Vyleesi Safety Signals & FDA Actions: What Prescribers and Patients Need to Know

What has FDA done with Vyleesi since approval?

Bremelanotide was approved as Vyleesi on June 21, 2019 (NDA 210557). The application is now held by Cosette Pharmaceuticals and was originally held by AMAG [1][2]. The label carries no boxed warning, and no REMS appears in the label or in the 2019 approval letter [1][2].

The most recent action is labeling supplement S-005, approved October 22, 2026, which updates Section 8 (Use in Specific Populations) and the patient information [3]. As of October 28, 2026 that revised text was not yet posted in DailyMed, so the pregnancy wording described below comes from the label version effective November 13, 2025 [1][3].

FDA states on its adverse event dashboard that reports cannot be used to estimate how often an event occurs, that duplicate and incomplete reports exist, and that a report does not establish that the drug caused the event [4].

Blood pressure and heart rate: what the numbers actually mean

Each dose transiently raises blood pressure and lowers heart rate [1]. In clinical studies the maximal increases were 6 mmHg systolic and 3 mmHg diastolic, peaking 2 to 4 hours after the dose, with a heart rate reduction of up to 5 beats per minute; values usually returned to baseline within 12 hours, and repeat daily dosing 24 hours apart for up to 16 days produced no additive effect [1]. Those are maximal figures, not averages.

The averages come from an open-label ambulatory monitoring study of 127 premenopausal women dosed once daily for 8 days: mean daytime blood pressure rose 1.9 mmHg systolic (95% CI 1.0 to 2.7) and 1.7 mmHg diastolic (95% CI 0.9 to 2.4), with a mean heart rate fall of 0.5 beats per minute, and readings taken 12 to 24 hours after a dose were similar to pre-dose values [1].

Vyleesi is contraindicated in patients with uncontrolled hypertension or known cardiovascular disease, and the label says it is not recommended for patients at high risk of cardiovascular disease [1]. The label tells prescribers to consider cardiovascular risk and to make sure blood pressure is well controlled before starting and periodically during treatment [1].

Nausea: the most common signal

Nausea was reported by 40.0% of Vyleesi-treated women versus 1.3% on placebo in the pooled phase 3 trials [1]. Median onset was within one hour and it lasted about two hours; it was highest after the first dose, reported in 21% of patients, then fell to about 3% with later doses [1]. Thirteen percent received an antiemetic, and 8% stopped the trials because of nausea, versus no placebo patients who stopped for that reason [1].

Taking ondansetron first was tested and did not help. In a phase 4 single-dose study, 228 healthy women were randomized to 8 mg oral ondansetron or placebo 30 minutes before a 1.75 mg dose, and there was no significant difference in nausea between the groups; the label therefore says pre-treatment with oral ondansetron is not recommended [1]. Ondansetron given after the dose or after nausea begins has not been formally studied [1]. The label says to consider discontinuing Vyleesi for persistent or severe nausea, or starting antiemetic therapy for patients who are bothered by nausea but wish to continue [1].

Focal hyperpigmentation

In the phase 3 trials, focal hyperpigmentation — including the face, gums and breasts — was reported by 1% of patients receiving up to 8 doses a month, versus none on placebo [1]. Frequency depends heavily on schedule: 38% of patients developed focal hyperpigmentation after daily dosing for 8 days, and among patients who continued daily Vyleesi for another 8 days, an additional 14% developed new areas of darkened skin [1]. Patients with darker skin were more likely to develop it, and resolution was not confirmed in all patients after the drug was stopped [1].

The mechanism is stated on the label: MC1R is expressed on melanocytes, and binding there leads to melanin expression and increased pigmentation [1]. The label does not recommend more than 8 doses per month and says to consider discontinuing Vyleesi if hyperpigmentation develops [1].

Other safety items in the label

Serious adverse reactions were reported in 1.1% of Vyleesi-treated patients versus 0.5% on placebo, and 18% versus 2% discontinued because of adverse reactions — most often nausea (8%), headache (2%), vomiting (1%), flushing (1%) and injection site reactions (1%) [1]. Most patients in the trials used Vyleesi two to three times a month and no more than once a week [1].

One case of acute hepatitis occurred in the open-label extension, in a patient who had received 10 doses over a year; transaminases exceeded 40 times the upper limit of normal, total bilirubin was 6 times the upper limit, liver tests returned to normal four months after the drug was stopped, and because another cause was not identified a role for Vyleesi could not be excluded [1].

On pregnancy, the label advises discontinuing Vyleesi if pregnancy is suspected and using effective contraception; in dogs, fetal harm occurred at exposures at least 16 times the human dose by AUC, and this is one of the sections being revised by the October 2026 supplement [1][3]. Exposure rises 1.5-fold in moderate and 2-fold in severe renal impairment, and 1.2-fold to 1.7-fold in hepatic impairment [1].

Interactions worth knowing

Vyleesi may slow gastric emptying and reduce absorption of oral medicines. The label says to avoid it with oral drugs that depend on threshold blood concentrations (antibiotics are its example) and to consider skipping a dose when a quick effect from an oral drug such as indomethacin is wanted [1]. It may significantly decrease exposure to oral naltrexone, and the label says to avoid the combination with naltrexone products intended to treat alcohol or opioid addiction because of the consequences of treatment failure [1]. In clinical pharmacology studies, only naltrexone and indomethacin were meaningfully affected [1].

Vyleesi versus PT-141 sold as a peptide

Vyleesi is the FDA-approved bremelanotide product, a 1.75 mg subcutaneous autoinjector for premenopausal women with acquired, generalized hypoactive sexual desire disorder (HSDD) [1]. Products sold as PT-141, whether compounded or labeled for research use, are not Vyleesi and are not FDA-approved drugs; compounded drugs are not reviewed by FDA for safety, effectiveness or quality before marketing [5][1]. Everything above — the trial rates, the label warnings, the approval history — describes Vyleesi at 1.75 mg in that population [1].