Pharmacy Prior Authorization Criteria

Gonadotropin-Releasing Hormone Agonists

Indications for Prior Authorization

Lupron Depot (leuprolide acetate) 1-Month 7.5 mg, Lupron Depot 3-Month 22.5 mg, Lupron Depot 4-Month 30 mg, Lupron Depot 6-Month 45 mg

• For diagnosis of Prostate Cancer
  Indicated for the treatment of advanced prostate cancer.

• For diagnosis of Gender Dysphoria [16, 17]
  Suppression of pubertal development and gonadal function is accomplished most effectively by gonadotropin suppression with gonadotropin releasing hormone analogues and antagonists. Analogues suppress gonadotropins after a short period of stimulation, whereas antagonists immediately suppress pituitary secretion. Since no long-acting antagonists are available for use as pharmacotherapy, long-acting analogues are the currently preferred treatment option. [16] Early use of puberty-suppressing hormones may avert negative social and emotional consequences of gender dysphoria more effectively than their later use would. [17]

Lupron Depot 1-Month 3.75 mg, Lupron Depot 3-Month 11.25 mg

• For diagnosis of Endometriosis
  Indicated for the management of endometriosis, including pain relief and reduction of endometriotic lesions. In combination with a norethindrone acetate, it is 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 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.

  Limitations of Use: The total duration of therapy with LUPRON DEPOT plus add-back therapy should not exceed 12 months due to concerns about adverse impact on bone mineral density.

• For diagnosis of Uterine Leiomyomata (Fibroids)
  Indicated for concomitant use with iron therapy for preoperative hematologic improvement of women with anemia caused by fibroids for whom three months of hormonal suppression is deemed necessary. 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: 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.

• For diagnosis of Gender Dysphoria [16, 17]
  Suppression of pubertal development and gonadal function is accomplished most effectively by gonadotropin suppression with gonadotropin releasing hormone analogues and antagonists. Analogues suppress gonadotropins after a short period of stimulation, whereas antagonists immediately suppress pituitary secretion. Since no long-acting antagonists are available for use as pharmacotherapy, long-acting analogues are the currently preferred treatment option. [16] Early use of puberty-suppressing hormones may avert negative social and emotional consequences of gender dysphoria more effectively than their later use would. [17]

Leuprolide Acetate

• For diagnosis of Prostate Cancer
  Indicated for the palliative treatment of advanced prostatic cancer.

• For diagnosis of Infertility
  Used for controlled ovarian hyperstimulation to enhance the in vitro fertilization-embryo transfer (IVF-ET) procedure. [5]

• For diagnosis of Gender Dysphoria [16, 17]
  Suppression of pubertal development and gonadal function is accomplished most effectively by gonadotropin suppression with gonadotropin releasing hormone analogues and antagonists. Analogues suppress gonadotropins after a short period of stimulation, whereas antagonists immediately suppress pituitary secretion. Since no long-acting antagonists are available for use as pharmacotherapy, long-acting analogues are the currently preferred treatment option. [16] Early use of puberty-suppressing hormones may avert negative social and emotional consequences of gender dysphoria more effectively than their later use would. [17]

Leuprolide Acetate Depot, Eligard (leuprolide acetate), Trelstar (triptorelin pamoate)

• For diagnosis of Prostate Cancer
  Indicated for the treatment of advanced prostate cancer.

• For diagnosis of Gender Dysphoria [16, 17]
  Suppression of pubertal development and gonadal function is accomplished most effectively by gonadotropin suppression with gonadotropin releasing hormone analogues and antagonists. Analogues suppress gonadotropins after a short period of stimulation, whereas antagonists immediately suppress pituitary secretion. Since no long-acting antagonists are available for use as pharmacotherapy, long-acting analogues are the currently preferred treatment option. [16] Early use of puberty-suppressing hormones may avert negative social and emotional consequences of gender dysphoria more effectively than their later use would. [17]

Lupron Depot-PED (leuprolide acetate)

• For diagnosis of Central Precocious Puberty (CPP)
  Indicated for the treatment of pediatric patients with central precocious puberty (CPP).

• For diagnosis of Gender Dysphoria [16, 17]
  Suppression of pubertal development and gonadal function is accomplished most effectively by gonadotropin suppression with gonadotropin releasing hormone analogues and antagonists. Analogues suppress gonadotropins after a short period of stimulation, whereas antagonists immediately suppress pituitary secretion. Since no long-acting antagonists are available for use as pharmacotherapy, long-acting analogues are the currently preferred treatment option. [16] Early use of puberty-suppressing hormones may avert negative social and emotional consequences of gender dysphoria more effectively than their later use would. [17]

Camcevi (leuprolide)

• For diagnosis of Prostate Cancer
  Indicated for the treatment of adult patients with advanced prostate cancer.

