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Horizon BCBSNJ
Uniform Medical Policy ManualSection:Drugs
Policy Number:019
Effective Date: 08/21/2020
Original Policy Date:07/27/1993
Last Review Date:07/14/2020
Date Published to Web: 07/14/2006
Subject:
Gonadotropin-Releasing Hormone Analogs

Description:
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IMPORTANT NOTE:

The purpose of this policy is to provide general information applicable to the administration of health benefits that Horizon Blue Cross Blue Shield of New Jersey and Horizon Healthcare of New Jersey, Inc. (collectively “Horizon BCBSNJ”) insures or administers. If the member’s contract benefits differ from the medical policy, the contract prevails. Although a service, supply or procedure may be medically necessary, it may be subject to limitations and/or exclusions under a member’s benefit plan. If a service, supply or procedure is not covered and the member proceeds to obtain the service, supply or procedure, the member may be responsible for the cost. Decisions regarding treatment and treatment plans are the responsibility of the physician. This policy is not intended to direct the course of clinical care a physician provides to a member, and it does not replace a physician’s independent professional clinical judgment or duty to exercise special knowledge and skill in the treatment of Horizon BCBSNJ members. Horizon BCBSNJ is not responsible for, does not provide, and does not hold itself out as a provider of medical care. The physician remains responsible for the quality and type of health care services provided to a Horizon BCBSNJ member.

Horizon BCBSNJ medical policies do not constitute medical advice, authorization, certification, approval, explanation of benefits, offer of coverage, contract or guarantee of payment.
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Leuprolide acetate is a synthetic analog of naturally occurring gonadotropin- releasing hormone (GnRH or LH-RH). The analog possesses greater potency than the natural hormone. Leuprolide acetate is marketed as Lupron by TAP Pharmaceuticals, Inc., Eligard by Sanofi-Synthelabo, and Fensolvi by Tolmar Inc. in several preparations. Lupron injection contains 5 mg/mL of leuprolide acetate and is administered as single daily subcutaneous injection. Lupron Depot is available in 3.75, 7.5, 11.25, 22.5, and 30 mg formulations of leuprolide acetate for depot suspension. Lupron Depot-Ped is available in 7.5, 11.25, and 15 mg formulations for pediatric depot suspension. Lupaneta Pack is available in a 1-month or 3-month pack, which includes leuprolide acetate for depot suspension 11.25 mg syringes and norethindrone acetate 5 mg tablets. Eligard is available in 7.5, 22.5 and 30 mg strengths. The Lupron depot formulations and Eligard may be administered monthly or up to a 3-4 month interval depending on the strength or indication. Fensolvi subcutaneous injection contains 45 mg of leuoprolide acetate and is administered once every 6 months by a healthcare professional.

Leuprolide acetate implant is manufactured by ALZA Corp. Viadur®, a brand product of leuprolide acetate implant manufactured by Bayer Corp, was discontinued and taken off the market in 2007. Each implant contains 65 mg. of leuprolide free base. The implant is inserted subcutaneously in the inner aspect of the upper arm and provides continuous release of leuprolide for 12 months of hormonal therapy.

Goserelin is a synthetic analogue of gonadotropin-releasing hormone and has agonist activity. Use of continuous therapeutic doses results in prolonged suppression of pituitary gonadotropins and gonadal steroid production. Goserelin is injected as a subcutaneous implant. The 3.6 mg implant administered every 28 days is indicated for prostate cancer, endometriosis, breast cancer and endometrial thinning. The 10.8 mg implant administered every 12 weeks is only indicated in prostate cancer. Goserelin is marketed as Zoladex.

Histrelin is a synthetic gonadotropin-releasing hormone analog. The usual dose of Histrelin for Central Idiopathic Precocious Puberty is 10 mcg/kg/day subcutaneously, given as a single daily dose at the same time each day and this product was marketed as Supprelin. Histrelin is available as a subcutaneous implant and is marketed in the US as Vantas and Supprelin LA. The recommended dose of Vantas for palliative treatment of advanced prostate cancer is 50 mg of histrelin implant every 12 months.

Nafarelin is a synthetic analogue of luteinizing hormone-releasing hormone and has agonist activity. The usual dose of Naferelin base in the treatment of endometriosis is 200 mcg twice daily by intranasal spray; although some patients may require 800 mcg/day. For the treatment of central precocious puberty, the recommended daily dose of nafarelin is 1600 micrograms/day (mcg/day). Nafarelin is marketed as Synarel.

Triptorelin is a gonadotropin releasing hormone agonist. The usual dose for prostate carcinoma is 3.75 mg intramuscularly once monthly or 11.25 mg intramuscularly every 84 days. Triptorelin is marketed as Trelstar Depot (3.75 mg) and Trelstar LA (11.25 mg). The usual dose of triptorelin in the treatment of precocious puberty is 22.5 mg intramuscularly, given once every 24 weeks. Triptorelin for the treatment of precocious puberty is marketed as Triptodur.

Abarelix, which was marketed as Plenaxis, was withdrawn from the market in May 2005. For safety reasons, Plenaxis is approved with marketing restrictions. Only physicians who have enrolled in the Plenaxis PLUS Program (Plenaxis User Safety Program), based on their attestation of qualifications and acceptance of prescribing responsibilities, may prescribe Plenaxis.

