bupropion (bupropion hydrochloride 200 mg) Dailymed

6 Adverse Reactions

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

• •Suicidal thoughts and behaviors in adolescents and young adults [see Boxed Warning, Warnings and Precautions (5.1)]
• •Neuropsychiatric symptoms and suicide risk in smoking cessation treatment [see Warnings and Precautions (5.2)]
• •Seizure [see Warnings and Precautions (5.3)]
• •Hypertension [see Warnings and Precautions (5.4)]
• •Activation of mania or hypomania [see Warnings and Precautions (5.5)]
• •Psychosis and other neuropsychiatric reactions [see Warnings and Precautions (5.6)]
• •Angle-closure glaucoma [see Warnings and Precautions (5.7)]
• •Hypersensitivity reactions [see Warnings and Precautions (5.8)]

Most common adverse reactions (incidence ≥5% and ≥2% more than placebo rate) are: headache, dry mouth, nausea, insomnia, dizziness, pharyngitis, constipation, agitation, anxiety, abdominal pain, tinnitus, tremor, palpitation, myalgia, sweating, rash, and anorexia. (6.1)

To report SUSPECTED ADVERSE REACTIONS, contact Solco Healthcare US, LLC at 1-866-257-2597 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.

6.1 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/day, and 400-mg/day groups, respectively, discontinued treatment due to adverse reactions. The specific adverse reactions leading to discontinuation in at least 1% of the 300-mg/day or 400-mg/day groups and at a rate at least twice the placebo rate are uled in Table 2.

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

Adverse Reaction	Placebo (n=385)	Bupropion hydrochloride extended-release (SR) tablets 300 mg/day (n=376)	Bupropion hydrochloride extended-release (SR) tablets 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 bupropion hydrochloride extended-release (SR) tablets and at a rate at least twice the placebo rate are uled below for the 300- and 400-mg/day dose groups.

Bupropion hydrochloride extended-release (SR) tablets 300 mg/day:

Anorexia, dry mouth, rash, sweating, tinnitus, and tremor.

Bupropion hydrochloride extended-release (SR) tablets 400 mg/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.
HeadacheInfectionAbdominal painAstheniaChest painPainFeverPalpitationFlushingMigraineHot flashesDry mouthNauseaConstipationDiarrheaAnorexiaVomitingDysphagiaMyalgiaArthralgiaArthritisTwitchInsomniaDizzinessAgitationAnxietyTremorNervousnessSomnolenceIrritabilityMemory decreasedParesthesiaCentral nervous system stimulationPharyngitisSinusitisIncreased coughSweatingRashPruritusUrticariaTinnitusTaste perversionBlurred vision or diplopiaUrinary frequencyUrinary urgencyVaginal hemorrhage^aUrinary tract infection^a Incidence based on the number of female subjects.
— Hyphen denotes adverse events occurring in greater than 0 but less than 0.5% of subjects.

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	Bupropion hydrochloride extended-release (SR) tablets 300 mg/day(n = 376)	Bupropion hydrochloride extended-release (SR) tablets 400 mg/day (n = 114)	Placebo (n = 385)
Body (general)
26%	25%	23%
8%	9%	6%
3%	9%	2%
2%	4%	2%
3%	4%	1%
2%	3%	2%
1%	2%	—
Cardiovascular
2%	6%	2%
1%	4%	—
1%	4%	1%
1%	3%	1%
Digestive
17%	24%	7%
13%	18%	8%
10%	5%	7%
5%	7%	6%
5%	3%	2%
4%	2%	2%
0%	2%	0%
Musculoskeletal
2%	6%	3%
1%	4%	1%
0%	2%	0%
1%	2%	—
Nervous system
11%	16%	6%
7%	11%	5%
3%	9%	2%
5%	6%	3%
6%	3%	1%
5%	3%	3%
2%	3%	2%
3%	2%	2%
—	3%	1%
1%	2%	1%
2%	1%	1%
Respiratory
3%	11%	2%
3%	1%	2%
1%	2%	1%
Skin
6%	5%	2%
5%	4%	1%
2%	4%	2%
2%	1%	0%
Special senses
6%	6%	2%
2%	4%	—
3%	2%	2%
Urogenital
2%	5%	2%
—	2%	0%
0%	2%	—
1%	0%	—

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 bupropion hydrochloride extended-release (SR) tablets (n = 3,100). All treatment-emergent adverse reactions are included except those uled in Table 3, those uled 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 uled 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	Bupropion hydrochloride extended-release (SR) tablets 300 mg/day (n = 339)	Bupropion hydrochloride extended-release (SR) tablets 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 bupropion hydrochloride extended-release (SR) tablets should be considered.

6.2 Postmarketing Experience

The following adverse reactions have been identified during postapproval use of bupropion hydrochloride extended-release (SR) tablets 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 (5.8)] .

Cardiovascular

Complete atrioventricular block, extrasystoles, hypotension, hypertension (in some cases severe), phlebitis, pulmonary embolism, and Brugada pattern/syndrome.

Digestive

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

Endocrine

Hyperglycemia, hypoglycemia, hyponatremia, and syndrome of inappropriate antidiuretic hormone secretion.

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, euphoria, extrapyramidal syndrome (dyskinesia, dystonia, hypokinesia, parkinsonism), hallucinations, increased libido, manic reaction, neuralgia, neuropathy, paranoid ideation, restlessness, suicide attempt, and unmasking tardive dyskinesia.

Respiratory

Pneumonia.

Skin and Subcutaneous Tissue Disorders

Alopecia, angioedema, exfoliative dermatitis, hirsutism, Stevens-Johnson syndrome, acute generalized exanthematous pustulosis, and drug reaction with eosinophilia and systemic symptoms (DRESS).

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.