Serzone

Nefazodone may cause side effects. Call your doctor if any of these symptoms are severe or do not go away:

• headache
• difficulty concentrating
• dry mouth
• heartburn
• flushing or feeling warm
• pain, burning, numbness, or tingling in the hands or feet
• constipation

Some side effects can be serious. If you experience any of the following symptoms or those listed in the IMPORTANT WARNINGS or SPECIAL PRECAUTIONS sections, call your doctor immediately:

• rash
• hives
• itching
• difficulty breathing or swallowing
• swelling of the face, throat, tongue, lips, eyes, hands, feet, ankles, or lower legs
• hoarseness
• slow heartbeat
• memory problems
• blurred vision or vision changes
• confusion
• seizures
• painful erection of the penis lasting more than 4 hours

Nefazodone may cause other side effects. Call your doctor if you have any unusual problems while you are taking this medication.

If you experience a serious side effect, you or your doctor may send a report to the Food and Drug Administration's (FDA) MedWatch Adverse Event Reporting program online (http://www.fda.gov/Safety/MedWatch) or by phone (1-800-332-1088).

Get emergency medical help if you have any of these signs of an allergic reaction: skin rash or hives; difficulty breathing; swelling of your face, lips, tongue, or throat.

Call your doctor at once if you have any new or worsening symptoms such as: mood or behavior changes, anxiety, panic attacks, trouble sleeping, or if you feel impulsive, irritable, agitated, hostile, aggressive, restless, hyperactive (mentally or physically), more depressed, or have thoughts about suicide or hurting yourself.

Stop taking nefazodone and call your doctor at once if you have a serious side effect such as:

• nausea, stomach pain, loss of appetite, itching, dark urine, clay-colored stools, jaundice (yellowing of the skin or eyes);
• confusion, hallucinations, unusual thoughts or behavior;
• seizure (convulsions);
• penis erection that is painful or lasts 4 hours or longer;
• fever, chills, body aches, flu symptoms; or
• feeling like you might pass out.

Less serious side effects may include:

• mild nausea, diarrhea, constipation;
• dizziness, drowsiness, weakness;
• sleep problems (insomnia);
• dry mouth, sore throat;
• vision problems;
• headache; or
• increased appetite.

This is not a complete list of side effects and others may occur. Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.

Medications can interact with certain foods. In some cases, this may be harmful and your doctor may advise you to avoid certain foods.

In the case of Serzone, there are no specific foods that you must exclude from your diet when receiving this medication.

Before taking Serzone, tell your doctor about all of your medical conditions. Especially tell your doctor if you:

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

Tell your doctor about all the medicines you take including prescription and non-prescription medicines, vitamins, and herbal supplements.

In deciding to use a medicine, the risks of taking the medicine must be weighed against the good it will do. This is a decision you and your doctor will make. For this medicine, the following should be considered:

Allergies

Tell your doctor if you have ever had any unusual or allergic reaction to this medicine or any other medicines. Also tell your health care professional if you have any other types of allergies, such as to foods, dyes, preservatives, or animals. For non-prescription products, read the label or package ingredients carefully.

Pediatric

Studies on nefazodone have been done only in adult patients, and there is no specific information comparing use of this medicine in children up to 18 years of age with use in other age groups.

Nefazodone must be used with caution in children with depression. Studies have shown occurrences of children thinking about suicide or attempting suicide in clinical trials for this medicine. More study is needed to be sure nefazodone is safe and effective in children.

Geriatric

The relationship of age to the effects of nefazodone has not been systematically studied in older people. However, blood levels of nefazodone have been found to be higher in older patients. An older adult may require a lower dose of nefazodone than a younger adult.

Pregnancy

Breast Feeding

Studies in women breastfeeding have demonstrated harmful infant effects. An alternative to this medication should be prescribed or you should stop breastfeeding while using this medicine.

Interactions with Medicines

Although certain medicines should not be used together at all, in other cases two different medicines may be used together even if an interaction might occur. In these cases, your doctor may want to change the dose, or other precautions may be necessary. When you are taking this medicine, it is especially important that your healthcare professional know if you are taking any of the medicines listed below. The following interactions have been selected on the basis of their potential significance and are not necessarily all-inclusive.

Using this medicine with any of the following medicines is not recommended. Your doctor may decide not to treat you with this medication or change some of the other medicines you take.

