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Indications l Pharmacology l Precautions l Side Effects l Consultation l Dosing |
VA CLASSIFICATION
Primary: CN609
Commonly used brand name(s): Serzone.
Note: For a listing of dosage forms and brand names by
country availability, see Dosage Forms section(s).
Category:
Antidepressant
Indications
Accepted
Depressive disorder, major (treatment)-Nefazodone is
indicated for the treatment of depression {01}{03}.
Pharmacology/Pharmacokinetics
Physicochemical characteristics:
Structurally related to trazodone {01}; structurally
unrelated to selective serotonin reuptake inhibitors,
tricyclic, tetracyclic, or monoamine oxidase inhibitors
{01}{03}.
Chemical group-
Molecular weight-
Nefazodone hydrochloride: 506.5 {01}
Mechanism of action/Effect:
The mechanism of action of nefazodone is unknown {01}.
However, nefazodone inhibits neuronal uptake of
serotonin and norepinephrine {01}. Nefazodone occupies
central 5-HT 2 receptors at nanomolar concentrations, where
it acts as an antagonist {01}. It has also been shown to
antagonize alpha 1-adrenergic receptors, a property which may
be associated with postural hypotension {01}.
In in vitro studies, nefazodone has not demonstrated
significant affinity for alpha 2-adrenergic, beta-adrenergic,
5-HT 1A, cholinergic, dopaminergic, or benzodiazepine
receptors {01}{03}.
Absorption:
Rapid and complete {01}{03}. However, due to extensive
metabolism, absolute bioavailability is low (about 20%) and
variable {01}{03}. Food delays absorption and decreases the
bioavailability by approximately 20% {01}{03}.
Distribution:
Nefazodone is widely distributed in body tissues, including
the central nervous system (CNS) {01}{03}. The volume of
distribution of nefazodone in humans ranges from 0.22 to 0.87
liters per kilogram (L/kg) {01}{03}.
Protein binding:
Very high (>99%) {01}{03}.
Biotransformation:
Nefazodone is extensively metabolized after oral
administration by N-dealkylation and aliphatic and aromatic
hydroxylation {01}{03}. Three metabolites have been identified
in the plasma: hydroxynefazodone (HO-NEF),
meta-chlorophenylpiperazine (mCPP), and a triazole-dione
metabolite. HO-NEF has a pharmacological profile
qualitatively and quantitatively similar to that of
nefazodone. Meta-chlorophenylpiperazine (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 been well
characterized.{01}{03} Several other metabolites have been
identified but not tested for pharmacological activity. {01}
Half-life:
2 to 4 hours {01}{03}.
Onset of action:
Full antidepressant effect may take several weeks to
achieve {01}{03}.
Time to peak concentration:
Approximately 1 to 3 hours {01}{03}.
Plasma concentrations
Both nefazodone and HO-NEF exhibit nonlinear kinetics for
both dose and time, with area under the plasma
concentration-time curve (AUC) and peak plasma concentrations
(C max) increasing more than proportionally with dose
increases {01}{03}.
Steady-state plasma concentrations
Attained within 4 to 5 days after initiation of twice-daily
dosing or upon dosage increase or decrease {01}{03}. In
studies involving 29 patients with renal function impairment
(creatinine clearances ranging from 7 to 60 mL/min/1.73 m 2),
no effect on steady-state plasma concentrations was observed
{01}. In a 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 {01}. In studies comparing single 300 mg doses of
nefazodone in younger and older patients, AUC and C max were
increased up to two-fold in older patients. However, with
multiple doses, increases were only 10 to 20% greater in the
older patients. Similarly, women exhibited a higher AUC and C
max after single doses of nefazodone, but no differences
after multiple dosing. {01}
Elimination:
Following oral administration of radiolabeled nefazodone,
approximately 50% to 65% of administered radioactivity was
excreted in the urine and about 20% to 40% in feces {01}{03}.
