Vyleesi and Addyi: The Two Approved HSDD Treatments, Compared

Two drugs are approved in the United States for hypoactive sexual desire disorder. They work differently, are dosed completely differently, and carry very different warnings.

They also share something that neither manufacturer advertises. Each product's pivotal trials reveal a limitation the other's do not: Addyi failed its pre-specified eDiary desire endpoint in two of three pivotal studies, while Vyleesi's two phase 3 trials did not show a statistically significant increase in satisfying sexual events.

Here is the comparison, built from both FDA labels.

The Short Answer

Addyi (flibanserin) is a tablet taken every day at bedtime, whether or not sex is anticipated. It carries a boxed warning for hypotension and syncope, and the label instructs stopping after eight weeks if it has not helped.

Vyleesi (bremelanotide) is an injection taken only when needed, at least 45 minutes before anticipated activity, up to eight times a month. It has no boxed warning, but is contraindicated in uncontrolled hypertension or known cardiovascular disease.

Both labels set the same review point: stop after eight weeks if there has been no improvement in symptoms.

On effectiveness, both produced small improvements, and the pattern is unexpected. Addyi increased satisfying sexual events by roughly half to one per month — but its co-primary desire endpoint failed in two of its three pivotal trials. Vyleesi improved desire and distress scores — but its trials did not show a statistically significant increase in satisfying sexual events.

Both produced modest average treatment effects in their pivotal trials.

One naming note, because most people arrive at this question from a PT-141 search. PT-141 is the development name commonly used for bremelanotide; Vyleesi® is the FDA-approved 1.75 mg subcutaneous bremelanotide product. Compounded preparations containing bremelanotide or "PT-141" are not Vyleesi and are not FDA-approved drug products. Everything on this page compares two approved products using their approved labels.

Who Each One Is Approved For

The indications are nearly identical in wording, with one meaningful difference.

Addyi is indicated for "women less than 65 years of age with acquired, generalized hypoactive sexual desire disorder (HSDD) as characterized by low sexual desire that causes marked distress or interpersonal difficulty," and not due to a co-existing medical or psychiatric condition, problems within the relationship, or the effects of another medication. It is not indicated in men, and not indicated to enhance sexual performance.

Vyleesi uses the same qualifying language but a narrower population: premenopausal women. Its label states it "is not indicated for the treatment of HSDD in postmenopausal women or in men."

So Addyi now covers women under 65 whether premenopausal or postmenopausal, while Vyleesi is premenopausal only. That broader Addyi population is recent: the current label lists Indications and Usage as a recent major change dated 12/2025, and the label itself was revised in December 2025. Anything written before then describes a narrower indication.

Both labels define the terms. Acquired means the problem developed in someone who previously had no difficulty with desire. Generalized means it occurs regardless of the type of stimulation, situation or partner.

How They Are Taken

This is the sharpest practical difference, and it is not a matter of preference — the label explains why each schedule exists.

Addyi: 100 mg daily, at bedtime

The dosing section states the reason plainly: "ADDYI is dosed at bedtime because administration during waking hours increases the risks of hypotension, syncope, accidental injury, and central nervous system (CNS) depression (such as somnolence and sedation)."

It is taken continuously, every night, independent of sexual activity.

The label also sets a clear stopping rule: "Discontinue ADDYI after 8 weeks if the patient does not report an improvement in her HSDD symptoms." As the next section shows, Vyleesi carries a near-identical instruction.

Vyleesi: 1.75 mg injected, only when needed

Subcutaneously into the abdomen or thigh, at least 45 minutes before anticipated sexual activity, no more than once in 24 hours and no more than eight times a month.

The label adds a candid limitation: "The duration of efficacy after each dose is unknown and the optimal window for VYLEESI administration has not been fully characterized."

In the trials, participants used a median of ten injections across 24 weeks — around two or three a month.

Both labels tell you when to stop

This is the cleanest thing the two labels agree on, and almost no comparison mentions it.

• Addyi: "Discontinue ADDYI after 8 weeks if the patient does not report an improvement in her HSDD symptoms."
• Vyleesi: "Discontinue VYLEESI after 8 weeks if the patient does not report an improvement in her symptoms."

Eight weeks, either way. Both instructions are addressed to the prescriber, and they exist because a treatment can otherwise be continued indefinitely without anyone formally asking whether it is working.

A deeper difference than daily versus on-demand

The schedules reflect two different strategies, not just two conveniences. Addyi is a continuous daily pharmacological treatment — taken every night regardless of sexual activity, with an effect assessed over weeks. Vyleesi is event-linked dosing — but the label is candid that the link is imprecise, stating that the duration of efficacy after each dose is unknown and the optimal administration window "has not been fully characterized." So one is a sustained treatment, and the other is timed to an event whose ideal timing has not been established.

