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Serzone

Serzone - General Information

Serzone hydrochloride (trade name Serzone) is an antidepressant drug marketed by Bristol-Myers Squibb. Its sale was discontinued in 2003 in some countries, due to the small possibility of hepatic (liver) injury, which could lead to the need for a liver transplant, or even death. The incidence of severe liver damage is approximately 1 in 250,000 to 300,000 patient-years. On May 20, 2004, Bristol-Myers Squibb discontinued the sale of Serzone in the United States. [Wikipedia]

 

Pharmacology of Serzone

Serzone, an antidepressant synthetically derived phenylpiperazine, is used to treat major depression. Although it is structurally similar to trazodone, nefazodone has a mechanism of action different from other antidepressants and, hence, lacks the risk for major cardiovascular toxicity seen with tricyclics and insomnia and inhibition of REM sleep seen with the selective serotonin reuptake inhibitors.

 

Serzone for patients

Prescribers or other health professionals should inform patients, their families, and their caregivers about the benefits and risks associated with treatment with SERZONE and should counsel them in its appropriate use. A patient Medication Guide About Using Antidepressants in Children and Teenagers is available for SERZONE. The prescriber or health professional should instruct patients, their families, and their caregivers to read the Medication Guide and should assist them in understanding its contents. Patients should be given the opportunity to discuss the contents of the Medication Guide and to obtain answers to any questions they may have. The complete text of the Medication Guide is reprinted at the end of this document.

Patients should be advised of the following issues and asked to alert their prescriber if these occur while taking SERZONE.

Clinical Worsening and Suicide Risk

Patients, their families, and their caregivers should be encouraged to be alert to the emergence of anxiety, agitation, panic attacks, insomnia, irritability, hostility, agressiveness, impulsivity, akathisia (psychomotor restlessness), hypomania, mania, other unusual changes in behavior, worsening of depression, and suicidal ideation, especially early during antidepressant treatment and when the dose is adjusted up or down. Families and caregivers of patients should be advised to observe for the emergence of such symptoms on a day-to-day basis, since changes may be abrupt. Such symptoms should be reported to the patient's prescriber or health professional, especially if they are severe, abrupt in onset, or were not part of the patient's presenting symptoms. Symptoms such as these may be associated with an increased risk for suicidal thinking and behavior and indicate a need for very close monitoring and possibly changes in the medication.

 

SERZONE®

Read this information completely before using SERZONE. Read the information each time you get more medicine. There may be new information. This leaflet provides a summary about SERZONE and does not include everything there is to know about your medicine.This information is not meant to take the place of talking with your doctor.

Before taking this medication, be sure to check the tablets in the bottle to make sure they match one of the following descriptions:

• 50 mg tablets are six-sided, light pink tablets imprinted with "BMS" and "50" on one face of the tablet;

• 100 mg tablets are six-sided, white tablets imprinted with "BMS" and "100" on one face of the tablet;

• 150 mg tablets are six-sided, peach-colored tablets imprinted with "BMS" and "150" on one face of the tablet;

• 200 mg tablets are six-sided, light yellow tablets imprinted with "BMS" and "200" on one face of the tablet; and

• 250 mg tablets are six-sided, white tablets imprinted with "BMS" and "250" on one face of the tablet.

What is the most important information that I should know about SERZONE?

Rarely,people who take SERZONE can develop serious liver problems. If you get any of the following symptoms while taking SERZONE, call your doctor right away because you may be developing a liver problem:

• Yellowing of the skin or whites of eyes (jaundice)

• Unusually dark urine

• Loss of appetite that lasts several days or longer

• Nausea

• Abdominal (lower stomach) pain

People who currently have liver problems should not take SERZONE (nefazodone hydrochloride).

What is SERZONE?

SERZONE (pronounced sir-ZONE) is a medicine used to treat depression.SERZONE is thought to treat depression by correcting an imbalance in the amounts of certain natural chemicals, such as serotonin and norepinephrine, which are in your brain.

Who should not take SERZONE?

Do not take SERZONE if you

• are allergic to SERZONE or the related medicine Desyrel® (trazodone).

• are taking Seldane® (terfenadine),an antihistamine; Hismanal® (astemizole),an antihistamine; Propulsid® (cisapride),used for heartburn; Halcion® (triazolam),used for insomnia; Orap® (pimozide),used to treat Tourette's syndrome; or Tegretol® (carbamazepine), used to control seizures.

