ModifiedCentenePolicy CP PHAR.136

Elagolix (Orilissa) and Elagolix/Estradiol/Norethindrone (Oriahnn) coverage

Defines medical necessity and prior authorization criteria for elagolix products (Orilissa and Oriahnn) for commercial, HIM, and Medicaid lines of business within Centene-affiliated health plans.

Policy Summary

PayerCentene

PolicyElagolix (Orilissa) and Elagolix/Estradiol/Norethindrone (Oriahnn) coverage

Policy CodePolicy CP PHAR.136

Change TypeModified (annual reviews with material and non-material edits)

Effective DateAug 28, 2018

Next Review Date

Key ActionSubmit prior authorization with diagnosis, prescriber specialty or consultation, age ≥18, 3-month trial documentation of specified alternatives, and confirmation of <24 months cumulative elagolix exposure.

SourceLink

POLICY UPDATE CHANGES

For Oriahnn, added HIM non-formulary disclaimer and reference to formulary exception policy HIMPA103.

Added requirement that member has not previously received 24 or more months of cumulative elagolix therapy and added Appendix D.

Updated Appendix C to include hypersensitivity reaction to any active ingredients for Orilissa.

Emphasized that 6-month duration of 200 mg twice daily is a lifetime limit and that dose-deescalated continuation after 400 mg/day will not be covered.

6 months200 mg BID maximum duration

24 months150 mg QD / Oriahnn max cumulative

400 mg/dayOrilissa max daily dose

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600 mg/dayOriahnn max daily dose

3 monthsRequired prior trial

150 mg QD or 200 mg BIDOrilissa dosing options

Coverage and Medical Necessity Criteria

Initial Therapy — Endometriosis Pain

Covered when ALL of the following are met

Endometriosis Pain initial therapy: 1) Diagnosis of pain due to endometriosis; 2) Request is for Orilissa; 3) Prescribed by or in consultation with a gynecologist or reproductive endocrinologist; 4) Age ≥ 18 years; 5) Failure of a 3-month trial within the last year of an agent from one of the following classes unless contraindicated or intolerant: a) non-steroidal anti-inflammatory drug; or b) oral or depot injectable progestin or progestin-containing contraceptive (see Appendix B for examples); 6) Member has not already received ≥ 24 cumulative months of treatment with elagolix-containing products (Orilissa, Oriahnn); 7) Dose does not exceed 400 mg per day; 8) Total duration: approval duration per regimen (6 months for 200 mg twice daily; 12 months for 150 mg once daily) and total lifetime therapy should not exceed 6 months for 200 mg twice daily or 24 months for 150 mg once daily.

Initial Therapy — Heavy Menstrual Bleeding (Fibroids)

Covered when ALL of the following are met

Uterine fibroids (Oriahnn) initial therapy: 1) Diagnosis of uterine leiomyomas (fibroids) confirmed by ultrasound; 2) Request is for Oriahnn; 3) Prescribed by or in consultation with a gynecologist or reproductive endocrinologist; 4) Age ≥ 18 years; 5) Member has experienced heavy menstrual bleeding for at least 2 consecutive cycles; 6) Failure of a 3-month trial of a combination estrogen-progestin contraceptive agent (see Appendix B for examples); 7) Dose does not exceed 600 mg of elagolix per day; 8) Member has not already received ≥ 24 cumulative months of treatment with elagolix-containing products (e.g., Orilissa, Oriahnn); 9) Total duration of therapy should not exceed 24 months.

Continued Therapy — Endometriosis Pain

Covered when ALL of the following are met

Endometriosis continued therapy: 1) Member is currently receiving medication via Centene benefit or has previously met initial approval criteria; 2) Request is for Orilissa; 3) Member is responding positively as evidenced by improvement in dysmenorrhea, dyspareunia, pelvic pain/induration/tenderness, or size of endometrial lesions; 4) Member has not already received ≥ 24 cumulative months of treatment with elagolix-containing products (Orilissa, Oriahnn); 5) If request is for a dose increase, new dose does not exceed 400 mg per day; 6) Total lifetime duration of therapy should not exceed 6 months for 200 mg twice daily or 24 months for 150 mg once daily. Requests for dose-deescalated continuation after 6 months of 200 mg twice daily will be denied due to lack of safety evidence for continued dosing beyond 6 months.

Continued Therapy — Heavy Menstrual Bleeding

Covered when ALL of the following are met

Fibroids continued therapy: 1) Member is currently receiving medication via Centene benefit or has previously met initial approval criteria; 2) Request is for Oriahnn; 3) Member is responding positively as evidenced by reduced menstrual blood loss; 4) Member has not already received ≥ 24 cumulative months of treatment with elagolix-containing products (Orilissa, Oriahnn); 5) If request is for a dose increase, new dose does not exceed 600 mg of elagolix per day; 6) Approval duration: up to 12 months; total duration should not exceed 24 months.