• Astemizole
• Bromopride
• Carbamazepine
• Cisapride
• Colchicine
• Conivaptan
• Dihydroergotamine
• Dronedarone
• Eletriptan
• Eliglustat
• Eplerenone
• Ergoloid Mesylates
• Ergonovine
• Ergotamine
• Flibanserin
• Furazolidone
• Isavuconazonium Sulfate
• Isocarboxazid
• Ivabradine
• Linezolid
• Lomitapide
• Lovastatin
• Lurasidone
• Maraviroc
• Methylergonovine
• Metoclopramide
• Naloxegol
• Nimodipine
• Phenelzine
• Pimozide
• Ranolazine
• Safinamide
• Silodosin
• Simvastatin
• Terfenadine
• Tolvaptan
• Triazolam
• Venetoclax

Using this medicine with any of the following medicines is usually not recommended, but may be required in some cases. If both medicines are prescribed together, your doctor may change the dose or how often you use one or both of the medicines.

• Abciximab
• Aceclofenac
• Acemetacin
• Ado-Trastuzumab Emtansine
• Alfentanil
• Almotriptan
• Amiodarone
• Amitriptyline
• Amoxapine
• Amphetamine
• Amtolmetin Guacil
• Apixaban
• Aprepitant
• Aspirin
• Atorvastatin
• Avanafil
• Axitinib
• Bedaquiline
• Benzphetamine
• Bosutinib
• Brentuximab Vedotin
• Brexpiprazole
• Brigatinib
• Bromfenac
• Bromocriptine
• Bufexamac
• Buprenorphine
• Bupropion
• Butorphanol
• Cabazitaxel
• Cabozantinib
• Calcifediol
• Cariprazine
• Celecoxib
• Ceritinib
• Choline Salicylate
• Cilostazol
• Clonixin
• Clopidogrel
• Clorgyline
• Clozapine
• Cobimetinib
• Codeine
• Crizotinib
• Cyclobenzaprine
• Dabrafenib
• Daclatasvir
• Dasatinib
• Deflazacort
• Delamanid
• Desvenlafaxine
• Dexibuprofen
• Dexketoprofen
• Dextroamphetamine
• Diclofenac
• Diflunisal
• Digoxin
• Dihydrocodeine
• Dipyridamole
• Dipyrone
• Docetaxel
• Dolasetron
• Domperidone
• Donepezil
• Doxorubicin
• Doxorubicin Hydrochloride Liposome
• Droperidol
• Droxicam
• Edoxaban
• Enzalutamide
• Eptifibatide
• Erlotinib
• Eszopiclone
• Etodolac
• Etofenamate
• Etoricoxib
• Everolimus
• Felbinac
• Fenoprofen
• Fentanyl
• Fepradinol
• Feprazone
• Floctafenine
• Flufenamic Acid
• Fluoxetine
• Flurbiprofen
• Fluticasone
• Fosaprepitant
• Granisetron
• Hydrocodone
• Hydromorphone
• Hydroxytryptophan
• Ibrutinib
• Ibuprofen
• Idelalisib
• Ifosfamide
• Iloperidone
• Indomethacin
• Iobenguane I 123
• Iproniazid
• Irinotecan
• Irinotecan Liposome
• Ivacaftor
• Ixabepilone
• Ketoconazole
• Ketoprofen
• Ketorolac
• Lapatinib
• Levomilnacipran
• Levorphanol
• Lisdexamfetamine
• Lorcaserin
• Lornoxicam
• Loxoprofen
• Lumiracoxib
• Macitentan
• Manidipine
• Meclofenamate
• Mefenamic Acid
• Meloxicam
• Meperidine
• Methadone
• Methamphetamine
• Methylene Blue
• Midostaurin
• Mifepristone
• Milnacipran
• Mirtazapine
• Moclobemide
• Morniflumate
• Morphine
• Morphine Sulfate Liposome
• Nabumetone
• Nalbuphine
• Naproxen
• Naratriptan
• Nepafenac
• Nialamide
• Nifedipine
• Niflumic Acid
• Nilotinib
• Nimesulide
• Nimesulide Beta Cyclodextrin
• Olaparib
• Oxaprozin
• Oxycodone
• Oxymorphone
• Oxyphenbutazone
• Palbociclib
• Palonosetron
• Panobinostat
• Parecoxib
• Pargyline
• Paroxetine
• Pazopanib
• Pentazocine
• Phenylbutazone
• Piketoprofen
• Pimavanserin
• Piperaquine
• Piroxicam
• Ponatinib
• Pranoprofen
• Prasugrel
• Procarbazine
• Proglumetacin
• Propyphenazone
• Proquazone
• Quetiapine
• Rasagiline
• Reboxetine
• Regorafenib
• Remifentanil
• Retapamulin
• Ribociclib
• Rivaroxaban
• Rizatriptan
• Rofecoxib
• Romidepsin
• Ruxolitinib
• Salicylic Acid
• Salmeterol
• Salsalate
• Selegiline
• Sibutramine
• Sildenafil
• Simeprevir
• Sodium Salicylate
• Sonidegib
• Sufentanil
• Sulindac
• Sumatriptan
• Sunitinib
• Suvorexant
• Tacrolimus
• Tadalafil
• Tamsulosin
• Tapentadol
• Temsirolimus
• Tenoxicam
• Thiotepa
• Tiaprofenic Acid
• Ticagrelor
• Ticlopidine
• Tirofiban
• Tolfenamic Acid
• Tolmetin
• Toloxatone
• Toremifene
• Trabectedin
• Tramadol
• Tranylcypromine
• Trazodone
• Valbenazine
• Valdecoxib
• Vemurafenib
• Venlafaxine
• Vilanterol
• Vilazodone
• Vincristine
• Vincristine Sulfate Liposome
• Vinflunine
• Vorapaxar
• Vortioxetine
• Ziprasidone
• Zolmitriptan
• Zolpidem