Precautions to Consider
Cross-sensitivity and/or related problems
Patients sensitive to other phenylpiperazine antidepressants
(e.g., trazodone) may be sensitive to nefazodone also {01}.
Carcinogenicity/Tumorigenicity
There is no evidence of carcinogenicity with nefazodone {01}.
No increased incidence of tumors was demonstrated after two
years of administration of nefazodone to rats and mice at
daily doses of up to 200 and 800 mg per kg of body weight
(mg/kg), respectively. (These doses correlate to
approximately 3 and 6 times, respectively, the maximum human
daily dose on a mg per square meter of body surface area
[mg/m 2] basis.) {01} No evidence of teratogenicity was
exhibited by rats or rabbits in studies of nefazodone given
at 16 to 25 times the maximum human daily dose of 600 mg.{03}
Mutagenicity
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 {01}.
Pregnancy/Reproduction
Fertility-
A fertility study in rats showed a slight decrease in
fertility when nefazodone was administered at a dose of 200
mg/kg per day (approximately 3 times the maximum human daily
dose on a mg/m 2 basis); however, this effect was not
demonstrated at a dose of 100 mg/kg per day (approximately
1.5 times the maximum human daily dose on a mg/m 2 basis)
{01}.
Pregnancy-
There are no adequate and well-controlled studies in pregnant
women {01}.
No malformations attributable to nefazodone were observed in
the offspring of rabbits and rats receiving daily doses up to
200 and 300 mg/kg, respectively (approximately 6 and 5 times,
respectively, the maximum human daily dose on a mg/m 2
basis). 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 unknown. The no-effect dose for
rat pup mortality was 1.3 times the human dose on a mg/m 2
basis. {01}
FDA Pregnancy Category C {01}.
Labor and delivery-
The effect of nefazodone on labor and delivery in humans is
unknown {01}.
Breast-feeding
It is not known if nefazodone or its metabolites are
distributed into human breast milk {01}. Nefazodone and 2 of
its active metabolites (hydroxynefazodone and
meta-chlorophenylpiperazine) are distributed into the milk of
lactating rats.{03}
Pediatrics
No information is available on the relationship of age to the
effects of nefazodone in pediatric patients. Safety and
efficacy in children up to 18 years of age have not been
established. {01}{03}
Geriatrics
The relationship of age to the effects of nefazodone has not
been systematically studied in geriatric patients. However,
peak plasma concentrations and AUC were 10% to 20% higher in
patients 65 years of age and older compared with patients
less than 65 years of age, after multiple doses of
nefazodone.{03} , Therefore, decreases in initial dosing in
geriatric patients are recommended. {01}{03}
Pharmacogenetics
About 3 to 10% of the population have reduced activity of the
drug-metabolizing enzyme cytochrome P450 2D6 (CYP2D6) and are
referred to as poor metabolizers of drugs such as
debrisoquin, dextromethorphan, and the tricyclic
antidepressants. The pharmacokinetics of nefazodone and its
major metabolite HO-NEF are not altered in this population,
but plasma concentrations of the mCPP metabolite are
increased. However, dosage adjustment of nefazodone in poor
metabolizers is not necessary. {01}
Dental
Because nefazodone has the potential to decrease or inhibit
salivary flow, it may contribute to the development of
caries, periodontal disease, oral candidiasis, and
discomfort.
Surgical
Since little is known about the potential for interaction
between nefazodone and general anesthetics, nefazodone should
be discontinued for as long as clinically feasible prior to
elective surgery {01}.
