Serzone
Serzone Information
Serzone (nefazodone) is indicated for the treatment of depression.
The efficacy of Serzone (nefazodone) in the treatment of depression was established in 6-8 week controlled trials of outpatients whose diagnoses corresponded most closely to the DSM-III or DSM-IIIR category of major depressive disorder.
A major depressive episode implies a prominent and relatively persistent depressed or dysphoric mood that usually interferes with daily functioning (nearly every day for at least 2 weeks). It must include either depressed mood or loss of interest or pleasure and at least 5 of the following 9 symptoms: depressed mood, loss of interest in usual activities, significant change in weight and/or appetite, insomnia or hypersomnia, psychomotor agitation or retardation, increased fatigue, feelings of guilt or worthlessness, slowed thinking or impaired concentration, a suicide attempt or suicidal ideation.
The antidepressant effectiveness of Serzone (nefazodone) in hospitalized depressed patients has not been adequately studied.
The effectiveness of Serzone (nefazodone) in long-term use, that is, for more than 6 to 8 weeks, has not been systematically evaluated in controlled trials. Therefore, the physician who elects to use Serzone (nefazodone) for extended periods should periodically re-evaluate the long-term usefulness of the drug for the individual patient.
The coadministration of triazolam and Serzone (nefazodone) causes significant increase in the plasma level of triazolam, and a 75% reduction in the initial triazolam dosage is recommended if the two drugs are to be given together. Because not all commerically available dosage forms of triazolam permit a sufficient dosage reduction, the coadministration of triazolam and Serzone (nefazodone) should be avaoided in most patients, including the elderly.
Serzone Ingredients and Composition
How Does Serzone Work?
The mechanism of action of Serzone (nefazodone), as with other antidepressants, is unknown.
Preclinical studies have shown that Serzone (nefazodone) inhibits neuronal uptake of serotonin and norepinephrine.
Serzone (nefazodone) occupies central 5-HT2 receptors at nanomolar concentrations, and acts as an antagonist at this receptor. Serzone (nefazodone) was shown to antagonize alpha1-adrenergic receptors, a property which may be associated with postural hypotension. In vitro binding studies showed that nefazodone had no significant affinity for the following receptors: alpha2 and beta adrenergic, 5-HT1A, cholinergic, dopaminergic, or benzodiazepine.
How To Take Serzone and Serzone Dosage and Administration
Initial Treatment
The recommended starting dose for Serzone (nefazodone) is 200 mg/day, administered in two divided doses (b.i.d.). In the controlled clinical trials establishing the anti-depressant efficacy of Serzone (nefazodone), the effective dose range was generally 300 to 600 mg/day. Consequently, most patients, depending on tolerability and the need for further clinical effect, should have dose increased. Dose increases should occur in increments of 100 mg/day to 200 mg/day, again on a b.i.d. schedule, at intervals of no less than 1 week. As with all antidepressants, several weeks on treatment may be required to obtain a full antidepressant response.
Dosage for Elderly or Debilitated Patients
The recommended dose for elderly or debilitated patients is 100 mg/day on a b.i.d. schedule. These patients often have reduced Serzone (nefazodone) clearance and/or increased sensitivity to the side effects of CNS-active drugs. It may also be appropriate to modify the rate of subsequent dose titration. As steady-state plasma levels do not change with age, the final target Serzone (nefazodone) dose based on a careful assessment of the patient's clinical response may be similar in healthy younger and older patients.
Maintenance/Continuation/Extended Treatment
There is no body of evidence available from controlled trials to indicate how long the depressed patients should be treated with Serzone (nefazodone). It is generally agreed, however, that pharmacological treatment for acute episodes of depression should continue for up to six months or longer. Whether the dose of antidepressant needed to induce remission is identical to the dose needed to maintain euthymia is unknown. Although there are no efficacy data that specifically address maintenance antidepressant treatment with Serzone (nefazodone), the safety of Serzone (nefazodone) in long-term use is supported by data from both double-blind and open-label trials involving more than 250 patients treated for at least one year.
Switch Patients to or From a Monoamine Oxidase Inhibitor
At least 14 days should elapse between discontinuation of an MAOI and initiation of therapy with Serzone (nefazodone). In addition, at least 7 days should be allowed after stopping Serzone (nefazodone) before starting an MAOI.