Using this medicine with any of the following medicines may cause an increased risk of certain side effects, but using both drugs may be the best treatment for you. If both medicines are prescribed together, your doctor may change the dose or how often you use one or both of the medicines.

• Alprazolam
• Aripiprazole Lauroxil
• Buspirone
• Cyclosporine
• Foxglove
• Ginkgo
• Haloperidol
• Methylprednisolone
• Pravastatin
• Ritonavir
• St John's Wort

Interactions with Food/Tobacco/Alcohol

Certain medicines should not be used at or around the time of eating food or eating certain types of food since interactions may occur. Using alcohol or tobacco with certain medicines may also cause interactions to occur. The following interactions have been selected on the basis of their potential significance and are not necessarily all-inclusive.

Other Medical Problems

The presence of other medical problems may affect the use of this medicine. Make sure you tell your doctor if you have any other medical problems, especially:

• Convulsions (seizures) (history of)—The risk of seizures may be increased

• Dehydration or
• Hypovolemia (low blood volume)—May increase the chance that low blood pressure (hypotension) will occur

• Heart disease or
• Stroke (or history of)—Nefazodone may make these conditions worse by causing low blood pressure (hypotension)

• Liver function problems—If your liver does not function well, due to liver problems or liver disease and you take nefazodone, the amount of nefazodone in your blood may be too high. This may cause serious disease or damage in your liver.

• Liver function problems when taking this medicine before and you had to stop taking it—You may have a greater chance of having liver problems if you take nefazodone again. Tell your doctor immediately if you have taken this medicine before.

• Mania (a type of mental illness) (history of)—Nefazodone may cause this problem to recur

Along with its needed effects, a medicine may cause some unwanted effects. Although not all of these side effects may occur, if they do occur they may need medical attention.

Check with your doctor as soon as possible if any of the following side effects occur:

• Blurred vision or other changes in vision
• clumsiness or unsteadiness
• lightheadedness or fainting
• ringing in the ears
• skin rash or itching

• Bladder pain
• bloody or cloudy
• cough or hoarseness
• diarrhea
• excessive muscle tone
• eye pain
• feeling dizzy
• frequent urge to urinate
• itching of the vagina or genital area
• muscle stiffness
• muscle tension or tightness
• nausea
• pain during sexual intercourse
• painful, burning, or difficult urination
• shortness of breath, tightness in chest, or wheezing
• stomach pain
• thick, white vaginal discharge with no odor or with a mild odor
• troubled breathing

