This is probably more than you ever wanted, but here is the PDR breakdown of
Wellbutrin. I do NOT claim any of the following to be of my creation, but a
representation of the PDR's listing for Wellbutrin. Well, ok the signature
is mine. This can be a bit overwhelming if you're not used to reading the
PDR. A medical dictionary might help the novice.
Ciao!
DESCRIPTION
WELLBUTRIN SR (bupropion hydrochloride), an antidepressant of the
aminoketone class, is chemically unrelated to tricyclic, tetracyclic,
selective serotonin re-uptake inhibitor, or other known antidepressant
agents. Its structure closely resembles that of diethylpropion; it is
related to phenylethylamines. It is designated as
(±)-1-(3-chlorophenyl)-2-[(1,1-dimethylethyl)amino]-1-propanone
hydrochloride. The molecular weight is 276.2. The molecular formula is C 13
H 18 ClNO·HCl. Bupropion hydrochloride powder is white, crystalline, and
highly soluble in water. It has a bitter taste and produces the sensation of
local anesthesia on the oral mucosa.
WELLBUTRIN SR Tablets are supplied for oral administration as 100-mg (blue)
and 150-mg (purple), film-coated, sustained-release tablets. Each tablet
contains the labeled amount of bupropion hydrochloride and the inactive
ingredients: carnauba wax, cysteine hydrochloride, hydroxypropyl
methylcellulose, magnesium stearate, microcrystalline cellulose,
polyethylene glycol, and titanium dioxide and is printed with edible black
ink. In addition, the 100-mg tablet contains FD&C Blue No. 1 Lake and
polysorbate 80, and the 150-mg tablet contains FD&C Blue No. 2 Lake, FD&C
Red No. 40 Lake, and polysorbate 80.
CLINICAL PHARMACOLOGY
Pharmacodynamics Bupropion is a relatively weak inhibitor of the neuronal
uptake of norepinephrine, serotonin, and dopamine, and does not inhibit
monoamine oxidase. While the mechanism of action of bupropion, as with other
antidepressants, is unknown, it is presumed that this action is mediated by
noradrenergic and/or dopaminergic mechanisms.
Pharmacokinetics Bupropion is a racemic mixture. The pharmacologic
activity and pharmacokinetics of the individual enantiomers have not been
studied.
Following oral administration of WELLBUTRIN SR Tablets to healthy
volunteers, peak plasma concentrations of bupropion are achieved within 3
hours. Food increased C max and AUC of bupropion by 11% and 17%,
respectively, indicating that there is no clinically significant food
effect.
In vitro tests show that bupropion is 84% bound to human plasma proteins at
concentrations up to 200 mcg/mL. The extent of protein binding of the
hydroxybupropion metabolite is similar to that for bupropion, whereas the
extent of protein binding of the threohydrobupropion metabolite is about
half that seen with bupropion.
Following oral administration of 200 mg of 14 C-bupropion in humans, 87% and
10% of the radioactive dose were recovered in the urine and feces,
respectively. The fraction of the oral dose of bupropion excreted unchanged
was only 0.5%, a finding consistent with the extensive metabolism of
bupropion.
The mean elimination half-life (±SD) of bupropion after chronic dosing is 21
(±9) hours, and steady-state plasma concentrations of bupropion are reached
within 8 days.
Bupropion is extensively metabolized in humans. Three metabolites have been
shown to be active: hydroxybupropion, which is formed via hydroxylation of
the tert -butyl group of bupropion, and the amino-alcohol isomers
threohydrobupropion and erythrohydrobupropion, which are formed via
reduction of the carbonyl group. In vitro findings suggest that cytochrome
P450II2B6 (CYP2B6) is the principal isoenzyme involved in the formation of
hydroxybupropion, while cytochrome P450 isoenzymes are not involved in the
formation of threohydrobupropion. Oxidation of the bupropion side chain
results in the formation of a glycine conjugate of meta-chlorobenzoic acid,
which is then excreted as the major urinary metabolite. The potency and
toxicity of the metabolites relative to bupropion have not been fully
characterized. Nevertheless, they may be clinically important because their
plasma concentrations are higher than those of bupropion.
Because bupropion is extensively metabolized, there is the potential for
drug-drug interactions, particularly with those agents that are metabolized
by the cytochrome P450IIB6 (CYP2B6) isoenzyme. Although bupropion is not
metabolized by cytochrome P450IID6 (CYP2D6), there is the potential for
drug-drug interactions when bupropion is co-administered with drugs
metabolized by this isoenzyme (see PRECAUTIONS : Drug Interactions ).
Following a single dose in humans, peak plasma concentrations of
hydroxybupropion occur approximately 6 hours after administration of
WELLBUTRIN SR Tablets. Peak plasma concentrations of hydroxybupropion are
approximately 10 times the peak level of the parent drug at steady state.
The elimination half-life of hydroxybupropion is approximately 20 (±5)
hours, and its AUC at steady state is about 17 times that of bupropion. The
times to peak concentrations for the erythrohydrobupropion and
threohydrobupropion metabolites are similar to that of the hydroxybupropion
metabolite. However, their elimination half-lives are longer, 33 (±10) and
37 (±13) hours, respectively, and steady-state AUCs are 1.5 and 7 times that
of bupropion, respectively.
In a study comparing chronic dosing with WELLBUTRIN SR Tablets 150 mg twice
daily to the immediate-release formulation of bupropion at 100 mg three
times daily, peak plasma concentrations of bupropion at steady state for
WELLBUTRIN SR Tablets were approximately 85% of those achieved with the
immediate-release formulation. There was equivalence for bupropion AUCs, as
well as equivalence for both peak plasma concentration and AUCs for all
three of the detectable bupropion metabolites. Thus, at steady state,
WELLBUTRIN SR Tablets, given twice daily, and the immediate-release
formulation of bupropion, given three times daily, are essentially
bioequivalent for both bupropion and the three quantitatively important
metabolites.
Bupropion and its metabolites exhibit linear kinetics following chronic
administration of 300 to 450 mg/day.
Population Subgroups: Factors or conditions altering metabolic capacity
(e.g., liver disease, congestive heart failure [CHF], age, concomitant
medications, etc.) or elimination may be expected to influence the degree
and extent of accumulation of the active metabolites of bupropion. The
elimination of the major metabolites of bupropion may be affected by reduced
renal or hepatic function because they are moderately polar compounds and
are likely to undergo further metabolism or conjugation in the liver prior
to urinary excretion.
Hepatic: The disposition of bupropion following a single 200-mg oral dose
was compared in eight healthy volunteers and eight weight- and age-matched
volunteers with alcoholic liver disease. The half-life of the
hydroxybupropion was significantly prolonged in subjects with alcoholic
liver disease (32 hours [±41%] versus 21 hours [±23%]). The differences in
half-life for bupropion and the other metabolites in the two patient groups
were minimal.
Renal The effect of renal disease on the pharmacokinetics of bupropion has
not been studied. The elimination of the major metabolites of bupropion may
be affected by reduced renal function.
