This document is posted to help you gain knowledge. Please leave a comment to let me know what you think about it! Share it to your friends and learn new things together.
Transcript
MN_PS_ Androgens_Anabolic_Steroids _PA_QL_ProgSum_AR1019 Page 1 of 22
Testosterone replacement therapy should be initiated in symptomatic men with
hypogonadism with a subnormal serum testosterone.12,47 Signs and symptoms of hypogonadism include:12
• Specific symptoms and signs:
o Incomplete or delayed sexual development o Loss of body (axillary and pubic) hair
o Very small testes (especially <6 ml) • Suggestive symptoms and signs:
o Reduced sexual desire (libido) and activity o Decreased spontaneous erections, erectile dysfunction
o Breast discomfort, gynecomastia o Eunuchoidal body proportions
o Inability to father children, low sperm count
o Height loss, low trauma fracture, low bone mineral density o Hot flushes, sweats
• Nonspecific symptoms and signs: o Decreased energy, motivation, initiative, and self-confidence
o Feeling sad or blue, depressed mood, persistent low-grade depressive disorder o Poor concentration and memory
o Sleep disturbance, increased sleepiness o Mild unexplained anemia (normochromic, normocytic)
o Reduced muscle bulk and strength
o Increased body fat, body mass index
Low testosterone levels should be assessed to confirmed diagnosis. The principal goal of testosterone therapy is to restore serum testosterone concentration to normal
range.12, 47 Hereditary Angioedema (HAE)
Danazol is no longer recommended as a first line option for prophylaxis of HAE though it is
FDA approved.40,49
Off Label Use – AIDS/HIV Androgens and anabolic steroids have been studied for use in AIDS/HIV-associated wasting
syndrome. Clinical studies support the use of the following agents in men for AIDS/HIV-associated wasting syndrome: testosterone transdermal system16, testosterone
enanthate17,18,21, oxandrolone19,20, and cypionate42. The use of topical testosterone to treat AIDS wasting in women is supported by several studies.28,29 Oxandrolone was studied in both
male and female pediatric patients.20
Off Label Use – Turner Syndrome
The Turner Syndrome Consensus Study Group, sponsored by the National Institutes of Health’s National Institute of Child Health and Human Development, recommends
oxandrolone for treatment of Turner syndrome, when used in conjunction with growth hormone (GH).15 Recommended dose of oxandrolone is 0.05 mg/kg/d or less in conjunction
with growth hormone only. Therapy may be continued until a satisfactory height has been attained or until little growth potential remains (bone age > 14 yr and growth velocity <2
cm/yr).
Off Label Use – Chronic Kidney Disease Anemia
MN_PS_ Androgens_Anabolic_Steroids _PA_QL_ProgSum_AR1019 Page 10 of 22
The National Kidney Foundation’s Kidney Disease Outcomes Quality Initiative (KDOQI) Clinical Practice Guidelines and Clinical Practice Recommendations for Anemia in Chronic Kidney
Disease have a strong recommendation against the use of androgens as adjuvant to erythropoiesis-stimulating agent (ESA) treatment in anemia patients with chronic kidney
disease.22 The current guideline has serious safety concerns and states evidence for androgens’ efficacy is low quality. Before the availability of epoetin therapy, androgens were
used regularly in the treatment of anemia in dialysis patients.
Off Label Use – Duchenne Muscular Dystrophy
The DMD (Duchenne muscular dystrophy) Care Considerations Working Group guidelines recommend glucocorticoids as first-line treatment for Duchenne muscular dystrophy.
Glucocorticoids are the only medication currently available that slow the decline in muscle strength and function in DMD, which in turn reduces the risk of scoliosis and stabilizes
pulmonary function. Oxandrolone is not considered necessary or appropriate, either with or without glucocorticoid therapy.23
Off Label Use – Vulvar Skin Disorder
The American Congress of Obstetricians and Gynecologists (ACOG) guidelines for vulvar skin
disorders recommend a high potency topical steroid such as clobetasol propionate for treatment of lichen sclerosus. Topical testosterone has shown inconsistent results in trials.24
The British Association of Dermatologists’ guidelines state that “there appears to be no evidence base for the use of topical testosterone” for treatment of female anogenital lichen
sclerosus.27 Testosterone propionate has been used for decreased libido and vulva atrophy/dystrophy; such indications are not FDA approved. The Endocrine Society
recommends against the generalized use of testosterone by women because the indications are inadequate and evidence of long-term studies is lacking.25
Off Label Use – Erectile Dysfunction The American Urology Association (AUA) recommends that phosphodiesterase type 5
inhibitors should be first-line therapy for erectile dysfunction. AUA also recommend that testosterone therapy is not indicated for the treatment of erectile dysfunction in patients with
a normal serum testosterone level. Also, the role of testosterone therapy in men with sexual dysfunction with low, borderline normal, and normal testosterone levels is not well defined.37
Off Label Use – Myeloproliferative Neoplasms
Management of myelofibrosis associated anemia includes epoetin or darbepoetin for
individuals with serum epoetin levels <500 mU/mL. Those with no response or loss of response should be managed as patients with serum epoetin ≥500 mU/mL.