Drug interactions and/or related problems
The following drug interactions and/or related problems have
been selected on the basis of their potential clinical
significance (possible mechanism in parentheses where
appropriate)-not necessarily inclusive (≫ = major clinical
significance):
Note: Nefazodone has been shown in vitro to be an inhibitor
of cytochrome P450 3A4 (CYP3A4), and caution is indicated in
the combined use of nefazodone with any drugs known to be
metabolized by CYP3A4 {01}(e.g., some calcium channel
antagonists, cyclosporine, clarithromycin,
erythromycin, ketoconazole, itraconazole,
lovastatin, simvastatin, atorvastatin, midazolam,
or vinblastine).{03} Rhabdomyolysis involving patients
receiving the combination of nefazodone and simvastatin or
lovastatin has been reported in post-marketing clinical
studies.{04}
Nefazodone and its metabolites have been shown in vitro to be
extremely weak inhibitors of CYP2D6; therefore, it is
unlikely that nefazodone will decrease the metabolic
clearance of drugs metabolized by this isoenzyme {01}{03}.
Nefazodone and its metabolites have been shown in vitro not
to inhibit CYP1A2; metabolic interactions between nefazodone
and drugs metabolized by this isoenzyme are unlikely {01}{03}.
Because of nefazodone's high degree of binding to plasma
proteins, concurrent administration with another highly
protein-bound medication may displace that agent and cause
increased free concentrations of that agent, potentially
resulting in adverse effects. Conversely, displacement of
nefazodone by other highly protein-bound medications may
result in adverse effects. {01}{03}
Combinations containing any of the following medications,
depending on the amount present, may also interact with this
medication.
Alcohol or
CNS-active medications (although nefazodone did not
potentiate the cognitive and psychomotor effects of alcohol
in normal subjects, the concomitant use of nefazodone with
alcohol in depressed patients is not advised{03})
(the use of nefazodone in combination with other CNS-active
agents has not been systematically evaluated; caution is
advised)
≫ Alprazolam or
≫ Triazolam (triazolobenzodiazepines metabolized by CYP3A4
have demonstrated significantly increased plasma
concentrations when administered concomitantly with
nefazodone; initial alprazolam dosage should be
reduced by 50%;{03} initial triazolam dosage
should be reduced by 75%, and many patients
[e.g., the elderly] should not receive triazolam
and nefazodone concurrently; coadministration of
nefazodone potentiated the effects of triazolam on
psychomotor performance tests)
Antihypertensives (potential hypotensive effects of these
medications can enhance hypotensive effects of
nefazodone{03})
≫ Astemizole or
≫ Cisapride or
≫ Terfenadine (as an inhibitor of CYP3A4, nefazodone can
block the metabolism of these medications, resulting in
increased plasma concentrations, which are associated with QT
prolongation; rare cases of cardiovascular adverse effects,
including death, principally due to torsades de pointes, have
been reported with other inhibitors of CYP3A4; concomitant
use with nefazodone is contraindicated {01} {02}{03})
Digoxin (coadministration of nefazodone and digoxin to male
volunteers who were phenotyped as extensive metabolizers of
CYP2D6 substrates resulted in elevated plasma
concentrations of digoxin; because of digoxin's narrow
therapeutic index, caution should be exercised and monitoring
of digoxin plasma concentrations is recommended {01}{03})
Fluoxetine (concomitant administration of fluoxetine
significantly increases the AUC of the nefazodone metabolite
meta-chlorophenylpiperazine by approximately 3 to 6 fold;
patients who are transferred from fluoxetine to
nefazodone should have an intervening wash-out
period of 4 to 8 weeks {03})
Haloperidol (concomitant administration of a single oral 5-mg
dose of haloperidol with nefazodone [200 mg twice a day] at
steady-state resulted in a 35% decrease in apparent clearance
of haloperidol with no significant increase in peak
concentrations or time to peak concentration; pharmacodynamic
effects of haloperidol were generally not altered
significantly; the clinical significance of decreased
clearance is unknown, but dosage adjustments of
haloperidol may be necessary during
coadministration {01}{03})
≫ Monoamine oxidase (MAO) inhibitors (serious and sometimes
fatal reactions have occurred in patients receiving an MAO
inhibitor in combination with antidepressants with
pharmacological properties similar to those of nefazodone;
reactions have included hyperthermia, rigidity, myoclonus,
autonomic instability with possible rapid fluctuations of
vital signs, and mental status changes including extreme
