazodone (Rx)

Brand and Other Names:Serzone, Nefazodone 5HT2, more...Serzone 5HT2
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Dosing & Uses


Dosage Forms & Strengths


  • 50mg
  • 100mg
  • 150mg
  • 200mg
  • 250mg


Initial: 100 mg PO q12hr

Increase by 50-100 mg/dose at 1 week intervals


Initial: 50 mg PO q12hr (reduced clearance, increased side effects)

Increase by 50-100 mg/dose at 1 week intervals

Maintenance: 200-400 mg/day divided q12hr

Safety & efficacy not established



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            Adverse Effects


            Headache (31-35%)

            Somnolence (21-25%)

            Nausea (21-25%)

            Xerostomia (21-25%)

            Dizziness (15-20%)

            Asthenia (11-15%)

            Constipation (11-15%)

            Insomnia (11-15%)


            Infection (6-10%)

            Dyspepsia (6-10%)

            Lightheadedness (6-10%)

            Confusion (6-10%)

            Blurred vision (6-10%)

            Abnormal vision (6-10%)

            Increased appetite (1-5%)

            Memory loss (1-5%)

            Paresthesia (1-5%)

            Vasodilation (1-5%)

            Decreased concentration (1-5%)

            Ataxia (1-5%)

            Decreased libido (1-5%)

            Breast pain (1-5%)

            Decreased hematocrit (1-5%)

            Agitation with discontinuation (1-5%)

            Orthostatic hypotension (2.6%)

            Bradycardia (1.5%)

            Frequency Not Defined




            Suicidal thoughts


            Worsening depression

            Liver failure (rare, 1 in 250,000-300,000)



            Black Box Warnings

            In short-term studies, antidepressants increased the risk of suicidal thinking and behavior in children, adolescents, and young adults (<24 yr of age) taking antidepressants for major depressive disorders and other psychiatric illnesses

            This increase was not seen in patients aged >24 years; a slight decrease in suicidal thinking was seen in adults >65 years

            In children and young adults, risks must be weighed against the benefits of taking antidepressants

            Patients should be monitored closely for changes in behavior, clinical worsening, and suicidal tendencies; this should be done during initial 1-2 months of therapy and dosage adjustments

            The patient’s family should communicate any abrupt changes in behavior to the healthcare provider

            Worsening behavior and suicidal tendencies that are not part of the presenting symptoms may require discontinuation of therapy

            This drug is not approved for use in pediatric patients


            Co-administration with terfenadine (discontinued), astemizole (discontinued), cisapride, pimozide, carbamazepine

            Concurrent administration with triazolam (75% dose reduction may be needed but not all commercially available dosage forms of triazolam may permit sufficient dosage reduction)

            Hypersensitivity to nefazadone or other phenylpiperazine antidepressants

            Co-administration with MAO inhibitors or within 14 days of administration

            Liver injury resulting from previous nefazodone treatment


            Clinical worsening & suicide ideation may occur despite medication in adolescents & young adults (18-24 yo)

            May take several weeks to achieve full response

            May cause anticholinergic effects

            Use caution in patients experiencing xerostomia, visual problems, paralytic ileus, BPH, urinary retention, or decreased motility

            The pupillary dilation that occurs following use of many antidepressant drugs may trigger an angle-closure attack in a patient with anatomically narrow angles who does not have a patent iridectomy

            Postural hypotension reported; the prescriber should be aware that there is some risk of postural hypotension in association with this therapy; it should be used with caution in patients with known cardiovascular or cerebrovascular disease that could be exacerbated by hypotension (history of myocardial infarction, angina, or ischemic stroke) and conditions that would predispose patients to hypotension (dehydration, hypovolemia, and treatment with antihypertensive medication)

            Rare occurrences of convulsions (including grand mal seizures) following administration of this drug reported since market introduction; a causal relationship has not been established

            While priapism did not occur during premarketing experience, rare reports of priapism have been received since market introduction; a causal relationship to this drug has not been established; if patients present with prolonged or inappropriate erections, they should discontinue therapy immediately and consult their physicians; if the condition persists for more than 24 hours, a urologist should be consulted to determine appropriate management

