Statement Regarding FDA Trial: The UNC Center for Maternal & Infant Health is dedicated to reducing preterm births in North Carolina and that has included the application of the drug 17-alpha hydroxyprogesterone caproate (17P). This drug was approved by the Food and Drug Administration in 2011 to treat women at risk of delivering a second premature baby. AMAG, the company that produces the 17P drug called MakenaTM has recently completed a large, international FDA required trial of the drug. We are currently awaiting the results, including findings regarding subgroup analyses. It is our recommendation that at this time there should be no change in the standard of care concerning the use of this drug among eligible women. We will share any new guidance or information as soon as it becomes available.
The implementation of a strong 17P program requires the commitment of the full clinic team. Health care providers, patients, case managers, office managers and payers must come together to identify all eligible women, develop a collaborative plan to conveniently deliver and track 17P use, and assure that the woman and provider/clinic are reimbursed for this treatment. It takes effort to establish a strong 17P program in your clinic. We are here to help! Please utilize and adapt the resources provided at the right as well as refer to this site often for up-to-date information.
Please refer to the following information to assist your practice in the delivery of 17P to all eligible women.
Health care providers do not have many tools to use once preterm labor has begun. Tocolytic therapy has proven to have only minimal impact on preventing preterm delivery. At best, delivery can be delayed for 48 hours allowing for the administration of antenatal steroids to enhance fetal lung maturity. Even the prolonged use of oral tocolytics has not proven effective in averting premature delivery.
Without the ability to stop preterm labor, health care providers continue to look to ways to prevent preterm labor in the first place. In 2003, Meis et al. reported that the weekly injection of 250 mg of a naturally occurring progesterone (17-hydroxyprogesterone) could result in a 33% reduction in the rate of preterm delivery prior to 35 weeks’ gestation and a 42% reduction prior to 32 weeks’ gestation. This study was the first to demonstrate a decrease in morbidity in the NICU – significantly lower rates of necrotizing enterocolitis, intraventricular hemorrhage, and the need for supplemental oxygen. In a second randomized study from Brazil, a daily 100 mg progesterone vaginal suppository decreased the incidence of preterm delivery from 28.5% (placebo group) to 13.8%. Delivery prior to 34 weeks’ gestation was reduced from 18.5% to 2.7%.
The exact mechanism by which progesterone prevents preterm birth is unknown although it has been shown to decrease inflammation and to block the effect of oxytocin on the myometrium, keeping the uterus from contracting. Studies to date have demonstrated that hydroxyprogesterone is not associated with congenital anomalies or other neonatal developmental problems.
An important feature of both reported studies is that enrollment was limited to singleton gestations in patients with a previous history of spontaneous preterm delivery. Studies to date have indicated that progesterone is not effective in preventing premature delivery in pregnancies at low risk for prematurity, multiple gestations, or in patients for whom preterm contractions have occurred. Current candidates for progesterone should meet the following criteria: previous spontaneous preterm delivery (<37 weeks gestation) of a single baby.
A preferred use of progesterone is weekly intramuscular injections of 250 mg of 17-hydroxyprogesterone ideally starting at 16 weeks gestation and continuing to 36 weeks and 6 days. Vaginal progesterone is recommended as a management option to reduce the risk of preterm birth in asymptomatic women with a singleton gestation without a prior preterm birth with an incidentally identified very short cervical length less than or equal to 20 mm before or at 24 weeks of gestation.
Meis PJ. 17 hydroxyprogesterone for the prevention of preterm delivery. Obstet Gynecol 2005;105:1128-35.
Meis PJ, Klebanoff M, Thom E, Dombrowski MP, Sibai B, Moawad Ah, et al. Prevention of recurrent preterm delivery by 17 alpha-hydroxyprogesterone caproate. N Eng J Med 2003;348:2379-85.
da Fonseca EB, Bittar RE, Carvalho MH, Zugaub M. Prophylactic administration of progesterone by vaginal suppository to reduce the incidence of spontaneous preterm birth in women at increased risk: A randomized placebo-controlled double-blind study. Am J Obstet Gynecol 2003;188:419-24.
