ANDRODERM, Testosterone Form

Testosterone transdermal system (Androderm®) is a topical androgen. FDA Approved Indication(s) Androderm is indicated for replacement therapy in males for conditions associated with a deficiency or absence of endogenous testosterone:
• Primary hypogonadism (congenital or acquired) - testicular failure due to conditions such as cryptorchidism, bilateral torsion, orchitis, vanishing testes syndrome, orchiectomy, Klinefelter Syndrome, chemotherapy, or toxic damage from alcohol or heavy metals. These men usually have low serum testosterone concentrations and gonadotropins (FSH, LH) above the normal range. • Hypogonadotropic hypogonadism (congenital or acquired) - gonadotropic lutenizing hormone-releasing hormone deficiency, or pituitary - hypothalamic injury from tumors, trauma, or radiation. These men have low testosterone serum concentrations but have gonadotropins in the normal or low range. Limitation(s) of use: • Safety and efficacy of Androderm in men with “age-related hypogonadism” (also referred to as “late-onset hypogonadism”) have not been established. • Safety and efficacy of Androderm in males less than 18 years old have not been established. 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 Androderm is medically necessary when the following criteria are met:
I. Initial Approval Criteria
A. Hypogonadism (must meet all):

1. Diagnosis of primary hypogonadism or hypogonadotropic hypogonadism;
   2. Age ≥ 18 years;
   3. Documentation of serum testosterone level < 300 ng/dL on at least 2 separate days within the last 6 months;

2. Failure* of testosterone cypionate or testosterone enanthate injection at up to maximally indicated dose unless clinically significant adverse effects are experienced or both are contraindicated;
   Page 1 of 7

   CLINICAL POLICY Testosterone *Failure is demonstrated by lower than normal total testosterone levels as compared to laboratory reference values

3. Dose does not exceed 6 mg per day; as a combination of one 2 mg and one 4 mg patch. Approval duration: 12 months
   B. Gender Dysphoria, Female-to-Male Transition (off-label) (must meet all):
4. Diagnosis of gender dysphoria or request is for gender transition;
   2. Age ≥ 18 years;
   3. 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);
5. Member must use testosterone cypionate or testosterone enanthate injection, unless clinically significant adverse effects are experienced or both are contraindicated;
   5. Member demonstrates understanding of expected testosterone treatment outcomes and has given consent for such treatment;
6. If member has a psychiatric comorbidity, member is followed by mental health provider;
7. Psychosocial support will be provided during treatment;
   8. 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: 6 months
      C. Other diagnoses/indications (must meet 1 or 2):
8. 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: HIM.PA.33 for health insurance marketplace; 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: HIM.PA.103 for health insurance marketplace; or
9. 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: HIM.PA.154 for health insurance marketplace.
   II. Continued Therapy A. Hypogonadism (must meet all):

10. 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 2 of 7

    CLINICAL POLICY Testosterone 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. Member is responding positively to therapy;
    3. If request is for a dose increase, new dose does not exceed 6 mg per day; as a combination of one 2 mg and one 4 mg patch.
       Approval duration: 12 months
       B. Gender Dysphoria, Female-to-Male Transition (off-label) (must meet all):
11. 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);
12. Member is responding positively to therapy (e.g., developing a masculinized body while minimizing feminine characteristics, consistent with member’s gender goals);
13. 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: 12 months
    C. Other diagnoses/indications (must meet 1 or 2):
14. 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: HIM.PA.33 for health insurance marketplace; 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: HIM.PA.103 for health insurance marketplace; or

15. 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: HIM.PA.154 for health insurance marketplace.
    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 – HIM.PA.154 for health insurance marketplace or evidence of coverage documents; B. Age-related hypogonadism or late-onset hypogonadism.
    IV. Appendices/General Information Appendix A: Abbreviation/Acronym Key FDA: Food and Drug Administration Page 3 of 7

    CLINICAL POLICY Testosterone 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 testosterone cypionate
    testosterone enanthate injection 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. Male hypogonadism: 50 to 400 mg IM once every 2 to 4 weeks Male hypogonadism: 50 to 400 mg IM once every 2 to 4 weeks Dose Limit/ Maximum Dose 400 mg every 2 to 4 weeks 400 mg every 2 to 4 weeks Appendix C: Contraindications/Boxed Warnings • Contraindication(s): o Men with carcinoma of the breast or known or suspected carcinoma of the prostate
    o Pregnant or breastfeeding women (testosterone may cause fetal harm) • Boxed warning(s): none reported Appendix D: General Information • Per the Endocrine Society (2018), the diagnosis of hypogonadism requires unequivocally and consistently low testosterone levels on at least 2 separate mornings. Although the lower limit of normal for testosterone can vary depending on the laboratory used, clinical trials for a number of testosterone agents defined it as < 300 ng/dL. Additionally, the American Urological Association suggests < 300 ng/dL as a reasonable cut-off in support of low testosterone diagnosis (2018). • Patients with primary hypogonadism usually have low serum testosterone concentrations and gonadotropins (follicle stimulating hormone and luteinizing hormone) above the normal range. Patients with hypogonadotropic hypogonadism have low serum testosterone concentrations but have gonadotropins in the normal or low range.
    • 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 Page 4 of 7

    CLINICAL POLICY Testosterone 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. V. Dosage and Administration
    Indication Hypogonadism Dosing Regimen 1 patch topically nightly for 24 hours Maximum Dose 6 mg/day VI. Product Availability
    Transdermal system: 2 mg/day, 4 mg/day VII.