CurrentCentenePolicy CP PHAR.529

Relugolix (Orgovyx), Relugolix/Estradiol/Norethindrone (Myfembree) Coverage Criteria

Defines medical necessity and prior authorization criteria for relugolix (Orgovyx) and relugolix/estradiol/norethindrone (Myfembree) across Centene lines of business (Commercial, HIM, Medicaid). Applies to prescribers requesting coverage under Centene-affiliated health plans.

Policy Summary

PayerCentene

PolicyRelugolix (Orgovyx), Relugolix/Estradiol/Norethindrone (Myfembree) Coverage Criteria

Policy CodePolicy CP PHAR.529

Change TypeNo material change

Effective DateJun 1, 2021

Next Review Date

Key ActionSubmit prior authorization with documentation showing diagnosis, prescriber specialty, prior therapy or step failure (when required), dosing, and duration to support approval.

SourceLink

POLICY UPDATE CHANGES

No material clinical or coverage changes in this revision.

24 monthsmaximum cumulative Myfembree therapy duration

12 monthsstandard approval duration

120 mgtypical maintenance dose

thromboembolicboxed warning

Coverage Criteria

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Initial Therapy — Orgovyx

Covered when ALL of the following are met for Orgovyx (relugolix) - Prostate cancer:

Orgovyx initial therapy: 1. Diagnosis of prostate cancer; 2. Request is for Orgovyx; 3. Prescribed by or in consultation with an oncologist or urologist; 4. Age >= 18 years; 5. For brand Orgovyx requests, member must use generic relugolix if available unless contraindicated or clinically significant adverse effects are experienced; 6. Initial (loading) dose does not exceed 360 mg (3 tablets) given on day 1; 7. Maintenance dose does not exceed 120 mg (1 tablet) per day (maintenance may be increased to 240 mg/day if coadministered with combined P-gp and strong CYP3A inducers and unavoidable); 8. Prescribed regimen must be FDA-approved or recommended by NCCN or supported by practice guidelines/peer-reviewed literature for relevant off-label use.

Initial Therapy — Myfembree (Fibroids)

Covered when ALL of the following are met for Myfembree — Heavy Menstrual Bleeding due to uterine fibroids:

Myfembree initial therapy - fibroids: 1. Diagnosis of uterine leiomyomas (fibroids) confirmed by ultrasound; 2. Request is for Myfembree; 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 unless contraindicated or adverse effects occurred; 7. Member has not already received >= 24 cumulative months of Myfembree therapy; 8. Dose does not exceed 40 mg relugolix (1 tablet) per day.

Initial Therapy — Myfembree (Endometriosis)

Covered when ALL of the following are met for Myfembree — Endometriosis pain:

Myfembree initial therapy - endometriosis: 1. Diagnosis of pain due to endometriosis; 2. Request is for Myfembree; 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 drug classes unless clinically significant adverse effects are experienced or all are contraindicated: a) Non-steroidal anti-inflammatory drug (NSAID) or b) Oral or depot injectable progestin or progestin-containing contraceptive; 6. Member has not already received >= 24 cumulative months of Myfembree therapy; 7. Dose does not exceed 40 mg relugolix (1 tablet) per day.

Continued Therapy

Continued therapy covered when ALL of the following are met:

Continued therapy general: 1. Member is currently receiving the medication via Centene benefit or documentation supports current use for a covered indication and at least 30 days of therapy; 2. Request is for the same product (Orgovyx or Myfembree) as appropriate to the indication; 3. Member is responding positively to therapy (clinical improvement documented); 4. For brand Orgovyx requests, member must use generic relugolix if available unless contraindicated or clinically significant adverse effects are experienced; 5. If request is for a dose increase, the new dose does not exceed documented dose limits (Orgovyx maintenance 120 mg/day or up to 240 mg/day if coadministered with combined P-gp and strong CYP3A inducers and unavoidable), or the new dose is supported by practice guidelines/peer‑reviewed literature with supporting documentation; 6. Prescribed regimen must be FDA-approved or recommended by NCCN.