Policy:
(NOTE: For Medicare Advantage, please refer to the Medicare Coverage Section below for coverage guidance.)

(NOTE: For Gonadotropin Releasing Hormone (GnRH) use in Gender Dysphoria, please refer to policy 141 Drug Therapy for Transgender Policy.)

I. The prescriber is a specialist in the area of the patient’s diagnosis (e.g. endocrinologist, oncologist, etc.) and is the treating physician.

II. Gonadotropin Releasing Hormone analogs are considered medically necessary when used for one of the following indications below and are subject to their corresponding guidelines based on FDA approved package inserts:
    A. Palliative treatment of advanced prostatic cancer as an alternative treatment when orchiectomy or estrogen administration is either not indicated or unacceptable to the member. (Lupron, Eligard, Trelstar Depot, Zoladex, Vantas) Zoladex 10.8 mg is also appropriate for use in combination with radiotherapy and flutamide for the management of locally confined T2b to T4 (Stage B2 to C) carcinoma of the prostate. Treatment with Zoladex and flutamide should start 8 weeks prior to initiating radiation therapy and continue during radiation therapy.
      • Initial and continuation approval for 12 months
    B. Management of endometriosis, including pain relief and reduction of endometriotic lesions, subject to the following guidelines: (Lupron, Lupaneta Pack, Zoladex 3.6 mg, and Synarel only)
      • member is not pregnant, not breast feeding,or does not have an undiagnosed abnormal vaginal bleeding
      • member is at least 18 years of age
      • member has tried and failed non-steroidal anti-inflammatory drugs (NSAIDs)
      • approval for 6 months of therapy
      • member consideration for second or later episode of treatment
        [INFORMATIONAL NOTE: Retreatment with Lupron or Lupaneta Pack for 6 months may be considered if the endometriosis symptoms reoccur after 6 month course of therapy. Lupron is not recommended monotherapy and is only considered for retreatment in combination with norethindrone. Retreatment beyond this second 6 month of therapy is not recommended.]
    C. Preoperative hematologic improvement of members with anemia caused by uterine leiomyomata (fibroids), subject to the following guidelines: (Lupron only)
      • member is not pregnant, not breast feeding, or does not have an undiagnosed abnormal vaginal bleeding
      • member is at least 18 years of age
      • member has not previously had surgery
        [INFORMATIONAL NOTE: It is recommended that clinicians consider a one-month trial period on iron alone inasmuch as some of the patients will respond to iron alone, and if the response to iron alone is considered inadequate, Lupron may be added.
        Long term treatment of uterine fibroids with Lupron is not medically necessary. If severe uterine bleeding is present and surgery is planned, treatment is medically necessary for short term therapy prior to surgery.]
      • approval up to 3 months of therapy
[INFORMATIONAL NOTE: If the symptoms associated with uterine leiomyomata recur following discontinuation of therapy, an additional retreatment may be considered, however, bone density should be assessed prior to initiation of therapy to ensure values are within normal limits]

    D. Treatment of children with precocious puberty (sexual maturation before age 8 in girls and age 9 in boys), subject to the following guidelines: (Lupron-Ped, Synarel, Triptodur, Supprelin LA, and Fensolvi)
      • for true or central precocious puberty only
        [INFORMATIONAL NOTE: Clinical diagnosis should be confirmed prior to initiation of therapy by a pubertal response to a GnRH stimulation test and bone age advanced one year beyond the chronological age.]
      • tumor has been ruled out by appropriate diagnostic procedure(s)
      • treatment will be approved for 12 months until puberty is desired. (Discontinuation of leuprolide therapy should be considered before age 11 in girls and 12 in boys.)
    E. Palliative treatment of advanced breast cancer in premenopausal and perimenopausal women. (Zoladex 3.6 mg only)
      · For the management of advanced breast cancer, Zoldadex is intended for long-term administration unless clinically inappropriate
      • Initial and continued approval for 12 months
      [INFORMATIONAL NOTE: Estrogen and progesterone receptor values may help predict whether Zoladex therapy is likely to be beneficial. The 10.8 mg Zoladex implant should not be used for this indication because it has not been shown to suppress serum estradiol reliably.]
    F. Endometrial thinning agent prior to endometrial ablation, subject to the following guidelines: (Zoladex 3.6 mg only)
      • member is not pregnant , not breast feeding, or does not have an undiagnosed abnormal vaginal bleeding
      • member is at least 18 years of age
        [INFORMATIONAL NOTE: As per the FDA prescribing information, for use as an endometrial-thinning agent prior to endometrial ablation, the dosing recommendation is one or two depots (with each depot given four weeks apart).]
      • Approval for 2 months of therapy
[INFORMATIONAL NOTE: Based on the FDA approved package insert, below notes the dosage strenght and frequency for specific dosage formulations

