ELIGARD, Leuprolide Acetate (3 Month) LUPRON DEPOT-PED, Leuprolide Acetate (CPP) LUPRON DEPOT, Leuprolide Acetate LUPANETA PACK, Leuprolide Acetate & Norethindrone Acetate Form

Leuprolide acetate (Eligard®, Fensolvi®, Lupaneta Pack® [with norethindrone acetate tablets], Lupron Depot®, Lupron Depot-Ped®) and leuprolide mesylate (Camcevi™) are gonadotropin- releasing hormone (GnRH) receptor agonists. FDA Approved Indication(s) Leuprolide acetate is indicated for: • Palliative treatment of advanced prostate cancer: o Leuprolide acetate injection • • Treatment of advanced prostate cancer: o Lupron Depot (7.5, 22.5, 30, 45) o Eligard
Initial management of the painful symptoms of endometriosis and for management of recurrence of symptoms: o Lupaneta Pack (3.75, 11.25) Limitation(s) of use: Initial treatment course is limited to 6 months and use is not recommended longer than a total of 12 months due to concerns about adverse impact on bone mineral density. • Management of endometriosis, including pain relief and reduction of endometriotic lesions; In combination with a norethindrone acetate for initial management of the painful symptoms of endometriosis and for management of recurrence of symptoms: o Lupron Depot (3.75, 11.25) Limitation(s) of use: total duration of therapy plus add-back therapy should not exceed 12 months due to concerns about adverse impact on bone mineral density • Concomitant use with iron therapy for preoperative hematologic improvement of women with anemia caused by uterine leiomyomata [fibroids] for whom three months of hormonal suppression is deemed necessary: o Lupron Depot (3.75, 11.25)
Limitation of use: not indicated for combination use with norethindrone acetate add-back therapy for the preoperative hematologic improvement of women with anemia caused by heavy menstrual bleeding due to fibroids • Treatment of children with central precocious puberty (CPP): o Fensolvi o Leuprolide acetate o Lupron Depot-Ped (7.5, 11.25, 15, 30, 45) Page 1 of 18

CLINICAL POLICY Leuprolide Acetate, Leuprolide Mesylate Camcevi is indicated for the treatment of adult patients with advanced prostate cancer. Policy/Criteria Provider must submit documentation (such as office chart notes, lab results or other clinical information) supporting that member has met all approval criteria.
It is the policy of health plans affiliated with Centene Corporation® that leuprolide acetate, Camcevi, Eligard, Fensolvi, Lupaneta Pack, Lupron Depot, and Lupron Depot-Ped are medically necessary when the following criteria are met:
I. Initial Approval Criteria
A. Prostate Cancer (must meet all):

1. Diagnosis of prostate cancer;
2. Request is for one of the following (a, b, c, or d): a. Leuprolide acetate injection; b. Camcevi; c. Eligard; d. Lupron Depot;
   3. Prescribed by or in consultation with an oncologist or urologist;
3. Age ≥ 18 years;
4. Request meets one of the following (a, b, c, or d): a. Leuprolide acetate injection (SC): Dose does not exceed 1 mg per day; b. Camcevi (SC): Dose does not exceed 42 mg per 6 months; c. Eligard (SC)/Lupron Depot (IM): Dose does not exceed 7.5 mg per month, 22.5 mg per 3 months, 30 mg per 4 months, 45 mg per 6 months; d. Dose is supported by practice guidelines or peer-reviewed literature for the relevant off-label use (prescriber must submit supporting evidence). Prescribed regimen must be FDA-approved or recommended by NCCN Approval duration:
   Medicaid/HIM – 12 months Commercial – 6 months or to member’s renewal date, whichever is longer B. Endometriosis (must meet all):
5. Diagnosis of endometriosis;
6. Request is for one of the following (a or b): a. Lupron Depot (3.75 mg, 11.25 mg); b. Lupaneta Pack (3.75 mg, 11.25 mg);
   3. Prescribed by or in consultation with a gynecologist;
7. Age ≥ 18 years;

8. Endometriosis as a cause of pain is one of the following (a or b): a. Surgically confirmed; b. Both of the following (i and ii): i. Clinically suspected; ii. Failure of a 3-month trial of one of the following within the last year, unless clinically adverse effects are experienced or all are contraindicated (1, 2, or 3): 1) A nonsteroidal anti-inflammatory drug (see Appendix B for examples); Page 2 of 18

