NEFAZODONE HYDROCHLORIDE tablet

Nefazodone Hydrochloride by

Drug Labeling and Warnings

Nefazodone Hydrochloride by is a Prescription medication manufactured, distributed, or labeled by Rebel Distributors Corp. Drug facts, warnings, and ingredients follow.

Drug Details [pdf]

Alcohol

Patients should be advised to avoid alcohol while taking nefazodone.

Allergic Reactions

Patients should be advised to notify their physician if they develop a rash, hives, or a related allergic phenomenon.

Visual Disturbances

There have been reports of visual disturbances associated with the use of nefazodone, including blurred vision, scotoma, and visual trails. Patients should be advised to notify their physician if they develop visual disturbances. (See ADVERSE REACTIONS.)

Laboratory Tests

There are no specific laboratory tests recommended.

Drug Interactions

Drugs Highly Bound to Plasma Protein

Because nefazodone is highly bound to plasma protein (see CLINICAL PHARMACOLOGY, Pharmacokinetics), administration of nefazodone 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 – See WARNINGS.

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 – See CONTRAINDICATIONS and WARNINGS.

Alcohol – Although nefazodone did not potentiate the cognitive and psychomotor effects of alcohol in experiments with normal subjects, the concomitant use of nefazodone 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 (e.g., 2.5 mg QD) is recommended. Subsequent dose adjustment of either drug should be based on clinical assessment.

Pimozide – See CONTRAINDICATIONS, WARNINGS, and PRECAUTIONS, 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 triazole-dione 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 triazole-dione 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 triazole-dione, 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%, respectively. 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 nefazodone, it is recommended that nefazodone 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, nefazodone hydrochloride 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 nefazodone 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 to 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 (i.e., 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 triazole-dione 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 nefazodone hydrochloride, 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 nefazodone because, in the same study, nefazodone 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 nefazodone 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 nefazodone is 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 nefazodone 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 nefazodone. Both cyclosporine and tacrolimus are substrates of CYP3A4, and nefazodone is known to inhibit this enzyme. If either cyclosporine or tacrolimus is administered with nefazodone, 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 (see CONTRAINDICATIONS and WARNINGS).

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 nefazodone 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.

Electroconvulsive Therapy (ECT)

There are no clinical studies of the combined use of ECT and nefazodone.

Carcinogenesis, Mutagenesis, Impairment of Fertility

Carcinogenesis

There is no evidence of carcinogenicity with nefazodone. The dietary administration of nefazodone to rats and mice for 2 years at daily doses of up to 200 mg/kg and 800 mg/kg, respectively, which are approximately 3 and 6 times, respectively, the maximum human daily dose on a mg/m2 basis, produced no increase in tumors.

Mutagenesis

Nefazodone has been shown to have no genotoxic effects based on the following assays: bacterial mutation assays, a DNA repair assay in cultured rat hepatocytes, a mammalian mutation assay in Chinese hamster ovary cells, an in vivo cytogenetics assay in rat bone marrow cells, and a rat dominant lethal study.

Impairment of Fertility

A fertility study in rats showed a slight decrease in fertility at 200 mg/kg/day (approximately three times the maximum human daily dose on a mg/m2 basis) but not at 100 mg/kg/day (approximately 1.5 times the maximum human daily dose on a mg/m2 basis).

Pregnancy

Teratogenic Effects

Pregnancy category C

Reproduction studies have been performed in pregnant rabbits and rats at daily doses up to 200 and 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 the offspring as a result of nefazodone treatment. 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 a mg/m2 basis. There are no adequate and well-controlled studies in pregnant women. Nefazodone should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus.

Labor and Delivery

The effect of nefazodone on labor and delivery in humans is unknown.

Nursing Mothers

It is 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 nefazodone is administered to a nursing woman.

Pediatric Use

Safety and effectiveness in the pediatric population have not been established (see BOXWARNING and WARNINGS, Clinical Worsening and Suicide Risk). Two placebo-controlled trials in 286 pediatric patients with MDD have been conducted with nefazodone, and the data were not sufficient to support a claim for use in pediatric patients. Anyone considering the use of nefazodone hydrochloride tablets in a child or adolescent must balance the potential risks with the clinical need.