Left Ventricular Dysfunction: During a chronic dosing study with bupropion
in 14 depressed patients with left ventricular dysfunction (history of CHF
or an enlarged heart on x-ray), no apparent effect on the pharmacokinetics
of bupropion or its metabolites, compared to healthy normal volunteers, was
revealed.
Age: The effects of age on the pharmacokinetics of bupropion and its
metabolites have not been fully characterized, but an exploration of
steady-state bupropion concentrations from several depression efficacy
studies involving patients dosed in a range of 300 to 750 mg/day, on a three
times daily schedule, revealed no relationship between age (18 to 83 years)
and plasma concentration of bupropion. A single-dose pharmacokinetic study
demonstrated that the disposition of bupropion and its metabolites in
elderly subjects was similar to that of younger subjects. These data suggest
there is no prominent effect of age on bupropion concentration (see
PRECAUTIONS : Geriatric Use ).
Gender: A single-dose study involving 12 healthy male and 12 healthy
female volunteers revealed no sex-related differences in the pharmacokinetic
parameters of bupropion.
Smokers: The effects of cigarette smoking on the pharmacokinetics of
bupropion were studied in 34 healthy male and female volunteers; 17 were
chronic cigarette smokers and 17 were nonsmokers. Following oral
administration of a single 150-mg dose of bupropion, there was no
statistically significant difference in C max , half-life, t max , AUC, or
clearance of bupropion or its active metabolites between smokers and
nonsmokers.
CLINICAL TRIALS
The efficacy of the immediate-release formulation of bupropion as a
treatment for depression was established in two 4-week, placebo-controlled
trials in adult inpatients with depression and in one 6-week,
placebo-controlled trial in adult outpatients with depression. In the first
study, patients were titrated in a bupropion dose range of 300 to 600 mg/day
on a three times daily schedule; 78% of patients received maximum doses of
450 mg/day or less. This trial demonstrated the effectiveness of the
immediate-release formulation of bupropion on the Hamilton Depression Rating
Scale (HDRS) total score, the depressed mood item (item 1) from that scale,
and the Clinical Global Impressions (CGI) severity score. A second study
included two fixed doses of the immediate-release formulation of bupropion
(300 and 450 mg/day) and placebo. This trial demonstrated the effectiveness
of the immediate-release formulation of bupropion, but only at the
450-mg/day dose; the results were positive for the HDRS total score and the
CGI severity score, but not for HDRS item 1. In the third study, outpatients
received 300 mg/day of the immediate-release formulation of bupropion. This
study demonstrated the effectiveness of the immediate-release formulation of
bupropion on the HDRS total score, HDRS item 1, the Montgomery-Asberg
Depression Rating Scale, the CGI severity score, and the CGI improvement
score.
Although there are not as yet independent trials demonstrating the
antidepressant effectiveness of the sustained-release formulation of
bupropion, studies have demonstrated the bioequivalence of the
immediate-release and sustained-release forms of bupropion under
steady-state conditions, i.e., bupropion sustained-release 150 mg twice
daily was shown to be bioequivalent to 100 mg three times daily of the
immediate-release formulation of bupropion, with regard to both rate and
extent of absorption, for parent drug and metabolites.
INDICATIONS AND USAGE
WELLBUTRIN SR is indicated for the treatment of depression.
The efficacy of bupropion in the treatment of depression was established in
two 4-week controlled trials of depressed inpatients and in one 6-week
controlled trial of depressed outpatients whose diagnoses corresponded most
closely to the Major Depression category of the APA Diagnostic and
Statistical Manual (DSM) (see CLINICAL PHARMACOLOGY ).
A major depressive episode (DSM-IV) implies the presence of 1) depressed
mood or 2) loss of interest or pleasure; in addition, at least five of the
following symptoms have been present during the same 2-week period and
represent a change from previous functioning: depressed mood, markedly
diminished interest or pleasure in usual activities, significant change in
weight and/or appetite, insomnia or hypersomnia, psychomotor agitation or
retardation, increased fatigue, feelings of guilt or worthlessness, slowed
thinking or impaired concentration, a suicide attempt or suicidal ideation.
Effectiveness of bupropion in long-term use (more than 6 weeks) has not been
systematically evaluated in controlled trials. Therefore, the physician who
elects to use WELLBUTRIN SR Tablets for extended periods should periodically
reevaluate the long-term usefulness of the drug for the individual patient.
CONTRAINDICATIONS
WELLBUTRIN SR is contraindicated in patients with a seizure disorder.
WELLBUTRIN SR is contraindicated in patients treated with ZYBAN® (bupropion
hydrochloride) Sustained-Release Tablets, or any other medications that
contain bupropion because the incidence of seizure is dose dependent.
WELLBUTRIN SR is contraindicated in patients with a current or prior
diagnosis of bulimia or anorexia nervosa because of a higher incidence of
seizures noted in patients treated for bulimia with the immediate-release
formulation of bupropion. The concurrent administration of WELLBUTRIN SR
Tablets and a monoamine oxidase (MAO) inhibitor is contraindicated. At least
14 days should elapse between discontinuation of an MAO inhibitor and
initiation of treatment with WELLBUTRIN SR Tablets. WELLBUTRIN SR is
contraindicated in patients who have shown an allergic response to bupropion
or the other ingredients that make up WELLBUTRIN SR Tablets.
WARNINGS
Patients should be made aware that WELLBUTRIN SR contains the same active
ingredient found in ZYBAN, used as an aid to smoking cessation treatment,
and that WELLBUTRIN SR should not be used in combination with ZYBAN, or any
other medications that contain bupropion.
Seizures: Bupropion is associated with a dose-related risk of seizures.
The risk of seizures is also related to patient factors, clinical
situations, and concomitant medications, which must be considered in
selection of patients for therapy with WELLBUTRIN SR.
Dose: At doses of WELLBUTRIN SR up to a dose of 300 mg/day, the incidence of
seizure is approximately 0.1% (1/1000) and increases to approximately 0.4%
(4/1000) at the maximum recommended dose of 400 mg/day.
Data for the immediate-release formulation of bupropion revealed a seizure
incidence of approximately 0.4% (i.e., 13 of 3200 patients followed
prospectively) in patients treated at doses in a range of 300 to 450 mg/day.
The 450-mg/day upper limit of this dose range is close to the currently
recommended maximum dose of 400 mg/day for WELLBUTRIN SR Tablets. This
seizure incidence (0.4%) may exceed that of other marketed antidepressants
and WELLBUTRIN SR Tablets up to 300 mg/day by as much as fourfold. This
relative risk is only an approximate estimate because no direct comparative
studies have been conducted.
Additional data accumulated for the immediate-release formulation of
bupropion suggested that the estimated seizure incidence increases almost
tenfold between 450 and 600 mg/day, which is twice the usual adult dose and
one and one-half the maximum recommended daily dose (400 mg) of WELLBUTRIN
SR Tablets. This disproportionate increase in seizure incidence with dose
incrementation calls for caution in dosing.
