Prior Auth Protocol

FDA Approved Indications:

To reduce the risk of preterm birth in women with a singleton pregnancy who have a history of singleton spontaneous preterm birth.

Health Net Approved Indications and Usage Guidelines:

AND

AND

History of single fetus spontaneous preterm birth at less than 37 weeks of gestation

Coverage is Not Authorized For:

Non-FDA approved indications, which are not listed in the Health Net Approved Indications and Usage Guidelines section, unless there is sufficient documentation of efficacy and safety in the published literature.
For use in women with multiple gestations

General Information:

The FDA approved indication has a limitation of use: Makena is not intended for use in women with multiple gestations or other risk factors for preterm birth. Studies of hydroxyprogesterone for multi-fetal gestations found no benefit to support its use with 41.5% of 17P treated patients experiencing delivery or fetal death before 35 weeks vs. 37.3% of placebo treated patients.
The hydroxyprogesterone caproate product distributed by ANI Pharmaceuticals, Inc. is not a generic for Makena and is not indicated for prevention of preterm birth in pregnant women.
Data are inconclusive on the benefits of initiating hydroxyprogesterone therapy after 20 weeks, 6 days of gestation.
In a study by Durnwald et al., administration of Makena did not reduce preterm birth in women with twin gestations before 35 weeks among those with either a short cervix (64.3 vs. 45.8%, p=0.18) or a long cervix and 38.1 vs. 35.5%, p=0.85).
In a trial by Grobman WA, et al. in nulliparous women with a midtrimester CL<30 mm, delivery <37 weeks of gestation occurred in 25.1% of women in the Makena group and 24.2% of women in the placebo group (relative risk, 1.03; 95% confidence interval, 0.79 -1.35).
In a trial by Combs CA, et al. Mothers carrying dichorionic-diamniotic twins were randomly assigned to weekly injections of 250 mg of Makena or placebo, starting at 16-24 weeks and continued until 34 weeks. Mean gestational age at delivery was not affected by Makena (35.3 vs. 35.9 weeks, p=0.10).

Therapeutic Alternatives:

Drug	Dosing Regimen	Dose Limit/ Maximum Dose
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* Requires Prior Authorization

Recommended Dosing Regimen and Authorization Limit:

Drug	Dosing Regimen	Authorization Limit
Makena	Inject 250 mg (1 mL) IM once weekly (every 7 days) until week 37 of gestation or delivery, whichever occurs first. Begin treatment between 16 weeks, 0 days and 20 weeks, 6 days of gestation.	Up to 21 weeks, through the 36^th week of pregnancy or to member's renewal period, whichever is sooner.

Product Availability:

5 mL multidose vial (250 mg/mL) contains 1,250 mg hydroxyprogesterone caproate

References:

Makena [package insert]. Bloomington, IN: Baxter Pharmaceutical Solutions. February 2015.
Rouse DJ, Caritis SN, Peaceman AM, et al. A trial of 17 alpha-hydroxyprogesterone caproate to prevent prematurity in twins. N Engl J Med. 2007;357:454-461.
Durnwald CP, Momirova V, Rouse DJ, et al. Second trimester cervical length and risk of preterm birth in women with twin gestations treated with 17-a hydroxyprogesterone caproate. J Matern Fetal Neonatal Med. 2010;23:1360-4.
Grobman WA, Thom EA, Spong CY, et al. 17 alpha-hydroxyprogesterone caproate to prevent prematurity in nulliparas with cervical length less than 30 mm. Am J Obstet Gynecol. 2012;207:390.e1-8.
Combs CA, Garite T, Maurel K, et al. 17-hydroxyprogesterone caproate for twin pregnancy:a double-blind, randomized clinical trial. Am J Obstet Gynecol. 2011;221.e1-8.
DRUGDEX^R System [Internet database]. Greenwood Village, Colo: Thomson Healthcare. Updated periodically. Accessed January 4, 2016.
Makena. American Hospital Formulary Service Drug Information. Available at: http://www.medicinescomplete.com/mc/ahfs/current/. Accessed January 4, 2016.
Clinical Pharmacology Web site. Available at: http://cpip.gsm.com/. Accessed January 4, 2016.