Other Indications / Off-Label

Other diagnoses/indications: 1) If the drug has undergone a recent label change (within the last 6 months) not yet reflected in this policy, follow the applicable no-coverage or off-label policies depending on formulary status (see referenced policy numbers); 2) For non‑FDA‑approved indications not addressed in this policy, coverage is not authorized unless sufficient documentation per the off-label use policies for the relevant line of business is provided.

Coverage criteria (dosing, duration, prescriber, prior exposure, contraindications)

Covered when dosing and duration limits and prescriber/exposure conditions are met

Orilissa dosing and duration: Member receiving Orilissa must be prescribed 150 mg PO once daily or 200 mg PO twice daily; maximum cumulative durations: 150 mg/day up to 24 months (unless coexisting conditions indicate otherwise) and 200 mg twice daily up to 6 months; dose does not exceed 400 mg/day and the 6-month duration for 200 mg twice daily is a lifetime limit.see text

BMD loss is dose- and duration-dependent (Appendix D).

Oriahnn dosing and duration: Member receiving Oriahnn must be prescribed the AM and PM capsule regimen (one capsule in the morning and one in the evening; each AM/PM capsule contains elagolix 300 mg with estradiol and norethindrone acetate) for up to 24 months; dose does not exceed regimen-specific maximums (up to 600 mg elagolix/day) and product may be non‑formulary for some lines of business requiring a formulary exception per HIMPA103.up to 24 months

References to product availability and dosing in Appendices.

Requests for elagolix (Orilissa) or elagolix/estradiol/norethindrone acetate (Oriahnn) for non‑FDA approved indications that are not specifically addressed in this policy are not authorized unless the provider supplies sufficient documentation of efficacy and safety consistent with the applicable off‑label use policies: CP.CPA.09 (commercial), HIM.PA.154 (health insurance marketplace), or CP.PMN.53 (Medicaid), or other applicable evidence of coverage documents.

Elagolix products have specific contraindications and boxed warnings that must be confirmed before approval. Contraindications listed in Appendix C include pregnancy, known osteoporosis, severe hepatic impairment, and concomitant use of strong OATP1B1 inhibitors (for example, cyclosporine or gemfibrozil).

Additional safety exclusions apply by product: Orilissa includes hypersensitivity to the product or its inactive components (reports include anaphylaxis and angioedema). Oriahnn is contraindicated in patients with a high risk of arterial, venous thrombotic, or thromboembolic disorders (examples: women >35 who smoke; history of DVT/PE; vascular disease; uncontrolled hypertension; inherited/acquired hypercoagulopathies), and carries a boxed warning for thromboembolic disorders and vascular events. These conditions must be considered when assessing medical appropriateness.

Dose‑deescalated continuation after receiving 400 mg/day (200 mg twice daily) for 6 months will not be covered. The policy emphasizes that the 6‑month duration at 200 mg twice daily is a lifetime limit, and continuation beyond specified lifetime limits is not authorized.

Key Coding and Cumulative Limits

inv-10: Cumulative elagolix therapy — Not previously received 24 or more months

Cumulative prior elagolix exposureMember must not have previously received 24 or more months of cumulative elagolix therapy.

Policy change historyRequirement added in 4Q 2022 annual review (P&T Approval Date 11.22).

Verification requiredPrior authorization must document cumulative elagolix exposure to confirm <24 months prior therapy.

Prior Authorization, Documentation, and Step Therapy Requirements

Prior Authorization

Prior Authorization Required

Prior authorization required. Provider must document diagnosis, prescriber specialty (or consultation), age ≥ 18 years, and prior treatment history supporting medical necessity.

Diagnosis documented in chart notes (endometriosis pain for Orilissa; uterine fibroids with heavy menstrual bleeding for Oriahnn).
Prescriber is a gynecologist or reproductive endocrinologist or request is in consultation with one.
Member age ≥ 18 years.

Note

Prior Authorization and Formulary Note

Requests for Orilissa and Oriahnn are managed with specific dosing limits and cumulative duration limits per product labeling and this policy. Oriahnn may be subject to formulary status or non-formulary disclaimers; follow the plan’s formulary/exception procedures.

Dose limits: do not exceed 400 mg/day total for elagolix-containing therapy; Orilissa dosing: 150 mg QD or 200 mg BID. Oriahnn dosing: per product regimen (two capsules daily as specified).