agitation progressing to delirium and coma; some cases
presented with features resembling neuroleptic malignant
syndrome, such as severe hyperthermia and seizures, sometimes
fatal )
(the effects of nefazodone combined with MAO inhibitors have
not been evaluated in humans or animals; however, because
nefazodone is an inhibitor of both serotonin and
norepinephrine reuptake, concomitant use is not
recommended; in addition, at least 14 days should
elapse between discontinuation of an MAO
inhibitor and initiation of therapy with
nefazodone; at least 7 days should elapse between
discontinuation of nefazodone and initiation of
therapy with an MAO inhibitor {01}{03})
Propranolol (coadministration of propranolol and nefazodone
to healthy male volunteers [3 poor and 15 extensive CYP2D6
metabolizers] resulted in significant decreases in AUC and C
max of propranolol and in C max of the metabolite
4-hydroxypropranolol; the kinetics of nefazodone, HO-NEF, and
the triazole-dione metabolite were unaffected; however, the
peak and nadir plasma concentrations and AUC of mCPP were
increased; no change in the initial dose of either
drug is necessary, and dosage adjustments should
be made on the basis of clinical response {01})
Laboratory value alterations
The following have been selected on the basis of their
potential clinical significance (possible effect in
parentheses where appropriate)?not necessarily inclusive (≫
= major clinical significance):
With diagnostic test results
Electrocardiogram (ECG) (during premarketing studies, a
statistically significant difference in the incidence of
sinus bradycardia was observed in 1.5% of patients receiving
nefazodone as compared with 0.4% of patients receiving
placebo who met the defined criteria of a potentially
important decrease in heart rate: £ 50 bpm and a decrease of
³ 15 bpm; there was no obvious clinical significance of the
observed changes in these patients)
With physiology/laboratory test values
Growth hormone concentration and
Prolactin concentration (nefazodone has been associated with
dose-dependent increases in plasma prolactin and growth
hormone concentrations in healthy male volunteers; mean
plasma prolactin concentrations were double baseline values
[but still within the normal range] at 150 minutes after a
single 200-mg dose; mean plasma concentrations of growth
hormone were increased approximately 15-fold over baseline
values at 150 minutes after single doses of 100 to 200 mg;
however, when nefazodone was given as 100-mg doses two times
a day for 7 days, plasma concentrations declined to normal
range within the dosing interval; endocrine effects of
nefazodone in females have not been studied{03})
Hematocrit (during premarketing studies, a potentially
important decrease in hematocrit [£ 37% in males or £ 32%
in females] was reported in 2.8% of patients receiving
nefazodone as compared to 1.5% of patients receiving placebo;
decreases in hematocrit, presumably dilutional, have been
reported with other medications that block alpha 1-adrenergic
receptors; there was no apparent clinical significance of the
observed changes in these patients )
Medical considerations/Contraindications
The medical considerations/contraindications included have
been selected on the basis of their potential clinical
significance (reasons given in parentheses where
appropriate)- not necessarily inclusive (≫ = major clinical
significance).
Risk-benefit should be considered when the
following medical problems exist
≫ Cardiovascular disease, including angina, ischemic stroke,
or history of myocardial infarction or
≫ Cerebrovascular disease (may be exacerbated by potential
hypotensive effects of nefazodone {03})
≫ Dehydration or
≫ Hypovolemia (nefazodone-induced hypotension may be
exacerbated{03})
Drug abuse or dependence, or history of (patients with a
history of drug abuse should be observed closely for signs of
misuse or abuse, as with any new central nervous system [CNS]
drug)
≫ Hepatic function impairment{04} (plasma concentrations of
nefazodone and its metabolites may be increased; cases of
life-threatening hepatic failure have been reported following
both short- and long-term therapy with nefazodone; although
injury has been rare and usually has been reversible, hepatic
failure and death have been reported; nefazodone should be
used with caution in patients with hepatic function
impairment but should not be initiated in patients exhibiting
clinical evidence of active liver disease or elevated serum
baseline transaminase levels. Patients should be advised to
be alert for signs and symptoms of liver dysfunction
(jaundice, anorexia, gastrointestinal complaints, malaise)
and to report them to their doctor immediately if they occur.
