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Serzone (Nefazodone Hydrochloride) - Side Effects and Adverse Reactions

 
 



ADVERSE REACTIONS

Associated with Discontinuation of Treatment

Approximately 16% of the 3496 patients who received SERZONE (nefazodone hydrochloride) in worldwide premarketing clinical trials discontinued treatment due to an adverse experience. The more common (≥1%) events in clinical trials associated with discontinuation and considered to be drug related (ie, those events associated with dropout at a rate approximately twice or greater for SERZONE 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 SERZONE (incidence of 5% or greater) and not seen at an equivalent incidence among placebo-treated patients (ie, significantly higher incidence for SERZONE 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 SERZONE-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 SERZONE-treated patients who participated in short-term (6- to 8-week) placebo-controlled trials in which patients were dosed with SERZONE (nefazodone hydrochloride) 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 Trials1, SERZONE 300 to 600 mg/day Dose Range
Percent of Patients
Body SystemPreferred TermSERZONE
(n=393)
Placebo
(n=394)
1 Events reported by at least 1% of patients treated with SERZONE and more frequent than the placebo group are included; incidence is rounded to the nearest 1% (<1% indicates an incidence less than 0.5%). Events for which the SERZONE incidence was equal to or less than placebo are not listed in the table, but included the following: abdominal pain, pain, back pain, accidental injury, chest pain, neck pain, palpitation, migraine, sweating, flatulence, vomiting, anorexia, tooth disorder, weight gain, edema, myalgia, cramp, agitation, anxiety, depression, hypesthesia, CNS stimulation, dysphoria, emotional lability, sinusitis, rhinitis, dysmenorrhea4, dysuria.
2 Vasodilatation—flushing, feeling warm.
3 Abnormal vision—scotoma, visual trails.
4 Incidence adjusted for gender.
Body as a WholeHeadache3633
Asthenia115
Infection86
Flu syndrome32
Chills21
Fever21
Neck rigidity10
CardiovascularPostural hypotension41
Hypotension21
DermatologicalPruritus21
Rash21
GastrointestinalDry mouth2513
Nausea2212
Constipation148
Dyspepsia97
Diarrhea87
Increased appetite5 3
Nausea & vomiting21
MetabolicPeripheral edema32
Thirst1<1
MusculoskeletalArthralgia1<1
NervousSomnolence2514
Dizziness175
Insomnia119
Lightheadedness103
Confusion72
Memory impairment42
Paresthesia42
Vasodilatation242
Abnormal dreams32
Concentration decreased31
Ataxia20
Incoordination 21
Psychomotor retardation21
Tremor21
Hypertonia10
Libido decreased1<1
Respiratory Pharyngitis65
Cough increased31
Special SensesBlurred vision93
Abnormal vision371
Tinnitus21
Taste perversion21
Visual field defect20
UrogenitalUrinary frequency21
Urinary tract infection21
Urinary retention21
Vaginitis421
Breast pain41<1

Dose Dependency of Adverse Events

The table that follows enumerates adverse events that were more frequent in the SERZONE (nefazodone hydrochloride) dose range of 300 to 600 mg/day than in the SERZONE 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 SERZONE dose ranges as well as a difference between the high dose range and placebo.

Dose Dependency of Adverse Events in Placebo-Controlled Trials1
Percent of Patients
Body System Preferred Term SERZONE
300–600 mg/day
(n=209)
SERZONE
≤300 mg/day
(n=211)
Placebo

(n=212)
1Events for which there was a statistically significant difference (p≤0.05) between the nefazodone dose groups.
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 SERZONE. (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, ie, 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, ie, 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 SERZONE

During its premarketing assessment, multiple doses of SERZONE (nefazodone hydrochloride) 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 SERZONE 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 SERZONE who experienced an event of the type cited on at least one occasion while receiving SERZONE. 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 SERZONE, 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: impotence.a Infrequent: cystitis, urinary urgency, metrorrhagiaa, amenorrheaa, polyuria, vaginal hemorrhagea, breast enlargementa, menorrhagiaa, urinary incontinence, abnormal ejaculationa, hematuria, nocturia, and kidney calculus. Rare: uterine fibroids enlargeda, uterine hemorrhagea, anorgasmia, and oliguria.

aAdjusted for gender.

Postintroduction Clinical Experience

Postmarketing experience with SERZONE has shown an adverse experience profile similar to that seen during the premarketing evaluation of nefazodone. Voluntary reports of adverse events temporally associated with SERZONE 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 SERZONE and lovastatin or simvastatin (see PRECAUTIONS); serotonin syndrome; Stevens-Johnson syndrome; and thrombocytopenia.



REPORTS OF SUSPECTED SERZONE SIDE EFFECTS / ADVERSE REACTIONS

Below is a sample of reports where side effects / adverse reactions may be related to Serzone. The information is not vetted and should not be considered as verified clinical evidence.

Possible Serzone side effects / adverse reactions in 30 year old male

Reported by a consumer/non-health professional from United States on 2011-12-23

Patient: 30 year old male weighing 133.8 kg (294.4 pounds)

Reactions: Weight Increased, Activities of Daily Living Impaired, Depressed Level of Consciousness, Suicide Attempt, Withdrawal Syndrome

Adverse event resulted in: life threatening event, hospitalization, disablity

Suspect drug(s):
Serzone

Other drugs received by patient: Klonopin; Paxil; Risperdal



Possible Serzone side effects / adverse reactions in 47 year old female

Reported by a physician from United States on 2012-02-27

Patient: 47 year old female weighing 142.0 kg (312.4 pounds)

Reactions: Acute Hepatic Failure, Mental Status Changes

Adverse event resulted in: hospitalization

Suspect drug(s):
Serzone

Other drugs received by patient: Ultram; Ibuprofen Tablets



Possible Serzone side effects / adverse reactions in 53 year old male

Reported by a consumer/non-health professional from United States on 2012-03-26

Patient: 53 year old male weighing 81.6 kg (179.6 pounds)

Reactions: Tinnitus

Suspect drug(s):
Serzone
    Dosage: 100.0 mg
    Administration route: Oral
    Indication: Obsessive-Compulsive Disorder
    Start date: 2001-11-05
    End date: 2001-11-17

Serzone
    Dosage: 100.0 mg
    Administration route: Oral
    Indication: Depression
    Start date: 2001-11-05
    End date: 2001-11-17



See index of all Serzone side effect reports >>

Drug label data at the top of this Page last updated: 2007-06-23

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