DrugDose Frequency
Eligard7.5 mg1 month
22.5 mg3 months
30 mg4 months
45 mg6 months
Lupron 3.75 mg1 Month
7.5 mg1 Month
11.25 mg3 Months
22.5 mg3 Months
30 mg4 Months
45 mg6 Months
Lupron Ped7.5 mg 1 month
11.25 mg1 month or 3 months
15 mg1 month
30 mg3 months
Lupaneta Pack3.75 mg1 month
11.25 mg3 months
Trelstar Depot3.75 mg1 month
11.25 mg3 months
22.5 mg6 months
Zoladex3.6 mg1 month
10.8 mg3 months
Vantas50 mg12 months
Supprelin LA50 mg12 months
Fensolvi 45 mg 6 months
Triptodur3.75 mg1 month
11.25 mg3 months
22.5 mg6 months

III. Medically necessary "off-label" uses include the following, if ALL of the criteria below are met:

    A. In the palliative treatment of advanced breast carcinoma in premenopausal and perimenopausal women. ( Lupron) (Zoladex 3.6 mg has an FDA approval for this indication.)
    B. Endometrial Ablation (for dysfunctional uterine bleeding) (Lupron, and Synarel)
      • member is not pregnant, not breast feeding, or does not have an undiagnosed abnormal vaginal bleeding
      • member is at least 18 years of age
    C. Controlled ovarian hyperstimulation during the embryo transfer procedure in in-vitro fertilization. (Lupron 5 mg/ml injection only)
      [INFORMATIONAL NOTE: Coverage for leuprolide acetate (Lupron) used in conjunction with Assisted Reproductive Technology (ART) procedures (e.g., IVF, GIFT, ZIFT, etc.) is subject to applicable contractual limitations and exclusions pertaining to ART under the insured’s contract.]
    D. Used in combination with adjuvant therapy (radiotherapy and/or chemotherapy) in premenopausal or perimenopausal women with operable, early breast cancer. (Zoladex only)
    E. Ovarian cancer (Lupron Depot 3.75 mg, 11.25 mg only)
    Epithelial Ovarian Cancer/Fallopian Tube Cancer/Primary Peritoneal Cancer
      • Hormonal therapy as a single agent for persistent disease or recurrence
    F. Prostate Cancer; Adenocarcinoma (Lupron, Zoladex , Trelstar, Eligard and Vantas)
      • Androgen deprivation therapy (ADT) as a single agent if life expectancy ≤5 years and asymptomatic in selected patients with high- or very high-risk disease where complications such as hydronephrosis or metastasis can be expected within 5 years or in patients with regional or metastatic disease
      • Adjuvant androgen deprivation therapy (ADT) as a single agent with or without external beam radiation therapy (EBRT) if lymph node metastasis found during pelvic lymph node dissection (PLND) for patients in the very low risk group and ≥20 year expected survival or for patients in the low or intermediate risk groups and ≥10 year expected survival or for patients in the high or very high risk groups and >5 year expected survival
      • Androgen deprivation therapy (ADT) as a single agent or in combination with first-generation antiandrogen if life expectancy ≤5 years and asymptomatic
        • in selected patients with high or very high risk disease where complications such as hydronephrosis or metastasis can be expected within 5 years
        • in patients with regional risk disease
      • Initial androgen deprivation therapy (ADT) as a single agent or in combination with a first-generation antiandrogen if life expectancy >5 years or symptomatic
        • for 4 months in combination with external beam radiation therapy (EBRT) with or without brachytherapy for patients in the unfavorable intermediate risk group
        • for 1.5-3 years in combination with EBRT for patients in the high or very high risk group
        • for 2-3 years in combination with EBRT followed by docetaxel and concurrent steroid after completion of radiation in selected patients in the high or very high risk group who are fit for chemotherapy
        • for 1-3 years in combination with EBRT and brachytherapy for patients in the high or very high risk group
        • for patients in the regional risk group
      • Initial androgen deprivation therapy (ADT) as a single agent with or without abiraterone and prednisone for patients in the regional risk group if life expectancy >5 years or symptomatic
      • Single-agent treatment for patients who progressed on observation of localized disease
      • Used for M0 or M1 castration-resistant disease as androgen deprivation therapy (ADT) to maintain castrate serum levels of testosterone (<50 ng/dL)
      • Used for castration-naive disease
          • as a single agent* (First-generation antiandrogen must be given for ≥7 days to prevent testosterone flare if metastases are present in weight-bearing bone) for M0 or M1 disease
          • in combination with a first-generation antiandrogen for M0 or M1 disease
          • in combination with docetaxel and concurrent steroid with or without a first-generation antiandrogen for M1 disease
          • in combination with abiraterone and prednisone for M1 disease
          • in combination with either apalutamide or enzalutamide for M1 disease
          • as a single agent or in combination with a first-generation antiandrogen and external beam radiation therapy (EBRT) to the primary tumor for low volume M1 disease
      • Androgen deprivation therapy (ADT) as a single agent or in combination with a first-generation antiandrogen for M0 PSA persistence/recurrence
          • after radical prostatectomy in combination with external beam radiation therapy (EBRT) if studies negative for distant metastatic disease
          • or positive digital rectal examination (DRE) after EBRT if biopsy negative and studies negative for distant metastatic disease
          • or positive DRE after EBRT in patients who are not candidates for local therapy (especially if bone scan positive)
      • Adjuvant androgen deprivation therapy (ADT) as a single agent or in combination with a first-generation antiandrogen for 6 months with external beam radiation therapy (EBRT) if adverse features (i.e. positive margins, seminal vesicle invasion, extracapsular extension, or detectable PSA) noted after radical prostatectomy (RP)
          • in the very low risk group and ≥20 year expected survival
          • in the low risk group and ≥10 year expected survival
          • with or without pelvic lymph node dissection (PLND) in the favorable or unfavorable intermediate risk group and ≥10 year expected survival
          • with or without PLND in the high risk group and >5 year expected survival or symptomatic
    G. Invasive Breast Cancer: Treatment of premenopausal women* (men with breast cancer should be treated similarly to postmenopausal women, except that use of an aromatase inhibitor is ineffective without concomitant supprression of testicular steroidogenesis) with hormone receptor-positive disease in combination with adjuvant endocrine therapy or endocrine therapy for recurrent or stage IV (M1) disease (Lupron, Zoladex)
    H. Head and Neck Cancers - Salivary Gland Tumors: Treatment for androgen receptor positive recurrent disease with distant metastases in patients with a performance status (PS) of 0-3 (Eligard, Lupron Depot 7.5 mg 1 month, Lupron Depot 22.5 mg 3 month)