Indication-specific coverage criteria

Covered when the following indication- and duration-based conditions are met for the respective product:

Myfembree initial/continuation therapy: Member has diagnosis of heavy menstrual bleeding due to uterine fibroids or endometriosis-related pain AND prescribed Myfembree 1 tablet PO QD with total therapy duration not to exceed 24 months24 months

Therapeutic alternatives should be considered and prior therapy history may be required

Orgovyx therapy: Member has indication of prostate cancer AND prescribed Orgovyx with loading dose 360 mg PO on day 1 then 120 mg PO QD maintenance; avoid combined P-gp and strong CYP3A inducers when possible — if coadministration is unavoidable increase Orgovyx maintenance to 240 mg PO QD as specifieddose adjustments per interacting inducers

Avoid combined P-gp and strong CYP3A inducers when possible

Non‑FDA indications not specifically addressed in this policy will not be authorized unless the prescriber submits sufficient supporting documentation per the applicable off‑label use policies (see CP.CPA.09 for Commercial, HIM.PA.154 for Health Insurance Marketplace, and CP.PMN.53 for Medicaid). Documentation should demonstrate efficacy and safety consistent with those off‑label use requirements.

Use of relugolix products is contraindicated in members with the conditions listed in Appendix C. These include: pregnancy; current or prior hormone‑sensitive breast cancer or other hormone‑sensitive tumors; known osteoporosis; known hepatic impairment or disease; undiagnosed abnormal uterine bleeding; and known hypersensitivity to the product components. For Myfembree specifically, a high risk of arterial, venous thrombotic, or thromboembolic disorder is an additional contraindication.

Myfembree carries specific thrombotic and vascular safety concerns that inform coverage. The product has a boxed warning for thromboembolic disorders and vascular events, and Myfembree is contraindicated in patients at high risk of arterial, venous thrombotic, or thromboembolic disorder. These risks should be considered before authorization; members who are pregnant or have current or prior hormone‑sensitive breast cancer, known osteoporosis, or significant hepatic impairment are also excluded from therapy. Providers must document assessment of thrombotic risk and rationale if considering therapy in situations where risk factors exist.

Initial Therapy Criteria

Initial therapy criteria per indication

Orgovyx initial: Refer to the Orgovyx initial therapy criteria: diagnosis of prostate cancer; request for Orgovyx; prescriber specialty (oncologist or urologist); age >=18; generic-first for relugolix when available; loading and maintenance dose limits (360 mg day 1; maintenance 120 mg/day, 240 mg/day if required with interacting inducers); prescribed regimen must be FDA-approved or guideline-supported.

Myfembree initial - fibroids: Refer to Myfembree initial therapy (fibroids): ultrasound-confirmed uterine leiomyomas; request for Myfembree; prescriber specialty (gynecologist or reproductive endocrinologist); age >18; heavy menstrual bleeding for >=2 consecutive cycles; failure of a 3-month trial of combination estrogen-progestin contraceptive; cumulative Myfembree therapy < 24 months; dose limit 1 tablet (40 mg relugolix component) per day.

Myfembree initial - endometriosis: Refer to Myfembree initial therapy (endometriosis): diagnosis of endometriosis-related pain; request for Myfembree; prescriber specialty (gynecologist or reproductive endocrinologist); age >=18; failure of a 3-month trial within the last year of an NSAID or oral/depot progestin/progestin-containing contraceptive unless contraindicated; cumulative Myfembree therapy < 24 months; dose limit 1 tablet (40 mg relugolix component) per day.

Initial therapy coverage conditions

Initial therapy coverage conditions:

Orgovyx initial: Prescribed for prostate cancer with loading dose 360 mg PO on day 1 followed by 120 mg PO QD maintenance; avoid combined P-gp and strong CYP3A inducers (e.g., rifampin); if coadministration with such inducers is unavoidable, increase maintenance to 240 mg PO QD.

