BlueCross BlueShield of Tennessee Medical Policy Manual

Leuprolide Suspension (Lupron Depot®, Leuprolide Acetate Depot) 1-Month 3.75mg, 3-Month 11.25 mg) 

IMPORTANT REMINDER

We develop Medical Policies to provide guidance to Members and Providers.  This Medical Policy relates only to the services or supplies described in it.  The existence of a Medical Policy is not an authorization, certification, explanation of benefits or a contract for the service (or supply) that is referenced in the Medical Policy.  For a determination of the benefits that a Member is entitled to receive under his or her health plan, the Member's health plan must be reviewed.  If there is a conflict between the medical policy and a health plan or government program (e.g., TennCare), the express terms of the health plan or government program will govern.

POLICY

1. INDICATIONS

The indications below including FDA-approved indications and compendial uses are considered a covered benefit provided that all the approval criteria are met and the member has no exclusions to the prescribed therapy.

1. FDA-Approved Indications

1. Endometriosis

Lupron Depot 1- Month 3.75 mg and Lupron Depot-3 Month 11.25 mg are indicated for management of endometriosis, including pain relief and reduction of endometriotic lesions. Lupron Depot 1-Month 3.75 mg and Lupron Depot 3-Month 11.25 mg with norethindrone acetate 5 mg daily are also indicated for initial management of the painful symptoms of endometriosis and for management of recurrence of symptoms.

Use of norethindrone acetate in combination with Lupron Depot 3.75 mg and Lupron Depot 11.25 mg is referred to as add-back therapy, and is intended to reduce the loss of bone mineral density (BMD) and reduce vasomotor symptoms associated with use of Lupron Depot 3.75 mg and Lupron Depot 11.25 mg.

2. Uterine Leiomyomata (Fibroids)

When used concomitantly with iron therapy, Lupron Depot 1-Month 3.75 mg and Lupron Depot 3- Month 11.25 mg are indicated for preoperative hematologic improvement of women with anemia caused by fibroids for whom three months of hormonal suppression is deemed necessary. The clinician may wish to consider a one-month trial period on iron alone, as some women will respond to iron alone. Lupron Depot may be added if the response to iron alone is considered inadequate.

Limitations of Use:

For endometriosis: The total duration of therapy with Lupron Depot 3.75 mg and 11.25 mg plus add-back therapy should not exceed 12 months due to concerns about adverse impact on bone mineral density.

For uterine leiomyomata: Lupron Depot 3.75 mg and 11.25 mg are 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.

2. Compendial Uses

1. Breast cancer
2. Ovarian cancer – Epithelial ovarian cancer/fallopian tube cancer/primary peritoneal cancer, and less common ovarian cancers (grade 1 endometrioid carcinoma, low-grade serous carcinoma, carcinosarcoma [malignant mixed Müllerian tumors], mucinous carcinoma of the ovary, or clear cell carcinoma of the ovary)
   3. Androgen receptor positive salivary gland tumors

1. 4. Gender dysphoria (also known as transgender and gender diverse (TGD) persons)
   5. Preservation of ovarian function
   6. Prevention of recurrent menstrual related attacks in acute porphyria

All other indications are considered experimental/investigational and not medically necessary.

2. PRESCRIBER SPECIALTIES

1. Gender dysphoria

The medication must be prescribed by or in consultation with a provider specialized in the care of transgender youth (e.g., pediatric endocrinologist, family or internal medicine physician, obstetrician-gynecologist) that has collaborated care with a mental health provider for members less than 18 years of age.

2. Prevention of recurrent menstrual related attacks in acute porphyria

The medication must be prescribed by or in consultation with a provider experienced in the management of porphyrias. 

3. CRITERIA FOR INITIAL APPROVAL

1. Endometriosis

Authorization of up to 6 months (one treatment course) may be granted to members for initial treatment of endometriosis.

2. Uterine leiomyomata (fibroids)

Authorization of up to 3 months may be granted for initial treatment of uterine leiomyomata (fibroids) when either of the following criteria is met:

1. Member has anemia due to uterine leiomyomata,
2. Lupron Depot will be used prior to surgery for uterine leiomyomata.

3. Breast cancer

Authorization of 12 months may be granted for treatment of hormone receptor-positive breast cancer.

