{"site":"Bremelanotide Rx","url":"https://bremelanotiderx.com","format":"evidence-manifest/v1","claim_count":69,"claims":[{"id":"BMT-001","text":"FDA approved bremelanotide (Vyleesi) on June 21, 2019 under NDA 210557 as a Type 1 new molecular entity; the application is now held by Cosette Pharmaceuticals.","source_url":"https://www.accessdata.fda.gov/scripts/cder/daf/index.cfm?event=overview.process&ApplNo=210557","grade":"regulatory","grade_label":"Regulatory record","used_on":["https://bremelanotiderx.com/monograph","https://bremelanotiderx.com/entity","https://bremelanotiderx.com/faq","https://bremelanotiderx.com","https://bremelanotiderx.com/comparison"]},{"id":"BMT-002","text":"The approved indication is the treatment of premenopausal women with acquired, generalized hypoactive sexual desire disorder (HSDD), characterized by low sexual desire causing marked distress or interpersonal difficulty and not due to a co-existing medical or psychiatric condition, relationship problems, or the effects of a medication or drug substance.","source_url":"https://api.fda.gov/drug/label.json?search=openfda.brand_name:%22VYLEESI%22&limit=1","grade":"fda-label","grade_label":"FDA label","used_on":["https://bremelanotiderx.com/monograph","https://bremelanotiderx.com/entity","https://bremelanotiderx.com/faq","https://bremelanotiderx.com/decision_aid","https://bremelanotiderx.com","https://bremelanotiderx.com/comparison"]},{"id":"BMT-003","text":"Label Limitations of Use: Vyleesi is not indicated for the treatment of HSDD in postmenopausal women or in men, and is not indicated to enhance sexual performance.","source_url":"https://api.fda.gov/drug/label.json?search=openfda.brand_name:%22VYLEESI%22&limit=1","grade":"fda-label","grade_label":"FDA label","used_on":["https://bremelanotiderx.com/monograph","https://bremelanotiderx.com/faq","https://bremelanotiderx.com","https://bremelanotiderx.com/decision_aid","https://bremelanotiderx.com/comparison"]},{"id":"BMT-004","text":"The recommended dosage is 1.75 mg injected subcutaneously in the abdomen or thigh via 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.","source_url":"https://api.fda.gov/drug/label.json?search=openfda.brand_name:%22VYLEESI%22&limit=1","grade":"fda-label","grade_label":"FDA label","used_on":["https://bremelanotiderx.com/monograph","https://bremelanotiderx.com/faq","https://bremelanotiderx.com/decision_aid","https://bremelanotiderx.com/tools","https://bremelanotiderx.com/comparison"]},{"id":"BMT-005","text":"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.","source_url":"https://api.fda.gov/drug/label.json?search=openfda.brand_name:%22VYLEESI%22&limit=1","grade":"fda-label","grade_label":"FDA label","used_on":["https://bremelanotiderx.com/monograph","https://bremelanotiderx.com/faq","https://bremelanotiderx.com/tools"]},{"id":"BMT-006","text":"The label instructs discontinuing Vyleesi after 8 weeks if the patient does not report an improvement in her symptoms.","source_url":"https://api.fda.gov/drug/label.json?search=openfda.brand_name:%22VYLEESI%22&limit=1","grade":"fda-label","grade_label":"FDA label","used_on":["https://bremelanotiderx.com/monograph","https://bremelanotiderx.com/decision_aid","https://bremelanotiderx.com/faq","https://bremelanotiderx.com/comparison"]},{"id":"BMT-007","text":"Vyleesi is supplied as 1.75 mg bremelanotide in 0.3 mL solution in a single-dose, disposable prefilled autoinjector; Drugs@FDA lists it as the only approved bremelanotide product.","source_url":"https://api.fda.gov/drug/label.json?search=openfda.brand_name:%22VYLEESI%22&limit=1","grade":"regulatory","grade_label":"Regulatory record","used_on":["https://bremelanotiderx.com/monograph","https://bremelanotiderx.com/faq","https://bremelanotiderx.com/tools","https://bremelanotiderx.com/comparison"]},{"id":"BMT-008","text":"Vyleesi is contraindicated in patients who have uncontrolled hypertension or known cardiovascular disease.","source_url":"https://api.fda.gov/drug/label.json?search=openfda.brand_name:%22VYLEESI%22&limit=1","grade":"fda-label","grade_label":"FDA label","used_on":["https://bremelanotiderx.com/monograph","https://bremelanotiderx.com/faq","https://bremelanotiderx.com/decision_aid","https://bremelanotiderx.com","https://bremelanotiderx.com/comparison"]},{"id":"BMT-009","text":"Vyleesi transiently increases blood pressure and reduces heart rate after each dose: maximal increases of 6 mmHg systolic and 3 mmHg diastolic peaking 2 to 4 hours post dose, heart rate down up to 5 beats per minute, with return to baseline usually within 12 hours; it is not recommended in patients at high risk for cardiovascular disease.","source_url":"https://api.fda.gov/drug/label.json?search=openfda.brand_name:%22VYLEESI%22&limit=1","grade":"fda-label","grade_label":"FDA