• currently have liver problems.

• are taking or have taken within the last 14 days one of the medicines for depression known as monoamine oxidase inhibitors (MAOIs), such as Nardil® or Parnate®.

Be sure to tell your doctor if you

• have ever had liver problems;

• are taking any other medicine, vitamin supplement, or herbal remedy, including those sold without a prescription (over-the-counter);

• have heart problems or have had a heart attack or stroke;

• have had manic episodes (extreme agitation or excitability);

• have ever attempted suicide;

• have had convulsions (seizures);

• are pregnant or breast-feeding.

How should I take SERZONE?

• Take SERZONE at the same time every day exactly as prescribed by your doctor.You may take SERZONE with or without food.

• It may take a while for you to feel that SERZONE is working. You may not feel the full effect for several weeks.Once you feel better,it is important to keep taking SERZONE as directed by your doctor.

• If you miss a dose of SERZONE, skip that dose and continue with your regular schedule. Never take 2 doses at the same time.

• If you think that you have taken more SERZONE than prescribed, contact your doctor, local poison control center, or emergency room right away.

What should I avoid while taking SERZONE?

• Do not drive or operate possibly dangerous machinery (such as an automobile, power mower, or power tool) or participate in any hazardous activity that requires full mental alertness until you know how SERZONE affects you.

• Before taking SERZONE, tell your doctor about any medicines you are taking, including vitamin supplements, herbal remedies, and any non-prescription (over-the-counter) medicines. Some of these medicines may affect how SERZONE works and should not be used in combination without talking to your doctor.

• Do not drink alcoholic beverages while taking SERZONE.

• 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.

• Talk with your doctor before taking SERZONE if you are breast-feeding. It is not known whether SERZONE can pass through your breast milk to the baby.

What are the possible side effects of SERZONE?

The most common side effects of SERZONE are sleepiness, dry mouth, nausea, dizziness, constipation, weakness, lightheadedness, problems with vision, and confusion.

Call your doctor right away if you have any of the following side effects:

• Yellowing of the skin or whites of eyes (jaundice)

• Unusually dark urine

• Loss of appetite that lasts several days or longer

• Severe nausea

• Abdominal (lower stomach) pain

• Rash or hives

• Seizure (convulsion)

• Fainting

• Erection that lasts too long

Tell your doctor right away about any side effects that you have or discomfort that you experience. Do not change your dose or stop taking SERZONE (nefazodone hydrochloride) without talking with your doctor first.

What else should I know about SERZONE?

Patients with depression may experience worsening of their symptoms, which may include thinking about or planning suicide, whether or not they are taking medicine for their depression. There has been a concern that medicines to treat depression may contribute to this worsening of depression and/or new thoughts or plans about suicide in some patients, especially children and teenagers.

Patients and their families should be encouraged to be aware of the development of symptoms such as anxiety, agitation, panic attacks, difficulty sleeping, irritability, hostility, impulsiveness, restlessness, difficulty concentrating, worsening of depression, or thoughts of suicide, especially early on while taking medicine to treat depression. If patients have any of these symptoms they should contact their doctor, especially if the symptoms are severe, began suddenly, or were not seen before they began taking SERZONE.

Medicines are sometimes prescribed for conditions that are not mentioned in patient information leaflets. Your doctor has prescribed SERZONE for you and you alone. Do not give SERZONE to other people, even if they have the same condition. It may harm them.

This leaflet provides a summary of the most important information about SERZONE. If you would like more information, talk with your doctor or pharmacist.You can ask for information about SERZONE that is written for healthcare professionals. You can also get more information by visiting www.serzone.com.

SERZONE® is a registered trademark of Bristol-Myers Squibb Company.Other brand names listed are trademarks of their respective owners and are not trademarks of Bristol-Myers Squibb Company.

 

Medication Guide

About Using Antidepressants in Children and Teenagers

What is the most important information I should know if my child is being prescribed an antidepressant?

Parents or guardians need to think about 4 important things when their child is prescribed an antidepressant:

  1. There is a risk of suicidal thoughts or actions
  2. How to try to prevent suicidal thoughts or actions in your child
  3. You should watch for certain signs if your child is taking an antidepressant
  4. There are benefits and risks when using antidepressants

1. There is a Risk of Suicidal Thoughts or Actions

Children and teenagers sometimes think about suicide, and many report trying to kill themselves.