Data for WELLBUTRIN SR Tablets revealed a seizure incidence of approximately
0.1% (i.e., 3 of 3100 patients followed prospectively) in patients treated
at doses in a range of 100 to 300 mg/day. It is not possible to know if the
lower seizure incidence observed in this study involving the
sustained-release formulation of bupropion resulted from the different
formulation or the lower dose used. However, as noted above, the
immediate-release and sustained-release formulations are bioequivalent with
regard to both rate and extent of absorption during steady state (the most
pertinent condition to estimating seizure incidence), since most observed
seizures occur under steady-state conditions.
Patient factors: Predisposing factors that may increase the risk of seizure
with bupropion use include history of head trauma or prior seizure, central
nervous system (CNS) tumor, and concomitant medications that lower seizure
threshold. Clinical situations: Circumstances associated with an increased
seizure risk include, among others, excessive use of alcohol; abrupt
withdrawal from alcohol or other sedatives; addiction to opiates, cocaine,
or stimulants; use of over-the-counter stimulants and anorectics; and
diabetes treated with oral hypoglycemics or insulin.
Concomitant medications: Many medications (e.g., antipsychotics,
antidepressants, theophylline, systemic steroids) and treatment regimens
(e.g., abrupt discontinuation of benzodiazepines) are known to lower seizure
threshold. Recommendations for Reducing the Risk of Seizure:
Retrospective analysis of clinical experience gained during the development
of bupropion suggests that the risk of seizure may be minimized if
the total daily dose of WELLBUTRIN SR Tablets does not exceed 400 mg, the
daily dose is administered twice daily, and the rate of incrementation of
dose is gradual. No single dose should exceed 200 mg to avoid high peak
concentrations of bupropion and/or its metabolites. WELLBUTRIN SR should be
administered with extreme caution to patients with a history of seizure,
cranial trauma, or other predisposition(s) toward seizure, or patients
treated with other agents (e.g., antipsychotics, other antidepressants,
theophylline, systemic steroids, etc.) or treatment regimens (e.g., abrupt
discontinuation of a benzodiazepine) that lower seizure threshold.
Potential for Hepatotoxicity: In rats receiving large doses of bupropion
chronically, there was an increase in incidence of hepatic hyperplastic
nodules and hepatocellular hypertrophy. In dogs receiving large doses of
bupropion chronically, various histologic changes were seen in the liver,
and laboratory tests suggesting mild hepatocellular injury were noted.
PRECAUTIONS
General: Agitation and Insomnia: Patients in placebo-controlled trials
with WELLBUTRIN SR Tablets experienced agitation, anxiety, and insomnia as
shown in Table 1.
Table 1: Incidence of Agitation, Anxiety, and Insomnia
in Placebo-Controlled Trials Adverse
Event Term WELLBUTRIN
SR
300 mg/day
(n = 376) WELLBUTRIN
SR
400 mg/day
(n = 114) Placebo
(n = 385)
Agitation 3% 9% 2%
Anxiety 5% 6% 3%
Insomnia11% 16% 6%
In clinical studies, these symptoms were sometimes of sufficient magnitude
to require treatment with sedative/hypnotic drugs.
Symptoms were sufficiently severe to require discontinuation of treatment in
1% and 2.6% of patients treated with 300 and 400 mg/day, respectively, of
WELLBUTRIN SR Tablets and 0.8% of patients treated with placebo.
Psychosis, Confusion, and Other Neuropsychiatric Phenomena:
Depressed patients treated with an immediate-release formulation of
bupropion or with WELLBUTRIN SR Tablets have been reported to show a variety
of neuropsychiatric signs and symptoms, including delusions, hallucinations,
psychosis, concentration disturbance, paranoia, and confusion. In some
cases, these symptoms abated upon dose reduction and/or withdrawal of
treatment.
Activation of Psychosis and/or Mania: Antidepressants can precipitate
manic episodes in bipolar disorder patients during the depressed phase of
their illness and may activate latent psychosis in other susceptible
patients. WELLBUTRIN SR is expected to pose similar risks.
Altered Appetite and Weight: In placebo-controlled studies, patients
experienced weight gain or weight loss as shown in Table 2.
Table 2: Incidence of Weight Gain and Weight Loss
in Placebo-Controlled Trials Weight Change WELLBUTRIN
SR
300 mg/day
(n = 339) WELLBUTRIN
SR
400 mg/day
(n = 112) Placebo
(n = 347)
Gained >5 lbs 3% 2% 4%
Lost >5 lbs 14% 19% 6%
In studies conducted with the immediate-release formulation of bupropion,
35% of patients receiving tricyclic antidepressants gained weight, compared
to 9% of patients treated with the immediate-release formulation of
bupropion. If weight loss is a major presenting sign of a patient'
depressive illness, the anorectic and/or weight-reducing potential of
WELLBUTRIN SR Tablets should be considered.
Suicide The possibility of a suicide attempt is inherent in depression and
may persist until significant remission occurs. Accordingly, prescriptions
for WELLBUTRIN SR Tablets should be written for the smallest number of
tablets consistent with good patient management.
Allergic Reactions: Anaphylactoid/anaphylactic reactions characterized by
symptoms such as pruritus, urticaria, angioedema, and dyspnea requiring
medical treatment have been reported in clinical trials with bupropion. In
addition, there have been rare spontaneous postmarketing reports of erythema
multiforme, Stevens-Johnson syndrome, and anaphylactic shock associated with
bupropion. A patient should stop taking WELLBUTRIN SR and consult a doctor
if experiencing allergic or anaphylactoid/anaphylactic reactions (e.g., skin
rash, pruritus, hives, chest pain, edema, and shortness of breath) during
treatment.
Use in Patients With Systemic Illness: There is no clinical experience
establishing the safety of WELLBUTRIN SR Tablets in patients with a recent
history of myocardial infarction or unstable heart disease. Therefore, care
should be exercised if it is used in these groups. Bupropion was well
tolerated in patients who had previously developed orthostatic hypotension
while receiving tricyclic antidepressants, and was also generally well
tolerated in a group of 36 depressed inpatients with stable congestive heart
failure (CHF). However, bupropion was associated with a rise in supine blood
pressure in the study of patients with CHF, resulting in discontinuation of
treatment in two patients for exacerbation of baseline hypertension.
Because bupropion and its metabolites are almost completely excreted through
the kidney and metabolites are likely to undergo conjugation in the liver
prior to urinary excretion, treatment of patients with renal or hepatic
impairment should be initiated at reduced dosage as bupropion and its
metabolites may accumulate in such patients to a greater extent than usual.
The patient should be closely monitored for possible toxic effects of
elevated blood and tissue levels of drug and metabolites.
Information for Patients: See the tear-off leaflet at the end of this
labeling for Information for the Patient.
Patients should be made aware that WELLBUTRIN SR contains the same active
ingredient found in ZYBAN, used as an aid to smoking cessation treatment,
and that WELLBUTRIN SR should not be used in combination with ZYBAN or any
other medications that contain bupropion hydrochloride.
