Vyleesi
(bremelanotide)Dosage & Administration
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Vyleesi Prescribing Information
VYLEESI is indicated for the treatment of premenopausal women with acquired, generalized hypoactive sexual desire disorder (HSDD), as characterized by low sexual desire that causes marked distress or interpersonal difficulty and is NOT due to:
- A co-existing medical or psychiatric condition,
- Problems with the relationship, or
- The effects of a medication or drug substance.
Acquired HSDD refers to HSDD that develops in a patient who previously had no problems with sexual desire. Generalized HSDD refers to HSDD that occurs regardless of the type of stimulation, situation or partner.
Limitations of Use
- VYLEESI is not indicated for the treatment of HSDD in postmenopausal women or in men.
- VYLEESI is not indicated to enhance sexual performance.
Recommended Dosage
The recommended dosage of VYLEESI is 1.75 mg administered subcutaneously in the abdomen or thigh, as needed, at least 45 minutes before anticipated sexual activity. The duration of efficacy after each dose is unknown and the optimal window for VYLEESI administration has not been fully characterized. Patients may decide the optimal time for VYLEESI administration based on how they experience the duration of effect on desire and any adverse reactions such as nausea [ see Warnings and Precautions ( 5.3)].
Patients should not administer more than one dose within 24 hours. The efficacy of consecutive doses within 24 hours has not been established and administering doses close together may increase the risk of additive effects on blood pressure [see Warnings and Precautions ( 5.1)].
Administering more than 8 doses per month is not recommended. Few patients in the phase 3 program received more than 8 doses per month. Also, more frequent dosing increases the risk for focal hyperpigmentation and the length of time per month when blood pressure is increased [see Warnings and Precautions ( 5.1, 5.2)].
VYLEESI is self-administered via a prefilled autoinjector pen. Visually inspect the drug product for particulate matter and discoloration prior to administration, whenever solution and container permit. Discard if the solution is cloudy, discolored, or visible particles are observed.
Discontinuation of VYLEESI
Discontinue VYLEESI after 8 weeks if the patient does not report an improvement in her symptoms.
Subcutaneous injection: 1.75 mg/0.3 mL clear solution in a single-dose autoinjector.
Pregnancy
Pregnancy Exposure Registry
There will be a pregnancy exposure registry that monitors pregnancy outcomes in women exposed to VYLEESI during pregnancy. Pregnant women exposed to VYLEESI and healthcare providers are encouraged to call the VYLEESI Pregnancy Exposure Registry at (800) 972-5220.
Risk Summary
The few pregnancies in women exposed to VYLEESI in clinical trials are insufficient for determining whether there is a drug-associated risk for major birth defects, miscarriage or adverse maternal or fetal outcomes.
Based on findings in animal studies, the use of VYLEESI in pregnant women may be associated with the potential for fetal harm. In animal reproduction and development studies, daily subcutaneous administration of bremelanotide to pregnant dogs during the period of organogenesis at exposures greater than or equal to 16 times the maximum recommended dose (based on area under the concentration-time curve or AUC) produced fetal harm. In mice subcutaneously dosed with bremelanotide during pregnancy and lactation, developmental effects were observed in the offspring at greater than or equal to 125-times the maximum recommended dose (based on AUC) [ see Data]. However, the lowest bremelanotide dose associated with fetal harm has not been identified for either species. For this reason, women should use effective contraception while taking VYLEESI and discontinue VYLEESI if pregnancy is suspected.
In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2% to 4% and 15% to 20%, respectively.
Data
Human Data
There were 7 pregnancies reported in the clinical trials of more than 1057 patients treated with VYLEESI for up to 12 months. Among these 7 pregnancies, no major congenital anomalies were reported. There was one spontaneous abortion (miscarriage), five full-term live births, and one outcome was unknown due to loss to follow-up.
Animal Data
An embryofetal development study was conducted in the dog and a pre- and postnatal development study was conducted in the mouse to inform developmental risk. These two species are not routinely used for reproductive toxicity assessment but were the only two species that could be successfully dosed by the subcutaneous route during gestation.
Bremelanotide was administered subcutaneously to pregnant dogs (8/dose) at 2, 8, or 20 mg/kg from gestation day (GD) 18-35, corresponding to the period from implantation to late embryogenesis in the dog. Embryofetal toxicity, as measured by post-implantation loss, was elevated approximately 3 to 8-fold compared to controls across all treated groups but was not dose-dependent. A developmental no-observed-effect level (NOEL) was not set. At the low dose of 2 mg/kg/day in the dog, exposure was approximately 16 times the human exposure based on AUC.