Geriatric Use

Of the approximately 7000 patients in clinical studies who received nefazodone for the treatment of depression, 18% were 65 years and older, while 5% were 75 years and older. Based on monitoring of adverse events, vital signs, electrocardiograms, and results of laboratory tests, no overall differences in safety between elderly and younger patients were observed in clinical studies. Efficacy in the elderly has not been demonstrated in placebo-controlled trials. Other reported clinical experience has not identified differences in responses between elderly and younger patients, but greater sensitivity of some older individuals cannot be ruled out.

Due to the increased systemic exposure to nefazodone seen in single-dose studies in elderly patients (see CLINICAL PHARMACOLOGY, Pharmacokinetics), treatment should be initiated at half the usual dose, but titration upward should take place over the same range as in younger patients (see DOSAGE AND ADMINISTRATION). The usual precautions should be observed in elderly patients who have concomitant medical illnesses or who are receiving concomitant drugs.

  • ADVERSE REACTIONS

    Associated with Discontinuation of Treatment

    Approximately 16% of the 3496 patients who received nefazodone in worldwide premarketing clinical trials discontinued treatment due to an adverse experience. The more common (³ 1%) events in clinical trials associated with discontinuation and considered to be drug related (i.e., those events associated with dropout at a rate approximately twice or greater for nefazodone compared to placebo) included: nausea (3.5%), dizziness (1.9%), insomnia (1.5%), asthenia (1.3%), and agitation (1.2%).

    Incidence in Controlled Trials

    Commonly Observed Adverse Events in Controlled Clinical Trials

    The most commonly observed adverse events associated with the use of nefazodone (incidence of 5% or greater) and not seen at an equivalent incidence among placebo-treated patients (i.e., significantly higher incidence for nefazodone compared to placebo, p ≤ 0.05), derived from the table below, were: somnolence, dry mouth, nausea, dizziness, constipation, asthenia, lightheadedness, blurred vision, confusion, and abnormal vision.

    Adverse Events Occurring at an Incidence of 1% or More Among Nefazodone-Treated Patients

    The table that follows enumerates adverse events that occurred at an incidence of 1% or more, and were more frequent than in the placebo group, among nefazodone-treated patients who participated in short-term (6 to 8 week) placebo-controlled trials in which patients were dosed with nefazodone to ranges of 300 to 600 mg/day. This table shows the percentage of patients in each group who had at least one episode of an event at some time during their treatment. Reported adverse events were classified using standard COSTART-based Dictionary terminology.

    The prescriber should be aware that these figures cannot be used to predict the incidence of side effects in the course of usual medical practice where patient characteristics and other factors differ from those which prevailed in the clinical trials. Similarly, the cited frequencies cannot be compared with figures obtained from other clinical investigations involving different treatments, uses, and investigators. The cited figures, however, do provide the prescribing physician with some basis for estimating the relative contribution of drug and nondrug factors to the side-effect incidence rate in the population studied.

    Treatment-Emergent Adverse Experience Incidence in 6 to 8 Week Placebo-Controlled Clinical Trials, Nefazodone 300 to 600 mg/day Dose Range
    Percent of Patients
    Body SystemPreferred TermNefazodone (n = 393)Placebo (n = 394)
    Body as a WholeHeadache3633
    Asthenia115
    Infection86
    Flu syndrome32
    Chills21
    Fever21
    Neck rigidity10
    CardiovascularPostural hypotension41
    Hypotension21
    DermatologicalPruritus21
    Rash21
    GastrointestinalDry mouth2513
    Nausea2212
    Constipation148
    Dyspepsia97
    Diarrhea87
    Increased appetite53
    Nausea & vomiting21
    MetabolicPeripheral edema32
    Thirst1< 1
    MusculoskeletalArthralgia1< 1
    NervousSomnolence2514
    Dizziness175
    Insomnia119
    Lightheadedness103
    Confusion72
    Memory impairment42
    Paresthesia42
    Vasodilatation42
    Abnormal dreams32
    Concentration decreased31
    Ataxia20
    Incoordination21
    Psychomotor retardation21
    Tremor21
    Hypertonia10
    Libido decreased1< 1
    RespiratoryPharyngitis65
    Cough increased31
    Special SensesBlurred vision93
    Abnormal vision71
    Tinnitus21
    Taste perversion21
    Visual field defect20
    UrogenitalUrinary frequency21
    Urinary tract infection21
    Urinary retention21
    Vaginitis21
    Breast pain1< 1