Two Things Widely Repeated About Addyi That Are Out of Date

Both appear constantly in coverage of this drug, and neither reflects the current label.

Alcohol is a timing rule, not a contraindication

Addyi is frequently described as contraindicated with alcohol. Alcohol is no longer listed as a blanket contraindication; the current boxed warning uses timing and skip-dose instructions instead. It says:

"Counsel patients to wait at least two hours after consuming one or two standard alcoholic drinks before taking ADDYI at bedtime or to skip their ADDYI dose if they have consumed three or more standard alcoholic drinks that evening."

That is a timing and skip-dose instruction. The original 2015 labelling was stricter; this is the current wording.

The restrictive REMS programme is gone

Addyi was launched under a Risk Evaluation and Mitigation Strategy requiring prescribers and pharmacies to be certified. Those certification requirements were removed in 2019, and Addyi is no longer dispensed under that restricted certification structure. The current label carries no REMS statement.

Anyone writing that Addyi is "only available through a restricted programme" is describing a system that no longer operates.

What the Boxed Warning Actually Covers

Addyi's boxed warning is headed "HYPOTENSION and SYNCOPE IN CERTAIN SETTINGS" and has three parts:

• Alcohol — using Addyi and alcohol close together increases the risk of severe hypotension and syncope, handled by the timing rule above.
• CYP3A4 inhibitors — moderate or strong inhibitors raise flibanserin levels and are contraindicated.
• Hepatic impairment — also raises levels, and is contraindicated.

The full contraindications list is those two plus known hypersensitivity, where reactions including anaphylaxis and angioedema have been reported.

Vyleesi does not carry an FDA boxed warning, but it does have important contraindications and warnings. Its entire contraindications section reads: uncontrolled hypertension or known cardiovascular disease. The label adds that it is not recommended for people at high cardiovascular risk, because each dose transiently raises blood pressure by up to 6 mmHg systolic and 3 mmHg diastolic, peaking two to four hours later.

It also carries a labelled warning that has no counterpart on the Addyi label: focal hyperpigmentation, including of the face, gingiva and breasts. About 1% developed it in the phase 3 trials, where use was up to eight doses a month. That rose to 38% after eight consecutive daily doses — but daily dosing is not the FDA-approved regimen, so the 38% figure describes an exposure the label does not permit rather than a real-world rate under labelled use. 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.

Side Effects, Side by Side

Addyi — premenopausal trial population

Rates on Addyi 100 mg at bedtime (n = 1,543) against placebo (n = 1,556):

• Dizziness — 11.4% (placebo 2.2%)
• Somnolence — 11.2% (placebo 2.9%)
• Nausea — 10.4% (placebo 3.9%)
• Fatigue — 9.2% (placebo 5.5%)
• Insomnia — 4.9% (placebo 2.8%)
• Dry mouth — 2.4% (placebo 1.0%)

In postmenopausal participants the same effects appeared at lower rates — dizziness 7.9%, somnolence 7.7%, nausea 6.6%.

The label also reports accidental injury in 2.7% on Addyi against 2.5% on placebo — but notes that among injured participants, symptoms of CNS depression in the preceding day were present in 21% of the Addyi group against 6% of placebo.

Discontinuation because of adverse reactions: 13% on Addyi against 6% on placebo in the premenopausal trials, and 9% against 5% in the postmenopausal trials.

Vyleesi

Rates on bremelanotide (n = 627) against placebo (n = 620):

• 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%)

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

Full detail: PT-141 Side Effects: Every Number the Label Reports.

Comparing the dropout numbers without mixing them up

This is where side-by-sides usually go wrong, because each label reports two different discontinuation figures and they are easy to confuse.

Discontinuation specifically because of adverse reactions — the direct tolerability measure, and the one to compare:

• Addyi: 13% against 6% on placebo (premenopausal trials); 9% against 5% (postmenopausal trials)
• Vyleesi: 18% against 2% on placebo

All-cause discontinuation — everyone who left early, for any reason, including withdrawn consent, loss to follow-up and personal circumstances:

• Addyi: the label reports completion across the three premenopausal trials of 69% on Addyi and 78% on placebo — so roughly 31% against 22% did not finish
• Vyleesi: 40% and 39% discontinued early in the two trials, against 13% and 25% on placebo

Comparing Addyi's 13% adverse-reaction figure against Vyleesi's 40% all-cause figure — as many pages do — makes the gap look roughly three times larger than the tolerability data supports. Matched like with like, the difference is real but narrower: 18% against 13% for adverse-reaction dropout, and about 40% against 31% for leaving early at all.

