Recommended Topic Related To:

Wellbutrin SR

"Dec. 31, 2012 -- Depression is common among older people who go on to develop Alzheimer's disease, leading to widespread speculation that it may be one possible cause for age-related dementias.

Now, a new study suggests that rather th"...

Wellbutrin SR

Side Effects
Interactions

SIDE EFFECTS

The following adverse reactions are discussed in greater detail in other sections of the labeling:

Clinical Trials Experience

Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared with rates in the clinical trials of another drug and may not reflect the rates observed in clinical practice.

Adverse Reactions Leading to Discontinuation of Treatment

In placebo-controlled clinical trials, 4%, 9%, and 11% of the placebo, 300-mg-per-day, and 400-mg-per-day groups, respectively, discontinued treatment due to adverse reactions. The specific adverse reactions leading to discontinuation in at least 1% of the 300-mg-per-day or 400-mg-per-day groups and at a rate at least twice the placebo rate are listed in Table 2.

Table 2: Treatment Discontinuations Due to Adverse Reactions in Placebo-Controlled Trials

Adverse Reaction Placebo
(n = 385)
WELLBUTRIN SR 300 mg/day
(n = 376)
WELLBUTRIN SR 400 mg/day
(n = 114)
Rash 0.0% 2.4% 0.9%
Nausea 0.3% 0.8% 1.8%
Agitation 0.3% 0.3% 1.8%
Migraine 0.3% 0.0% 1.8%

Commonly Observed Adverse Reactions

Adverse reactions from Table 3 occurring in at least 5% of subjects treated with WELLBUTRIN SR and at a rate at least twice the placebo rate are listed below for the 300- and 400-mg-per-day dose groups.

WELLBUTRIN SR 300 mg per day: Anorexia, dry mouth, rash, sweating, tinnitus, and tremor.

WELLBUTRIN SR 400 mg per day: Abdominal pain, agitation, anxiety, dizziness, dry mouth, insomnia, myalgia, nausea, palpitation, pharyngitis, sweating, tinnitus, and urinary frequency.

Adverse reactions reported in placebo-controlled trials are presented in Table 3. Reported adverse reactions were classified using a COSTART-based Dictionary.

Table 3: Adverse Reactions Reported by at Least 1% of Subjects and at a Greater Frequency Than Placebo in Controlled Clinical Trials

Body System/ Adverse Reaction 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%
  Blurred vision or diplopia 3% 2% 2%
Urogenital
  Urinary frequency 2% 5% 2%
  Urinary urgency 2% 0%
  Vaginal hemorrhagea 0% 2%
  Urinary tract infection 1% 0%
aIncidence based on the number of female subjects.
— Hyphen denotes adverse events occurring in greater than 0 but less than 0.5% of subjects.

Other Adverse Reactions Observed During the Clinical Development of Bupropion

In addition to the adverse reactions noted above, the following adverse reactions have been reported in clinical trials with the sustained-release formulation of bupropion in depressed subjects and in nondepressed smokers, as well as in clinical trials with the immediate-release formulation of bupropion.

Adverse reaction frequencies represent the proportion of subjects who experienced a treatment-emergent adverse reaction on at least one occasion in placebo-controlled trials for depression (n = 987) or smoking cessation (n = 1,013), or subjects who experienced an adverse reaction requiring discontinuation of treatment in an open-label surveillance trial with WELLBUTRIN SR (n = 3,100). All treatment-emergent adverse reactions are included except those listed in Table 3, those listed in other safety-related sections of the prescribing information, those subsumed under COSTART terms that are either overly general or excessively specific so as to be uninformative, those not reasonably associated with the use of the drug, and those that were not serious and occurred in fewer than 2 subjects.

Adverse reactions are further categorized by body system and listed in order of decreasing frequency according to the following definitions of frequency: Frequent adverse reactions are defined as those occurring in at least 1/100 subjects. Infrequent adverse reactions are those occurring in 1/100 to 1/1,000 subjects, while rare events are those occurring in less than 1/1,000 subjects.

Body (General): Infrequent were chills, facial edema, and photosensitivity. Rare was malaise.

Cardiovascular: Infrequent were postural hypotension, stroke, tachycardia, and vasodilation. Rare were syncope and myocardial infarction.

Digestive: Infrequent were abnormal liver function, bruxism, gastric reflux, gingivitis, increased salivation, jaundice, mouth ulcers, stomatitis, and thirst. Rare was edema of tongue.

Hemic and Lymphatic: Infrequent was ecchymosis.

Metabolic and Nutritional: Infrequent were edema and peripheral edema.

Musculoskeletal: Infrequent were leg cramps.

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.

