PT-141 Side Effects: Every Number the Label Reports

Most pages describing PT-141's side effects use adjectives. The FDA-approved label uses numbers, and they are more useful.

This article reports them — including two the label discusses at length and almost nobody else mentions.

The Short Answer

First, whose numbers these are. PT-141 is the development name commonly used for bremelanotide. Vyleesi® is the FDA-approved product: a 1.75 mg subcutaneous bremelanotide injection. Every figure below comes from Vyleesi's label and its clinical trials. Compounded preparations containing bremelanotide or "PT-141" are not Vyleesi and are not FDA-approved drug products, and there is no comparable FDA-reviewed adverse-reaction dataset establishing rates for them.

Nausea affected 40.0% of Vyleesi-treated participants in the clinical trials, against 1.3% on placebo. It was worst after the first dose, reported by 21%, then fell to around 3% with later doses.

8% of Vyleesi-treated participants stopped the trials because of nausea. None on placebo did. A separate study tested whether an anti-nausea medication taken beforehand would help. It did not, and the label says so.

Vyleesi does not carry an FDA boxed warning, but it does have important contraindications and warnings. The contraindications section is one line: uncontrolled hypertension or known cardiovascular disease.

And there is a pigmentation effect that becomes substantial with frequent dosing, is more likely in people with dark skin, and did not always resolve after stopping.

Whose Side Effects These Are

This distinction decides how much of the article applies to any particular person.

• Bremelanotide is the drug substance.
• PT-141 is the development code from its research history — what most people search, and what most compounded products are marketed under. It specifies no strength, route or manufacturer.
• Vyleesi® is the FDA-approved finished product, and the only one with an approved label, an approved indication and the trial dataset reported below.

Compounded preparations are prepared by pharmacies rather than approved as drug products, so the FDA has not evaluated them for safety, effectiveness or manufacturing quality. The rates on this page were measured in 627 people given 1.75 mg subcutaneously. They describe that product at that dose by that route. These percentages should therefore not be presented as known side-effect rates for a compounded oral, sublingual, nasal, troche, film, gummy or differently dosed bremelanotide product. Published safety data for compounded formulations are far more limited and cannot be assumed to match the Vyleesi rates — and the absence of reported side effects for an unstudied preparation is not evidence that it has fewer.

The Full Adverse Reaction Table

These figures come from the pooled phase 3 trials of Vyleesi — 627 people receiving bremelanotide 1.75 mg subcutaneously against 620 receiving placebo — as published in the label.

• Nausea — 40.0% (placebo 1.3%)
• Flushing — 20.3% (placebo 0.3%)
• Injection site reactions — 13.2% (placebo 8.4%)
• Headache — 11.3% (placebo 1.9%)
• Vomiting — 4.8% (placebo 0.2%)
• Cough — 3.3% (placebo 1.3%)
• Fatigue — 3.2% (placebo 0.5%)
• Hot flush — 2.7% (placebo 0.2%)
• Paraesthesia — 2.6% (placebo 0.0%)
• Dizziness — 2.2% (placebo 0.5%)
• Nasal congestion — 2.1% (placebo 0.5%)

Two details the label adds beneath those percentages, which a table alone hides. Most headaches were not serious, but one participant experienced a serious headache — intractable pain leading to hospitalisation — and 1% discontinued because of headache. Of the flushing events, none were serious and fewer than 1% were severe, with 1% discontinuing because of it.

Read the current VYLEESI prescribing information on DailyMed.

Nausea, in Detail

Nausea is not a footnote in this drug's profile. It is the defining tolerability issue, and the label devotes an unusual amount of space to it.

Four things it reports:

It starts fast and does not last long. The label states that "the median onset of nausea was within one-hour post-dose and lasted about two hours in duration."

It is front-loaded. The incidence "was highest after the first VYLEESI dose (reported in 21% of patients) then declined to about 3% after subsequent doses." For most people who experience it, the worst episode is the first one.

Many participants medicated for it. "Thirteen percent of VYLEESI-treated patients received an anti-emetic medication."