Myfembree initial: Prescribed for heavy menstrual bleeding due to uterine fibroids or endometriosis pain, dosed 1 tablet PO QD; therapy duration limited to up to 24 months; therapeutic alternatives (NSAIDs, progestin-containing contraceptives, depot medroxyprogesterone, combination estrogen-progestin contraceptives) should be considered prior to combination therapy.

Continuation / Renewal Criteria

Continuation Therapy

Continued therapy requirements per indication

Orgovyx continuation: Member is currently receiving Orgovyx via Centene benefit or documentation supports current use for a covered indication and at least 30 days of therapy; member is responding positively to therapy; dose limits and generic-use requirements apply; approval duration 12 months.

Myfembree continuation: Member is currently receiving Myfembree via Centene benefit or previously met initial approval criteria; member is responding positively to therapy (reduced menstrual blood loss or improvement in endometriosis symptoms); member has not exceeded 24 cumulative months of Myfembree therapy; dose does not exceed 40 mg relugolix component (1 tablet) per day; approval duration 12 months.

Continuation therapy limits

Continuation approval conditions:

Myfembree continuation: Member has been on Myfembree previously and cumulative therapy has not exceeded 24 months; continuation requests must document prior duration of therapy<= 24 months

Policy reiterates existing 24-month approval duration for Myfembree

Provider Actions and Requirements

Prior Authorization

Prior Authorization Required

Prior authorization is required for Orgovyx and Myfembree. Initial approvals are diagnosis-specific and will be granted only when the applicable indication-specific criteria are met (e.g., prostate cancer for Orgovyx; heavy menstrual bleeding due to uterine fibroids or endometriosis pain for Myfembree). Approval durations: Myfembree initial approval = 12 months; total therapy should not exceed 24 months. Orgovyx dosing limits include a 360 mg loading dose on day 1 and maintenance dosing per labeling (see dosing callout).

Prior authorization required for Orgovyx and Myfembree
Myfembree initial approval duration: 12 months; cumulative therapy ≤ 24 months
Approvals are indication-specific (prostate cancer; uterine fibroids HMB; endometriosis pain)

Documentation Required

Providers must submit supporting clinical documentation with the prior authorization request. Acceptable documentation includes chart notes, diagnostic imaging reports (e.g., ultrasound confirming fibroids), labs, prior medication trial records, and consultation notes from specialists. Failure to provide required documentation may result in a request for additional information or denial of the request.

Include chart notes, labs, imaging (e.g., ultrasound for fibroids), and specialist consultation notes
Document prior medication trials (drug name, dose, duration, and reason for failure/intolerance)
Omission of documentation may trigger denial or requests for more information

Documentation Required

Required Dosing and Product Documentation

Required dosing and product details must be documented on the request: for Orgovyx document the loading dose (360 mg PO on day 1) and maintenance dosing (120 mg PO QD; increase to 240 mg PO QD only if co-administered with combined P-gp and strong CYP3A inducers). For Myfembree, document the tablet strength (relugolix 40 mg / estradiol 1 mg / norethindrone acetate 0.5 mg) and intended dosing of 1 tablet PO QD for up to 24 months. Verify product availability if relevant.

Orgovyx: 360 mg loading dose day 1; maintenance 120 mg PO QD (240 mg PO QD if combined P-gp + strong CYP3A inducers and unavoidable)
Myfembree: fixed-dose tablet (relugolix 40 mg / estradiol 1 mg / norethindrone acetate 0.5 mg); 1 tablet PO QD, max duration 24 months
Document the exact product and dosing on the PA request

Step Therapy

Step Therapy — Myfembree (Endometriosis Pain)

Step therapy applies for Myfembree when requested for endometriosis pain: the member must have failed a 3-month trial within the past year of at least one agent from the listed classes unless all are contraindicated or not tolerated. Illinois HIM requests: step therapy requirements do not apply as of 1/1/2026 per IL HB 5395.

