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Prior Authorization Protocol
CRINONER (progesterone gel), ENDOMETRINR (progesterone vaginal insert)

NATL
Coverage of drugs is first determined by the member’s pharmacy or medical benefit. Please consult with or refer to the Evidence of Coverage document.
  1. FDA Approved Indications:
    Crinone 4%
    • For the treatment of secondary amenorrhea.
    Crinone 8%
    • For progesterone supplementation or replacement as part of an Assisted Reproductive Technology ("ART") treatment for infertile women with progesterone deficiency.
    • For the treatment of secondary amenorrhea in women who have failed to respond to treatment with Crinone 4%.
    Endometrin
    • To support embryo implantation and early pregnancy by supplementation of corpus luteal function as part of an Assisted Reproductive Technology (ART) treatment program for infertile women
  2. Health Net Approved Indications and Usage Guidelines:
    • ART treatment in patients with premature ovarian failure: Crinone 8%, Endometrin (benefit exclusion for Medi-Cal members)

    AND

      • Patient must have infertility coverage (optional pharmacy benefit)
    OR

    • Luteal phase support (i.e., history of spontaneous abortions): Crinone 8%, Endometrin

    OR

    • Secondary amenorrhea: Crinone 4%, 8%

    AND

      • Failure or clinically significant adverse effects to at least one alternative progestin (e.g., medroxyprogesterone, norethindrone)
    OR
    • Prevention of preterm birth in women with a short cervix

    OR

    • Singleton pregnancy and a history of spontaneous preterm birth
  3. 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.
  4. General Information:
    • Micromedex recommendation IIa for the use of progesterone as prophylaxis of premature birth of newborn in women with short cervix. Studies cited used the following progesterones: Progesterone 90 mg vaginal gel once daily; or Micronized progesterone 200 mg intravaginally at bedtime.
    • In clinical trials, less than 25 mm is the length most frequently used to define short cervix measured mid-pregnancy (prior to 24 weeks gestation).
    • According to the American College of Obstetrics and Gynecologists Opinion, current evidence does not support the routine use of progesterone in women with multiple gestations.
  5. Therapeutic Alternatives:
    Drug Dosing Regimen Dose Limit/ Maximum Dose
    Medroxyprogesterone (e.g., ProveraR)
    Secondary amenorrhea
    5 to 10 mg PO QD for 5 to 10 days
    10 mg/day x 10 days

    Norethindrone Acetate (AygestinR)

    Secondary amenorrhea
    2.5 to 10 mg PO QD for 5 -10 days

    10 mg/day x 10 days

    * Requires Prior Authorization
  6. Recommended Dosing Regimen and Authorization Limit:
    Drug Dosing Regimen Authorization Limit

    Crinone Gel

    Premature Ovarian failure as replacement in ART
    8% (90 mg) PV BID
    As supplementation in ART
    8% (90 mg) PV QD
    Secondary amenorrhea
    4% (45 mg) PV QOD up to a total of 6 doses
    If 4% fails, 8% PV QOD up to a total of 6 doses
    Prophylaxis of premature birth
    90 mg vaginally QD
    Begin treatment prior to 24 weeks gestation

    Premature Ovarian failure as replacement in ART
    Once pregnancy occurs, treatment may be continued until placental autonomy is achieved, up to 10-12 weeks.
    As supplementation in ART
    Once pregnancy occurs, treatment may be continued until placental autonomy is achieved, up to 10-12 weeks.
    Secondary amenorrhea
    6 applicators (12 days/authorization)
    Reauthorization will depend on chart documentation of patient's response to the medication
    Prophylaxis of premature birth
    Until delivery

    Endometrin, vaginal insert

    As supplementation in ART
    100 mg PV BID or TID
    Prophylaxis of premature birth
    200 mg vaginally at bedtime
    Begin treatment prior to 24 weeks gestation

    As supplementation in ART
    Administration of drug starts day after oocyte retrieval
    and continues for up to 10 weeks
    Prophylaxis of premature birth
    Until delivery

  7. Product Availability:
    Crinone 4% gel (45 mg of progesterone) in 6 single-use applicators
    Crinone 8% gel (90 mg of progesterone) in, 15 single-use applicators
    Endometrin (100 mg) in 21 vaginal inserts
  8. References:
    1. Crinone [Prescribing Information] Parsippany, NJ: Watson, Pharma,Inc; August 2013.
    2. Endometrin [Prescribing Information] Parsippany, NJ: Ferring Pharmaceuticals Inc; February 2008.
    3. Micromedex Healthcare Series [Internet database]. Greenwood Village, Colo: Thomson Reuterus (Healthcare). Updated periodically. Accessed July 8, 2015.
    4. Clinical Pharmacology Website. Available at: http://www.clinicalpharmacology-ip.com/. Accessed July 8, 2015.
    5. Progesterone. American Hospital Formulary Service Drug Information. Available at http://www.medicinescomplete.com/mc/ahfs/current/. Accessed July 8, 2015.
    6. Hassan SS, Romero R, Vidyadhari D, et al. Vaginal progesterone reduces the rate of preterm birth in women with a sonographic short cervix: a multicenter, randomized, double-blind, placebo controlled trial. Ultrasound in Obstet Gynecoll 2011;38:18-31.
    7. Fonseca EB, Celik E, Parra M, et al. Progesterone and the Risk of Preterm Birth among Women with a Short Cervix. NEJM. 2007;357:462-469.
    8. DeFranco E, Obrien JM, Adair CD et al. Vaginal progesterone is associated with a decrease in risk for early preterm birth and improved neonatal outcome in women with a short cervix: a secondary analysis from a randomized, double-blind, placebo-controlled trial. Ultrasound Obstet Gynecol 2007;30:697-705.
    9. Use of Progesterone to Reduce Preterm Birth; ACOG Committee Opinion No. 419. October 2008.
    10. daFonseca EB, Bittar RE, Carvalho MHB et al. 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 - 424.
    11. Norwitz E, Phaneuf L, Caughey Progesterone Supplementation and the Prevention of Preterm Birth. Obstetrics and Gynecology 2011 Summer; 4(2): 60-72.
The material provided to you are guidelines used by this plan to authorize, modify or determine coverage for persons with similar illnesses or conditions. Specific care and treatment may vary depending on individual need and the benefits covered under your contract.