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Zyban (Bupropion Hydrochloride) - Side Effects and Adverse Reactions

 
 



ADVERSE REACTIONS (SEE ALSO WARNINGS AND PRECAUTIONS)

The information included under ADVERSE REACTIONS is based primarily on data from the dose-response trial and the comparative trial that evaluated ZYBAN for smoking cessation (see CLINICAL TRIALS). Information on additional adverse events associated with the sustained-release formulation of bupropion in depression trials, as well as the immediate-release formulation of bupropion, is included in a separate section (see Other Events Observed During the Clinical Development and Postmarketing Experience of Bupropion).

Adverse Events Associated With the Discontinuation of Treatment:   Adverse events were sufficiently troublesome to cause discontinuation of treatment in 8% of the 706 patients treated with ZYBAN and 5% of the 313 patients treated with placebo. The more common events leading to discontinuation of treatment with ZYBAN included nervous system disturbances (3.4%), primarily tremors, and skin disorders (2.4%), primarily rashes.

Incidence of Commonly Observed Adverse Events:   The most commonly observed adverse events consistently associated with the use of ZYBAN were dry mouth and insomnia. The most commonly observed adverse events were defined as those that consistently occurred at a rate of 5 percentage points greater than that for placebo across clinical studies.

Dose Dependency of Adverse Events:   The incidence of dry mouth and insomnia may be related to the dose of ZYBAN. The occurrence of these adverse events may be minimized by reducing the dose of ZYBAN. In addition, insomnia may be minimized by avoiding bedtime doses.

Adverse Events Occurring at an Incidence of 1% or More Among Patients Treated With ZYBAN:   Table 4 enumerates selected treatment-emergent adverse events from the dose-response trial that occurred at an incidence of 1% or more and were more common in patients treated with ZYBAN compared to those treated with placebo. Table 5 enumerates selected treatment-emergent adverse events from the comparative trial that occurred at an incidence of 1% or more and were more common in patients treated with ZYBAN, NTS, or the combination of ZYBAN and NTS compared to those treated with placebo. Reported adverse events were classified using a COSTART-based dictionary.

Table 4. Treatment-Emergent Adverse Event Incidence in the Dose-Response Trial *
Body System/
Adverse Experience
ZYBAN
100 to 300 mg/day
(n = 461)
%
Placebo
(n = 150)
%
Body (General)
   Neck pain
  2 <1  
   Allergic reaction   1   0
Cardiovascular
   Hot flashes
  1   0
   Hypertension   1 <1  
Digestive
   Dry mouth
11   5
   Increased appetite   2 <1
   Anorexia   1 <1
Musculoskeletal
   Arthralgia
  4   3
   Myalgia   2   1
Nervous system
   Insomnia
31 21
   Dizziness   8   7
   Tremor   2   1
   Somnolence   2   1
   Thinking abnormality   1   0
Respiratory
   Bronchitis
  2   0
Skin
   Pruritus
  3 <1  
   Rash   3 <1  
   Dry skin   2   0
   Urticaria   1   0
Special senses
   Taste perversion
  2 <1
*Selected adverse events with an incidence of at least 1% of patients treated with ZYBAN and more frequent than in the placebo group.

Table 5. Treatment-Emergent Adverse Event Incidence in the Comparative Trial *
Adverse Experience
(COSTART Term)
ZYBAN
300 mg/day
(n = 243)
%
Nicotine
Transdermal
System (NTS)
21 mg/day
(n = 243)
%
ZYBAN
and NTS
(n = 244)
%
Placebo
(n = 159)
%
Body
   Abdominal pain
  3   4   1   1
   Accidental injury   2   2   1   1
   Chest pain <1   1   3   1
   Neck pain   2   1 <1     0
   Facial edema <1   0   1   0
Cardiovascular
   Hypertension
  1 <1   2   0
   Palpitations   2   0   1   0
Digestive
   Nausea
  9   7 11   4
   Dry mouth 10   4   9   4
   Constipation   8   4   9   3
   Diarrhea   4   4   3   1
   Anorexia   3   1   5   1
   Mouth ulcer   2   1   1   1
   Thirst <1 <1   2   0
Musculoskeletal
   Myalgia
  4   3   5   3
   Arthralgia   5   3   3   2
Nervous system
   Insomnia
40 28 45 18
   Dream abnormality   5 18 13   3
   Anxiety   8   6   9   6
   Disturbed concentration   9   3   9   4
   Dizziness 10   2   8   6
   Nervousness   4 <1     2   2
   Tremor   1 <1     2   0
   Dysphoria <1     1   2   1
Respiratory
   Rhinitis
12 11   9   8
   Increased cough   3   5 <1   1
   Pharyngitis   3   2   3   0
   Sinusitis   2   2   2   1
   Dyspnea   1   0   2   1
   Epistaxis   2   1   1   0
Skin
   Application site reaction **/*
11 17 15   7
   Rash   4   3   3   2
   Pruritus   3   1   5   1
   Urticaria   2   0   2   0
Special senses
   Taste perversion
  3   1   3   2
   Tinnitus   1   0 <1   0
*Selected adverse events with an incidence of at least 1% of patients treated with either ZYBAN, NTS, or the combination of ZYBAN and NTS and more frequent than in the placebo group.
**/* Patients randomized to ZYBAN or placebo received placebo patches.