IV. Gonadotropin-releasing hormone agonists are considered investigational for all other indications, including but not limited to, the treatment of premenstrual syndrome, polycystic ovarian syndrome (PCOS), ovarian suppression for fertility preservation during chemotherapy, ACTH-dependent Cushing’s syndrome, inducing amenorrhea, obesity, benign prostatic hyperplasia (BPH), and autoimmune progesterone dermatitis.

Medicare Coverage

There is no National Coverage Determination (NCD). In the absence of an NCD, coverage decisions are left to the discretion of Local Medicare Carriers. Please refer to Novitas Solutions Inc, LCD Luteinizing Hormone-Releasing Hormone (LHRH) Analogs (L34822) for eligibility and coverage. Available at: https://www.cms.gov/medicare-coverage-database/details/lcd-details.aspx?LCDId=34822&ContrId=323&ver=8&ContrVer=1&Date=10%2f05%2f2015&DocID=L34822&bc=iAAAAAgAAAAAAA%3d%3d&

Per Local Coverage Article A53127 Self-Administered Drug Exclusion List, Medicare covers drugs that are furnished “incident to” a physician’s service provided that the drugs are medically reasonable and necessary, approved by the Food and Drug Administration (FDA) and are not usually administered by the patients who take them. Therefore, Medicare Advantage Products will cover Gonadotropin Releasing Hormone analogs subcutaneous when administered by a licensed medical provider as part of a physician service when LCD L34822 policy criteria is met.

Local Coverage Article:Self-Administered Drug Exclusion List: (A53127). Available to be accessed at Novitas Solutions, Inc., Medical Policy Search page: https://www.novitas-solutions.com/webcenter/portal/MedicareJL/pagebyid?contentId=00024370.

Medicaid Coverage

For Horizon NJ Health members, please follow this link for the corresponding HNJH drug policy https://services3.horizon-bcbsnj.com/ddn/NJhealthWeb.nsf

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Horizon BCBSNJ Medical Policy Development Process:

This Horizon BCBSNJ Medical Policy (the “Medical Policy”) has been developed by Horizon BCBSNJ’s Medical Policy Committee (the “Committee”) consistent with generally accepted standards of medical practice, and reflects Horizon BCBSNJ’s view of the subject health care services, supplies or procedures, and in what circumstances they are deemed to be medically necessary or experimental/ investigational in nature. This Medical Policy also considers whether and to what degree the subject health care services, supplies or procedures are clinically appropriate, in terms of type, frequency, extent, site and duration and if they are considered effective for the illnesses, injuries or diseases discussed. Where relevant, this Medical Policy considers whether the subject health care services, supplies or procedures are being requested primarily for the convenience of the covered person or the health care provider. It may also consider whether the services, supplies or procedures are more costly than an alternative service or sequence of services, supplies or procedures that are at least as likely to produce equivalent therapeutic or diagnostic results as to the diagnosis or treatment of the relevant illness, injury or disease. In reaching its conclusion regarding what it considers to be the generally accepted standards of medical practice, the Committee reviews and considers the following: all credible scientific evidence published in peer-reviewed medical literature generally recognized by the relevant medical community, physician and health care provider specialty society recommendations, the views of physicians and health care providers practicing in relevant clinical areas (including, but not limited to, the prevailing opinion within the appropriate specialty) and any other relevant factor as determined by applicable State and Federal laws and regulations.

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Index:
Gonadotropin-Releasing Hormone Analogs
Eligard (Leuprolide Acetate)
Goserelin (Zoladex)
Histrelin (Supprelin or Vantas)
Leuprolide Acetate (Lupron, Lupron Depot, Viadur, Fensolvi)
Lupron (Leuprolide Acetate)
Lupron Depot (Leuprolide Acetate)
Nafarelin (Synarel)
Supprelin (Histrelin)
Synarel (Nafarelin)
Trelstar Depot (Triptorelin)
Triptorelin (Trelstar Depot)
Vantas (Histrelin)
Viadur (Leuprolide Acetate)
Zoladex (Goserelin)
Fensolvi (Leuprolide Acetate)

References:

1. 2004 Physicians' Desk Reference. 58th Edition. Medical Economics Publishing Company.

