Vyleesi (Bremelanotide) Complete Drug-Drug Interaction Profile

What does the Vyleesi label actually list?

The drug interactions section of the Vyleesi label has two parts [1]. One is a general warning that Vyleesi may slow gastric emptying and affect absorption of oral medicines [1]. The other is a specific instruction about oral naltrexone [1].

Oral naltrexone for alcohol or opioid addiction

The label says Vyleesi may significantly decrease the systemic exposure of orally administered naltrexone [1]. It tells patients to avoid Vyleesi with an oral naltrexone-containing product intended to treat alcohol or opioid addiction because naltrexone treatment failure would be a severe consequence [1]. The instruction is written for oral naltrexone products used for those addiction indications [1].

Slowed gastric emptying and oral absorption

The broader warning is that Vyleesi may slow gastric emptying and reduce the rate and extent of absorption of oral medicines [1]. The label tells patients to avoid Vyleesi when taking oral drugs that depend on threshold concentrations for efficacy, such as antibiotics [1]. It also says to consider discontinuing Vyleesi if an oral medicine has a delayed effect when a quick onset is wanted, such as indomethacin for pain relief [1]. In clinical pharmacology studies, only naltrexone and indomethacin were meaningfully affected [1].

Which oral medicines does the label name?

Antibiotics are the example for an oral drug that depends on a threshold concentration for efficacy [1]. Indomethacin is the example for an oral drug whose quick effect matters [1]. The label does not provide a separate timing schedule for either example [1].

Beyond antibiotics and indomethacin, the label specifically says to avoid Vyleesi with oral naltrexone products used to treat alcohol or opioid addiction [1]. For other oral medicines the label gives the general absorption warning but no product-specific instruction, and its drug interactions section names no other drug classes [1].

Does Vyleesi interact with birth control pills?

Oral contraceptives are not named in the label's drug interactions section [1]. The general warning about slowed gastric emptying applies to oral medicines as a class, but the label gives no oral-contraceptive-specific instruction or timing separation [1]. The label separately says to use effective contraception while taking Vyleesi and to discontinue Vyleesi if pregnancy is suspected [1].

Does alcohol interact with Vyleesi?

A placebo-controlled, randomized, double-blind, three-period crossover study gave 24 healthy volunteers alcohol 0.6 g/kg with a single 20 mg intranasal dose of bremelanotide [1]. The intranasal dose produces a mean Cmax about 2.5-fold higher than Vyleesi [1]. Alcohol did not change the pharmacokinetic profile of bremelanotide [1]. Flushing was more frequent with bremelanotide plus alcohol than with alcohol alone but similar to bremelanotide alone; headache was more frequent than with bremelanotide alone but similar to alcohol alone [1].

Does Vyleesi interact with blood pressure medicines or other vasoactive drugs?

The label's drug interactions section does not name antihypertensives, triptans, ergots, decongestants, or stimulants [1]. The label does say that each Vyleesi dose transiently increases blood pressure and reduces heart rate [1]. In clinical studies, the maximal increases were 6 mmHg systolic and 3 mmHg diastolic, with a heart rate reduction of up to 5 beats per minute, and values usually returned to baseline within 12 hours [1]. In an open-label ambulatory study of 127 premenopausal women dosed once daily for 8 days, mean daytime blood pressure rose 1.9 mmHg systolic and 1.7 mmHg diastolic, with a mean heart rate decrease of 0.5 beats per minute [1].

The label lists uncontrolled hypertension or known cardiovascular disease as contraindications and says Vyleesi is not recommended in patients at high risk of cardiovascular disease [1]. It also says to consider the patient's cardiovascular risk and ensure blood pressure is well controlled before starting and periodically during treatment [1].

Does Vyleesi have CYP450 interactions?

Bremelanotide is metabolized by hydrolysis of amide bonds; after a dose, 64.8% of radioactivity is recovered in urine and 22.8% in feces [1]. The label's drug interactions section describes gastric emptying and oral naltrexone, not CYP450 inhibition or induction [1]. It also does not list CYP3A4 inhibitors or inducers as interactions [1].