ADVERSE REACTIONS (see also Warnings and Precautions)
Adverse events commonly encountered in patients treated with WELLBUTRIN are agitation, dry mouth, insomnia, headache/migraine, nausea/vomiting, constipation, and tremor.
Adverse events were sufficiently troublesome to cause discontinuation of treatment with WELLBUTRIN in approximately 10% of the 2,400 patients and volunteers who participated in clinical trials during the product’s initial development. The more common events causing discontinuation include neuropsychiatric disturbances (3.0%), primarily agitation and abnormalities in mental status; gastrointestinal disturbances (2.1%), primarily nausea and vomiting; neurological disturbances (1.7%), primarily seizures, headaches, and sleep disturbances; and dermatologic problems (1.4%), primarily rashes. It is important to note, however, that many of these events occurred at doses that exceed the recommended daily dose.
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. Consequently, Table 2 is presented solely to indicate the relative frequency of adverse events reported in representative controlled clinical studies conducted to evaluate the safety and efficacy of WELLBUTRIN under relatively similar conditions of daily dosage (300 to 600 mg), setting, and duration (3 to 4 weeks). 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 must differ from those which 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 is provided in WARNINGS and PRECAUTIONS.
Table 2. Treatment-Emergent Adverse Experience Incidence in Placebo-Controlled Clinical Trials* (Percent of Patients Reporting) |
Adverse Experience
|
WELLBUTRIN Patients
(n = 323)
|
Placebo Patients
(n = 185)
|
|
Cardiovascular
| | |
|
Cardiac arrhythmias
|
5.3
|
4.3
|
|
Dizziness
|
22.3
|
16.2
|
|
Hypertension
|
4.3
|
1.6
|
|
Hypotension
|
2.5
|
2.2
|
|
Palpitations
|
3.7
|
2.2
|
|
Syncope
|
1.2
|
0.5
|
|
Tachycardia
|
10.8
|
8.6
|
|
Dermatologic
| | |
|
Pruritus
|
2.2
|
0.0
|
|
Rash
|
8.0
|
6.5
|
|
Gastrointestinal
| | |
|
Anorexia
|
18.3
|
18.4
|
|
Appetite increase
|
3.7
|
2.2
|
|
Constipation
|
26.0
|
17.3
|
|
Diarrhea
|
6.8
|
8.6
|
|
Dyspepsia
|
3.1
|
2.2
|
|
Nausea/vomiting
|
22.9
|
18.9
|
|
Weight gain
|
13.6
|
22.7
|
|
Weight loss
|
23.2
|
23.2
|
|
Genitourinary
| | |
|
Impotence
|
3.4
|
3.1
|
|
Menstrual complaints
|
4.7
|
1.1
|
|
Urinary frequency
|
2.5
|
2.2
|
|
Urinary retention
|
1.9
|
2.2
|
|
Musculoskeletal
| | |
|
Arthritis
|
3.1
|
2.7
|
|
Neurological
| | |
|
Akathisia
|
1.5
|
1.1
|
|
Akinesia/bradykinesia
|
8.0
|
8.6
|
|
Cutaneous temperature disturbance
|
1.9
|
1.6
|
|
Dry mouth
|
27.6
|
18.4
|
|
Excessive sweating
|
22.3
|
14.6
|
|
Headache/migraine
|
25.7
|
22.2
|
|
Impaired sleep quality
|
4.0
|
1.6
|
|
Increased salivary flow
|
3.4
|
3.8
|
|
Insomnia
|
18.6
|
15.7
|
|
Muscle spasms
|
1.9
|
3.2
|
|
Pseudoparkinsonism
|
1.5
|
1.6
|
|
Sedation
|
19.8
|
19.5
|
|
Sensory disturbance
|
4.0
|
3.2
|
|
Tremor
|
21.1
|
7.6
|
|
Neuropsychiatric
| | |
|
Agitation
|
31.9
|
22.2
|
|
Anxiety
|
3.1
|
1.1
|
|
Confusion
|
8.4
|
4.9
|
|
Decreased libido
|
3.1
|
1.6
|
|
Delusions
|
1.2
|
1.1
|
|
Disturbed concentration
|
3.1
|
3.8
|
|
Euphoria
|
1.2
|
0.5
|
|
Hostility
|
5.6
|
3.8
|
|
Nonspecific
| | |
|
Fatigue
|
5.0
|
8.6
|
|
Fever/chills
|
1.2
|
0.5
|
|
Respiratory
| | |
|
Upper respiratory complaints
|
5.0
|
11.4
|
|
Special Senses
| | |
|
Auditory disturbance
|
5.3
|
3.2
|
|
Blurred vision
|
14.6
|
10.3
|
|
Gustatory disturbance
|
3.1
|
1.1
|
*Events reported by at least 1% of patients receiving WELLBUTRIN are included.