2. 1998 Physicians' Desk Reference Generics. 4th Edition. Medical Economics Publishing Company.

3. Zelefsky MJ, Harrison A. Neoadjuvant androgen ablation prior to radiotherapy for prostate cancer: reducing the potential morbidity of therapy. Urology. March 1997;49(3A Suppl):38-45.

4. Forman JD, Kumar R, Haas G, et al. Neoadjuvant hormonal downsizing of localized carcinoma of the prostate: effects on the volume of normal tissue irradiation. Cancer Invest. 1995;13(1):8-15.

5. Fowler Jr JE, Gottesman JE, Freidric Reid C, et al. Safety and efficacy of an implantable leuprolide delivery system in patients with advanced prostate cancer. Journal of Urology. 2000 September;64(3):730-734.

6. Fowler Jr JE, Flanagan M, Gleason DM, et al. Evaluation of an implant that delivers leuprolide for 1 year for the palliative treatment of prostate cancer. Urology. 2000;55(5):639-642.

7. Oncology Drugs in Drug Evaluations Subscription, AMA, 1991 Spring, Vol 3;5:11.

8. Dowsett M, et al. Clinical and endocrine effects of leuprolide acetate in pre- and postmenopausal patients with advanced breast cancer. Clinical Therapeutics 1992;14(Suppl A):97-103.

9. Savino L, et al. GnRH analogs in gynecological oncology: a review. J Chemother 1992 Oct;4(5):312-320.

10. Hamm JT, et al. New hormonal approaches to the treatment of breast cancer. Crit Rev Oncol Hematol 1991;11(1):29-41.

11. Dowsett M, et al. A dose-comparative endocrine-critical study of leuprorelin in premenopausal breast cancer patients. Br J Cancer 1990;62(5):834-837.

12. Crighton IL, et al. Use of luteinising hormone-releasing hormone agonist (leuprorelin) in advanced post-menopausal breast cancer: clinical and endocrine effects. Br J Cancer 1989 Oct;60(4):644-648.

13. Harvey HA, et al. Medical castration produced by the GnRH analogue leuprolide to treat metastatic breast cancer. J Clinical Oncology 1985 Aug;3(8):1068-1072.

14. Boccardo F, Rubagotti A, Amoroso D, et al. Endocrinological and clinical evaluation of two depot formulations of leuprolide acetate in pre- and postmenopausal breast cancer patients. Cancer Chemother Pharmacol 1999;43(6):461-466.

15. Gazet JC, Coombes RC, Ford HT, et al. Assessment of the effect of pretreatment with neoadjuvant therapy on primary breast cancer. Br J Cancer 1996 Mar;73(6):758-762.

16. Shamonki MI, Ziegler WF, Badger GJ, et al. Prediction of endometrial ablation success according to perioperative findings. Am J Obstet Gynecol 2000 May;182(5):1005-1007.

17. Nathanson HG, Phillips DR, Milim SJ, et al. Relationship of endometrial thickness with the menstrual timing of leuprolide acetate administration for preoperative preparation for hysteroscopic surgery. J Am Assoc Gynecol Laparosc 1997 Feb;4(2):191-194.

18. Shwayder JM. Effect of a Single 3.75-mg Dose of Leuprolide Acetate for Preoperative Suppression before Endometrial Ablation. J Am Assoc Gynecol Laparosc 1996 Aug;3(4, Supplement):S46.

19. Thurman SA et al. Radiation therapy for the treatment of locally advanced and metastatic prostate cancer. Hematol Oncol Clin North Am 2001;15(3):423-43.

20. Seidenfeld J et al. Single therapy androgen suppression in men with advanced prostate cancer: a systematic review and meta-analysis. Ann Intern Med 2000;132(7):566-77.

21. Lapp T. ACOG Issues Recommendations for the Management of Endometriosis. Am Fam Physician 2000 62(6):1431, 1434.

22. Waller KG, Shaw RW. Gonadotropin-releasing hormone analogues for the treatment of endometriosis: long-term follow-up. Fertil Steril 1993;59:511-515.

23. Leather AT et al. The treatment of severe premenstrual syndrome with goserelin with and without 'add-back' estrogen therapy: a placebo-controlled study. Gynecol Endocrinol 1999;13(1):48-55.

24. Sundstom I et al. Treatment of premenstrual syndrome with gonadotropin-releasing hormone agonist in a low dose regimen. Acta Obstet Gynecol Scand 1999;78(10):891-9.

25. Schmidt PJ et al. Differential behavioral effects of gonadal steroids in women with and in those without premenstrual syndrome. N Eng J Med 1998;338(4):209-16.

26. Kessel B. Premenstrual syndrome. Advances in diagnosis and treatment. Obstet Gynecol Clin North Am 2000;27(3):625-39.

27. Benagiano G et al. Zoladex (goserelin acetate) and the anemic patient: results of a multicenter fibroid study. Fertil Steril 1996;66(2):223-9.

