Bupropion (Wellbutrin ®, Zyban ®)
Antidepressant of the aminoketone class. Used in smoking cessation.
Molecular weight: 276.2
CATEGORY:B

"Reproduction studies have been performed in rabbits and rats at doses up to 15 to 45 times the human daily dose and have revealed no definitive evidence of impaired fertility or harm to the fetus due to bupropion. (In rabbits, a slightly increased incidence of fetal abnormalities was seen in 2 studies, but there was no increase in any specific abnormality)." [1]

As of February 2003,  764 pregnancies involving exposure to bupropion had been prospectively registered with The Glaxo Wellcome Bupropion Pregnancy Registry.  As of June 2003, 154 pregnancies were pending delivery, 213 cases were lost to follow up, and 397 cases with 401 outcomes were obtained.  The indications for use of bupropion in the latter were depression in 251 patients, smoking cessation in 95 patients, depression and smoking cessation in 16 patients, bipolar affective disorder in one patient, and unspecified in 34 patients.

Of 322 outcomes involving bupropion exposure in the first trimester there were 261 live births without birth defects, 40 spontaneous pregnancy losses, 11 induced abortions, 1 induced abortion with evidence of Down syndrome on prenatal testing, and 9 infants born alive with birth defects.

The defects in infants born alive included one infant with  bilateral club feet, one infant with  Klinefelter's syndrome (no physical  abnormalities), and  7 infants with heart defects (1 abnormal aortic valve thickening with mild aortic insufficiency,  1 ventricular septal defect, 1 trivial pulmonic stenosis with atrial septal defect, 1 coarctation with ventricular septal defect, 1 thickened heart muscle, 1 pulmonary stenosis, and 1 coarctation of the aorta).

The observed proportion of birth defects in pregnancies with prenatal exposure to bupropion in the first trimester was 3.7%.

The registry's Advisory Committee noted the increased number of prospective reports of defects involving the heart and great vessels. Given the small sample size and the potential bias from the large percentage of cases lost to follow up an accurate assessment of a potential effect of bupropion on the developing cardiovascular system could not be made. To further evaluate the possible association of  bupropion with cardiovascular defects The Committee plans to conduct a retrospective cohort study entitled "Bupropion in Pregnancy and the Risk of Cardiovascular and Overall Major Congenital Malformations". (2).

Healthcare providers can obtain interim registry results and register patients by calling the registry project office directly at 1-800-336-2176 (toll-free) or (910) 256-0549 (collect)

BREAST FEEDING: Bupropion is excreted into human milk. In one mother taking bupropion 100 mg three times daily peak milk concentrations occurred 2 hours after a 100 mg dose, The milk-to-plasma ratio ranged between 2.49 and 8.72  over 6 hours after after a 100-mg dose. Bupropion and its metabolites were not detected in the infant's plasma [3]. Milk-to-plasma ratios ranged from 2.51 to 8.58 over a six-hour interval.

Baab SW et al. reported no quantifiable levels of bupropion nor its active metabolite hydroxybupropion were found in serum samples of two breast fed infants after maternal ingestion of either bupropion 75 mg b.i.d. or bupropion SR 150 mg daily[4].

The infants studied in the above reports were all healthy infants at least several months of age. These results may not  be applicable to newborns or infants with health problems.

The American Academy of Pediatrics has classified bupropion as a drug "for which the effect on nursing infants is unknown but may be of concern" [5].


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