Medication Policy Manual

Transcription

1 Medication Policy Manual Topic: Non-preferred testosterone replacement therapy products (Androderm, Androgel, Aveed, Axiron, Fortesta, Natesto, Striant, Testim Gel, Testopel, Vogelxo, compounded testosterone products, non-preferred generic products) Policy No: dru297 Date of Origin: March 15, 2013 Committee Approval Date: April 13, 2015 Next Review Date: April 2016 Effective Date: September 1, 2015 IMPORTANT REMINDER This Medical Policy has been developed through consideration of medical necessity, generally accepted standards of medical practice, and review of medical literature and government approval status. Benefit determinations should be based in all cases on the applicable contract language. To the extent there are any conflicts between these guidelines and the contract language, the contract language will control. The purpose of medical policy is to provide a guide to coverage. Medical Policy is not intended to dictate to providers how to practice medicine. Providers are expected to exercise their medical judgment in providing the most appropriate care. Description Testosterone replacement therapy (TRT) products are used in the treatment of hypogonadism (testosterone deficiency). The effectiveness of TRT is monitored by assessing serum testosterone levels, as well as improvement in sexual function, mood, fatigue, bone mineral density, and well-being. dru297.3 Page 1 of 10

2 Policy/Criteria I. Most contracts require prior authorization approval of non-preferred testosterone replacement therapy (TRT) products, as listed in Appendix 1, prior to coverage. Products listed in Appendix 1 may be considered medically necessary when criteria A and B below are met. A. One of the following two conditions is met: 1. A diagnosis of primary (Testicular) hypogonadism or secondary (Pituitary-Hypothalamic) hypogonadism when documentation of at least two low testosterone levels (less than 300 ng/dl for total testosterone, or less than 9 ng/dl for free testosterone) drawn prior to 10 AM on two separate days is provided. OR 2. As a continuous therapy for gender dysphoria when all of the following criteria are met: a. Clinical records document that the patient has the capacity to make fully informed decisions and consent for treatment. AND b. A licensed behavioral health practitioner has diagnosed gender dysphoria as defined by the DSM-5 criteria. AND c. At least one of the following criteria must be met for a period of 3 or more months prior to the initiation of hormone therapy i. Documentation of living as the desired gender; and/or ii. Psychotherapy with a licensed behavioral practitioner. AND B. Injectable testosterone cypionate or testosterone enanthate has been ineffective, contraindicated, or not tolerated. II. III. The use of testosterone undecanoate injection (Aveed) is considered not medically necessary. Administration, Quantity Limitations, and Authorization Period A. OmedaRx considers oral, nasal, topical, and transdermal testosterone replacement therapy (TRT) products to be self-administered medications. B. OmedaRx does not consider Aveed or Testopel to be self-administered medications. C. When prior authorization is approved, TRT products may be authorized as follows: dru297.3 Page 2 of 10

3 TRT Products Transdermal testosterone topical gel 1% (AndroGel 25 mg and 50 mg packets) testosterone topical gel 1% (AndroGel Pump ); 12.5 mg per actuation testosterone topical gel 1.62% (AndroGel 40.5 mg packets) testosterone topical gel 1.62% (AndroGel Pump ); mg per actuation testosterone topical solution (Axiron ); 30 mg per actuation testosterone topical gel 2% (Fortesta ); 10 mg per actuation testosterone topical gel 1% (Testim Gel 50 mg/5 gm tubes) testosterone topical gel 1% (Vogelxo 50 mg /5 gm tube or packet) testosterone topical gel 1% (Vogelxo pump bottle); 12.5 mg per actuation testosterone transdermal patch 2-4 mg/24 hours (Androderm ) Quantity Level Limitation (per Month, unless noted) 60 packets 4 pump bottles (60 actuations/bottle) 60 packets 2 pump bottles (60 actuations/bottle) 2 pump bottles (60 actuations/bottle) 2 pump bottles (120 actuations/bottle) 60 tubes 60 tubes or packets pump bottles (60 actuations per bottle) 2-mg/24 hour: 60 patches 4-mg/24 hour: 30 patches Subcutaneous pellet testosterone 75 mg pellet (Testopel ) Oral/Buccal testosterone 30 mg extended-release buccal tablets (Striant ) Nasal gel testosterone nasal gel 4.5% (Natesto metereddose pump bottle); 5.5 mg per actuation 450 mg (6 pellets) every 3 months 60 tablets 3 pump bottles (60 actuations per bottle) D. Quantities above the listed quantity limits are considered not medically necessary. E. Authorization shall be reviewed in the timeframes defined below: 1. Primary (Testicular) hypogonadism/secondary (Pituitary- Hypothalamic) hypogonadism: Authorization shall be reviewed after 6 months, and then at least annually to assure the testosterone level does not exceed 700 ng/dl. (See Appendix 2, Lab Monitoring Guidelines for TRT Products) dru297.3 Page 3 of 10