Antidepressants increase suicidal thoughts and actions in some children and teenagers. But suicidal thoughts and actions can also be caused by depression, a serious medical condition that is commonly treated with antidepressants. Thinking about killing yourself or trying to kill yourself is called suicidality or being suicidal.

A large study combined the results of 24 different studies of children and teenagers with depression or other illnesses. In these studies, patients took either a placebo (sugar pill) or an antidepressant for 1 to 4 months. No one committed suicide in these studies, but some patients became suicidal. On sugar pills, 2 out of every 100 became suicidal. On the antidepressants, 4 out of every 100 patients became suicidal.

For some children and teenagers, the risks of suicidal actions may be especially high. These include patients with

  • Bipolar illness (sometimes called manic-depressive illness)
  • A family history of bipolar illness
  • A personal or family history of attempting suicide

If any of these are present, make sure you tell your healthcare provider before your child takes an antidepressant.

2. How to Try to Prevent Suicidal Thoughts and Actions

To try to prevent suicidal thoughts and actions in your child, pay close attention to changes in her or his moods or actions, especially if the changes occur suddenly. Other important people in your child's life can help by paying attention as well (e.g., your child, brothers and sisters, teachers, and other important people). The changes to look out for are listed in Section 3, on what to watch for.

Whenever an antidepressant is started or its dose is changed, pay close attention to your child.

After starting an antidepressant, your child should generally see his or her healthcare provider:

  • Once a week for the first 4 weeks
  • Every 2 weeks for the next 4 weeks
  • After taking the antidepressant for 12 weeks
  • After 12 weeks, follow your healthcare provider's advice about how often to come back
  • More often if problems or questions arise

You should call your child's healthcare provider between visits if needed.

3. You Should Watch for Certain Signs If Your Child is Taking an Antidepressant

Contact your child's healthcare provider right away if your child exhibits any of the following signs for the first time, or if they seem worse, or worry you, your child, or your child's teacher:

  • Thoughts about suicide or dying
  • Attempts to commit suicide
  • New or worse depression
  • New or worse anxiety
  • Feeling very agitated or restless
  • Panic attacks
  • Difficulty sleeping (insomnia)
  • New or worse irritability
  • Acting aggressive, being angry, or violent
  • Acting on dangerous impulses
  • An extreme increase in activity and talking
  • Other unusual changes in behavior or mood

Never let your child stop taking an antidepressant without first talking to his or her healthcare provider. Stopping an antidepressant suddenly can cause other symptoms.

4. There are Benefits and Risks When Using Antidepressants

Antidepressants are used to treat depression and other illnesses. Depression and other illnesses can lead to suicide. In some children and teenagers, treatment with an antidepressant increases suicidal thinking or actions. It is important to discuss all the risks of treating depression and also the risks of not treating it. You and your child should discuss all treatment choices with your healthcare provider, not just the use of antidepressants.

Other side effects can occur with antidepressants.

Of all the antidepressants, only fluoxetine (Prozac®) has been FDA approved to treat pediatric depression.

For obsessive compulsive disorder in children and teenagers, FDA has approved only fluoxetine (Prozac®)*, sertraline (Zoloft®)*, fluvoxamine, and clomipramine (Anafranil®)*.

Your healthcare provider may suggest other antidepressants based on the past experience of your child or other family members.

Is this all I need to know if my child is being prescribed an antidepressant?

No. This is a warning about the risk for suicidality. Other side effects can occur with antidepressants. Be sure to ask your healthcare provider to explain all the side effects of the particular drug he or she is prescribing. Also ask about drugs to avoid when taking an antidepressant. Ask your healthcare provider or pharmacist where to find more information.

*The following are registered trademarks of their respective manufacturers: Prozac®/Eli Lilly and Company; Zoloft®/Pfizer Pharmaceuticals; Anafranil®/Mallinckrodt Inc.

This Medication Guide has been approved by the U.S. Food and Drug Administration for all antidepressants.


Revised January 2005
Based on package insert dated 01/05

 

Serzone Interactions

Drugs Highly Bound to Plasma Protein

Because nefazodone is highly bound to plasma protein,administration of SERZONE to a patient
taking another drug that is highly protein bound may cause increased free concentrations of
the other drug, potentially resulting in adverse events. Conversely, adverse effects could
result from displacement of nefazodone by other highly bound drugs.