Supprelin LA (histrelin acetate)

• For diagnosis of Central Precocious Puberty (CPP)
  Indicated for the treatment of children with CPP. Children with CPP (neurogenic or idiopathic) have an early onset of secondary sexual characteristics (earlier than 8 years of age in females and 9 years of age in males). They also show a significantly advanced bone age that can result in diminished adult height attainment. Prior to initiation of treatment a clinical diagnosis of CPP should be confirmed by measurement of blood concentrations of total sex steroids, luteinizing hormone (LH) and follicle stimulating hormone (FSH) following stimulation with a GnRH analog, and assessment of bone age versus chronological age. Baseline evaluations should include height and weight measurements, diagnostic imaging of the brain (to rule out intracranial tumor), pelvic/testicular/adrenal ultrasound (to rule out steroid secreting tumors), human chorionic gonadotropin levels (to rule out a chorionic gonadotropin secreting tumor), and adrenal steroids to exclude congenital adrenal hyperplasia.

• For diagnosis of Gender Dysphoria [16, 17]
  Suppression of pubertal development and gonadal function is accomplished most effectively by gonadotropin suppression with gonadotropin releasing hormone analogues and antagonists. Analogues suppress gonadotropins after a short period of stimulation, whereas antagonists immediately suppress pituitary secretion. Since no long-acting antagonists are available for use as pharmacotherapy, long-acting analogues are the currently preferred treatment option. [16] Early use of puberty-suppressing hormones may avert negative social and emotional consequences of gender dysphoria more effectively than their later use would. [17]

Triptodur (triptorelin), Fensolvi (leuprolide acetate)

• For diagnosis of Central Precocious Puberty (CPP)
  Indicated for the treatment of pediatric patients 2 years of age and older with central precocious puberty (CPP).

• For diagnosis of Gender Dysphoria [16, 17]
  Suppression of pubertal development and gonadal function is accomplished most effectively by gonadotropin suppression with gonadotropin releasing hormone analogues and antagonists. Analogues suppress gonadotropins after a short period of stimulation, whereas antagonists immediately suppress pituitary secretion. Since no long-acting antagonists are available for use as pharmacotherapy, long-acting analogues are the currently preferred treatment option. [16] Early use of puberty-suppressing hormones may avert negative social and emotional consequences of gender dysphoria more effectively than their later use would. [17]

Criteria

Camcevi, Lupron Depot (7.5 mg, 22.5 mg, 30 mg and 45 mg)

Prior Authorization (Initial Authorization)

Length of Approval: 12 Month(s)
For diagnosis of Prostate Cancer

• Diagnosis of advanced or metastatic prostate cancer

Eligard, Brand Leuprolide Acetate (22.5 mg), Generic leuprolide acetate, Trelstar

Prior Authorization (Initial Authorization)

Length of Approval: 12 Month(s)
For diagnosis of Prostate Cancer

• Diagnosis of advanced or metastatic prostate cancer
AND
• Trial and failure, contraindication, or intolerance to any brand Lupron formulation

Camcevi, Eligard, Brand Leuprolide Acetate (22.5 mg), Generic leuprolide acetate, Lupron Depot (7.5 mg, 22.5 mg, 30 mg and 45 mg), Trelstar

Prior Authorization (Reauthorization)

Length of Approval: 12 Month(s)
For diagnosis of Prostate Cancer

• Patient does not show evidence of progressive disease while on therapy

Lupron Depot (3.75 mg and 11.25 mg)

Prior Authorization (Initial Authorization)

Length of Approval: 6 Month(s)
For diagnosis of Endometriosis

• Diagnosis of endometriosis
AND
• One of the following: [8, 12]
• History of inadequate pain control response following a trial of at least 6 months, or history of intolerance or contraindication to one of the following:
• Danazol
• Combination (estrogen/progestin) oral contraceptive
• Progestins
OR
• Patient has had surgical ablation to prevent recurrence

Lupron Depot (3.75 mg and 11.25 mg)

Prior Authorization (Reauthorization)

Length of Approval: 6 Month(s)
For diagnosis of Endometriosis

• Recurrence of symptoms following a trial of at least 6 months with leuprolide acetate
AND
• Used in combination with one of the following:
• Norethindrone 5 mg daily
• Other "add-back" sex-hormones (e.g., estrogen, medroxyprogesterone)
• Other bone-sparing agents (e.g., bisphosphonates such as alendronate, risedronate)