ZYBAN was well-tolerated in the long-term maintenance trial, that evaluated chronic administration of ZYBAN for up to 1 year and in the COPD trial that evaluated patients with mild-to-moderate COPD for a 12-week period. Adverse events in both studies were quantitatively and qualitatively similar to those observed in the dose-response and comparative trials.

Other Events Observed During the Clinical Development and Postmarketing Experience of Bupropion:   In addition to the adverse events noted above, the following events have been reported in clinical trials and postmarketing experience with the sustained-release formulation of bupropion in depressed patients and in nondepressed smokers, as well as in clinical trials and postmarketing clinical experience with the immediate-release formulation of bupropion.

Adverse events for which frequencies are provided below occurred in clinical trials with bupropion sustained-release. The frequencies represent the proportion of patients who experienced a treatment-emergent adverse event on at least one occasion in placebo-controlled studies for depression (n = 987) or smoking cessation (n = 1,013), or patients who experienced an adverse event requiring discontinuation of treatment in an open-label surveillance study with bupropion sustained-release tablets (n = 3,100). All treatment-emergent adverse events are included except those listed in Tables 4 and 5, those events listed in other safety-related sections of the insert, those adverse events subsumed under COSTART terms that are either overly general or excessively specified so as to be uninformative, those events not reasonably associated with the use of the drug, and those events that were not serious and occurred in fewer than 2 patients.

Events are further categorized by body system and listed in order of decreasing frequency according to the following definitions of frequency: 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.

Adverse events for which frequencies are not provided occurred in clinical trials or postmarketing experience with bupropion. Only those adverse events not previously listed for sustained-release bupropion are included. The extent to which these events may be associated with ZYBAN is unknown.

Body (General):   Frequent were asthenia, fever, and headache. Infrequent were back pain, chills, inguinal hernia, musculoskeletal chest pain, pain, and photosensitivity. Rare was malaise. Also observed were arthralgia, myalgia, and fever with rash and other symptoms suggestive of delayed hypersensitivity. These symptoms may resemble serum sickness (see PRECAUTIONS).

Cardiovascular:   Infrequent were flushing, migraine, postural hypotension, stroke, tachycardia, and vasodilation. Rare was syncope. Also observed were cardiovascular disorder, complete AV block, extrasystoles, hypotension, hypertension (in some cases severe, see PRECAUTIONS), myocardial infarction, phlebitis, and pulmonary embolism.

Digestive:   Frequent were dyspepsia, flatulence, and vomiting. Infrequent were abnormal liver function, bruxism, dysphagia, gastric reflux, gingivitis, glossitis, jaundice, and stomatitis. Rare was edema of tongue. Also observed were colitis, esophagitis, gastrointestinal hemorrhage, gum hemorrhage, hepatitis, increased salivation, intestinal perforation, liver damage, pancreatitis, stomach ulcer, and stool abnormality.

Endocrine:   Also observed were hyperglycemia, hypoglycemia, and syndrome of inappropriate antidiuretic hormone.

Hemic and Lymphatic:   Infrequent was ecchymosis. Also observed were anemia, leukocytosis, leukopenia, lymphadenopathy, pancytopenia, and thrombocytopenia. Altered PT and/or INR, infrequently associated with hemorrhagic or thrombotic complications, were observed when bupropion was co-administered with warfarin.

Metabolic and Nutritional:   Infrequent were edema, increased weight, and peripheral edema. Also observed was glycosuria.

