K4 Elite
K4 Elite
Bremelanotide is a cyclic melanocortin-receptor agonist approved by the US FDA in 2019 (Vyleesi) for premenopausal women with acquired, generalized hypoactive sexual desire disorder. Approval rested on two identical 24-week, randomized, placebo-controlled phase 3 trials (RECONNECT; n=1,247 in the safety population) with 52-week open-label extensions. The FDA label defines the regimen, adverse-reaction rates, contraindications and drug interactions summarised here. Earlier phase 1/2 work in men used intranasal and subcutaneous formulations.
Each row records what a published study did: who it enrolled, the regimen it administered to those subjects, and what it reported. These are historical study descriptions, not protocols to follow.
| Study | Population | Regimen as reported | Primary findings |
|---|---|---|---|
| Kingsberg et al., Obstet Gynecol 2019 — RECONNECT Studies 301 and 302 (Phase 3) Registry: NCT02333071, NCT02338960
|
1,267 premenopausal women with acquired, generalized HSDD randomized 1:1 (safety population n=1,247; modified ITT n=1,202); mean age 39; 85.6% white; 96.6% US sites | Participants self-administered bremelanotide 1.75 mg or placebo subcutaneously via autoinjector as needed, approximately 45 minutes before anticipated sexual activity, for 24 weeks (no more than one dose per 24 h and no more than 12 doses per month in the trials); a 52-week open-label extension followed. | Bremelanotide produced statistically significant increases versus placebo in the FSFI desire domain (integrated difference 0.35, p<0.001) and reductions in FSDS-DAO item 13 distress (integrated difference -0.33, p<0.001); nausea, flushing and headache each occurred in >=10% of bremelanotide-treated women. |
| FDA Prescribing Information, Section 14 Clinical Studies (Study 1 and Study 2) Registry: NCT02333071, NCT02338960
|
Premenopausal women with acquired, generalized HSDD of >=6 months (bremelanotide n=635; placebo n=632) | Participants were randomized to subcutaneous bremelanotide 1.75 mg or placebo, self-administered as needed about 45 minutes before sexual activity; the median number of injections was 10 in the 24-week double-blind period and 12 in the open-label extension, and most patients used it two to three times per month. | Mean FSFI-Desire change from baseline was 0.5 vs 0.2 (Study 1) and 0.6 vs 0.2 (Study 2); there was no significant difference from placebo in the number of satisfying sexual events. Premature discontinuation in the double-blind period was 40% vs 13% (Study 1) and 39% vs 25% (Study 2). |
| FDA Prescribing Information, Section 12.2 — ambulatory blood-pressure study | 127 premenopausal women | Participants received bremelanotide once daily for 8 days in an open-label ambulatory blood-pressure monitoring study. | Mean daytime systolic and diastolic blood pressure rose by 1.9 mmHg and 1.7 mmHg respectively after 8 days, with peak effects within 4-8 hours post-dose and return to pre-dose values by 12-24 hours. |
Effects recorded in the cited reports. Frequencies are those the source reported, in the population that source studied.
| Effect | Frequency / context | Source |
|---|---|---|
| Nausea | 40.0% bremelanotide vs 1.3% placebo in pooled phase 3 trials (n=627 vs 620); 13% received an anti-emetic and 8% discontinued because of nausea; incidence 21% after the first dose, declining to ~3% after subsequent doses (FDA label Table 1 / 5.3). | VYLEESI (bremelanotide injection) US Prescribing Information, FDA, June 2019 ↗ |
| Flushing | 20.3% vs 0.3% placebo; 1% discontinued due to flushing (FDA label Table 1). | VYLEESI (bremelanotide injection) US Prescribing Information, FDA, June 2019 ↗ |
| Injection site reactions | 13.2% vs 8.4% placebo (includes pain, erythema, hematoma, pruritus, bruising) (FDA label Table 1). | VYLEESI (bremelanotide injection) US Prescribing Information, FDA, June 2019 ↗ |
| Headache | 11.3% vs 1.9% placebo; one serious case (intractable pain requiring hospitalization); 2% discontinued due to headache (FDA label 6.1). | VYLEESI (bremelanotide injection) US Prescribing Information, FDA, June 2019 ↗ |
| Vomiting | 4.8% vs 0.2% placebo (FDA label Table 1). | VYLEESI (bremelanotide injection) US Prescribing Information, FDA, June 2019 ↗ |
| Cough / fatigue / hot flush / paraesthesia / dizziness / nasal congestion | 3.3% / 3.2% / 2.7% / 2.6% / 2.2% / 2.1% with bremelanotide vs 1.3% / 0.5% / 0.2% / 0.0% / 0.5% / 0.5% placebo (FDA label Table 1). | VYLEESI (bremelanotide injection) US Prescribing Information, FDA, June 2019 ↗ |
| Focal hyperpigmentation (face, gingiva, breasts) | 1% of patients receiving up to 8 doses/month vs 0% placebo in phase 3; 38% after 8 consecutive daily doses in a separate study, with a further 14% on 8 more daily doses; more frequent in darker skin; resolution not confirmed in all patients (FDA label 5.2). | VYLEESI (bremelanotide injection) US Prescribing Information, FDA, June 2019 ↗ |
| Transient blood-pressure increase and heart-rate decrease | Maximal mean increases of 6 mmHg systolic and 3 mmHg diastolic peaking 2-4 h post-dose, with heart rate reduced by up to 5 bpm, usually resolving within 12 h (FDA label 5.1). | VYLEESI (bremelanotide injection) US Prescribing Information, FDA, June 2019 ↗ |
| Discontinuation due to adverse reactions | 18% bremelanotide vs 2% placebo; serious adverse reactions 1.1% vs 0.5% (FDA label 6.1). | VYLEESI (bremelanotide injection) US Prescribing Information, FDA, June 2019 ↗ |
| Acute hepatitis (single case) | One case in the open-label extension after 10 doses over one year (transaminases >40x ULN), resolving 4 months after discontinuation; causality could not be excluded (FDA label 6.1). | VYLEESI (bremelanotide injection) US Prescribing Information, FDA, June 2019 ↗ |
Interactions documented in trial reports, prescribing information or pharmacology references.
| Agent | Type | Note | Source |
|---|---|---|---|
| Oral naltrexone | pharmacokinetic (reduced absorption) | The label states bremelanotide may significantly decrease systemic exposure of orally administered naltrexone and advises avoiding co-use with oral naltrexone products for alcohol or opioid dependence because of the risk of naltrexone treatment failure (Section 7.2). | VYLEESI (bremelanotide injection) US Prescribing Information, FDA, June 2019 ↗ |
| Oral medications generally (e.g., antibiotics, indomethacin) | pharmacokinetic (slowed gastric emptying) | Bremelanotide may slow gastric emptying and reduce the rate and extent of absorption of concomitant oral drugs; the label notes indomethacin absorption was affected in clinical pharmacology studies (Sections 7.1, 12.3). | VYLEESI (bremelanotide injection) US Prescribing Information, FDA, June 2019 ↗ |
| Alcohol | pharmacodynamic | In a crossover study of a 20 mg intranasal dose with 0.6 g/kg ethanol in 24 healthy adults, alcohol did not alter bremelanotide pharmacokinetics; flushing and headache incidences were described relative to each agent alone, and orthostatic blood-pressure reductions were comparable to ethanol alone (Section 12.2). | VYLEESI (bremelanotide injection) US Prescribing Information, FDA, June 2019 ↗ |
Exclusions and label contraindications recorded in the cited sources.