Wellbutrin XL NDA 21-515

451 studies are not always predictive of human response, this drug should be used during pregnancy

452 only if clearly needed.

453 To monitor fetal outcomes of pregnant women exposed to WELLBUTRIN XL,

454 GlaxoSmithKline maintains a Bupropion Pregnancy Registry. Health care providers are

455 encouraged to register patients by calling (800) 336-2176.

456 Labor and Delivery: The effect of WELLBUTRIN XL Tablets on labor and delivery in

457 humans is unknown.

458 Nursing Mothers: Like many other drugs, bupropion and its metabolites are secreted in human

459 milk. Because of the potential for serious adverse reactions in nursing infants from

460 WELLBUTRIN XL Tablets, a decision should be made whether to discontinue nursing or to

461 discontinue the drug, taking into account the importance of the drug to the mother.

462 Pediatric Use: The safety and effectiveness of WELLBUTRIN XL Tablets in pediatric

463 patients below 18 years old have not been established. The immediate-release formulation of

464 bupropion was studied in 104 pediatric patients (age range, 6 to 16) in clinical trials of the drug

465 for other indications. Although generally well tolerated, the limited exposure is insufficient to

466 assess the safety of bupropion in pediatric patients.

467 Geriatric Use: Of the approximately 6,000 patients who participated in clinical trials with

468 bupropion sustained-release tablets (depression and smoking cessation studies), 275 were ≥ 65

469 years old and 47 were ≥75 years old. In addition, several hundred patients 65 and over

470 participated in clinical trials using the immediate-release formulation of bupropion (depression

471 studies). No overall differences in safety or effectiveness were observed between these subjects

472 and younger subjects. Reported clinical experience has not identified differences in responses

473 between the elderly and younger patients, but greater sensitivity of some older individuals cannot

474 be ruled out.

475 A single-dose pharmacokinetic study demonstrated that the disposition of bupropion and its

476 metabolites in elderly subjects was similar to that of younger subjects; however, another

477 pharmacokinetic study, single and multiple dose, has suggested that the elderly are at increased

478 risk for accumulation of bupropion and its metabolites (see CLINICAL PHARMACOLOGY).

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

480 metabolized and excreted by the kidneys. The risk of toxic reaction to this drug may be greater in

481 patients with impaired renal function. Because elderly patients are more likely to have decreased

482 renal function, care should be taken in dose selection, and it may be useful to monitor renal

483 function (see PRECAUTIONS: Renal Impairment and DOSAGE AND ADMINISTRATION).

484 ADVERSE REACTIONS (See also WARNINGS and PRECAUTIONS.)

485 WELLBUTRIN XL has been demonstrated to have similar bioavailability to the

486 immediate-release formulation of bupropion (see CLINICAL PHARMACOLOGY). The

487 information included under the Incidence in Controlled Trials subsection of ADVERSE

488 REACTIONS is based primarily on data from controlled clinical trials with WELLBUTRIN SR

489 tablets, the sustained-release formulation of bupropion. WELLBUTRIN XL has not been