label","used_on":["https://bremelanotiderx.com/monograph","https://bremelanotiderx.com/faq","https://bremelanotiderx.com/decision_aid","https://bremelanotiderx.com/tools"]},{"id":"BMT-010","text":"In an ambulatory blood pressure monitoring study of 127 premenopausal women dosed once daily, daytime systolic pressure rose a mean 1.9 mmHg and diastolic 1.7 mmHg after 8 days, with transient peaks of 2.8 mmHg (4 to 8 hours) and 2.7 mmHg (0 to 4 hours) and values back to pre-dose levels by 12 to 24 hours.","source_url":"https://api.fda.gov/drug/label.json?search=openfda.brand_name:%22VYLEESI%22&limit=1","grade":"fda-label","grade_label":"FDA label","used_on":["https://bremelanotiderx.com/monograph","https://bremelanotiderx.com/faq"]},{"id":"BMT-011","text":"Focal hyperpigmentation, including of the face, gingiva and breasts, was reported by 1% of patients receiving up to 8 doses per month versus no placebo patients; with daily dosing for 8 days, 38% developed focal hyperpigmentation, and among those continuing 8 more consecutive days an additional 14% developed new pigmentary changes; risk was higher with darker skin, and resolution was not confirmed in all patients after stopping.","source_url":"https://api.fda.gov/drug/label.json?search=openfda.brand_name:%22VYLEESI%22&limit=1","grade":"fda-label","grade_label":"FDA label","used_on":["https://bremelanotiderx.com/monograph","https://bremelanotiderx.com/faq","https://bremelanotiderx.com/tools"]},{"id":"BMT-012","text":"Nausea was reported by 40% of Vyleesi-treated patients in the phase 3 trials versus 1.3% on placebo; it required anti-emetic therapy in 13% and led 8% to discontinue; median onset was within one hour post-dose with a duration of about two hours; incidence was 21% after the first dose, declining to about 3% after subsequent doses, and it improves for most patients with the second dose.","source_url":"https://api.fda.gov/drug/label.json?search=openfda.brand_name:%22VYLEESI%22&limit=1","grade":"fda-label","grade_label":"FDA label","used_on":["https://bremelanotiderx.com/monograph","https://bremelanotiderx.com/faq","https://bremelanotiderx.com","https://bremelanotiderx.com/tools","https://bremelanotiderx.com/comparison"]},{"id":"BMT-013","text":"A phase 4 randomized study in 228 healthy women found that pre-treatment with 8 mg oral ondansetron 30 minutes before Vyleesi did not reduce the incidence of Vyleesi-associated nausea and is not recommended.","source_url":"https://api.fda.gov/drug/label.json?search=openfda.brand_name:%22VYLEESI%22&limit=1","grade":"fda-label","grade_label":"FDA label","used_on":["https://bremelanotiderx.com/monograph","https://bremelanotiderx.com/faq","https://bremelanotiderx.com/tools"]},{"id":"BMT-014","text":"Common adverse reactions in the pooled phase 3 trials (Vyleesi vs placebo): nausea 40.0% vs 1.3%, flushing 20.3% vs 0.3%, injection site reactions 13.2% vs 8.4%, headache 11.3% vs 1.9%, vomiting 4.8% vs 0.2%, cough 3.3% vs 1.3%, fatigue 3.2% vs 0.5%, hot flush 2.7% vs 0.2%, paraesthesia 2.6% vs 0.0%, dizziness 2.2% vs 0.5%, nasal congestion 2.1% vs 0.5%.","source_url":"https://api.fda.gov/drug/label.json?search=openfda.brand_name:%22VYLEESI%22&limit=1","grade":"fda-label","grade_label":"FDA label","used_on":["https://bremelanotiderx.com/monograph","https://bremelanotiderx.com/tools","https://bremelanotiderx.com/faq"]},{"id":"BMT-015","text":"Discontinuation due to adverse reactions was 18% with Vyleesi versus 2% with placebo; the most common reasons in the Vyleesi group were nausea (8%), headache (2%), vomiting (1%), flushing (1%) and injection site reactions (1%).","source_url":"https://api.fda.gov/drug/label.json?search=openfda.brand_name:%22VYLEESI%22&limit=1","grade":"fda-label","grade_label":"FDA label","used_on":["https://bremelanotiderx.com/monograph","https://bremelanotiderx.com/tools","https://bremelanotiderx.com"]},{"id":"BMT-016","text":"Serious adverse reactions occurred in 1.1% of Vyleesi patients versus 0.5% on placebo; a single case of acute hepatitis (transaminases over 40 times the upper limit of normal) was reported in the open-label extension after 10 doses over one year, resolving 4 months after discontinuation, with the drug's role not definitively excluded and no program-wide hepatotoxicity signal.","source_url":"https://api.fda.gov/drug/label.json?search=openfda.brand_name:%22VYLEESI%22&limit=1","grade":"fda-label","grade_label":"FDA label","used_on":["https://bremelanotiderx.com/monograph"]},{"id":"BMT-017","text":"Vyleesi may slow gastric emptying and reduce the rate and extent of absorption of oral medications taken at the same time; the label instructs avoiding Vyleesi when taking oral drugs dependent on threshold concentrations for efficacy, such as antibiotics, and considering discontinuation if a quick-onset oral drug such as indomethacin is