In a pre- and postnatal development study, female mice (30/dose) were dosed subcutaneously at 0, 30, 75, and 150 mg/kg/day from GD 6 through lactation day (LD) 28, and two generations of offspring were assessed (F1 and F2). There were no effects on reproductive parameters in parental (F0) or F1 generation animals at doses up to 150 mg/kg/day (approximately 760 times the human AUC). However, developmental delays were observed in the F1 generation mice at ≥ 30 mg/kg/day (approximately 125 times the human AUC). For that reason, a developmental NOEL was not set. There were no significant effects on the growth and development of F2 generation pups.
Lactation
Risk Summary
There is no information on the presence of bremelanotide or its metabolites in human milk, the effects on the breastfed infant, or the effects on milk production.
The developmental and health benefits of breastfeeding should be considered along with the mother's clinical need for VYLEESI and any potential adverse effects on the breastfed child from VYLEESI or from the underlying maternal condition.
Females and Males of Reproductive Potential
Contraception
Use of VYLEESI during pregnancy is not recommended [ see Use in Specific Populations ( 8.1)]. Advise females of reproductive potential to use effective contraception while taking VYLEESI, and to discontinue VYLEESI if pregnancy is suspected.
Pediatric Use
The safety and effectiveness of VYLEESI have not been established in pediatric patients.
Geriatric Use
The safety and effectiveness of VYLEESI have not been established in geriatric patients.
Renal Impairment
No dosing adjustments are recommended for patients with mild to moderate (eGFR 30-89 mL/min/1.73 m 2) renal impairment. Use with caution in patients with severe (eGFR <30 mL/min/1.73 m 2) renal impairment, because these patients may have an increase in the incidence and severity of adverse reactions (e.g., nausea and vomiting) [see Clinical Pharmacology ( 12.3)] .
Hepatic Impairment
No dosing adjustments are recommended for patients with mild to moderate (Child-Pugh A and B; score 5-9) hepatic impairment. VYLEESI has not been evaluated in patients with severe hepatic impairment. Use with caution in patients with severe (Child-Pugh C; score 10-15) hepatic impairment, because these patients may have an increase in the incidence and severity of adverse reactions (e.g., nausea and vomiting) [see Clinical Pharmacology ( 12.3)].
VYLEESI is contraindicated in patients who have uncontrolled hypertension or known cardiovascular disease [see Warnings and Precautions ( 5.1)].
Transient Increase in Blood Pressure and Reduction in Heart Rate
VYLEESI transiently increases blood pressure and reduces heart rate after each dose. In clinical studies, VYLEESI induced maximal increases of 6 mmHg in systolic blood pressure (SBP) and 3 mmHg in diastolic blood pressure (DBP) that peaked between 2 to 4 hours post dose. There was a corresponding reduction in heart rate up to 5 beats per minute. Blood pressure and heart rate returned to baseline usually within 12 hours post-dose. No additive effects were seen for blood pressure or heart rate following repeat daily dosing 24-hours apart for up to 16 days [ see Clinical Pharmacology ( 12.2) ].
Before initiating VYLEESI, and periodically during treatment, consider the patient's cardiovascular risk and ensure blood pressure is well-controlled. VYLEESI is not recommended for patients at high risk for cardiovascular disease and is contraindicated in patients with uncontrolled hypertension or known cardiovascular disease [ see Contraindications ( 4) ].
To minimize the risk of more pronounced blood pressure effects, advise patients to not take more than one VYLEESI dose within 24 hours [see Dosage and Administration ( 2.1)].
Focal Hyperpigmentation
In the phase 3 placebo-controlled trials, focal hyperpigmentation, including involvement of the face, gingiva, and breasts, was reported in 1% of patients who received up to 8 doses per month of VYLEESI compared to no placebo-treated patients. In another clinical study, 38% of patients developed focal hyperpigmentation after receiving VYLEESI daily for 8 days; among patients who continued VYLEESI for 8 more consecutive days, an additional 14% developed new focal pigmentary changes. Patients with dark skin were more likely to develop focal hyperpigmentation. Resolution of the focal hyperpigmentation was not confirmed in all patients after discontinuation of VYLEESI. More than 8 monthly doses of VYLEESI is not recommended. Consider discontinuing VYLEESI if hyperpigmentation develops.
Nausea
In the phase 3 placebo-controlled trials, nausea was the most commonly reported adverse reaction, reported in 40% of VYLEESI-treated patients, requiring anti-emetic therapy in 13% of VYLEESI-treated patients and leading to premature discontinuation from the trials for 8% of VYLEESI-treated patients. Nausea improves for most patients with the second dose [see Adverse Reactions ( 6.1)] . Consider discontinuing VYLEESI for persistent or severe nausea or initiating anti-emetic therapy for those patients who are bothered by nausea but wish to continue with VYLEESI treatment.