• Asthma
• bleeding from the rectum
• bloody or black, tarry stools
• change in sexual desire or performance
• chest pain
• double vision
• dryness of eye
• ear pain
• fainting
• fast heartbeat
• fever, chills, or sore throat
• hallucinations (seeing, hearing, or feeling things that are not there)
• hives
• increased sense of hearing
• increased sensitivity to sun
• irritation or soreness of mouth
• joint or muscle pain or stiffness
• kidney stones
• large pupils of eyes
• lower back, side, or stomach pain
• menstrual changes
• mood or mental changes
• nerve pain or twitching
• pelvic pain
• problems in speaking
• problems with urination
• prolonged, painful, inappropriate penile erection
• red or irritated eyes
• sensitivity of eyes to light
• swelling of face
• swollen glands
• talking, feeling, and acting with excitement and activity you cannot control
• unusual bleeding or bruising
• unusual feeling of well-being
• unusual tiredness or weakness
• vomiting of blood or material that looks like coffee grounds

• Blistering, peeling, or loosening of skin
• light-colored stools
• confusion
• dark urine
• decreased urine output
• fever
• increased thirst
• itching
• lack of appetite
• large, hive-like swelling on face, eyelids, lips, tongue, throat, hands, legs, feet, or sex organs
• muscle pain or cramps
• muscle spasm or jerking of all extremities
• muscle stiffness
• pain, warmth, or burning in fingers, toes, and legs
• red skin lesions, often with a purple center
• sore throat
• sudden loss of consciousness
• sweating
• vomiting

Some side effects may occur that usually do not need medical attention. These side effects may go away during treatment as your body adjusts to the medicine. Also, your health care professional may be able to tell you about ways to prevent or reduce some of these side effects. Check with your health care professional if any of the following side effects continue or are bothersome or if you have any questions about them:

• Abnormal dreams
• agitation
• confusion
• constipation
• diarrhea
• dizziness
• drowsiness
• dryness of mouth
• flushing or feeling of warmth
• headache
• heartburn
• increased appetite
• increased cough
• memory problems
• nausea
• swelling of arms or legs
• tingling, burning, or prickly sensations
• tremor
• trouble in sleeping
• vomiting

• Breast pain
• generalized slowing of mental and physical activity
• increased thirst
• loss of strength or energy
• muscle weakness

• Unexpected or excess milk flow from breasts
• swelling of the breasts or breast soreness in males

Other side effects not listed may also occur in some patients. If you notice any other effects, check with your healthcare professional.

Call your doctor for medical advice about side effects. You may report side effects to the FDA at 1-800-FDA-1088.

Pharmacodynamics

The mechanism of action of nefazodone, as with other antidepressants, is unknown.

Preclinical studies have shown that nefazodone inhibits neuronal uptake of serotonin and norepinephrine.

Nefazodone occupies central 5-HT2 receptors at nanomolar concentrations, and acts as an antagonist at this receptor. 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.

Pharmacokinetics

Nefazodone hydrochloride is rapidly and completely absorbed but is subject to extensive metabolism, so that its absolute bioavailability is low, about 20%, and variable. Peak plasma concentrations occur at about one hour and the half-life of nefazodone is 2–4 hours.

Both nefazodone and its pharmacologically similar metabolite, hydroxynefazodone, exhibit nonlinear kinetics for both dose and time, with AUC and Cmax increasing more than proportionally with dose increases and more than expected upon multiple dosing over time, compared to single dosing. For example, in a multiple-dose study involving BID dosing with 50, 100, and 200 mg, the AUC for nefazodone and hydroxynefazodone increased by about 4-fold with an increase in dose from 200 to 400 mg per day; Cmax increased by about 3-fold with the same dose increase. In a multiple-dose study involving BID dosing with 25, 50, 100, and 150 mg, the accumulation ratios for nefazodone and hydroxynefazodone AUC, after 5 days of BID dosing relative to the first dose, ranged from approximately 3 to 4 at the lower doses (50–100 mg/day) and from 5 to 7 at the higher doses (200–300 mg/day); there were also approximately 2- to 4-fold increases in Cmax after 5 days of BID dosing relative to the first dose, suggesting extensive and greater than predicted accumulation of nefazodone and its hydroxy metabolite with multiple dosing. Steady-state plasma nefazodone and metabolite concentrations are attained within 4 to 5 days of initiation of BID dosing or upon dose increase or decrease.