Musculoskeletal:   Infrequent were leg cramps and twitching. Also observed were arthritis and muscle rigidity/fever/rhabdomyolysis, and muscle weakness.

Nervous System:   Frequent were agitation, depression, and irritability. Infrequent were abnormal coordination, CNS stimulation, confusion, decreased libido, decreased memory, depersonalization, emotional lability, hostility, hyperkinesia, hypertonia, hypesthesia, paresthesia, suicidal ideation, and vertigo. Rare were amnesia, ataxia, derealization, and hypomania. Also observed were abnormal electroencephalogram (EEG), akinesia, aphasia, coma, delirium, delusions, dysarthria, dyskinesia, dystonia, euphoria, extrapyramidal syndrome, hallucinations, hypokinesia, increased libido, manic reaction, neuralgia, neuropathy, paranoid reaction, and unmasking tardive dyskinesia.

Respiratory:   Rare was bronchospasm. Also observed was pneumonia.

Skin:   Frequent was sweating. Infrequent was acne and dry skin. Rare was maculopapular rash. Also observed were alopecia, angioedema, exfoliative dermatitis, and hirsutism.

Special Senses:   Frequent was amblyopia. Infrequent were accommodation abnormality and dry eye. Also observed were deafness, diplopia, and mydriasis.

Urogenital:   Frequent was urinary frequency. Infrequent were impotence, polyuria, and urinary urgency. Also observed were abnormal ejaculation, cystitis, dyspareunia, dysuria, gynecomastia, menopause, painful erection, prostate disorder, salpingitis, urinary incontinence, urinary retention, urinary tract disorder, and vaginitis.

DRUG ABUSE AND DEPENDENCE

ZYBAN is likely to have a low abuse potential.

Humans:   There have been few reported cases of drug dependence and withdrawal symptoms associated with the immediate-release formulation of bupropion. In human studies of abuse liability, individuals experienced with drugs of abuse reported that bupropion produced a feeling of euphoria and desirability. In these subjects, a single dose of 400 mg (1.33 times the recommended daily dose) of bupropion produced mild amphetamine-like effects compared to placebo on the Morphine-Benzedrine Subscale of the Addiction Research Center Inventories (ARCI), which is indicative of euphorigenic properties and a score intermediate between placebo and amphetamine on the Liking Scale of the ARCI.

Animals:   Studies in rodents and primates have shown that bupropion exhibits some pharmacologic actions common to psychostimulants. In rodents, it has been shown to increase locomotor activity, elicit a mild stereotyped behavioral response, and increase rates of responding in several schedule-controlled behavior paradigms. In primate models to assess the positive reinforcing effects of psychoactive drugs, bupropion was self-administered intravenously. In rats, bupropion produced amphetamine- and cocaine-like discriminative stimulus effects in drug discrimination paradigms used to characterize the subjective effects of psychoactive drugs.

The possibility that bupropion may induce dependence should be kept in mind when evaluating the desirability of including the drug in smoking cessation programs of individual patients.



REPORTS OF SUSPECTED ZYBAN SIDE EFFECTS / ADVERSE REACTIONS

Below is a sample of reports where side effects / adverse reactions may be related to Zyban. The information is not vetted and should not be considered as verified clinical evidence.

Possible Zyban side effects / adverse reactions in 31 year old female

Reported by a consumer/non-health professional from Turkey on 2011-10-27

Patient: 31 year old female

Reactions: Maternal Exposure During Pregnancy, Abortion Induced

Suspect drug(s):
Zyban



Possible Zyban side effects / adverse reactions in 25 year old male

Reported by a consumer/non-health professional from United States on 2012-01-27

Patient: 25 year old male

Reactions: Pharyngeal Oedema, Joint Swelling, Urticaria, Swelling

Suspect drug(s):
Wellbutrin
    Administration route: Oral
    Indication: Depression
    Start date: 2005-01-01

Zyban
    Administration route: Oral
    Indication: EX-Tobacco User
    Start date: 2002-01-01

Other drugs received by patient: NO Concurrent Medication



Possible Zyban side effects / adverse reactions in 30 year old male

Reported by a pharmacist from United States on 2012-04-12

Patient: 30 year old male

Reactions: Pharyngeal Oedema

Adverse event resulted in: disablity

Suspect drug(s):
Zyban



See index of all Zyban side effect reports >>

Drug label data at the top of this Page last updated: 2006-01-25

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