4. Ovarian cancer

Authorization of 12 months may be granted for treatment of persistent disease or recurrence of any of the following types of ovarian cancer when used as a single agent:

1. 1. 1. 1. Epithelial ovarian cancer
         2. Fallopian tube cancer
         3. Primary peritoneal cancer
         4. Grade 1 endometrioid carcinoma
         5. Low-grade serous carcinoma
         6. Carcinosarcoma (malignant mixed Müllerian tumors)
         7. Mucinous carcinoma of the ovary
         8. Clear cell carcinoma of the ovary

5. Salivary gland tumors

Authorization of 12 months may be granted for treatment of recurrent, unresectable, or metastatic  salivary gland tumors as a single agent when the tumor is androgen receptor positive.  

6. Gender dysphoria

*Individual is age 18 or older or the individual is less than age 18 as permissive under applicable law

1. Authorization of 12 months may be granted for pubertal hormonal suppression in an adolescent member when all of the following criteria are met:

1. The member has a diagnosis of gender dysphoria.
2. The member is able to make an informed decision to engage in treatment.
3. The member has reached Tanner stage 2 of puberty or greater.

4. The member’s comorbid conditions are reasonably controlled.
5. The member has been educated on any contraindications and side effects to therapy.
6. The member has been informed of fertility preservation options

2. Authorization of 12 months may be granted for gender transition when all of the following criteria are met:

1. The member has a diagnosis of gender dysphoria.
2. The member is able to make an informed decision to engage in treatment.
3. The member will receive the requested medication concomitantly with gender-affirming hormones.
4. The member’s comorbid conditions are reasonably controlled.
5. The member has been educated on any contraindications and side effects to therapy.
6. The member has been informed of fertility preservation options.

7. Preservation of ovarian function

Authorization of 3 months may be granted for preservation of ovarian function when the member is premenopausal and undergoing chemotherapy.

8. Prevention of recurrent menstrual related attacks in acute porphyria

Authorization of 12 months may be granted for prevention of recurrent menstrual related attacks in members with acute porphyria.

4. CONTINUATION OF THERAPY

1. Endometriosis

Authorization of up to 6 months (for a lifetime maximum of 12 months total) may be granted for retreatment of endometriosis when both of the following criteria are met:

1. The member has had a recurrence of symptoms.
2. The member has a bone mineral density within normal limits.

2. Uterine leiomyomata (fibroids)

Authorization of up to 3 months (for a lifetime maximum of 6 months total) may be granted when either of the following criteria is met:

1. Member has anemia due to uterine leiomyomata,
2. Lupron Depot will be used prior to surgery for uterine leiomyomata.

3. Breast cancer, ovarian cancer, and salivary gland tumors

Authorization of 12 months may be granted for continued treatment of breast cancer, ovarian cancer, and salivary gland tumors in members requesting reauthorization when there is no evidence of unacceptable toxicity or disease progression while on the current regimen.

4. Gender dysphoria

*Individual is age 18 or older or the individual is less than age 18 as permissive under applicable law

1. 1. Authorization of 12 months may be granted for continued treatment for pubertal hormonal suppression in adolescent members requesting reauthorization when all of the following criteria are met:
      1. 1. 1. The member has a diagnosis of gender dysphoria.
            2. The member is able to make an informed decision to engage in treatment.
            3. The member has previously reached Tanner stage 2 of puberty or greater.
            4. The member’s comorbid conditions are reasonably controlled.
            5. The member has been educated on any contraindications and side effects to therapy.
            6. Before the start of therapy, the member has been informed of fertility preservation options.
2. Authorization of 12 months may be granted for continued treatment for gender transition in members requesting reauthorization when all of the following criteria are met:

1. The member has a diagnosis of gender dysphoria.
2. The member is able to make an informed decision to engage in treatment.
3. The member will receive requested medication concomitantly with gender-affirming hormones.
4. The member’s comorbid conditions are reasonably controlled.
5. The member has been educated on any contraindications and side effects to therapy.
6. Before the start of therapy, the member has been informed of fertility preservation options.

5. All members (including new members) requesting authorization for continuation of therapy for the specified indications below must meet all initial authorization criteria:

1.   Preservation of ovarian function

2.   Prevention of recurrent menstrual related attacks in acute porphyria           

5. OTHER

Per state regulatory guidelines around gender dysphoria, age restrictions may apply.     