The honest comparison

The adverse-effect patterns are different in kind. Addyi is taken nightly, so dizziness and somnolence at around 11% occur in the context of continuous daily treatment. Vyleesi is taken intermittently, and its most common adverse effect — nausea in four of ten participants — is concentrated around individual doses and heaviest on the first.

Effectiveness: Each Failed What the Other Passed

This is the part that does not appear in any side-by-side we could find, and it is the most useful thing on this page.

Addyi moved satisfying sexual events. Its desire story is mixed.

Across three trials (1,187 on Addyi against 1,188 on placebo), the label reports treatment differences in satisfying sexual events per 28 days of 0.9 (95% CI 0.3–1.4), 0.6 (95% CI −0.03–1.2) and 1.0 (95% CI 0.4–1.5). Median differences were about half an event to one extra event per month.

On the desire measure, the label states: "In Study 1 and 2, there were no statistically significant differences between ADDYI and placebo for the eDiary sexual desire endpoint." The treatment differences were 2.3 (95% CI −0.1 to 4.7) and 1.7 (95% CI −0.5 to 4.0), both non-significant.

The consequence is written into the label's own tables: for those two trials, "p-value not reported for secondary endpoints because the trial failed on the eDiary Desire co-primary efficacy endpoint."

But Study 3 used a different desire endpoint, and it succeeded. The label explains that Studies 1 and 2 used the eDiary score as the desire co-primary, while Study 3 used the FSFI Desire domain — and "in Study 3 there was statistically significant improvement in the change from baseline to Week 24 in sexual desire (using the FSFI Desire Domain) with ADDYI compared to placebo."

The label adds that "the FSFI Desire Domain findings were consistent across all three trials," where it served as a secondary endpoint in Studies 1 and 2. Treatment differences on that measure were 0.4, 0.3 and 0.3 points.

So the accurate summary is not "Addyi's desire endpoint failed." It is that Addyi failed the daily-diary desire measure it pre-specified in two trials, and met a questionnaire-based desire measure in the third — with that questionnaire pointing the same direction in all three.

Vyleesi moved desire and distress. Its satisfying-events endpoint did not move.

Across its two trials (1,267 women randomised), bremelanotide improved the FSFI desire domain by +0.30 and +0.42 points against placebo, and reduced distress on the Female Sexual Distress Scale item 13 by −0.37 and −0.29. Both co-primary endpoints were met in both trials.

The trials did not show a statistically significant increase in satisfying sexual events in either trial — p = 0.76 and p = 0.70.

What that leaves

One drug increased the count of satisfying encounters by about half an event a month, while its pre-specified daily-diary desire measure failed in two of three trials. The other improved desire and distress questionnaires without showing a statistically significant increase in the encounter count.

Both sets of effect sizes are small. The two programmes happen to share one measure — the FSFI desire domain, which runs from 1.2 to 6.0 — and the placebo-adjusted changes on it were numerically similar: around 0.3 to 0.4 points for Addyi, and 0.30 to 0.42 for Vyleesi. That similarity is worth noticing, but it is not a head-to-head result: the trials were separate programmes with different populations, designs and analytic methods, and numbers from different studies cannot be treated as if they had been compared directly.

Nothing here supports describing either as clearly better, and nothing supports describing either as strong.

What This Comparison Cannot Do

These figures come from separate trial programmes with different designs, different populations and different endpoints. No head-to-head trial of the two drugs has been conducted, so any statement that one outperforms the other is a comparison between studies, not a finding.

Which — if either — is appropriate for a particular person depends on their medical history, other medications, liver function, cardiovascular status, alcohol use, and whether what they are experiencing meets the definition both labels describe. Several of those are disqualifying for one drug and not the other.

That assessment belongs to a prescriber. Related reading: What PT-141 Actually Is, Who It Is Approved For, and What the Trials Found and Low Libido in Women: Causes, HSDD and Treatment Options.

Frequently Asked Questions

What is the difference between Addyi and Vyleesi?

Addyi is a 100 mg tablet taken every night at bedtime, continuously, with a boxed warning for hypotension and syncope. Vyleesi is a 1.75 mg injection taken only when needed, at least 45 minutes before anticipated activity, up to eight times a month, with no boxed warning but a contraindication in uncontrolled hypertension or known cardiovascular disease. Addyi is approved for women under 65; Vyleesi for premenopausal women only.

What are the side effects of Addyi?