Step: 3-month trial within last year of an NSAID OR an oral/depot progestin or progestin-containing contraceptive
Document dates, agents, doses, duration, and reason for failure/intolerance
IL exception: step therapy does not apply for Illinois HIM as of 2026-01-01 per IL HB 5395

Note

Therapeutic Alternatives May Be Preferred

Therapeutic alternatives may be preferred prior to authorizing Myfembree for heavy menstrual bleeding or endometriosis pain. Consider NSAIDs, progestin-only therapies (oral or depot), and combination estrogen–progestin contraceptives as alternatives or step options where appropriate. Document prior use and reason for discontinuation or intolerance when asserting failure of alternatives.

NSAIDs (e.g., ibuprofen, naproxen, mefenamic acid) — document a 3-month trial when used for step purposes
Progestin therapies: oral norethindrone or depot medroxyprogesterone acetate (Depo-Provera/Depo-SubQ Provera 104) per labeled regimens
Combination estrogen–progestin contraceptives — 1 tablet PO QD regimens; list agent, dose, and trial duration in documentation

Denial Risk

Contraindication-Based Denial Risks

Contraindications and boxed warnings must be reviewed and documented; requests should be denied when contraindications are present. For Myfembree, contraindications include pregnancy, current or history of breast cancer or other hormone-sensitive cancers, known osteoporosis, known hepatic impairment, high risk of thrombotic or thromboembolic disorder, undiagnosed abnormal uterine bleeding, or hypersensitivity to components. Boxed warning for Myfembree: thromboembolic disorders and vascular events.

Do not approve Myfembree for pregnant members or those with hormone-sensitive cancer
Assess thrombotic risk and hepatic function prior to approval; document findings
Verify allergy history to product components

Step Therapy Requirements

Coverage requirement	Details / notes
Step therapy required prior to Myfembree for endometriosis pain
Failure of a 3-month trial within the last year of an agent from one of the following classes is required unless clinically significant adverse effects are experienced or all are contraindicated: 1) Non‑steroidal anti‑inflammatory drug (NSAID); 2) Oral or depot injectable progestin or progestin‑containing contraceptive. For Illinois HIM requests, the step therapy requirements do not apply as of 1/1/2026 per IL HB 5395.
Age and prescriber requirements
Prescribed by or in consultation with a gynecologist or reproductive endocrinologist; patient must be >= 18 years of age.
Duration and dose limits
Member must not have already received >= 24 cumulative months of Myfembree therapy; dose must not exceed relugolix 40 mg (1 tablet) per day.

Preferred alternative	Example agents / dosing
Non‑steroidal anti‑inflammatory drugs (NSAIDs)
Examples: ibuprofen, naproxen, fenoprofen, ketoprofen, mefenamic acid, meclofenamate, indomethacin, tolmetin, diclofenac, etodolac, diflunisal, meloxicam, piroxicam. Dosing varies per prescribing information.
Progestin‑containing oral contraceptives
Examples: norethindrone; combination ethinyl estradiol + progestin formulations (desogestrel, ethynodiol diacetate, drospirenone, etonogestrel, levonorgestrel, norelgestromin, norgestimate, norgestrel); estradiol valerate + dienogest; mestranol + norethindrone. Typical dosing: 1 tablet PO QD.
Depot injectable progestin
Example: medroxyprogesterone acetate (Depo‑Provera / Depo‑SubQ Provera 104). Dosing: IM 150 mg every 13 weeks or SC 104 mg every 12–14 weeks.
Combination estrogen‑progestin contraceptives
Examples: ethinyl estradiol + progestin combinations as listed above. Typical dosing: 1 tablet PO QD.

OpenPayer

Relugolix (Orgovyx), Relugolix/Estradiol/Norethindrone (Myfembree) Coverage Criteria

Coverage Criteria

Initial Therapy Criteria

Continuation / Renewal Criteria

Provider Actions and Requirements

Step Therapy Requirements

Quantity and Dosing Limits

Definitions and Abbreviations

Background