Wellbutrin XL NDA 21-515

544 Decreased libido (3% vs 2%), hostility (6% vs 4%), auditory disturbance (5% vs 3%), and

545 Gustatory disturbance (3% vs 1%).

546 Incidence of Commonly Adverse Events in Controlled Clinical Trials:

547 Adverse events from Table 4 occurring in at least 5% of patients treated with the

548 sustained-release formulation of bupropion and at a rate at least twice the placebo rate are listed

549 below for the 300- and 400-mg/day dose groups.

550 300 mg/day of the Sustained-Release Formulation: Anorexia, dry mouth, rash,

551 sweating, tinnitus, and tremor.

552 400 mg/day of the Sustained-Release Formulation: Abdominal pain, agitation,

553 anxiety, dizziness, dry mouth, insomnia, myalgia, nausea, palpitation, pharyngitis, sweating,

554 tinnitus, and urinary frequency.

555 Other Events Observed During the Clinical Development and Postmarketing

556 Experience of Bupropion: In addition to the adverse events noted above, the following

557 events have been reported in clinical trials and postmarketing experience with the

558 sustained-release formulation of bupropion in depressed and in nondepressed smokers,

559 as well as in clinical trials and postmarketing clinical experience with the immediate-release

560 formulation of bupropion.

561 Adverse events for which frequencies are provided below occurred in clinical trials with the

562 sustained-release formulation of bupropion. The frequencies represent the proportion of patients

563 who experienced a treatment-emergent adverse event on at least one occasion in

564 placebo-controlled studies for depression (n=987) or smoking cessation (n=1,013), or patients

565 who experienced an adverse event requiring discontinuation of treatment in an open-label

566 surveillance study with the sustained-release formulation of bupropion (n=3,100). All

567 treatment-emergent adverse events are included except those listed in Tables 1 through 4, those

568 events listed in other safety-related sections, those adverse events subsumed under COSTART

569 terms that are either overly general or excessively specific so as to be uninformative, those

570 events not reasonably associated with the use of the drug, and those events that were not serious

571 and occurred in fewer than 2 patients. Events of major clinical importance are described in the

572 WARNINGS and PRECAUTIONS sections of the labeling.

573 Events are further categorized by body section and listed in order of decreasing frequency

574 according to the following definitions of frequency: Frequent adverse events are defined as those

575 occurring in at least 1/100 patients. Infrequent adverse events are those occurring in 1/100 to

576 1/1,000 patients, while rare events are those occurring in less than 1/1,000 patients.

577 Adverse events for which frequencies are not provided occurred in clinical trials or

578 postmarketing experience with bupropion. Only those adverse events not previously listed for

579 sustained-release bupropion are included. The extend to which these events may be associated

580 with WELLBUTRIN XL is unknown.

581 Body (General): Infrequent were chills, facial edema, musculoskeletal chest pain, and

582 photosensitivity. Rare was malaise. Also observed were arthralgia, myalgia, and fever with rash