delayed.","source_url":"https://api.fda.gov/drug/label.json?search=openfda.brand_name:%22VYLEESI%22&limit=1","grade":"fda-label","grade_label":"FDA label","used_on":["https://bremelanotiderx.com/monograph","https://bremelanotiderx.com/faq","https://bremelanotiderx.com/decision_aid"]},{"id":"BMT-018","text":"Because Vyleesi may significantly decrease systemic exposure of oral naltrexone, the label instructs patients to avoid using it with orally administered naltrexone products for alcohol or opioid addiction, due to the severe consequence of naltrexone treatment failure.","source_url":"https://api.fda.gov/drug/label.json?search=openfda.brand_name:%22VYLEESI%22&limit=1","grade":"fda-label","grade_label":"FDA label","used_on":["https://bremelanotiderx.com/monograph","https://bremelanotiderx.com/faq","https://bremelanotiderx.com/decision_aid"]},{"id":"BMT-019","text":"The label advises effective contraception during use and discontinuing Vyleesi if pregnancy is suspected; in animal studies, daily subcutaneous bremelanotide produced fetal harm in pregnant dogs at exposures 16 times the maximum recommended human dose and developmental delays in mouse offspring at 125 times or more, with no developmental no-observed-effect level set; among 7 human pregnancies in the trials, no major congenital anomalies were reported.","source_url":"https://api.fda.gov/drug/label.json?search=openfda.brand_name:%22VYLEESI%22&limit=1","grade":"fda-label","grade_label":"FDA label","used_on":["https://bremelanotiderx.com/monograph","https://bremelanotiderx.com/faq","https://bremelanotiderx.com/decision_aid"]},{"id":"BMT-020","text":"Bremelanotide is a melanocortin receptor agonist that nonselectively activates several receptor subtypes with potency order MC1R, MC4R, MC3R, MC5R, MC2R; at therapeutic doses binding to MC1R and MC4R is most relevant; the mechanism by which it improves HSDD is unknown; MC1R on melanocytes drives melanin expression and increased pigmentation.","source_url":"https://api.fda.gov/drug/label.json?search=openfda.brand_name:%22VYLEESI%22&limit=1","grade":"fda-label","grade_label":"FDA label","used_on":["https://bremelanotiderx.com/monograph","https://bremelanotiderx.com/faq","https://bremelanotiderx.com/entity","https://bremelanotiderx.com/comparison"]},{"id":"BMT-021","text":"Bremelanotide pharmacokinetics after subcutaneous Vyleesi: median Tmax approximately 1.0 hour (range 0.5 to 1.0), mean terminal half-life approximately 2.7 hours (range 1.9 to 4.0), absolute bioavailability about 100%, mean volume of distribution 25.0 L, clearance 6.5 L/hr, 21% serum protein binding, mean Cmax 72.8 ng/mL and AUC 276 hr*ng/mL.","source_url":"https://api.fda.gov/drug/label.json?search=openfda.brand_name:%22VYLEESI%22&limit=1","grade":"fda-label","grade_label":"FDA label","used_on":["https://bremelanotiderx.com/monograph","https://bremelanotiderx.com/faq","https://bremelanotiderx.com/tools"]},{"id":"BMT-022","text":"Plasma concentrations rise less than dose-proportionally between 0.3 and 10 mg, with mean Cmax reaching a plateau at the 7.5 mg subcutaneous dose, approximately 4.3 times the maximum recommended dose.","source_url":"https://api.fda.gov/drug/label.json?search=openfda.brand_name:%22VYLEESI%22&limit=1","grade":"fda-label","grade_label":"FDA label","used_on":["https://bremelanotiderx.com/monograph","https://bremelanotiderx.com/faq","https://bremelanotiderx.com/tools"]},{"id":"BMT-023","text":"As a 7-amino-acid peptide, bremelanotide is metabolized by multiple hydrolyses of the amide bonds of the cyclic peptide; after a radiolabeled dose, 64.8% of radioactivity was recovered in urine and 22.8% in feces.","source_url":"https://api.fda.gov/drug/label.json?search=openfda.brand_name:%22VYLEESI%22&limit=1","grade":"fda-label","grade_label":"FDA label","used_on":["https://bremelanotiderx.com/monograph"]},{"id":"BMT-024","text":"Bremelanotide exposure (AUC) increases 1.2-fold in mild, 1.5-fold in moderate and 2-fold in severe renal impairment, and 1.2-fold in mild and 1.7-fold in moderate hepatic impairment; severe hepatic impairment was not studied.","source_url":"https://api.fda.gov/drug/label.json?search=openfda.brand_name:%22VYLEESI%22&limit=1","grade":"fda-label","grade_label":"FDA label","used_on":["https://bremelanotiderx.com/monograph"]},{"id":"BMT-025","text":"Storage: store Vyleesi at or below 25 C (77 F); do not freeze; protect from light; each autoinjector is single-dose and disposable.","source_url":"https://api.fda.gov/drug/label.json?search=openfda.brand_name:%22VYLEESI%22&limit=1","grade":"fda-label","grade_label":"FDA label","used_on":["https://bremelanotiderx.com/monograph","https://bremelanotiderx.com/tools"]},{"id":"BMT-026","text":"Bremelanotide is a synthetic cyclic heptapeptide, Ac-Nle-cyclo-(Asp-His-D-Phe-Arg-Trp-Lys-OH); molecular