Physicians are advised to discuss the following issues with patients:
As dose is increased during initial titration to doses above 150 mg/day,
patients should be instructed to take WELLBUTRIN SR Tablets in two divided
doses, preferably with at least 8 hours between successive doses, to
minimize the risk of seizures. Patients should be told that any CNS-active
drug like WELLBUTRIN SR Tablets may impair their ability to perform tasks
requiring judgment or motor and cognitive skills. Consequently, until they
are reasonably certain that WELLBUTRIN SR Tablets do not adversely affect
their performance, they should refrain from driving an automobile or
operating complex, hazardous machinery. Patients should be told that the
use and cessation of use of alcohol may alter the seizure threshold, and,
therefore, that the consumption of alcohol should be minimized, and, if
possible, avoided completely. Patients should be advised to inform their
physicians if they are taking or plan to take any prescription or
over-the-counter drugs. Concern is warranted because WELLBUTRIN SR Tablets
and other drugs may affect each other's metabolism.
Patients should be advised to notify their physicians if they become
pregnant or intend to become pregnant during therapy.
Patients should be advised to swallow WELLBUTRIN SR Tablets whole so that
the release rate is not altered. Do not chew, divide, or crush tablets.
Laboratory Tests: There are no specific laboratory tests recommended.
Drug Interactions: Few systemic data have been collected on the metabolism
of WELLBUTRIN SR following concomitant administration with other drugs or,
alternatively, the effect of concomitant administration of WELLBUTRIN SR on
the metabolism of other drugs.
Because bupropion is extensively metabolized, the coadministration of other
drugs may affect its clinical activity. In vitro studies indicate that
bupropion is primarily metabolized to hydroxybupropion by the CYP2B6
isoenzyme. Therefore, the potential exists for a drug interaction between
WELLBUTRIN SR and drugs that affect the CYP2B6 isoenzyme (e.g., orphenadrine
and cyclophosphamide). The threohydrobupropion metabolite of bupropion does
not appear to be produced by the cytochrome P450 isoenzymes. The effects of
concomitant administration of cimetidine on the pharmacokinetics of
bupropion and its active metabolites were studied in 24 healthy young male
volunteers. Following oral administration of two 150-mg WELLBUTRIN SR
tablets with and without 800 mg of cimetidine, the pharmacokinetics of
bupropion and hydroxybupropion were unaffected. However, there were 16% and
32% increases in the AUC and C max , respectively, of the combined moieties
of threohydrobupropion and erythrohydrobupropion.
While not systematically studied, certain drugs may induce the metabolism of
bupropion (e.g., carbamazepine, phenobarbital, phenytoin).
Animal data indicated that bupropion may be an inducer of drug-metabolizing
enzymes in humans. In one study, following chronic administration of
bupropion, 100 mg three times daily to eight healthy male volunteers for 14
days, there was no evidence of induction of its own metabolism.
Nevertheless, there may be the potential for clinically important
alterations of blood levels of coadministered drugs.
Drugs Metabolized By Cytochrome P450IID6 (CYP2D6): Many drugs, including
most antidepressants (SSRIs, many tricyclics), beta-blockers,
antiarrhythmics, and antipsychotics are metabolized by the CYP2D6 isoenzyme.
Although bupropion is not metabolized by this isoenzyme, bupropion and
hydroxybupropion are inhibitors of CYP2D6 isoenzyme in vitro. In a study of
15 male subjects (ages 19 to 35 years) who were extensive metabolizers of
the CYP2D6 isoenzyme, daily doses of bupropion given as 150 mg twice daily
followed by a single dose of 50 mg desipramine increased the C max , AUC,
and t ½ of desipramine by an average of approximately two-, five- and
two-fold, respectively. The effect was present for at least 7 days after the
last dose of bupropion. Concomitant use of bupropion with other drugs
metabolized by CYP2D6 has not been formally studied.
Therefore, co-administration of bupropion with drugs that are metabolized by
CYP2D6 isoenzyme including certain antidepressants (e.g., nortriptyline,
imipramine, desipramine, paroxetine, fluoxetine, sertraline), antipsychotics
(e.g., haloperidol, risperidone, thioridazine), beta-blockers (e.g.,
metoprolol), and Type 1C antiarrhythmics (e.g., propafenone, flecainide),
should be approached with caution and should be initiated at the lower end
of the dose range of the concomitant medication. If bupropion is added to
the treatment regimen of a patient already receiving a drug metabolized by
CYP2D6, the need to decrease the dose of the original medication should be
considered, particularly for those concomitant medications with a narrow
therapeutic index.
MAO Inhibitors: Studies in animals demonstrate that the acute toxicity of
bupropion is enhanced by the MAO inhibitor phenelzine (see CONTRAINDICATIONS
).
Levodopa Limited clinical data suggest a higher incidence of adverse
experiences in patients receiving concurrent administration of bupropion and
levodopa. Administration of WELLBUTRIN SR Tablets to patients receiving
levodopa concurrently should be undertaken with caution, using small initial
doses and gradual dose increases.
Drugs that Lower Seizure Threshold: Concurrent administration of
WELLBUTRIN SR Tablets and agents (e.g., antipsychotics, other
antidepressants, theophylline, systemic steroids, etc.) or treatment
regimens (e.g., abrupt discontinuation of benzodiazepines) that lower
seizure threshold should be undertaken only with extreme caution (see
WARNINGS ). Low initial dosing and gradual dose increases should be
employed.
Nicotine Transdermal System: Data from a comparative study of the
sustained-release formulation of bupropion, HABITROL® (nicotine transdermal
system) (NTS), the combination of sustained-release bupropion plus NTS, and
placebo as an aid to smoking cessation suggest a higher incidence of
treatment-emergent hypertension in patients treated with the combination of
bupropion and NTS. In this study, 6.1% of patients treated with the
combination of bupropion and NTS had treatment-emergent hypertension
compared to 2.5%, 1.6%, and 3.1% of patients treated with bupropion, NTS,
and placebo, respectively. Monitoring for treatment-emergent hypertension is
recommended in patients receiving the combination of bupropion and NTS.
Carcinogenesis, Mutagenesis, Impairment of Fertility: Lifetime
carcinogenicity studies were performed in rats and mice at doses up to 300
and 150 mg/kg per day, respectively. These doses are approximately seven and
two times the maximum recommended human dose (MRHD), respectively, on a mg/m
2 basis. In the rat study there was an increase in nodular proliferative
lesions of the liver at doses of 100 to 300 mg/kg per day (approximately two
to seven times the MRHD on a mg/m 2 basis); lower doses were not tested. The
question of whether or not such lesions may be precursors of neoplasms of
the liver is currently unresolved. Similar liver lesions were not seen in
the mouse study, and no increase in malignant tumors of the liver and other
organs was seen in either study.
Bupropion produced a positive response (two to three times control mutation
rate) in two of five strains in the Ames bacterial mutagenicity test and an
increase in chromosomal aberrations in one of three in vivo rat bone marrow
cytogenetic studies.
A fertility study in rats at doses up to 300 mg/kg revealed no evidence of
impaired fertility.
