OVERVIEW

PRODUCT INFORMATION

REPRESENTATIVE TRADE NAMES

Bremelanotide – Vyleesi®

DRUG CLASS

Female Hypoactive Sexual Desire Disorder Agents

COMPLETE LABELING

Product labeling at DailyMed, National Library of Medicine, NIH

CHEMICAL FORMULA AND STRUCTURE

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DRUG	CAS REGISTRY NUMBER	MOLECULAR FORMULA	STRUCTURE
Bremelanotide	189691-06-3	C50-H68-N14-O10

ANNOTATED BIBLIOGRAPHY

References updated: 20 August 2021

• Zimmerman HJ. Hepatotoxicity: the adverse effects of drugs and other chemicals on the liver. 2nd ed. Philadelphia: Lippincott, 1999.

  (Textbook of hepatotoxicity published in 1999, before the availability of bremelanotide).
• Schimmer BP, Funder JW. Adrenocorticotropic hormone, adrenal steroids, and the adrenal cortex. In, Brunton LL, Hilal-Dandan R, Knollman BC, eds. Goodman & Gilman’s the pharmacological basis of therapeutics. 13th ed. New York: McGraw-Hill, 2018, pp. 845-61.

  (Textbook of pharmacology and therapeutics).
• FDA. https://www​.accessdata​.fda.gov/drugsatfda_docs​/nda/2019/210557Orig1s000MultidisciplineR.pdf.

  (FDA website with product label and comprehensive multidiscipline review of the efficacy and safety of bremelanotide that supported its approval for use in female hypoactive sexual desire disorder, mentions that a single case of acute hepatitis occurred in a 52 year old woman who developed fatigue and weight loss approximately 10 days after receiving her last of 20 doses of bremelanotide with peak ALT 1163 U/L, Alk P 164 U/L and bilirubin 7.6 mg/dL, resolving over the next several months with normal values in follow up 1 to 2 years later [Simon 2019]).
• Clayton AH, Althof SE, Kingsberg S, DeRogatis LR, Kroll R, Goldstein I, Kaminetsky J, et al. Bremelanotide for female sexual dysfunctions in premenopausal women: a randomized, placebo-controlled dose-finding trial. Womens Health (Lond). 2016;12:325–37. [PMC free article: PMC5384512] [PubMed: 27181790]

  (Among 293 premenopausal women with hypoactive sexual desire disorder treated with self-administered, as desired injections of bremelanotide [0.75, 1.25 and 1.75 mg] or placebo for 12 weeks, the numbers of sexually satisfying events increased by 0.7 per month with bremelanotide vs 0.2 with placebo, and adverse events included nausea [18-24% vs 3%], flushing [14-17% vs 0], and headache [9-14% vs 3%], while “clinical laboratory findings showed no clinically significant trends”).
• Clayton AH, Lucas J, DeRogatis LR, Jordan R. Phase I randomized placebo-controlled, double-blind study of the safety and tolerability of bremelanotide coadministered with ethanol in healthy male and female participants. Clin Ther. 2017;39:514–526.e14. [PubMed: 28189361]

  (Among 24 healthy adults given intranasal bremelanotide with or without alcohol or placebo on days 1, 4 and 7 in a three-way cross over study, side effects were similar in the 3 groups, although “a small number of participants had mild increases in ALT” of 1.5 to 3.0 times the upper limit of normal, one transiently rising to an ALT of 124 U/L, largely attributed to the alcohol).
• Bremelanotide (Vyleesi) for hypoactive sexual desire disorder. Med Lett Drugs Ther. 2019;61(1577):114–6. [PubMed: 31381550]

  (Concise review of the mechanism of action, clinical efficacy, and safety of bremelanotide shortly after its approval in the US mentions side effects of nausea [40%], flushing, injection site reactions, headaches, and vomiting as well as transient increases in blood pressure and focal hyperpigmentation; no mention of ALT elevations or hepatotoxicity).
• Dhillon S, Keam SJ. Bremelanotide: First Approval. Drugs. 2019;79:1599–606. [PubMed: 31429064]

  (Review of the structure, mechanism of action, history of development, pharmacokinetics, clinical efficacy and safety of bremelanotide shortly after its approval for use in the US mentions a case of acute icteric hepatitis that occurred in a patient who had received 8 doses of bremelanotide over a one year period in an open label extension study).
• Kingsberg SA, Clayton AH, Portman D, Williams LA, Krop J, Jordan R, Lucas J, et al. Bremelanotide for the treatment of hypoactive sexual desire disorder: two randomized phase 3 trials. Obstet Gynecol. 2019;134:899–908. [PMC free article: PMC6819021] [PubMed: 31599840]

  (Among 1267 premenopausal women with hypoactive sexual desire disorder treated for 24 weeks with bremelanotide or placebo self-administered injections as needed before anticipated sexual activity, scores of sexual desire improved and those of sexual distressed decreased with bremelanotide and adverse reactions were common but generally mild-to-moderate in severity, and “no clinically significant effects on clinical laboratory tests…were observed”).
• Simon JA, Kingsberg SA, Portman D, Williams LA, Krop J, Jordan R, Lucas J, et al. Long-term safety and efficacy of bremelanotide for hypoactive sexual desire disorder. Obstet Gynecol. 2019;134:909–17. [PMC free article: PMC6819023] [PubMed: 31599847]

  (Among 684 patients enrolled in an open-label extension study after participation in a 24 week controlled trial of bremelanotide of whom only 272 completed the extension period; while the authors state that “no new safety signals were observed”, one patient developed an acute hepatitis after receiving a year of therapy with serum aminotransferases rising to above 20 times ULN and bilirubin to twice ULN with minor elevations present six but not 12 months later).
• Kingsberg SA, Simon JA. Female hypoactive sexual desire disorder: a practical guide to causes, clinical diagnosis, and treatment. J Womens Health (Larchmt). 2020;29:1101–12. [PubMed: 32460605]

  (Review of the pathogenesis, clinical features and therapy of female hypoactive sexual desire disorder).
• Spielmans GI. Re-analyzing Phase III bremelanotide trials for "hypoactive sexual desire disorder" in Women. J Sex Res. 2021:1–21. Epub ahead of print. [PubMed: 33678061]

  (Critical analysis of the two controlled trials of bremelanotide [Kingberg 2019] in regard to changes in primary outcome during the course of analysis and the rather modest improvement in symptom scores).
• Kingsberg SA, Clayton AH, Portman D, Krop J, Jordan R, Lucas J, Simon JA. Failure of a meta-analysis: a commentary on Glen Spielmans's "Re-Analyzing Phase III Bremelanotide Trials for 'Hypoactive Sexual Desire Disorder in Women'". J Sex Res. 2021 Apr 9;:1–2. Epub ahead of print. [PubMed: 33835907]

  (Reply to the critical analysis of Spielmans [2021] stressing the statistical rigor of the analysis and acceptance of the clinical endpoints used by the FDA).