INDICATIONS

Sustained Release and Immediate Release Tablets: Treatment for Depression

Bupropion HCl is indicated for the treatment of depression.

The efficacy of bupropion HCl in the treatment of depression was established in two 4-week controlled trials of depressed inpatients and in one 6-week controlled trial of depressed outpatients for the sustained release tablets (two trials of approximately 3 weeks' duration in depressed patients and one of approximately 6 weeks' duration in depressed outpatients) whose diagnoses corresponded most closely to the Major Depression category of the APA Diagnostic and Statistical Manual (DSM) III (see CLINICAL PHARMACOLOGY.)

A major depressive episode (DSM-IV) implies the presence of 1) depressed mood or 2) loss of interest or pleasure; in addition, at least five of the following symptoms have been present during the same 2-week period and represent a change from previous functioning: depressed mood, markedly diminished interest or pleasure in usual activities or decrease in sex drive, significant change in weight and/or appetite, insomnia or hypersomia, psychomotor agitation or retardation, increased fatigue, feeling of guilt or worthlessness, slowed thinking or impaired concentration, a suicide attempt or suicidal ideation.

Effectiveness of bupropion in long-term use (more than 6 weeks) has not been systematically evaluated in controlled trials. Therefore, the physician who elects to use bupropion sustained release tablets for extended periods should periodically reevaluate the long-term usefulness of the drug for the individual patient.

Additional Information for the Immediate Release Tablets: A physician considering bupropion HCl sustained release tablets for the management of a patient's first episode of depression should be aware that the drug may cause generalized seizures in a dose-dependent manner with an approximate incidence of 0.4% (4/1000). This incidence of seizures may exceed that of other marketed antidepressants by as much as fourfold. This relative risk is only an approximate estimate because no direct comparative studies have been conducted (see WARNINGS).

Sustained Release Tablets: Treatment for Smoking Cessation

Bupropion is indicated as a smoking cessation treatment.

DOSAGE AND ADMINISTRATION

General Dosing Considerations: It is particularly important to administer bupropion HCl in a manner most likely to minimize the risk of seizure (see WARNINGS.) Gradual escalation in dosage is also important if agitation, motor restlessness, and insomnia, often seen during the initial days of treatment, are to be minimized. If necessary, these effects may be managed by temporary reduction of dose or the short-term administration of an intermediate to long-acting sedative hypnotic. A sedative hypnotic usually is not required beyond the first week of treatment. Insomnia may also be minimized by avoiding bedtime doses. If distressing, untoward effects supervene, dose escalation should be stopped.

Treatment of Depression

Initial Treatment

Sustained Release: The usual adult target dose for bupropion sustained release tablets is 300 mg/day, given as 150 mg, twice daily. Dosing with bupropion sustained release tablets should begin at 150 mg/day given as a single daily dose in the morning. If the 150 mg initial dose is adequately tolerated, an increase to the 300 mg/day target dose, given as 150 mg twice daily, may be made as early as day 4 of dosing. There should be an interval of at least 8 hours between successive doses.

Immediate Release: Increases in dose should not exceed 100 mg/day in a 3-day period. No single dose of bupropion HCl should exceed 150 mg. Bupropion HCl should be administered three times daily, preferably with at least 6 hours between successive doses.

The usual adult dose is 300 mg/day, given three times daily. Dosing should begin at 200 mg/day given as 100 mg twice daily. Based on clinical response, this dose may be increased to 300 mg/day, given as 100 mg 3 times daily, no sooner than 3 days after beginning therapy. (See TABLE 10.)

TABLE 10 Dosing Regimen
			Number of Tablets
Treatment Day	Total Daily Dose	Tablet Strength	Morning	Midday	Evening
1	200 mg	100 mg	1		1
4	300 mg	100 mg	1	1	1

Increasing the Dosage Above 300 mg/day: As with other antidepressants, the full antidepressant effect of bupropion HCl may not be evident until 4 weeks of treatment or longer. An increase in dosage to the maximum of 400 mg/day, given as 200 mg twice daily, (450 mg/day for the immediate release, given as in doses not more than 150 mg each) may be considered for patients in whom no clinical improvement is noted after several weeks of treatment at 300 mg/day. For the Immediate Release Tablets Only: Dosing above 300 mg/day may be accomplished using the 75 or 100 mg tablets. The 100 mg tablet must be administered 4 times daily with at least 4 hours between successive doses, in order to not exceed the limit of 150 mg in a single dose. Bupropion HCl should be discontinued in patients who do not demonstrate an adequate response after an appropriate period of treatment at 450 mg/day.