    Dose Dependency of Adverse Events

    The table that follows enumerates adverse events that were more frequent in the nefazodone dose range of 300 to 600 mg/day than in the nefazodone dose range of up to 300 mg/day. This table shows only those adverse events for which there was a statistically significant difference (p ≤ 0.05) in incidence between the nefazodone dose ranges as well as a difference between the high dose range and placebo.

    Dose Dependency of Adverse Events in Placebo-Controlled Trials
    Percent of Patients
    Body SystemPreferred TermNefazodone 300 to 600 mg/day (n = 209)Nefazodone ≤ 300 mg/day   (n = 211)Placebo (n = 212)
    GastrointestinalNausea231412
    Constipation17109
    NervousSomnolence281613
    Dizziness22114
    Confusion821
    Special SensesAbnormal Vision1002
    Blurred Vision932
    Tinnitus301

    Visual Disturbances

    In controlled clinical trials, blurred vision occurred in 9% of nefazodone-treated patients compared to 3% of placebo-treated patients. In these same trials abnormal vision, including scotomata and visual trails, occurred in 7% of nefazodone-treated patients compared to 1% of placebo-treated (see Treatment-Emergent Adverse Experience table, above). Dose-dependency was observed for these events in these trials, with none of the scotomata and visual trails at doses below 300 mg/day. However, scotomata and visual trails observed at doses below 300 mg/day have been reported in postmarketing experience with nefazodone. (See PRECAUTIONS, Information for Patients.)

    Vital Sign Changes

    (See PRECAUTIONS, Postural Hypotension.)

    Weight Changes

    In a pooled analysis of placebo-controlled premarketing studies, there were no differences between nefazodone and placebo groups in the proportions of patients meeting criteria for potentially important increases or decreases in body weight (a change of ≥ 7%).

    Laboratory Changes

    Of the serum chemistry, serum hematology, and urinalysis parameters monitored during placebo-controlled premarketing studies with nefazodone, a pooled analysis revealed a statistical trend between nefazodone and placebo for hematocrit, i.e., 2.8% of nefazodone patients met criteria for a potentially important decrease in hematocrit (≤ 37% male or ≤ 32% female) compared to 1.5% of placebo patients (0.05 < p ≤ 0.10). Decreases in hematocrit, presumably dilutional, have been reported with many other drugs that block alpha1-adrenergic receptors. There was no apparent clinical significance of the observed changes in the few patients meeting these criteria.

    ECG Changes

    Of the ECG parameters monitored during placebo-controlled premarketing studies with nefazodone, a pooled analysis revealed a statistically significant difference between nefazodone and placebo for sinus bradycardia, i.e., 1.5% of nefazodone patients met criteria for a potentially important decrease in heart rate (≤ 50 bpm and a decrease of ≥ 15 bpm) compared to 0.4% of placebo patients (p < 0.05). There was no obvious clinical significance of the observed changes in the few patients meeting these criteria.

    Other Events Observed During the Premarketing Evaluation of Nefazodone

    During its premarketing assessment, multiple doses of nefazodone were administered to 3496 patients in clinical studies, including more than 250 patients treated for at least one year. The conditions and duration of exposure to nefazodone varied greatly, and included (in overlapping categories) open and double-blind studies, uncontrolled and controlled studies, inpatient and outpatient studies, fixed-dose and titration studies. Untoward events associated with this exposure were recorded by clinical investigators using terminology of their own choosing. Consequently, it is not possible to provide a meaningful estimate of the proportion of individuals experiencing adverse events without first grouping similar types of untoward events into a smaller number of standardized event categories.

