Wellbutrin XL NDA 21-515

292 Allergic Reactions: Anaphylactoid/anaphylactic reactions characterized by symptoms such

293 as pruritus, urticaria, angioedema, and dyspnea requiring medical treatment have been reported

294 in clinical trials with bupropion. In addition, there have been rare spontaneous postmarketing

295 reports of erythema multiforme, Stevens-Johnson syndrome, and anaphylactic shock associated

296 with bupropion. A patient should stop taking WELLBUTRIN XL and consult a doctor if

297 experiencing allergic or anaphylactoid/anaphylactic reactions (e.g., skin rash, pruritus, hives

298 chest pain, edema, and shortness of breath) during treatment.

299 Arthralgia, myalgia, and fever with rash and other symptoms suggestive of delayed

300 hypersensitivity have been reported in association with bupropion. These symptoms may

301 resemble serum sickness.

302 Cardiovascular Effects: In clinical practice, hypertension, in some cases severe, requiring

303 acute treatment, has been reported in patients receiving bupropion alone with in combination with

304 nicotine replacement therapy. These events have been observed in both patients with and without

305 evidence of pre-existing hypertension.

306 Data from a comparative study of the sustained-release formulation of bupropion (ZYBAN®

307 sustained-Release Tablets), nicotine transdermal systems (NTS), the combination of

308 sustained-release bupropion plus NTS, and placebo as an aid to smoking cessation suggest a

309 higher incidence of treatment-emergent hypertension in patients treated with the combination of

310 sustained-release bupropion and NTS. In this study, 6.1% of patients treated with the

311 combination of sustained-release bupropion and NTS had treatment-emergent hypertension

312 compared to 2.5%, 1.6%, and 3.1% of patients treated with sustained-release bupropion, NTS

313 and placebo, respectively. The majority of these patients had evidence of pre-existing

314 hypertension. Three patients (1.2%) treated with the combination of ZYBAN and NRT and

315 1 patient (0.4%) treated with NTS had study medication discontinued due to hypertension

316 compared to none of the patients treated with ZYBAN or placebo. Monitoring of blood pressure

317 is recommended in patients who receive the combination of bupropion and nicotine replacement.

318 There is no clinical experience establishing the safety of WELLBUTRIN XL Tablets in

319 patients with a recent history of myocardial infarction or unstable heart disease. Therefore, care

320 should be exercised if it is used in these groups. Bupropion was well tolerated in depressed

321 patients who had previously developed orthostatic hypotension while receiving tricyclic

322 antidepressants, and was also generally well tolerated in a group of 36 depressed patients with

323 stable congestive heart failure (CHF). However, bupropion was associated with a rise in supine

324 blood pressure in the study with patients with CHF, resulting in discontinuation of treatment in

325 2 patients for exacerbation of baseline hypertension.

326 Hepatic Impairment: WELLBUTRIN XL should be used with extreme caution in patients

327 with severe hepatic cirrhosis. In these patients, a reduced frequency and/or dose is required.

328 WELLBUTRIN XL should be used with caution in patients with hepatic impairment (including)

329 mild to moderate hepatic cirrhosis) and reduced frequency and/or dose should be considered in

330 patients with mild to moderate hepatic cirrhosis.