Maintenance: The lowest dose that maintains remission is recommended. Although it is not known how long the patient should remain on bupropion HCl, it is generally recognized that acute episodes of depression require several months or longer of antidepressant drug treatment.

Treatment for Smoking Cessation

Usual Dosage for Adults: The recommended and maximum dose of bupropion HCl sustained release tablets for smoking cessation is 300 mg/day, given as 150 mg twice daily. Dosing should begin at 150 mg/day given every day for the first 3 days, followed by a dose increase for most patients to the recommended usual dose of 300 mg/day. There should be an interval of at least 8 hours between successive doses. Doses above 300 mg/day should not be used (see WARNINGS). Treatment with bupropion HCl sustained release tablets should be initiated while the patient is still smoking, since approximately 1 week of treatment is required to achieve steady-state blood levels of bupropion. Patients should set a "target quit date" within the first 2 weeks of treatment with bupropion HCl, generally in the second week. Treatment with bupropion HCl should be continued for 7 to 12 weeks; duration of treatment should be based on the relative benefits and risks for individual patients. If a patient has not made significant progress toward abstinence by the seventh week of therapy with bupropion HCl, it is unlikely that he or she will quit during that attempt, and treatment should probably be discontinued. Dose tapering of bupropion is not required when discontinuing treatment. It is important that patients continue to receive counseling and support throughout treatment with bupropion, and for a period of time thereafter.

Individualization of Therapy: Patients are more likely to quit smoking and remain abstinent if they are seen frequently and receive support from their physicians or other health care professionals. It is important to ensure that patients read the instructions provided to them and have their questions answered. Physicians should review the patient's overall smoking cessation program that includes treatment with bupropion HCl. Patients should be advised of the importance of participating in the behavioral interventions, counseling, and/or support services to be used in conjunction with bupropion HCl. See information for patients at the end of the package insert.

The goal of therapy with bupropion HCl is complete abstinence. If a patient has not made significant progress towards abstinence by the seventh week of therapy with bupropion HCl, it is unlikely that he or she will quit during that attempt, and treatment should be discontinued.

Patients who fail to quit smoking during an attempt may benefit from interventions to improve their chances for success on subsequent attempts. Patinets who are unsuccessful should be evaluated to determine why they failed. A new quit attempt should be encouraged when factors that contributed to failure can be eliminated or reduced, and conditions are more favorable.

Maintenance: Although clinical data are not available regarding the long-term use (>12 weeks) of bupropion for smoking cessation, bupropion has been used for longer periods of time in the treatment of depression. Whether to continue treatment with bupropion HCl for periods longer than 12 weeks for smoking cessation must be determined for individual patients.

Combination Treatment with Bupropion HCl and a Nicotine Transdermal System (NTS): Combination treatment with bupropion HCl and NTS may be prescribed for smoking cessation. The prescriber should review the complete prescribing information for both bupropion HCl and NTS before using combination treatment. See also CLINICAL STUDIES for methods and dosing used in the bupropion HCl and NTS combination trial. Monitoring for treatment-emergent hypertension in patients treated with the combination of bupropion and NTS is recommended.

HOW SUPPLIED

Wellbutrin Immediate Release Tablets: The 75 mg tablets are yellow-gold, round, biconvex tablets printed with "Wellbutrin 75". The 100 mg tablets are red, round, biconvex tablets printed with "Wellbutrin 100".

Wellbutrin SR Sustained Release Tablets: The 100 mg tablets are blue, round, biconvex, film-coated tablets printed with “WELLBUTRIN SR 100”. The 150 mg tablets are purple, round, biconvex, film-coated tablets printed with “WELLBUTRIN SR 150”.

Zyban Sustained Release Tablets: The 150 mg tablets are purple, round, biconvex, film-coated tablets printed with "ZYBAN 150".

Storage: Store at controlled room temperature, 20-25°C (68-77°F) The immediate release tablet can be stored at temperatures as low as 15°C (59°F). Dispense in a tight, light-resistant container as defined in the USP.

PRODUCT LISTING

, Extended Release - Oral - 100 mg
60's	Wellbutrin Sr, Glaxo Wellcome	00173-0947-55
Tablet, Extended Release - Oral - 150 mg
60's	Wellbutrin Sr, Glaxo Wellcome	00173-0135-55
60's	Zyban Sr, Glaxo Wellcome	00173-0556-01
60's	Zyban Sr Refill, Glaxo Wellcome	00173-0556-02