Nefazodone is extensively metabolized after oral administration by n-dealkylation and aliphatic and aromatic hydroxylation, and less than 1% of administered nefazodone is excreted unchanged in urine. Attempts to characterize three metabolites identified in plasma, hydroxynefazodone (HO-NEF), meta-chlorophenylpiperazine (mCPP), and a triazole-dione metabolite, have been carried out. The AUC (expressed as a multiple of the AUC for nefazodone dosed at 100 mg BID) and elimination half-lives for these three metabolites were as follows:

HO-NEF possesses a pharmacological profile qualitatively and quantitatively similar to that of nefazodone. mCPP has some similarities to nefazodone, but also has agonist activity at some serotonergic receptor subtypes. The pharmacological profile of the triazole-dione metabolite has not yet been well characterized. In addition to the above compounds, several other metabolites were present in plasma but have not been tested for pharmacological activity.

After oral administration of radiolabelled nefazodone, the mean half-life of total label ranged between 11 and 24 hours. Approximately 55% of the administered radioactivity was detected in urine and about 20–30% in feces.

DistributionNefazodone is widely distributed in body tissues, including the central nervous system (CNS). In humans the volume of distribution of nefazodone ranges from 0.22 to 0.87 L/kg.

Protein BindingAt concentrations of 25–2500 ng/mL nefazodone is extensively (>99%) bound to human plasma proteins in vitro. The administration of 200 mg BID of nefazodone for 1 week did not increase the fraction of unbound warfarin in subjects whose prothrombin times had been prolonged by warfarin therapy to 120-150% of the laboratory control (see PRECAUTIONS: Drug Interactions). While nefazodone did not alter the in vitro protein binding of chlorpromazine, desipramine, diazepam, diphenylhydantoin, lidocaine, prazosin, propranolol, or verapamil, it is unknown whether displacement of either nefazodone or these drugs occurs in vivo. There was a 5% decrease in the protein binding of haloperidol; this is probably of no clinical significance.

Effect of Food Food delays the absorption of nefazodone and decreases the bioavailability of nefazodone by approximately 20%.

Renal DiseaseIn studies involving 29 renally impaired patients, renal impairment (creatinine clearances ranging from 7 to 60 mL/min/1.73m2) had no effect on steady-state nefazodone plasma concentrations.

Liver DiseaseIn a multiple-dose study of patients with liver cirrhosis, the AUC values for nefazodone and HO-NEF at steady state were approximately 25% greater than those observed in normal volunteers.

Age/Gender Effects After single doses of 300 mg to younger (18-45 years) and older patients (>65years), Cmax and AUC for nefazodone and hydroxynefazodone were up to twice as high in the older patients. With multiple doses, however, differences were much smaller, 10–20%. A similar result was seen for gender, with a higher Cmax and AUC in women after single doses but no difference after multiple doses.

Treatment with Serzone should be initiated at half the usual dose in elderly patients, especially women (see DOSAGE AND ADMINISTRATION), but the therapeutic dose range is similar in younger and older patients.

Clinical Efficacy Trial Results

During its premarketing development, the efficacy of Serzone was evaluated at doses within the therapeutic range in five well-controlled, short-term (6–8 weeks) clinical investigations. These trials enrolled outpatients meeting DSM-III or DSM-IIIR criteria for major depressive disorder. Among these trials, two demonstrated the effectiveness of Serzone, and two provided additional support for that conclusion.

One trial was a 6-week dose-titration study comparing Serzone in two dose ranges (up to 300 mg/day and up to 600 mg/day [mean modal dose for this group was about 400 mg/day], on a BID schedule) and placebo. The second trial was an 8-week dose-titration study comparing Serzone (up to 600 mg/day; mean modal dose was 375 mg/day), imipramine (up to 300 mg/day), and placebo, all on a BID schedule. Both studies demonstrated Serzone, at doses titrated between 300 mg to 600 mg/day (therapeutic dose range), to be superior to placebo on at least three of the following four measures: 17-Item Hamilton Depression Rating Scale or HDRS (total score), Hamilton Depressed Mood item, Clinical Global Impressions (CGI) Severity score, and CGI Improvement score. Significant differences were also found for certain factors of the HDRS (eg, anxiety factor, sleep disturbance factor, and retardation factor). In the two supportive studies, Serzone was titrated up to 500 or 600 mg/day (mean modal doses of 462 mg/day and 363 mg/day). In the fifth study, the differentiation in response rates between Serzone and placebo was not statistically significant. Three additional trials were conducted using subtherapeutic doses of Serzone.