formula C50H68N14O10, molecular weight 1025.2 (free base); PubChem CID 9941379; CAS 189691-06-3.","source_url":"https://api.fda.gov/drug/label.json?search=openfda.brand_name:%22VYLEESI%22&limit=1","grade":"chemical-reference","grade_label":"Chemical reference","used_on":["https://bremelanotiderx.com/monograph","https://bremelanotiderx.com/entity"]},{"id":"BMT-027","text":"In an alcohol-interaction study, a 20 mg intranasal bremelanotide dose (about 2.5 times the Cmax of Vyleesi) co-administered with 0.6 g/kg ethanol showed no effect of alcohol on bremelanotide pharmacokinetics and no excess of abnormal orthostatic blood pressure reductions versus ethanol alone; a 20 mg intranasal dose also did not prolong the QTc interval to any clinically relevant extent.","source_url":"https://api.fda.gov/drug/label.json?search=openfda.brand_name:%22VYLEESI%22&limit=1","grade":"fda-label","grade_label":"FDA label","used_on":["https://bremelanotiderx.com/monograph","https://bremelanotiderx.com/faq","https://bremelanotiderx.com/comparison"]},{"id":"BMT-028","text":"Two-year carcinogenicity studies (intranasal in rats; subcutaneous in mice at up to 111 times the human Cmax) found no significant increases in tumor incidence; bremelanotide was not genotoxic or mutagenic in a standard battery; no fertility effects were seen in mice at exposures up to 375 to 760 times the human AUC.","source_url":"https://api.fda.gov/drug/label.json?search=openfda.brand_name:%22VYLEESI%22&limit=1","grade":"animal","grade_label":"Animal","used_on":["https://bremelanotiderx.com/monograph"]},{"id":"BMT-029","text":"The RECONNECT program consisted of two identical phase 3 randomized double-blind placebo-controlled trials (NCT02333071 and NCT02338960), randomizing 1,267 premenopausal women with acquired generalized HSDD 1:1 to bremelanotide 1.75 mg or placebo autoinjector as needed for a 24-week core phase followed by a 52-week open-label extension.","source_url":"https://api.fda.gov/drug/label.json?search=openfda.brand_name:%22VYLEESI%22&limit=1","grade":"human-rct","grade_label":"Human RCT","used_on":["https://bremelanotiderx.com/monograph","https://bremelanotiderx.com/studies","https://bremelanotiderx.com/faq","https://bremelanotiderx.com"]},{"id":"BMT-030","text":"In the phase 3 trials, most patients used Vyleesi two to three times per month and no more than once a week; the median number of injections was 10 during the 24-week double-blind period and 12 during the 52-week open-label extension; the trial protocol allowed up to 12 doses per month, while the approved label recommends no more than 8.","source_url":"https://api.fda.gov/drug/label.json?search=openfda.brand_name:%22VYLEESI%22&limit=1","grade":"fda-label","grade_label":"FDA label","used_on":["https://bremelanotiderx.com/monograph","https://bremelanotiderx.com/tools"]},{"id":"BMT-031","text":"Study 1 co-primary results (label, modified intent-to-treat): FSFI desire domain (scale 1.2 to 6.0) mean change +0.5 with Vyleesi versus +0.2 with placebo (p=0.0002; median change 0.6 vs 0); FSDS-DAO Question 13 distress (scale 0 to 4) mean change -0.7 versus -0.4 (p<0.0001; median -1 vs 0).","source_url":"https://api.fda.gov/drug/label.json?search=openfda.brand_name:%22VYLEESI%22&limit=1","grade":"human-rct","grade_label":"Human RCT","used_on":["https://bremelanotiderx.com/monograph","https://bremelanotiderx.com/studies","https://bremelanotiderx.com/faq","https://bremelanotiderx.com"]},{"id":"BMT-032","text":"Study 2 co-primary results (label, modified intent-to-treat): FSFI desire domain mean change +0.6 with Vyleesi versus +0.2 with placebo (p<0.0001; median 0.6 vs 0); FSDS-DAO Question 13 mean change -0.7 versus -0.4 (p=0.0053; median -1 vs 0).","source_url":"https://api.fda.gov/drug/label.json?search=openfda.brand_name:%22VYLEESI%22&limit=1","grade":"human-rct","grade_label":"Human RCT","used_on":["https://bremelanotiderx.com/monograph","https://bremelanotiderx.com/studies","https://bremelanotiderx.com/faq"]},{"id":"BMT-033","text":"The published RECONNECT report gives placebo-adjusted treatment differences of +0.30 (study 301), +0.42 (study 302) and +0.35 (integrated) on the FSFI desire domain, and -0.37, -0.29 and -0.33 on FSDS-DAO item 13 distress, all statistically significant.","source_url":"https://pmc.ncbi.nlm.nih.gov/articles/PMC6819021/","grade":"human-rct","grade_label":"Human RCT","used_on":["https://bremelanotiderx.com/monograph","https://bremelanotiderx.com/studies","https://bremelanotiderx.com/faq","https://bremelanotiderx.com"]},{"id":"BMT-034","text":"The current FDA label states there was no significant difference between treatment groups in the change from baseline in the number of satisfying sexual events (SSEs), a secondary endpoint: mean change 0.0 with Vyleesi versus -0.1 with placebo in Study 1 (p=0.76) and 0.0 versus 0.0 in Study 2 (p=0.70).","source_url":"https://api.fda.gov/drug/label.json?search=openfda.brand_name:%22VYLEESI%22&limit=1","grade":"fda-label","grade_label":"FDA label","used_on":["https://bremelanotiderx.com/monograph","https://bremelanotiderx.com/studies","https://bremelanotiderx.com/faq","https://bremelanotiderx.com","https://bremelanotiderx.com/comparison"]},{"id":"BMT-035","text":"In the published report, satisfying sexual events were the key secondary endpoint; because the difference did not reach significance (study 301: 0.0 vs -0.1, P=.764; study 302: 0.0 vs 0.0, P=.702; integrated: 0.0 vs -0.1, P=.630), the remaining ranked secondary endpoints became supportive and exploratory.","source_url":"https://pmc.ncbi.nlm.nih.gov/articles/PMC6819021/","grade":"human-rct","grade_label":"Human RCT","used_on":["https://bremelanotiderx.com/monograph","https://bremelanotiderx.com/studies","https://bremelanotiderx.com/faq"]},{"id":"BMT-036","text":"More patients on bremelanotide than placebo left the 24-week double-blind period early: 40% versus 13% in Study 1 and 39% versus 25% in Study 2 (label); in the published report, 8.1% discontinued due to nausea specifically, and 3.5% simultaneously reported vomiting.","source_url":"https://api.fda.gov/drug/label.json?search=openfda.brand_name:%22VYLEESI%22&limit=1","grade":"human-rct","grade_label":"Human RCT","used_on":["https://bremelanotiderx.com/monograph","https://bremelanotiderx.com/studies","https://bremelanotiderx.com/faq"]},{"id":"BMT-037","text":"The trials' anchor-based responder thresholds were an increase of at least 1.2 points in the FSFI desire domain and a decrease of at least 1 point on FSDS-DAO Question 13; the label presents responder percentages for completers in figures rather than numbers in the text.","source_url":"https://api.fda.gov/drug/label.json?search=openfda.brand_name:%22VYLEESI%22&limit=1","grade":"fda-label","grade_label":"FDA label","used_on":["https://bremelanotiderx.com/monograph"]},{"id":"BMT-038","text":"In the 52-week uncontrolled open-label extension, 684 of 856 eligible patients enrolled and 272 completed; the most common drug-related adverse events were nausea (40.4%), flushing (20.6%) and headache (12.0%); cumulative FSFI-desire changes from core baseline ranged 1.25 to 1.30 for women who had received bremelanotide in the core phase versus 0.70 to 0.77 for those who had received placebo, with no placebo comparison during the extension itself.","source_url":"https://pmc.ncbi.nlm.nih.gov/articles/PMC6819023/","grade":"human-trial","grade_label":"Human trial","used_on":["https://bremelanotiderx.com/monograph","https://bremelanotiderx.com/studies","https://bremelanotiderx.com/faq"]},{"id":"BMT-039","text":"In the phase 2b dose-finding trial (NCT01382719; 327 patients in the efficacy analysis), pooled bremelanotide 1.25/1.75 mg versus placebo changed satisfying sexual events by +0.7 versus +0.2 per month (p=0.0180), FSFI total score by +3.6 versus +1.9 (p=0.0017) and FSDS-DAO total by -11.1 versus -6.8 (p=0.0014); 1.75 mg was selected for phase 3.","source_url":"https://pmc.ncbi.nlm.nih.gov/articles/PMC5384512/","grade":"human-rct","grade_label":"Human RCT","used_on":["https://bremelanotiderx.com/monograph","https://bremelanotiderx.com/studies","https://bremelanotiderx.com/faq","https://bremelanotiderx.com/tools"]},{"id":"BMT-040","text":"The satisfying-sexual-events endpoint behaved differently across phases: it improved significantly in the 12-week phase 2b trial (+0.7 vs +0.2 per month, pooled doses) but showed no significant difference in either 24-week phase 3 trial; this comparison is computed from the two cited trial reports.","source_url":"https://api.fda.gov/drug/label.json?search=openfda.brand_name:%22VYLEESI%22&limit=1","grade":"derived","grade_label":"Derived from cited data","used_on":["https://bremelanotiderx.com/monograph","https://bremelanotiderx.com/faq"]},{"id":"BMT-041","text":"In the RECONNECT publication's discussion, the placebo response was high, approximately 35%, which the authors note is typical of subjective endpoints where expectations, anxiety and reward are involved.","source_url":"https://pmc.ncbi.nlm.nih.gov/articles/PMC6819021/","grade":"human-rct","grade_label":"Human RCT","used_on":["https://bremelanotiderx.com/monograph"]},{"id":"BMT-042","text":"In a 2004 double-blind placebo-controlled study of intranasal PT-141 in healthy men and Viagra-responsive ED patients, erectile responses measured by RigiScan were statistically significant versus placebo at doses above 7 mg, with first erections at about 30 minutes; median Tmax was 0.5 hours and half-life 1.85 to 2.09 hours; flushing and nausea were the most common adverse events.","source_url":"https://europepmc.org/article/MED/14963471","grade":"human-rct","grade_label":"Human