WELLBUTRIN XL SIDE EFFECTS
- Generic Name: bupropion hydrochloride extended-release
- Brand Name: Wellbutrin XL
- Drug Class: Smoking Cessation Aids, Antidepressants, Dopamine Reuptake Inhibitors, Antidepressants, Other
SIDE EFFECTS
The following adverse reactions are discussed in greater detail in other sections of the labeling:
- Suicidal thoughts and behaviors in children, adolescents, and young adults
- Neuropsychiatric symptoms and suicide risk in smoking cessation treatment
- Seizure
- Hypertension
- Activation of mania or hypomania
- Psychosis and other neuropsychiatric events
- Angle-Closure Glaucoma
- Hypersensitivity reactions
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 to rates in the clinical trials of another drug and may not reflect the rates observed in clinical practice.
Commonly Observed Adverse Reactions In Controlled Clinical Trials Of Sustained-Release Bupropion Hydrochloride
Adverse reactions that occurred in at least 5% of patients treated with bupropion HCl sustained-release (300 mg and 400 mg per day) and at a rate at least twice the placebo rate are listed below.
300 mg/day of bupropion HCl sustained-release: anorexia, dry mouth, rash, sweating, tinnitus, and tremor.
400 mg/day of bupropion HCl sustained-release: abdominal pain, agitation, anxiety, dizziness, dry mouth, insomnia, myalgia, nausea, palpitation, pharyngitis, sweating, tinnitus, and urinary frequency.
WELLBUTRIN XL has been demonstrated to have similar bioavailability both to the immediate-release and sustained-release formulations of bupropion. The information included under this subsection and under subsection 6.2 is based primarily on data from controlled clinical trials with the sustained-release and extended-release formulations of bupropion hydrochloride.
Major Depressive Disorder
Adverse Reactions Leading to Discontinuation of Treatment with Bupropion HCl Immediate-Release, Bupropion HCl Sustained-Release, and Bupropion HCl Extended-Release in Major Depressive Disorder Trials
In placebo-controlled clinical trials with bupropion HCl sustained-release, 4%, 9%, and 11% of the placebo, 300 mg/day and 400 mg/day groups, respectively, discontinued treatment because of 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 listed in Table 1.
Table 1: Treatment Discontinuation Due to Adverse Reactions in Placebo-Controlled Trials in MDD
| Adverse Reaction Term | Placebo (n=385) |
Bupropion HCl Sustained-Release 300 mg/day (n=376) |
Bupropion HCl Sustained-Release 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% |
In clinical trials with bupropion HCl immediate-release, 10% of patients and volunteers discontinued due to an adverse reaction. Reactions resulting in discontinuation (in addition to those listed above for the sustained-release formulation) included vomiting, seizures, and sleep disturbances.
Adverse Reactions Occurring at an Incidence of > 1% in Patients Treated with Bupropion HCl Immediate-Release or Bupropion HCl Sustained-Release in MDD
Table 2 summarizes the adverse reactions that occurred in placebo-controlled trials in patients treated with bupropion HCl sustained-release 300 mg/day and 400 mg/day. These include reactions that occurred in either the 300 mg or 400 mg group at an incidence of 1% or more and were more frequent than in the placebo group.