Clinical Background

Elagolix is a gonadotropin‑releasing hormone (GnRH) receptor antagonist available as Orilissa (elagolix monotherapy) for management of moderate to severe pain associated with endometriosis and as the combination product Oriahnn (elagolix with estradiol and norethindrone acetate) for heavy menstrual bleeding due to uterine fibroids in premenopausal women. Product‑specific dosing regimens and duration limits were added and refined across annual reviews to reflect FDA indications and safety concerns (notably dose‑ and duration‑dependent effects on bone mineral density), including labeling of maximum daily doses and defined treatment durations.

Defined Terms

inv-20: BMD — bone mineral density

AbbreviationBMD = bone mineral density

Clinical relevanceElagolix products cause dose-dependent decreases in BMD; loss is greater with longer duration and may not be completely reversible.

Monitoring noteBMD loss impact on long-term bone health and future fracture risk is unknown; see Appendix D for details.

inv-21: GnRH — gonadotropin-releasing hormone

AbbreviationGnRH = gonadotropin-releasing hormone

Mechanism contextElagolix is a GnRH receptor antagonist used in indications covered by this policy.

Policy Summary

PayerCentene

PolicyElagolix (Orilissa) and Elagolix/Estradiol/Norethindrone (Oriahnn) coverage

Policy CodePolicy CP PHAR.136

Change TypeModified (annual reviews with material and non-material edits)

Effective DateAug 28, 2018

Next Review Date

SourceLink

On This Page

Prior exposure restriction: Member must not have previously received 24 or more months of cumulative elagolix therapy.<24 months previous exposure

Requirement added in 4Q 2022 review.

Safety contraindications/boxed warnings: Contraindications include pregnancy, known osteoporosis (previously removed as a required confirmation), severe hepatic impairment, concomitant use of strong OATP1B1 inhibitors, hypersensitivity to product components, and increased risk of thromboembolic disorders; Oriahnn carries boxed warnings for thromboembolic disorders and vascular events (see Appendix C).N/A

See Appendix C for full list.

Formulary note: Oriahnn may be non-formulary under some lines of business — refer to formulary and HIMPA103 for formulary exceptions.

Denial Risk

Requests Exceeding Labeled Maximum Cumulative Durations

Requests that seek treatment beyond the labeled maximum cumulative durations require explicit documentation and will be subject to denial if criteria are not met.

Total therapy limits: Orilissa 150 mg once daily — up to 24 months; Orilissa 200 mg twice daily — up to 6 months.
Continuation beyond these labeled maximums (e.g., >6 months for 200 mg BID or >24 months for 150 mg QD) requires clear justification in the medical record and is subject to denial.
Dose-deescalated continuation after 400 mg/day for 6 months will not be covered.

Documentation Required

Prescriber and Prior Exposure Documentation

Prescriber specialty and prior elagolix exposure must be documented in the request. Provider must attest member has not previously received ≥ 24 cumulative months of elagolix therapy unless the request meets exception criteria.

Document prescriber specialty or consultation with a gynecologist or reproductive endocrinologist.
Document cumulative prior elagolix exposure (total months of therapy across products).
Requests will be reviewed for prior cumulative elagolix use; ≥24 months cumulative prior therapy disqualifies routine approval.

Step Therapy

Step Therapy Trials Required

Step therapy: prior trials are required before approval. Provider must document failure (lack of adequate response), intolerance, or contraindication to required agents.

Endometriosis pain (Orilissa): failure of a 3-month trial within the last year of an agent from at least one of the following classes unless contraindicated or not tolerated: (a) a non-steroidal anti-inflammatory drug (NSAID), (b) an oral or depot injectable non-contraceptive progestin or a progestin-containing contraceptive.
Heavy menstrual bleeding due to uterine fibroids (Oriahnn): failure of a 3-month trial of a combination estrogen-progestin contraceptive agent unless contraindicated or not tolerated.
Documentation should include dates, agents tried, dosing, and reason for failure/intolerance.

Defined in Appendix A (Abbreviation/Acronym Key).

inv-22: Orilissa — Elagolix monotherapy dosing and duration limits

Dosing optionsOrilissa (elagolix) dosing: 150 mg PO once daily or 200 mg PO twice daily.

Duration limitsMaximum: 150 mg/day up to 24 months (if no coexisting conditions) or 400 mg/day up to 6 months; 200 mg twice daily is limited to 6 months (lifetime limit).

Safety noteBMD loss is dose- and duration-dependent; higher doses and longer durations increase risk (Appendix D).

inv-23: Oriahnn — Combination product dosing per capsule and indication for uterine fibroids

Capsule regimenOriahnn is administered as one AM capsule (elagolix 300 mg, estradiol 1 mg, norethindrone acetate 0.5 mg) and one PM capsule (elagolix 300 mg) daily.

Daily elagolix doseTotal elagolix exposure with Oriahnn is 600 mg/day (300 mg AM + 300 mg PM).

Duration limitTreatment with Oriahnn is for up to 24 months.