Drug Interactions between bremelanotide and naltrexone

GENERALLY AVOID: Bremelanotide may slow gastric emptying and reduce the rate and extent of absorption of concomitantly administered oral medications. In clinical pharmacology studies, bremelanotide 1.75 mg given subcutaneously did not affect the absorption of most of the tested oral medications to any clinically relevant degree, including amlodipine, bupropion, celecoxib, ethinyl estradiol, furosemide, hydrochlorothiazide, lisinopril, losartan, metformin, metoprolol, norethindrone, phentermine, pseudoephedrine, sertraline, and venlafaxine. However, naltrexone peak plasma concentration (Cmax) and systemic exposure (AUC) decreased by approximately 60% and 40%, respectively, relative to administration alone. Indomethacin Cmax and AUC decreased by approximately 35% and 20%, respectively, relative to administration alone.

MANAGEMENT: Patients should avoid the use of bremelanotide when taking concomitant oral medications that are dependent on threshold concentrations for efficacy (e.g., antibiotics). Patients should also consider avoiding bremelanotide when a quick onset of therapeutic effect is desired for concomitant oral medications (e.g., drugs for pain relief such as indomethacin).

GENERALLY AVOID: Coadministration of naltrexone with other agents known to induce hepatotoxicity may potentiate the risk of liver injury. Naltrexone, especially in larger than recommended doses (more than 50 mg/day), has been associated with hepatocellular injury, hepatitis, and elevations in liver transaminases and bilirubin. Other potential causative or contributory etiologies identified include preexisting alcoholic liver disease, hepatitis B and/or C infection, and concomitant usage of other hepatotoxic drugs.

MANAGEMENT: The use of naltrexone with other potentially hepatotoxic agents should be avoided whenever possible (e.g., acetaminophen; alcohol; androgens and anabolic steroids; antituberculous agents; azole antifungal agents; ACE inhibitors; cyclosporine (high dosages); disulfiram; endothelin receptor antagonists; interferons; ketolide and macrolide antibiotics; kinase inhibitors; minocycline; nonsteroidal anti-inflammatory agents; nucleoside reverse transcriptase inhibitors; proteasome inhibitors; retinoids; sulfonamides; tamoxifen; thiazolidinediones; tolvaptan; vincristine; zileuton; anticonvulsants such as carbamazepine, hydantoins, felbamate, and valproic acid; lipid-lowering medications such as fenofibrate, lomitapide, mipomersen, niacin, and statins; herbals and nutritional supplements such as black cohosh, chaparral, comfrey, DHEA, kava, pennyroyal oil, and red yeast rice). Patients should be advised to seek medical attention if they experience potential signs and symptoms of hepatotoxicity such as fever, rash, itching, anorexia, nausea, vomiting, fatigue, malaise, right upper quadrant pain, dark urine, pale stools, and jaundice. Periodic monitoring of hepatic function is advisable.