There is no evidence that pre-existing liver disease
increases the likelihood of developing liver failure;
however, baseline abnormalities can complicate patient
monitoring. Nefazodone should be discontinued if transaminase
values become greater than three times the upper limit of
normal or if jaundice develops{04})
≫ Mania or hypomania, history of (condition may be
activated{03})
≫ Seizures, history of (although not documented to occur
with nefazodone, as with other antidepressants, the condition
potentially may be exacerbated{03})
≫ Sensitivity to nefazodone or other phenylpiperazine
antidepressants
Patient monitoring
The following may be especially important in patient
monitoring (other tests may be warranted in some patients,
depending on condition; ≫ = major clinical significance):
Careful supervision of depressed patients with suicidal
tendencies (recommended especially during early treatment
phase before peak effectiveness of nefazodone is achieved;
prescribing the smallest number of tablets necessary for good
patient management is recommended to decrease the risk of
overdose {01}{03})
Alanine aminotransferase (ALT [SGPT]){01} and
Aspartate aminotransferase (AST [SGOT]){01} (in
postintroduction clinical experience, elevations greater than
three times the upper limit of normal were observed in
nefazodone-treated patients. These patients should be
presumed to be at increased risk for liver injury.
Accordingly, such patients should not be considered for
re-treatment.{04})
Side/Adverse Effects
Note: Rare occurrences of priapism have been associated with
use of nefazodone; in some of the reported cases, surgical
intervention was required.{03} If priapism occurs, the
medication should be immediately discontinued and the
physician consulted. If the condition persists for longer
than 24 hours, a urologist should be consulted to determine
appropriate management. {01}{03}
Note: Cases of life-threatening hepatic failure have been
reported following both short- and long-term therapy with
nefazodone; although injury has been rare, hepatic failure
and death have been reported; nefazodone should not be
initiated in patients with active liver disease or elevated
serum baseline transaminase levels.{04}
The following side/adverse effects have been selected on the
basis of their potential clinical significance (possible
signs and symptoms in parentheses where appropriate)-not
necessarily inclusive:
Those indicating need for medical attention
Incidence more frequent
Abnormal gait or ataxia (clumsiness or unsteadiness)
abnormal vision, including blurred vision
scotoma
visual trails
or visual field defects (changes in vision){03}
hypotension or postural hypotension
{03}(lightheadedness or fainting)
skin rash or itching
tinnitus (ringing in the ears)
Note: Abnormal vision and tinnitus appear to be
dose-related.