    In the tabulations that follow, reported adverse events were classified using standard COSTART-based Dictionary terminology. The frequencies presented, therefore, represent the proportion of the 3496 patients exposed to multiple doses of nefazodone who experienced an event of the type cited on at least one occasion while receiving nefazodone. All reported events are included except those already listed in the Treatment-Emergent Adverse Experience Incidence table, those events listed in other safety-related sections of this insert, those adverse experiences subsumed under COSTART terms that are either overly general or excessively specific so as to be uninformative, those events for which a drug cause was very remote, and those events which were not serious and occurred in fewer than two patients.

    It is important to emphasize that, although the events reported occurred during treatment with nefazodone, they were not necessarily caused by it.

    Events are further categorized by body system and listed in order of decreasing frequency according to the following definitions: frequent adverse events are those occurring on one or more occasions in at least 1/100 patients (only those not already listed in the tabulated results from placebo-controlled trials appear in this listing); infrequent adverse events are those occurring in 1/100 to 1/1000 patients; rare events are those occurring in fewer than 1/1000 patients.

    Body as a whole – Infrequent: allergic reaction, malaise, photosensitivity reaction, face edema, hangover effect, abdomen enlarged, hernia, pelvic pain, and halitosis. Rare: cellulitis.

    Cardiovascular system – Infrequent: tachycardia, hypertension, syncope, ventricular extrasystoles, and angina pectoris. Rare: AV block, congestive heart failure, hemorrhage, pallor, and varicose vein.

    Dermatological system – Infrequent: dry skin, acne, alopecia, urticaria, maculopapular rash, vesiculobullous rash, and eczema.

    Gastrointestinal system – Frequent: gastroenteritis. Infrequent: eructation, periodontal abscess, abnormal liver function tests, gingivitis, colitis, gastritis, mouth ulceration, stomatitis, esophagitis, peptic ulcer, and rectal hemorrhage. Rare: glossitis, hepatitis, dysphagia, gastrointestinal hemorrhage, oral moniliasis, and ulcerative colitis.

    Hemic and lymphatic system – Infrequent: ecchymosis, anemia, leukopenia, and lymphadenopathy.

    Metabolic and nutritional system – Infrequent: weight loss, gout, dehydration, lactic dehydrogenase increased, SGOT increased, and SGPT increased. Rare: hypercholesteremia and hypoglycemia.

    Musculoskeletal system – Infrequent: arthritis, tenosynovitis, muscle stiffness, and bursitis. Rare: tendinous contracture.

    Nervous system – Infrequent: vertigo, twitching, depersonalization, hallucinations, suicide attempt, apathy, euphoria, hostility, suicidal thoughts, abnormal gait, thinking abnormal, attention decreased, derealization, neuralgia, paranoid reaction, dysarthria, increased libido, suicide, and myoclonus. Rare: hyperkinesia, increased salivation, cerebrovascular accident, hyperesthesia, hypotonia, ptosis, and neuroleptic malignant syndrome.

    Respiratory system – Frequent: dyspnea and bronchitis. Infrequent: asthma, pneumonia, laryngitis, voice alteration, epistaxis, hiccup. Rare: hyperventilation and yawn.

    Special senses – Frequent: eye pain. Infrequent: dry eye, ear pain, abnormality of accommodation, diplopia, conjunctivitis, mydriasis, keratoconjunctivitis, hyperacusis, and photophobia. Rare: deafness, glaucoma, night blindness, and taste loss.

    Urogenital system – Frequent: impotencea8. Infrequent: cystitis, urinary urgency, metrorrhagiaa9, amenorrheaa10, polyuria, vaginal hemorrhagea11, breast enlargementa12, menorrhagiaa13, urinary incontinence, abnormal ejaculationa14, hematuria, nocturia, and kidney calculus. Rare: uterine fibroids enlargeda15, uterine hemorrhagea16, anorgasmia, and oliguria.

    17

  • 8

    a Adjusted for gender.

  • 9

    a Adjusted for gender.

  • 10

    a Adjusted for gender.

  • 11

    a Adjusted for gender.

  • 12

    a Adjusted for gender.