4 2. Gender reassignment therapy: authorization may be reviewed at least annually to confirm that current medical necessity criteria are met and that the medication is effective. IV. Non-preferred TRT products, as listed in Appendix 1, are considered not medically necessary for the following: A. Age-related hypogonadism B. Low libido in women C. Weight gain in HIV-infected men Position Statement - Testosterone replacement therapy (TRT) is commonly used for treatment of hypogonadism in men and as part of gender reassignment therapy. All products are considered effective for increasing serum testosterone levels. - There is no evidence demonstrating that any one TRT product is safer or more effective than less costly generic injectable options. There are no studies that directly compare the clinical effects of different TRT products. - Hypogonadism may be caused either by failure of the testicles to produce testosterone (primary), or by central defects in the hypothalamus or pituitary gland which lead to secondary testicular failure. [1] - A diagnosis of hypogonadism is confirmed by measuring serum testosterone levels. [1] - Testosterone levels vary throughout the day and are highest in the morning. Normal ranges for serum testosterone levels are usually established using morning blood samples. [1] - Threshold testosterone levels below which adverse health symptoms occur are not known. Likewise, optimal levels of testosterone at which TRT improves outcomes are not known. For most symptoms in younger men, the average testosterone threshold corresponds to the lower limit of the normal range. [1] - Because testosterone levels vary significantly due to body rhythms, episodic secretion, and measurement variations, at least two levels should be obtained to confirm a diagnosis of hypogonadism. [1] - Normal ranges for testosterone vary among laboratories and assays. The Endocrine Society recommends that a lower limit for normal testosterone levels is 300 ng/dl for total testosterone and 9.0 ng/dl for free testosterone. [1] - The Endocrine Society Clinical Guideline recommends evaluating patients 3 to 6 months after initiating treatment to evaluate patients for side effects and to make sure total testosterone levels are between 400 ng/dl and 700 ng/dl. [1] - Overall, TRT products are well tolerated. dru297.3 Page 4 of 10

5 - In March 2015, the FDA released a drug safety communication clarifying that the benefits and safety of TRT have not been established for the treatment of low testosterone levels due to aging, even if a man s symptoms seem related to low testosterone. The communication also stated that there is a possible increased cardiovascular risk associated with testosterone use. [2] - TRT should not be started in men who are at high risk for, or who have, prostate cancer. - While branded TRT products are comparable in price, testosterone cypionate and testosterone enanthate offer members the best value and they are available at preferred copayments. - Due to serious adverse events, such as pulmonary oil microembolism (POME) reactions and anaphylaxis, that are not present with other products, the use of testosterone undecanoate (Aveed) is considered not medically necessary. [3] - Due to the availability of injectable formulations, quantities above the quantity limits listed criterion II.B. are considered not medically necessary. The quantity limits listed correspond with the manufacturer s prescribing information for each medication. There is a lack of literature showing improved health outcomes and safety when the maximum dosing is exceeded. Clinical Efficacy No single testosterone replacement therapy (TRT) product has been proven in reliable clinical studies to be more effective than another TRT product. - All TRT products appear to be similarly effective based on pharmacokinetic data. There is pharmacokinetic evidence that all topical testosterone products replete testosterone levels in men with hypogonadism. [3-13] - The FDA accepts open-label, non-comparative trials of new TRT formulations as sufficient to provide evidence of safety and efficacy. More clinically relevant endpoints would be trials with validated disease outcome measures, showing meaningful improvements in symptoms, such as low mood, sexual function, lean muscle mass, and energy levels. - There are no trials comparing any branded TRT formulation, therefore there is no evidence that one branded TRT product is superior to another. - Long-term health outcomes of TRT, such as decreased incidence of fracture or cardiovascular risk, are uncertain. [2,14] - Clinical guidelines recognize TRT as standard of care and effective for treatment of hypogonadism in men. All products are considered effective in raising testosterone levels. Choice of TRT product is based on pharmacokinetics, patient preference, and cost. However, oral TRT is not recommended due to poor absorption and liver toxicity. [9,10] - The efficacy of TRT has not been established in men with age-related hypogonadism. - There are no valid, reliable, clinically relevant endpoints for studies assessing the effect of testosterone on desire, frequency of sexual activity, erectile function, mood, energy, overall quality of life, body composition (lean and fat body mass), and bone mineral density in men with age-related hypogonadism. dru297.3 Page 5 of 10