Lupron Depot (3.75 mg and 11.25 mg)

Prior Authorization

Length of Approval: 4 Month(s)
For diagnosis of Uterine Leiomyomata (Fibroids) - For the reduction of the size of fibroids [off-label]

• For use prior to surgery to reduce the size of fibroids to facilitate a surgical procedure (e.g., myomectomy, hysterectomy) [5]

Lupron Depot (3.75 mg and 11.25 mg)

Prior Authorization

Length of Approval: 3 Month(s)
For diagnosis of Uterine Leiomyomata (Fibroids) - Anemia [4,6]

• For the treatment of anemia
AND
• Anemia is caused by uterine leiomyomata (fibroids)
AND
• Patient has tried and had an inadequate response to at least 1 month of monotherapy with iron
AND
• Used in combination with iron therapy
AND
• For use prior to surgery

Fensolvi, Lupron Depot-PED, Supprelin LA, Triptodur

Prior Authorization (Initial Authorization)

Length of Approval: 12 Month(s)
For diagnosis of Central Precocious Puberty (CPP)

• Diagnosis of central precocious puberty (idiopathic or neurogenic)
AND
• Early onset of secondary sexual characteristics in one of the following:
• Females less than 8 years of age
• Males less than 9 years of age
AND
• Advanced bone age of at least one year compared with chronological age
AND
• One of the following:
• Both of the following:
• Patient has undergone gonadotropin-releasing hormone agonist (GnRHa) testing
• Peak luteinizing hormone (LH) level above pre-pubertal range
OR
• Patient has a random LH level in the pubertal range
AND
• One of the following:
• Patient had one of the following diagnostic evaluations to rule out tumors, when suspected:
• Diagnostic imaging of the brain (MRI or CT scan) (in patients with symptoms suggestive of a brain tumor or in those 6 years of age or younger)
• Pelvic/testicular/adrenal ultrasound (if steroid levels suggest suspicion)
• Adrenal steroids to rule out congenital adrenal hyperplasia (when pubarche precedes thelarche or gonadarche)
OR
• Patient has no suspected tumors
AND
• Prescribed by or in consultation with an endocrinologist

Fensolvi, Lupron Depot-PED, Supprelin LA, Triptodur

Prior Authorization (Reauthorization)

Length of Approval: 12 Month(s)
For diagnosis of Central Precocious Puberty (CPP)

• Patient demonstrates positive clinical response to therapy (e.g., lack of progression or stabilization of secondary sexual characteristics, decrease in height velocity, a decrease in the ratio of bone age to chronological age, improvement in final height prediction, LH levels have been suppressed to pre-pubertal levels) [22]
AND
• Patient is currently younger than the appropriate time point for the onset of puberty (e.g., females younger than 11 years of age, males younger than 12 years of age) [22]
AND
• Prescribed by or in consultation with an endocrinologist

Generic leuprolide acetate*

*Please consult client-specific resources to confirm whether benefit exclusions should be reviewed for medical necessity.

Prior Authorization

Length of Approval: 2 Month [A] (or per plan benefit design)
For diagnosis of Treatment of Infertility (off-label) [5]

• Diagnosis of infertility
AND
• Used as part of an assisted reproductive technology (ART) protocol

Lupron Depot, Lupron Depot-PED, Brand Leuprolide Acetate (22.5 mg), Generic leuprolide acetate, Eligard, Supprelin LA, Trelstar, Triptodur, Camcevi, Fensolvi

Prior Authorization

Length of Approval: 12 Month(s)
For diagnosis of Gender Dysphoria/Gender Incongruence (off-label) [16, 17]

• Using gonadotropin for suppression of puberty [16,17]
AND
• Diagnosis of gender dysphoria/gender incongruence

P & T Revisions

2024-08-19, 2023-08-21, 2023-05-26, 2022-12-20, 2022-09-22, 2022-08-02, 2022-05-31, 2021-09-07, 2021-05-19, 2021-01-04, 2020-08-27, 2020-06-30, 2020-02-22, 2020-01-03

