PT-141 (Bremelanotide) and Acetaminophen Interaction: What Clinicians and Patients Need to Know

Does bremelanotide interact with acetaminophen?

Bremelanotide is the active drug in Vyleesi, a 1.75 mg subcutaneous autoinjector approved for acquired, generalized hypoactive sexual desire disorder in premenopausal women. It is injected into the abdomen or thigh as needed, at least 45 minutes before anticipated sexual activity, no more than once in 24 hours, and more than 8 doses a month is not recommended [1].

The label's Drug Interactions section says Vyleesi may slow gastric emptying and therefore has the potential to reduce the rate and extent of absorption of oral medicines taken at the same time [1]. The warning is written for oral medicines in general, and acetaminophen is not among the examples the label gives.

What the label names

The Drug Interactions section names three situations [1]:

• Oral drugs that depend on threshold blood levels for efficacy, with antibiotics as the example. The label says to avoid Vyleesi when taking these [1].
• Oral drugs where a quick effect is wanted, with the pain reliever indomethacin as the example. The label says patients should consider discontinuing Vyleesi if a delayed effect of the oral medicine is a concern [1].
• Oral naltrexone products used for alcohol or opioid addiction. The label says to avoid the combination because Vyleesi may significantly decrease naltrexone exposure and treatment failure would have severe consequences [1].

The label also states that in clinical pharmacology studies only naltrexone and indomethacin were meaningfully affected [1].

Is there a shared liver pathway?

Acetaminophen can cause dose-related liver injury [4]. Vyleesi's label describes bremelanotide as metabolized by hydrolysis of amide bonds; after a 1.75 mg subcutaneous dose, 64.8% of radioactivity was recovered in urine and 22.8% in feces, and mean terminal half-life was about 2.7 hours [1].

The label does carry one liver signal of its own: a single case of acute hepatitis in the open-label extension, after 10 doses over a year, with transaminases above 40 times the upper limit of normal and bilirubin 6 times normal, returning to normal 4 months after the drug was stopped. Another cause was not identified, so a role for Vyleesi could not be excluded. There was no imbalance between treatment groups in transaminase outliers across the development program [1]. Exposure to bremelanotide is also higher with liver impairment: AUC rises 1.2-fold in mild and 1.7-fold in moderate hepatic impairment [1].

Acetaminophen's own liver risk

In a prospective US study of 662 patients with acute liver failure at 22 centers, 275 cases (42%) were attributed to acetaminophen. The median dose ingested was 24 g. Unintentional overdose accounted for 48% of those cases, and within that group 38% had taken two or more acetaminophen preparations and 63% had used narcotic-containing products [2].

What about PT-141 sold as a research peptide?

PT-141 sold as a compounded or research-use peptide is not Vyleesi and is not an FDA-approved drug; compounded drugs are not reviewed by FDA for safety, effectiveness or quality before marketing [3][1]. The label statements above apply to the Vyleesi 1.75 mg autoinjector.