Pregnancy: Teratogenic Effects: Pregnancy Category B. Teratology studies
have been performed at doses up to 450 mg/kg in rats, and at doses up to 150
mg/kg in rabbits (approximately 7 to 11 and 7 times the MRHD, respectively,
on a mg/m 2 basis), and have revealed no evidence of harm to the fetus due
to bupropion. There are no adequate and well-controlled studies in pregnant
women. Because animal reproduction studies are not always predictive of
human response, this drug should be used during pregnancy only if clearly
needed.
To monitor fetal outcomes of pregnant women exposed to WELLBUTRIN SR, Glaxo
Wellcome Inc. maintains a Bupropion Pregnancy Registry. Health care
providers are encouraged to register patients by calling (800) 336-2176.
Labor and Delivery: The effect of WELLBUTRIN SR Tablets on labor and
delivery in humans is unknown.
Nursing Mothers: Like many other drugs, bupropion and its metabolites are
secreted in human milk. Because of the potential for serious adverse
reactions in nursing infants from WELLBUTRIN SR Tablets, a decision should
be made whether to discontinue nursing or to discontinue the drug, taking
into account the importance of the drug to the mother.
Pediatric Use: The safety and effectiveness of WELLBUTRIN SR Tablets in
pediatric patients below 18 years old have not been established. The
immediate-release formulation of bupropion was studied in 104 pediatric
patients (age range, 6 to 16) in clinical trials of the drug for other
indications. Although generally well tolerated, the limited exposure is
insufficient to assess the safety of bupropion in pediatric patients.
Geriatric Use: Of the approximately 6000 patients who participated in
clinical trials with bupropion sustained-release tablets (depression and
smoking cessation studies), 275 were 65 and over and 47 were 75 and over. In
addition, several hundred patients 65 and over participated in clinical
trials using the immediate-release formulation of bupropion (depression
studies). No overall differences in safety or effectiveness were observed
between these subjects and younger subjects, and other reported clinical
experience has not identified differences in responses between the elderly
and younger patients, but greater sensitivity of some older individuals
cannot be ruled out.
A single-dose pharmacokinetic study demonstrated that the disposition of
bupropion and its metabolites in elderly subjects was similar to that of
younger subjects (see CLINICAL PHARMACOLOGY ).
Bupropion hydrochloride and its metabolites are almost completely excreted
through the kidney and metabolites are likely to undergo conjugation in the
liver prior to urinary excretion. The risk of toxic reaction to this drug
may be greater in patients with impaired renal function. Because elderly
patients are more likely to have decreased renal function, care should be
taken in dose selection, and it may be useful to monitor renal function (see
Use in Patients with Systemic Illness).
ADVERSE REACTIONS: (See also WARNINGS and PRECAUTIONS )
The information included under the Incidence in Controlled Trials subsection
of ADVERSE REACTIONS is based primarily on data from controlled clinical
trials with WELLBUTRIN SR Tablets. Information on additional adverse events
associated with the sustained-release formulation of bupropion in smoking
cessation trials, as well as the immediate-release formulation of bupropion,
is included in a separate section (see Other Events Observed During the
Clinical Development and Postmarketing Experience of Bupropion ).
Incidence in Controlled Trials With WELLBUTRIN SR: Adverse Events
Associated With Discontinuation of Treatment Among Patients Treated With
WELLBUTRIN SR Tablets: In placebo-controlled clinical trials, 9% and 11% of
patients treated with 300 and 400 mg/day, respectively, of WELLBUTRIN SR
Tablets and 4% of patients treated with placebo discontinued treatment due
to adverse events. The specific adverse events in these trials that led to
discontinuation in at least 1% of patients treated with either 300 or 400
mg/day of WELLBUTRIN SR Tablets and at a rate at least twice the placebo
rate are listed in Table 3.
Table 3: Treatment Discontinuations Due to Adverse
Events in Placebo-Controlled Trials Adverse
Event Term WELLBUTRIN
SR
300 mg/day
(n = 376) WELLBUTRIN
SR
400 mg/day
(n = 114) Placebo
(n = 385)
Rash2.4% 0.9% 0.0%
Nausea0.8% 1.8% 0.3%
Agitation 0.3% 1.8% 0.3%
Migraine0.0% 1.8% 0.3%
Adverse Events Occurring at an Incidence of 1% or More Among Patients
Treated With WELLBUTRIN SR Tablets: Table 4 enumerates treatment-emergent
adverse events that occurred among patients treated with 300 and 400 mg/day
of WELLBUTRIN SR Tablets and with placebo in placebo-controlled trials.
Events that occurred in either the 300- or 400-mg/day group at an incidence
of 1% or more and were more frequent than in the placebo group are included.
Reported adverse events were classified using a COSTART-based Dictionary.
Accurate estimates of the incidence of adverse events associated with the
use of any drug are difficult to obtain. Estimates are influenced by drug
dose, detection technique, setting, physician judgments, etc. The figures
cited cannot be used to predict precisely the incidence of untoward events
in the course of usual medical practice where patient characteristics and
other factors differ from those that prevailed in the clinical trials. These
incidence figures also cannot be compared with those obtained from other
clinical studies involving related drug products as each group of drug
trials is conducted under a different set of conditions.
Finally, it is important to emphasize that the tabulation does not reflect
the relative severity and/or clinical importance of the events. A better
perspective on the serious adverse events associated with the use of
WELLBUTRIN SR Tablets is provided in the WARNINGS and PRECAUTIONS sections.
Table 4: Treatment-Emergent Adverse Events
in Placebo-Controlled Trials * Body System/
Adverse Event WELLBUTRIN
SR
300 mg/day
(n = 376) WELLBUTRIN
SR
400 mg/day
(n = 114) Placebo
(n = 385)
Body (General)
Headache 26% 25% 23%
Infection 8% 9% 6%
Abdominal pain 3% 9% 2%
Asthenia 2% 4% 2%
Chest pain 3% 4% 1%
Pain 2% 3% 2%
Fever 1% 2% --
Cardiovascular
Palpitation 2% 6% 2%
Flushing 1% 4% --
Migraine 1% 4% 1%
Hot flashes 1% 3% 1%
Digestive
Dry mouth 17% 24% 7%
Nausea 13% 18% 8%
Constipation 10% 5% 7%
Diarrhea 5% 7% 6%
Anorexia 5% 3% 2%
Vomiting 4% 2% 2%
Dysphagia 0% 2% 0%
Musculoskeletal
Myalgia 2% 6% 3%
Arthralgia 1% 4% 1%
Arthritis 0% 2% 0%
Twitch 1% 2% --
Nervous system
Insomnia 11% 16% 6%
Dizziness 7% 11% 5%
Agitation 3% 9% 2%
Anxiety 5% 6% 3%
Tremor 6% 3% 1%
Nervousness 5% 3% 3%
Somnolence 2% 3% 2%
Irritability 3% 2% 2%
Memory decreased -- 3% 1%
Paresthesia 1% 2% 1%
Central nervous system stimulation 2% 1% 1%
Respiratory
Pharyngitis 3% 11% 2%
Sinusitis 3% 1% 2%
Increased cough 1% 2% 1%
Skin
Sweating 6% 5% 2%
Rash 5% 4% 1%
Pruritus 2% 4% 2%
Urticaria 2% 1% 0%
Special senses
Tinnitus 6% 6% 2%
Taste perversion 2% 4% --
Amblyopia 3% 2% 2%
Urogenital
Urinary frequency 2% 5% 2%
Urinary urgency -- 2% 0%
Vaginal hemorrhage ** 0% 2% --
Urinary tract infection 1% 0% --
*Adverse events that occurred in at least 1% of patients treated with either
300 or 400 mg/day of WELLBUTRIN SR Tablets, but equally or more frequently
in the placebo group, were: abnormal dreams, accidental injury, acne,
appetite increased, back pain, bronchitis, dysmenorrhea, dyspepsia,
flatulence, flu syndrome, hypertension, neck pain, respiratory disorder,
rhinitis, and tooth disorder.