Immunomodulatory agents (lenalidomide or thalidomide) with or without prednisone or danazol are recommended for the treatment of anemia in patients with serum epoetin levels
≥500 mU/mL.52
Off Label Use – Gender Identity Disorder / Gender Dysphoria / Gender Incongruence
The Endocrine Society states the following for the diagnosis and treatment of gender identity
• Recommend that a diagnosis be made by a mental health professional (MHP). For
children and adolescents, the MHP must also be training in child and adolescent developmental psychopathology
• Recommend all transsexual individuals should be informed and counseled regarding option for fertility preservation prior to initiating puberty suppression in
adolescents and prior to treating with hormonal therapy of the affirmed gender in both adolescents and adults
• For the treatment of adolescents
MN_PS_ Androgens_Anabolic_Steroids _PA_QL_ProgSum_AR1019 Page 11 of 22
▪ Mental health concerns, if present, must be reasonably well controlled
Generally, transdermal testosterone, parenteral testosterone, and oral testosterone
undecenoate can be used in (female to male) FTM transition. Other forms of testosterone (e.g. implantable and buccal) are also available.45,46
Safety
Androgens and anabolic steroids are associated with cardiomyopathy, increased low density
lipoprotein (LDL), decreased high density lipoprotein (HDL), hepatotoxicity (including hepatic neoplasms), hypertrophy of the prostate and anabolic-androgenic steroids-induced
hypogonadism.13 Testosterone treatment in men aged 65 years and older who have limitations in mobility was associated with an increased risk for cardiovascular events,
including myocardial infarction and hypertension, according to a study published by Basaria, et al.14 Anabolic steroids are mainly abused by males and athletes to increase muscle mass
and improve athletic performance.
On September 17, 2014, the FDA Bone, Reproductive and Urologic Drugs Advisory
Committee stated that the available studies informing the cardiovascular safety signal with testosterone therapy are limited in scope, quality, design, and size. Nonetheless, there was
agreement amongst committee members that a weak signal of cardiovascular risk had emerged from results of cardiovascular-related adverse events with testosterone use. The
committee agreed that additional studies on the risk of therapy are needed to assess cardiovascular and other risks associated with short term and long-term use of testosterone
for age-related hypogonadism.33
In an FDA safety communication [03-03-2015], FDA cautioned that the benefit and safety of
these medications 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. Testosterone product
manufacturers must clarify approved uses, and add information to labeling regarding possible increased risk of heart attacks and strokes in patients taking testosterone. Testosterone is
FDA-approved as replacement therapy only for men who have low testosterone levels due to disorders of the testicles, pituitary gland, or brain that cause a condition called
hypogonadism. Examples of these disorders include failure of the testicles to produce testosterone due to genetic problems, or damage from chemotherapy or infection. FDA has
become aware that testosterone is being used extensively in attempts to relieve symptoms in
men who have low testosterone for no apparent reason other than aging. The benefits and safety of this use have not been established.39
Prescribing information (2015) for testosterone products contains the following warnings:
Venous thromboembolism (VTE), including deep vein thrombosis (DVT) and pulmonary embolism (PE) have been reported in patients using testosterone products. Some post-
marketing studies have shown an increased risk of myocardial infarction and stroke associated with the use of testosterone replacement therapy. Safety and efficacy in men with
“age-related hypogonadism” have not been established. Safety and efficacy in males less
than 18 years old have not been established.