American College of Obstetricians and Gynecologists (ACOG). (2008, reaffirmed 2012). ACOG practice bulletin number 130: Prediction and prevention of preterm birth. Obstetrics and Gynecology, 120(4):964-973.
Woman-Centered 17P Care
Research has shown that patients who perceive themselves as having a high-quality relationship with their clinicians are more likely to adhere to treatment recommendations. Studies show that the clinician-patient relationship is a crucial factor affecting adherence, especially as treatment continues over the long term.
Adherence, persistence and compliance are three distinct behaviors.
Study results suggested that ongoing nursing involvement can facilitate longer-term adherence.
According to Becker’s Health Belief Model (Ogden 2005), the tendency of patients to engage in treatment depends on four types of expectations: 1) the perceived severity of the illness, 2) the perceived vulnerability to that illness, 3) perceived benefits expected from the specific health behavior, and 4) perceived barriers to engaging in the specific health behavior. The clinician can work with the patient to explore each of these expectations and provide information that will help inform an accurate patient perspective.
Recent research offers these tips for supporting patient adherence:
- Physicians should discuss possible adverse effects and share a benefit-risk profile.
- Physicians should take time to answer women’s questions. Women who reported having received detailed answers to their questions also reported better adherence.
- Physicians should not rely on presenting written information but should mainly engage in giving answers.4
Ogden J. Health psychology. In: Hewstone M, Fincham F, Foster J, editors. Psychology.Hoboken, NJ: Wiley-Blackwell; 2005.
Quality Improvement & Facilitative Treatment
Integrating 17P treatment into care requires thought across the treatment “cascade” from screening through treatment counseling, acceptance and adherence. There are many places across this continuum where improvements can be made.
Angela Aina, former CDC Public Health Prevention Service Fellow, conducted focus groups with Pregnancy Medical Home care managers across North Carolina in December 2014 and January 2015. She conducted phone interviews in May 2015 with women eligible for 17P treatment across North Carolina. The following are expressed barriers and facilitators to receiving 17 treatment.
- Transportation, especially long distances or across counties
- Lack of perceived risk of preterm birth among women
- Competing stressors and priorities (no child care; not able to leave work for weekly appointments)
- Injection site discomforts and inconsistencies in injection administration
- Costs of 17P and payer billing issues
- Lack of provider buy-in toward the treatment
- CMIH-produced 17P booklet content, resources, and tools were helpful in answering women’s questions.
- Care managers’ praise, encouragement, counseling and continued education about 17P benefits aided treatment compliance.
- Statewide marketing of preterm birth and of the benefits of 17P treatment boosted public awareness.
- Adoption of best practices in care management in North Carolina’s Pregnancy Medical Home program aided treatment compliance.
Suggestions for Improvement
- Physicians should provide ongoing encouragement and support during 17P treatment as adhering to weekly injections is difficult.
- Patients need to be continually reassured that 17P is safe for mom and baby.
- Physicians should discuss 17P treatment during the postpartum visit with all patients who had spontaneous preterm births.
- Minimize the pain of injections by applying pressure to the gluteal area prior to giving the intramuscular injection and by administering the drug slowly; care in administering shots may motivate women to complete treatment.
- Assign the same nurse to administer the shot at each appointment – if she is good at giving the shot!
- Incorporate injections into home visits or traveling nurse’s responsibility.
- Increase awareness and marketing of 17P treatment and preterm birth to the general public and to reproductive age women.
Which Insurance Plans Pay for 17P?
For patients with private health insurance, clinics should contact the insurance company to inquire about their protocol and procedures for purchasing and billing for this treatment. If the patient is unable to afford the copay for Makena (the commercial 17P product) they can call the Makena Patient Assistance program at 1-800-847-3418 for assistance.
What if my patient is uninsured?
The NC 17P Initiative’s program for uninsured women state funding ended on May 31, 2014. Currently, clinics and providers can contact the Makena Patient Assistance Program and enroll their patient in their program for women without health insurance.