            Sinus bradycardia, defined as heart rate ≤ 50 bpm and a decrease of at least 15 bpm from baseline, reported with therapy; because patients with a recent history of myocardial infarction or unstable heart disease were excluded from clinical trials, such patients should be treated with caution

            Clinical worsening of suicide risk

            • Patients with major depressive disorder (MDD), both adult and pediatric, may experience worsening of their depression and/or the emergence of suicidal ideation and behavior (suicidality) or unusual changes in behavior, whether or not they are taking antidepressant medications, and this risk may persist until significant remission occurs
            • There has been a long-standing concern that antidepressants may have a role in inducing worsening of depression and the emergence of suicidality in certain patients. A causal role for antidepressants in inducing suicidality has been established in pediatric patients
            • All patients being treated with antidepressants for any indication should be monitored appropriately and observed closely for clinical worsening, suicidality, and unusual changes in behavior, especially during the initial 1-2 months of a course of drug therapy, or at times of dosage adjustments, either increases or decreases
            • The following symptoms, anxiety, agitation, panic attacks, insomnia, irritability, hostility, aggressiveness, impulsivity, akathisia (psychomotor restlessness), hypomania, and mania, have been reported in adult and pediatric patients being treated with antidepressants for major depressive disorder as well as for other indications, both psychiatric and nonpsychiatric
            • Although a causal link between emergence of such symptoms and either the worsening of depression and/or the emergence of suicidal impulses has not been established, there is concern that such symptoms may represent precursors to emerging suicidality
            • Consideration should be given to changing therapeutic regimen, including possibly discontinuing medication, in patients whose depression is persistently worse, or who are experiencing emergent suicidality or symptoms that might be precursors to worsening depression or suicidality, especially if these symptoms are severe, abrupt in onset, or were not part of the patient’s presenting symptoms
            • Families and caregivers of patients being treated with antidepressants for major depressive disorder or other indications, both psychiatric and nonpsychiatric, should be alerted about the need to monitor patients for emergence of agitation, irritability, unusual changes in behavior, and other symptoms described above, as well as emergence of suicidality, and to report such symptoms immediately to health care providers; such monitoring should include daily observation by families and caregivers.
            • Prescription should be written for smallest quantity of tablets consistent with good patient management, in order to reduce drug overdose

            Screening for bipolar disorder

            • Activation of mania/hypomania is a known risk in a small proportion of patients with major affective disorder treated with other marketed antidepressants; as with all antidepressants, this drug should be used cautiously in patients with a history of mania
            • A major depressive episode may be initial presentation of bipolar disorder; it is generally believed (though not established in controlled trials) that treating such an episode with an antidepressant alone may increase likelihood of precipitation of a mixed/manic episode in patients at risk for bipolar disorder
            • Prior to initiating treatment with an antidepressant, patients with depressive symptoms should be adequately screened to determine if they are at risk for bipolar disorder; such screening should include a detailed psychiatric history, including a family history of suicide, bipolar disorder, and depression; this drug is not approved for treating bipolar depression.


            • The reported rate in the United States is about 1 case of liver failure resulting in death or transplant per 250,000 to 300,000 patient-years of nefazodone treatment; this represents a rate of about 3-4 times estimated background rate of liver failure; there is no evidence that preexisting liver disease increases likelihood of developing liver failure; however, may complicate patient monitoring due to baseline abnormalities
            • The time to liver injury for the reported liver failure cases resulting in death or transplant generally ranged from 2 weeks to 6 months of therapy; although some reports described dark urine and nonspecific prodromal symptoms (eg, anorexia, malaise, and gastrointestinal symptoms), other reports did not describe the onset of clear prodromal symptoms prior to onset of jaundice
            • The physician may consider the value of liver function testing; periodic serum transaminase testing has not been proven to prevent serious injury but it is generally believed that early detection of drug-induced hepatic injury along with immediate withdrawal of the suspect drug enhances the likelihood for recovery
            • Patients should be advised to be alert for signs and symptoms of liver dysfunction (jaundice, anorexia, gastrointestinal complaints, malaise, etc.) and to report them to their doctor immediately if they occur; ongoing clinical assessment of patients should govern physician interventions, including diagnostic evaluations and treatment
            • Therapy should be discontinued if clinical signs or symptoms suggest liver failure; patients who develop evidence of hepatocellular injury such as increased serum AST or serum ALT levels ≥ 3 times the upper limit of normal, while on nefazodone should be withdrawn from the drug; these patients should be presumed to be at increased risk for liver injury if nefazodone is reintroduced; accordingly, such patients should not be considered for re-treatment