** Incidence based on the number of female patients.
--Hyphen denotes adverse events occurring in greater than 0 but less than
0.5% of patients.
Incidence of Commonly Observed Adverse Events in Controlled Clinical Trials:
Adverse events from Table 4 occurring in at least 5% of patients treated
with WELLBUTRIN SR Tablets and at a rate at least twice the placebo rate are
listed below for the 300- and 400-mg/day dose groups.
WELLBUTRIN SR 300 mg/day: Anorexia, dry mouth, rash, sweating, tinnitus,
and tremor.
WELLBUTRIN SR 400 mg/day: Abdominal pain, agitation, anxiety, dizziness,
dry mouth, insomnia, myalgia, nausea, palpitation, pharyngitis, sweating,
tinnitus, and urinary frequency.
Other Events Observed During the Clinical Development and Postmarketing
Experience of Bupropion: In addition to the adverse events noted above,
the following events have been reported in clinical trials and postmarketing
experience with the sustained-release formulation of bupropion in depressed
patients and in nondepressed smokers, as well as in clinical trials and
postmarketing clinical experience with the immediate-release formulation of
bupropion.
Adverse events for which frequencies are provided below occurred in clinical
trials with the sustained-release formulation of bupropion. The frequencies
represent the proportion of patients who experienced a treatment-emergent
adverse event on at least one occasion in placebo-controlled studies for
depression (n = 987) or smoking cessation (n = 1013), or patients who
experienced an adverse event requiring discontinuation of treatment in an
open-label surveillance study with WELLBUTRIN SR Tablets (n = 3100). All
treatment-emergent adverse events are included except those listed in Tables
1 through 4, those events listed in other safety-related sections, those
adverse events subsumed under COSTART terms that are either overly general
or excessively specific so as to be uninformative, those events not
reasonably associated with the use of the drug, and those events that were
not serious and occurred in fewer than two patients. Events of major
clinical importance are described in the WARNINGS and PRECAUTIONS sections
of the labeling. Events are further categorized by body system and listed in
order of decreasing frequency according to the following definitions of
frequency: Frequent adverse events are defined as those occurring in at
least 1/100 patients. Infrequent adverse events are those occurring in 1/100
to 1/1000 patients, while rare events are those occurring in less than
1/1000 patients.
Adverse events for which frequencies are not provided occurred in clinical
trials or postmarketing experience with bupropion. Only those adverse events
not previously listed for sustained-release bupropion are included. The
extent to which these events may be associated with WELLBUTRIN SR is
unknown.
Body (General): Infrequent were chills, facial edema, musculoskeletal
chest pain, and photosensitivity. Rare was malaise.
Cardiovascular: Infrequent were postural hypotension, stroke, tachycardia,
and vasodilation. Rare was syncope. Also observed were complete
atrioventricular block, extrasystoles, hypotension, myocardial infarction,
phlebitis, and pulmonary embolism.
Digestive: Infrequent were abnormal liver function, bruxism, gastric
reflux, gingivitis, glossitis, increased salivation, jaundice, mouth ulcers,
stomatitis, and thirst. Rare was edema of tongue. Also observed were
colitis, esophagitis, gastrointestinal hemorrhage, gum hemorrhage,
hepatitis, intestinal perforation, liver damage, pancreatitis, and stomach
ulcer.
Endocrine: Also observed were hyperglycemia, hypoglycemia, and syndrome of
inappropriate antidiuretic hormone.
Hemic and Lymphatic: Infrequent was ecchymosis. Also observed were anemia,
leukocytosis, leukopenia, lymphadenopathy, pancytopenia, and
thrombocytopenia.
Metabolic and Nutritional: Infrequent were edema and peripheral edema.
Also observed was glycosuria.
Musculoskeletal: Infrequent were leg cramps. Also observed were muscle
rigidity/fever/rhabdomyolysis and muscle weakness.
Nervous System: Infrequent were abnormal coordination, decreased libido,
depersonalization, dysphoria, emotional lability, hostility, hyperkinesia,
hypertonia, hypesthesia, suicidal ideation, and vertigo. Rare were amnesia,
ataxia, derealization, and hypomania. Also observed were abnormal
electroencephalogram (EEG), akinesia, aphasia, coma, delirium, dysarthria,
dyskinesia, dystonia, euphoria, extrapyramidal syndrome, hypokinesia,
increased libido, manic reaction, neuralgia, neuropathy, paranoid reaction,
and unmasking tardive dyskinesia.
Respiratory: Rare was bronchospasm. Also observed was pneumonia.
Skin: Rare was maculopapular rash. Also observed were alopecia,
angioedema, exfoliative dermatitis, and hirsutism.
Special Senses: Infrequent were accommodation abnormality and dry eye.
Also observed were deafness, diplopia, and mydriasis.
Urogenital: Infrequent were impotence, polyuria, and prostate disorder.
Also observed were abnormal ejaculation, cystitis, dyspareunia, dysuria,
gynecomastia, menopause, painful erection, salpingitis, urinary
incontinence, urinary retention, and vaginitis.
DRUG ABUSE AND DEPENDENCE
Controlled Substance Class: Bupropion is not a controlled substance.
Humans: Controlled clinical studies of bupropion conducted in normal
volunteers, in subjects with a history of multiple drug abuse, and in
depressed patients showed some increase in motor activity and
agitation/excitement.
In a population of individuals experienced with drugs of abuse, a single
dose of 400 mg of bupropion produced mild amphetamine-like activity as
compared to placebo on the Morphine-Benzedrine Subscale of the Addiction
Research Center Inventories (ARCI), and a score intermediate between placebo
and amphetamine on the Liking Scale of the ARCI. These scales measure
general feelings of euphoria and drug desirability.
Findings in clinical trials, however, are not known to reliably predict the
abuse potential of drugs. Nonetheless, evidence from single-dose studies
does suggest that the recommended daily dosage of bupropion when
administered in divided doses is not likely to be especially reinforcing to
amphetamine or stimulant abusers. However, higher doses that could not be
tested because of the risk of seizure might be modestly attractive to those
who abuse stimulant drugs.
