OVERVIEW

PRODUCT INFORMATION

REPRESENTATIVE TRADE NAMES

Histrelin – Supprelin®

Histrelin – Vantas®

DRUG CLASS

Antineoplastic Agents

COMPLETE LABELING

Product labeling at DailyMed, National Library of Medicine, NIH

CHEMICAL FORMULA AND STRUCTURE

View in own window

DRUG	CAS REGISTRY NO.	MOLECULAR FORMULA	STRUCTURE
Histrelin	76712-82-8	C66-H86-N18-O12

ANNOTATED BIBLIOGRAPHY

References updated: 28 May 2023

Abbreviations: FSH, follicle stimulating hormone; GnRH, gonadotropin releasing hormone; LH, luteinizing hormone; PSA, prostate specific antigen.

• Zimmerman HJ. Hepatotoxic effects of oncotherapeutic and immunosuppressive agents. In, Zimmerman HJ. Hepatotoxicity: the adverse effects of drugs and other chemicals on the liver. 2nd ed. Philadelphia: Lippincott, 1999, pp. 699.

  (Expert review of hepatotoxicity published in 1999; GnRH analogues such as histrelin are not discussed).
• Chitturi S, Farrell GC. Estrogen receptor antagonists. Adverse effects of hormones and hormone antagonists on the liver. In, Kaplowitz N, DeLeve LD, eds. Drug-induced liver disease. 3rd ed. Amsterdam: Elsevier, 2013, pp. 610-2.

  (Review of hepatotoxicity of hormonal products; does not discuss the GnRH agonists such as histrelin).
• Levin ER, Vitek WS, Hammes SR. Estrogens, progestins, and the female reproductive tract. In, Brunton LL, Halal-Dandan R, Knollman BC, eds. Goodman & Gilman's the pharmacological basis of therapeutics. 13th ed. New York: McGraw-Hill, 2018, pp. 803-31.

  (Textbook of pharmacology and therapeutics).
• Snyder PJ. Androgens and the male reproductive tract. In, Brunton LL, Halal-Dandan R, Knollman BC, eds. Goodman & Gilman's the pharmacological basis of therapeutics. 13th ed. New York: McGraw-Hill, 2018, pp. 833-43.

  (Textbook of pharmacology and therapeutics).
• Isaacs C, Wellstein A, Riegel AT. Hormones and related agents in the therapy of cancer. In, Brunton LL, Halal-Dandan R, Knollman BC, eds. Goodman & Gilman's the pharmacological basis of therapeutics. 13th ed. New York: McGraw-Hill, 2018, pp. 1237-47.

  (Textbook of pharmacology and therapeutics).
• Chertin B, Spitz IM, Lindenberg T, Algur N, Zer T, Kuzma P, Young AJ, et al. An implant releasing the gonadotropin hormone-releasing hormone agonist histrelin maintains medical castration for up to 30 months in metastatic prostate cancer. J Urol. 2000;163:838–44. [PubMed: 10687989]

  (Among 21 men with advanced prostate cancer who were treated with a long acting implant of histrelin, LH and testosterone levels were suppressed long term, while adverse events included loss of libido; ALT elevations were not mentioned).
• Schlegel PN, Kuzma P, Frick J, Farkas A, Gomahr A, Spitz I, Chertin B, et al. Effective long-term androgen suppression in men with prostate cancer using a hydrogel implant with the GnRH agonist histrelin. Urology. 2001;58:578–82. [PubMed: 11597543]

  (Among 42 men with advanced prostate cancer who were treated with 1 to 4 hydrogel implants of histrelin, testosterone suppression lasted for at least 12 months and adverse events included implant site pain or irritation and 50% had hot flashes; there were no serious adverse events attributable to the histrelin and no mention of ALT elevations or hepatotoxicity).
• Eugster EA, Clarke W, Kletter GB, Lee PA, Neely EK, Reiter EO, Saenger P, et al. Efficacy and safety of histrelin subdermal implant in children with central precocious puberty: a multicenter trial. J Clin Endocrinol Metab. 2007;92:1697–704. [PubMed: 17327379]

