Makena versus compounded 17-hydroxyprogesterone: Will you be intimidated?

By now all of you have heard the story of Makena. The announcement that KV Pharmaceuticals' Makena brand of 17-hydroxyprogesterone caproate (17-OHP) had been approved by the US Food and Drug Administration (FDA) in February 2011 was something that ob/gyns had been waiting for for many years. This is the same medication that we have been using for the last 7 years to decrease the risk of preterm birth in patients who have had a previous preterm delivery. The company succeeded in getting this form of 17-OHP through the FDA orphan drug approval process.

This long-awaited announcement was followed within 2 weeks by what in my opinion was the shocking announcement that the medication we had been obtaining through compounding pharmacies was going to increase the cost of care from an average of about $200 to $400 per pregnancy to up to $30,000 per pregnancy. The same medication that previously had cost $10 to $40 per injection when obtained from compounding pharmacies was now going to cost $1,500 per injection. This price increase without any substantial incremental improvement in healthcare caused a tremendous outcry from obstetricians across the country.

Advocacy efforts by the Society for Maternal-Fetal Medicine (SMFM), the American College of Obstetricians and Gynecologists (ACOG), the March of Dimes (MOD), and the American Academy of Family Physicians (AAFP) as well as by legislators such as Senator Sherrod Brown (D-Ohio) and Representative Allyson Schwartz (D-Pennsylvania), insurers, and caring obstetricians from all over the country have resulted in monumental changes in this situation.

On March 30, 2011, the FDA released a statement that said: "In order to support access to this important drug, at this time and under this unique situation, FDA does not intend to take enforcement action against pharmacies that compound hydroxyprogesterone caproate based on a valid prescription for an individually identified patient unless the compounded products are unsafe, of substandard quality, or are not being compounded in accordance with appropriate standards for compounding sterile products. As always, FDA may at any time revisit a decision to exercise enforcement discretion."¹

This statement specifically addressed the communication that was sent by KV Pharmaceuticals informing compounding pharmacies that they needed to "cease and desist" compounding a drug that now was available as an FDA-approved drug, Makena.

As a result of the FDA's statement, both Medicaid and the Centers for Medicare & Medicaid Services (CMS) released statements that continued use of compounded medication will be covered by these programs that insure 40% to 45% of all pregnant women.² Commercial insurers are instituting programs to allow physicians to preferentially prescribe the compounded 17-OHP as opposed to the more expensive Makena.

SMFM and ACOG acknowledge that the continued use of compounded 17-OHP is consistent with the standard of care

On April 1, 2011, ACOG and SMFM released a joint statement related to the relative merits of compounded 17-OHP versus Makena. They stated that: "There is no evidence that Makena is more effective or safer than the currently used compounded version. Furthermore, the evidence used to obtain FDA approval for Makena relied primarily on data obtained using the compounded product."³ In my opinion, this statement essentially "indemnifies" physicians and insurers who use the affordable compounded 17-OHP from allegations that the use of the compounded 17-OHP rather than the FDA-approved Makena is not consistent with evidence-based medicine or the standard of care. Moreover, KV Pharmaceuticals' assertion that the FDA-approved Makena will necessarily be better than the compounded product seems a bit ironic to me, given the findings of multiple FDA inspections of KV's manufacturing facilities that identified misbranding and concerns about the manufacturing process.⁴