28. Stoval TG et al. A randomized trial evaluating leuprolide acetate before hysterectomy as treatment for leiomyomas. Am J Obstet Gynecol 1991;164(6 Pt 1):1420-3 discussion 1423-5.

29. Perino A et al. Role of leuprolide acetate depot in hysteroscopic surgery: a controlled study. Fertil Steril 1993;59(3):507-10.

30. Pilepich MV et al. Androgen deprivation with radiation therapy locally advanced prostatic carcinoma: a randomized comparative trial of the Radiation Oncology Group. Urology 1995;45:616-23.

31. Sowter MC. Pre-operative endometrial thinning agents before hysteroscopic surgery for heavy menstrual bleeding. Cochrane Database Syst Rev 2000;(2):CD001124.

32. Synarel® package insert. GD Searle LLC Division of Pfizer Inc, December 2017.

33. Blamey RW, Jonat W, Kaufmann M, et al: Goserelin depot in the treatment of premenopausal advanced breast cancer. Eur J Cancer 1992;810-814.

34. Bajetta E, Zilembo N, Buzzoni R, et al: Goserelin in premenopausal advanced breast cancer: Clinical and endocrine evaluation of responsive patients. Oncology 1994;51:262-269.

35. Brambilla C, Escobedo A, Artioli R, et al: Treatment of pre-menopausal advanced breast cancer with goserelin--A long-acting luteinizing hormone releasing hormone agonist. Anticancer Drugs 1992;3:3-8.

36. Kaufmann M, Jonat W, Schachner-Wunschmann E, et al: The depot GnRH analogue goserelin in the treatment of premenopausal patients with metastatic breast cancer--A 5-year experience and further endocrine therapies. Cooperative German Zoladex Study Group. Onkologie 1991;14:22-24, 26-28, 30.

37. Gazet JC et al: Assessment of the effect of pretreatment with neoadjuvant therapy on primary breast cancer. Br J Cancer 1996;73(6):758-62.

38. Harvey HA et al: Medical castration produced by the GnRH analogue leuprolide to treat metastatic breast cancer. J Clin Oncol 1985;3(3): 1068-72.

39. Taylor CW, Green S, Dalton WS, et al: Multicenter randomized clinical trial of goserelin versus surgical ovariectomy in premenopausal patients with receptor-positive metastatic breast cancer: An Intergroup Study. J Clin Oncol 1998;16:994-9.

40. Vantas package insert. Valera Pharmaceuticals. November 2019.

41. Plenaxis package insert. Praecis Pharmaceutics. November 2003.

42. Sowter MC, Lethaby A, Singla AA. Pre-operative endometrial thinning agents before endometrial destruction for heavy menstrual bleeding. Cochrane Database Sys Rev 2002;(3):CD001124.

43. Gimpelson RJ, Kaigh J. Mechanical preparation of the endometrium prior to endometrial ablation. J Reprod Med 1992 Aug;37(8):691-694.

44. Roche H, Kerbrat P, Bonneterre J, et al. Complete hormonal blockade versus epirubicin-based chemotherapy in premenopausal, one to three node-positive, and hormone-receptor positive, early breast cancer patients: 7-year follow-up results of French Adjuvant Study Group 06 randomised trial. Annals of Oncology 2006;17:1221-1227.

45. Baum M, Hackshaw A, Houghton J, et al. Adjuvant goserelin in pre-menopausal patients with early breast cancer: Results from the ZIPP study. European Journal of Cancer 2006;42:895-904.

46. Supprelin LA package insert. Indevus Pharmaceuticals. November 2019.

47. Geller J, et al. Therapeutic controversies: clinical treatment of benign prostatic hyperplasia. J Clin Endocrinol Metab 1995 Mar;80(3):745-7.

48. Samraj GP, Kuritzky L, et al. Polycystic Ovary Syndrome [PCOS]: Comprehensive Management In Primary Care. Comprehensive Therapy 2007 Apr 28(3):208-221.

49. DrugLib.com. Plenaxis® (Abarelix) – Indications and Dosage. August 2004. [Available at: http://www.druglib.com/druginfo/plenaxis/indications_dosage/]. Accessed June 3, 2009.

50. Schrlock ED. GnRH agonists. Clin Obstet Gynecol 1989;32(3):550-563.

51. Macdonald R. Modern treatment of menorrhagia. Br J Obstet Gynecol 1990;97:3-7.

52. Beneventi F, Persiani P, Feloni G, et al. Combined use of goserelin acetate and human menopausal gonadotropin in the induction of follicular growth in a program of fertilization in vitro and embryo transfer. Minerva Ginecol 1994 Dec. 46(12):645-50.

53. Vlaisavljevic V, Reljic M, Lovrec VG, et al. Comparable effectiveness using flexible single-dose GnRH antagonist (cetrorelix) and single-dose long GnRH agonist (goserelin) protocol for IVF cycles - a prospective, randomized study. Reprod Biomed Online 2003 Oct. 7(3):301-8.

