Adverse Reactions
(see also WARNINGS and PRECAUTIONS) Adverse events commonly encountered in patients treated with bupropion are agitation, dry mouth, insomnia, headache/migraine, nausea/vomiting, constipation, and tremor.
Adverse events were sufficiently troublesome to cause discontinuation of treatment with bupropion in approximately ten percent of the 2400 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, the table below
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 bupropion 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 bupropion is provided in
WARNINGS and PRECAUTIONS.
TREATMENT EMERGENT ADVERSE EXPERIENCE
INCIDENCE IN PLACEBO-CONTROLLED CLINICAL TRIALS *
(Percent of Patients Reporting) |
| Adverse Experience |
Bupropion
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 Vission |
14.6 |
10.3 |
| Gustatory Disturbance |
3.1 |
1.1 |
* Events reported by at least 1% of patients receiving bupropion are included.
Other Events Observed During the Development of Bupropion:
The conditions and duration of exposure to bupropion 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 bupropion. The following enumeration is organized by organ system and described 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 1/1000 patients, while rare events are those occurring
in less than 1/1000 patients.
Cardiovascular: Frequent was edema; infrequent were chest pain, EKG 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, G.I. 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, dysparenuia, 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 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:
Cardiovascular: orthostatic hypotension, third degree heart block
Endocrine: syndrome of inappropriate antidiuretic hormone secretion
Gastrointestinal: esophagitis, hepatitis
Hemic and Lymphatic: ecchymosis, leukocytosis, leukopenia
Musculoskeletal: arthralgia, myalgia, muscle rigidity/fever/rhabdomyolysis
Nervous: coma, delirium, dream abnormalities, paresthesia, unmasking of tardive dyskinesia
Skin and Appendages: Stevens-Johnson syndrome, angioedema, exfoliative dermatitis, urticaria
Special Senses: tinnitus
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