References

1. Leuprolide acetate prescribing information. Sandoz Inc. Princeton, NJ. June 2020.
2. Lupron Depot (3.75 mg) prescribing information. AbbVie Inc. North Chicago, IL. October 2023.
3. Lupron Depot (3-Month 11.25 mg) prescribing information. AbbVie Inc. North Chicago, IL. October 2023.
4. Friedman AJ, Harrison-Atlas D, Barbieri RL, et al. A randomized, placebo-controlled, double-blind study evaluating the efficacy of leuprolide acetate depot in the treatment of uterine leiomyomata. Fertil Steril 1989;51:251-256.
5. DRUGDEX System [Internet database]. Greenwood Village, Colorado: Thomson Micromedex. Updated periodically. Accessed July 22, 2024.
6. Lethaby A, Vollenhoven B, Sowter M. Pre-operative GnRH analogue therapy before hysterectomy or myomectomy for uterine fibroids. Cochrane Database Syst Rev. 2001;(2):CD000547.
7. Supprelin LA prescribing information. Endo USA. Malvern, PA. April 2022.
8. Ferrero, S., Barra, F. & Leone Roberti Maggiore, U. Current and Emerging Therapeutics for the Management of Endometriosis. Drugs 78, 995–1012 (2018).
9. Lupron Depot (7.5 mg, 22.5 mg, 30 mg, 45 mg) prescribing information. AbbVie Inc. North Chicago, IL. March 2024.
10. Eligard prescribing information. Tolmar Pharmaceuticals, Inc. Fort Collins, CO. May 2024.
11. Trelstar prescribing information. Verity Pharmaceuticals, Inc. Ewing, NJ. April 2024.
12. Practice bulletin no. 114: management of endometriosis. Obstet Gynecol. 2010 Jul; 116 (1): 223-36.
13. Per clinical consult with reproductive endocrinologist, April 10, 2013.
14. National Comprehensive Cancer Network Drugs and Biologics Compendium (NCCN Compendium). Available at: http://www.nccn.org/professionals/drug_compendium/content/contents.asp. Accessed August 31, 2022.
15. Lupron Depot-PED prescribing information. AbbVie Inc. North Chicago, IL. April 2023.
16. Hembree, Wylie C, Cohen-Kettenis P, Delemarre-van de Waal HA, et al. "Endocrine treatment of transsexual persons: an Endocrine Society clinical practice guideline." The Journal of clinical endocrinology and metabolism 94.9 (2009):3132-3154.
17. Coleman E, Bockting W, Botzer M et al. Standards of Care for the Health of Transsexual, Transgender, and Gender-Nonconforming People, Version 7. International Journal of Transgenderism. 13:165-232, 2011.
18. Triptodur prescribing information. Azurity Pharmaceuticals, Inc. Woburn, MA. November 2023.
19. Fensolvi prescribing information. Tolmar Inc. Fort Collins, CO. April 2023.
20. Camcevi Prescriber Information. Accord BioPharma, Inc. Raleigh, NC. November 2023.
21. Leuprolide Acetate Depot prescribing information. Cipla USA, Inc. Warren, NJ. November 2023.
22. Harrington, J, Palmert, M. Treatment of precocious puberty. UpToDate. 2022. https://www.uptodate.com/contents/treatment-of-precocious-puberty?search=central%20precocious%20puberty&source=search_result&selectedTitle=2~30&usage_type=default&display_rank=2. Accessed July 2, 2024.

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Revision History

• 2024-08-19: 2024 annual review: Removed "pediatric" from pediatric endocrinologist prescriber requirement for Central Precocious Puberty (CPP) indication and added examples of bisphosphonates for endometriosis indication. background updates.
• 2023-08-21: Updated reauth criteria for central precocious puberty indication. Added Camcevi and Fensolvi to gender dysphoria/gender incongruence indication. Removed criteria for obsolete Lupaneta and Vantas products.
• 2023-05-26: Addition of new Lupron Depot 45 mg pediatric kit as target for the existing CPP indication
• 2022-12-20: Updated guideline to include new formulations, leuprolide acetate depot and generic leuprolide kit.
• 2022-09-22: Annual review: Updated protesterone to progestin in "Combination (estrogen/progestin) oral contraceptive" for endometriosis indication. No other criteria changes.
• 2022-08-02: Update to Gender dysphoria criteria
• 2022-05-31: Updated guideline to include new product, Camcevi and update indication for Lupron depot
• 2021-09-07: Annual Review
• 2021-05-19: Addition of EHB formulary to guideline, no changes to criteria
• 2021-01-04: Program Update to remove CPP indication for leuprolide acetate
• 2020-08-27: Annual Review: references updated
• 2020-06-30: Program Update. Added new drug Fensolvi as target for the existing CPP criteria.
• 2020-02-22: For target drugs Eligard, Generic leuprolide acetate, Trelstar, and Vantas updated initial criteria for PC indication.
• 2020-01-03: Added examples of other add-back sex hormones and other bone-sparing agents where applicable.

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