Table 2: Adverse Reactions in Placebo-Controlled Trials in Patients with MDD
| Body System/ Adverse Reaction |
Placebo (n=385) |
Bupropion HCl Sustained-Release 300 mg/day (n=376) |
Bupropion HCl Sustained-Release 400 mg/day (n=114) |
| Body (General) | |||
| Headache | 23% | 26% | 25% |
| Infection | 6% | 8% | 9% |
| Abdominal pain | 2% | 3% | 9% |
| Asthenia | 2% | 2% | 4% |
| Chest pain | 1% | 3% | 4% |
| Pain | 2% | 2% | 3% |
| Fever | — | 1% | 2% |
| Cardiovascular | |||
| Palpitation | 2% | 2% | 6% |
| Flushing | — | 1% | 4% |
| Migraine | 1% | 1% | 4% |
| Hot flashes | 1% | 1% | 3% |
| Digestive | |||
| Dry mouth | 7% | 17% | 24% |
| Nausea | 8% | 13% | 18% |
| Constipation | 7% | 10% | 5% |
| Diarrhea | 6% | 5% | 7% |
| Anorexia | 2% | 5% | 3% |
| Vomiting | 2% | 4% | 2% |
| Dysphagia | 0% | 0% | 2% |
| Musculoskeletal | |||
| Myalgia | 3% | 2% | 6% |
| Arthralgia | 1% | 1% | 4% |
| Arthritis | 0% | 0% | 2% |
| Twitch | — | 1% | 2% |
| Nervous System | |||
| Insomnia | 6% | 11% | 16% |
| Dizziness | 5% | 7% | 11% |
| Agitation | 2% | 3% | 9% |
| Anxiety | 3% | 5% | 6% |
| Tremor | 1% | 6% | 3% |
| Nervousness | 3% | 5% | 3% |
| Somnolence | 2% | 2% | 3% |
| Irritability | 2% | 3% | 2% |
| Memory decreased | 1% | — | 3% |
| Paresthesia | 1% | 1% | 2% |
| Central nervous system stimulation | 1% | 2% | 1% |
| Respiratory | |||
| Pharyngitis | 2% | 3% | 11% |
| Sinusitis | 2% | 3% | 1% |
| Increased cough | 1% | 1% | 2% |
| Skin | |||
| Sweating | 2% | 6% | 5% |
| Rash | 1% | 5% | 4% |
| Pruritus | 2% | 2% | 4% |
| Urticaria | 0% | 2% | 1% |
| Special Senses | |||
| Tinnitus | 2% | 6% | 6% |
| Taste perversion | — | 2% | 4% |
| Blurred vision or diplopia | 2% | 3% | 2% |
| Urogenital | |||
| Urinary frequency | 2% | 2% | 5% |
| Urinary urgency | 0% | — | 2% |
| Vaginal hemorrhage1 | — | 0% | 2% |
| Urinary tract infection | —2 | 1% | 0% |
| 1Incidence based on the number of female patients. 2Hyphen denotes adverse reactions occurring in greater than 0 but less than 0.5% of patients |
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The following additional adverse reactions occurred in controlled trials of bupropion HCl immediate-release (300 to 600 mg per day) at an incidence of at least 1% more frequently than in the placebo group were: cardiac arrhythmia (5% vs. 4%), hypertension (4% vs. 2%), hypotension (3% vs. 2%), menstrual complaints (5% vs. 1%), akathisia (2% vs. 1%), impaired sleep quality (4% vs. 2%), sensory disturbance (4% vs. 3%), confusion (8% vs. 5%), decreased libido (3% vs. 2%), hostility (6% vs. 4%), auditory disturbance (5% vs. 3%), and gustatory disturbance (3% vs. 1%).
Seasonal Affective Disorder
In placebo-controlled clinical trials in SAD, 9% of patients treated with WELLBUTRIN XL and 5% of patients treated with placebo discontinued treatment because of adverse reactions. The adverse reactions leading to discontinuation in at least 1% of patients treated with bupropion and at a rate numerically greater than the placebo rate were insomnia (2% vs. < 1%) and headache (1% vs. < 1%).
Table 3 summarizes the adverse reactions that occurred in patients treated with WELLBUTRIN XL for up to approximately 6 months in 3 placebo-controlled trials. These include reactions that occurred at an incidence of 2% or more and were more frequent than in the placebo group.
Table 3: Adverse Reactions in Placebo-Controlled Trials in Patients with SAD
| System Organ Class/ Preferred Term |
Placebo (n=511) |
Bupropion HCl Extended-Release (n=537) |
| Gastrointestinal Disorder | ||
| Dry mouth | 15% | 26% |
| Nausea | 8% | 13% |
| Constipation | 2% | 9% |
| Flatulence | 3% | 6% |
| Abdominal pain | < 1% | 2% |
| Nervous System Disorders | ||
| Headache | 26% | 34% |
| Dizziness | 5% | 6% |
| Tremor | < 1% | 3% |
| Infections and Infestations | ||
| Nasopharyngitis | 12% | 13% |
| Upper respiratory tract infection | 8% | 9% |
| Sinusitis | 4% | 5% |
| Psychiatric Disorders | ||
| Insomnia | 13% | 20% |
| Anxiety | 5% | 7% |
| Abnormal dreams | 2% | 3% |
| Agitation | < 1% | 2% |
| Musculoskeletal and Connective Tissue Disorders | ||
| Myalgia | 2% | 3% |
| Pain in extremity | 2% | 3% |
| Respiratory, Thoracic, and Mediastinal Disorders | ||
| Cough | 3% | 4% |
| General Disorders and Administration Site Conditions | ||
| Feeling jittery | 2% | 3% |
| Skin and Subcutaneous Tissue Disorders | ||
| Rash | 2% | 3% |
| Metabolism and Nutrition Disorders | ||
| Decreased appetite | 1% | 4% |
| Reproductive System and Breast Disorders | ||
| Dysmenorrhea | < 1% | 2% |
| Ear and Labyrinth Disorders | ||
| Tinnitus | < 1% | 3% |
| Vascular Disorders | ||
| Hypertension | 0% | 2% |
Changes In Body Weight
Table 4 presents the incidence of body weight changes ( ≥ 5 lbs) in the short-term MDD trials using bupropion HCl sustained-release. There was a dose-related decrease in body weight.