6 Safety [3-13] - Overall, testosterone topical replacement (TRT) is well tolerated. Common adverse effects ( 3%) include acne, gynecomastia, oral irritation (buccal formulation), headache, and enlarged prostate. The most commonly reported adverse event with topical TRT is application site reactions. However, testosterone transdermal patch (Androderm ) is associated with a significantly higher rate of skin reactions, including blistering of the skin. - TRT may be associated with increased risk of adverse cardiovascular outcomes (increased mortality, myocardial infarction, and stroke). Although findings in several large observational studies and meta-analyses are inconsistent, the FDA s Bone, Reproductive and Urologic Drugs Advisory Committee concluded that there is a small signal of risk. Based on conclusions reached in the advisory committee, the FDA subsequently released a drug safety communication related to the CV risk and will require labeling changes for all prescription testosterone products. [2,14-17] - TRT is contraindicated in men with known or suspected prostate cancer. - Testosterone undecanoate (Aveed) has boxed warnings for pulmonary oil microembolism (POME) reactions and anaphylaxis. POME reactions may be life threatening; symptoms include cough, dyspnea, throat tightening, chest pain, dizziness, and syncope. Patients who received testosterone undecanoate (Aveed) must be monitored in a healthcare setting for 30 minute post-dose in case of serious POME reactions or anaphylaxis. - In 2009, the FDA issued a MedWatch safety alert of inadvertent (secondary) testosterone exposure with topical testosterone gel (Testim and AndroGel), based on eight case reports of exposure in children, age nine months to five years old. Signs of virilization (development of male secondary sexual characteristics) and bone aging were observed. Black box warnings are now required on all topical gel and solution formulations of testosterone, as well as educational REMS programs to reduce secondary exposure. [18] dru297.3 Page 6 of 10

7 Appendix 1: Non-Preferred Testosterone Replacement Therapy (TRT) Products Topical testosterone topical solution 2% (Axiron ) testosterone topical gel 1% and 1.62% (AndroGel and AndroGel Pump ) testosterone topical gel 2% (Fortesta ) testosterone topical gel 1% (Testim Gel ) testosterone topical gel 1% (Vogelxo ) testosterone transdermal patch 2-4 mg/24 hours (Androderm ) Oral/Buccal testosterone 30 mg extended-release buccal tablets (Striant ) Nasal gel testosterone nasal gel 4.5% (Natesto ) Subcutaneous Pellet testosterone pellets 75 mg (Testopel ) dru297.3 Page 7 of 10

8 Appendix 2: Lab Monitoring Guidelines for TRT Products Transdermal patches Androderm Measure morning testosterone (following application of the patch the previous evening) Transdermal gels and solutions AndroGel, AndroGel Pump, Testim Fortesta Axiron Vogelxo Measure pre-dose morning testosterone level Measure testosterone 2 hours after application Measure testosterone 2 to 8 hours after application Measure testosterone 4 to 8 hours after application Subcutaneous pellet Testopel Measure pre-dose level and periodically during therapy Buccal tablet Striant Measure pre-dose morning testosterone level Nasal gel Natesto Measure pre-dose level Injectable testosterone cypionate (generics) testosterone enanthate (generics) Measure pre-dose level and periodically during therapy Measure pre-dose level and periodically during therapy dru297.3 Page 8 of 10

