Nefazodone

Nefazodone is a prescription medication used for the treatment of depression.

• Nefazodone is available under the following different brand names: Serzone, Nefazodone 5HT2, Serzone 5HT2

Common side effects of Nefazodone include:

• dizziness
• drowsiness
• lightheadedness
• headache
• weakness
• nausea
• dry mouth
• sore throat
• diarrhea
• constipation
• sleep problems (insomnia)
• increased appetite
• vision problems

Serious side effects of Nefazodone include:

• confusion
• fainting
• seizures
• easy bleeding or bruising

Rare side effects of Nefazodone include:

• none

Seek medical care or call 911 at once if you have the following serious side effects:

• Severe headache, confusion, slurred speech, arm or leg weakness, trouble walking, coordination loss, unsteady, very stiff muscles, high fever, profuse sweating, or tremors
• Serious eye symptoms such as sudden vision loss, blurred vision, tunnel vision, eye pain or swelling, or seeing halos around lights
• Serious heart symptoms include fast, irregular, or pounding heartbeats; fluttering in the chest; shortness of breath; sudden dizziness, light-headedness, or passing out

This is not a complete list of side effects and other serious side effects or health problems that may occur because of the use of this drug. Call your doctor for medical advice about serious side effects or adverse reactions. You may report side effects or health problems to FDA at 1-800-FDA-1088.

Adult dosage

Tablet

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

Depression

Adult dosage

• Initial: 100 mg orally every 12 hours
• Increase by 50-100 mg/dose at 1-week intervals

Geriatric dosage

• Initial: 50 mg orally every 12 hours (reduced clearance, increased side effects)
• Increase by 50-100 mg/dose at 1-week intervals
• Maintenance: 200-400 mg/day divided every 12 hours

Dosage Considerations – Should be Given as Follows:

• See “Dosages”

If your medical doctor is using this medicine to treat your pain, your doctor or pharmacist may already be aware of any possible drug interactions and may be monitoring you for them. Do not start, stop, or change the dosage of any medicine before checking with your doctor, healthcare provider, or pharmacist first.

• Nefazodone has severe interactions with at least 35 other drugs
• Nefazodone has serious interactions with at least 249 other drugs
• Nefazodone has moderate interactions with at least 288 other drugs
• Nefazodone has minor interactions with at least 34 other drugs

This information does not contain all possible interactions or adverse effects. Visit the RxList Drug Interaction Checker for any drug interactions. Therefore, before using this product, tell your doctor or pharmacist about all the products you use. Keep a list of all your medications with you and share this information with your doctor and pharmacist. Check with your healthcare professional or doctor for additional medical advice, health questions, or concerns.

Contraindications

• Coadministration with terfenadine (discontinued), astemizole (discontinued), cisapride, pimozide, and 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 nefazodone or other phenylpiperazine antidepressants
• Coadministration with monoamine oxidase inhibitors or within 14 days of administration
• Liver injury resulting from previous nefazodone treatment

Effects of drug abuse

• None

Short-Term Effects

• See "What Are Side Effects Associated with Using Nefazodone?"

Long-Term Effects

• See "What Are Side Effects Associated with Using Nefazodone?"

Cautions

• Clinical worsening and suicide ideation may occur despite medication in adolescents and young adults (18-24 years)
• May take several weeks to achieve a full response
• May cause anticholinergic effects
• Use caution in patients experiencing xerostomia, visual problems, paralytic ileus, benign prostatic hypertrophy, urinary retention, or decreased motility
• The pupillary dilation that occurs following the 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 for 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 the 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 a heart rate of 50 bpm and less and a decrease of at least 15 bpm from baseline, was 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 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 the 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
  • Symptoms, such as 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 MDD and for other indications, both psychiatric and nonpsychiatric
  • Although a causal link between the 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 MDD or other indications, both psychiatric and nonpsychiatric, should be alerted about the need to monitor patients for the emergence of agitation, irritability, unusual changes in behavior, and other symptoms described above, as well as the emergence of suicidality, and to report such symptoms immediately to healthcare providers; such monitoring should include daily observation by families and caregivers
  • Prescriptions should be written for the smallest quantity of tablets consistent with good patient management 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 the 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 the likelihood of precipitation of a mixed/manic episode in patients at a 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 a 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 US 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 the estimated background rate of liver failure; there is no evidence that preexisting liver disease increases the likelihood of developing liver failure; however, may complicate patient monitoring owing 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 the 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 of 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 aspartate aminotransferase or serum alanine transaminase levels of 3 times and more than the upper limit of normal, while on nefazodone should be withdrawn from the drug; these patients should be presumed to be at an increased risk for liver injury if nefazodone is reintroduced; accordingly, such patients should not be considered for re-treatment

Pregnancy and Lactation

• There are no adequate and well-controlled studies in pregnant women; therapy should be administered during pregnancy only if the potential benefit justifies the potential risk to the fetus
• Reproduction studies have been conducted in pregnant rabbits and rats at daily doses up to 200-300 mg/kg, respectively (approximately 6 and 5 times, respectively, the maximum human daily dose on a 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 the 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 woman