Animals: Studies in rodents and primates have shown that bupropion
exhibits some pharmacologic actions common to psychostimulants. In rodents,
it has been shown to increase locomotor activity, elicit a mild stereotyped
behavioral response, and increase rates of responding in several
schedule-controlled behavior paradigms. In primate models to assess the
positive reinforcing effects of psychoactive drugs, bupropion was
self-administered intravenously. In rats, bupropion produced
amphetamine-like and cocaine-like discriminative stimulus effects in drug
discrimination paradigms used to characterize the subjective effects of
psychoactive drugs.
OVERDOSAGE
Human Overdose Experience: There has been very limited experience with
overdosage of WELLBUTRIN SR Tablets; three cases were reported during
clinical trials. One patient ingested 3000 mg of WELLBUTRIN SR Tablets and
vomited quickly after the overdose; the patient experienced blurred vision
and lightheadedness. A second patient ingested a "handful" of WELLBUTRIN SR
Tablets and experienced confusion, lethargy, nausea, jitteriness, and
seizure. A third patient ingested 3600 mg of WELLBUTRIN SR Tablets and a
bottle of wine; the patient experienced nausea, visual hallucinations, and
"grogginess." None of the patients experienced further sequelae.
There has been extensive experience with overdosage of the immediate-release
formulation of bupropion. Thirteen overdoses occurred during clinical
trials. Twelve patients ingested 850 to 4200 mg and recovered without
significant sequelae. Another patient who ingested 9000 mg of the
immediate-release formulation of bupropion and 300 mg of tranylcypromine
experienced a grand mal seizure and recovered without further sequelae.
Since introduction, overdoses of up to 17,500 mg of the immediate-release
formulation of bupropion have been reported. Seizure was reported in
approximately one third of all cases. Other serious reactions reported with
overdoses of the immediate-release formulation of bupropion alone included
hallucinations, loss of consciousness, and sinus tachycardia. Fever, muscle
rigidity, rhabdomyolysis, hypotension, stupor, coma, and respiratory failure
have been reported when the immediate-release formulation of bupropion was
part of multiple drug overdoses.
Although most patients recovered without sequelae, deaths associated with
overdoses of the immediate-release formulation of bupropion alone have been
reported rarely in patients ingesting massive doses of the drug. Multiple
uncontrolled seizures, bradycardia, cardiac failure, and cardiac arrest
prior to death were reported in these patients.
Overdosage Management: Ensure an adequate airway, oxygenation, and
ventilation. Monitor cardiac rhythm and vital signs. EEG monitoring is also
recommended for the first 48 hours post-ingestion. 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. There is no experience with the
use of forced diuresis, dialysis, hemoperfusion, or exchange transfusion in
the management of bupropion overdoses. No specific antidotes for bupropion
are known.
Due to the dose-related risk of seizures with WELLBUTRIN SR, hospitalization
following suspected overdose should be considered. Based on studies in
animals, it is recommended that seizures be treated with intravenous
benzodiazepine administration and other supportive measures, as appropriate.
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
General Dosing Considerations: It is particularly important to administer
WELLBUTRIN SR Tablets in a manner most likely to minimize the risk of
seizure (see WARNINGS ). Gradual escalation in dosage is also important if
agitation, motor restlessness, and insomnia, often seen during the initial
days of treatment, are to be minimized. If necessary, these effects may be
managed by temporary reduction of dose or the short-term administration of
an intermediate to long-acting sedative hypnotic. A sedative hypnotic
usually is not required beyond the first week of treatment. Insomnia may
also be minimized by avoiding bedtime doses. If distressing, untoward
effects supervene, dose escalation should be stopped.
Initial Treatment: The usual adult target dose for WELLBUTRIN SR Tablets
is 300 mg/day, given as 150 mg twice daily. Dosing with WELLBUTRIN SR
Tablets should begin at 150 mg/day given as a single daily dose in the
morning. If the 150-mg initial dose is adequately tolerated, an increase to
the 300-mg/day target dose, given as 150 mg twice daily, may be made as
early as day 4 of dosing. There should be an interval of at least 8 hours
between successive doses.
Increasing the Dosage Above 300 mg/day: As with other antidepressants, the
full antidepressant effect of WELLBUTRIN SR Tablets may not be evident until
4 weeks of treatment or longer. An increase in dosage to the maximum of 400
mg/day, given as 200 mg twice daily, may be considered for patients in whom
no clinical improvement is noted after several weeks of treatment at 300
mg/day.
Maintenance The lowest dose that maintains remission is recommended.
Although it is not known how long the patient should remain on WELLBUTRIN SR
Tablets, it is generally recognized that acute episodes of depression
require several months or longer of antidepressant drug treatment.
HOW SUPPLIED
WELLBUTRIN SR Sustained-Release Tablets, 100 mg of bupropion hydrochloride,
are blue, round, biconvex, film-coated tablets printed with "WELLBUTRIN SR
100" in bottles of 60 (NDC 0173-0947-55) tablets.
WELLBUTRIN SR Sustained-Release Tablets, 150 mg of bupropion hydrochloride,
are purple, round, biconvex, film-coated tablets printed with "WELLBUTRIN SR
150" in bottles of 60 (NDC 0173-0135-55) tablets.
Store at controlled room temperature, 20° to 25°C (68° to 77°F) [see USP].
Dispense in a tight, light-resistant container as defined in the USP.
PRODUCT PHOTO(S):
Information for the Patient
WELLBUTRIN SR® (bupropion hydrochloride)
Sustained-Release Tablets
Please read this information before you start taking WELLBUTRIN SR. Also
read this leaflet each time you renew your prescription, in case anything
has changed. This information is not intended to take the place of
discussions between you and your doctor. You and your doctor should discuss
WELLBUTRIN SR as it relates to the treatment of your depression. Do not let
anyone else use your WELLBUTRIN SR.
IMPORTANT WARNING:
At a dose of 300 mg each day, there is a chance that approximately 1 out of
every 1000 people taking bupropion hydrochloride, the active ingredient in
WELLBUTRIN SR, will have a seizure. At a dose of 400 mg each day, there is a
chance that approximately 4 out of every 1000 people will have a seizure.
The chance of this happening increases if you:
have a seizure disorder (for example, epilepsy);
have or have had an eating disorder (for example, bulimia or anorexia
nervosa);
take more than the recommended amount of WELLBUTRIN SR; or
take other medicines with the same active ingredient that is in WELLBUTRIN
SR, such as ZYBAN® (bupropion hydrochloride) Sustained-Release Tablets (used
to help people quit smoking).
You can reduce the chance of experiencing a seizure by following your
doctor' directions on how to take WELLBUTRIN SR. You should also discuss
with your doctor whether WELLBUTRIN SR is right for you.
What is WELLBUTRIN SR?
WELLBUTRIN SR is a prescription medicine used to treat depression.
Who should not take WELLBUTRIN SR:
You should not take WELLBUTRIN SR if you:
have a seizure disorder (for example, epilepsy);
are already taking ZYBAN or any other medicines that contain bupropion
hydrochloride;
have or have had an eating disorder (for example, bulimia or anorexia
nervosa);
are currently taking or have recently taken a monoamine oxidase inhibitor
(MAOI); or
are allergic to bupropion.
Are there special concerns for women?