Incidence less frequent
Bronchitis (shortness of breath, tightness in chest, or
wheezing)
dyspnea (troubled breathing)
eye pain
gastroenteritis (diarrhea; nausea; stomach pain)
Incidence rare
Allergic reactions, including photosensitivity
(increased sensitivity to sun), facial edema (swelling of
face), and urticaria (hives)
anemia (unusual tiredness or weakness)
arthritis, bursitis, tenosynovitis, or muscle
stiffness (joint or muscle pain or stiffness)
asthma
cardiovascular effects, including angina pectoris
(chest pain), hypertension
syncope (fainting), or tachycardia (fast heartbeat)
CNS effects, including abnormal thinking
apathy
decreased concentration
depersonalization
derealization
hostility or paranoid reaction (mood or mental
changes), dysarthria ( problems in speaking), euphoria
(unusual feeling of well-being ), hallucinations (seeing,
hearing, or feeling things that are not there), mania or
hypomania (talking, feeling, and acting with excitement and
activity you cannot control)
neuralgia (nerve pain), or twitching
ear pain or hyperacusis (increased sense of hearing)
ecchymosis (unusual bleeding or bruising)
eye problems, including dryness of eyes
abnormality of accommodation (blurred vision ),
diplopia (double vision), conjunctivitis or
keratoconjunctivitis (red or irritated eyes),
mydriasis ( large pupils), photophobia (sensitivity of
eyes to light )
gastrointestinal bleeding ( bloody or black, tarry
stools; vomiting of blood or material that looks like coffee
grounds)
{03}
gout (joint pain; lower back or side, or stomach pain)
leukopenia (fever, chills, or sore throat)
lymphadenopathy (swollen glands)
menstrual problems, including amenorrhea
menorrhagia
metrorrhagia
or vaginal hemorrhage (menstrual changes)
mouth ulcers or stomatitis (irritation or soreness of
mouth)
pelvic pain
rectal hemorrhage (bleeding from the rectum)
sexual dysfunction, including increased or
decreased libido
impotence
priapism (prolonged, painful, inappropriate penile erection
){03}, or abnormal ejaculation (change in sexual desire
or performance)
urinary effects, including cystitis
urinary urgency
polyuria
hematuria
nocturia
urinary incontinence (problems with urination), or
kidney calculus (kidney stones)
Incidence not determined
- Observed during clinical practice with nefazodone;
estimates of frequency cannot be determined{04}
Angioedema (large, hive-like swelling on face, eyelids,
lips, tongue, throat, hands, legs, feet, or sex organs)
convulsions, including grand mal seizures (muscle
spasm or jerking of all extremities; sudden loss of
consciousness)
hyponatremia (increased thirst; confusion; decreased urine
output; muscle pain or cramps)
liver failure ( light-colored stools or dark urine;
gastrointestinal complaints; lack of appetite; unusual
tiredness)
rhabdomyolysis, in combination with lovastatin or
simvastatin (dark-colored urine; fever; muscle pain or
stiffness; unusual tiredness or weakness)
serotonin syndrome (agitation; diarrhea; sweating; poor
coordination )
Stevens-Johnson syndrome (blistering, peeling,
loosening of skin; itching red skin lesions, often with a
purple center; unusual tiredness or weakness )
thrombocytopenia (black, sticky stools; pain, warmth, or
burning in fingers, toes and legs; sore throat; dizziness )
Those indicating need for medical attention only
if they continue or are bothersome
Incidence more frequent
Abnormal dreams {03}
agitation
confusion {03}
constipation {03}
diarrhea {03}
dizziness {03}
drowsiness
dryness of mouth {03}
dyspepsia (heartburn)
fever or chills {03}
flushing or a feeling of warmth
headache {03}
increased appetite
increased cough
insomnia {03}(trouble in sleeping)
memory impairment {03}
nausea {03}
paresthesias {03}(tingling, burning, or prickly
sensations)
peripheral edema (swelling of arms or legs)
pharyngitis (sore throat)
tremor
vomiting {03}
Note: Confusion, constipation, dizziness, drowsiness, and
nausea are dose-related.
Incidence less frequent or rare
Abdominal pain (pain in stomach or abdomen){03}
arthralgia (joint pain)
asthenia (loss of strength or energy; muscle pain or
weakness){03}
breast pain
increased thirst
Incidence not determined
- Observed during clinical practice with nefazodone;
estimates of frequency cannot be determined{04}
galactorrhea (unexpected or excess milk flow from breasts)
gynecomastia, male (swelling of the breasts or breast
soreness in males)
Overdose
For more information on the management of overdose or
unintentional ingestion, contact a Poison Control
Center {01} (see Poison Control Center Listing).
