in VYLEESI-treated patients(20%) than placebo-treated patients (<1%). None of the flushing events were serious and few were severe(<1%), and 1% of patients who received VYLEESI discontinued the study due to flushing.
Less Common Adverse ReactionsLess common adverse reactions occurring in <2% of VYLEESI-treated patients and at an incidence greater thanin the placebo group were upper abdominal pain, diarrhea, myalgia, arthralgia, pain, restless leg syndrome,rhinorrhea, increased creatine phosphokinase, blood pressure increased, pain in extremity and focal skinhyperpigmentation.
Acute hepatitis
In the open-label, uncontrolled extension phase of one study, a single case of acute hepatitis was reported in apatient who had received 10 doses of VYLEESI over one year. She presented with serum transaminasesexceeding 40 times the upper limit of normal (ULN), total bilirubin 6 times the ULN, and alkaline phosphataseless than 2 times ULN. Liver tests returned to normal 4 months after study drug discontinuation. Becauseanother etiology was not identified, the role of VYLEESI could not definitively be excluded. There was noimbalance between treatment groups in serum transaminase outliers or other signals for hepatotoxicity in theclinical development program.
7 DRUG INTERACTIONS
7.1 Effect of VYLEESI on Other Drugs
VYLEESI may slow gastric emptying and thus has the potential to reduce the rate and extent of absorption ofconcomitantly administered oral medications. Instruct patients to avoid the use of VYLEESI when takingconcomitant oral drugs that are dependent on threshold concentrations for efficacy (e.g., antibiotics). Inaddition, patients should consider discontinuing VYLEESI if there is a delayed drug effect of concomitant oralmedications when a quick onset of drug effect is desired (e.g. drugs for pain relief such as indomethacin).
7.2 Naltrexone
As VYLEESI may significantly decrease the systemic exposure of orally-administered naltrexone, patientsshould avoid using VYLEESI with an orally administered naltrexone-containing product that is intended to treatalcohol and opioid addiction due to the severe consequence of naltrexone treatment failure [see Clinical
Pharmacology (12.3)].
8 USE IN SPECIFIC POPULATIONS
8.1 Pregnancy
Pregnancy Exposure Registry
There will be a pregnancy exposure registry that monitors pregnancy outcomes in women exposed to VYLEESIduring pregnancy. Pregnant women exposed to VYLEESI and healthcare providers are encouraged to call theVYLEESI Pregnancy Exposure Registry at (877) 411- 2510.
Risk Summary
The few pregnancies in women exposed to VYLEESI in clinical trials are insufficient for determining whetherthere 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 thepotential for fetal harm. In animal reproduction and development studies, daily subcutaneous administration ofbremelanotide to pregnant dogs during the period of organogenesis at exposures greater than or equal to 16times the maximum recommended dose (based on area under the concentration-time curve or AUC) producedfetal harm. In mice subcutaneously dosed with bremelanotide during pregnancy and lactation, developmentaleffects were observed in the offspring at greater than or equal to 125-times the maximum recommended dose(based on AUC) [see Data]. However, the lo |
