Vyleesi (Bremelanotide) Geriatric Dosing: What Clinicians and Patients 65+ Need to Know

Is there a separate Vyleesi dose for people 65 and older?

No. The label gives one regimen: 1.75 mg injected subcutaneously into the abdomen or thigh with the prefilled autoinjector, as needed, at least 45 minutes before anticipated sexual activity; no more than one dose within 24 hours; more than 8 doses per month is not recommended [1]. If there is no improvement after 8 weeks, the label says to stop [1]. The dosing section sets no different amount or schedule for older adults [1]. The label's geriatric use section says safety and effectiveness have not been established in geriatric patients [4].

Who the label covers, and who the trials enrolled

The indication is narrow and defined by menopausal status: premenopausal women with acquired, generalized HSDD, meaning low sexual desire that causes marked distress or interpersonal difficulty and is not due to a coexisting medical or psychiatric condition, relationship problems, or a medication or drug [1]. The limitations of use state that Vyleesi is not indicated for HSDD in postmenopausal women or in men, and is not indicated to enhance sexual performance [1].

The two identical phase 3 trials behind approval randomized 1,267 premenopausal women (1,247 in the safety population, 1,202 in the efficacy analysis), with a mean age of 39 and an age range of 19 to 56 [1][2]. The 52-week open-label extension enrolled 684 of the 856 women who completed the double-blind phase [3].

Blood pressure: the caution that matters most

The label lists uncontrolled hypertension or known cardiovascular disease as contraindications [1]. It also says Vyleesi is not recommended for patients at high risk for cardiovascular disease, that cardiovascular risk should be considered before starting and periodically during treatment, and that blood pressure should be well controlled [1].

Each dose produces a transient rise in blood pressure and a fall in heart rate. In clinical studies the maximal increases were 6 mmHg systolic and 3 mmHg diastolic, peaking 2 to 4 hours after the dose, with a heart rate reduction of up to 5 beats per minute; values usually returned to baseline within 12 hours, and no additive effect appeared with repeat daily dosing 24 hours apart for up to 16 days [1]. Those are maximal figures. In a separate open-label ambulatory monitoring study of 127 premenopausal women dosed once daily for 8 days, mean daytime blood pressure rose 1.9 mmHg systolic (95% CI 1.0 to 2.7) and 1.7 mmHg diastolic (95% CI 0.9 to 2.4), with a mean heart rate decrease of 0.5 beats per minute [1].

Both datasets come from premenopausal women [1].

Nausea and skin darkening: what the label reports

Nausea is the most common adverse reaction: 40.0% of Vyleesi-treated patients versus 1.3% on placebo in the pooled phase 3 trials, 13% received an antiemetic, and 8% stopped treatment because of it [1]. It was highest after the first dose (21% of patients) and fell to about 3% with later doses, with median onset within one hour and a duration of about two hours [1]. Pretreating with oral ondansetron 8 mg 30 minutes before the injection did not reduce nausea in a phase 4 single-dose study of 228 healthy women, and the label does not recommend it [1].

Focal hyperpigmentation, meaning darkening of skin, gums or breasts, including the face, was reported by 1% of patients given up to 8 doses per month versus none on placebo [1]. In a separate study 38% of patients developed it after daily dosing for 8 days, and a further 14% after 8 more consecutive days; patients with darker skin were more likely to develop it, and resolution was not confirmed in all patients after stopping [1]. The label says to consider discontinuing Vyleesi if hyperpigmentation develops [1].

Across the phase 3 program, 18% of Vyleesi-treated patients stopped because of adverse reactions versus 2% on placebo, and serious adverse reactions occurred in 1.1% versus 0.5% [1].

Kidney and liver function

Bremelanotide is metabolized by hydrolysis of amide bonds, and 64.8% of radioactivity was recovered in urine and 22.8% in feces [1]. After a 1.75 mg subcutaneous dose, mean Cmax is 72.8 ng/mL, AUC is 276 hr*ng/mL, median time to peak is about 1 hour, and mean terminal half-life is about 2.7 hours [1].

Exposure rises 1.5-fold in moderate renal impairment and 2-fold in severe renal impairment, and 1.2-fold (mild) to 1.7-fold (moderate) in hepatic impairment [1]. For mild to moderate renal impairment (eGFR 30-89 mL/min/1.73 m2) and mild to moderate hepatic impairment (Child-Pugh A and B), the label says no dosing adjustments are recommended, and it says to use with caution in severe renal impairment (eGFR below 30) and severe hepatic impairment (Child-Pugh C) [4]. One case of acute hepatitis, with liver enzymes above 40 times normal, occurred in a patient after 10 doses in the open-label extension; because another cause was not found, a role for Vyleesi could not be excluded [1].

Interactions named on the label

The label names two interaction problems. Vyleesi may significantly decrease the systemic exposure of oral naltrexone, and the label says to avoid using it with oral naltrexone-containing products intended to treat alcohol or opioid addiction because of the severe consequence of naltrexone treatment failure [1]. Vyleesi may also slow gastric emptying and reduce absorption of oral medicines; the label says to avoid it with oral drugs that depend on threshold blood concentrations, such as antibiotics, and to consider skipping a dose when a quick effect from an oral medicine such as indomethacin is wanted [1]. In clinical pharmacology studies only naltrexone and indomethacin were meaningfully affected [1].

Alcohol did not change bremelanotide blood levels in a crossover study of 24 healthy male and female volunteers given 0.6 g/kg alcohol; that study used a 20 mg intranasal dose, which produces about 2.5-fold the peak concentration of Vyleesi [1].

What the label says about women 65 and older

The label says safety and effectiveness have not been established in geriatric patients [4]. The trial population stopped at 56, so the reported results do not describe how blood pressure, nausea or hyperpigmentation would behave in women 65 or older [1][2].