Prescribing to protect case series: naltrexone as a novel intervention to prevent fentanyl overdose in people who use cocaine

Background The rise in fentanyl contamination of cocaine has contributed to a surge in opioid-involved overdose deaths among people who use cocaine (PWUC). Existing harm reduction strategies, including naloxone distribution, drug checking, and counseling people to use with others, are inadequate in fully addressing this risk. Despite robust evidence supporting contingency management (CM) as an effective treatment for cocaine use disorder (CUD), its implementation remains limited. Naltrexone, a potent opioid antagonist, has been evaluated for treatment of CUD and has not been found to be effective. No pharmacotherapies are FDA approved for CUD. However, naltrexone may provide opioid overdose protection for individuals at risk of unwitting fentanyl exposure through fentanyl contamination of cocaine. Case presentation We conducted a retrospective case series of three adults with cocaine use disorder receiving care at the Stimulant Treatment and Recovery Team (START) Clinic at Boston Medical Center. All three patients with cocaine use disorder reported cocaine use with unintentional fentanyl exposure, and two had prior nonfatal opioid-involved overdoses. Oral or intramuscular naltrexone was initiated in all cases and was tolerated without reported adverse effects or precipitated withdrawal. Patients continued naltrexone for several months, and no opioid-involved overdoses were reported. Conclusions In this case series of patients with cocaine use disorder, the initiation of naltrexone for opioid overdose risk prevention was feasible, acceptable, and well tolerated. Naltrexone warrants study as a component of overdose prevention strategies in stimulant treatment settings where fentanyl contamination poses increased risk.