It ended trials. "Overall, 8% of VYLEESI-treated patients and no placebo-treated patients prematurely discontinued the trials due to nausea."

Pre-medicating does not work

This is the most practically useful finding on the label, and it is absent from every page currently ranking for this query.

A phase 4 study tested the obvious workaround. 228 healthy women were randomised one-to-one to 8 mg of oral ondansetron — a standard anti-nausea drug — or placebo, taken 30 minutes before a single 1.75 mg subcutaneous dose of Vyleesi. No significant difference in nausea appeared between the groups. The label's conclusion: pre-treatment with oral ondansetron "does not reduce the incidence of VYLEESI-associated nausea and is not recommended."

Note precisely what was tested. That study looked at ondansetron taken beforehand. The label adds that "treatment with ondansetron after VYLEESI administration or after the onset of nausea has not been formally studied" — so this is a negative result about pre-medicating, not a finding that anti-nausea medication is useless once nausea has begun. Thirteen percent of trial participants did take an anti-emetic.

The Pigmentation Effect

MC1R, one of the two receptors bremelanotide binds most relevantly at therapeutic doses, sits on melanocytes — the cells that produce skin pigment. The label states that binding there "leads to melanin expression and increased pigmentation."

What that means in practice depends heavily on how often the drug is used.

• In the phase 3 trials, where participants used up to eight doses per month, about 1% developed focal hyperpigmentation, against none on placebo.
• But 38% of patients developed focal hyperpigmentation after receiving VYLEESI daily for eight days, and among those who continued daily for eight more days, a further 14% developed new pigmentary changes.

Daily use is not the FDA-approved dosing schedule. Those two figures come from a study that dosed far more frequently than the label allows, and they illustrate exactly why the label caps use at eight doses a month and warns that pigmentation risk rises with frequent dosing.

Two further details from the same section matter and are rarely repeated.

"Patients with dark skin were more likely to develop focal hyperpigmentation." That is the label's own wording, and it means the risk is not evenly distributed.

"Resolution of the focal hyperpigmentation was not confirmed in all patients after discontinuation." Stopping the drug did not reliably reverse it in everyone studied.

The label directs that the face, gums and breasts be examined before starting and periodically during treatment.

Blood Pressure, and the One-Line Contraindication

The entire contraindications section of the VYLEESI label reads: uncontrolled hypertension or known cardiovascular disease. The label adds that it "is not recommended for patients at high risk for cardiovascular disease."

The reason is a measured haemodynamic effect after each dose. The label reports that VYLEESI "transiently increases blood pressure and reduces heart rate after each dose," with:

• Maximal increases of 6 mmHg systolic and 3 mmHg diastolic, peaking two to four hours after dosing
• A corresponding heart-rate reduction of up to 5 beats per minute
• Blood pressure and heart rate returning to baseline "usually within 12 hours post-dose"

Those are average maximum changes observed in the clinical studies; they do not predict the response of an individual patient. The contraindication exists because the effect is not equally tolerable for everyone — which is precisely the assessment a prescriber makes and an article cannot.

One Rare Serious Event — and One Important Drug Interaction

A single case of acute hepatitis. During the open-label extension study, one participant who had received ten doses over a year developed acute hepatitis, with transaminases more than 40 times the upper limit of normal and bilirubin six times the upper limit. Liver tests returned to normal four months after stopping. Because another cause was not identified, the label states that the drug's role could not definitively be excluded.

Context matters here, and the label supplies it: there was no imbalance between treatment groups in transaminase outliers, and no other signals for liver toxicity anywhere else in the clinical development programme. One unresolved case is worth knowing about; it is not an established liver-toxicity signal.

Slowed gastric emptying, and what it does to oral medicines. Bremelanotide can slow gastric emptying, which may reduce the rate and extent of absorption of oral medications taken around the same time. The label advises avoiding it with oral drugs that depend on threshold concentrations to work — antibiotics are its example — and considering discontinuation if a medicine needing a fast onset, such as indomethacin for pain, is delayed.

