Should FDA Limit Interstate Shipment of Compounded Pharmaceuticals?

By Ronald L. Scott
rscott@central.uh.edu

Pursuant to the Food and Drug Administration (FDA) Modernization Act, the FDA is proposing a "memorandum of understanding" (MOU) to establish cooperative programs between the states and the FDA regarding the regulation of interstate distribution of compounded drug products, i.e., products custom-mixed by a pharmacist in accordance with a physicianís order. See http://www.fda.gov/cder/pharmcomp/2142dft.pdf. Compounded pharmaceuticals are exempt from many of the requirements of the Food and Drug Act, including requirements that labeling be reviewed and approved by the FDA and important quality control standards for manufacturing pharmaceuticals. One controversial provision of the MOU prevents a pharmacy or physician from filling more than 20% of its compounded prescriptions for out-of-state delivery.

The dilemma faced by the FDA may be better understood by considering one product currently available only by compounding--topical testosterone cream. (Topical testosterone is commercially available in patch form, and at least one company has recently filed a New Drug Application for testosterone cream). A number of web sites devoted to bodybuilding, alternative medicine, and nutritional supplements promote testosterone cream as a panacea that will help increase muscle mass, improve brain functions such as memory, visual acuity and concentration, and reduce high cholesterol, blood pressure, and blood sugar levels. Men seeking these benefits should be aware of the risks before they buy and use the products promoted on the sites, such as testosterone cream. A physician, preferably a specialist such as an endocrinologist, should closely monitor any hormone replacement therapy. Additionally, users of topical testosterone should be aware of risks to third parties, particularly children and sexual partners, when using such products. However, without stringent labeling requirements, it is difficult to determine whether users are being adequately informed of such risks.

The damage to children in regular contact with users of topical testosterone may be significant. For example, the August 1999 issue of Pediatrics reported a case of sexual development in a two-year-old boy induced by topical exposure to testosterone. The article is available on line at http://www.pediatrics.org/cgi/content/full/104/2/e23. Over a 4 to 5 month period, the child developed progressive enlargement of his penis (to 3.6 inches) together with facial acne and pubic hair. After ruling out other causes, his physicians determined that his father had been applying a topical testosterone to his arms and back as part of a body building regimen. The child had close contact with his father and his fatherís body building equipment and mats, which were smeared with the cream. Although long-term effects to the child are not well understood, four months after stopping exposure to the testosterone cream his facial acne and pubic hair were significantly diminished, although his penis size remained the same. The authors point out that cases of early sexual development caused by exposure to steroids are rare in the medical literature, but they suspect that given the availability of steroids in our society this may not be an isolated incident. (Topical testosterone cream does not increase adult penile size, and may in fact have the opposite effect, since testosterone supplementation may signal the body to produce less testosterone, resulting in smaller rather than larger sexual organs).

Children are not the only ones at risk. Exposing women to testosterone can also be dangerous. Also, as the Physicians Desk Reference dryly notes, "Virilization of female sexual partners has been reported with male use of a topical testosterone solution." Virilization is the process of developing masculine sex characteristics in a female, which may include an increase in body hair, facial hair, deepening of the voice, male-pattern baldness, and clitoral enlargement. Drug information at http://www.drkoop.com advises patients using topical testosterone to advise their physician if a female partner experiences these symptoms or menstrual irregularities. See http://www.drkoop.com/drugstore/pharmacy/leaflets/english/d04273a1.asp. Testosterone may also cause fetal harm.

Some advocacy groups oppose the FDAís proposed limits on interstate shipments of compounded pharmaceuticals. An article in AIDS Treatment News argues that the 20% limit is arbitrary and will block patients from obtaining treatments their physicians feel are necessary. The article includes a comment filed with the FDA in response to the draft MOU describing a time period when there was a serious shortage of FDA-approved injectable testosterone required by some persons with AIDS and other illnesses, and patients were able to substitute compounded testosterone cream. See http://www.thebody.com/atn/320.html.

In addition to its efforts to limit interstate distribution of compounded drugs, the FDA is also pursuing new efforts to help curb illegal prescription drug marketing the Internet. See http://www.fda.gov/bbs/topics/NEWS/NEW00686.html.

08/31/99