Wellbutrin XL NDA 21-515

331 All patients with hepatic impairment should be closely monitored for possible adverse effects

332 that could indicate high drug and metabolite levels (See CLINICAL PHARMACOLOGY,

333 WARNINGS, and DOSAGE AND ADMINISTRATION).

334 Renal Impairment: No studies have been conducted in patients with renal impairment.

335 Bupropion is extensively metabolized in the liver to active metabolites, which are further

336 metabolized and subsequently excreted by the kidneys. WELLBUTRIN XL should be used with

337 caution in patients with renal impairment and a reduced frequency and/or dose should be

338 considered as bupropion and its metabolites may accumulate in such patients to a greater extent

339 than usual. The patient should be closely monitored for possible adverse effects that could

340 indicate high drug or metabolite levels.

341 Information for Patients: See the tear-off leaflet at the end of this labeling for Patient

342 Information.

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

344 found in ZYBAN, used as an aid to smoking cessation treatment, and that WELLBUTRIN XL

345 should not be used in combination with ZYBAN or any other medications that contain bupropion

346 hydrochloride (such as WELLBUTRIN SR, the sustained-release formulation, and

347 WELLBUTRIN, the immediate-release formulation).

348 Physicians are advised to discuss the following issues with patients:

349 Patients should be told that WELLBUTRIN XL should be discontinued and not restarted if

350 they experience a seizure while on treatment.

351 Patients should be told that any CNS-active drug like WELLBUTRIN XL Tablets may impair

352 their ability to perform tasks requiring judgment or motor or cognitive skills. Consequently,

353 until they are reasonably certain that WELLBUTRIN XL Tablets do not adversely affect their

354 performance, they should refrain from driving an automobile or operating complex, hazardous

355 machinery.

356 Patients should be told that the excessive use or abrupt discontinuation of alcohol or sedatives

357 (including benzodiazepines) may alter the seizure threshold. Some patients have reported lower

358 alcohol tolerance during treatment with WELLBUTRIN XL. Patients should be advised that the

359 consumption of alcohol should be minimized or avoided.

360 Patients should be advised to inform their physicians if they are taking or plan to take any

361 prescription or over-the-counter drugs. Concern is warranted because WELLBUTRIN XL

362 Tablets and other drugs may affect each other’s metabolism.

363 Patients should be advised to notify their physicians if they become pregnant or intend to

364 become pregnant during therapy.

365 Patients should be advised to swallow WELLBUTRIN XL Tablets whole so that the release

366 rate is not altered. Do not chew, divide, or crush tablets.

367 Patients should be advised that they may notice in their stool something that looks like a

368 tablet. This is normal. The medication in WELLBUTRIN XL is contained in a non-absorbable

369 shell that has been specially designed to slowly release drug in the body. When this process is

370 completed, the empty shell is eliminated from the body.