Vyleesi is a shot of bremelanotide, the peptide also called PT-141, approved for low sexual desire in premenopausal women. It is injected, so it never passes through the stomach. It can still change how pills taken by mouth are absorbed.
That effect is the root of every interaction on its label. This page goes through the label’s drug interaction sections, the tested drug list, and the alcohol study. Dosing limits are covered in PT-141 dosage.
Why an injection affects pills
The label states that Vyleesi may slow gastric emptying [1]. A slower stomach can reduce the rate and extent of absorption of oral medicines taken at the same time.
Bremelanotide acts quickly and leaves quickly. The label gives a median time to peak level of about 1 hour, and a mean half-life of about 2.7 hours [1]. How long its effects last is covered in how long PT-141 lasts.
What the label tells patients to avoid
Section 7 of the label gives two instructions [1]. The first concerns oral drugs that only work above a threshold level in the blood. Patients are told to avoid Vyleesi when taking these, and the label gives antibiotics as its example.
The second part of that section covers drugs where a quick effect matters. If an oral drug’s effect is delayed, the label says patients should consider stopping Vyleesi. Its example is a pain reliever, indomethacin.
The only named drug to avoid outright is naltrexone. The label says Vyleesi may significantly decrease exposure to oral naltrexone [1]. Patients should avoid combining the two when naltrexone treats alcohol or opioid addiction, because naltrexone failing there has severe consequences.
Which oral drugs were tested
Section 12.3 reports clinical pharmacology studies with a 1.75 mg dose of Vyleesi under the skin [1]. Its Figure 1 lists 17 oral drugs taken alongside it.
The label’s conclusion is one sentence. Vyleesi did not affect absorption of the tested drugs to any clinically relevant degree, except for naltrexone and indomethacin.
| Group | Drugs tested | Label's finding |
|---|---|---|
| Flagged by the label | Naltrexone, indomethacin | Lower exposure; see section 7 |
| Birth control hormones | Ethinyl estradiol, norethindrone | Not flagged |
| Blood pressure drugs | Amlodipine, lisinopril, losartan, metoprolol, hydrochlorothiazide, furosemide | Not flagged |
| Mood drugs | Bupropion, sertraline, venlafaxine | Not flagged |
| Others | Celecoxib, metformin, phentermine, pseudoephedrine | Not flagged |
The figure plots peak level and total exposure for each drug. For several drugs the peak dropped more than total exposure did, which fits a slower stomach. The label judged only two of them clinically relevant.
A 2022 review of the whole development program reached the same result [2]. The program covered 3,500 subjects in 43 completed studies. Most drug interactions were not clinically significant, except those lowering indomethacin and naltrexone levels.
Birth control pills
The label’s tested list includes ethinyl estradiol and norethindrone, and neither is flagged as a clinically relevant interaction [1].
That result covers those two hormones taken by mouth. The label does not report tests of other progestins, or of patches, rings, implants or intrauterine devices.
Contraception comes up in the label for another reason. Section 8.3 advises women who could become pregnant to use effective contraception while taking Vyleesi, and to stop it if pregnancy is suspected [1].
The label bases that on animal studies. In pregnant dogs given bremelanotide at 16 or more times the human exposure, it caused fetal harm. The trials of more than 1,057 patients recorded 7 pregnancies, with no major birth defects reported.
Alcohol
The label describes a placebo-controlled crossover study in 12 healthy men and 12 healthy women [1]. Each took a single 20 mg intranasal dose of bremelanotide, 10 minutes after a placebo drink or alcohol at 0.6 g/kg.
The label equates that amount to three 12-ounce cans of 5% beer for a 70 kg person. The intranasal dose reached a mean peak level 2.5-fold higher than Vyleesi’s.
Alcohol had no effect on bremelanotide’s levels [1]. Abnormal drops in blood pressure on standing were about as common with bremelanotide plus alcohol as with alcohol alone. Flushing was more common than with alcohol alone, and similar to bremelanotide alone.
The published report of the study reached the same conclusion [3]. No participant stopped because of side effects. Its limits are plain: 24 healthy volunteers, single doses, and a nasal form rather than the approved injection.
A 2020 pharmacy review summed up the record as limited drug interactions, with no clinically significant interaction with ethanol [4].
What this means
The label’s interaction list is short. Oral naltrexone for addiction is the one combination to avoid. Oral drugs that depend on a set blood level, or need to work fast, are the ones to raise with a prescriber.
Blood pressure and heart rate effects are a separate question, covered in bremelanotide side effects. For other options, start at the sexual health goal page.