Committee Approval Date: October 14, 2014 Next Review Date: March 2015

Transcription

1 Medication Policy Manual Topic: Testosterone replacement therapy products: - Androderm, - Axiron, - Fortesta, - Striant, - Testim Gel, - Natesto, - Vogelxo Policy No: dru297 Date of Origin: March 15, 2013 Committee Approval Date: October 14, 2014 Next Review Date: March 2015 Effective Date: November 1, 2014 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) and as part of gender reassignment therapy. 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. dru297.2 Page 1 of 8

2 Policy/Criteria I. Most contracts require prior authorization approval of non-preferred branded 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. AndroGel or AndroGel Pump (testosterone topical gel) has been ineffective, contraindicated, or not tolerated. dru297.2 Page 2 of 8

3 II. Administration, Quantity Limitations, and Authorization Period A. RegenceRx considers branded testosterone replacement therapy (TRT) products to be self-administered medications. B. When prior authorization is approved, branded TRT products may be authorized as follows: Branded 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 ) 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 Quantity Level Limitation (per Month) 60 packets 2 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 4 pump bottles (60 actuations per bottle) 2-mg/24 hour: 60 patches 4-mg/24 hour: 30 patches 60 tablets 3 pump bottles (60 actuations per bottle) dru297.2 Page 3 of 8

4 C. 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 total testosterone level does not exceed 700 ng/dl. (See Appendix 2, Lab Monitoring Guidelines for TRT Products) 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. III. Non-preferred, branded TRT products, as listed in Appendix 1, are considered not medically necessary for the following: A. Low libido in women B. 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 topical medication alternatives such as testosterone topical gel (AndroGel or AndroGel Pump ). 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. - A diagnosis of hypogonadism is confirmed by measuring serum testosterone levels. [10] - 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. [10] - 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. [10] - 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. [10] dru297.2 Page 4 of 8

5 - 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. [10] - 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. [10] - Overall, TRT products, including testosterone topical gel (AndroGel ), are well tolerated. - The FDA is in the process of evaluating the long-term cardiovascular effects of TRT. - 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, AndroGel and AndroGel Pump offer members the best value and they are available at preferred copayments. 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. [1-7] - The FDA accepts open-label, non-comparative trials of new TRT formulations sufficient to provide evidence of safety and efficacy. More clinically meaningfully would be trials with disease outcomes, such as improvement 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. [8] - Clinical guidelines recognize TRT as standard of care and effective for treatment of hypogonadism in men. All products are considered effective. 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] Safety - Overall, testosterone topical replacement (TRT) is well tolerated. Common adverse effects ( 3%) include acne, gynecomastia, oral irritation (buccal formulation), headache, and enlarged prostate. [1-7] 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. [1-7] dru297.2 Page 5 of 8

6 - TRT is contraindicated in men with known or suspected prostate cancer. [1-7] - 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. [11] - TRT was found to be associated with increased risk of adverse cardiovascular outcomes (increased mortality, myocardial infarction, and stroke) in a large observational study (JAMA, 2013). [12] The FDA is currently in the process of evaluating the potential cardiovascular risks of TRT. Appendix 1: Branded 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 ) dru297.2 Page 6 of 8

7 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 Buccal tablet Striant Measure pre-dose morning testosterone level Nasal gel Natesto Measure pre-dose level Cross References Testosterone Replacement Therapies, BlueCross BlueShield Association Medical Policy, , Issue 12:2013 Transgender Services, Medical Policy. Medicine, Policy No. 153 AndroGel, AndroGel Pump topical testosterone gel 1% and 1.62%, RegenceRx Medication Policy Manual, Policy No. dru360 Codes Number Description N/A dru297.2 Page 7 of 8

8 References 1. AndroGel and AndroGel Pump 1% [package insert]. North Chicago, IL: Abbott Laboratories; September AndroGel and AndroGel Pump 1.62% [package insert]. North Chicago, IL: Abbott Laboratories; September Axiron [package insert]. Indianapolis, IN: Lilly USA, LLC; December Fortesta [package insert]. Malvern, PA: Endo Pharmaceuticals Inc.; December Testim [package insert]. Malvern, PA: Auxilium Pharmaceuticals, Inc.; November Androderm [package insert]. Parsippany, NJ: Watson Laboratories, Inc.; April Striant [package insert]. Livingston, NJ: Columbia Laboratories, Inc.; Snyder PJ. Hypogonadism in elderly men--what to do until the evidence comes. N Engl J Med Jan 29;350(5): PMID: Petak SM, Nankin HR, Spark RF, Swerdloff RS, Rodriguez-Rigau LJ. American Association of Clinical Endocrinologists Medical Guidelines for clinical practice for the evaluation and treatment of hypogonadism in adult male patients update. Endocr Pract Nov- Dec;8(6): PMID: Bhasin S, Cunningham GR, Hayes FJ, et al. Testosterone therapy in men with androgen deficiency syndromes: an Endocrine Society clinical practice guideline. J Clin Endocrinol Metab. Jun;95(6): PMID: MedWatch. FDA news release: Testosterone Gel Safety Concerns Prompt FDA to Require Label Changes, Medication Guide. 7May2009. [cited 2/16/2011]; Available from: Vigen R, O'Donnell CI, Barón AE, Grunwald GK, Maddox TM, et al. Association of testosterone therapy with mortality, myocardial infarction, and stroke in men with low testosterone levels. JAMA Nov 6;310(17): PMID: Vogelxo [package insert]. Maple Grove, MN: Upsher-Smith Laboratories, Inc.; June Natesto [package insert]. Durants, Christ Church, Barbados: Trimel BioPharma SRL; May dru297.2 Page 8 of 8