News Release

FDA approves Wellbutrin XL(TM)

New, once-daily antidepressant

Business Announcement

Cooney Waters Group, Inc.

Research Triangle Park, NC (August 28, 2003) -- GlaxoSmithKline announced today that the U.S. Food and Drug Administration has approved Wellbutrin XL™ (bupropion hydrochloride extended-release tablets) for the treatment of major depressive disorder in patients 18 and older. The new once-daily medication will offer patients an effective and convenient option to treat their depression, with a low risk of sexual side effects and weight gain. Sexual function and weight change are important considerations in selecting antidepressant therapy, as they may be a side effect of the medication or a symptom of the depression itself. GlaxoSmithKline expects Wellbutrin XL to be available in pharmacies by mid-September.

"Approximately 14 million adults in the U.S. suffer from depression, and while the number of available treatments has increased in the past decade, some antidepressant medications have left patients coping with other problems, such as side effects, which may include sexual dysfunction and weight change," said Anita Clayton, M.D., Professor of Psychiatry at the University of Virginia Health System. "Wellbutrin XL is a long-awaited treatment option because it offers a low risk of sexual side effects and weight gain – with the convenience of once-daily dosing."

Wellbutrin XL tablets have a two-layered coating designed to release drug slowly in the body. GlaxoSmithKline licensed this once-daily formulation of bupropion hydrochloride from Biovail Corporation in October 2001. Wellbutrin XL will be available in two strengths, 150 mg and 300 mg, to allow for dosing flexibility. The usual target dose is 300 mg given once daily – initiated at 150 mg/day and then increased to 300 mg/day as early as day four, if adequately tolerated. The maximum total daily dose of Wellbutrin XL is 450 mg.

"Wellbutrin XL builds on a strong foundation. Through the first half of 2003, our twice-daily formulation, Wellbutrin SR®, has remained the number one prescribed antidepressant among U.S. psychiatrists," said Chris Viehbacher, President, US Pharmaceuticals, GlaxoSmithKline. "Yet we know that for many doctors twice-daily dosing is a major prescribing barrier. We are confident that the convenient once-daily dosing of Wellbutrin XL will be a welcome improvement for patients coping with depressive illness and for the physicians who are treating them."


Wellbutrin XL is the first and only once-daily norepinephrine and dopamine reuptake inhibitor (NDRI) for the treatment of depression in adults. The active ingredient in Wellbutrin XL – bupropion hydrochloride – is believed to act upon norepinephrine and dopamine, two chemicals in the brain known to help regulate different aspects of mood, cognition, and behavior. Imbalances in these brain chemicals are associated with depressed mood and other symptoms of depression. Bupropion has no clinically significant impact on serotonin, a third brain chemical involved in mood regulation.

"In my clinical practice of treating patients with depression, sexual problems and weight change may be related to the depression itself, or these problems may arise as side effects of the antidepressant treatment," said James F. Pradko, M.Sc., M.D. a practicing physician and the director of the Bay Pointe Depression Clinic in Detroit MI. "In either case, sexual function and weight issues relating to depression should be addressed and can have an impact on a patient's treatment and well-being."


The approval of Wellbutrin XL was based on bioequivalence to Wellbutrin® Tablets (the immediate-release formulation of bupropion). Wellbutrin XL has also been proven bioequivalent to Wellbutrin SR® Tablets (the sustained-release formulation of bupropion).

The efficacy of bupropion in the treatment of a major depressive episode was established using the immediate-release formulation in two four-week controlled trials of inpatients and one six-week controlled trial of outpatients who met criteria for major depression. The efficacy of bupropion in maintaining an antidepressant response for up to 44 weeks was established with the sustained-release formulation in a placebo-controlled trial. Bupropion has also been shown to be effective in preventing relapse of depression. In other clinical studies, the active ingredient in Wellbutrin XL has proven comparable to Zoloft®* in treating moderate to severe recurrent major depression.


Wellbutrin XL has been proven bioequivalent to both Wellbutrin® Tablets and Wellbutrin SR® tablets. Given that there are multiple formulations of bupropion, familiarity with the different names and dosing schedules is important to avoid dosing errors.

Placebo-controlled trials of Wellbutrin SR show it to be generally well tolerated. Adverse events reported in at least 10 percent of patients treated with Wellbutrin SR 300 mg/day or 400 mg/day and at a rate at least twice that of placebo were dry mouth, nausea, insomnia, dizziness, weight loss, and pharyngitis. Similar adverse events would be expected with Wellbutrin XL.

Wellbutrin XL is contraindicated in patients who have or have had a seizure disorder, patients being treated with Zyban® (bupropion hydrochloride) Sustained-Release Tablets or Wellbutrin SR® or any other medications that contain bupropion, patients who have or had bulimia or anorexia nervosa, patients undergoing abrupt discontinuation of alcohol or sedatives (including benzodiazepines), and patients taking monoamine oxidase (MAO) inhibitors.

In treating depression, physicians should be aware that Wellbutrin XL™ is associated with a risk of seizures which is dose-related. While Wellbutrin XL has not been formally evaluated in clinical trials, its incidence of seizure may be similar to that of the immediate-release and the sustained-release formulations of bupropion, since it has demonstrated bioequivalence to both. At doses of up to 300 mg/day of the sustained-release formulation (Wellbutrin SR®), the incidence of seizure is approximately 0.1 percent. At doses of 300 mg/day to 450 mg/day of the immediate-release (Wellbutrin), the incidence of seizure is approximately 0.4 percent. To reduce the risk of seizures, refer to the Warnings section of the Prescribing Information for patient selection considerations, including concomitant medications and dosing recommendations.

The weight loss potential of Wellbutrin XL should be considered if weight loss is a major presenting sign of the depressive illness.

When treating patients with severe hepatic cirrhosis, extreme caution should be exercised and a reduced dosage and/or frequency is required to avoid accumulation.


GlaxoSmithKline, one of the world's leading research-based pharmaceutical and healthcare companies, is committed to improving the quality of human life by enabling people to do more, feel better and live longer. GlaxoSmithKline has U.S. operations in Philadelphia and Research Triangle Park, N.C.


For full prescribing information or product photo, please contact Holly Russell at 919-483-2839.

* Zoloft (sertraline HCl) is a registered trademark of Pfizer Inc.

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