Wellbutrin XL NDA 21-515

659 bupropion alone included hallucinations, loss of consciousness, and sinus tachycardia. Fever,

660 muscle rigidity, rhabomyolysis, hypotension, stupor, coma, and respiratory failure have been

661 reported when the immediate-release formulation of bupropion was part of multiple drug

662 overdoses.

663 Although most patients recovered without sequelae, deaths associated with overdoses of the

664 immediate-release formulation of bupropion alone have been reported rarely in patients ingesting

665 massive doses of the drug. Multiple uncontrolled seizures, bradycardia, cardiac failure, an

666 cardiac arrest prior to death were reported in these patients.

667 Overdosage Management: Ensure an adequate airway, oxygenation, and ventilation.

668 Monitor cardiac rhythm and vital signs. EEG monitoring is also recommended for the first

669 48 hours post-ingestion. General supportive and symptomatic measures are also recommended.

670 Induction of emesis is not recommended. Gastric lavage with a large-bore orogastric tube with

671 appropriate airway protection, if needed, may be indicated if performed soon after ingestion or in

672 symptomatic patients.

673 Activated charcoal should be administered. There is no experience with the use of forced

674 diuresis, dialysis, hemoperfusion, or exchange transfusion in the management of bupropion

675 overdoses. No specific antidotes for bupropion are known.

676 Due to the dose-related risk of seizures with WELLBUTRIN XL, hospitalization following

677 suspected overdose should be considered. Based on studies in animals, it is recommended that

678 seizures be treated with intravenous benzodiazepine administration and other supportive

679 measures, as appropriate.

680 In managing overdosage, consider the possibility of multiple drug involvement. The physician

681 should consider contacting a poison control center for additional information on the treatment of

682 any overdose. Telephone numbers for certified poison control centers are listed in the

683 Physicians’ Desk Reference (PDR).

684 DOSAGE AND ADMINISTRATION

685 General Dosing Considerations: It is particularly important to administer

686 WELLBUTRIN XL Tablets in a manner most likely to minimize the risk of seizure (see

687 WARNINGS). Gradual escalation in dosage is also important if agitation, motor restlessness,

688 and insomnia, often seen during the initial days of treatment, are to be minimized. If necessary,

689 these effects may be managed by temporary reduction of dose or the short-term administration of

690 an intermediate to long-acting sedative hypnotic. A sedative hypnotic usually is not required

691 beyond the first week of treatment. Insomnia may also be minimized by avoiding bedtime doses.

692 If distressing, untoward effects supervene, dose escalation should be stopped.

693 WELLBUTRIN XL should be swallowed whole and not crushed, divided, or chewed.

694 WELLBUTRIN XL may be taken without regard to meals.

695 Initial Treatment: The usual adult target dose for WELLBUTRIN XL Tablets is 300 mg/day

696 Given once daily in the morning. Dosing with WELLBUTRIN XL Tablets should begin at

697 150 mg/day given as a single daily dose in the morning. If the 150-mg initial dose is adequately