The label gives oral naltrexone its own section, because the consequences are more serious than a delayed effect: reduced absorption of a naltrexone product prescribed for alcohol or opioid dependence could cause treatment failure. The label advises avoiding that combination.

Pregnancy Is a Separate Label Warning

Not an adverse reaction, but part of the safety picture and easy to miss.

The label advises using effective contraception while taking Vyleesi and discontinuing it if pregnancy is suspected, because animal studies identified potential fetal harm — in dogs at exposures at or above 16 times the maximum recommended dose, and in mice at or above 125 times. The lowest dose associated with fetal harm has not been identified in either species.

Human experience is too limited to draw conclusions: the label reports seven pregnancies among more than 1,057 patients treated with Vyleesi, which it describes as "insufficient for determining whether there is a drug-associated risk." There is a pregnancy exposure registry for women exposed during pregnancy.

The Number That Frames All the Others — and How to Read It

Adverse-reaction incidence and treatment discontinuation answer different questions. One describes how often reactions were reported; the other shows how often reactions were serious or bothersome enough to make people stop.

Across the two phase 3 trials, overall completion was lower in the Vyleesi groups:

• Study 1: 40% discontinued the 24-week treatment period early, against 13% on placebo
• Study 2: 39% against 25%

Those are all-cause discontinuation figures, not side-effect discontinuation rates. People leave clinical trials for many reasons — withdrawal of consent, loss to follow-up, protocol deviations, lack of perceived benefit, personal circumstances — and it would be wrong to read the whole gap as caused by adverse effects.

The direct tolerability measure is narrower and still striking:

• Discontinuation specifically because of adverse reactions: 18% on Vyleesi against 2% on placebo.

That is the number to quote, and it is the one least likely to appear on a page selling the treatment. Nearly one in five participants stopped because of a reaction to the drug, against one in fifty on placebo.

For what the same trials found on efficacy, and the trial result that did not go the drug's way: What PT-141 Actually Is, Who It Is Approved For, and What the Trials Found.

What This Article Cannot Tell You

These are group rates from trial populations given Vyleesi. They describe how often something occurred among several hundred people; they do not predict what will happen to any particular person, and they cannot weigh a side-effect profile against an individual's circumstances, other medications or health history. They also do not describe any compounded preparation.

Anyone experiencing a reaction to a prescribed medication should raise it with the clinician who prescribed it rather than acting on published averages. Related reading: Low Libido in Women: Causes, HSDD and Treatment Options.

Frequently Asked Questions

What are the most common PT-141 side effects?

From the label's pooled trial data: nausea 40.0%, flushing 20.3%, injection site reactions 13.2%, headache 11.3% and vomiting 4.8%, against placebo rates of 1.3%, 0.3%, 8.4%, 1.9% and 0.2% respectively.

How bad is the nausea?

Severity varies between individuals. What the label reports is frequency and timing: nausea occurred in 40% of Vyleesi-treated trial participants, with a median onset within about one hour of dosing and lasting around two hours. It was most common after the first dose, reported by 21%, declining to about 3% with later doses. Thirteen percent received an anti-emetic, and 8% discontinued treatment because of it, compared with none on placebo.

Does PT-141 nausea get better after the first dose?

On trial averages, usually. Nausea was reported after the first dose by 21% of participants and fell to around 3% following subsequent doses, and the label states that it "improves for most patients with the second dose." That is an average across a trial population, not a guarantee — it can recur with later injections.

How long do PT-141 side effects last?

It depends on the effect. Nausea had a median onset within about one hour of dosing and lasted about two hours in the phase 3 trials, though it could last longer. Blood-pressure and heart-rate changes generally returned to baseline within 12 hours. Focal hyperpigmentation is the exception: the label states that resolution after stopping was not confirmed in all patients. Other reactions have no single established duration.

Can you take something to prevent the nausea?