A retrospective cohort study (2015) compared cardiovascular safety of testosterone injections, patches, and gels. Adult male initiators (N=431,687) of new dosage formulations
of testosterone patches, gels, or injections following 180 days free of any testosterone use were followed for up to one year of use. Of the subjects followed, 36% used injection
products, 9% used patch products, and 55% used gel products. Testosterone injections were associated with a greater risk of CV events, hospitalizations, and deaths vs. gels. Patches and
gels had similar risk profiles. This study did not assess whether patients met criteria for use
MN_PS_ Androgens_Anabolic_Steroids _PA_QL_ProgSum_AR1019 Page 13 of 22
of testosterone and did not assess the safety of testosterone among users compared to non-users of the drug.41
On October 25th, 2016, the FDA approved a class wide labeling changes for all prescription
testosterone products, adding a new Warning and updating the Abuse and Dependence section to include new safety information from published literature and case reports regarding
the risks associated with abuse and dependence of testosterone and other Androgen, Anabolic Steroids (AAS). The new Warning will alert prescribers to the abuse potential of
testosterone and the serious adverse outcomes, especially those related to heart and mental
health that have been reported in association with testosterone/AAS abuse. In addition to the new Warning, all testosterone labeling has been revised to include information in the
Abuse and Dependence section about adverse outcomes reported in association with abuse and dependence of testosterone/AAS, and information in the Warning and Precautions section
advising prescribers of the importance of measuring serum testosterone concentration if abuse is suspected.44
For additional clinical information see Prime Therapeutics Formulary Chapter 4.2:
Androgens/Anabolic Steroids.
REFERENCES
1. Androderm prescribing information. Actavis Pharma, Inc. October 2016. 2. AndroGel 1% prescribing information. AbbVie Inc. February 2019.
3. AndroGel 1.62% prescribing information. AbbVie Inc. February 2019. 4. Axiron prescribing information. Lilly USA. July 2017.
5. Fortesta prescribing information. Endo Pharma, Inc. May 2019. 6. Striant prescribing information. Actient Pharmaceuticals LLC. October 2016.
7. Testim prescribing information. Auxilium Pharma, Inc. May 2019.
8. Oxandrin prescribing information. Savient Pharma, Inc. June 2005. 9. Anadrol-50 prescribing information. Unimed Pharma, Inc. October 2012.
10. testosterone enanthate prescribing information. Actavis Pharma, Inc. June 2015. 11. DailyMed. https://dailymed.nlm.nih.gov/dailymed/index.cfm. Accessed 8/9/2018.
12. Shalender B, Brito JP, Cunningham GR, et al. Testosterone therapy in men with hypogonadism: an endocrine society clinical practice guideline. The Journal of Clinical
Endocrinology & Metabolism, Volume 103, Issue 5, 1 May 2018, Pages 1715–1744. 13. Kanayama G, Hudson JI, Pope HG Jr. Illicit anabolic-androgenic steroid use. Horm
Behav. 2010 Jun;58(1):111-21.
14. Basaria S, Coviello AD, Travison T, et al. Adverse events associated with testosterone administration. N Engl J Med 2010;363(2):109-122.
15. Bondy CA, for the Turner Syndrome Consensus Study Group. Care of girls and women with Turner syndrome: a guideline of the Turner Syndrome Study Group. J Clin
Endocrinol Metab 2007;92:10-25. 16. Bhasin S, Storer TW, Asbel-Sethi N, et al. Effects of testosterone replacement with a
nongenital, transdermal system, Androderm, in human immunodeficiency virus-infected men with low testosterone levels. J Clin Endocrinol Metab. 1998
Sep;83(9):3155-62.
17. Grinspoon S, Corcoran C, Askari H, et al. Effects of androgen administration in men with the AIDS wasting syndrome: a randomized, double-blind, placebo-controlled trial.
Ann Intern Med 1998;129:18-26. 18. Grinspoon S, Corcoran C, Parlman K, et al. Effects of testosterone and progressive
resistance training in eugonadal men with AIDS wasting. Ann Intern Med 2000;133:348-355.
19. Berger JR, Pall L, Hall CD, et al. Oxandrolone in AIDS-wasting myopathy. AIDS 1996;10:1657-1662.
20. Fox-Wheeler S, Heller L, Salata CM, et al. Evaluation of the effects of oxandrolone on
21. Coodley GO, Coodley MK. A trial of testosterone therapy for HIV-associated weight loss. AIDS. 1997 Sep;11(11):1347-52.
