What it is

PT-141 is the development code for bremelanotide, a synthetic cyclic heptapeptide sold in the United States as Vyleesi, with initial U.S. approval in 2019 [1][4]. Vyleesi is a melanocortin receptor agonist supplied as a clear solution in a single-dose autoinjector for subcutaneous injection [1]. FDA approved it on June 21, 2019 under NDA 210557 for premenopausal women with acquired, generalized hypoactive sexual desire disorder (HSDD) [3]. The label defines HSDD as low sexual desire that causes marked distress or interpersonal difficulty and is not explained by another medical or psychiatric condition, a relationship problem, or a medication [1]. It is not indicated for postmenopausal women or men, and not indicated to enhance sexual performance [1]. The current DailyMed label is marketed by Cosette Pharmaceuticals and was revised in March 2024 [2].

How it works

Bremelanotide activates several melanocortin receptor subtypes nonselectively, with potency in the order MC1R, MC4R, MC3R, MC5R, MC2R [1]. At therapeutic exposure, binding to MC1R and MC4R matters most [1]. MC4R-expressing neurons are found in many parts of the central nervous system, but the mechanism by which the drug improves HSDD is unknown [1]. MC1R is expressed on melanocytes, and binding there increases melanin expression and pigmentation, which is why focal hyperpigmentation appears as a labeled warning [1]. The peptide is cleared mainly by hydrolysis of the amide bonds of its cyclic structure, and after a radiolabeled dose 64.8% of radioactivity was recovered in urine and 22.8% in feces [1]. Absolute bioavailability after subcutaneous injection was about 100%, with peak plasma levels at roughly 1 hour [1].

What the evidence shows

Approval rested on two identical 24-week, randomized, double-blind, placebo-controlled phase 3 trials (NCT02333071 and NCT02338960) in 1,247 premenopausal women with acquired, generalized HSDD [1]. Participants self-administered Vyleesi or placebo as needed before anticipated sexual activity; the median number of injections was 10 over the 24-week double-blind period [1]. Both trials showed a statistically significant increase in the FSFI Desire domain score and a statistically significant decrease in the FSDS-DAO Question 13 distress score versus placebo, with treatment differences of similar size in each trial [1]. Both trials also included a 52-week open-label extension in which 684 patients received Vyleesi [1]. The label states that the duration of effect after each dose is unknown and that the optimal timing window has not been fully characterized [1].

Regulatory status

Bremelanotide is an FDA-approved prescription drug: NDA 210557 was approved effective June 21, 2019, for use as described in the agreed-upon labeling [3]. The approved indication is limited to premenopausal women with acquired, generalized HSDD; the label states it is not indicated for postmenopausal women or men [1]. The label was revised in October 2020 and again in March 2024, when the DailyMed listing named Cosette Pharmaceuticals as the marketer [1][2]. Vyleesi is contraindicated in uncontrolled hypertension or known cardiovascular disease [1]. The label describes a pregnancy exposure registry and advises effective contraception during use [1]. The label also sets an 8-week point at which the prescriber decides whether to continue based on reported improvement [1]. STACK uses the Vyleesi label as its reference for this compound; a compounded “PT-141” vial is a different product with its own pharmacy label.

Half-life and what it means for a level curve

The Vyleesi label reports a mean terminal half-life of approximately 2.7 hours (range 1.9–4.0 hours) after a single subcutaneous dose, with clearance of 6.5 ± 1.0 L/hr and a volume of distribution of 25.0 ± 5.8 L [1]. Median time to peak plasma concentration is about 1.0 hour (range 0.5–1.0 hours) [1]. The reference half-life in STACK is 2.7 hours. With a half-life this short, the estimated level peaks within the first hour, halves roughly every 2.7 hours, and is near zero within a day, so each dose shows as a separate spike. A level reaches ~97% of steady state after about 5 half-lives with regular dosing; here that would be under 14 hours, but the label describes as-needed use, so there is normally no steady state to reach [1]. STACK’s curve is an estimate from this published half-life, not a blood level. Exposure is higher with renal or hepatic impairment, which the curve does not model [1].

Reported side effects

In the pooled phase 3 trials the most common adverse reactions were nausea (40.0% vs 1.3% placebo), flushing (20.3% vs 0.3%), injection site reactions (13.2% vs 8.4%), headache (11.3% vs 1.9%) and vomiting (4.8% vs 0.2%) [1]. Nausea usually began within an hour, lasted about two hours, and was most frequent after the first dose; 13% used an anti-emetic and 8% stopped because of it [1]. Discontinuation for any adverse reaction was 18% with Vyleesi versus 2% with placebo [1]. The label warns of a transient blood pressure rise (up to 6 mmHg systolic and 3 mmHg diastolic, peaking 2–4 hours post-dose) with a heart-rate decrease of up to 5 beats per minute, usually resolving within 12 hours [1]. Focal hyperpigmentation of the face, gingiva or breasts occurred in 1% of trial patients, more often with darker skin, and did not always resolve [1]. Vyleesi can slow gastric emptying and reduce absorption of oral drugs, notably naltrexone [1].

Storage and handling

The current label says to store Vyleesi at or below 25°C (77°F), not to freeze it, and to protect it from light [2]. Each autoinjector is single-dose and disposable, supplied in cartons of two or four [2]. The label instructs users to inspect the solution before use and discard it if it is cloudy, discolored or contains visible particles [1]. The product is a ready-to-use solution of 1.75 mg bremelanotide in 0.3 mL with glycerin and sterile water, so no reconstitution is involved [1]. If your prescriber has given you a compounded bremelanotide vial instead of Vyleesi, the pharmacy’s label governs storage; the STACK reconstitution calculator can do the volume math for you, but it does not suggest doses. Call your prescriber or pharmacist with any handling question.

What STACK tracks for it

STACK logs each Vyleesi or bremelanotide dose exactly as your prescriber wrote it, with the date, time and injection site (the label names the abdomen and thigh) [1]. Because the half-life is short, the estimated level view mainly shows timing: when a dose was taken and how quickly the estimate returns toward zero. You can record side effects such as nausea, flushing, headache or any skin darkening, and note blood pressure readings if your prescriber asked you to watch them [1]. STACK also keeps a count of autoinjectors on hand so you know when a refill is due, and lets you mark the label’s 8-week check-in at which the prescriber decides whether to continue [1]. STACK shows your own data; it never suggests when or how much to inject.

The reference half-life in STACK

STACK's simulator and the app use 2.7 h for PT-141 (bremelanotide): ~2.7 h (range 1.9–4.0 h). Measured in: adults after a single subcutaneous dose of Vyleesi (FDA label, section 12.3).