Other Events Observed During the Development of WELLBUTRIN
The conditions and duration of exposure to WELLBUTRIN varied greatly, and a substantial proportion of the experience was gained in open and uncontrolled clinical settings. During this experience, numerous adverse events were reported; however, without appropriate controls, it is impossible to determine with certainty which events were or were not caused by WELLBUTRIN. The following enumeration is organized by organ system and describes events in terms of their relative frequency of reporting in the data base. Events of major clinical importance are also described in WARNINGS and PRECAUTIONS.
The following definitions of frequency are used: Frequent adverse events are defined as those occurring in at least 1/100 patients. Infrequent adverse events are those occurring in 1/100 to 1/1,000 patients, while rare events are those occurring in less than 1/1,000 patients.
Cardiovascular
Frequent was edema; infrequent were chest pain, electrocardiogram (ECG) abnormalities (premature beats and nonspecific ST-T changes), and shortness of breath/dyspnea; rare were flushing, pallor, phlebitis, and myocardial infarction.
Dermatologic
Frequent were nonspecific rashes; infrequent were alopecia and dry skin; rare were change in hair color, hirsutism, and acne.
Endocrine
Infrequent was gynecomastia; rare were glycosuria and hormone level change.
Gastrointestinal
Infrequent were dysphagia, thirst disturbance, and liver damage/jaundice; rare were rectal complaints, colitis, gastrointestinal bleeding, intestinal perforation, and stomach ulcer.
Genitourinary
Frequent was nocturia; infrequent were vaginal irritation, testicular swelling, urinary tract infection, painful erection, and retarded ejaculation; rare were dysuria, enuresis, urinary incontinence, menopause, ovarian disorder, pelvic infection, cystitis, dyspareunia, and painful ejaculation.
Hematologic/Oncologic
Rare were lymphadenopathy, anemia, and pancytopenia.
Musculoskeletal
Rare was musculoskeletal chest pain.
Neurological
(see WARNINGS) Frequent were ataxia/incoordination, seizure, myoclonus, dyskinesia, and dystonia; infrequent were mydriasis, vertigo, and dysarthria; rare were electroencephalogram (EEG) abnormality, abnormal neurological exam, impaired attention, sciatica, and aphasia.
Neuropsychiatric
(see PRECAUTIONS) Frequent were mania/hypomania, increased libido, hallucinations, decrease in sexual function, and depression; infrequent were memory impairment, depersonalization, psychosis, dysphoria, mood instability, paranoia, formal thought disorder, and frigidity; rare was suicidal ideation.
Oral Complaints
Frequent was stomatitis; infrequent were toothache, bruxism, gum irritation, and oral edema; rare was glossitis.
Respiratory
Infrequent were bronchitis and shortness of breath/dyspnea; rare were epistaxis, rate or rhythm disorder, pneumonia, and pulmonary embolism.
Special Senses
Infrequent was visual disturbance; rare was diplopia.
Nonspecific
Frequent were flu-like symptoms; infrequent was nonspecific pain; rare were body odor, surgically related pain, infection, medication reaction, and overdose.
Postintroduction Reports
Voluntary reports of adverse events temporally associated with bupropion that have been received since market introduction and which may have no causal relationship with the drug include the following:
Body (General)
arthralgia, myalgia, and fever with rash and other symptoms suggestive of delayed hypersensitivity. These symptoms may resemble serum sickness (see PRECAUTIONS).
Cardiovascular
hypertension (in some cases severe, see PRECAUTIONS), orthostatic hypotension, third degree heart block
Endocrine
syndrome of inappropriate antidiuretic hormone secretion, hyperglycemia, hypoglycemia
Gastrointestinal
esophagitis, hepatitis, liver damage
Hemic and Lymphatic
ecchymosis, leukocytosis, leukopenia, thrombocytopenia. Altered PT and/or INR, infrequently associated with hemorrhagic or thrombotic complications, were observed when bupropion was coadministered with warfarin.
Musculoskeletal
arthralgia, myalgia, muscle rigidity/fever/rhabdomyolysis, muscle weakness
Nervous
aggression, coma, delirium, dream abnormalities, paranoid ideation, paresthesia, restlessness, unmasking of tardive dyskinesia
Skin and Appendages
Stevens-Johnson syndrome, angioedema, exfoliative dermatitis, urticaria
Special Senses
tinnitus, increased intraocular pressure
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