Clinical effects of overdose
The following effects have been selected on the basis of
their potential clinical significance (possible signs and
symptoms in parentheses where appropriate)?not necessarily
inclusive:
Acute effects
Bradycardia {03}
hypotension {01}{03}
nausea {01}{03}
somnolence {01}{03}
vomiting {01}{03}
Note: Overdosage of nefazodone may cause an increase in
incidence or severity of any of the reported adverse
reactions {01}.
Treatment of overdose
Note: The possibility of multiple drug involvement should be
considered in managing overdose {01}{03}.
There is no specific antidote for nefazodone {01}{03}.
Treatment is essentially symptomatic and supportive {01}{03}.
To decrease absorption-Gastric lavage should be initiated in
any patient suspected of having taken an overdose of
nefazodone {01}{03}.
Supportive care-Patients in whom intentional overdose is
known or suspected should be referred for psychiatric
consultation.
Patient Consultation
As an aid to patient consultation, refer to Advice for the
Patient, Nefazodone (Systemic).
In providing consultation, consider emphasizing the following
selected information (≫ = major clinical significance):
Before using this medication
≫ Conditions affecting use, especially:
Sensitivity to nefazodone or trazodone
Pregnancy-In studies in rats, increased early pup mortality
was seen 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 unknown
Contraindicated medications
Astemizole, cisapride, and terfenadine
Other medications, especially alprazolam, monoamine oxidase
(MAO) inhibitors, and triazolam
Other medical problems, especially cardiovascular or
cerebrovascular disease, dehydration or hypovolemia, hepatic
function impairment, history of mania or hypomania, or
history of seizures
Proper use of this medication
≫ Compliance with therapy; not taking more or less medicine
than prescribed
≫ Several weeks of treatment may be required before
antidepressant effects are achieved
≫ Proper dosing
Taking as soon as possible; continuing on regular schedule
with next dose; not doubling doses
≫ Proper storage
Precautions while using this medication
Regular visits to physician to check progress of therapy
≫ Not taking astemizole, cisapride, or terfenadine because
of possible life-threatening cardiac arrhythmias
≫ Not taking an MAO inhibitor with or less than 7 days after
taking nefazodone; not taking nefazodone less than 14 days
after taking an MAO inhibitor
≫ Avoiding use of alcoholic beverages; not taking other
CNS-active agents unless prescribed by physician
≫ Possible blurred vision, drowsiness, impairment of
judgment, thinking, or motor skills; caution when driving or
doing jobs requiring alertness
≫ Possible dizziness or lightheadedness; caution when
getting up suddenly from a lying or sitting position
≫ Possible dryness of mouth; using sugarless gum or candy,
ice, or saliva substitute for relief; checking with physician
or dentist if dry mouth continues for more than 2 weeks
Side/adverse effects
Signs of potential side effects, especially abnormal gait or
ataxia; abnormal vision; angioedema, convulsions (including
grand mal seizures), hypotension or postural hypotension,
skin rash or itching, tinnitus, bronchitis, dyspnea, eye
pain, gastroenteritis, allergic reactions, anemia, arthritis,
bursitis, tenosynovitis, or muscle stiffness, asthma,
cardiovascular effects, CNS effects, ear pain or hyperacusis,
ecchymosis, eye problems, gastrointestinal bleeding, gout,
hyponatremia, leukopenia, liver failure, lymphadenopathy,
menstrual problems, mouth ulcers or stomatitis, pelvic pain,
rectal hemorrhage, rhabdomyolysis, in combination with
lovastatin or simvastatin, serotonin syndrome, sexual
dysfunction, including priapism, Stevens-Johnson syndrome,
thrombocytopenia and urinary effects
General Dosing Information
There is no body of evidence from controlled trials to
indicate how long a 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 six months or longer. It is unknown
whether the dose of antidepressant needed to induce remission
is identical to the dose needed to maintain euthymia. {01}
Potentially suicidal patients should not have access to large
quantities of this medication since depressed patients,
particularly those who may use alcohol excessively, may
continue to exhibit suicidal tendencies until significant
improvement occurs. Some clinicians recommend that the
patient be supplied with the smallest quantity of medication
necessary for satisfactory patient management. {01}{03}
Activation of hypomania or mania has been reported in
depressed patients treated with nefazodone {01}{03}.