Overall, approximately two thirds of patients in these trials were women, and an analysis of the effects of gender on outcome did not suggest any differential responsiveness on the basis of sex. There were too few elderly patients in these trials to reveal possible age-related differences in response.

Since its initial marketing as an antidepressant drug product, additional clinical investigations of Serzone have been conducted. These studies explored Serzone’s use under conditions not evaluated fully at the time initial marketing approval was granted.

Two studies were conducted to evaluate Serzone’s effectiveness in hospitalized patients with major depressive disorder. These were 6-week, dose-titration trials comparing Serzone (up to 600 mg/day) and placebo, on a BID schedule. In one study, Serzone was superior to placebo. In this study, the mean modal dose of Serzone was 503 mg/day, and 85% of these inpatients were melancholic; at baseline, patients were distributed at the higher end of the 7-point CGI Severity scale, as follows: 4=moderately ill (17%); 5=markedly ill (48%); 6=severely ill (32%). In the other study, the differentiation in response rates between Serzone and placebo was not statistically significant. This result may be explained by the “high” rate of spontaneous improvement among the patients randomized to placebo.

Two studies were conducted to assess Serzone’s capacity to maintain a clinical remission in acutely depressed patients who were judged to have responded adequately (HDRS total score ≤10) after a 16-week period of open treatment with Serzone (titration up to 600 mg/day). In one study, Serzone was superior to placebo. In this study, patients (n=131) were randomized to continuation on Serzone or placebo for an additional 36 weeks (1 year total). This study demonstrated a significantly lower relapse rate (HDRS total score ≥18) for patients taking Serzone compared to those on placebo. The second study was of appropriate design and power, but the sample of patients admitted for evaluation did not suffer relapses at a high enough incidence to provide a meaningful test of Serzone’s efficacy for this use.

Highly variable results have been seen in the clinical development of all antidepressant drugs. Furthermore, in those circumstances when the drugs have not been studied in the same controlled clinical trial(s), comparisons among the findings of studies evaluating the effectiveness of different antidepressant drug products are inherently unreliable. Because conditions of testing (eg, patient samples, investigators, doses of the treatments administered and compared, outcome measures, etc) vary among trials, it is virtually impossible to distinguish a difference in drug effect from a difference due to one or more of the confounding factors just enumerated.

Human Experience

In premarketing clinical studies, there were seven reports of nefazodone overdose alone or in combination with other pharmacological agents. The amount of 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 methocarbamol and alcohol; this person reportedly experienced a convulsion (type not documented). None of these patients died.

In postmarketing experience, overdose with Serzone alone and in combination with alcohol and/or other substances has been reported. Commonly reported symptoms were similar to those reported from overdose in premarketing experience. While there have been rare reports of fatalities in patients taking overdoses of nefazodone, predominantly in combination with alcohol and/or other substances, no causal relationship to nefazodone has been established.

Overdosage Management

Treatment should consist of those general measures employed in the management of overdosage with any antidepressant.

Ensure an adequate airway, oxygenation, and ventilation. Monitor cardiac rhythm and vital signs. General supportive and symptomatic measures are also recommended. Induction of emesis is not recommended. Gastric lavage with a large-bore orogastric tube with appropriate airway protection, if needed, may be indicated if performed soon after ingestion, or in symptomatic patients.

Activated charcoal should be administered. Due to the wide distribution of nefazodone in body tissues, forced diuresis, dialysis, hemoperfusion, and exchange transfusion are unlikely to be of benefit. No specific antidotes for nefazodone are known.

In managing overdosage, consider the possibility of multiple drug involvement. The physician should consider contacting a poison control center for additional information on the treatment of any overdose. Telephone numbers for certified poison control centers are listed in the Physicians’ Desk Reference (PDR).

Take Serzone exactly as directed by your doctor. If you do not understand these directions, ask your pharmacist, nurse, or doctor to explain the instructions to you.

Take each dose with a full glass of water.

Do not stop taking Serzone without first talking to your doctor. It may be several weeks before you begin to feel better, and you may require continuous treatment for quite some time.

Store Serzone at room temperature away from moisture and heat.

Do not take Serzone if you are taking any of the following drugs:

• a monoamine oxidase inhibitor (MAOI) such as isocarboxazid (Marplan), phenelzine (Nardil), or tranylcypromine (Parnate);
• terfenadine (Seldane, Seldane-D);
• astemizole (Hismanal);
• cisapride (Propulsid);
• carbamazepine (Tegretol, Tegretol XR, Epitol, Carbatrol);
• triazolam (Halcion); or
• pimozide (Orap).

