Nafarelin Acetate (Synarel)

Coverage Summary

Coverage stance: Covered with criteria. Synarel (nafarelin acetate) is covered for central precocious puberty (CPP) and endometriosis when the policy's specific diagnostic, prescriber, age, prior therapy, dosing, and duration requirements are met, and is covered as an off-label use for gender dysphoria / gender transition only when the policy’s off-label criteria are satisfied (including state coverage restrictions for HIM/ICHRA).

Highlights: maximum treatment durations and dose caps included in the criteria are: CPP approval and continued therapy durations of 12 months with a CPP maximum dose of 1,800 micrograms/day; endometriosis experience limited to adults and a total therapy duration limit of 6 months with an endometriosis maximum dose of 800 micrograms/day; gender dysphoria/gender transition is an off-label indication with an approval duration of 12 months and dose must be within the FDA maximum for any approved indication or supported by guideline/peer-reviewed evidence (prescriber must submit supporting evidence).

Scope summary (brief): the policy defines medical necessity criteria, initial and continuation approval requirements, dosing limits, approved and non-approved indications, administrative/documentation requirements, and specific HIM/ICHRA state coverage limitations for gender dysphoria/gender transition requests.

Initial Therapy Criteria

I. Initial Approval Criteria

It is the policy of health plans affiliated with Centene Corporation® that Synarel is medically necessary when the following criteria are met:

Indication

A. Central Precocious Puberty (must meet all)
- Diagnosis of central precocious puberty (CPP) confirmed by all of the following (a, b, and c):
- ALL of the following
  - Elevated basal luteinizing hormone (LH) level > 0.2 - 0.3 mIU/mL (dependent on type of assay used) and/or elevated leuprolide-stimulated LH level > 3.3 - 5 IU/L (dependent on type of assay used)
  - Difference between bone age and chronological age > 1 year
  - Age at onset of secondary sex characteristics: Female: < 8 years; Male: < 9 years
- Prescribed by or in consultation with a pediatric endocrinologist

Documentation Required

Submit supporting documentation

Submit supporting documentation: Provider must submit documentation (e.g., office chart notes, lab results, imaging, surgical reports) to support that the member meets the specific approval criteria for the requested indication.

Examples: basal/stimulated LH results, bone age assessment, operative reports confirming endometriosis, Tanner staging documentation, mental health evaluation or documentation of gender-affirming hormone trials

Prior Authorization

Prescriber specialty requirements

Prescriber specialty requirements: Prior authorization requests must include that the medication is prescribed by or in consultation with the required specialist per indication (pediatric endocrinologist for CPP; gynecologist for endometriosis; endocrinologist and a provider experienced in transgender medicine for gender dysphoria requests). Include documentation of consultation when applicable.

Required consultations: pediatric endocrinology (CPP); gynecology (endometriosis); endocrinology and certified transgender medicine provider or mental health specialist (gender dysphoria)

Prior Authorization

State coverage limitation for gender dysphoria (HIM/ICHRA)

State coverage limitation for gender dysphoria (HIM/ICHRA): For HIM/ICHRA line of business, requests for gender dysphoria/gender transition are not coverable in certain states. Provider must attest that the member’s state does not appear on the exclusion list and that state regulations permit coverage.

States where gender dysphoria/gender transition treatment is NOT a covered benefit for HIM/ICHRA: AL, AZ, AR, FL, GA, IN, IA, KS, KY, LA, MS, MO, NE, NH, NC, OH, OK, SC, TN
Provider attestation required: confirm member's state allows coverage or that coverage is otherwise permitted under applicable state regulations

Documentation Required

Supporting evidence for off-label dosing

Supporting evidence for off-label dosing: When request is for an off‑label dose (including for gender dysphoria or other non‑FDA indications), prescriber must submit peer-reviewed literature or practice guideline support demonstrating the safety and efficacy of the proposed dosing regimen.

Include citations to practice guidelines or peer‑reviewed literature supporting the off‑label dose
If dose exceeds FDA maximum for approved indications, provide clear rationale and supporting evidence

Continuation Therapy Criteria

Continued Therapy

Continued therapy is authorized when criteria below are met for the relevant indication.