Respiratory: Rare was bronchospasm.

Special Senses: Infrequent were accommodation abnormality and dry eye.

Urogenital: Infrequent were impotence, polyuria, and prostate disorder.

Changes in Body Weight

In placebo-controlled trials, subjects experienced weight gain or weight loss as shown in Table 4.

Table 4: Incidence of Weight Gain and Weight Loss ( ≥ 5 lbs.) 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 clinical trials conducted with the immediate-release formulation of bupropion, 35% of subjects receiving tricyclic antidepressants gained weight, compared with 9% of subjects treated with the immediate-release formulation of bupropion. If weight loss is a major presenting sign of a patient's depressive illness, the anorectic and/or weight-reducing potential of WELLBUTRIN SR should be considered.

Postmarketing Experience

The following adverse reactions have been identified during post-approval use of WELLBUTRIN SR and are not described elsewhere in the label. Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure.

Body (General): Arthralgia, myalgia, and fever with rash and other symptoms suggestive of delayed hypersensitivity. These symptoms may resemble serum sickness [see WARNINGS AND PRECAUTIONS].

Cardiovascular: Complete atrioventricular block, extrasystoles, hypotension, hypertension (in some cases severe), phlebitis, and pulmonary embolism.

Digestive: Colitis, esophagitis, gastrointestinal hemorrhage, gum hemorrhage, hepatitis, intestinal perforation, pancreatitis, and stomach ulcer.

Endocrine: Hyperglycemia, hypoglycemia, and syndrome of inappropriate antidiuretic hormone.

Hemic and Lymphatic: Anemia, leukocytosis, leukopenia, lymphadenopathy, pancytopenia, and thrombocytopenia. Altered PT and/or INR, infrequently associated with hemorrhagic or thrombotic complications, were observed when bupropion was coadministered with warfarin.

Metabolic and Nutritional: Glycosuria.

Musculoskeletal: Muscle rigidity/fever/rhabdomyolysis and muscle weakness.

Nervous System: Abnormal electroencephalogram (EEG), aggression, akinesia, aphasia, coma, completed suicide, delirium, delusions, dysarthria, dyskinesia, dystonia, euphoria, extrapyramidal syndrome, hallucinations, hypokinesia, increased libido, manic reaction, neuralgia, neuropathy, paranoid ideation, restlessness, suicide attempt, and unmasking tardive dyskinesia.

Respiratory: Pneumonia.

Skin: Alopecia, angioedema, exfoliative dermatitis, hirsutism, and Stevens-Johnson syndrome.

Special Senses: Deafness, increased intraocular pressure, and mydriasis.

Urogenital: Abnormal ejaculation, cystitis, dyspareunia, dysuria, gynecomastia, menopause, painful erection, salpingitis, urinary incontinence, urinary retention, and vaginitis.

Read the Wellbutrin SR (bupropion hydrochloride sustained-release) Side Effects Center for a complete guide to possible side effects

DRUG INTERACTIONS

Potential For Other Drugs To Affect WELLBUTRIN SR

Bupropion is primarily metabolized to hydroxybupropion by CYP2B6. Therefore, the potential exists for drug interactions between WELLBUTRIN SR and drugs that are inhibitors or inducers of CYP2B6.

Inhibitors of CYP2B6

Ticlopidine and Clopidogrel: Concomitant treatment with these drugs can increase bupropion exposure but decrease hydroxybupropion exposure. Based on clinical response, dosage adjustment of WELLBUTRIN SR may be necessary when coadministered with CYP2B6 inhibitors (e.g., ticlopidine or clopidogrel) [see CLINICAL PHARMACOLOGY].

Inducers of CYP2B6

Ritonavir, Lopinavir, and Efavirenz: Concomitant treatment with these drugs can decrease bupropion and hydroxybupropion exposure. Dosage increase of WELLBUTRIN SR may be necessary when coadministered with ritonavir, lopinavir, or efavirenz [see CLINICAL PHARMACOLOGY] but should not exceed the maximum recommended dose.

Carbamazepine, Phenobarbital, Phenytoin: While not systematically studied, these drugs may induce the metabolism of bupropion and may decrease bupropion exposure [see CLINICAL PHARMACOLOGY]. If bupropion is used concomitantly with a CYP inducer, it may be necessary to increase the dose of bupropion, but the maximum recommended dose should not be exceeded.