   CLINICAL POLICY Leuprolide Acetate, Leuprolide Mesylate 2) An oral or injectable depot contraceptive (see Appendix B for examples); 3) A progestin (see Appendix B for examples);

   6. For members currently receiving treatment with leuprolide, total duration of therapy has not exceeded 12 months;
   7. Dose does not exceed 3.75 mg per month or 11.25 mg per 3 months. Approval duration:
      Medicaid/HIM – 6 months Commercial – 6 months or to member’s renewal date, whichever is longer C. Uterine Fibroids (must meet all):
   8. Diagnosis of anemia secondary to uterine leiomyomata (fibroids);
9. Diagnosis is confirmed by ultrasound;
10. Request is for Lupron Depot (3.75 mg, 11.25 mg);
11. Prescribed by or in consultation with gynecologist;
12. Age ≥ 18 years;
13. Lupron Depot is prescribed concurrently with iron therapy;
14. Prescribed preoperatively to reduce fibroid size and improve hematologic control;
15. For members currently receiving treatment with leuprolide, total duration of therapy has not exceeded 3 months per treatment course;
    9. Dose does not exceed 3.75 mg per month or 11.25 mg per 3 months. Approval duration: 3 months D. Central Precocious Puberty (must meet all):
    10. Member meets one of the following (a or b): a. Diagnosis of CPP confirmed by all of the following (i, ii, and iii): i. 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); ii. Difference between bone age and chronological age was > 1 year (bone age- chronological age); iii. Age at onset of secondary sex characteristics (1 or 2): 1) Female: < 8 years; 2) Male: < 9 years; b. Request is for diagnostic use;
    11. Request is for one of the following (a, b, or c): a. Fensolvi; b. Leuprolide acetate; c. Lupron Depot-Ped: 7.5 mg, 11.25 mg, 15 mg, 30 mg, 45 mg;
16. Prescribed by or in consultation with a pediatric endocrinologist;

17. Member meets one of the following age requirements (a or b):
    a. Female: 2 - 11 years; b. Male: 2 - 12 years;

    5. Dose does not exceed the following (a, b, c, or d): a. Diagnostic use: Leuprolide acetate: 20 mcg/kg or as needed; b. Therapeutic use: Fensolvi: 45 mg per 6 months; Page 3 of 18

    CLINICAL POLICY Leuprolide Acetate, Leuprolide Mesylate c. Therapeutic use: Leuprolide acetate (SC): Initial: 50 mcg/kg per day; titrate dose upward by 10 mcg/kg per day if down-regulation is not achieved (higher mg/kg doses may be required in younger children). d. Therapeutic use: Lupron Depot-Ped (IM): 15 mg per month (1-month formulation), 30 mg per 3 months (3-month formulation) or 45 mg per 6 months (6-month formulation) (dosing is weight-based for a 1-month and a 3-month formulations). Approval duration:
    Medicaid/HIM – 12 months Commercial – 6 months or to member’s renewal date, whichever is longer E. Breast and Ovarian Cancer (off-label) (must meet all):

    1. Diagnosis of hormone receptor-positive breast cancer or ovarian cancer (including fallopian tube and primary peritoneal cancer);
    2. Request is for Lupron Depot;
18. Prescribed by or in consultation with an oncologist;
19. Age ≥ 18 years;
20. Request meets one of the following (a, b, or c): a. Breast or ovarian cancer: Dose does not exceed 3.75 mg per month or 11.25 mg per 3 months; b. Ovarian cancer: Dose does not exceed 7.5 mg per month, 11.25 mg per 3 months, 22.5 mg per 3 months; c. Dose is supported by practice guidelines or peer-reviewed literature for the relevant off-label use (prescriber must submit supporting evidence). Prescribed regimen must be FDA-approved or recommended by NCCN Approval duration:
    Medicaid/HIM – 12 months Commercial – 6 months or to member’s renewal date, whichever is longer F. Gender Dysphoria, Gender Transition (off-label) (must meet all):
21. Diagnosis of gender dysphoria or request is for gender transition;
22. Request is for a leuprolide product other than Lupaneta Pack;
23. Prescribed by or in consultation with both of the following (a and b): a. An endocrinologist; b. A provider with expertise in gender dysphoria and transgender medicine based on a certified training program or affiliation with local transgender health services (e.g., mental health professional such as psychologist, psychiatrist, see Appendix D);
    4. Age and pubertal development - meets one of the following (a or b): a. Member is < 18 years of age and has reached or passed through Tanner Stage 2; Age ranges approximating Tanner Stage 2 pubertal development extend from 8 to 13 years of age in girls and 9 to 14 years of age in boys. b. Member is ≥ 18 years of age and has failed to achieve physiologic hormone levels with gender-affirming hormonal therapy (e.g., estrogen, testosterone) unless contraindicated or clinically significant adverse effects are experienced;