If you suspect a Serzone Overdose
Human Experience
There is very limited experience with Serzone (nefazodone) overdose. In premarketing clinical studies, there were seven reports of nefazodone overdose alone or in combination with other pharmacological agents. The amount of Serzone (nefazodone) ingested ranged from 1000 mg to 11,200 mg. Commonly reported symptoms from overdose of nefazodone included nausea, vomiting, and somnolence. One nonstudy participant took 2000-3000 mg of nefazodone with methocarbonal and alcohol; this person reportedly experienced a convulsion (type not documented). None of the patients died.
Overdose Management
Overdosage may cause an increase in incidence or severity of any of the reported adverse reactions.
There is no specific antidote for nefazodone. Treatment should be symptomatic and supportive in the case of hypotension or excessive sedation. Any patient suspected of having taken an overdose should have the stomach emptied by gastric lavage.
In managing Serzone overdosage, consider the possibility of multiple drug involvement/The physician should consider contacting a poison control center on the treatment of the Serzone overdose.
Serzone Side Effects
Serzone Precautions and Contraindications
Hepatotoxicity (See WARNINGS)
Cases of life-threatening hepatic failure have been reported in patients treated with Serzone.
The reported rate in the United States is about 1 case of liver failure resulting in death or transplant per 250,000 - 300,000 patient-years of Serzone treatment. This represents a rate of about 3-4 times the estimated background rate of liver failure. This rate is an underestimate because of under reporting, and the true risk could be considerably greater than this. A large cohort study of antidepressant users found no cases of liver failure leading to death or transplant among Serzone users in about 30,000 patient-years of exposure. The spontaneous report data and the cohort study results provide estimates of the upper and lower limits of the risk of liver failure in nefazodone-treated patients, but are not capable of providing a precise risk estimate.
The time to liver injury for the reported liver failure cases resulting in death or transplant generally ranged from 2 weeks to 6 months on Serzone therapy. Although some reports described dark urine and nonspecific prodromal symptoms (e.g., anorexia, malaise, and gastrointestinal symptoms), other reports did not describe the onset of clear prodromal symptoms prior to the onset of jaundice.
The physician administering Serzone 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 taking Serzone should govern physician interventions, including diagnostic evaluations and treatment.
Serzone 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 Serzone should be withdrawn from the drug. These patients should be presumed to be at increased risk for liver injury if Serzone is reintroduced. Accordingly, such patients should not be considered for re-treatment.
Suicide
The possibility of a suicide attempt is inherent in depression and may persist until significant remission occurs. Close supervision of high risk patients should accompany initial Serzone therapy. Prescriptions for nefazodone should be written for the smallest quantity of tablets consistent with good patients management in order to reduce the risk of overdose.
Seizures
During premarketing testing, a recurrence of petit mal seizure was observed in a patient receiving Serzone (nefazodone) who had a history of such seizures. In addition, one nonstudy participant reportedly experienced a convulsion (type not documented) following a multiple-drug overdose. Rare occurances of convulsions (including grand mal seizures) following nefazodone administration have benn reported since market introduction. A causal relationship to Serzone (nefazodone) has not been established.
Priapism
While priapism did not occur during premarketing experience with Serzone (nefazodone), rare reports of priapism have been reported since market introduction. 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 treatment.
Contraindications to Serzone
Coadministration of terfenadine, astemizole, cisapride, pimozide, or carbamazepine with Serzone (nefazodone hydrochloride) is contraindicated.
Serzone tablets are contraindicated in patients who were withdrawn from Serzone because of evidence of liver injury. Serzone tablets are also contraindicated in patients who have demonstrated hypersensitivity to nefazodone hydrochloride, its inactive ingredients, or other phenylpiperazine antidepressants.
The coadministration of triazolam and nefazodone causes a significant increase in the plasma level of triazolam, and a 75% reduction in the initial triazolam dosage is recommended if the two drugs are to be given together. Because not all commercially available dosage forms of triazolam permit a sufficient dosage reduction, the coadministration of triazolam and Serzone should be avoided for most patients, including the elderly.
Serzone Warnings
Serzone Clinical Trials and Studies
Serzone and Alcohol Interaction
Do not drink alcoholic beverages while taking Serzone.
Taking Serzone during Pregnancy or Breast-feeding
Tell your doctor if you are pregnant, planning to become pregnant, or become pregnant while taking Serzone. It is not known whether Serzone can harm your unborn baby.
Storing Serzone
Store Serzone (nefazodone) at room temperature, below 40°C (104°F) and dispense in a tight container.
