On June 15, 2012, the FDA issued an updated statement on compounded versions of hydroxyprogesterone caproate, the active ingredient in Makena, a drug used for the reduction of the risk of certain preterm births in women who have had at least one prior preterm birth.
The FDA approved Makena in February 2011. For many years prior to the drug?s approval, hydroxyprogesterone caproate was available to patients whose physicians requested the drug from a pharmacist who compounded the drug. In November, the FDA issued a statement to clarify the agency?s enforcement priorities regarding compounded versions of hydroxyprogesterone caproate. They stated that they would not take enforcement action against pharmacies that compounded the drug and would conduct a thorough review.
The FDA tested 16 samples of hydroxyprogesterone caproate, and all 16 samples passed USP tests for potency (97-103%) and purity, but failed the Makena NDA?s limit for unidentified impurities. The FDA also tested 13 samples of compounded hydroxyprogesterone caproate prepared by eight pharmacies. One of the 13 samples was in the range of 80% of declared potency (standard potency is 90-110%). Two of the 13 samples failed to meet the standard for unidentified impurities.
The FDA emphasizes that:
The drugs that pharmacists compound (including compounded hydroxyprogesterone caproate) are not FDA approved, which means they do not undergo premarket review nor do they have an FDA finding of safety and efficacy. Compounding large volumes of drugs that are copies of FDA-approved drugs circumvents important public health requirements, including the Federal Food, Drug, and Cosmetic Act?s drug approval provisions.
Makena (hydroxyprogesterone caproate injection) is indicated for the reduction of the risk of certain preterm births in women who have had at least one prior preterm birth. The FDA originally approved hydroxyprogesterone caproate in 1956 under the brand name Delalutin. In 1999, Delalutin was withdrawn from the market. Makena was approved by the FDA on February 3, 2011 and is marketed by KV Pharmaceuticals.
Using data from AERS, from 01/01/2004 to 3/31/2012, aggregated and standardized by the AdverseEvent RxFilter process, we identified 107 total patients who experienced a serious adverse event where Makena or generic hydroxyprogesterone caproate was identified as a suspect drug causing the event and 86 patients who experienced a serious adverse event where Makena or generic hydroxyprogesterone caproate was identified as the primary suspect.
The most commonly reported side effects were maternal exposure during pregnancy, premature baby, and premature labor. We identified 31 hospitalizations and 12 patient deaths where Makena or generic hydroxyprogesterone caproate was identified as the primary suspect.