  • 13

    a Adjusted for gender.

  • 14

    a Adjusted for gender.

  • 15

    a Adjusted for gender.

  • 16

    a Adjusted for gender.

  • 17

    a Adjusted for gender.

    • Postintroduction Clinical Experience

    Postmarketing experience with nefazodone has shown an adverse experience profile similar to that seen during the premarketing evaluation of nefazodone. Voluntary reports of adverse events temporally associated with nefazodone have been received since market introduction that are not listed above and for which a causal relationship has not been established. These include:

    Anaphylactic reactions; angioedema; convulsions (including grand mal seizures); galactorrhea; gynecomastia (male); hyponatremia; liver necrosis and liver failure, in some cases leading to liver transplantation and/or death (see WARNINGS); priapism (see PRECAUTIONS); prolactin increased; rhabdomyolysis involving patients receiving the combination of nefazodone and lovastatin or simvastatin (see PRECAUTIONS); serotonin syndrome; and Stevens-Johnson syndrome; and thrombocytopenia.

  • DRUG ABUSE AND DEPENDENCE

    Controlled Substance Class

    Nefazodone is not a controlled substance.

    Physical and Psychological Dependence

    In animal studies, nefazodone did not act as a reinforcer for intravenous self-administration in monkeys trained to self-administer cocaine, suggesting no abuse liability. In a controlled study of abuse liability in human subjects, nefazodone showed no potential for abuse.

    Nefazodone has not been systematically studied in humans for its potential for tolerance, physical dependence, or withdrawal. While the premarketing clinical experience with nefazodone did not reveal any tendency for a withdrawal syndrome or any drug-seeking behavior, it is not possible to predict on the basis of this limited experience the extent to which a CNS-active drug will be misused, diverted, and/or abused once marketed. Consequently, physicians should carefully evaluate patients for a history of drug abuse and follow such patients closely, observing them for signs of misuse or abuse of nefazodone (e.g., development of tolerance, dose escalation, drug-seeking behavior).

  • OVERDOSAGE

    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 to 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 nefazodone 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).

  • DOSAGE AND ADMINISTRATION

    When deciding among the alternative treatments available for depression, the prescriber should consider the risk of hepatic failure associated with nefazodone hydrochloride treatment (see WARNINGS).

    Initial Treatment

    The recommended starting dose for nefazodone hydrochloride tablets is 200 mg/day, administered in two divided doses (BID). In the controlled clinical trials establishing the antidepressant efficacy of 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 their dose increased. Dose increases should occur in increments of 100 mg/day to 200 mg/day, again on a BID 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 initial dose for elderly or debilitated patients is 100 mg/day, administered in two divided doses (BID). These patients often have reduced 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 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 patient should be treated with nefazodone. It is generally agreed, however, that pharmacological treatment for acute episodes of depression should continue for up to 6 months or longer. Whether the dose of antidepressant needed to induce remission is identical to the dose needed to maintain euthymia is unknown. Systematic evaluation of the efficacy of nefazodone has shown that efficacy is maintained for periods of up to 36 weeks following 16 weeks of open-label acute treatment (treated for 52 weeks total) at dosages that averaged 438 mg/day. For most patients, their maintenance dose was that associated with response during acute treatment. (See CLINICAL PHARMACOLOGY.) The safety of 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.

    Switching Patients to or from a Monoamine Oxidase Inhibitor

    At least 14 days should elapse between discontinuation of an MAOI and initiation of therapy with nefazodone. In addition, at least 7 days should be allowed after stopping nefazodone before starting an MAOI.

  • HOW SUPPLIED

    Nefazodone hydrochloride tablets, 100 mg, are white to off-white, capsule-shaped tablets, debossed “1024” on one side and scored on the other side with a debossed “93” on one side of the score. They are available in bottles of 60. NDC: 21695-174-60

    Nefazodone hydrochloride tablets, 150 mg, are peach (mottled), capsule-shaped tablets, debossed “7113” on one side and scored on the other side with a debossed “93” on one side of the score. They are available in bottles of 60 NDC: 21695-175-60.

