By: RADM (Ret.) Sandra L. Kweder, M.D., F.A.C.P.
There’s a lot happening these days with regard to the personalization of medicine and how drugs work differently in people, particularly in men versus women. FDA has a long history in understanding and analyzing these effects.
We’ve issued guidance to the pharmaceutical industry explaining in detail our expectations about analyzing clinical data for sex-related differences as well as differences according to other demographic groupings. Those assessments, depending on the drug, may start with routine animal studies, in case a difference is evident by sex, but become most important when drugs begin to be tested in humans to see if data signal potential differences that require follow-up.
Both women and men participate in drug studies. (As early as 2001, a report from the U.S. Government Accountability Office showed women were included in all drug trials at a statistically significant level, and women were the majority of participants in trials supporting half of the applications analyzed.) We also consider separately the effects of drugs on men and women to determine whether sex differences exist and whether we need more information to assess variations, if they exist at all.
We take action if variations are suspected or found. For instance, last year FDA updated the dosing recommendation for sleep medications, such as those containing zolpidem (Ambien and other brands), lowering the recommended starting dose for women to 5 mg (from 10 mg). We did this because women were found to be especially susceptible to zolpidem’s side effects, largely because it is cleared from the body more slowly in women than in men. Moreover, new information became available to FDA last year about how sensitive to blood levels one important side effect of zolpidem is – that of driving impairment. New methods of studying the relationship between drug levels and certain driving tests were key to this understanding. We learned that even when individuals with certain blood levels of zolpidem don’t report feeling drowsy, their driving skills can still be affected. This is true of men and women, but because of women’s slower clearance of the drug from their system they are more likely to be at risk the morning after taking zolpidem.
This zolpidem case highlights how biologic differences can sometimes play out in individuals’ responses to medications. Some differences in how drugs affect men versus women can relate to variations in metabolism and rates of absorption, and sometimes even because a particular illness has different characteristics in men and women. So we expect our reviewers and pharmaceutical companies to routinely look for sex differences in their new drug applications. Despite looking, it is rare for us to find that drugs differ based on sex alone.
Many drug labels already comment on dose considerations or side effect profiles related to age, health problems, or sex. Some drugs are only approved for one sex. For example, Lotronex (alosetron), a drug used to treat irritable bowel syndrome (IBS), is only approved for women because clinical trial data showed the drug is not effective in men. And Giazo (balsalazide) is used to to treat mildly to moderately active ulcerative colitis in males age 18 and older because it was shown to be ineffective in female patients.
FDA also monitors all human drugs on the market via our surveillance programs. When findings suggest safety issues we think are important, we work with companies to put that information in labeling (if it is not already present), and sometimes we require companies to do additional studies. If you, as a patient, have any concerns about your specific medication or dose, you should talk to your health care professional. A drug can act differently in people not just because of their sex, but also due to factors such as weight and other medications taken.
Our staff, including those in our longstanding Office of Women’s Health, are dedicated to protecting and advancing women’s health through policy, science, and outreach. We’ll continue to advocate for the inclusion of women in clinical trials and for analyses of how their bodies process medications. Our recent zolpidem decision is an example of how science evolves – and shows the importance of using new information to review previous decisions when needed. This is an exciting area of science.
Sandra L. Kweder, M.D., is the Deputy Director of the Office of New Drugs at FDA’s Center for Drug Evaluation and Research