Patients should be advised to be alert for signs and symptoms
of liver dysfunction (jaundice, anorexia, gastrointestinal
symptoms, malaise, etc.) and to report them to their doctor
immediately if they occur.{04}
Oral Dosage Forms
NEFAZODONE HYDROCHLORIDE TABLETS
Usual adult dose
Antidepressant
Oral, initially 100 to 200 mg a day, administered in
two divided doses. The dosage may be increased, as needed
and tolerated, in increments of 100 to 200 mg a day at
intervals of no less than one week. The effective dosage
range in clinical trials was generally 300 to 600
mg a day. {01}{03}
Note: For dosage for debilitated patients, see Usual
geriatric dose. In patients with liver disease, therapy
should be initiated at one-half the usual dose, with
titration based on therapeutic response.{03} In patients with
severe renal impairment, doses on the lower end of the dosage
range are advised.{03}
Usual pediatric dose
Safety and efficacy in children up to 18 years of age have
not been established {01}{03}.
Usual geriatric dose
Antidepressant
Oral, initially 100 mg a day administered in two divided
doses. Since these patients may have reduced nefazodone
clearance and/or increased sensitivity to the CNS side
effects, the subsequent titration rate of nefazodone dosage
may need to be modified. Final dosage determination should be
based on the patient's clinical response; since steady-state
plasma levels do not change with age, the target dose may be
similar in healthy younger and older patients. {01}{03}
Strength(s) usually available
U.S.-
50 mg (Rx) [Serzone (microcrystalline cellulose) (povidone)
(sodium starch glycolate ) (colloidal silicon dioxide) (
magnesium stearate) (iron oxides)]
100 mg (Rx) [Serzone (scored) (microcrystalline cellulose)
(povidone) ( sodium starch glycolate) (colloidal silicon
dioxide ) (magnesium stearate) ( iron oxides)]
150 mg (Rx) [Serzone (scored) (microcrystalline cellulose)
(povidone) ( sodium starch glycolate) (colloidal silicon
dioxide ) (magnesium stearate) ( iron oxides)]
200 mg (Rx) [Serzone (microcrystalline cellulose)
(povidone) (sodium starch glycolate ) (colloidal silicon
dioxide) ( magnesium stearate) (iron oxides)]
250 mg (Rx) [Serzone (microcrystalline cellulose) (povidone)
(sodium starch glycolate ) (colloidal silicon dioxide) (
magnesium stearate) (iron oxides)]
Canada-
50 mg (Rx) [Serzone (colloidal silicon dioxide) (magnesium
stearate) (microcrystalline cellulose) (povidone) ( red
ferric oxide) (sodium starch glycolate)]{03}
100 mg (Rx) [Serzone (scored) ( colloidal silicon dioxide)
(magnesium stearate) (microcrystalline cellulose) (povidone )
(sodium starch glycolate)]{03}
150 mg (Rx) [Serzone (scored) (colloidal silicon dioxide)
(magnesium stearate) (microcrystalline cellulose) (povidone )
(red ferric oxide) ( sodium starch glycolate) (yellow ferric
oxide)]{03}
200 mg (Rx) [Serzone (colloidal silicon dioxide) (magnesium
stearate) (microcrystalline cellulose) (povidone) ( sodium
starch glycolate) (yellow ferric oxide)]{03}
Packaging and storage:
Store below 40 °C (104 °F) unless otherwise specified by
manufacturer. Dispense in a tight container. {01}
Auxiliary labeling:
-Avoid alcoholic beverages.
-May cause dizziness or drowsiness.
Developed: 09/27/1995
Revised: 01/04/2002
References
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