24. Member demonstrates understanding of expected GnRH analogue treatment outcomes and has given consent for such treatment; Page 4 of 18

    CLINICAL POLICY Leuprolide Acetate, Leuprolide Mesylate

    6. If member has a psychiatric comorbidity, member is followed by mental health provider;
    7. Psychosocial support will be provided during treatment;
25. Dose is within FDA maximum limit for any FDA-approved indication (see Section V) or is supported by practice guidelines or peer-reviewed literature for the relevant off-label use (prescriber must submit supporting evidence). Approval duration:
    Medicaid/HIM – 12 months Commercial – 6 months or to member’s renewal date, whichever is longer G. Salivary Gland Tumors (off-label) (must meet all):
    1. Diagnosis of salivary gland tumors;
26. Disease is androgen receptor positive and recurrent, unresectable, or metastatic;
27. Prescribed by or in consultation with an oncologist;

28. Request is for one of the following (a or b): a. Eligard; b. Lupron Depot;

    5. Dose is within FDA maximum limit for any FDA-approved indication (see Section V) or is supported by practice guidelines or peer-reviewed literature for the relevant off-label use (prescriber must submit supporting evidence). *Prescribed regimen must be FDA-approved or recommended by NCCN Approval duration:
       Medicaid/HIM – 12 months Commercial – 6 months or to member’s renewal date, whichever is longer H. Other diagnoses/indications (must meet 1 or 2):
    6. If this drug has recently (within the last 6 months) undergone a label change (e.g., newly approved indication, age expansion, new dosing regimen) that is not yet reflected in this policy, refer to one of the following policies (a or b): a. For drugs on the formulary (commercial, health insurance marketplace) or PDL (Medicaid), the no coverage criteria policy for the relevant line of business: CP.CPA.190 for commercial, HIM.PA.33 for health insurance marketplace, and CP.PMN.255 for Medicaid; or b. For drugs NOT on the formulary (commercial, health insurance marketplace) or PDL (Medicaid), the non-formulary policy for the relevant line of business: CP.CPA.190 for commercial, HIM.PA.103 for health insurance marketplace, and CP.PMN.16 for Medicaid; or
    7. If the requested use (e.g., diagnosis, age, dosing regimen) is NOT specifically listed under section III (Diagnoses/Indications for which coverage is NOT authorized) AND criterion 1 above does not apply, refer to the off-label use policy for the relevant line of business: CP.CPA.09 for commercial, HIM.PA.154 for health insurance marketplace, and CP.PMN.53 for Medicaid.
       II. Continued Therapy A. Prostate Cancer (must meet all):
    8. Currently receiving medication via Centene benefit, or documentation supports that member is currently receiving leuprolide acetate injection, Camcevi, Eligard, or Page 5 of 18

    CLINICAL POLICY Leuprolide Acetate, Leuprolide Mesylate Lupron Depot for prostate cancer and has received this medication for at least 30 days;

    2. Request is for one of the following (a, b, c, or d): a. Leuprolide acetate injection; b. Camcevi; c. Eligard; d. Lupron Depot;
    3. Member is responding positively to therapy;
29. If request is for a dose increase, request meets one of the following (a, b, c, or d): a. Leuprolide acetate injection (SC): New dose does not exceed 1 mg per day; b. Camcevi (SC): New dose does not exceed 42 mg per 6 months; c. Eligard (SC)/Lupron Depot (IM): New dose does not exceed 7.5 mg per month, 22.5 mg per 3 months, 30 mg per 4 months, 45 mg per 6 months; d. New dose is supported by practice guidelines or peer-reviewed literature for the relevant off-label use (prescriber must submit supporting evidence). Prescribed regimen must be FDA-approved or recommended by NCCN Approval duration:
    Medicaid/HIM – 12 months Commercial – 6 months or to member’s renewal date, whichever is longer B. Endometriosis (must meet all):
    1. Member meets one of the following (a or b): a. Currently receiving medication via Centene benefit or member has previously met initial approval criteria; b. Member is currently receiving medication and is enrolled in a state and product with continuity of care regulations (refer to state specific addendums for CC.PHARM.03A and CC.PHARM.03B);
    2. Request is for Lupron Depot/Lupaneta Pack (3.75 mg, 11.25 mg);
30. Member is responding positively to therapy as evidenced by, including but not limited to, improvement in any of the following parameters: improvement in dysmenorrhea, dyspareunia, pelvic pain/induration/tenderness, or size of endometrial lesions;
    4. Total duration of leuprolide therapy has not exceeded 12 months;