            Pregnancy & Lactation


            There are no adequate and well-controlled studies in pregnant women; therapy should be administered during pregnancy only if potential benefit justifies potential risk to fetus

            Reproduction studies have been performed in pregnant rabbits and rats at daily doses up to 200 and 300 mg/kg, respectively (approximately 6 and 5 times, respectively, the maximum human daily dose on mg/m2 basis)

            No malformations were observed in offspring as a result of therapy; however, increased early pup mortality was seen in rats at a dose approximately five times maximum human dose, and decreased pup weights were seen at this and lower doses, when dosing began during pregnancy and continued until weaning; the cause of these deaths is not known; the no-effect dose for rat pup mortality was 1.3 times the human dose on mg/m2 basis


            Not known whether nefazodone or its metabolites are excreted in human milk; because many drugs are excreted in human milk, caution should be exercised when this drug is administered to a nursing woman

            Pregnancy Categories

            A: Generally acceptable. Controlled studies in pregnant women show no evidence of fetal risk.

            B: May be acceptable. Either animal studies show no risk but human studies not available or animal studies showed minor risks and human studies done and showed no risk.

            C: Use with caution if benefits outweigh risks. Animal studies show risk and human studies not available or neither animal nor human studies done.

            D: Use in LIFE-THREATENING emergencies when no safer drug available. Positive evidence of human fetal risk.

            X: Do not use in pregnancy. Risks involved outweigh potential benefits. Safer alternatives exist.

            NA: Information not available.



            Mechanism of Action

            Antidepressant structurally unrelated to SSRI, tricyclics, tetracyclics, or MAO inhibitors but inhibits neuronal reuptake of serotonin & norepinephrine; it is also a 5-HT2 and alpha1 receptor antagonist


            Half-life elimination: 2-4 hrs

            Peak Plasma Time: 1 hr

            Bioavailability: 20% (decreased by food)

            Protein Bound: >99%

            Vd: 0.22-0.87 L/kg

            Metabolism: hepatic P450 enzyme CYP3A4

            Metabolites: hydroxynefazodone (HO-NEF), metachlorphenylpiperazine (mCPP)

            Excretion: Urine (55%); feces (20-30%)

            Dialyzable: No

            Enzymes inhibited: CYP3A4



            nefazodone oral
            250 mg tablet
            nefazodone oral
            200 mg tablet
            nefazodone oral
            50 mg tablet
            nefazodone oral
            150 mg tablet
            nefazodone oral
            100 mg tablet

            Copyright © 2010 First DataBank, Inc.


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            Tier Description
            1 This drug is available at the lowest co-pay. Most commonly, these are generic drugs.
            2 This drug is available at a middle level co-pay. Most commonly, these are "preferred" (on formulary) brand drugs.
            3 This drug is available at a higher level co-pay. Most commonly, these are "non-preferred" brand drugs.
            4 This drug is available at a higher level co-pay. Most commonly, these are "non-preferred" brand drugs or specialty prescription products.
            5 This drug is available at a higher level co-pay. Most commonly, these are "non-preferred" brand drugs or specialty prescription products.
            6 This drug is available at a higher level co-pay. Most commonly, these are "non-preferred" brand drugs or specialty prescription products.
            NC NOT COVERED – Drugs that are not covered by the plan.
            Code Definition
            PA Prior Authorization
            Drugs that require prior authorization. This restriction requires that specific clinical criteria be met prior to the approval of the prescription.
            QL Quantity Limits
            Drugs that have quantity limits associated with each prescription. This restriction typically limits the quantity of the drug that will be covered.
            ST Step Therapy
            Drugs that have step therapy associated with each prescription. This restriction typically requires that certain criteria be met prior to approval for the prescription.
            OR Other Restrictions
            Drugs that have restrictions other than prior authorization, quantity limits, and step therapy associated with each prescription.
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            Medscape prescription drug monographs are based on FDA-approved labeling information, unless otherwise noted, combined with additional data derived from primary medical literature.