    Nefazodone hydrochloride tablets, 200 mg, are light-yellow to yellow (mottled), capsule-shaped tablets, debossed “1025” on one side and debossed “93” on the other side. They are available in bottles of 30 NDC: 21695-176-30 and bottles of 60 NDC: 21695-176-60

    Nefazodone hydrochloride tablets, 250 mg, are white to off-white, capsule-shaped tablets, debossed “1026” on one side and debossed “93” on the other side. They are available in bottles of 30 NDC: 21695-177-30 and bottles of 60 NDC: 21695-177-60

    Store at 20° to 25°C (68° to 77°F) [See USP Controlled Room Temperature].

    Dispense in a tight, light-resistant container as defined in the USP, with a child-resistant closure (as required).

  • REFERENCES

    18

    19

    20

    21

    22

  • 18

    1 HALCION® and XANAX® are registered trademarks of Pharmacia & Upjohn.

  • 19

    2 SELDANE® is a registered trademark of Hoechst Marion Roussel Inc. (now Aventis Pharmaceuticals).

  • 20

    3 HISMANAL® and PROPULSID® are registered trademarks of Janssen Pharmaceutica Products, L.P.

  • 21

    4 ORAP® is a registered trademark of Gate Pharmaceuticals, a division of Teva Pharmaceuticals USA.

  • 22

    5 TEGRETOL® is a registered trademark of Novartis Pharmaceuticals Corporation.

  • PATIENT INFORMATION

    NEFAZODONE HYDROCHLORIDE TABLETS

    Read this information completely before using nefazodone. Read the information each time you get more medicine. There may be new information. This leaflet provides a summary about nefazodone 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.

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

    Rarely, people who take nefazodone can develop serious liver problems. If you get any of the following symptoms while taking nefazodone, 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 nefazodone.

    What is nefazodone?

    Nefazodone is a medicine used to treat depression. Nefazodone 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 nefazodone?

    Do not take nefazodone if you

    • are allergic to nefazodone 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 nefazodone?

    • Take nefazodone at the same time every day exactly as prescribed by your doctor. You may take nefazodone with or without food.
    • It may take a while for you to feel that nefazodone is working. You may not feel the full effect for several weeks. Once you feel better, it is important to keep taking nefazodone as directed by your doctor.
    • If you miss a dose of nefazodone, 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 nefazodone than prescribed, contact your doctor, local poison control center, or emergency room right away.

    What should I avoid while taking nefazodone?

    • 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 nefazodone affects you.
    • Before taking nefazodone, 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 nefazodone works and should not be used in combination without talking to your doctor.
    • Do not drink alcoholic beverages while taking nefazodone.
    • Tell your doctor if you are pregnant, planning to become pregnant, or become pregnant while taking nefazodone. It is not known whether nefazodone can harm your unborn baby.
    • Talk with your doctor before taking nefazodone if you are breast-feeding. It is not known whether nefazodone can pass through your breast milk to the baby.

    What are the possible side effects of nefazodone?

    The most common side effects of nefazodone 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 nefazodone without talking with your doctor first.

    Medicines are sometimes prescribed for conditions that are not mentioned in patient information leaflets. Your doctor has prescribed nefazodone for you and you alone. Do not give nefazodone 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 nefazodone. If you would like more information, talk with your doctor or pharmacist. You can ask for information about nefazodone that is written for healthcare professionals.

    Seldane® is a registered trademark of Hoechst Marion Roussel Inc. (now Aventis Pharmaceuticals).

    Hismanal® and Propulsid® are registered trademarks of Janssen Pharmaceutica Products, L.P.

    Nardil® is a registered trademark of Parke-Davis.

    Parnate® is a registered trademark of SmithKline Beecham Pharmaceuticals.

    Halcion® is a registered trademark of Pharmacia & Upjohn.

    Orap® is a registered trademark of Gate Pharmaceuticals, a division of TEVA Pharmaceuticals USA.

    Tegretol® is a registered trademark of Novartis Pharmaceuticals Corporation.

  • 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 (see Section 3)

    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 (see section below).

