What is the recommended treatment and dosage of PT-141 (bremelanotide) for patients with hypoactive sexual desire disorder or erectile dysfunction?

PT-141 (Bremelanotide) for Hypoactive Sexual Desire Disorder

Bremelanotide (PT-141/VYLEESI) is FDA-approved at 1.75 mg subcutaneous injection for premenopausal women with acquired, generalized hypoactive sexual desire disorder (HSDD), administered at least 45 minutes before anticipated sexual activity, with a maximum of 1 dose per 24 hours and no more than 8 doses per month. 1

FDA-Approved Indication and Dosing

Bremelanotide is specifically indicated for HSDD in premenopausal women only—it is NOT approved for postmenopausal women or for erectile dysfunction in men. 1

Dosing Protocol

• Standard dose: 1.75 mg subcutaneous injection into abdomen or thigh 1
• Timing: Administer at least 45 minutes before anticipated sexual activity 1, 2
• Frequency limitations:
  • Maximum 1 dose within any 24-hour period 1
  • Maximum 8 doses per month 1
  • More frequent dosing increases risk of pronounced blood pressure elevations 1

Administration Technique

• Self-administered using autoinjector device 1, 3
• Injection sites: abdomen or thigh (site does not affect systemic exposure) 1
• Absolute bioavailability approximately 100% 1

Mechanism and Efficacy

Bremelanotide is a melanocortin receptor agonist that nonselectively activates MC1R, MC4R, MC3R, MC5R, and MC2R, though the exact mechanism for improving HSDD remains unknown 1. Clinical trials demonstrated statistically significant improvements in sexual desire and reduced distress across multiple patient subgroups, including varying age, weight, BMI, and baseline testosterone levels 3.

The clinical benefit is modest: approximately 1 additional satisfying sexual event every 2 months compared to placebo 4. Despite this limited magnitude of effect, bremelanotide represents one of only two FDA-approved options for HSDD in premenopausal women 4.

Contraindications and Precautions

Absolute Contraindications

• Uncontrolled hypertension 1
• Known cardiovascular disease 1

Serious Warnings

Transient blood pressure increases and heart rate decreases occur after each dose: Mean increases of 1.9 mmHg systolic and 1.7 mmHg diastolic BP with peak effects 4-8 hours post-dose, typically resolving within 12 hours 1. Using bremelanotide more frequently than prescribed significantly increases cardiovascular risk 1.

Focal hyperpigmentation can occur, particularly on face, gingiva, and breasts, especially in patients with darker skin 1. This may not completely resolve after discontinuation 1.

Common Adverse Effects

• Nausea: Most common with first injection, typically lasting 2 hours but may persist longer; anti-emetic medications may be necessary 1
• Flushing 2, 5
• Headache 2, 5

Special Populations

Renal Impairment

Bremelanotide exposure increases with declining renal function: 1.2-fold in mild, 1.5-fold in moderate, and 2-fold in severe renal impairment 1. Use with caution and monitor closely.

Hepatic Impairment

Exposure increases 1.2-fold in mild and 1.7-fold in moderate hepatic impairment 1. Severe hepatic impairment has not been studied 1.

Pregnancy and Contraception

• Women of reproductive potential should use effective contraception during treatment 1
• Discontinue immediately if pregnancy suspected 1
• Pregnancy registry available (800-972-5220) 1

Treatment Algorithm for HSDD in Premenopausal Women

1. First-line FDA-approved options: Flibanserin (100 mg daily at bedtime) OR bremelanotide (1.75 mg as needed before sexual activity) 4

2. Selection between flibanserin and bremelanotide:

   • Choose bremelanotide for patients preferring on-demand dosing rather than daily medication 4
   • Choose flibanserin for patients with uncontrolled hypertension or cardiovascular disease (contraindications to bremelanotide) 1
   • Consider patient preference regarding injection vs. oral administration 4

3. Reassess after 8 weeks: If symptoms have not improved, consider alternative treatments or referral 1

4. Second-line off-label options (if FDA-approved treatments fail or are contraindicated): Bupropion or buspirone 4

Critical Pitfalls to Avoid

• Do NOT use bremelanotide in postmenopausal women—it is not FDA-approved for this population 1
• Do NOT use bremelanotide for erectile dysfunction in men—while early studies showed erectogenic effects 5, it is not approved for male ED and current guidelines recommend PDE5 inhibitors as first-line for male ED 6
• Do NOT exceed dosing frequency limits—more than 1 dose per 24 hours or more than 8 doses per month increases cardiovascular risk 1
• Do NOT prescribe to patients with uncontrolled hypertension or known cardiovascular disease 1
• Set realistic expectations: the clinical benefit is modest (approximately 1 additional satisfying sexual event every 2 months) 4

Drug Interactions

Bremelanotide may reduce rate and extent of absorption of concomitantly administered oral medications due to slowing gastric motility 1. Clinically significant interactions documented with naltrexone and indomethacin 1.