In premenopausal trial participants: dizziness 11.4%, somnolence 11.2%, nausea 10.4%, fatigue 9.2%, insomnia 4.9% and dry mouth 2.4%, against placebo rates of 2.2%, 2.9%, 3.9%, 5.5%, 2.8% and 1.0%. Thirteen percent discontinued because of adverse reactions, against 6% on placebo. Rates were lower in postmenopausal participants.

Can you drink alcohol on Addyi?

The current label does not contraindicate alcohol. Its boxed warning instructs waiting at least two hours after one or two standard drinks before taking the bedtime dose, or skipping that night's dose after three or more drinks. Earlier labelling was stricter, which is why the contraindication claim is still widely repeated.

Is Addyi still under a REMS?

The prescriber and pharmacy certification requirements were removed in 2019, and the current label carries no REMS statement. Descriptions of Addyi as available only through a restricted programme are out of date.

Which works better, Addyi or Vyleesi?

No head-to-head trial exists, so any comparison is between separate studies. On the one measure both programmes used — the FSFI desire domain — the placebo-adjusted changes were numerically similar and both small. Addyi increased satisfying sexual events by roughly half to one per month; Vyleesi improved desire and distress scores but its trials did not show a statistically significant increase in satisfying sexual events. Addyi's picture is mixed rather than simply negative: its pre-specified daily-diary desire endpoint failed in Studies 1 and 2, but the FSFI desire domain was the co-primary in Study 3 and did reach significance there.

Is PT-141 the same as Vyleesi?

Not exactly. PT-141 is the development name for the drug substance bremelanotide; Vyleesi® is the FDA-approved 1.75 mg subcutaneous bremelanotide product, with an approved label and indication. Compounded preparations containing bremelanotide or "PT-141" are not Vyleesi and are not FDA-approved drug products, and neither the trial results nor the safety data on this page describe them.

Why is Addyi taken daily and Vyleesi only when needed?

They act differently and are dosed accordingly. Addyi is a daily oral medication taken at bedtime specifically because, in the label's words, daytime dosing "increases the risks of hypotension, syncope, accidental injury, and central nervous system depression." Vyleesi is an on-demand injection taken at least 45 minutes before anticipated activity.

Do Addyi and Vyleesi work immediately?

Neither label makes an immediate-onset claim. Vyleesi is dosed at least 45 minutes before anticipated sexual activity, but its label states that the duration of efficacy after each dose is unknown and the optimal timing window has not been fully characterised. Addyi is taken every night and is not an on-demand medication at all; instead of an onset claim, its label gives an eight-week stopping rule if symptoms have not improved. Vyleesi's label sets the same eight-week review point.

How long does Addyi take to work?

The label gives no onset claim, but it does set a stopping point: discontinue after eight weeks if there has been no improvement in HSDD symptoms.

Can postmenopausal women take either?

As of the December 2025 label update, Addyi's indication covers women under 65, premenopausal and postmenopausal, and its label reports separate adverse-reaction rates for both groups. Vyleesi's label states it is not indicated for postmenopausal women.

Is Addyi or Vyleesi better after menopause?

The approved populations differ, which settles the question before effectiveness enters it. Vyleesi is not FDA-approved for postmenopausal women. Addyi is FDA-approved for women under 65, including postmenopausal women who meet the HSDD criteria on its label — a change reflected in the December 2025 labelling update. That does not make Addyi automatically appropriate or more effective for any particular postmenopausal woman; it means only one of the two has an approved indication covering her. Whether it suits her depends on her medical history, other medications, liver function and alcohol use, which is a prescriber's assessment.

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References

1. ADDYI (flibanserin) tablets — U.S. Prescribing Information. DailyMed, U.S. National Library of Medicine. Label revised 12/2025. Boxed Warning, Recent Major Changes, and sections 1, 2.1, 2.3, 4, 6.1 and 14.
2. VYLEESI (bremelanotide) injection — U.S. Prescribing Information. DailyMed, U.S. National Library of Medicine. Sections 1, 2.1, 2.2, 4, 5.1, 5.2 and 6.1.
3. 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 the contents of FDA-approved prescribing information and does not recommend either treatment, or any dose. The bremelanotide information here describes Vyleesi®, the FDA-approved product, and does not describe compounded preparations. No head-to-head trial of these two medications has been conducted, and figures from separate trial programmes are not directly comparable. Questions about whether a treatment is appropriate should be discussed with a qualified healthcare professional. AmalfiDuo Journal articles are written by AmalfiDuo Editorial and are not medically reviewed — see our Editorial Policy.

ADDYI® and VYLEESI® are trademarks of their respective owners. AmalfiDuo is not affiliated with or endorsed by the owners or manufacturers of these brands.