Because the use of Zyban (Bupropion) is associated with an increased risk of seizures, doses over 300 milligrams per day for smoking cessation should not be used. The risk of seizures is also related to patient factors, clinical situation, and other drugs that are being taken together with Zyban, which must be considered in selection of patients for treatment with this drug. Zyban should be discontinued and not restarted in patients who experience a seizure while on treatment.
The seizure rate associated with doses of sustained-release Zyban up to 300 milligrams per day is approximately 0.1% (1/1,000). This incidence was prospectively determined during an eight-week treatment exposure in approximately 3,100 depressed patients. Data for the immediate-release formulation of Zyban revealed a seizure incidence of approximately 0.4% (4/1,000) in depressed patients treated at doses in a range of 300 to 450 milligrams per day. In addition, the estimated seizure incidence increases almost 10-fold between 450 and 600 milligrams per day.
Predisposing factors that may increase the risk of seizure with Zyban use include history of head trauma or prior seizure, central nervous system (CNS) tumor, the presence of severe hepatic (liver) cirrhosis, and concomitant medications that lower seizure threshold.
Situations associated with an increased seizure risk include, among others, excessive use of alcohol or sedatives (including benzodiazepines); addiction to opiates, cocaine, or stimulants; use of over-the-counter stimulants and anorectics; and diabetes treated with oral hypoglycemics or insulin.
Many drugs, for example, antipsychotics, antidepressants, theophylline, and systemic steroids, are known to lower seizure threshold. Zyban should be used with extreme caution in patients with severe hepatic cirrhosis. In these patients a reduced frequency of dosing is required, as peak Zyban levels are substantially increased, and accumulation is likely to occur in such patients to a greater extent than usual. The dose should not exceed 150 milligrams every other day in these patients.