These drugs can have very serious interactions with Serzone that could lead to seizures, heart damage, and even death.

Many other drugs may interact with Serzone. Talk to your doctor before taking any other medications during treatment with Serzone, especially any of the following:

• haloperidol (Haldol);
• alprazolam (Xanax);
• lorazepam (Ativan);
• cyclosporine (Neoral, Sandimmune);
• tacrolimus (Prograf);
• digoxin (Lanoxin, Lanoxicaps);
• phenytoin (Dilantin);
• warfarin (Coumadin); or
• atorvastatin (Lipitor), lovastatin (Mevacor), or simvastatin (Zocor).

You may require a dosage adjustment or special monitoring during treatment if you are taking any of these medicines.

Drugs other than those listed here may also interact with Serzone. Talk to your doctor and pharmacist before taking any prescription or over-the-counter medicines, including herbal products.

Applies to nefazodone: oral tablet

Along with its needed effects, nefazodone (the active ingredient contained in Serzone) may cause some unwanted effects. Although not all of these side effects may occur, if they do occur they may need medical attention.

Check with your doctor as soon as possible if any of the following side effects occur while taking nefazodone:

• Blurred vision or other changes in vision
• clumsiness or unsteadiness
• lightheadedness or fainting
• ringing in the ears
• skin rash or itching

• Bladder pain
• bloody or cloudy
• cough or hoarseness
• diarrhea
• excessive muscle tone
• eye pain
• feeling dizzy
• frequent urge to urinate
• itching of the vagina or genital area
• muscle stiffness
• muscle tension or tightness
• nausea
• pain during sexual intercourse
• painful, burning, or difficult urination
• shortness of breath, tightness in chest, or wheezing
• stomach pain
• thick, white vaginal discharge with no odor or with a mild odor
• troubled breathing

• Asthma
• bleeding from the rectum
• bloody or black, tarry stools
• change in sexual desire or performance
• chest pain
• double vision
• dryness of eye
• ear pain
• fainting
• fast heartbeat
• fever, chills, or sore throat
• hallucinations (seeing, hearing, or feeling things that are not there)
• hives
• increased sense of hearing
• increased sensitivity to sun
• irritation or soreness of mouth
• joint or muscle pain or stiffness
• kidney stones
• large pupils of eyes
• lower back, side, or stomach pain
• menstrual changes
• mood or mental changes
• nerve pain or twitching
• pelvic pain
• problems in speaking
• problems with urination
• prolonged, painful, inappropriate penile erection
• red or irritated eyes
• sensitivity of eyes to light
• swelling of face
• swollen glands
• talking, feeling, and acting with excitement and activity you cannot control
• unusual bleeding or bruising
• unusual feeling of well-being
• unusual tiredness or weakness
• vomiting of blood or material that looks like coffee grounds

• Blistering, peeling, or loosening of skin
• light-colored stools
• confusion
• dark urine
• decreased urine output
• fever
• increased thirst
• itching
• lack of appetite
• large, hive-like swelling on face, eyelids, lips, tongue, throat, hands, legs, feet, or sex organs
• muscle pain or cramps
• muscle spasm or jerking of all extremities
• muscle stiffness
• pain, warmth, or burning in fingers, toes, and legs
• red skin lesions, often with a purple center
• sore throat
• sudden loss of consciousness
• sweating
• vomiting

Some side effects of nefazodone may occur that usually do not need medical attention. These side effects may go away during treatment as your body adjusts to the medicine. Also, your health care professional may be able to tell you about ways to prevent or reduce some of these side effects. Check with your health care professional if any of the following side effects continue or are bothersome or if you have any questions about them:

• Abnormal dreams
• agitation
• confusion
• constipation
• diarrhea
• dizziness
• drowsiness
• dryness of mouth
• flushing or feeling of warmth
• headache
• heartburn
• increased appetite
• increased cough
• memory problems
• nausea
• swelling of arms or legs
• tingling, burning, or prickly sensations
• tremor
• trouble in sleeping
• vomiting

• Breast pain
• generalized slowing of mental and physical activity
• increased thirst
• loss of strength or energy
• muscle weakness

• Unexpected or excess milk flow from breasts
• swelling of the breasts or breast soreness in males