Company Tries to Clear Up Confusion About Bupropion

GlaxoSmithKline (GSK) is continuing its efforts to educate prescribers and pharmacists about reports of medication errors involving patients taking the company's Wellbutrin brand of bupropion. Confusion between the Wellbutrin XL formulation (bupropion extended release), Wellbutrin SR (bupropion sustained release), and some generic forms of Wellbutrin SR have led to patients' receiving higher than intended doses of bupropion and experiencing serious adverse events.

In March 2005 GSK, in consultation with the Food and Drug Administration (FDA), sent a “Dear Healthcare Provider” letter primarily devoted to required new labeling on all antidepressants related to the possibility of increased risk of suicidality. In that same letter, GSK noted the multiple formulations of bupropion and their differing dosage schedules.“ Awareness of these various formulations,” the company said,“ is important to help avoid confusion and potential medication errors involving these products.”

Then, this past January, GSK sent out a “Dear Pharmacist” letter, again advising of the various formulations and the occurrence of medication errors due to confusion between them. Now the company is reaching out again in an effort to avoid further medication errors.

The problem stems from confusion between the XL formulation of the product, which as an extended-release product is dosed only once a day using 150 mg or 300 mg tablets for a total daily dose of 300 mg to 450 mg of bupropion. No generic versions of the XL formulation are available in the United States.

The SR formulation of bupropion, in contrast, is a sustained-release product that is taken twice a day using 100 mg, 150 mg, or 200 mg tablets to achieve a total daily dose of between 300 mg and 400 mg bupropion. Generic versions of the Wellbutrin SR formulation are available in the United States.

It seems that both prescribing and dispensing errors have occurred. Prescribing errors have occurred “whereby the prescription was written as Wellbutrin XL twice daily, instead of once daily, which resulted in a higher exposure to bupropion,” than recommended, company documents show. Because bupropion is associated with a dose-related risk of seizure, patients receiving in excess of the maximum recommended daily dose of 450 mg are at increased risk for seizure.

According to the FDA-approved labeling, “At doses of up to 300mg/day of the sustained-release formulation (Wellbutrin SR), the incidence of seizure is approximately 0.1 percent, or a seizure possibly occurring in 1 out of every 1,000 patients. At doses of 300 mg/day to 450 mg/day of the immediate-release formulation (Wellbutrin [bupropion HCl]), the incidence of seizure is approximately 0.4 percent, or possibly 4 patients with a seizure out of every 1,000 patients.”

In addition to prescribing errors, dispensing errors may occur because of the United States Pharmacopeia's (USP) nomenclature for generic equivalents to Wellbutrin SR. USP officially designates the SR formulation as“ bupropion hydrochloride; tablet, extended release.” The generic name for the XL formulation is “bupropion hydrochloride; tablet, extended release.” Although the generic drug names are the same, the two products are not therapeutically equivalent or interchangeable.

In an effort to help reduce bupropion-dispensing errors, some drug references (for example, Wolters Kluwer Health's Facts and Comparisons-2006) now list the SR product as “bupropion HCl; tablets-sustained release (12 hour)” and the XL formulation as“ bupropion HCl; tablets-extended release (24 hour).” However, confusion may continue, as pharmaceutical manufacturers are required to use USP official nomenclature on drug labels for distribution in the United States.

More information is posted at<www.wellbutrin-xl.com>. Health care providers with questions regarding bupropion formulations also may call GSK's Medical Information Department at (888) 825-5249.▪