9 Appendix 3: Examples of Causes of Primary (Testicular) and Secondary (Pituitary- Hypothalamic) hypogonadism Primary (Testicular) Hypogonadism Cryptorchidism Bilateral Torsion Orchitis Vanishing testis syndrome Klinefelter s syndrome Toxic damage from chemotherapy, alcohol, or heavy metals Secondary (Pituitary-Hypothalamic) hypogonadism Congenital GnRH deficiency Hyperprolactinemia Idiopathic gonadotropic or luteinizing hormone-releasing hormone deficiency Kallman Syndrome Pituitary-hypothalamic injury from tumors, trauma, or radiation Cross References Testosterone Replacement Therapies, BlueCross BlueShield Association Medical Policy, , Issue 12:2014 Transgender Services, Medical Policy. Medicine, Policy No AndroGel, AndroGel Pump topical testosterone gel 1% and 1.62%, Medication Policy Manual, Policy No. dru360 Codes Number Description HCPCS J3145 Testosterone undecanoate, 1 mg HCPCS S1089 Testosterone pellet, 75 mg dru297.3 Page 9 of 10

10 References 1. Bhasin, S, Cunningham, GR, Hayes, FJ, et al. Testosterone therapy in men with androgen deficiency syndromes: an Endocrine Society clinical practice guideline. The Journal of clinical endocrinology and metabolism. 2010;95: PMID: U.S. Food and Drug Administration. Summary Minutes of the Joint Meeting of the Bone, Reproductive and Urologic Drugs Advisory Committee and the Drug Safety and Risk Management Advisory Committee. [cited 11/7/2014]; Available from: roductivehealthdrugsadvisorycommittee/ucm pdf. 3. Aveed [package insert]. Malvern, PA: Endo Pharmaceuticals; September Androderm [package insert]. Parsippany, NJ: Watson Pharma; April Androgel 1% [package insert]. North Chicago, IL: Abbvie; November Androgel 1.62% [package insert]. North Chicago, IL: Abbvie; November Axiron [package insert]. Indianapolis, IN: Eli Lilly and Company; June Fortesta [package insert]. Malvern, PA: Endo Pharmaceuticals; June Natesto [package insert]. Malvern, PA: Endo Pharmaceuticals; November Testim [package insert]. Chesterbrook, PA: Auxilium Pharmaceuticals; June Testopel [package insert]. Chesterbrook, PA: Auxilium Pharmaceuticals; January Vogelxo [package insert]. Maple Grove, MN: Upsher-Smith Laboratories; June Striant [package insert]. Chesterbrook, PA: Actient Pharmaceuticals; June U.S. Food and Drug Administration. FDA Briefing Information for the September 17, 2014 Joint Meeting of the Bone, Reproductive and Urologic Drugs Advisory Committee and the Drug Safety and Risk Management Advisory Committee Meeting. [cited 11/7/2014]; Available from: roductivehealthdrugsadvisorycommittee/ucm pdf. 15. Vigen, R, O'Donnell, CI, Baron, AE, et al. Association of testosterone therapy with mortality, myocardial infarction, and stroke in men with low testosterone levels. United States, p Xu, L, Freeman, G, Cowling, BJ, Schooling, CM. Testosterone therapy and cardiovascular events among men: a systematic review and meta-analysis of placebo-controlled randomized trials. BMC Med. 2013;11:108. PMID: Finkle, WD, Greenland, S, Ridgeway, GK, et al. Increased risk of non-fatal myocardial infarction following testosterone therapy prescription in men. United States, p. e MedWatch. FDA news release: Testosterone Gel Safety Concerns Prompt FDA to Require Label Changes, Medication Guide. 7May2009. [cited 2/16/2011]; Available from: dru297.3 Page 10 of 10