54. Tapanainen J, Hovatta O, Juntunen K, et al. Subcutaneous goserelin versus intranasal buserelin for pituitary down-regulation in patients undergoing IVF: a randomized comparative study. Hum Reprod 1993 Dec. 8(12):2052-5.

55. Simons AH, Roelofs HJ, Roozenberg BJ, et al. Early cessation of triptorelin in in-vitro fertilization: a double-blind, randomized study. Fertil Steril 2005 Apr. 83(4):889-96.

56. Fenichel P, Grimaldi M, Olivero JF, et al. Systematic inhibition of the luteinizing hormone with a gonadoliberin analog, triptorelin, during ovarian stimulation for fertilization in vitro. Choice of protocol. Presse Med 1988 Apr. 17(15):719-22.

57. Zhu WJ, Li XM, Chen XM, et al. Effect of low-dose triptorelin on pituitary down-regulation for patients undergoing in vitro fertilization and embryo transfer. Zhong Hua Nan Ke Xue 2003 Aug.9(5):367-9.

58. Janssens RMJ, Lambalk CB, Vermeiden JPW, et al. Dose-finding study of triptorelin acetate for prevention of a premature LH surge in IVF: a prospective, randomized, double- blind, placebo-controlled study. Hum Reprod 2000; 15(11):2333-2340.

59. Martinez-Aguayo A, Hernandez MI, Beas F, et al. Treatment of central precocious puberty with triptorelin 11.25 mg depot formulation. J Pediatr Endocrinol Metab 2006 Aug;19(8):963-70.

60. Carel JC, Blumberg J, Seymour C, et al. Three-month sustained-release triptorelin (11.25 mg) in the treatment of central precocious puberty. Eur J Endocrinol 2006 Jan;154(1):119-24.

61. Messaaoui A, Massa G, Tenoutasse S, et al. Treatment of central precocious puberty with Gonadotropin-Releasing Hormone agonist (triptorelin) in girls: breast development, skeletal maturation, height and weight evolution during and after treatment. Rev Med Brux 2005 Feb;26(1):27-32.

62. Bajpai A, Sharma J, Kabra M, et al. Long-acting GnRH analogue triptorelin therapy in central isosexual precocious puberty. Indian Pediatr 2002 Jul;39(7):633-9.

63. Boucekkine C, Blumberg-Tick J, Roger M, et al. Treatment of central precocious puberty with sustained-release triptorelin. Arch Pediatr 1994 Dec;1(12):1127-37.

64. MICROMEDEX® Healthcare Series - DRUGDEX® Evaluations: Non-FDA Labeled Indications. Triptorelin – In Vitro Fertilization. March 27, 2009. [Available at: http://www.thomsonhc.com/hcs/librarian/ND_T/HCS/ND_PR/Main/CS/178424/DUPLICATIONSHIELDSYNC/C0CA75/ND_PG/PRIH/ND_B/HCS/SBK/2/ND_P/Main/PFPUI/zR129UG31fkFUT/PFActionId/hcs.common.RetrieveDocumentCommon/DocId/1537/ContentSetId/31#therapeuticUsesSection]. Accessed June 6, 2009.

65. MICROMEDEX® Healthcare Series - DRUGDEX® Evaluations: Non-FDA Labeled Indications. Goserelin – In Vitro Fertilization. March 27, 2009. [Available at: http://www.thomsonhc.com/hcs/librarian/ND_T/HCS/ND_PR/Main/CS/178424/DUPLICATIONSHIELDSYNC/C0CA75/ND_PG/PRIH/ND_B/HCS/SBK/4/ND_P/Main/PFPUI/zR129UG31fuph5/PFActionId/hcs.common.RetrieveDocumentCommon/DocId/2351/ContentSetId/31#therapeuticUsesSection]. Accessed June 7, 2009.

66. MICROMEDEX® Healthcare Series - DRUGDEX® Evaluations: Non-FDA Labeled Indications. Triptorelin – Central Precocious Puberty. March 27, 2009. [Available at: http://www.thomsonhc.com/hcs/librarian/ND_T/HCS/ND_PR/Main/CS/178424/DUPLICATIONSHIELDSYNC/C0CA75/ND_PG/PRIH/ND_B/HCS/SBK/2/ND_P/Main/PFPUI/zR129UG31fkFUT/PFActionId/hcs.common.RetrieveDocumentCommon/DocId/1537/ContentSetId/31#therapeuticUsesSection]. Accessed June 9, 2009.

67. Plenaxis™ (Abarelix) Drug Information: Uses, Side Effects, Drug Interactions, and Warnings. March 2008. [Available at: http://www.rxlist.com/plenaxis-drug.htm]. Accessed 6/6/09.

68. Mayo Clinic. Abarelix Drug Information. June 1, 2009. [Available at: http://www.mayoclinic.com/health/drug-information/DR600007]. Accessed June 12, 2009.

69. Abbvie Inc. Lupron Depot (leuprolide acetate for depot suspension). North Chicago, IL. April 2018.

70. AstraZeneca. Zoladex (goserelin acetate). Wilmington, DE. February 2019.

71. Trelstar Depot and LA (triptorelin pamoate for injectable suspension) [Prescribing Information]. Watson Pharmaceuticals. Parsippany, NJ. December 2018.