Warfarin: There were no effects on the prothrombin or bleeding times or upon the pharmacokinetics
of R-warfarin when nefazodone (200 mg BID) was administered for 1 week to subjects who had been
pretreated for 2 weeks with warfarin. Although the coadministration of nefazodone did decrease
the subjects' exposure to S-warfarin by 12%, the lack of effects on the prothrombin and bleeding
times indicates this modest change is not clinically significant. Although these results suggest
no adjustments in warfarin dosage are required when nefazodone is administered to patients
stabilized on warfarin, such patients should be monitored as required by standard medical practices.

CNS-Active Drugs

Monoamine Oxidase Inhibitors

Haloperidol: When a single oral 5-mg dose of haloperidol was coadministered with nefazodone (200 mg BID)
at steady state, haloperidol apparent clearance decreased by 35% with no significant increase in peak
haloperidol plasma concentrations or time of peak. This change is of unknown clinical significance.
Pharmacodynamic effects of haloperidol were generally not altered significantly. There were no changes
in the pharmacokinetic parameters for nefazodone. Dosage adjustment of haloperidol may be necessary
when coadministered with nefazodone.

Lorazepam: When lorazepam (2 mg BID) and nefazodone (200 mg BID) were coadministered to steady state,
there was no change in any pharmacokinetic parameter for either drug compared to each drug administered
alone. Therefore, dosage adjustment is not necessary for either drug when coadministered.

Triazolam/Alprazolam

Alcohol: Although nefazodone did not potentiate the cognitive and psychomotor effects of alcohol in
experiments with normal subjects, the concomitant use of SERZONE and alcohol in depressed patients is
not advised.

Buspirone: In a study of steady-state pharmacokinetics in healthy volunteers, coadministration of
buspirone (2.5 or 5 mg BID) with nefazodone (250 mg BID) resulted in marked increases in plasma buspirone
concentrations (increases up to 20-fold in Cmax and up to 50-fold in AUC) and statistically significant
decreases (about 50%) in plasma concentrations of the buspirone metabolite 1-pyrimidinylpiperazine. With
5-mg BID doses of buspirone, slight increases in AUC were observed for nefazodone (23%) and its metabolites
hydroxynefazodone (17%) and mCPP (9%). Subjects receiving nefazodone 250 mg BID and buspirone 5 mg BID
experienced lightheadedness, asthenia, dizziness, and somnolence, adverse events also observed with either
drug alone. If the two drugs are to be used in combination, a low dose of buspirone (eg, 2.5 mg QD) is
recommended. Subsequent dose adjustment of either drug should be based on clinical assessment.

Pimozide: Pharmacokinetics of Nefazodone in "Poor Metabolizers" and Potential Interaction with Drugs that
Inhibit and/or Are Metabolized by Cytochrome P450 Isozymes.

Fluoxetine: When fluoxetine (20 mg QD) and nefazodone (200 mg BID) were administered at steady state there
were no changes in the pharmacokinetic parameters for fluoxetine or its metabolite, norfluoxetine. Similarly,
there were no changes in the pharmacokinetic parameters of nefazodone or HO-NEF; however, the mean AUC levels
of the nefazodone metabolites mCPP and triazoledione increased by 3- to 6-fold and 1.3-fold,respectively.
When a 200-mg dose of nefazodone was administered to subjects who had been receiving fluoxetine for 1 week,
there was an increased incidence of transient adverse events such as headache, lightheadedness, nausea, or
paresthesia, possibly due to the elevated mCPP levels. Patients who are switched from fluoxetine to nefazodone
without an adequate washout period may experience similar transient adverse events. The possibility of this
happening can be minimized by allowing a washout period before initiating nefazodone therapy and by reducing
the initial dose of nefazodone. Because of the long half-life of fluoxetine and its metabolites, this washout
period may range from one to several weeks depending on the dose of fluoxetine and other individual patient
variables.

Phenytoin: Pretreatment for 7 days with 200 mg BID of nefazodone had no effect on the pharmacokinetics of a
single 300-mg oral dose of phenytoin. However, due to the nonlinear pharmacokinetics of phenytoin, the failure
to observe a significant effect on the single-dose pharmacokinetics of phenytoin does not preclude the possibility
of a clinically significant interaction with nefazodone when phenytoin is dosed chronically. However, no change
in the initial dosage of phenytoin is considered necessary and any subsequent adjustment of phenytoin dosage
should be guided by usual clinical practices. Desipramine: When nefazodone (150 mg BID) and desipramine (75 mg QD)
were administered together there were no changes in the pharmacokinetics of desipramine or its metabolite,
2-hydroxy desipramine. There were also no changes in the pharmacokinetics of nefazodone or its triazoledione
metabolite, but the AUC and Cmax of mCPP increased by 44% and 48%, respectively, while the AUC of HO-NEF decreased
by 19%. No changes in doses of either nefazodone or desipramine are necessary when the two drugs are given
concomitantly. Subsequent dose adjustments should be made on the basis of clinical response.

