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
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
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
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.▪