31. If request is for a dose increase, new dose does not exceed 3.75 mg per month or 11.25 mg per 3 months. Approval duration:
    Medicaid/HIM – up to a total treatment duration of 12 months Commercial – 6 months or to member’s renewal date, whichever is longer C. Uterine Fibroids:

    1. Re-authorization is not permitted. Members must meet the initial approval criteria.
       Approval duration: Not applicable D. Central Precocious Puberty (must meet all):
    2. Member meets one of the following (a or b): a. Currently receiving medication via Centene benefit or member has previously met initial approval criteria; Page 6 of 18

    CLINICAL POLICY Leuprolide Acetate, Leuprolide Mesylate b. Member is currently receiving medication and is enrolled in a state and product with continuity of care regulations (refer to state specific addendums for CC.PHARM.03A and CC.PHARM.03B);

    2. Request is for one of the following (a, b, or c): a. Fensolvi; b. Leuprolide acetate; c. Lupron Depot-Ped: 7.5 mg, 11.25 mg, 15 mg, 30 mg, 45 mg;
    3. Member is responding positively to therapy as evidenced by, including but not limited to, improvement in any of the following parameters: decreased growth velocity, cessation of menses, softening of breast tissue or testes, arrested pubertal progression;
    4. Member meets one of the following age requirements (a or b):
       a. Female: ≤ 11 years; b. Male: ≤ 12 years;
    5. If request is for a dose increase, new dose does not exceed one of the following (a, b, or c):
       a. Leuprolide acetate (SC): Initial: 50 mcg/kg per day; titrate dose upward by 10 mcg/kg per day if down-regulation is not achieved (higher mg/kg doses may be required in younger children); b. Lupron Depot-Ped (IM): 15 mg per month (1-month formulation), 30 mg per 3 months (3-month formulation) or 45 mg per 6 months (6-month formulation) (dosing is weight-based for a 1-month and a 3-month formulations); c. Fensolvi: 45 mg per 6 months. Approval duration:
       Medicaid/HIM – 12 months Commercial – 6 months or to member’s renewal date, whichever is longer E. Breast and Ovarian Cancer (off-label) (must meet all):
    6. Currently receiving medication via Centene benefit, or documentation supports that member is currently receiving Lupron Depot for hormone receptor-positive breast cancer or ovarian cancer and has received this medication for at least 30 days;
    7. Request is for Lupron Depot;
32. Member is responding positively to therapy;

33. If request is for a dose increase, request meets one of the following (a, b, or c): a. Breast or ovarian cancer: New dose does not exceed 3.75 mg per month or 11.25 mg per 3 months; b. Ovarian cancer: New dose does not exceed 7.5 mg per month, 11.25 mg per 3 months, 22.5 mg per 3 months; c. New dose is supported by practice guidelines or peer-reviewed literature for the relevant off-label use (prescriber must submit supporting evidence). Prescribed regimen must be FDA-approved or recommended by NCCN Approval duration:
    Medicaid/HIM – 12 months Commercial – 6 months or to member’s renewal date, whichever is longer Page 7 of 18

    CLINICAL POLICY Leuprolide Acetate, Leuprolide Mesylate F. Gender Dysphoria, Gender Transition (off-label) (must meet all):

