Switching From or To Vyleesi (Bremelanotide): Protocols, Timelines, and Clinical Guidance

Timing after a dose

Vyleesi is not a daily drug. After a 1.75 mg subcutaneous dose, the median time to peak plasma concentration is about 1 hour and the mean terminal half-life is about 2.7 hours (range 1.9 to 4.0) [1]. The label states that the duration of efficacy after each dose is unknown and that the optimal window for administration has not been fully characterized; it says patients may decide their own timing from how they experience the duration of effect on desire and any adverse reactions such as nausea [1].

Cardiovascular checks before starting

Vyleesi is indicated for premenopausal women with acquired, generalized hypoactive sexual desire disorder, meaning low sexual desire that causes marked distress or interpersonal difficulty and is not due to a medical or psychiatric condition, relationship problems, or a drug. The label states it is not indicated for postmenopausal women, for men, or to enhance sexual performance [1]. It is contraindicated in uncontrolled hypertension or known cardiovascular disease, and the label says it is not recommended for patients at high risk for cardiovascular disease and that cardiovascular risk and blood pressure control should be considered before starting and periodically during treatment [1].

Each dose transiently raises blood pressure and lowers heart rate. In clinical studies the maximal increases were 6 mmHg systolic and 3 mmHg diastolic, peaking 2 to 4 hours after the injection, with heart rate down up to 5 beats per minute and values usually back to baseline within 12 hours [1]. Those are maximal figures; in an open-label ambulatory study of 127 premenopausal women dosed once daily for 8 days, the mean daytime rise was 1.9 mmHg systolic and 1.7 mmHg diastolic [1].

What the label says about dosing and stopping

The Vyleesi label recommends a 1.75 mg injection under the skin of the abdomen or thigh at least 45 minutes before anticipated sexual activity. It limits dosing to once in 24 hours, does not recommend more than eight doses a month, and says to stop after eight weeks without improvement in symptoms [1]. The label links more frequent dosing to a greater risk of focal hyperpigmentation and to more time each month with raised blood pressure [1].

Nausea is the most common adverse reaction. In the pooled phase 3 trials of 1,247 premenopausal women, it occurred in 40.0% of Vyleesi users versus 1.3% on placebo, 13% needed anti-nausea medicine and 8% stopped the trials because of it; it was highest after the first dose (21% of patients) and fell to about 3% after later doses [1]. In a phase 4 study of 228 healthy women, 8 mg of oral ondansetron taken 30 minutes before the injection did not reduce nausea, and the label does not recommend pre-treatment with it [1].

Interactions to check at the point of a switch

Vyleesi may slow gastric emptying and reduce absorption of oral medicines. The label says to avoid it with oral drugs that depend on threshold blood concentrations for efficacy, such as antibiotics, and to consider discontinuing Vyleesi if an oral medicine such as indomethacin has a delayed effect when a quick effect is wanted [1]. It also says Vyleesi may significantly decrease blood levels of oral naltrexone, and that Vyleesi should be avoided with oral naltrexone-containing products intended to treat alcohol or opioid addiction because of the severe consequences of naltrexone treatment failure [1]. In clinical pharmacology studies, only naltrexone and indomethacin were meaningfully affected [1].

Compounded PT-141 is not Vyleesi

Vyleesi is the FDA-approved bremelanotide product. Products sold as compounded or research-use PT-141 are not Vyleesi and are not FDA-approved drugs; compounded drugs are not reviewed by FDA for safety, effectiveness or quality before marketing [2][1]. Moving between a compounded PT-141 product and Vyleesi is not the same as switching between two approved drugs.