Place of Service Histrelin implant (Vantas®) Office Administration
Outpatient Facility Infusion
Administration Infusion Center Administration
HCPCS: J9225 per 50 mg How supplied: 50 mg implant
Condition listed in policy (see criteria for details) • Gender dysphoria in adolescents • Prostate cancer, advanced
AHFS therapeutic class: Gonadotropin
Mechanism of action: Luteinizing hormone-releasing hormone [LH-RH] agonist
Technician extension of authority (EOA) Section (2) diagnoses: No indication in Section (2) For member new to Blue Shield (within the past 6 months), approve for Section (2) diagnoses if: No indication in Section (2)
(1) Special Instructions and pertinent Information Covered under the Medical Benefit, please submit clinical information for prior authorization review via fax.
(2) Prior Authorization/Medical Review is required for the following condition(s) All requests for Vantas® (histrelin) NOT listed in section 3 must be sent for clinical review and receive authorization prior to drug administration or claim payment.
(3) The following condition(s) DO NOT require Prior Authorization/Preservice All requests for Vantas® (histrelin) NOT listed in section 3 must be sent for clinical review and receive authorization prior to drug administration or claim payment.
Gender dysphoria in adolescents
Covered Doses 1 implant (50 mg of histrelin acetate) inserted subcutaneously every 12 months.
ICD-10: F64.1, F64.2, F64.9
Prostate cancer, advanced
Covered Doses 1 implant (50 mg of histrelin acetate) inserted subcutaneously every 12 months.
Coverage Period Annually based on continued response Commercial Histrelin (Vantas®)
Effective: 09/29/2021 Page 1 of 6
ICD-10: C61
(4) This Medication is NOT medically necessary for the following condition(s) Blue Shield’s research indicates there is inadequate clinical evidence to support off-label use of this drug for the following conditions (Health and Safety Code 1367.21):
• Precocious Puberty Supprelin LA (histrelin) implant is FDA-indicated for central precocious puberty Coverage for a Non-FDA approved indication, requires that criteria outlined in Health and Safety Code § 1367.21, including objective evidence of efficacy and safety are met for the proposed indication.
Please refer to the Provider Manual and User Guide for more information.
(5) Additional Information How supplied: 50 mg subcutaneous implant
Table 1. Endocrine Society Clinical Practice Guideline for Endocrine Treatment of Gender- Dysphoric/Gender-Incongruent Persons (2017)1 Adolescents are eligible for GnRH agonist treatment if: 1. A qualified MHP has confirmed that: a. the adolescent has demonstrated a long-lasting and intense pattern of gender nonconformity or gender dysphoria (whether suppressed or expressed) b. gender dysphoria worsened with the onset of puberty c. any coexisting psychological, medical, or social problems that could interfere with treatment (e.g., that may compromise treatment adherence) have been addressed, such that the adolescent’s situation and functioning are stable enough to start treatment, d. the adolescent has sufficient mental capacity to give informed consent to this (reversible) treatment 2. And the adolescent: a. has been informed of the effects and side effects of treatment (including potential loss of fertility if the individual subsequently continues with sex hormone treatment) and options to preserve fertility, b. has given informed consent and (particularly when the adolescent has not reached the age of legal medical consent, depending on applicable legislation) the parents or other caretakers or guardians have consented to the treatment and are involved in supporting the adolescent throughout the treatment process 3. And a pediatric endocrinologist or other clinician experienced in pubertal assessment: a. agrees with the indication for GnRH agonist treatment, b. has confirmed that puberty has started in the adolescent (Tanner stage ≥G2/B2) c. has confirmed that there are no medical contraindications to GnRH agonist treatment.
Commercial Histrelin (Vantas®)
Effective: 09/29/2021 Page 2 of 6
Table 2. WPATH (2012) recommendations for use puberty suppression in adolescents with gender dysphoria2 Recommendations for puberty suppression in adolescent males and females: 1. GnRH analogs are the preferred treatment for puberty suppression. 2. Alternative treatments include progestins. Continuous oral contraceptives or depot medroxyprogesterone may be used to suppress menses.