    1. Member meets one of the following (a or b): a. Currently receiving medication via Centene benefit or member has previously met initial approval criteria; b. Member is currently receiving medication and is enrolled in a state and product with continuity of care regulations (refer to state specific addendums for CC.PHARM.03A and CC.PHARM.03B);
    2. Request is for a leuprolide product other than Lupaneta Pack;
34. Member is responding positively to therapy (e.g., member continues to meet their individual goals of therapy for gender dysphoria);
    4. If request is for a dose increase, new dose is within FDA maximum limit for any FDA-approved indication (see Section V) or is supported by practice guidelines or peer-reviewed literature for the relevant off-label use (prescriber must submit supporting evidence).
       Approval duration:
       Medicaid/HIM – 12 months Commercial – 6 months or to member’s renewal date, whichever is longer G. Salivary Gland Tumors (off-label) (must meet all):
    5. Currently receiving medication via Centene benefit, or documentation supports that member is currently receiving Eligard or Lupron Depot for salivary gland tumors and has received this medication for at least 30 days ;
    6. Request is for one of the following (a or b): a. Eligard; b. Lupron Depot;
    7. Member is responding positively to therapy;

35. If request is for a dose increase, new dose is within FDA maximum limit for any FDA-approved indication (see Section V) or is supported by practice guidelines or peer-reviewed literature for the relevant off-label use (prescriber must submit supporting evidence).
    Approval duration:
    Medicaid/HIM – 12 months Commercial – 6 months or to member’s renewal date, whichever is longer H. Other diagnoses/indications (must meet 1 or 2):

    1. If this drug has recently (within the last 6 months) undergone a label change (e.g., newly approved indication, age expansion, new dosing regimen) that is not yet reflected in this policy, refer to one of the following policies (a or b): a. For drugs on the formulary (commercial, health insurance marketplace) or PDL (Medicaid), the no coverage criteria policy for the relevant line of business: CP.CPA.190 for commercial, HIM.PA.33 for health insurance marketplace, and CP.PMN.255 for Medicaid; or b. For drugs NOT on the formulary (commercial, health insurance marketplace) or PDL (Medicaid), the non-formulary policy for the relevant line of business: CP.CPA.190 for commercial, HIM.PA.103 for health insurance marketplace, and CP.PMN.16 for Medicaid; or Page 8 of 18

    CLINICAL POLICY Leuprolide Acetate, Leuprolide Mesylate

    2. If the requested use (e.g., diagnosis, age, dosing regimen) is NOT specifically listed under section III (Diagnoses/Indications for which coverage is NOT authorized) AND criterion 1 above does not apply, refer to the off-label use policy for the relevant line of business: CP.CPA.09 for commercial, HIM.PA.154 for health insurance marketplace, and CP.PMN.53 for Medicaid. III. Diagnoses/Indications for which coverage is NOT authorized:
       A. Non-FDA approved indications, which are not addressed in this policy, unless there is sufficient documentation of efficacy and safety according to the off label use policies – CP.CPA.09 for commercial, HIM.PA.154 for health insurance marketplace, and CP.PMN.53 for Medicaid, or evidence of coverage documents.
       IV. Appendices/General Information Appendix A: Abbreviation/Acronym Key CPP: central precocious puberty DSM-5: Diagnostic and Statistical Manual of Mental Disorders, 5th edition FDA: Food and Drug Administration GnRH: gonadotropin-releasing hormone
       LH: luteinizing hormone NCCN: National Comprehensive Cancer Network WPATH: World Professional Association for Transgender Health
       Appendix B: Therapeutic Alternatives
       This table provides a listing of preferred alternative therapy recommended in the approval criteria. The drugs listed here may not be a formulary agent for all relevant lines of business and may require prior authorization.
       Drug Name Dosing Regimen NSAIDs*: ibuprofen, naproxen, fenoprofen, ketoprofen, mefenamic acid, meclofenamate, indomethacin, tolmetin, diclofenac, etodolac, diflunisal, meloxicam, piroxicam Combined oral estrogen-progesterone contraceptives: ethinyl estradiol + (desogestrel, ethynodiol diacetate, drospirenone, etonogestrel, levonorgestrel, norelgestromin, norethindrone, norgestimate, or norgestrel); estradiol valerate + dienogest; mestranol + norethindrone Progestin-only oral contraceptives: norethindrone Depot injection progestin contraceptives: medroxyprogesterone acetate Dose Limit/ Maximum Dose Varies – refer to specific prescribing information 1 tablet per day (may vary per specific prescribing information) Endometriosis Varies – refer to specific prescribing information Endometriosis 1 tablet PO QD (may vary per specific prescribing information) 0.35 mg per day See regimen Endometriosis 0.35 mg PO QD Endometriosis IM: 150 mg per 3 months (every 13 weeks) Page 9 of 18