  (Among 36 children [ages 2 to 11 years] with precocious puberty treated with a 50 mg histrelin implant, peak LH and sex steroid levels were suppressed in all children to prepubertal levels for 12 months in all children and there were no serious adverse events and “no clinically significant findings” in clinical laboratory test results).
• Lewis KA, Eugster EA. Experience with the once-yearly histrelin (GnRHa) subcutaneous implant in the treatment of central precocious puberty. Drug Des Devel Ther. 2009;3:1–5. [PMC free article: PMC2769233] [PubMed: 19920916]

  (Review of the use of histrelin implants in management of precocious puberty including results from 3 studies in a total of 78 children mentions that the most common adverse reactions are complications at the implant site, and that there have been "no reported significant abnormalities in...clinical laboratory evaluations").
• Deeks ED. Histrelin: in advanced prostate cancer. Drugs. 2010;70:623–30. [PubMed: 20329807]

  (Review of the pharmacology, clinical efficacy and safety of histrelin implants which can result in testosterone suppression to castrate levels for up to a year; major side effects are those of androgen deprivation; no mention of ALT elevations or hepatotoxicity).
• Ricker JM, Foody WF, Shumway NM, Shaw JC. Drug-induced liver injury caused by the histrelin (Vantus) subcutaneous implant. South Med J. 2010;103:84–6. [PubMed: 19996852]

  (69 year old man with prostate cancer developed liver test abnormalities while on ketoconazole and marked worsening one month after placement of a histrelin implant [bilirubin not given, ALT ~1000 U/L, Alk P ~300 U/L], resolving within a month of removal of the implant).
• Shore N, Cookson MS, Gittelman MC. Long-term efficacy and tolerability of once-yearly histrelin acetate subcutaneous implant in patients with advanced prostate cancer. BJU Int. 2012;109:226–32. [PubMed: 21851539]

  (Review of efficacy and safety of histrelin implant therapy of advanced prostate cancer; mentions side effects of hot flashes, fatigue, testicular atrophy, gynecomastia, decrease in libido and erectile dysfunction, but does not mention ALT elevations or hepatotoxicity).
• Van Poppel H, Klotz L. Gonadotropin-releasing hormone: an update review of the antagonists versus agonists. Int J Urol. 2012;19:594–601. [PubMed: 22416801]

  (Review of androgen deprivation therapy for prostate cancer using GnRH agonists and antagonists stressing the more rapid onset of action and similar if not better safety profile of GnRH antagonists).
• Walker LM, Tran S, Robinson JW. Luteinizing hormone--releasing hormone agonists: a quick reference for prevalence rates of potential adverse effects. Clin Genitourin Cancer. 2013;11:375–84. [PubMed: 23891497]

  (Systematic review of adverse event profile of long term use of GnRH agonists which mostly relate to the hormonal changes that occur: hot flashes, gynecomastia, genital shrinkage, hair loss, osteoporosis, mild anemia, hyperglycemia, increased weight, loss of skeletal muscle mass, emotional lability, depression, loss of sexual desire and erectile dysfunction; no mention of ALT elevations or hepatotoxicity).
• Björnsson ES, Bergmann OM, Björnsson HK, Kvaran RB, Olafsson S. Incidence, presentation and outcomes in patients with drug-induced liver injury in the general population of Iceland. Gastroenterology. 2013;144:1419–25. [PubMed: 23419359]

  (In a population based study of drug induced liver injury from Iceland, 96 cases were identified over a 2 year period, but none of the 96 were attributed to histrelin or any of the GnRH analogues).
• Chalasani N, Bonkovsky HL, Fontana R, Lee W, Stolz A, Talwalkar J, Reddy KR, et al.; United States Drug Induced Liver Injury Network. Features and outcomes of 899 patients with drug-induced liver injury: The DILIN Prospective Study. Gastroenterology 2015; 148: 1340-52.e.7. [PMC free article: PMC4446235] [PubMed: 25754159]