Criteria for Puberty-Suppressing Hormones: In order for adolescents to receive puberty-suppressing hormones, the following minimum criteria must be met: 1. The adolescent has demonstrated a long-lasting and intense pattern of gender nonconformity or gender dysphoria (whether suppressed or expressed); 2. Gender dysphoria emerged or worsened with the onset of puberty; 3. Any coexisting psychological, medical, or social problems that could interfere with treatment (e.g., that may compromise treatment adherence) have been addressed, such that the adolescent’s situation and functioning are stable enough to start treatment; 4. The adolescent has given informed consent and, particularly when the adolescent has not reached the age of medical consent, the parents or other caretakers or guardians have consented to the treatment and are involved in supporting the adolescent throughout the treatment process.
Table 3. Description of Tanner stages of breast development and male external genitalia1 For breast development: 1. Prepubertal. 2. Breast and papilla elevated as small mound; areolar diameter increased. 3. Breast and areola enlarged, no contour separation. 4. Areola and papilla form secondary mound. 5. Mature; nipple projects, areola part of general breast contour.
For penis and testes: 1. Prepubertal, testicular volume <4 mL 2. Slight enlargement of penis; enlarged scrotum, pink texture altered, testes 4-6 mL 3. Penis longer, testes larger (8-12 mL) 4. Penis larger, glans and breadth increase in size; testes larger (12-15 mL), scrotum dark. 5. Penis and testes adult size, testicular volume >15 mL
(6) References • AHFS®. Available by subscription at http://www.lexi.com • DrugDex®. Available by subscription at http://www.micromedexsolutions.com • Hembree WC, Cohen-Kettenis PT, Gooren L, Hannema SE, Meyer WJ, Murad MH, Rosenthal SM, Safer JD, Tangpricha V, T'Sjoen GG. Endocrine Treatment of Gender-Dysphoric/Gender- Incongruent Persons: An Endocrine Society Clinical Practice Guideline. J Clin Endocrinol Metab. 2017;102(11):3869-3903. • National Comprehensive Cancer Network (NCCN) Clinical Practice Guidelines in Oncology: Prostate Cancer, v.2.2020. Available at: http://www.nccn.org. • Vantas® (histrelin acetate) [Prescribing Information]. Endo Pharmaceuticals Solutions Inc.: Malvern, PA: Endo Pharmaceuticals Inc.; 11/2019. • World Professional Association for Transgender Health (2011) Standards of Care for the Health of Transsexual, Transgender, and Gender Nonconforming People (Version 7). 2012. Available at: http://www.wpath.org/uploaded_files/140/files/Standards%20of%20Care,%20V7%20Full%20B ook.pdf
1. Hembree WC, Cohen-Kettenis PT, Gooren L, Hannema SE, Meyer WJ, Murad MH, Rosenthal SM, Safer JD, Tangpricha V, T'Sjoen GG. Endocrine Treatment of Gender-Dysphoric/Gender-
Commercial Histrelin (Vantas®)
Effective: 09/29/2021 Page 3 of 6
Incongruent Persons: An Endocrine Society Clinical Practice Guideline. J Clin Endocrinol Metab. 2017;102(11):3869-3903. 2. World Professional Association for Transgender Health (2011) Standards of Care for the Health of Transsexual, Transgender, and Gender Nonconforming People (Version 7). 2012. Available at: http://www.wpath.org/uploaded_files/140/files/Standards%20of%20Care,%20V7%20Full%20B ook.pdf
(7) Policy Update Date of last review: 3Q2021 Date of next review: 3Q2022 Changes from previous policy version: • No clinical change to policy following routine annual review.
(8) Previous Policy Update History (effective date) – INTERNAL USE 11-12-2007: • New policy
12/27/2007: • Section (1): Fax form information updated
9-22-2008: • No change to policy following routine review
3-25-2010: • Section (3): Updated coverage criteria to require diagnosis of advance prostate cancer only and dispensing limit of 1 implant per 12 month period. Previously required pre-service review for this diagnosis under section (2) including a response to Lupron or Trelstar and medical necessity reason for use of a 12-month continuous delivery of gonadotropin releasing hormone.
