Phentermine plus topiramate in the treatment of obesity

Despite some limitations, echocardiography is useful for measuring pulmonary pressure and for determining cardiac abnormalities in patients with pulmonary hypertension.4 Several centrally acting anorectic substances have been withdrawn from the market owing to cardiovascular toxicity in past years: aminorex, fenfluramine, sibutramine, and benflu orex.5 Before drawing definitive conclusions on the usefulness of the combination of phentermine and topi ramate in the treatment of obesity, very robust evidence of its cardiovascular safety should be provided. The FDA's concern in this regard seems to have been heightened by an abstract5 which describes data from the North American Antiepileptic Drug Pregnancy Registry and showed that major malformations occurred significantly more often in topiramate-exposed pregnancies than i ? the unexposed (3-8% vs 1-3%, relative risk 2-8, 95% Cl 1-0-8-1); cleft lip occurred in four (1-4%) of 289 infants exposed to top i ramate (two cases [0-69%] were isolated)- a rate markedly higher than the expected prevalence of isolated cleft lip of 0-07%. CAP and WWD are employees of Vivus. * Kishore M Gadde, Donna H Ryan, Craig A Peterson, Wesley W Day gadde001@mc.duke.edu Obesity Clinical Trials Programme, Duke University Medical Center, Durham, NC 27710, USA (KMG); Pennington Biomedical Research Center, Baton Rouge, LA, USA (DHR); and Vivus Ine, Mountain View, CA, USA (CAP, WWD) 1 Rich S, Rubin L, Walker AM, et al.