Lithium: In 13 healthy subjects the coadministration of nefazodone (200 mg BID) with lithium (500 mg BID) for 5
days (steady-state conditions) was found to be well tolerated. When the two drugs were coadministered, there were
no changes in the steady-state pharmacokinetics of either lithium, nefazodone, or its metabolite HO-NEF; however,
there were small decreases in the steady-state plasma concentrations of two nefazodone metabolites, mCPP and
triazoledione, which are considered not to be of clinical significance. Therefore, no dosage adjustment of either
lithium or nefazodone is required when they are coadministered.

Carbamazepine: The coadministration of nefazodone (200 mg BID) for 5 days to 12 healthy subjects on carbamazepine
who had achieved steady state (200 mg BID) was found to be well tolerated. Steady-state conditions for carbamazepine,
nefazodone, and several of their metabolites were achieved by day 5 of coadministration. With coadministration of
the two drugs there were significant increases in the steady-state Cmax and AUC of carbamazepine (23% and 23%,
respectively), while the steady-state Cmax and the AUC of the carbamazepine metabolite, 10, 11 epoxycarbamazepine,
decreased by 21% and 20%, respectively. The coadministration of the two drugs significantly reduced the steady-state
Cmax and AUC of nefazodone by 86% and 93%, respec-tively.Similar reductions in the Cmax and AUC of HO-NEF were also
observed (85% and 94%),while the reductions in Cmax and AUC of mCPP and triazole-dione were more modest (13% and 44%
for the former and 28% and 57% for the latter).Due to the potential for coadministration of carbamazepine to result
in insufficient plasma nefazodone and hydroxynefazodone concentrations for achieving an antidepressant effect for
SERZONE, it is recommended that SERZONE not be used in combination with carbamazepine (see CONTRAINDICATIONS and
WARNINGS).

General Anesthetics: Little is known about the potential for interaction between nefazodone and general anesthetics;
therefore, prior to elective surgery, SERZONE should be discontinued for as long as clinically feasible.

Other CNS-Active Drugs: The use of nefazodone in combination with other CNS-Active drugs has not been systematically
evaluated. Consequently, caution is advised if concomitant administration of SERZONE (nefazodone hydrochloride) and
such drugs is required.

Cimetidine

When nefazodone (200 mg BID) and cimetidine (300 mg QID) were coadministered for one week, no change in the steady-state
pharmacokinetics of either nefazodone or cimetidine was observed compared to each dosed alone. Therefore, dosage
adjustment is not necessary for either drug when coadministered.

Theophylline

When nefazodone (200 mg BID) was given to patients being treated with theophylline (600-1200 mg/day) for chronic
obstructive pulmonary disease,there was no change in the steady-state pharmacokinetics of either nefazodone or
theophylline. FEV1 measurements taken when theophylline and nefazodone were coadministered did not differ from
baseline dosage (ie, when theophylline was administered alone).Therefore, dosage adjustment is not necessary for
either drug when coadministered.

Cardiovascular-Active Drugs

Digoxin: When nefazodone (200 mg BID) and digoxin (0.2 mg QD) were coadministered for 9 days to healthy male volunteers
(n=18) who were phenotyped as CYP2D6 extensive metabolizers, Cmax, Cmin, and AUC of digoxin were increased by 29%, 27%,
and 15%, respectively. Digoxin had no effects on the pharmacokinetics of nefazodone and its active metabolites. Because
of the narrow therapeutic index of digoxin,caution should be exercised when nefazodone and digoxin are coadministered;
plasma level monitoring for digoxin is recommended.

Propranolol: The coadministration of nefazodone (200 mg BID) and propranolol (40 mg BID) for 5.5 days to healthy male
volunteers (n=18), including 3 poor and 15 extensive CYP2D6 metabolizers, resulted in 30% and 14% reductions in Cmax
and AUC of propranolol, respectively, and a 14% reduction in Cmax for the metabolite, 4-hydroxypropranolol. The kinetics
of nefazodone, hydroxynefazodone, and triazoledione were not affected by coadministration of propranolol. However, Cmax,
Cmin, and AUC of m-chlorophenylpiperazine were increased by 23%, 54%, and 28%, respectively. No change in initial dose
of either drug is necessary and dose adjustments should be made on the basis of clinical response.