RCT","used_on":["https://bremelanotiderx.com/monograph","https://bremelanotiderx.com/studies","https://bremelanotiderx.com/faq","https://bremelanotiderx.com/tools"]},{"id":"BMT-043","text":"In a 2004 crossover study of subcutaneous PT-141, healthy men showed statistically significant RigiScan erectile responses at doses above 1.0 mg (range tested 0.3 to 10 mg), and ED patients with an inadequate response to sildenafil 100 mg responded significantly at 4 and 6 mg.","source_url":"https://europepmc.org/article/MED/14999221","grade":"human-rct","grade_label":"Human RCT","used_on":["https://bremelanotiderx.com/monograph","https://bremelanotiderx.com/studies","https://bremelanotiderx.com/faq","https://bremelanotiderx.com/tools"]},{"id":"BMT-044","text":"In a 2005 randomized crossover study of 19 ED patients, co-administration of 7.5 mg intranasal PT-141 with 25 mg sildenafil produced a significantly greater erectile response than sildenafil alone, without new adverse events.","source_url":"https://europepmc.org/article/MED/15833522","grade":"human-rct","grade_label":"Human RCT","used_on":["https://bremelanotiderx.com/monograph","https://bremelanotiderx.com/studies","https://bremelanotiderx.com/faq","https://bremelanotiderx.com/tools"]},{"id":"BMT-045","text":"A 2008 randomized double-blind trial reported that 10 mg intranasal bremelanotide in 342 sildenafil non-responders produced positive clinical results in 33.5% versus 8.5% on placebo (p=0.03), with more drug-related adverse effects; in January 2023 the Journal of Urology issued an Expression of Concern for this study.","source_url":"https://europepmc.org/article/MED/18206919","grade":"human-rct","grade_label":"Human RCT","used_on":["https://bremelanotiderx.com/monograph","https://bremelanotiderx.com/studies","https://bremelanotiderx.com/faq","https://bremelanotiderx.com/tools"]},{"id":"BMT-046","text":"The 2008 randomized trial of intranasal bremelanotide in women with sexual arousal disorder (Safarinejad, Journal of Sexual Medicine) has been retracted by the journal; its findings cannot be relied on.","source_url":"https://europepmc.org/article/MED/18179455","grade":"bibliographic","grade_label":"Bibliographic record","used_on":["https://bremelanotiderx.com/monograph","https://bremelanotiderx.com/studies","https://bremelanotiderx.com/faq"]},{"id":"BMT-047","text":"FDA's NDA 210557 review records that bremelanotide had a development period of roughly 20 years and that earlier development programs, including treatment of erectile dysfunction in males, did not lead to approved products.","source_url":"https://www.accessdata.fda.gov/drugsatfda_docs/nda/2019/210557Orig1s000MultidisciplineR.pdf","grade":"regulatory","grade_label":"Regulatory record","used_on":["https://bremelanotiderx.com/monograph","https://bremelanotiderx.com/faq","https://bremelanotiderx.com","https://bremelanotiderx.com/comparison"]},{"id":"BMT-048","text":"FDA's review records that the initial clinical studies in women used the intranasal route, and that due to variable systemic exposure via the intranasal route the treatment paradigm became as-needed subcutaneous bremelanotide 1.75 mg.","source_url":"https://www.accessdata.fda.gov/drugsatfda_docs/nda/2019/210557Orig1s000MultidisciplineR.pdf","grade":"regulatory","grade_label":"Regulatory record","used_on":["https://bremelanotiderx.com/monograph","https://bremelanotiderx.com/faq"]},{"id":"BMT-049","text":"During review, FDA's clinical team and the Division of Cardiovascular and Renal Products identified blood pressure increases of approximately 4 mmHg with clinical bremelanotide use, raising a cardiovascular concern, and recommended the ambulatory blood pressure monitoring study.","source_url":"https://www.accessdata.fda.gov/drugsatfda_docs/nda/2019/210557Orig1s000MultidisciplineR.pdf","grade":"regulatory","grade_label":"Regulatory record","used_on":["https://bremelanotiderx.com/monograph","https://bremelanotiderx.com/faq"]},{"id":"BMT-050","text":"In a 1998 double-blind placebo-controlled crossover study of 10 men with psychogenic erectile dysfunction, the bremelanotide precursor Melanotan-II produced clinically apparent erections in 8 of 10; mean duration of tip rigidity over 80% was 38.0 minutes versus 3.0 on placebo (p=0.0045), with nausea, stretching, yawning and decreased appetite as side effects.","source_url":"https://europepmc.org/article/MED/9679884","grade":"human-rct","grade_label":"Human RCT","used_on":["https://bremelanotiderx.com/monograph","https://bremelanotiderx.com/studies","https://bremelanotiderx.com/faq"]},{"id":"BMT-051","text":"In a 2000 double-blind crossover study of 10 men with erectile dysfunction and organic risk factors, Melanotan-II initiated erections in 12 of 19 injections versus 1 of 21 for placebo, with tip rigidity