  (Among 899 cases of drug induced liver injury enrolled in a US prospective study between 2004 and 2013, none were attributed to histrelin or any of the GnRH analogues).
• Silverman LA, Neely EK, Kletter GB, Lewis K, Chitra S, Terleckyj O, Eugster EA. Long-term continuous suppression with once-yearly histrelin subcutaneous implants for the treatment of central precocious puberty: a final report of a phase 3 multicenter trial. J Clin Endocrinol Metab. 2015;100(6):2354–63. [PMC free article: PMC4504932] [PubMed: 25803268]

  (Six year follow up on the 36 children treated with every-12-month histrelin [Eugster 2007], most of whom continued therapy for up to 6 years stated that 53% of children had local pain or discomfort from the implants but they provided prolonged suppression of LH levels and there were no treatment related serious adverse events; no mention of liver injury or ALT levels).
• Bolton EM, Lynch TH. Are all gonadotropin-releasing hormone agonists equivalent for the treatment of prostate cancer? A systematic review. BJU Int. 2018;122(3):371–83. [PubMed: 29438592]

  (Systematic review of literature on relative efficacy and safety of different GnRH agonists, indicates that there is little evidence of superiority of any of the four, largely because of lack of adequately powered, controlled studies comparing them).
• Cornford P, Jefferson K, Cole O, Gilbody J. Effects of initiating or switching to a six-monthly triptorelin formulation on prostate cancer patient-healthcare interactions and hospital resource use: a real-world, retrospective, non-interventional study. Oncol Ther. 2018;6:173–187. [PMC free article: PMC7359994] [PubMed: 32700031]

  (Among 41 adults with advanced prostate cancer who were switched from every 1 or 3 monthly GnRH regimen to 6 monthly triptorelin, healthcare visits, injections and PSA testing were less as were adverse side effects including fatigue [12% vs 26%], urinary frequency [9% vs 32%], and bone pain [7% vs 14%]; no mention of ALT elevations or hepatotoxicity).
• Swendiman RA, Vogiatzi MG, Alter CA, Nance ML. Histrelin implantation in the pediatric population: A 10-year institutional experience. J Pediatr Surg. 2019;54:1457–1461. [PubMed: 30262200]

  (Among 377 children [mean age 9.4 years] undergoing 866 histrelin implant insertions or removals to treat precocious puberty [n=343] or gender affirming therapy [n=34], complications of the procedure were rare [1%] and were largely local wound complications).
• Lambertini M, Boni L, Michelotti A, Magnolfi E, Cogoni AA, Mosconi AM, Giordano M, et al. GIM study group. Long-term outcomes with pharmacological ovarian suppression during chemotherapy in premenopausal early breast cancer patients. J Natl Cancer Inst. 2022;114:400–408. [PMC free article: PMC8902441] [PubMed: 34850043]

  (Among 281 women with early onset breast cancer treated with chemotherapy with or without a GnRH analogue to preserve ovarian function, disease-free and overall survival were similar in the two groups and those given the GnRH analogue were slightly more likely to have a successful pregnancy during follow up [6.5% vs 3.2%]; no mention of other adverse events, ALT levels or hepatotoxicity).
• Popovic J, Geffner ME, Rogol AD, Silverman LA, Kaplowitz PB, Mauras N, Zeitler P, et al. Gonadotropin-releasing hormone analogue therapies for children with central precocious puberty in the United States. Front Pediatr. 2022;10:968485. [PMC free article: PMC9577333] [PubMed: 36268040]

  (Review of the 3 GnRH analogues used to treat children with precocious puberty including leuprolide, triptorelin, and histrelin, which have different regimens of administration [intramuscular and subcutaneous] and durations of action [1-12 months]; no mention of liver adverse events).