APPLICABLE TENNESSEE STATE MANDATE REQUIREMENTS

BlueCross BlueShield of Tennessee’s Medical Policy complies with Tennessee Code Annotated Section 56-7-2352 regarding coverage of off-label indications of Food and Drug Administration (FDA) approved drugs when the off-label use is recognized in one of the statutorily recognized standard reference compendia or in the published peer-reviewed medical literature.

ADDITIONAL INFORMATION  

For appropriate chemotherapy regimens, dosage information, contraindications, precautions, warnings, and monitoring information, please refer to one of the standard reference compendia (e.g., the NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines®) published by the National Comprehensive Cancer Network®, Drugdex Evaluations of Micromedex Solutions at Truven Health, or The American Hospital Formulary Service Drug Information).

REFERENCES

1. Lupron Depot 3.75 mg [package insert]. North Chicago, IL: AbbVie Inc.; October 2023.
2. Lupron Depot-3 Month 11.25 mg [package insert.]. North Chicago, IL: AbbVie Inc.; October 2023.
3. The NCCN Drugs & Biologics Compendium® © 2024 National Comprehensive Cancer Network, Inc. http://www.nccn.org. Accessed February 12, 2024.
4. Management of symptomatic uterine leiomyomas: ACOG Practice Bulletin No. 228. American College of Obstetricians and Gynecologists. Obstet Gynecol. 2021 June 1;137(6):e100-e115.
5. Marret H, Fritel X, Ouldamer L, et al. Therapeutic management of uterine fibroid tumors: updated French guidelines. European Journal of Obstetrics and Gynecology and Reproductive Biology. 2012;165:156-164.
6. Hembree WC, Cohen-Kettenis PT, Gooren L, et al. Endocrine Treatment of gender-dysphoric/gender-incongruent persons: an Endocrine Society clinical practice guideline. J Clin Endocrinol Metab. 2017:102(11):3869–3903.
7. Gender Identity Research and Education Society. Guidance for GPs and other clinicians on the treatment of gender variant people. UK Department of Health. Published March 10, 2008.
8. Coleman E, Radix AE, Brown GR, et al. Standards of care for the health of transgender and gender diverse people, version 8. 2022;23 (Suppl 1): S1-S259. doi: 10.1080/26895269.2022.2100644.
9. Fertility preservation in patients with cancer: ASCO Clinical Practice Guideline Update. J Clin Oncol. 2018 Jul 1;36(19):1994-2001.

10. Clowse MEB, Behera MA, Anders CK, et al. Ovarian preservation by GnRH agonists during chemotherapy: a meta-analysis. J Womens Health (Larchmt). 2009 Mar; 18(3): 311–319. doi:10.1089/jwh.2008.0857
11. Stein P, Badminton M, Barth J, et al. British and Irish Porphyria Network. Best practice guidelines on clinical management of acute attacks of porphyria and their complications. Ann Clin Biochem. 2013 May;50(Pt 3):217-23.
12. Innala, E, Bäckström, T, Bixo, et. al. Evaluation of gonadotrophin-releasing hormone agonist treatment for prevention of menstrual-related attacks in acute porphyria. Acta Obstet Gynecol 2010;89:95–100.

13. Mahfouda S, Moore JK, Siafarikas A, et al. Puberty suppression in transgender children and adolescents. Lancet Diabetes Endocrinol. 2017; 5: 816-26.
14. Health Care for Transgender and Gender Diverse Individuals. ©2021 The American College of Obstetricians and Gynecologists. Available at: https://www.acog.org/clinical/clinical-guidance/committee-opinion/articles/2021/03/health-care-for-transgender-and-gender-diverse-individuals.
15. NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines): Head and Neck Cancers. Version 2.2024. Accessed February 15, 2024. https://www.nccn.org/professionals/physician_gls/pdf/head-and-neck.pdf.

ORIGINAL EFFECTIVE DATE:5/1/2004

MOST RECENT REVIEW DATE: 1/14/2025

ID_CHS

Policies included in the Medical Policy Manual are not intended to certify coverage availability. They are medical determinations about a particular technology, service, drug, etc. While a policy or technology may be medically necessary, it could be excluded in a member's benefit plan. Please check with the appropriate claims department to determine if the service in question is a covered service under a particular benefit plan. Use of the Medical Policy Manual is not intended to replace independent medical judgment for treatment of individuals. The content on this Web site is not intended to be a substitute for professional medical advice in any way. Always seek the advice of your physician or other qualified health care provider if you have questions regarding a medical condition or treatment.

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