Vyleesi (Bremelanotide) Dosing in Hepatic Impairment

What is the Vyleesi dose in liver disease?

Vyleesi comes in a prefilled autoinjector that delivers 1.75 mg of bremelanotide under the skin, into the abdomen or thigh [1]. The dosage instructions give one regimen: as needed, at least 45 minutes before anticipated sexual activity, no more than once in 24 hours, and more than 8 doses per month is not recommended [1]. The label reports how liver impairment changes blood levels and gives a statement for each degree of impairment [1][2].

How much higher are bremelanotide levels?

The label reports that bremelanotide exposure (AUC) is 1.2-fold higher in mild hepatic impairment and 1.7-fold higher in moderate hepatic impairment [1]. After a 1.75 mg subcutaneous dose, mean Cmax is 72.8 ng/mL and AUC is 276 hr*ng/mL [1]. The mean terminal half-life is about 2.7 hours, with a range of 1.9 to 4.0 hours [1].

How is bremelanotide cleared?

Bremelanotide is metabolized by hydrolysis of amide bonds [1]. After a dose, 64.8% of radioactivity is recovered in urine and 22.8% in feces [1].

What should be watched for at the standard dose?

Vyleesi transiently raises blood pressure and lowers heart rate after each dose [1]. In clinical studies the maximal increases were 6 mmHg systolic and 3 mmHg diastolic, peaking 2 to 4 hours after the dose, with heart rate down up to 5 beats per minute [1]. The label contraindicates Vyleesi in uncontrolled hypertension or known cardiovascular disease [1].

Nausea occurred in 40% of Vyleesi-treated patients versus 1.3% on placebo in the phase 3 trials; 13% used anti-nausea medicine and 8% stopped because of nausea [1].

One case of acute hepatitis occurred after 10 doses in the open-label extension; transaminases exceeded 40 times the upper limit of normal, another cause was not found, and a role for Vyleesi could not be excluded [1].

What about severe hepatic impairment?

The label says to use Vyleesi with caution in severe hepatic impairment (Child-Pugh C; score 10-15) [2]. For mild to moderate impairment (Child-Pugh A and B; score 5-9), it recommends no dosing adjustment [2]. The exposure figures in this page are the label's values for mild and moderate impairment [1].