A phase 4 study randomised 228 healthy women to 8 mg of oral ondansetron or placebo 30 minutes before a single dose. The label reports that pre-treatment "does not reduce the incidence of VYLEESI-associated nausea and is not recommended." Note the limit of that finding: the label adds that treatment with ondansetron after dosing, or after nausea has begun, "has not been formally studied."

Does PT-141 cause skin darkening?

It can, because one of the receptors it binds sits on pigment-producing cells. At up to eight doses a month about 1% developed focal hyperpigmentation, but 38% did after eight consecutive daily doses, with a further 14% over eight more days. The label states that patients with dark skin were more likely to develop it, and that resolution after stopping was not confirmed in all patients.

Does PT-141 raise blood pressure?

Transiently. The label reports maximal increases of 6 mmHg systolic and 3 mmHg diastolic peaking two to four hours after a dose, with heart rate falling by up to 5 beats per minute, generally returning to baseline within 12 hours. It is contraindicated in uncontrolled hypertension or known cardiovascular disease.

Does PT-141 have a black box warning?

Vyleesi does not carry an FDA boxed warning — "boxed warning" being the formal FDA term for what is commonly called a black box warning. It does have important contraindications and warnings: its contraindications section names uncontrolled hypertension and known cardiovascular disease, and focal hyperpigmentation and nausea are both labelled warnings in their own right.

Do these side effects apply to compounded PT-141?

Unknown. Every rate on this page was measured in trials of Vyleesi at 1.75 mg subcutaneously. Compounded preparations containing bremelanotide are not Vyleesi, have not been evaluated by the FDA, and do not have a comparable FDA-reviewed adverse-reaction dataset establishing rates equivalent to those in the Vyleesi label. A preparation at a different strength or by a different route has not been studied for safety in this way, and that absence of data should not be read as an absence of risk. Anyone taking a compounded preparation should direct questions to the prescriber and the pharmacy dispensing it.

How many people stopped taking it in the trials?

Two different figures answer that, and they mean different things. All-cause premature discontinuation of the 24-week period was 40% against 13% on placebo in one trial, and 39% against 25% in the other — but people leave trials for many reasons unrelated to side effects. The direct tolerability measure is that 18% of Vyleesi-treated participants discontinued because of adverse reactions, against 2% on placebo.

Are there any drug interactions?

Bremelanotide can slow gastric emptying and reduce the absorption of oral medicines taken around the same time. The label advises caution with oral drugs that depend on threshold concentrations to work, such as antibiotics, and specifically advises avoiding oral naltrexone prescribed for alcohol or opioid dependence, where reduced absorption could cause treatment failure. Any other medication should be reviewed by the prescriber.

AmalfiDuo Sexual Wellness Programs

If you're exploring ways to support your sexual wellness, AmalfiDuo offers private, provider-guided care programs for adults. A licensed clinician reviews your health information to determine whether treatment is appropriate.

Explore Sexual Wellness Programs

A prescription is never guaranteed.

References

1. VYLEESI (bremelanotide) injection — U.S. Prescribing Information. DailyMed, U.S. National Library of Medicine. Sections 4, 5.1, 5.2, 5.3, 6.1, 7.1, 7.2, 8.1 and 12.1.
2. Kingsberg SA, Clayton AH, Portman D, et al. Bremelanotide for the Treatment of Hypoactive Sexual Desire Disorder: Two Randomized Phase 3 Trials. Obstetrics & Gynecology. 2019;134(5):899–908. PMID 31599840.

This article is provided for general educational purposes only and is not a substitute for individualized medical advice, diagnosis or treatment. It reports adverse-reaction rates from FDA-approved prescribing information, which describe trial populations rather than individuals, and does not recommend any treatment or dose. The rates here describe Vyleesi®, the FDA-approved bremelanotide product, and do not describe compounded preparations. Anyone experiencing a reaction to a prescribed medication should contact the clinician who prescribed it. AmalfiDuo Journal articles are written by AmalfiDuo Editorial and are not medically reviewed — see our Editorial Policy.

VYLEESI® is a trademark of its respective owner. AmalfiDuo is not affiliated with or endorsed by the owners or manufacturers of this brand.