9-16-2010: • No change to policy following routine review
9-15-2011: • No change to policy following routine review
9-20-2012: • No change to policy following routine review
9-26-2013: • No change to policy following routine review • Updated version to new format
9-18-2014: • No change to policy following routine review
9-17-2015: • No change to policy following routine review
6-16-2016: • Section (3): Added coverage of gender dysphoria in adolescents based on diagnosis. Rationale: Coverage based guideline support from Endocrine Society clinical practice guideline and World Professional Association for Transgender Health (WPATH) standard of care publication. • Section (5): Added additional information (Tables 1-3) for indication of gender dysphoria in adolescents.
9-15-2016: • No change to policy following routine review. Commercial Histrelin (Vantas®)
Effective: 09/29/2021 Page 4 of 6
3-1-2017: • Section (9): Added denials
5-1-2017: • Section (6): Correction to NCCN reference citation.
10-1-2017: • No change to policy following routine review • Added tech EOA
11-1-2018: • Removed NDC in Header • Tech EOA COT added • Section (3): Removed ICD-9 codes • Section (4): Updated language approved by legal • Section (9): Denial codes. Updated A, B.
10-2-2019: • Section (3): Advanced prostate cancer – Removed Coverage Period. Not managed. • Section (6): References. Updated PI.
11-4-2020: • Section (5): Corrected reference for Table 3 • Section (6): References. Updated NCCN prostate. • Section (9): Denial language: Updated B, Added C.
9-29-2021: • Section (5): Updated Table 1 & 3 to align with updated guidelines • Section (6): References. Updated PI. Added Hembree WC, et al, Endocrine Treatment of Gender- Dysphoric/Gender-Incongruent Persons: An Endocrine Society Clinical Practice Guideline and updated it in endnotes. Added World Professional Association for Transgender Health (2011) Standards … (9) Coverage AA Codes-- INTERNAL USE AA codes General A The dose requested is
The information sent in does not meet the “OFF-LABEL DRUG USE” criteria approved by Blue Shield of California’s Pharmacy and Therapeutics Committee that aligns with the California Health and Safety Code (HSC 1367.21). We may cover off-label use of B a drug if it meets one of the following: (off-label CANCER) • The use of this drug for your condition is supported by one of these drug resources: Clinical Pharmacology, National Comprehensive Cancer Network (NCCN), American Hospital Formulary Service Drug Information, Thomson Micromedex DrugDex, and Lexicomp.
• The use of this drug for your condition is supported by at least two articles published in medical journals that are reviewed by medical experts (peer- reviewed). These articles must show the drug is safe and effective for your
Commercial Histrelin (Vantas®)
Effective: 09/29/2021 Page 5 of 6
condition. Also, there must not be any peer-reviewed articles showing the drug does not work for your condition.
Please talk with your doctor about your treatment options. The Food and Drug Administration (FDA) has not approved Vantas for
The information sent in does not meet the “OFF-LABEL DRUG USE” criteria approved by Blue Shield of California’s Pharmacy and Therapeutics Committee that aligns with the California Health and Safety Code (HSC 1367.21). We may cover off-label use of a drug if it meets one of the following: C (off-label • The use of this drug for your condition is supported by American Hospital NOT Formulary Service Drug Information (medical literature). CANCER) • The use of this drug for your condition is supported by at least two articles published in medical journals that are reviewed by medical experts (peer- reviewed). These articles must show the drug is safe and effective for your condition. Also, there must not be any peer-reviewed articles showing the drug does not work for your condition.
Please talk with your doctor about your treatment options.
BSC Drug Coverage Criteria to Determine Medical Necessity Reviewed by P&T Committee
Commercial Histrelin (Vantas®)
Effective: 09/29/2021 Page 6 of 6