22. National Kidney Foundation. KDOQI Clinical Practice Guidelines and Clinical Practice Recommendations for Anemia in Chronic Kidney Disease. Am J Kidney Dis. 2006 May;
47(5 Suppl 3):S11-145. 23. Bushby K, Finkel R, Birnkrant D, et al. for the DMD Care Considerations Working
Group. Diagnosis and management of Duchenne muscular dystrophy, part 1: diagnosis, and pharmacological and psychosocial management. Lancet Neurol. 2010
Jan;9(1):77-93.
24. American Congress of Obstetricians and Gynecologists (ACOG). ACOG Practice Bulletin No. 93: diagnosis and management of vulvar skin disorders. Obstet Gynecol. 2008
May;111(5):1243-53. Accessed October 2011. 25. Endocrine Society. Androgen Therapy in Women: An Endocrine Society Clinical
Practice Guideline. J Clin Endocrinol Metab. 2006 Oct;91(10):3697-710. Available at: http://www.endo-society.org/guidelines/final/upload/Androgens_in_Women_CG.pdf.
Accessed October 2011. 26. Depo-Testosterone prescribing information. Pharmacia and Upjohn Company LLC.
January 2017.
27. Neill SM, Lewis FM, Tatnall FM, Cox NH. British Association of Dermatologists’ guidelines for the management of lichen sclerosus 2010. Br J Dermatol.
2010;163:672-82. 28. Miller K, Corcoran C, Armstrong C, et al. Transdermal testosterone administration in
women with acquired immunodeficiency syndrome wasting: a pilot study. J Clin Endocrinol Metab. 1998;83:2712-2725
29. Dolan S, Wilkie S, Aliabadi N, et al. Effects of testosterone administration in human immunodeficiency virus-infected women with low weight. Arch Intern Med.
2004;164:897-904.
30. Aveed Prescribing Information. Endo Pharmaceutical Solutions Inc. January 2018. 31. Vogelxo prescribing information. Upsher-Smith Laboratories, Inc. May 2019.
32. Hereditary Angioedema guidelines 2012. Allergy 2012;67:147-157 33. Summary Minutes of Joint Meeting of the Bone, Reproductive and Urologic Drugs
Advisory Committee and the Drug Safety and Risk Management Advisory Committee. FDA Center for Drug Evaluation and Research. September 17, 2014.
34. Android Prescribing Information. Valeant Pharmaceuticals North America LLC. October 2016.
35. Methitest Prescribing Information. Global Pharmaceuticals, Division of Impax
Laboratories Inc. May 2019. 36. Testred Prescribing Information. Valeant Pharmaceuticals North America LLC. October
2016. 37. Management of Erectile Dysfunction (2005). American Urology Association.
http://www.auanet.org/education/guidelines/erectile-dysfunction.cfm. Accessed October 2014.
38. Natesto Gel prescribing information. Endo Pharmaceuticals Inc. October 2016. 39. FDA Drug Safety Communication: FDA cautions about using testosterone products for
low testosterone due to aging; requires labeling change to inform of possible increased
risk of heart attack and stroke with use March 2015. Accessed 6.10.2015 at: http://www.fda.gov/downloads/Drugs/DrugSafety/UCM436270.pdf
40. danazol prescribing information. Lannett Company, Inc. August 2017. 41. JAMA Intern Med. 2015;175(7): 1187–1196
42. Androgen Deficiency – AIDS/HIV. US Department of Veteran Affairs. Accessed 9/7/2016. http://www.hiv.va.gov/provider/manual-primary-care/androgen-
deficiency.asp.
43. Testopel prescribing information. Auxilium Pharmaceuticals, Inc. October 2016. 44. FDA approves new changes to testosterone labeling regarding the risks associated
with abuse and dependence of testosterone and other anabolic androgenic steroids
(AAS). US. Food and Drug Administration. Accessed 10/25/2016. http://www.fda.gov/Drugs/DrugSafety/ucm526206.htm?source=govdelivery&utm_me
dium=email&utm_source=govdelivery 45. Endocrine treatment of gender-dysphoric/gender-incongruent persons: an Endocrine
Society Clinical Practice Guideline. Journal of Clinical Endocrinology and Metabolism. November 2017, 102(11):3869-3903
46. Standards of care for the health of transsexual, transgender, and gender nonconforming people V7. The World Professional Association for Transgender Health.
2011.