72. AHFS Drug Information. Gonadotropins. American Society of Health-Systems Pharmacists. 68(18):3185. 2009.

73. MICROMEDEX® Healthcare Series - DRUGDEX® Evaluations: Non-FDA Labeled Indications. Triptorelin – ACTH dependent Cushing’s syndrome. [Available at: http://www.thomsonhc.com/hcs/librarian/ND_T/HCS/ND_PR/Main/CS/DC8629/DUPLICATIONSHIELDSYNC/77D26E/ND_PG/PRIH/ND_B/HCS/SBK/2/ND_P/Main/PFActionId/hcs.common.RetrieveDocumentCommon/DocId/2424/ContentSetId/31#secN12F33]. Accessed Feb 15, 2011.

74. MICROMEDEX® Healthcare Series - DRUGDEX® Evaluations: Non-FDA Labeled Indications. Triptorelin – Amenorrhea induction [Available at: http://www.thomsonhc.com/hcs/librarian/ND_T/HCS/ND_PR/Main/CS/DC8629/DUPLICATIONSHIELDSYNC/77D26E/ND_PG/PRIH/ND_B/HCS/SBK/2/ND_P/Main/PFActionId/hcs.common.RetrieveDocumentCommon/DocId/2424/ContentSetId/31#secN12F33]. Accessed March 31, 2014

75. Somers EC, Marder W, Christman GM, et al. Use of a Gonadotropin-Releasing Hormone Analog for Protection Against Premature Ovarian Failure During Cyclophosphamide Therapy in Women With Severe Lupus. Arthritis & Rheumatism 2005 Sep;52(9):2761-2767.

76. American Society for Reproductive Medicine. Etthics Committee Report: Fertility preservation and reproduction in cancer patients. Fertility and Sterility 2005 Jun;83(6):1622-1628.

77. Snyder KA, Pearse W. Discussing Fertility Preservation Optons With Patients With Cancer. JAMA 2011 Jul;306(2):202-203.

78. Eligard (leuprolide acetate) [prescribing information]. Sanofi-Aventis U.S. LLC. Bridgewater, NJ, 08807. April 2019.

79. Lupaneta Pack (leuprolide acetate for depot suspension; norethindrone acetate tablets) [prescribing information]. AbbVie Inc. North Chicago, IL. June 2015.

80. National Comprehensive Cancer Network (NCCN) Drugs and Biologics Compendium. 2017. Available at: http://www.nccn.org/professionals/drug_compendium/MatrixGenerator/Matrix.aspx?AID=387. Accessed September, 4 2018.

81. Gold Standard, Inc. Goserelin. Clinical Pharmacology [database online]. Available at: http://www.clinicalpharmacology.com. Accessed: March 10, 2015.

82. Gold Standard, Inc. Nafarelin. Clinical Pharmacology [database online]. Available at: http://www.clinicalpharmacology.com. Accessed: March 10, 2015.

83. Gold Standard, Inc. Leuprolide. Clinical Pharmacology [database online]. Available at: http://www.clinicalpharmacology.com. Accessed: March 10, 2015.

84. Gerald K. McEvoy, Pharm.D., ed. 2015. AHFS Drug Information® 56th Ed. Bethesda, MD. American Society of Health-System Pharmacists. ISBN-10: 1-58528-380-0, ISBN-13: 978-1-58528-380-4. STAT!Ref Online Electronic Medical Library. http://online.statref.com/Document.aspx?fxId=1&docId=305. 3/11/2015

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86. American Family Physician. ACOG Updates Guidelines on Diagnosis and Treatment of Endometriosis. 2011 Jan 1;83(1):84-85.

87. Triptodur® package insert. Arbor Pharmaceuticals, Atlanta GA. Last updated: October 2018.

88. National Comprehensive Cancer Network (NCCN) Drugs and Biologics Compendium. Zoladex . Available at: https://www.nccn.org/professionals/drug_compendium/content/ Accessed March 2, 2020

89. National Comprehensive Cancer Network (NCCN) Drugs and Biologics Compendium. Trelstar. Available at: https://www.nccn.org/professionals/drug_compendium/content/ . Accessed March 2, 2020

90. National Comprehensive Cancer Network (NCCN) Drugs and Biologics Compendium. Eligard . Available at: https://www.nccn.org/professionals/drug_compendium/content/ Accessed March 2, 2020

91. National Comprehensive Cancer Network (NCCN) Drugs and Biologics Compendium. Vantas . Available at: https://www.nccn.org/professionals/drug_compendium/content . Accessed March 2, 2020

92. Fensolvi (leuprolide acetate) [package insert]. Tolmar, Inc. Fort Collins, CO. May 2020.

Codes:
(The list of codes is not intended to be all-inclusive and is included below for informational purposes only. Inclusion or exclusion of a procedure, diagnosis, drug or device code(s) does not constitute or imply authorization, certification, approval, offer of coverage or guarantee of payment.)

CPT*

HCPCS
J1950
J3315
J3316
J9202
J9218
J9219
J9225
J9226
J9999
J9217


* CPT only copyright 2020 American Medical Association. All rights reserved. CPT is a registered trademark of the American Medical Association.

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