US Specialty Societies Statement on Withdrawal of Makena

The American College of Obstetricians and Gynecologists (ACOG) and Society for Maternal Fetal Medicine (SMFM), support the withdrawal of Makena and discourage the use of hydroxyprogesterone caproate for preterm birth. "On April 5, 2023, the US Food and Drug Administration (FDA) withdrew approval of 17-alpha hydroxyprogesterone caproate (17-OHPC), effective immediately, due to lack of evidence that it reduces the risk of recurrent spontaneous preterm birth (PTB). This decision withdraws approval for all formulations of 17-OHPC (both intramuscular and subcutaneous) and applies to both brand name (Makena) and generic versions of the medication. We agree with the FDA determination and discourage continued prescribing of 17-OHPC, including through compounding pharmacies. We do not recommend changing indications for cerclage, indications for vaginal progesterone in patients with short cervix, or recommendations against activity restriction based on the FDA withdrawal of 17-OHPC from the market. We recommend that discussion of the use of vaginal progesterone for primary prevention of recurrent PTB without input of cervical length or in those with a cervical length of 25 mm or greater include a shared decision-making process, especially if a progesterone formulation for PTB prevention was received in a prior pregnancy. The FDA determined that it would be inappropriate to delay the effective date of the withdrawal to allow patients currently receiving 17-OHPC to finish treatment. We agree with the FDA that there is no evidence of benefit with continued treatment. Patients currently receiving 17-OHPC can be counseled that the FDA's Center for Drug Evaluation and Research (CDER) has not identified evidence of harm from discontinuation prior to 37 weeks of gestation."

Clinical Criteria

When a drug is being reviewed for coverage under a member's medical benefit plan or is otherwise subject to clinical review (including prior authorization), the following criteria will be used to determine whether the drug meets any applicable medical necessity requirements for the intended/prescribed purpose.

Hydroxyprogesterone Caproate Injection

Requests for 17-hydroxyprogesterone caproate may be approved when the following criteria are met:

1. Individual is a non-pregnant woman; AND
2. Individual is using for one of the following:

• Management of amenorrhea (primary and secondary) and abnormal uterine bleeding due to hormonal imbalance in the absence of organic pathology (such as, submucous fibroids or uterine cancer); OR
• The treatment of advanced adenocarcinoma of the uterine corpus (Stage III or IV); OR
• As a test for endogenous estrogen production and for the production of secretory endometrium and desquamation.

Requests for hydroxyprogesterone caproate may not be approved for the following:

1. For prevention of pre-term delivery or any subgroup of this population; OR
2. When the above criteria are not met and for all other indications.

Coding

The following codes for treatments and procedures applicable to this document are included below for informational purposes. Inclusion or exclusion of a procedure, diagnosis or device code(s) does not constitute or imply member coverage or provider reimbursement policy. Please refer to the member's contract benefits in effect at the time of service to determine coverage or non-coverage of these services as it applies to an individual member.

HCPCS

• J1729

ICD-10 Diagnosis

• N91.0
• N91.1
• C54.9
• D25.0
• C55

Document History

Injection, hydroxyprogesterone caproate, not otherwise specified, 10mg

• Primary Amenorrhea
• Secondary Amenorrhea
• Malignant neoplasm of corpus uteri, unspecified
• Submucous leomyoma of uterus
• Malignant neoplasm of the uterus, part unspecified

Revised: 12/11/2023