Vyleesi and PPIs (Omeprazole, Pantoprazole) Interaction: What Patients and Clinicians Need to Know

Is there an interaction between Vyleesi and PPIs?

The drug interactions section of the Vyleesi label covers two things only: the effect of Vyleesi on other oral medicines, and oral naltrexone [1].

Bremelanotide is given as a subcutaneous injection, is about 100% bioavailable by that route, and is metabolized by hydrolysis of amide bonds [1]. For comparison, the Nexium (esomeprazole) label describes esomeprazole as inhibiting CYP2C19 activity and lists interactions with clopidogrel and citalopram [2].

What the Nexium label says about acid-dependent absorption

The Nexium label says esomeprazole can reduce the absorption of other drugs by lowering stomach acidity, and lists iron salts, erlotinib, dasatinib, nilotinib, mycophenolate mofetil, ketoconazole and itraconazole [2]. For mycophenolate mofetil, it says co-administration of omeprazole reduced exposure to the active metabolite, and that the clinical relevance for organ rejection has not been established [2].

These warnings concern oral drugs. After a 1.75 mg subcutaneous dose, bremelanotide reaches peak plasma levels at a median of about 1.0 hour, has absolute bioavailability of about 100%, and has a mean terminal half-life of about 2.7 hours [1].

Interactions the Vyleesi label does list

The Vyleesi label says the drug may slow gastric emptying and so has the potential to reduce the rate and extent of absorption of oral medicines taken at the same time. It instructs patients to avoid Vyleesi with oral drugs that depend on threshold blood concentrations to work, such as antibiotics, and says patients should consider skipping Vyleesi when a quick effect from an oral medicine such as indomethacin is wanted [1]. The label adds that in clinical pharmacology studies only naltrexone and indomethacin were meaningfully affected [1].

The label also says to avoid Vyleesi with oral naltrexone products intended to treat alcohol or opioid addiction, because Vyleesi may significantly decrease naltrexone exposure and the consequence of treatment failure is severe [1].

For dosing, the label says no more than one dose in 24 hours, because doses close together may increase additive effects on blood pressure, and no more than 8 doses a month, because more frequent dosing increases the risk of focal hyperpigmentation and the time per month that blood pressure is raised [1].

Nausea overlap

Nausea is the most common Vyleesi adverse reaction: 40% versus 1.3% on placebo, highest after the first dose (21%) and falling to about 3% with later doses, with median onset within an hour and a duration of about 2 hours [1]. Thirteen percent of patients received an anti-nausea medicine and 8% stopped the trials because of nausea [1]. The Nexium label also lists nausea among its common adverse reactions in adults, alongside headache, diarrhea and abdominal pain [2].

The Vyleesi label says to consider discontinuing Vyleesi for persistent or severe nausea, or starting anti-emetic therapy for patients who are bothered by nausea but wish to continue [1]. It also reports a phase 4 study of 228 healthy women in which 8 mg of oral ondansetron taken 30 minutes before a Vyleesi dose did not reduce nausea, so pre-treatment is not recommended; ondansetron given after Vyleesi, or after nausea begins, has not been formally studied [1]. That finding concerns Vyleesi and ondansetron, not PPIs.