Indication-specific continued therapy

A. Central Precocious Puberty (must meet all)
- Continuity of care/member history: Member meets one of the following: currently receiving medication via Centene benefit or member has previously met initial approval criteria; OR member is currently receiving medication and is enrolled in a state and product with continuity of care regulations (refer to state specific addendums CC.PHARM.03A and CC.PHARM.03B)
- Response to therapy: Member is responding positively to therapy as evidenced by, including but not limited to, decreased growth velocity, cessation of menses, softening of breast tissue or testes, arrested pubertal progression
- Age requirement

Diagnoses / Indications Not Authorized

Diagnoses/Indications Not Authorized

Non-FDA approved indications not addressed in this policy are not authorized unless there is sufficient documentation of efficacy and safety according to off-label use policies HIM.PA.154 or CP.PMN.53, or evidence of coverage documents

Prior Authorization

Off-label use policy references and documentation

If the requested use is off-label and not specifically listed, refer to the off-label use policies HIM.PA.154 (HIM/ICHRA) or CP.PMN.53 (Medicaid) and submit sufficient documentation per those policies to support medical necessity.

Applicable off‑label policies: HIM.PA.154 (HIM/ICHRA) and CP.PMN.53 (Medicaid)
Submit sufficient documentation of efficacy and safety per the referenced off-label policy

Applicable Codes

NDC / Product availabilityNDC|mixed

Nasal spray: 8 mL containing 2 mg/mL solution

Product availability description

Provider Actions & Administrative Requirements

Actionable prior authorization & documentation callouts

Billing/administrative rules & state-related limits

Clinical Evidence & References

Evidence sources referenced: the policy lists the Synarel Prescribing Information (Nov 2025) as the primary prescribing information reference and cites multiple clinical guidelines and sources (examples include the Endocrine Society guideline, WPATH Standards of Care, American Academy of Pediatrics statements, and a practice bulletin on endometriosis).

The policy explicitly references and integrates these guidelines when defining off-label use criteria for gender dysphoria/gender transition and requires that prescribers submit supporting evidence if an off-label dose or regimen exceeds FDA limits or is outside FDA dosing recommendations.

Appendix D and the references section are used to link to training/certification resources (WPATH, ITCA) and to the Movement Advancement Project for state coverage confirmation, reflecting that multiple guideline and regulatory sources inform the policy and prescriber documentation expectations.

Background

Background: Nafarelin acetate (Synarel) is a gonadotropin-releasing hormone (GnRH) receptor agonist indicated for treatment of central precocious puberty (CPP) in children of both sexes and for the management of endometriosis (experience limited to women ≥ 18 years treated for 6 months). The product is available as a nasal spray (8 mL containing 2 mg/mL).

Diagnostic and prescriber requirements that inform coverage: CPP requires biochemical confirmation (e.g., basal LH > 0.2–0.3 mIU/mL dependent on assay and/or leuprolide-stimulated LH > 3.3–5 IU/L), bone age advanced > 1 year versus chronological age, onset of secondary sex characteristics before 8 years in females or 9 years in males, and prescribing by or in consultation with a pediatric endocrinologist.

Endometriosis requirements: diagnosis of endometriosis, prescriber or consult with a gynecologist, age ≥ 18 years, either surgically confirmed disease or clinically suspected disease plus failure of a 3-month trial within the last year of an NSAID, an oral/depot contraceptive, or a progestin; total Synarel therapy must not exceed 6 months and dose must not exceed 800 micrograms/day.

Gender dysphoria/gender transition (off-label) requirements: diagnosis of gender dysphoria or request for gender transition; prescribing by or in consultation with an endocrinologist and a provider with transgender medicine expertise (per Appendix D resources such as WPATH/ITCA); for minors, attainment of Tanner Stage 2 (age approximations provided) or for adults failure to achieve physiologic hormone levels with gender-affirming hormones unless contraindicated; psychosocial/mental health support and informed consent required; HIM/ICHRA requests must comply with state coverage limitations; dose must be within FDA maximum for an approved indication or supported by practice guidelines/peer-reviewed literature and prescriber must submit supporting evidence.

Dosing notes from the label that inform criteria: CPP dosing regimens up to 1,800 micrograms/day (e.g., 1,600–1,800 mcg/day options) and endometriosis dosing starting at 400 micrograms/day with increase to 800 micrograms/day if needed; these FDA dosing limits are incorporated into the policy’s dose caps and continued therapy checks.

Revision History

07.21.22revised

4Q 2022 annual review: clarified endometriosis duration by adding requirement that total treatment duration should not exceed 12 months and modified continued approval duration from 6 months to up to a total treatment duration of 12 months; references updated; off-label criteria for gender dysphoria/transition added (02.16.23; P&T approval 05.23).

01.09.24revised

2Q 2024 annual review: revised endometriosis total treatment duration from 12 back to 6 months per prescribing information; clarified CPP bone age requirement as difference between bone age and chronological age > 1 year; corrected units for basal LH to mIU/mL; references updated; P&T approval date 05.24.

02.12.25added