    CLINICAL POLICY Leuprolide Acetate, Leuprolide Mesylate Drug Name Dose Limit/ Maximum Dose Dosing Regimen SC: 104 mg per 3 months (every 12 to 14 weeks) Therapeutic alternatives are listed as Brand name® (generic) when the drug is available by brand name only and generic (Brand name®) when the drug is available by both brand and generic. *Examples provided may not be all-inclusive Appendix C: Contraindications/Boxed Warnings • Contraindication(s): o Known hypersensitivity to GnRH, GnRH agonist analogs or any of the components of the individual products (all leuprolide products); o Pregnancy (all leuprolide products except Camcevi, Eligard); o Lupron 3.75 mg/11.25 mg and Lupaneta Pack:  Undiagnosed abnormal vaginal bleeding;  Breast-feeding;  If used with norethindrone acetate: • Thrombophlebitis, thromboembolic disorders, cerebral apoplexy, or a past history of these conditions; • Markedly impaired liver function or liver disease; • Known or suspected carcinoma of the breast. • Boxed warning(s): None reported Appendix D: General Information • World Professional Association for Transgender Health (WPATH) offers their Global Education Institute (GEI) Certified Training Courses: Best Practices in Transgender Medical and Mental Health Care. Additionally, the following link provides a search tool to locate WPATH member providers: https://www.wpath.org/provider/search • Transgender Care Therapy Certification Training is also offered by the International Transgender Certification Association (ITCA). Professionals with expertise in transgender care can be located using the following search tool: https://transgendercertification.com/locate-a-professional/ • The WPATH Standards of Care Version 8 recommend that adolescents are managed by a multidisciplinary care team that involves both medical and mental health professionals. The list of key disciplines includes but is not limited to: adolescent medicine/primary care, endocrinology, psychology, psychiatry, speech/language pathology, fertility, social work, support staff, and the surgical team. The need to include a healthcare professional with some expertise in mental health does not dictate the inclusion of a psychologist, psychiatrist or social work in every assessment. Instead, a general practitioner, nurse or other qualified clinician could fulfill this requirement as long as they have sufficient expertise to diagnose gender incongruence, recognize mental health concerns, distinguish between these concerns and gender dysphoria, incongruence or diversity, assist a transgender person in care planning and preparing for gender affirmative medical and surgical treatments, and refer to a mental health professional if needed. Page 10 of 18

    CLINICAL POLICY Leuprolide Acetate, Leuprolide Mesylate Appendix E: Additional Information on Diagnosis-specific HCPCS Codes, Billable Units, and Day Supply Diagnosis Requested Product HCPCS Code Billable Units 14 1 Day Supply 14 28 Prostate Cancer Leuprolide acetate, per 1 mg Lupron Depot 1-Month & Eligard 7.5 mg Lupron Depot 3-Month & Eligard 22.5 mg Lupron Depot 4-Month & Eligard 30 mg Lupron Depot 6-Month & Eligard 45 mg Camcevi 6-Month 42 mg Endometriosis Uterine Fibroids , Lupron Depot 1-Month 3.75 mg Lupron Depot 3-Month 11.25 mg Central Precocious Puberty Leuprolide acetate, per 1 mg Lupron Depot-Ped 7.5 mg Lupron Depot-Ped 11.25 mg Lupron Depot-Ped 15 mg Lupron Depot-Ped 30 mg Lupron Depot-Ped 45 mg Fensolvi 45 mg kit Ovarian Cancer Breast Cancer Lupron Depot 1-Month 3.75 mg Lupron Depot 1-Month 3.75 mg Lupron Depot 3-Month 11.25 mg Lupron Depot 1-Month & Eligard 7.5 mg Lupron Depot 3-Month & Eligard 22.5 mg Salivary Gland Tumors J9218 J9217 NA J1950 J9218 J1950 J1950 J1950 J9217 3 4 6 NA 1 3 14 2 3 4 8 12 12 1 1 3 1 3 84 112 168 168 28 84 14 28 28 28 84 168 168 28 28 84 28 84 NA – not available V. Dosage and Administration
    Drug Name Indication Dosing Regimen Leuprolide acetate injection Prostate cancer Leuprolide acetate (Lupron Depot 7.5, 22.5, 30, 45) Leuprolide acetate (Eligard 7.5, 22.5, 30, 45) Leuprolide mesylate (Camcevi) Camcevi (SC) – 42 mg every 6 months Leuprolide acetate injection (SC): 1 mg per day
    Lupron Depot (IM) - 7.5 mg per month; 22.5 mg per 3 months; 30 mg per 4 months; 45 mg per 6 months Eligard (SC) - 7.5 mg per month; 22.5 mg per 3 months; 30 mg per 4 months; 45 mg per 6 months Maximum Dose See regimen See regimen See regimen See regimen Page 11 of 18

