(21-25%) Dizziness (15-20%) Asthenia (11-15%) Constipation (11-15%) Insomnia (11-15%) 1-10% 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 Hypomania Mania Seizure Suicidal thoughts Suicide 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 patientsContraindications 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 Cautions 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. Hepatotoxicity 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 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 Lactation 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 womanPregnancy 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 Pharmacokinetics 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 BRAND FORM. UNIT PRICE PILL IMAGE nefazodone oral- 250 mg tabletnefazodone oral- 200 mg tabletnefazodone oral- 50 mg tabletnefazodone oral- 150 mg tabletnefazodone oral- 100 mg tabletCopyright © 2010 First DataBank, Inc.Print Patient Educationnefazodone oral NEFAZODONE - ORAL (neh-FAZZ-oh-doan) COMMON BRAND NAME(S): Serzone WARNING: Antidepressant medications are used to treat a variety of conditions, including depression and other mental/mood disorders. These medications can help prevent suicidal thoughts/attempts and provide other important benefits. However, studies have shown that a small number of people (especially people younger than 25) who take antidepressants for any condition may experience worsening depression, other mental/mood symptoms, or suicidal thoughts/attempts. It is very important to talk with the doctor about the risks and benefits of antidepressant medication (especially for people younger than 25), even if treatment is not for a mental/mood condition.Tell the doctor right away if you notice worsening depression/other psychiatric conditions, unusual behavior changes (including possible suicidal thoughts/attempts), or other mental/mood changes (including new/worsening anxiety, panic attacks, trouble sleeping, irritability, hostile/angry feelings, impulsive actions, severe restlessness, very rapid speech). Be especially watchful for these symptoms when a new antidepressant is started or when the dose is changed.Nefazodone has rarely caused very serious (possibly fatal) liver disease. Tell your doctor right away if you develop symptoms of liver disease, including nausea/vomiting that doesn't stop, severe stomach/abdominal pain, unusual tiredness, loss of appetite, dark urine, yellowing eyes/skin.Before using this medication, tell your doctor if you have liver disease or abnormal liver function tests.Your doctor should perform liver function tests periodically while you are taking this medication. If your doctor directs you to stop taking this medication because of liver problems or abnormal liver function tests, you should not take this drug again. Consult your doctor or pharmacist for more details. USES: This medication is used to treat depression. Because of the risk of liver disease, this medication is usually used after trying other drugs. Nefazodone works by helping to restore the balance of certain natural chemicals (neurotransmitters such as serotonin, norepinephrine) in the brain. HOW TO USE: Read the Medication Guide and Patient Information Leaflet provided by your pharmacist before you start using nefazodone and each time you get a refill. If you have any questions, consult your doctor or pharmacist.Take