    Of all the antidepressants, only fluoxetine (Prozac®)*23 has been FDA approved to treat pediatric depression.

    For obsessive compulsive disorder in children and teenagers, FDA has approved only fluoxetine (Prozac®)*24, sertraline (Zoloft®)*25, fluvoxamine, and clomipramine (Anafranil®)*26.

    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.

    27

    28

    29

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

    Manufactured In Israel By:

    TEVA PHARMACEUTICAL IND. LTD.

    Jerusalem, 91010, Israel

    Manufactured For:

    TEVA PHARMACEUTICALS USA

    Sellersville, PA 18960

    Rev. G 2/2005

    Repackaged by:

    Rebel Distributors Corp

    Thousand Oaks, CA 91320

  • 23

    * Prozac® is a registered trademark of Eli Lilly and Company.

  • 24

    * Prozac® is a registered trademark of Eli Lilly and Company.

  • 25

    * Zoloft® is a registered trademark of Pfizer Pharmaceuticals.

  • 26

    * Anafranil® is a registered trademark of Mallinckrodt Inc.

  • 27

    * Prozac® is a registered trademark of Eli Lilly and Company.

  • 28

    * Zoloft® is a registered trademark of Pfizer Pharmaceuticals.

  • 29

    * Anafranil® is a registered trademark of Mallinckrodt Inc.

