What is the history, usage, dosage, indications, contraindications, side effects, and approval status of Bremelanotide (PT 141) peptide, including its use in treating hypoactive sexual desire disorder (HSDD) in premenopausal women?

Bremelanotide (PT-141): History, Usage, and Clinical Profile

Bremelanotide (PT-141) is an FDA-approved melanocortin receptor agonist indicated specifically for the treatment of premenopausal women with acquired, generalized hypoactive sexual desire disorder (HSDD), administered as a subcutaneous injection as needed before sexual activity. 1

History and Development

• Bremelanotide was developed as a treatment for sexual dysfunction and received FDA approval in 2019 for treating HSDD in premenopausal women 1
• The drug was evaluated in extensive clinical trials, including two phase III randomized, double-blind, placebo-controlled multicenter studies (RECONNECT) that established its efficacy and safety profile 2
• The clinical development program included 3,500 subjects across 43 completed studies, with some participants taking bremelanotide for up to 18 months 3

Current Indications and Usage

• Bremelanotide is specifically indicated for premenopausal women with acquired, generalized HSDD characterized by low sexual desire causing marked distress or interpersonal difficulty 1
• HSDD must NOT be due to co-existing medical/psychiatric conditions, relationship problems, or effects of medications 1
• Important limitations of use:
  • Not indicated for HSDD treatment in postmenopausal women or men 1
  • Not indicated to enhance sexual performance 1

Dosage and Administration

• Recommended dosage: 1.75 mg administered subcutaneously in the abdomen or thigh, as needed, at least 45 minutes before anticipated sexual activity 1
• Administration guidelines:
  • No more than one dose within 24 hours 1
  • No more than 8 doses per month is recommended 1
  • Self-administered via a prefilled autoinjector pen 1
• Treatment should be discontinued after 8 weeks if the patient does not report symptom improvement 1, 4

Efficacy

• Clinical trials demonstrated that bremelanotide significantly improves sexual desire and reduces distress related to low sexual desire compared to placebo 2
• Efficacy was demonstrated across various subgroups including different age ranges, weights, BMI categories, and baseline testosterone levels 5
• Participants in the bremelanotide groups experienced statistically significant increases in sexual desire and statistically significant reductions in distress related to low sexual desire compared with placebo 6, 2

Contraindications and Warnings

• Contraindicated in patients with uncontrolled hypertension or known cardiovascular disease 1
• Key warnings:
  • Transient increases in blood pressure (up to 6 mmHg systolic, 3 mmHg diastolic) and reductions in heart rate (up to 5 beats per minute) that peak between 2-4 hours post-dose 1
  • Blood pressure and heart rate typically return to baseline within 12 hours 1
  • Should be used with caution in patients at risk for cardiovascular disease 3

Side Effects

• Most common adverse events (from phase 3 studies):
  • Nausea (40% vs. 1.3% placebo) - most common reason for discontinuation 3
  • Flushing (20.3% vs. 1.3% placebo) 3
  • Headache (11.3% vs. 1.9% placebo) 3
  • Injection site reactions (5.4% vs. 0.5% placebo) 3
• Focal hyperpigmentation was rare when dosed according to label recommendations but occurred in more than one-third of subjects following consecutive daily dosing 3

Drug Interactions

• May slow gastric emptying and impact absorption of concomitantly administered oral medications 1
• May significantly decrease systemic exposure of orally-administered naltrexone; avoid use with oral naltrexone-containing products intended to treat alcohol or opioid addiction 1
• Most drug-drug interactions were not clinically significant in studies 3

Regulatory Status

• FDA-approved in 2019 for treatment of premenopausal women with acquired, generalized HSDD 1, 2
• The National Comprehensive Cancer Network (NCCN) guidelines mention bremelanotide as an option for premenopausal individuals with low sexual desire, noting that while it hasn't been specifically studied in cancer survivors, it may be an appropriate option for some survivors with HSDD 6
• The FDA label specifies that bremelanotide is not indicated for postmenopausal women or men 1

Clinical Considerations

• Bremelanotide should be discontinued if hyperpigmentation develops 1
• Consider discontinuing bremelanotide or initiating anti-emetic therapy for persistent or severe nausea 1
• Blood pressure should be well-controlled during treatment 3
• The pathophysiology of HSDD involves inhibitory and excitatory hormones, neurotransmitters, and specific brain anatomy, making treatment complex 7