European Journal of Obstetrics & Gynecology and Reproductive Biology 116 (2004) 112
LETTER TO THE EDITOR—BRIEF COMMUNICATION
Exposure to sibutramine during pregnancy: a case series Dear Editors, Sibutramine is a serotonin–norepinephrine reuptake inhibitor indicated for the treatment of obesity. It was originally developed as an antidepressant in the 1980s [1,2] but was found to induce marked weight loss, affecting both food intake and energy expenditure. It also enhances the physiological process of satiety and stimulates thermogenesis. It was marketed in the US as a weight loss medication in 1997, following several randomized controlled trials involving over 12,000 subjects who found it efficacious for this indication [3–5]. High-dose teratogenicity studies in rats found one fetus per litter had a malformation, with no recognizable pattern. In a high-dose study in rabbits maternal toxicity and increased cardiovascular malformations were found [1]. No information is available on its use or safety in human pregnancy. The Motherisk Program is a counseling service for pregnant and lactating women and their health care providers, giving information on the safety/risk of drugs, chemicals, radiation, and infectious diseases. We followed up and recorded pregnancy outcomes for 10 women who had called us in early pregnancy because they had taken sibutramine. All 10 discontinued the medication in the first trimester. There were seven live births (normal healthy babies) and two spontaneous and one therapeutic abortion; the mean S:D: birth weight was 3528 482 g. We examined the use of the drug in these women, eliciting indications, dosage, and BMI scores. Nine of them took the drug to lose weight and one, for both weight loss and depression. Although the recommended dose is 10 mg per day, six of the women took higher doses (15–20 mg) and three simultaneously took other medications that were clearly contraindicated in the product monograph, e.g., allergy medicines, NSAIDS. The mean BMI scores were 33:5 6:4S.D., with a range of 25–48. To our knowledge, this is the first report of pregnancy outcomes in women who have taken sibutramine in pregnancy. It is possible that other women have become pregnant
while using it. Consequently, it is important to continue this surveillance to ascertain further outcomes of sibutramineexposed pregnancies. The drug is listed on the US FDA (Office of Women’s Health) Pregnancy Registries
[email protected], and in North America Motherisk can be reached under our toll-free number listed on this website by any women who has been exposed to sibutramine during pregnancy and wishes to be enrolled in our study. In the rest of the world we can also be contacted via our own website: http://www.Motherisk.org.
References [1] Meridia1 Product monograph. Compendium of pharmaceuticals and specialties (CPS), 2002. [2] Buckett WR, Thomas PC, Luscombe GP. The pharmacology of sibutramine hydrochloride (BTS 54 524), a new antidepressant which induces rapid noradrenergic down-regulation. Prog Neuropsychopharmacol Biol Psychiatr 1988;12(5):575–84. [3] James WP, Astrup A, Finer N, Hilsted J, Kopelman P, Rossner S, et al. Effect of sibutramine on weight maintenance after weight loss: a randomised trial. STORM Study Group: Sibutramine Trial of Obesity Reduction and Maintenance. Lancet 2000;356(9248):2119–25. [4] Luque CA, Rey JA. The discovery and status of sibutramine as an antiobesity drug. Eur J Pharmacol 2002;440(2–3):119–28. [5] Finer N. Sibutramine: its mode of action and efficacy. Int J Obes Relat Metab Disord 2002;26(Suppl 4):29–33.
A. Einarson* L. Bonari M. Sarkar K. McKenna G. Koren The Motherisk Program, Division of Clinical Pharmacology, The Hospital for Sick Children The University of Toronto, Toronto, Ont., Canada M5G 1X8 Corresponding author. Tel.: þ1-416-813-4927 fax: þ1-416-813-7562 E-mail address:
[email protected] (A. Einarson) Received 27 November 2003; received in revised form 13 January 2004; accepted 4 February 2004
0301-2115/$ – see front matter # 2004 Elsevier Ireland Ltd. All rights reserved. doi:10.1016/j.ejogrb.2004.02.035