HMG-CoA Reductase Inhibitors: When single 40-mg doses of simvastatin or atorvastatin, both substrates of CYP3A4, were
given to healthy adult volunteers who had received SERZONE 200 mg BID for 6 days, approximately 20-fold increases in
plasma concentrations of simvastatin and simvastatin acid and 3- to 4-fold increases in plasma concentrations of
atorvastatin and atorvastatin lactone were seen. These effects appear to be due to the inhibition of CYP3A4 by SERZONE
because, in the same study, SERZONE had no significant effect on the plasma concentrations of pravastatin, which is not
metabolized by CYP3A4 to a clinically significant extent.

There have been rare reports of rhabdomyolysis involving patients receiving the combination of SERZONE and either
simvastatin or lovastatin, also a substrate of CYP3A4 (see ADVERSE REACTIONS: Postintroduction Clinical Experience).
Rhabdomyolysis has been observed in patients receiving HMG-CoA reductase inhibitors administered alone (at recommended
dosages) and in particular, for certain drugs in this class, when given in combination with inhibitors of the CYP3A4
isozyme.

Caution should be used if SERZONEis administered in combination with HMG-CoA reductase inhibitors that are metabolized
by CYP3A4, such as simvastatin, atorvastatin, and lovastatin, and dosage adjustments of these HMG-CoA reductase inhibitors
are recommended. Since metabolic interactions are unlikely between SERZONE and HMG-CoA reductase inhibitors that undergo
little or no metabolism by the CYP3A4 isozyme, such as pravastatin or fluvastatin, dosage adjustments should not be
necessary.

Immunosuppressive Agents

There have been reports of increased blood concentrations of cyclosporine and tacrolimus into toxic ranges when patients
received these drugs concomitantly with SERZONE. Both cyclosporine and tacrolimus are substrates of CYP3A4, and nefazodone
is known to inhibit this enzyme. If either cyclosporine or tacrolimus is administered with SERZONE, blood concentrations
of the immunosuppressive agent should be monitored and dosage adjusted accordingly.

Pharmacokinetics of Nefazodone in "Poor Metabolizers" and Potential Interaction with Drugs that Inhibit and/or Are
Metabolized by Cytochrome P450 Isozymes

CYP3A4 Isozyme: Nefazodone has been shown in vitro to be an inhibitor of CYP3A4. This is consistent with the interactions
observed between nefazodone and triazolam, alprazolam, buspirone, atorvastatin, and simvastatin, drugs metabolized by this
isozyme. Consequently, caution is indicated in the combined use of nefazodone with any drugs known to be metabolized by
CYP3A4. In particular, the combined use of nefazodone with triazolam should be avoided for most patients, including the
elderly. The combined use of nefazodone with terfenadine, astemizole, cisapride, or pimozide is contraindicated.

CYP2D6 Isozyme: A subset (3% to 10%) of the population has reduced activity of the drug-metabolizing enzyme CYP2D6. Such
individuals are referred to commonly as "poor metabolizers" of drugs such as debrisoquin, dextromethorphan, and the
tricyclic antidepressants. The pharmacokinetics of nefazodone and its major metabolites are not altered in these "poor
metabolizers." Plasma concentrations of one minor metabolite (mCPP) are increased in this population; the adjustment of
SERZONE dosage is not required when administered to "poor metabolizers." Nefazodone and its metabolites have been shown
in vitro to be extremely weak inhibitors of CYP2D6. Thus, it is not likely that nefazodone will decrease the metabolic
clearance of drugs metabolized by this isozyme.

CYP1A2 Isozyme: Nefazodone and its metabolites have been shown in vitro not to inhibit CYP1A2. Thus, metabolic interactions
between nefazodone and drugs metabolized by this isozyme are unlikely.

 

Serzone Contraindications

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.