WELLBUTRIN SR is not recommended for women who are pregnant or
breast-feeding. Women should notify their doctor if they become pregnant or
intend to become pregnant while taking WELLBUTRIN SR.
How should I take WELLBUTRIN SR?
You should take WELLBUTRIN SR as directed by your doctor. The usual
recommended dosing is to begin treatment with WELLBUTRIN SR by taking one
150-mg tablet in the morning. As early as day 4 of treatment, your doctor
may increase your dose to one 150-mg tablet in the morning and one 150-mg
tablet in the early evening (for a total of 300 mg each day).
If your depression does not improve after several weeks, your doctor may
increase the dose of WELLBUTRIN SR to a total of 400 mg each day (taken as
200 mg in the morning and 200 mg in the early evening). Doses should be
taken at least 8 hours apart.
Never take an "extra" dose of WELLBUTRIN SR tablets for any reason, even if
you miss a dose. If you forget to take a dose, do not take an extra tablet
to "catch up" for the dose you forgot. Wait and take your next tablet at the
regular time. Do not take more tablets than your doctor prescribed. This is
important so you do not increase your chance of having a seizure.
It is important to swallow WELLBUTRIN SR tablets whole. Do not chew, divide,
or crush tablets.
How long should I take WELLBUTRIN SR?
Only you and your doctor can determine how long you should take WELLBUTRIN
SR. You and your doctor should discuss your signs and symptoms of depression
regularly to determine how long you should take WELLBUTRIN SR. Do not stop
taking your medicine or decrease the amount of medicine you are taking
without talking to your doctor first.
What are possible side effects of WELLBUTRIN SR?
Like all medicines, WELLBUTRIN SR may cause side effects.
The most common side effects of WELLBUTRIN SR in clinical studies were:
At 300 mg/day: Loss of appetite, dry mouth, skin rash, sweating, ringing in
the ears, and shakiness.
At 400 mg/day: Abdominal (stomach) pain, agitation, anxiety, dizziness, dry
mouth, difficulty sleeping, muscle pain, nausea, rapid heart beat, sore
throat, sweating, ringing in the ears, and urinating more often.
The side effects of WELLBUTRIN SR are generally mild and often disappear
after a few weeks. If you have nausea, you may want to take your medicine
with food. If you have difficulty sleeping, avoid taking your medicine too
close to bedtime.
The most common side effects that caused people to stop taking WELLBUTRIN SR
during clinical studies were skin rash, nausea, agitation, and migraine (a
severe type of headache).
Stop taking WELLBUTRIN SR and contact your doctor or health care
professional if you have signs of an allergic reaction such as a skin rash,
or difficulty in breathing. Discuss any other troublesome side effects with
your doctor.
Use caution before driving a car or operating complex, hazardous machinery
until you know if WELLBUTRIN SR affects your ability to perform these tasks.
Will taking WELLBUTRIN SR change my body weight?
In clinical studies with WELLBUTRIN SR, some people lost weight and other
people gained weight.
For people who lost weight, 14 out of 100 people taking 300 mg/day of
WELLBUTRIN SR lost more than 5 lbs, 19 out of 100 people taking 400 mg/day
lost more than 5 lbs, and 6 out of 100 people taking placebo (a sugar pill)
lost more than 5 lbs.
For people who gained weight, 3 out of 100 people taking 300 mg/day of
WELLBUTRIN SR gained more than 5 lbs, 2 out of 100 people taking 400 mg/day
gained more than 5 lbs, and 4 out of 100 people taking placebo (a sugar
pill) gained more than 5 lbs.
Since weight change (loss or gain) also can be a symptom of depression, you
should discuss with your doctor whether WELLBUTRIN SR is right for you.
Should I drink alcohol while I am taking WELLBUTRIN SR?
It is best to not drink alcohol at all or to drink very little while taking
WELLBUTRIN SR. If you usually drink a lot of alcohol, or if you drink a lot
of alcohol and suddenly stop, you may increase your chance of having a
seizure. Therefore, it is important to discuss your use of alcohol with your
doctor before you begin taking WELLBUTRIN SR.
Will WELLBUTRIN SR affect other medicines I am taking?
WELLBUTRIN SR may affect other medicines you're taking. It is important not
to take medicines that may increase the chance for you to have a seizure.
Therefore, you should make sure that your doctor knows about all
medicines--prescription and over-the-counter--you are taking or plan to
take.
Do WELLBUTRIN SR tablets have a characteristic odor?
WELLBUTRIN SR tablets may have a characteristic odor. If present, this odor
is normal.
How should I store WELLBUTRIN SR?
Store WELLBUTRIN SR at room temperature, out of direct sunlight.
Keep WELLBUTRIN SR in a tightly closed container.
Keep WELLBUTRIN SR out of the reach of children.
This summary provides important information about WELLBUTRIN SR. This
summary cannot replace the more detailed information that you need from your
doctor. If you have any questions or concerns about either WELLBUTRIN SR or
depression, talk to your doctor or other health care professional.
Distributed by:
Glaxo Wellcome Inc.
Research Triangle Park, NC 27709
Manufactured by:
Glaxo Wellcome Inc.
Research Triangle Park, NC 27709
or Catalytica Pharmaceuticals, Inc.
Greenville, NC 27834
Habitrol is a registered trademark of Ciba-Geigy Corporation.
US Patent Nos. 5,358,970; 5,427,798; and Re. 33,994
©Copyright 1996, 1998, 1999, Glaxo Wellcome Inc. All rights reserved.
May 1999/RL-707
Copyright©2000 Medical Economics
Charles R. Grefer, MS
Coordinator & Counselor, OR & START
112 College Road, Loch Sheldrake, NY 12759
1 800 577 5243; Ext: 4241
Nobody Expects The Spanish Inquisition. - Monty Python
A Few Website Affiliations:
http://www.uni.edu/mpact/pactcnf.htm <http://www.uni.edu/mpact/pactcnf.htm>
http://www.acpa.nche.edu/ <http://www.acpa.nche.edu/>
http://www.counseling.org/cacrep/ <http://www.counseling.org/cacrep/>
http://www.nbcc.org/ <http://www.nbcc.org/>
http://www.ksu.edu/nacada/ <http://www.ksu.edu/nacada/>
Favorite Sites:
http://www.egroups.com/group/work2play
<http://www.egroups.com/group/work2play>
http://wordsmith.org/ <http://wordsmith.org/>
http://webster.commnet.edu/HP/pages/darling/grammar/notorious.htm
<http://webster.commnet.edu/HP/pages/darling/grammar/notorious.htm>
http://www.m-w.com/netdict.htm <http://www.m-w.com/netdict.htm>
http://mentalhelp.net/dxtx.htm <http://mentalhelp.net/dxtx.htm>
-----Original Message-----
From: [log in to unmask] [ mailto:[log in to unmask]
<mailto:[log in to unmask]> ]
Sent: Monday, May 15, 2000 12:40 PM
To: [log in to unmask]; [log in to unmask]
Subject: Re: How soon does welbutren or other anti depressents work
i mean wellbutren
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