Wellbutrin XL NDA 21-515

193 Wellbutrin is contraindicated in patients undergoing abrupt discontinuation of

194 alcohol or sedatives (including benzodiazepines).

195 The concurrent administration of WELLBUTRIN XL Tablets and a monoamine oxidase

196 (MAO) inhibitor is contraindicated. At least 14 days should elapse between discontinuation of an

197 MAO inhibitor and initiation of treatment with WELLBUTRIN XL Tablets.

198 WELLBUTRIN XL is contraindicated in patients who have shown an allergic response to

199 bupropion or the other ingredients that make up WELLBUTRIN XL Tablets.

200 WARNINGS

201 Patients should be made aware that WELLBUTRIN XL contains the same active

202 ingredient found in ZYBAN, used as an aid to smoking cessation treatment, and that

203 WELLBUTRIN XL should not be used in combination with ZYBAN, or any other

204 medications that contain bupropion, such as WELLBUTRIN SR (bupropion

205 hydrochloride), the sustained-release formulation or WELLBUTRIN (bupropion

206 hydrochloride), the immediate-release formulation.

207 Seizures: Bupropion is associated with a dose-related risk of seizures. The risk of seizures

208 is also related to patient factors, clinical situations, and concomitant medications, which

209 must be considered in selection of patients for therapy with WELLBUTRIN XL.

210 WELLBUTRIN XL should be discontinued and not restarted in patients who experience a

211 seizure while on treatment.

212 As both WELLBUTRIN XL and the sustained-release formulation of bupropion

213 (WELLBUTRIN SR) are bioequivalent to the immediate-release formulation of bupropion,

214 the seizure incidence with WELLBUTRIN XL, while not formally evaluated in clinical

215 trials, may be similar to that presented below for the immediate-release and

216 sustained-release formulations of bupropion.

217 ● Dose: At doses up to 300 mg/day of the sustained-release formulation of bupropion

218 (WELLBUTRIN SR), the incidence of seizure is approximately 0.1% (1/1,000).

219 Data for the immediate-release formulation of bupropion revealed a seizure

220 incidence of approximately 0.4% (i.e., 13 of 3,200 patients followed prospectively) in

221 patients treated at doses in a range of 300 to 450 mg/day. This seizure incidence (0.4%)

222 may exceed that of some other marketed antidepressants.

223 Additional data accumulated for the immediate-release formulation of bupropion

224 suggests that the estimated seizure incidence increases almost enfold between 450 and

225 600 mg/day. The 600 mg dose is twice the usual adult dose and one and one-third the

226 maximum recommended daily dose (450 mg) of WELLBUTRIN XT Tablets. This

227 disproportionate increase in seizure incidence with dose incrementation calls for

228 caution in dosing.

229 ● Patient factors: Predisposing factors that may increase the risk of seizure with

230 bupropion use include history of head trauma or prior seizure, central nervous system