FDA: No major safety concerns with compounded hydroxyprogesterone caproate

FDA recently released the results of an analysis of a limited number of samples of hydroxyprogesterone caproate active pharmaceutical ingredients (APIs) and compounded hydroxyprogesterone caproate, finding no major safety concerns.

Hydroxyprogesterone caproate is the active ingredient in FDA-approved Makena, a synthetic progestin, which was approved in February 2011 for the reduction of the risk of certain preterm births in women who have had at least one prior preterm birth. However, a version of the active ingredient has been available to patients for many years whose physicians requested the drug from a compounding pharmacist.

Following concern by KV Pharmaceuticals about the purity and potency of these compounded versions of the drug, FDA examined a limited number of samples, some of which were provided by the drug manufacturer, and others that came from compounding pharmacies, doctor’s offices, API distributors, and APIs offered for importation.

Of 16 samples of hydroxyprogesterone caproate API, all passed potency and purity tests using the methods specified in the United States Pharmacopeia (USP) as well as the methods used in the Makena new drug application (NDA); however, they failed the Makena NDA’s limit for unidentified impurities. Four impurities were found, although they did not raise safety concerns, FDA noted.

In addition, 13 samples of compounded hydroxyprogesterone caproate prepared by eight pharmacies were assessed. One sample was subpotent, but all samples met the standard in the Makena NDA for total purity. Two samples failed the standard for unidentified impurities.

Although FDA did not find safety issues with compounded versions of the drug, it did recommend in a Questions and Answer statement, released June 29, that healthcare providers should prescribe FDA-approved Makena as a first-line therapy and offered guidance that could be passed on to patients on how to ensure that they are receiving Makena.

“Compounded drugs do not undergo the same premarket review and thus lack an FDA finding of safety and efficacy and lack an FDA finding of manufacturing quality,” according to the statement. “Therefore, when an FDA-approved drug is commercially available, the FDA recommends that practitioners prescribe the FDA-approved drug rather than a compounded drug unless the prescribing practitioner has determined that a compounded product is necessary for the particular patient and would provide a significant difference for the patient as compared to the FDA-approved commercially available drug product.”