    CLINICAL POLICY Leuprolide Acetate, Leuprolide Mesylate Drug Name Indication Dosing Regimen Leuprolide acetate (Lupron Depot 3.75, 11.25) Endometriosis Lupron Depot/Lupaneta Pack (IM) - 3.75 mg per month; 11.25 mg per 3 months Maximum Dose See regimen Uterine fibroids CPP Leuprolide acetate (Lupaneta Pack 3.75, 11.25) Leuprolide acetate (Lupron Depot 3.75) Leuprolide acetate injection Leuprolide acetate (Lupron Depot-Ped 7.5, 11.25, 15 [1 mo]; 11.25, 30 [3 mo]); 45 [6 mo] Fensolvi (leuprolide acetate) Lupron Depot (IM) - 3.75 mg/month, 11.25 mg per 3 months See Leuprolide acetate (SC):
    • Diagnostic: 20 mcg/kg or as needed;
    • Treatment: Initial: 50 mcg/kg/day; titrate dose upward by 10 mcg/kg/day if down- regulation is not achieved (higher mg/kg doses may be required in younger children). Lupron Depot-Ped (IM): Monthly administration weight-based starting dose: 7.5 mg (≤ 25 kg), 11.25 mg (> 25 to 37.5 kg), 15 mg (> 37.5 kg) (increase as needed to 15 mg/month); 3-month administration: 11.25 mg or 30 mg; 6-month administration: 45 mg Fensolvi (SC): 45 mg once every six months Lupron Depot (IM) 3.75 mg per month, 11.25 mg per 3 months regimen See regimen See regimen See regimen See regimen See regimen See regimen Breast cancer (off-label) Leuprolide acetate (Lupron Depot 3.75) Leuprolide acetate (Lupron Depot 3.75, 11.25) Leuprolide acetate (Lupron Depot 7.5, 22.5) Leuprolide acetate (Eligard 7.5, 22.5, 30, 45) Ovarian cancer (off-label) Salivary Gland tumors (off-label) Lupron Depot (IM) 3.75 mg per month, 11.25 mg per 3 months Lupron Depot (IM) - 7.5 mg per month; 22.5 mg per 3 months. Eligard (SC) - 7.5 mg per month; 22.5 mg per 3 months; 30 mg per 4 months; 45 mg per 6 months Page 12 of 18

    CLINICAL POLICY Leuprolide Acetate, Leuprolide Mesylate VI. Product Availability
    Drug Name Leuprolide acetate injection Leuprolide acetate (Eligard) Leuprolide acetate and norethindrone tablets (Lupaneta Pack) Leuprolide acetate (Lupron Depot) Leuprolide acetate (Lupron Depot 3.75) Leuprolide acetate (Lupron Depot 11.25) Leuprolide acetate (Lupron Depot-Ped) Availability Kit: 2.8 mL multi-dose vial (1 mg/0.2 mL) Kit: 7.5 mg (1 month), 22.5 mg (3 month), 30 mg (4 month), 45 mg (6 month) Pack: 3.75 mg leuprolide acetate syringe (1 month) with 5 mg norethindrone tablets
    Pack: 11.25 mg leuprolide acetate syringe (3 month) with 5 mg norethindrone tablets Prefilled syringe: 7.5 mg (1 month), 22.5 mg (3 month), 30 mg (4 month), 45 mg (6 month) Prefilled syringe: 3.75 mg (1 month) Prefilled syringe: 11.25 mg (3 month) Prefilled syringe: 7.5 mg (1 month), 11.25 mg (1 month), 15 mg (1 month) Prefilled syringe: 11.25 mg (3 month), 30 mg (3 month) Prefilled syringe: 45 mg (6 month) Leuprolide acetate (Fensolvi) Kit: syringe A: prefilled with diluent for reconstitution Leuprolide mesylate (Camcevi) and syringe B: prefilled with 45 mg lyophilized leuprolide acetate powder Injection emulsion: 42 mg VII.