Contact the Makena Care Connection at 1-800-847-3418 between 9am-6pm EST. They can help your patient access this medication. If you encounter any problems contact Erin McClain at 919-808-0989 or email@example.com. Additional directions and information are available on our website under Order 17P.
Can I order a stock vial for my clinic?
This may be an option if purchasing Makena via the Physician Drug Program. Go 17P Billing for more information.
What is a Point of Sale (POS) Pharmacy?
A prescription is sent to the pharmacy. Medicaid is billed directly under that patient’s Medicaid ID. Pregnant patients are exempt from Medicaid co-pays for medications. Medicaid is charged for the prescription by the pharmacy at the time it is dispensed.
What is the Physician Drug Program (PDP)?
The provider purchases the product up front (from a distributor, specialty pharmacy, etc.), then submits a claim to Medicaid when the product is administered to the patient. This program is often referred to as “buy and bill”. For products only covered under the Physician Drug Program, the patient cannot be sent to the pharmacy with a prescription or she will be expected to pay out of pocket.
Ordering 17P for Patients with Medicaid
Several forumulations of progesterone are covered by Medicaid under various structures, including compounded 17P through the Physician Drug Program and Makena through the Physician Drug Program and Point of Sale Pharmacy (as of June 1, 2014).
More Questions? Contact your Pregnancy Medical Home, OB Nurse Coordinator through your CCNC network.
Ordering 17P for Patients without Insurance
Clinics should contact the Makena Patient Assistance Program to obtain medication for their patients who do not have insurance. Makena Care Connection does have a patient assistance program and provides Makena to uninsured patients. To begin the process, follow the instructions on the Makena Referral Prescription Form.
Before approving the prescription, Makena Customer Service representatives will need to talk with the woman to ask her a few questions. They have representatives that speak Spanish as well as other languages. This conversation can take place while the patient is in the provider’s office. She will be asked if she has commercial insurance and if she is eligible for Medicaid. They will then ask her if she is currently pregnant with a single baby and if she has a history of spontaneous preterm labor. Finally they will ask her to verbally agree to receive the injections at their provider’s office. No questions are asked about documentation or financial eligibility. Providers must complete the application form entirely and fax to Makena Care Connection.
Once the form is received and the patient has been screened, the company will purchase the medication within 48 hours. The provider needs to check where the medication will be sent – check clinic as the patient assistance program requires the medication to be delivered to the provider’s office. If time is of the essence, write “RUSH” on the top of the form.
If you have any questions or have any problems you can email Erin McClain at firstname.lastname@example.org or call her at 919-808-0989 or contact your Pregnancy Medical Home, OB Nurse Coordinator through your CCNC network.
Makena® is the name of the FDA-approved, commercially available 17P product. Makena® is produced by Lumara Health. To learn more about Makena®, click here.
To order Makena® providers need to contact the Makena Care Connection program by calling 1-800-847-3418 or go to www.makena.com for more information. To start this process you will need to complete the Makena Referral/Prescription Form. Here is a link to that form. It is very important to fully complete the form. Note, that if your patient does not have insurance there is a box in Step 1 for you to check. Step 4 asks for your patient’s anticipated start date. If your patient is already taking 17P, fill this in with the date that she will need her next injection. If your patient is difficult to reach by phone, please make a note and list your office number instead of her phone number. Be sure to have your patient sign the form before you fax it. If you need the form to be processed very quickly, write RUSH on the top of the form. Once the form is completed it needs to be submitted to the company by fax to 1-800-847-3413.
Prior to approving, the Makena Care Connection team must speak with the patient. To speed up the process, the provider can call this team and put his/her patient on the telephone to speak with the customer assistant while faxing in the prescription form. Please note that the Care Connection team is able to provide services in multiple languages, including Spanish. Once approved, the medication will be sent to either the patient or the physician (as indicated on the form). Medicaid reimbursement requires that the provider give the medication to the patient, so it is recommended that the medication be sent to the clinic.