  • Principal Display Panel

    Nefazodone HCl 100mg

  • Principal Display Panel

    Nefazodone HCl 150mg

  • Principal Display Panel

    Nefazodone HCl 200mg

  • Principal Display Panel

    Nefazodone HCl 200mg

  • INGREDIENTS AND APPEARANCE
    NEFAZODONE HYDROCHLORIDE 
    nefazodone hydrochloride tablet
    Product Information
    Product TypeHUMAN PRESCRIPTION DRUGItem Code (Source)NDC: 21695-176(NDC:0093-1025)
    Route of AdministrationORAL
    Active Ingredient/Active Moiety
    Ingredient NameBasis of StrengthStrength
    nefazodone hydrochloride (UNII: 27X63J94GR) (nefazodone - UNII:59H4FCV1TF) nefazodone hydrochloride200 mg
    Inactive Ingredients
    Ingredient NameStrength
    SILICON DIOXIDE (UNII: ETJ7Z6XBU4)  
    magnesium stearate (UNII: 70097M6I30)  
    CELLULOSE, MICROCRYSTALLINE (UNII: OP1R32D61U)  
    SODIUM STARCH GLYCOLATE TYPE A POTATO (UNII: 5856J3G2A2)  
    POVIDONE (UNII: FZ989GH94E)  
    FERRIC OXIDE YELLOW (UNII: EX438O2MRT)  
    Product Characteristics
    ColorYELLOW (light yellow to yellow (mottled)) Scoreno score
    ShapeOVAL (capsule-shaped) Size16mm
    FlavorImprint Code 1025;93
    Contains    
    Packaging
    #Item CodePackage DescriptionMarketing Start DateMarketing End Date
    1NDC: 21695-176-3030 in 1 BOTTLE
    2NDC: 21695-176-6060 in 1 BOTTLE
    Marketing Information
    Marketing CategoryApplication Number or Monograph CitationMarketing Start DateMarketing End Date
    ANDAANDA07603709/16/2003
    NEFAZODONE HYDROCHLORIDE 
    nefazodone hydrochloride tablet
    Product Information
    Product TypeHUMAN PRESCRIPTION DRUGItem Code (Source)NDC: 21695-177(NDC:0093-1026)
    Route of AdministrationORAL
    Active Ingredient/Active Moiety
    Ingredient NameBasis of StrengthStrength
    nefazodone hydrochloride (UNII: 27X63J94GR) (nefazodone - UNII:59H4FCV1TF) nefazodone hydrochloride250 mg
    Inactive Ingredients
    Ingredient NameStrength
    SILICON DIOXIDE (UNII: ETJ7Z6XBU4)  
    magnesium stearate (UNII: 70097M6I30)  
    CELLULOSE, MICROCRYSTALLINE (UNII: OP1R32D61U)  
    SODIUM STARCH GLYCOLATE TYPE A POTATO (UNII: 5856J3G2A2)  
    POVIDONE (UNII: FZ989GH94E)  
    Product Characteristics
    ColorWHITE (white to off-white) Scoreno score
    ShapeOVAL (capsule-shaped) Size16mm
    FlavorImprint Code 1026;93
    Contains    
    Packaging
    #Item CodePackage DescriptionMarketing Start DateMarketing End Date
    1NDC: 21695-177-3030 in 1 BOTTLE
    2NDC: 21695-177-6060 in 1 BOTTLE
    Marketing Information
    Marketing CategoryApplication Number or Monograph CitationMarketing Start DateMarketing End Date
    ANDAANDA07603709/16/2003
    NEFAZODONE HYDROCHLORIDE 
    nefazodone hydrochloride tablet
    Product Information
    Product TypeHUMAN PRESCRIPTION DRUGItem Code (Source)NDC: 21695-175(NDC:0093-7113)
    Route of AdministrationORAL
    Active Ingredient/Active Moiety
    Ingredient NameBasis of StrengthStrength
    nefazodone hydrochloride (UNII: 27X63J94GR) (nefazodone - UNII:59H4FCV1TF) nefazodone hydrochloride150 mg
    Inactive Ingredients
    Ingredient NameStrength
    SILICON DIOXIDE (UNII: ETJ7Z6XBU4)  
    magnesium stearate (UNII: 70097M6I30)  
    CELLULOSE, MICROCRYSTALLINE (UNII: OP1R32D61U)  
    SODIUM STARCH GLYCOLATE TYPE A POTATO (UNII: 5856J3G2A2)  
    POVIDONE (UNII: FZ989GH94E)  
    FERRIC OXIDE RED (UNII: 1K09F3G675)  
    FERRIC OXIDE YELLOW (UNII: EX438O2MRT)  
    Product Characteristics
    ColorORANGE (peach (mottled)) Score2 pieces
    ShapeOVAL (capsule-shaped) Size14mm
    FlavorImprint Code 7113;93
    Contains    
    Packaging
    #Item CodePackage DescriptionMarketing Start DateMarketing End Date
    1NDC: 21695-175-6060 in 1 BOTTLE
    Marketing Information
    Marketing CategoryApplication Number or Monograph CitationMarketing Start DateMarketing End Date
    ANDAANDA07603709/16/2003
    NEFAZODONE HYDROCHLORIDE 
    nefazodone hydrochloride tablet
    Product Information
    Product TypeHUMAN PRESCRIPTION DRUGItem Code (Source)NDC: 21695-174(NDC:0093-1024)
    Route of AdministrationORAL
    Active Ingredient/Active Moiety
    Ingredient NameBasis of StrengthStrength
    nefazodone hydrochloride (UNII: 27X63J94GR) (nefazodone - UNII:59H4FCV1TF) nefazodone hydrochloride100 mg
    Inactive Ingredients
    Ingredient NameStrength
    SILICON DIOXIDE (UNII: ETJ7Z6XBU4)  
    magnesium stearate (UNII: 70097M6I30)  
    CELLULOSE, MICROCRYSTALLINE (UNII: OP1R32D61U)  
    SODIUM STARCH GLYCOLATE TYPE A POTATO (UNII: 5856J3G2A2)  
    POVIDONE (UNII: FZ989GH94E)  
    Product Characteristics
    ColorWHITE (white to off-white) Score2 pieces
    ShapeOVAL (capsule-shaped) Size12mm
    FlavorImprint Code 1024;93
    Contains    
    Packaging
    #Item CodePackage DescriptionMarketing Start DateMarketing End Date
    1NDC: 21695-174-6060 in 1 BOTTLE
    Marketing Information
    Marketing CategoryApplication Number or Monograph CitationMarketing Start DateMarketing End Date
    ANDAANDA07603709/16/2003
    Labeler - Rebel Distributors Corp (118802834)
    Establishment
    NameAddressID/FEIBusiness Operations
    Rebel Distributors Corp118802834RELABEL, REPACK
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