Potential For WELLBUTRIN SR To Affect Other Drugs

Drugs Metabolized by CYP2D6

Bupropion and its metabolites (erythrohydrobupropion, threohydrobupropion, hydroxybupropion) are CYP2D6 inhibitors. Therefore, coadministration of WELLBUTRIN SR with drugs that are metabolized by CYP2D6 can increase the exposures of drugs that are substrates of CYP2D6. Such drugs include certain antidepressants (e.g., venlafaxine, nortriptyline, imipramine, desipramine, paroxetine, fluoxetine, and sertraline), antipsychotics (e.g., haloperidol, risperidone, thioridazine), beta-blockers (e.g., metoprolol), and Type 1C antiarrhythmics (e.g., propafenone and flecainide). When used concomitantly with WELLBUTRIN SR, it may be necessary to decrease the dose of these CYP2D6 substrates, particularly for drugs with a narrow therapeutic index.

Drugs that require metabolic activation by CYP2D6 to be effective (e.g., tamoxifen) theoretically could have reduced efficacy when administered concomitantly with inhibitors of CYP2D6 such as bupropion. Patients treated concomitantly with WELLBUTRIN SR and such drugs may require increased doses of the drug [see CLINICAL PHARMACOLOGY].

Drugs That Lower Seizure Threshold

Use extreme caution when coadministering WELLBUTRIN SR with other drugs that lower seizure threshold (e.g., other bupropion products, antipsychotics, antidepressants, theophylline, or systemic corticosteroids). Use low initial doses and increase the dose gradually [see CONTRAINDICATIONS, WARNINGS AND PRECAUTIONS].

Dopaminergic Drugs (Levodopa And Amantadine)

Bupropion, levodopa, and amantadine have dopamine agonist effects. CNS toxicity has been reported when bupropion was coadministered with levodopa or amantadine. Adverse reactions have included restlessness, agitation, tremor, ataxia, gait disturbance, vertigo, and dizziness. It is presumed that the toxicity results from cumulative dopamine agonist effects. Use caution when administering WELLBUTRIN SR concomitantly with these drugs.

Use With Alcohol

In postmarketing experience, there have been rare reports of adverse neuropsychiatric events or reduced alcohol tolerance in patients who were drinking alcohol during treatment with WELLBUTRIN SR. The consumption of alcohol during treatment with WELLBUTRIN SR should be minimized or avoided.

MAO Inhibitors

Bupropion inhibits the reuptake of dopamine and norepinephrine. Concomitant use of MAOIs and bupropion is contraindicated because there is an increased risk of hypertensive reactions if bupropion is used concomitantly with MAOIs. Studies in animals demonstrate that the acute toxicity of bupropion is enhanced by the MAO inhibitor phenelzine. At least 14 days should elapse between discontinuation of an MAOI intended to treat depression and initiation of treatment with WELLBUTRIN SR. Conversely, at least 14 days should be allowed after stopping WELLBUTRIN SR before starting an MAOI antidepressant [see DOSAGE AND ADMINISTRATION, CONTRAINDICATIONS].

Drug-Laboratory Test Interactions

False-positive urine immunoassay screening tests for amphetamines have been reported in patients taking bupropion. This is due to lack of specificity of some screening tests. False-positive test results may result even following discontinuation of bupropion therapy. Confirmatory tests, such as gas chromatography/mass spectrometry, will distinguish bupropion from amphetamines.

Drug Abuse And Dependence

Controlled Substance

Bupropion is not a controlled substance.

Abuse

Humans

Controlled clinical trials of bupropion (immediate-release formulation) conducted in normal volunteers, in subjects with a history of multiple drug abuse, and in depressed subjects 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 with 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 trials does suggest that the recommended daily dosage of bupropion when administered in divided doses is not likely to be significantly reinforcing to amphetamine or CNS stimulant abusers. However, higher doses (that could not be tested because of the risk of seizure) might be modestly attractive to those who abuse CNS stimulant drugs.

Animals

Studies in rodents and primates demonstrated that bupropion exhibits some pharmacologic actions common to psychostimulants. In rodents, it has been shown to increase locomotor activity, elicit a mild stereotyped behavior response, and increase rates of responding in several schedule-controlled behavior paradigms. In primate models assessing 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.

Read the Wellbutrin SR Drug Interactions Center for a complete guide to possible interactions

Last reviewed on RxList: 7/31/2014
This monograph has been modified to include the generic and brand name in many instances.

Side Effects
Interactions
A A A

Wellbutrin SR - User Reviews

Wellbutrin SR User Reviews

Now you can gain knowledge and insight about a drug treatment with Patient Discussions.

Here is a collection of user reviews for the medication Wellbutrin SR sorted by most helpful. Patient Discussions FAQs

Report Problems to the Food and Drug Administration

 

You are encouraged to report negative side effects of prescription drugs to the FDA. Visit the FDA MedWatch website or call 1-800-FDA-1088.


Emotional Wellness

Get tips on therapy and treatment.