47. Testosterone treatment of male hypogonadism. UptoDate. Current through: June 2018. Updated: June 20, 2018.
48. Deleted. 49. International WAO/EAACI guideline: HAE. 2017. Allergy December 2018: 1-22. DOI:
10.1111/all.13384. 50. Xyosted prescribing information. Antares Pharma, Inc. September 2018.
51. Jatenzo prescribing information. Clarus Therapeutics, Inc. March 2019. 52. Myeloproliferative Neoplasms. NCCN Clinical Practice Guidelines in Oncology. Version
2.2019 – October 29, 2018
ADDITIONAL INFORMATION
HIV Wasting Syndrome HIV/AIDs wasting was historically common, particularly in later stages of the disease. The
incidence of wasting has declined since the introduction of anti-retroviral therapy (ART). Tissue wasting responds rapidly to ART, and the primary therapy for HIV wasting is ART.1 The
diagnosis of HIV wasting requires one of the following:3,4 • Weight loss of greater than:
o 10% within 12 months or from baseline visit
o 7.5% within 6 months o 5% within 3 months
• At least 5% total body cell mass (BCM) loss within 6 months • Body mass index (BMI) <20 kg/m2
• In men: BCM <35% of total body weight and BMI <27 kg/m2 • In women: BCM <23% of total body weight and BMI <27 kg/m2
Normal Testosterone Values
The Endocrine Society states “The normative ranges for total and free testosterone levels in
healthy young men vary among laboratories and assays. In some laboratories, the lower limit of the normal range for total testosterone level in healthy young men is 280–300 ng/dL (9.8–
10.4 nmol/liter). Similarly, in some reference laboratories, the lower limit of the normal range for serum free testosterone level, measured by the equilibrium dialysis method, is 5–9 pg/mL
(0.17–0.31 nmol/liter). The clinicians should use the lower limit of normal range for healthy young men established in their laboratory.”2
ADDITIONAL INFORMATION REFERENCES
1. Palliative care: issues in HIV/AIDS in adults. UptoDate. Current through 7/2018. Last
updated 6/2017. 2. Shalender B, Cunningham GR, Hayes FJ, et al. Testosterone therapy in men with
androgen deficiency syndromes: an endocrine society clinical practice guideline. J Clin Endocrinol Metab 2011;95:2536-2559.
3. Pol Polsky B, Kotler D, Steinhart C. HIV-associated wasting in the HAART era: guidelines for assessment, diagnosis, and treatment. AIDS Patient Care STDS.
2001;15(8):411-423. 4. Mangili A, Murman DH, Zampini AM, Wanke CA. Nutrition and HIV infection: review of
weight loss and wasting in the era of highly active antiretroviral therapy from the
nutrition for healthy living cohort. Clin Infect Dis. 2006;42(6):836-842
STEP THERAPY SUPPLEMENT OBJECTIVE The intent of the Step Therapy Supplement is to provide additional questions, to ensure
compliance to MN Statute 62Q.184. These questions will apply if the step therapy component within a Prior Authorization or Step Therapy program is not able to be approved. CONDITIONS FOR APPROVAL The requested agent will be approved when ONE of the following are met:
1. The patient is currently being treated with the requested agent as indicated by ALL of the following:
a. A statement by the prescriber that the patient is currently taking the requested agent
AND b. A statement by the prescriber that the patient is currently receiving a positive
therapeutic outcome on requested agent AND
c. The prescriber states that a change in therapy is expected to be ineffective or cause harm
OR 2. The patient’s medication history include the required prerequisite/preferred agent(s) as
indicated by: a. Evidence of a paid claim(s) within the past 999 days
OR b. The prescriber has stated that the patient has tried the required
prerequisite/preferred agent(s) in the past 999 days AND the required
prerequisite/preferred agent(s) was discontinued due to lack of effectiveness or an adverse event
OR 3. The prescriber has provided documentation that the required prerequisite/preferred
agent(s) cannot be used due to a documented medical condition or comorbid condition that is likely to cause an adverse reaction, decrease ability of the patient to achieve or maintain reasonable functional ability in performing daily activities or cause physical or mental harm
Length of Approval: As per program specific criteria
This program applies to FlexRx Closed, FlexRx Open, GenRx Closed, GenRx Open, Health Insurance Marketplace, FocusRx and KeyRx formularies. Please note, this does not include or apply to quantity limit questions.