over 80% lasting 45.3 versus 1.9 minutes (p=0.047), higher reported sexual desire, and severe nausea after 4 of 19 injections.","source_url":"https://europepmc.org/article/MED/11018622","grade":"human-rct","grade_label":"Human RCT","used_on":["https://bremelanotiderx.com/monograph","https://bremelanotiderx.com/studies","https://bremelanotiderx.com/faq"]},{"id":"BMT-052","text":"The erection-inducing property of this peptide family was discovered accidentally during University of Arizona tanning-peptide research on Melanotan-II, as documented by Hadley's 2005 account.","source_url":"https://europepmc.org/article/MED/15996790","grade":"review","grade_label":"Review or guideline","used_on":["https://bremelanotiderx.com/monograph","https://bremelanotiderx.com/faq"]},{"id":"BMT-053","text":"In ovariectomized hormone-primed female rats, PT-141 selectively stimulated solicitational behaviors without affecting lordosis, pacing or other sexual behaviors, without generalized motor activation, and without altering sexual reward perception.","source_url":"https://pmc.ncbi.nlm.nih.gov/articles/PMC454387/","grade":"animal","grade_label":"Animal","used_on":["https://bremelanotiderx.com/monograph","https://bremelanotiderx.com/studies","https://bremelanotiderx.com/faq"]},{"id":"BMT-054","text":"In estradiol-plus-progesterone-primed female rats, Melanotan-II increased solicitation-type behaviors (hops, darts, ear wiggling) without altering pacing or lordosis; with estradiol alone it had no effect, indicating hormone-context dependence.","source_url":"https://europepmc.org/article/MED/17113634","grade":"animal","grade_label":"Animal","used_on":["https://bremelanotiderx.com/monograph","https://bremelanotiderx.com/studies"]},{"id":"BMT-055","text":"PT-141 administration produces penile erections in rats and nonhuman primates, activates hypothalamic neurons (c-Fos), and produced rapid dose-dependent erectile activity in early human studies, per the 2003 program overview.","source_url":"https://europepmc.org/article/MED/12851303","grade":"review","grade_label":"Review or guideline","used_on":["https://bremelanotiderx.com/monograph","https://bremelanotiderx.com/studies"]},{"id":"BMT-056","text":"A 2007 preclinical review reports that bremelanotide's solicitation effects in female rats localize to the medial preoptic area rather than the ventromedial hypothalamus, and that the compound stimulates erection in men and male rats.","source_url":"https://europepmc.org/article/MED/17958619","grade":"review","grade_label":"Review or guideline","used_on":["https://bremelanotiderx.com/monograph","https://bremelanotiderx.com/studies"]},{"id":"BMT-057","text":"Cryo-EM structures of the melanocortin-4 receptor in complex with Gs protein have been solved bound to alpha-MSH, afamelanotide, bremelanotide and a small-molecule agonist, revealing a conserved binding mode for the peptide agonists.","source_url":"https://pmc.ncbi.nlm.nih.gov/articles/PMC8563965/","grade":"in-vitro","grade_label":"In vitro","used_on":["https://bremelanotiderx.com/monograph","https://bremelanotiderx.com/studies"]},{"id":"BMT-058","text":"In two phase 1 randomized placebo-controlled trials in obese premenopausal women, bremelanotide reduced body weight versus placebo (least-squares mean difference -1.3 kg over 16 days with three-times-daily dosing, p<0.0001; 1.7 vs 0.9 kg with twice-daily dosing, p<0.001) and cut caloric intake by roughly 400 kcal per day.","source_url":"https://pmc.ncbi.nlm.nih.gov/articles/PMC9314948/","grade":"human-rct","grade_label":"Human RCT","used_on":["https://bremelanotiderx.com/monograph","https://bremelanotiderx.com/studies","https://bremelanotiderx.com/faq"]},{"id":"BMT-059","text":"Bremelanotide was developed by Palatin Technologies, which sponsored the phase 3 trials and out-licensed exclusive North American rights to AMAG Pharmaceuticals, which submitted the New Drug Application; the 2019 approval was bremelanotide's first anywhere.","source_url":"https://europepmc.org/article/MED/31429064","grade":"review","grade_label":"Review or guideline","used_on":["https://bremelanotiderx.com/monograph"]},{"id":"BMT-060","text":"A 2022 peer-reviewed review of bremelanotide for HSDD attributes the transient blood pressure increase and heart rate decrease to MC4R activation and the hyperpigmentation adverse effect to MC1R activation.","source_url":"https://pmc.ncbi.nlm.nih.gov/articles/PMC8788464/","grade":"review","grade_label":"Review or guideline","used_on":["https://bremelanotiderx.com/monograph","https://bremelanotiderx.com/faq"]},{"id":"BMT-061","text":"Addyi (flibanserin), the other FDA-approved HSDD drug, was approved August 18, 2015 (NDA 022526); its current label indicates it for acquired, generalized HSDD in women less than 65 years of age, taken 100 mg orally once daily