Pharmacology Page 6
Cimetidine: The effects of concomitant administration of cimetidine on the pharmacokinetics of bupropion and its active metabolites were examined in a crossover study in 24 healthy young male volunteers, following oral
administration of two 150 mg bupropion tablets with and without 800 mg of cimetidine. A single dose of cimetidine had no effect on single dose pharmacokinetic parameter estimates for buproprion, or hydroxybupropion, but caused a small statistically
significant increase in the combined threohydro and erythrobupropion AUC (16%) and Cmax (32%).
Levodopa: Limited clinical data suggest a higher incidence of adverse experiences in patients receiving concurrent administration of the sustained- and immediate-release formulations of bupropion and L-dopa. Administration
of bupropion sustained release to patients receiving L-dopa concurrently should be undertaken with caution, using small initial doses and gradual dose increases.
Other Drugs with CNS Activity: The risk of using bupropion in combination with other CNS-active drugs has not been systematically evaluated. Consequently, caution is advised if the concomitant administration of bupropion and such drugs is required.
Transdermal Nicotine: Monitoring for treatment-emergent hypertension is recommended in patients receiving a combination of sustained-release bupropion and transdermal nicotine.
Adverse Reactions: The information included is based on data from clinical trials with the sustained release formulation of bupropion. Information on additional adverse events associated with the immediate release formulation
of bupropion is included in a separate subsection (see Events Observed During Development and Postmarketing Experience with the Immediate Release Formulation of Bupropion).
Adverse Events Associated with Discontinuation of Treatment: In placebo controlled studies of depression (987 patients treated with bupropion, and 385 treated with placebo), adverse events caused discontinuation in 7% of bupropion
treated patients and 3% of placebo-treated patients. The more common events leading to discontinuation of bupropion included nervous system disturbances (2.2%), primarily agitation, anxiety and insomnia; skin disorders (1.9%), primarily rashes,
pruritus, and urticaria ; general body complaints (1%), primarily headaches, and digestive system disturbances (1%), primarily nausea. Two patients in bupropion treatment groups discontinued due to hallucinations (auditory or visual). The rates
of premature discontinuation due to an adverse event were dose-related in these studies.
In an open label, uncontrolled (acute treatment and continuation) study of bupropion, 11% patients (361 out of 3 100) discontinued treatment due to an adverse event. Adverse events leading to premature discontinuation in 1% or more of patients
were: headache (1.1%), nausea (1%), and insomnia (1%). Adverse events leading to premature discontinuation in 0.5 to 1% of patients were: anxiety (0.8%), rash (0.8%), agitation (0.7%), irritability (0.5%), and dizziness (0.5%). In those patients
(n=1 577) who went into the continuation phase after 8 weeks of treatment, 6 (0.4%) discontinued due to alopecia. Because this study was uncontrolled, it is not possible to reliably assess the causal relationship of these events to treatment
with bupropion.
Incidence of Commonly Observed Adverse Events in Controlled Clinical Trials: Adverse events commonly encountered during the clinical development of bupropion (incidence of 5% or greater; and higher incidence in bupropion-treated, than placebo-treated
patients) were headache, constipation, dry mouth, nausea, dizziness, insomnia, tremor and tinnitus. |