Table 4: Incidence of Weight Gain or Weight Loss ( ≥ 5 lbs) in MDD Trials Using Bupropion HClSustained-Release
| Weight Change | Bupropion HCl Sustained-Release 300 mg/day (n=339) |
Bupropion HCl Sustained-Release 400 mg/day (n=112) |
Placebo (n=347) |
| Gained > 5 lbs | 3% | 2% | 4% |
| Lost > 5 lbs | 14% | 19% | 6% |
Table 5 presents the incidence of body weight changes ( ≥ 5 lbs) in the 3 SAD trials using bupropion HCl extended-release. A higher proportion of subjects in the bupropion group (23%) had a weight loss ≥ 5 lbs, compared to the placebo group (11%). These were relatively long-term trials (up to 6 months).
Table 5: Incidence of Weight Gain or Weight Loss ( ≥ 5 lbs) in SAD Trials Using Bupropion HCl Extended-Release
| Weight Change | Bupropion HCl Extended-Release 150 to 300 mg/day (n=537) |
Placebo (n=511) |
| Gained > 5 lbs | 11% | 21% |
| Lost > 5 lbs | 23% | 11% |
Postmarketing Experience
The following adverse reactions have been identified during post-approval use of WELLBUTRIN XL. 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)
Chills, facial edema, edema, peripheral edema, musculoskeletal chest pain, photosensitivity, and malaise.
Cardiovascular
Postural hypotension, hypertension, stroke, vasodilation, syncope, complete atrioventricular block, extrasystoles, myocardial infarction, phlebitis, and pulmonary embolism.
Digestive
Abnormal liver function, bruxism, gastric reflux, gingivitis, glossitis, increased salivation, jaundice, mouth ulcers, stomatitis, thirst, edema of tongue, colitis, esophagitis, gastrointestinal hemorrhage, gum hemorrhage, hepatitis, intestinal perforation, liver damage, pancreatitis, and stomach ulcer.
Endocrine
Hyperglycemia, hypoglycemia, and syndrome of inappropriate antidiuretic hormone secretion.
Hemic And Lymphatic
Ecchymosis, anemia, leukocytosis, leukopenia, lymphadenopathy, pancytopenia, and thrombocytopenia. Altered PT and/or INR, associated with hemorrhagic or thrombotic complications, were observed when bupropion was coadministered with warfarin.
Metabolic And Nutritional
Glycosuria.
Musculoskeletal
Leg cramps, fever/rhabdomyolysis, and muscle weakness.
Nervous System
Abnormal coordination, depersonalization, emotional lability, hyperkinesia, hypertonia, hypesthesia, vertigo, amnesia, ataxia, derealization, abnormal electroencephalogram (EEG), aggression, akinesia, aphasia, coma, dysarthria, dyskinesia, dystonia, euphoria, extrapyramidal syndrome, hypokinesia, increased libido, neuralgia, neuropathy, paranoid ideation, restlessness, suicide attempt, and unmasking tardive dyskinesia.
Respiratory
Bronchospasm and pneumonia.
Skin
Maculopapular rash, alopecia, angioedema, exfoliative dermatitis, and hirsutism.
Special Senses
Accommodation abnormality, dry eye, deafness, increased intraocular pressure, angle-closure glaucoma, and mydriasis.
Urogenital
Impotence, polyuria, prostate disorder, abnormal ejaculation, cystitis, dyspareunia, dysuria, gynecomastia, menopause, painful erection, salpingitis, urinary incontinence, urinary retention, and vaginitis.
SRC: NLM .