 

Additional information about Serzone

Serzone Indication: For the treatment of depression.
Mechanism Of Action: Within the serotonergic system, nefazodone acts as an antagonist at type 2 serotonin (5-HT2) post-synaptic receptors and, like fluoxetine-type antidepressants, inhibits pre-synaptic serotonin (5-HT) reuptake. These mechanisms increase the amount of serotonin available to interact with 5-HT receptors. Within the noradrenergic system, nefazodone inhibits norepinephrine uptake minimally. Serzone also antagonizes alpha(1)-adrenergic receptors, producing sedation, muscle relaxation, and a variety of cardiovascular effects. Serzone's affinity for benzodiazepine, cholinergic, dopaminergic, histaminic, and beta or alpha(2)-adrenergic receptors is not significant.
Drug Interactions: Almotriptan Increased risk of CNS adverse effects
Eletriptan Increased risk of CNS adverse effects
Naratriptan Increased risk of CNS adverse effects
Eletriptan Increased risk of CNS adverse effects
Frovatriptan Increased risk of CNS adverse effects
Zolmitriptan Increased risk of CNS adverse effects
Rizatriptan Increased risk of CNS adverse effects
Sumatriptan Increased risk of CNS adverse effects
Triazolam Serzone increases the effect of triazolam
Trazodone This strong CYP3A4 inhibitor increases the effect and toxicity of trazodone
Tacrolimus Serzone increases the effect and toxicity of tacrolimus
Sunitinib Possible increase in sunitinib levels
St. John's Wort St. John's Wort increases the effect and toxicity of the SSRI
Pimozide Serzone increases the effect and toxicity of pimozide
Buspirone Serzone increases the effect of buspirone
Carbamazepine Serzone increases the effect of carbamazepine
Cilostazol Serzone increases the effect of cilostazol
Cisapride Serzone increases serum levels of cisapride
Eplerenone Serzone increases the effect and toxicity of eplerenone
Erlotinib This CYP3A4 inhibitor increases levels/toxicity of erlotinib
Aprepitant This CYP3A4 inhibitor increases the effect and toxicity of aprepitant
Atorvastatin Serzone increases the effect and toxicity of the statin drug
Cerivastatin Serzone increases the effect and toxicity of the statin drug
Cyclosporine The antidepressant increases the effect and toxicity of cyclosporine
Lovastatin Serzone increases the effect and toxicity of the statin drug
Simvastatin Serzone increases the effect and toxicity of the statin drug
Solifenacin This potent CYP3A4 inhibitor slows darifenacin/solifenacin metabolism
Darifenacin This potent CYP3A4 inhibitor slows darifenacin/solifenacin metabolism
Tranylcypromine Possible severe adverse reaction with this combination
Rasagiline Possible severe adverse reaction with this combination
Phenelzine Possible severe adverse reaction with this combination
Isocarboxazid Possible severe adverse reaction with this combination
Astemizole Increased risk of cardiotoxicity and arrhythmias
Loratadine Increased risk of cardiotoxicity
Terfenadine Increased risk of cardiotoxicity and arrhythmias
Tramadol Increased risk of serotonin syndrome
Sibutramine Risk of serotoninergic syndrome
Linezolid Combination associated with possible serotoninergic syndrome
Dihydroergotamine Possible ergotism and severe ischemia with this combination
Ergotamine Possible ergotism and severe ischemia with this combination
Food Interactions: Avoid alcohol.
Take this medication either consistently with or without food as instructed by your doctor.
Limit garlic, ginger, gingko, and horse chestnut.
Avoid avocado.
Generic Name: Nefazodone
Synonyms: Nefazodona [Spanish]; Nefazodone Hcl; Nefazodone Hydrochloride; Nefazodonum [Latin]
Drug Category: Antidepressants; Analgesics; Serotonin Agents
Drug Type: Small Molecule; Approved; Withdrawn

Other Brand Names containing Nefazodone: Dutonin; Serzone;
Absorption: Nefazodone is rapidly and completely absorbed. Its absolute bioavailability is low (about 20%).
Toxicity (Overdose): Cases of life-threatening hepatic failure have been reported in patients treated
with nefazodone.
Protein Binding: Greater than 99% (in vitro, human plasma proteins).
Biotransformation: Hepatic.
Half Life: 2-4 hours
Dosage Forms of Serzone: Tablet Oral
Chemical IUPAC Name: 2-[3-[4-(3-chlorophenyl)piperazin-1-yl]propyl]-5-ethyl-4-[2-(phenoxy)ethyl]-1,2,4-triazol-3-one
Chemical Formula: C25H32ClN5O2
Nefazodone on Wikipedia: https://en.wikipedia.org/wiki/Nefazodone
Organisms Affected: Humans and other mammals