See Supplemental Patient Information
- Antidepressants may cause worsening of depression and the emergence of suicidality in some patients, especially children, adolescents, and young adults during the early stages of treatment [US Black Box Warning]
- All patients on antidepressant therapy must be closely observed by family members or caregivers for emergence of agitation, irritability, suicidality, behavioral changes, and worsening of depression. Occurrence of any symptoms should be promptly reported to HCPs [US Black Box Warning]
- Physicians should consider changing treatment regimen or discontinuing the drug if persistent worsening of depression is observed
- Patients showing depressive symptoms should be screened for risk of bipolar disorder before initiating treatment with antidepressants; nefazodone is not indicated for treatment of bipolar disorder
- Life-threatening hepatic failure, sometimes fatal or requiring transplant, has been observed in patients treated with nefazodone [US Black Box Warning]
- Regular monitoring of LFTs is advised in patients treated with nefazodone. Early detection of hepatic damage and prompt discontinuation of drug improves the chances of recovery [US Black Box Warning]
- Serum levels of AST and ALT that are three times above normal may indicate hepatocellular injury. Discontinue treatment with nefazodone if abnormal AST and ALT levels are observed and avoid re-treatment [US Black Box Warning]
- Concurrent administration of MAO inhibitors with nefazodone may cause serious and sometimes fatal reactions such as seizures, hyperthermia, rigidity, myoclonus, autonomic instability, changes in vital signs, agitation, delirium and coma
- Treatment with nefazodone should be started at least 14 days after discontinuation of MAOIs; also MAOIs should be started at least 7 days after stopping nefazodone
- Concomitant use of triazolam or alprazolam with nefazodone may increase the plasma concentrations of these drugs causing potential toxicity. Concomitant use of these two drugs should be avoided if possible or significant dose reduction is recommended
- Nefazodone should not be used concurrently with terfenadine, astemizole, cisapride, or pimozide as this may cause increased plasma concentrations of these drugs due to CYP3A4 inhibition
- Increased plasma concentrations of these drugs may cause QT prolongation and ventricular tachycardia of the torsade de pointes type, which may be fatal in some cases
- Concurrent use of carbamazepine and nefazodone may lead to decreased plasma levels of nefazodone, thereby reducing its antidepressant activity
- Postural hypotension has been reported with use of nefazodone. Caution should be exercised in patients with known cardiovascular or cerebrovascular disease
- Patients with major affective disorder treated with nefazodone are at risk of developing mania/hypomania; use with caution in patients with a history of mania
- Rare cases of seizures have been reported in patients treated with nefazodone
- Priapism has been reported in certain patients treated with nefazodone. If prolonged erection occurs, discontinue therapy and initiate appropriate treatment
- Use with caution in patients with a recent history of myocardial infarction or unstable heart disease, as nefazodone may cause sinus bradycardia
- Patients must promptly notify their physician about occurrence of any allergic reactions or visual disturbances
Cautions: Use cautiously in
- Hypotension
- Dehydration
- Hypovolemia
- Suicidal tendency
- Seizures
- Elderly patients
- Concomitant use of drugs metabolized by CYP3A4
Supplemental Patient Information
- Instruct patients to avoid performing activities such as driving or operating machinery until they are reasonably certain that the therapy does not adversely affect their ability to perform such tasks
- Advise families and caregivers to monitor patients for suicidality, behavioral changes, and worsening of depression and inform them to notify any observations to the physician
- Instruct patients to avoid drinking alcohol during therapy
- Inform patients to notify their physician if rashes, hives, or allergic reactions occur during therapy
- Advise patients receiving therapy to promptly report their physician if they develop any visual disturbances such as blurred vision, scotoma, and visual trails
Pregnancy Category:C
Breastfeeding: Possibly unsafe. Low levels of nefazodone are excreted in maternal milk, which is not likely to cause adverse effects in infants >2 months. An alternate drug may be preferred, especially while nursing a newborn or preterm infant. This information is based upon LactMed database (available at http://toxnet.nlm.nih.gov/cgi-bin/sis/htmlgen?LACT last accessed 22 June 2011). Manufacturer advises caution. Manufacturer advises patients to notify their physician if breastfeeding.