at bedtime, and states it is not indicated in men and not indicated to enhance sexual performance.","source_url":"https://api.fda.gov/drug/label.json?search=openfda.brand_name:%22ADDYI%22&limit=1","grade":"fda-label","grade_label":"FDA label","used_on":["https://bremelanotiderx.com/comparison","https://bremelanotiderx.com/faq"]},{"id":"BMT-062","text":"Addyi carries a boxed warning for hypotension and syncope: alcohol close in time increases the risk (patients must wait at least 2 hours after one or two standard drinks or skip that night's dose after three or more), moderate or strong CYP3A4 inhibitors are contraindicated, and hepatic impairment is contraindicated; Addyi is dosed at bedtime because daytime dosing increases hypotension, syncope, accidental injury and CNS depression risks, and it carries the same discontinue-after-8-weeks-if-no-improvement instruction as Vyleesi.","source_url":"https://api.fda.gov/drug/label.json?search=openfda.brand_name:%22ADDYI%22&limit=1","grade":"fda-label","grade_label":"FDA label","used_on":["https://bremelanotiderx.com/comparison","https://bremelanotiderx.com/faq"]},{"id":"BMT-063","text":"A 2016 JAMA Internal Medicine meta-analysis of eight flibanserin trials (5,914 women) found a pooled benefit of 0.49 additional satisfying sexual events per month (95% CI 0.32 to 0.67) versus placebo, with significantly increased risks of dizziness (RR 4.00), somnolence (RR 3.97), nausea (RR 2.35) and fatigue (RR 1.64), discontinuation due to adverse events (RR 2.19), and overall evidence quality graded very low.","source_url":"https://europepmc.org/article/MED/26927498","grade":"review","grade_label":"Review or guideline","used_on":["https://bremelanotiderx.com/comparison","https://bremelanotiderx.com/faq"]},{"id":"BMT-064","text":"FDA states that compounded drugs are not FDA-approved, meaning FDA does not verify their safety, effectiveness or quality before they are marketed.","source_url":"https://www.fda.gov/drugs/human-drug-compounding/compounding-and-fda-questions-and-answers","grade":"regulatory","grade_label":"Regulatory record","used_on":["https://bremelanotiderx.com/monograph","https://bremelanotiderx.com/faq","https://bremelanotiderx.com/comparison","https://bremelanotiderx.com/decision_aid"]},{"id":"BMT-065","text":"In a 22-week randomized double-blind placebo-controlled crossover trial of 30 pre- and postmenopausal women with sexual dysfunction, on-demand 32 IU intranasal oxytocin taken within 50 minutes before intercourse increased FSFI scores by 26% versus 31% with placebo, with no significant between-group difference.","source_url":"https://europepmc.org/article/MED/26151620","grade":"human-rct","grade_label":"Human RCT","used_on":["https://bremelanotiderx.com/comparison"]},{"id":"BMT-066","text":"In a naturalistic placebo-controlled study of 29 heterosexual couples, 24 IU intranasal oxytocin did not alter classical parameters of sexual function such as sexual drive, arousal, penile erection or lubrication.","source_url":"https://europepmc.org/article/MED/24503174","grade":"human-rct","grade_label":"Human RCT","used_on":["https://bremelanotiderx.com/comparison"]},{"id":"BMT-067","text":"No FDA-approved nasal oxytocin product is currently marketed: a Drugs@FDA query for oxytocin products with a nasal route returns only SYNTOCINON NASAL with marketing status Discontinued; oxytocin remains approved as an injectable obstetric drug.","source_url":"https://api.fda.gov/drug/drugsfda.json?search=products.active_ingredients.name:%22oxytocin%22+AND+products.route:%22NASAL%22&limit=5","grade":"regulatory","grade_label":"Regulatory record","used_on":["https://bremelanotiderx.com/comparison"]},{"id":"BMT-068","text":"Site content counts, recomputable from this pack's rendered arrays: 38 citations in the numbered reference list (25 peer-reviewed, 13 government/registry/chemical database); 15 rows in the study table; 12 rows with species human; 2 rows carrying journal integrity flags; 1 FDA-approved use.","source_url":"https://api.fda.gov/drug/label.json?search=openfda.brand_name:%22VYLEESI%22&limit=1","grade":"derived","grade_label":"Derived from cited data","used_on":["https://bremelanotiderx.com","https://bremelanotiderx.com/monograph","https://bremelanotiderx.com/faq"]},{"id":"BMT-069","text":"Bremelanotide (PT-141) is FDA-approved as Vyleesi for acquired hypoactive sexual desire disorder in premenopausal women. 'PT-141' vials sold outside licensed pharmacies are not the approved product.","source_url":"https://www.accessdata.fda.gov/scripts/cder/daf/index.cfm?event=overview.process&ApplNo=210557","grade":"regulatory","grade_label":"Regulatory record","used_on":["https://bremelanotiderx.com/entity","https://bremelanotiderx.com","https://bremelanotiderx.com/monograph","https://bremelanotiderx.com/copy"]}]}