PT-141 (Bremelanotide): What to Expect, Week-by-Week First Month

How many doses does a first month actually contain?

Vyleesi is used as needed, at least 45 minutes before anticipated sexual activity. The label says not to take more than one dose within 24 hours, and it does not recommend more than 8 doses a month [1]. In the two 24-week trials, most patients used it two to three times a month and no more than once a week, with a median of 10 injections across the whole double-blind period [1]. The first month therefore does not follow a fixed daily or weekly schedule.

The label also says the duration of effect after each dose is unknown and the optimal window for injecting has not been fully characterized. It says patients may decide the timing based on how they experience the effect on desire and side effects such as nausea [1].

Week 1: the first dose

The first dose is the one most likely to cause nausea. Nausea was reported by 21% of women after their first Vyleesi dose, with a median onset within one hour and a duration of about two hours in the trials [1]. Across the whole program, nausea was reported by 40% of women on Vyleesi versus 1.3% on placebo, 13% used an anti-nausea medicine and 8% stopped the trials because of it [1].

Other reactions recorded in the pooled trials, Vyleesi versus placebo: flushing 20.3% versus 0.3%, injection site reactions 13.2% versus 8.4%, headache 11.3% versus 1.9%, vomiting 4.8% versus 0.2% [1].

Blood pressure rises slightly after each dose and heart rate falls. The largest increases seen in clinical studies 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 [1]. Bremelanotide reaches peak blood levels at a median of about 1 hour after a subcutaneous dose and has a mean half-life of about 2.7 hours [1].

One thing that does not help: in a phase 4 single-dose study of 228 healthy women, 8 mg of oral ondansetron taken 30 minutes before a 1.75 mg dose did not reduce the incidence of nausea, and the label says pre-treatment with oral ondansetron is not recommended [1].

Weeks 2 to 4: what may change with later doses

Nausea improves for most patients with the second dose, and the label notes that the incidence was highest after the first dose and then declined to about 3% after subsequent doses [1]. That pattern is the main difference to expect across the first month. It is not a promise: 8% of women in the trials still stopped because of nausea [1].

Overall discontinuation because of adverse reactions was 18% on Vyleesi versus 2% on placebo; the most common reasons were nausea 8%, headache 2%, vomiting 1%, flushing 1% and injection site reactions 1% [1]. Most reported events were mild (31%) or moderate (40%) and transient [1].

Skin darkening: more common with daily dosing

Focal hyperpigmentation (darkening of the face, gums or breasts) was reported by 1% of women using up to 8 doses a month in the placebo-controlled trials, versus none on placebo [1]. With daily dosing the rate is far higher: 38% of patients developed focal hyperpigmentation after 8 consecutive days, and a further 14% developed new pigmentary changes after 8 more days [1]. Risk is higher in people with darker skin, and the label states that resolution was not confirmed in all patients after the drug was stopped [1]. The label ties that risk to more frequent dosing, says more than 8 doses a month is not recommended, and says discontinuation should be considered if hyperpigmentation develops [1].

When desire changes, according to the trials

Both trials measured the Female Sexual Function Index desire domain and a distress question (FSDS-DAO item 13) at the end of the double-blind period, which was week 24 for women who completed it [1]. Mean desire scores rose 0.5 points on Vyleesi versus 0.2 on placebo in study 1, and 0.6 versus 0.2 in study 2 [1]. The integrated analysis reported a 0.35-point desire improvement versus placebo (P<0.001) and a fall in desire-related distress, with no significant difference in the number of satisfying sexual events [2].

Because those are end-of-study averages, they do not describe what happens after dose one, two or four. The label's practical instruction is different: it says to stop Vyleesi after 8 weeks if there has been no improvement in symptoms [1].

Safety points that matter in the first month

• The label contraindicates Vyleesi in uncontrolled hypertension or known cardiovascular disease and says it is not recommended for patients at high risk of cardiovascular disease [1]. It also says to consider cardiovascular risk before starting and periodically during treatment and to make sure blood pressure is well controlled [1].
• Vyleesi may significantly decrease the blood levels of oral naltrexone, and the label says to avoid using it with oral naltrexone products intended to treat alcohol or opioid addiction [1].
• Vyleesi may slow stomach emptying and reduce absorption of oral medicines. The label says to avoid it with oral drugs that depend on threshold blood concentrations, such as antibiotics, and to consider skipping it when a quick effect from an oral medicine such as indomethacin is wanted [1].
• In animals, fetal harm occurred in dogs at exposures at least 16 times (by AUC) the maximum recommended dose, and the label says to use effective contraception and to stop Vyleesi if pregnancy is suspected [1].
• One case of acute hepatitis, with liver enzymes more than 40 times the upper limit of normal, occurred after 10 doses over a year in an open-label extension; other causes were not identified, so a role for Vyleesi could not be excluded [1].
• In a crossover study of 24 healthy volunteers, alcohol at 0.6 g/kg did not change bremelanotide blood levels when tested with a 20 mg intranasal dose, which produced about 2.5 times the maximum concentration of Vyleesi; flushing and headache rates were similar to the higher rate with either treatment alone [1].

Is the product you have the same one that was studied?

The FDA approved bremelanotide as Vyleesi on June 21, 2019 (NDA 210557) [1][3]. Products sold as PT-141, whether compounded or as research-use peptide, are not Vyleesi and are not FDA-approved drugs, and compounded drugs are not reviewed by FDA for safety, effectiveness or quality before marketing [4][1]. The dosing and side-effect figures on this page describe Vyleesi, the FDA-approved product [1].