Unintentional overdose involving opioids has become a leading cause of injury-related death in the United States. “Notwithstanding, several interventions promoted to address opioid-related morbidity and mortality, but few have been rigorously studied,” says Phillip O. Coffin, MD. “One key approach is to provide naloxone—a fast-acting medication used to block the effects of opioids—to patients who may experience an opioid overdose.” In rigorous observational studies, this strategy has led to substantial reductions in opioid overdose mortality.

Recently, Dr. Coffin and colleagues expanded upon a naloxone distribution approach that had long served people who used illicit opioids. “We found that providing naloxone to people who use drugs was associated with a substantial decline in heroin-related deaths,” Dr. Coffin says. “However, we had not made a dent in the number of deaths from opioid analgesics, and our research showed that most of those decedents had been prescribed opioids. We decided to implement and study if we could reach this at-risk population by co-prescribing naloxone to patients in primary care settings when they receive their opioid prescriptions.”

Testing a New Approach

For a study published in Annals of Internal Medicine, Dr. Coffin and colleagues developed a standardized naloxone co-prescribing program (Naloxone for Opioid Safety Evaluation, or NOSE) at primary care clinics in a safety-net system in San Francisco. The study assessed the feasibility of introducing and scaling up naloxone co-prescribing to patients who were prescribed opioids for chronic pain at six safety-net primary care clinics in the region.

The authors also assessed the association of naloxone co-prescribing with emergency room utilization and prescribed opioid dose. The 2-year non-randomized study included 1,985 adults receiving long-term opioid therapy for pain. “Providers and clinic staff received training and support in naloxone prescribing as part of the intervention,” notes Dr. Coffin. Providers were also encouraged to avoid the word “overdose” and instead refer to naloxone as a rescue medication for bad reactions to opioids in which one stops breathing or cannot be woken up.

Assessing the Results

The researchers found that about 38% of patients receiving long-term opioids were prescribed naloxone. “Our data indicate that co-prescribing is feasible,” says Dr. Coffin. Patients who had previous opioid-related emergency room visits or were on higher opioid doses were more likely to be prescribed naloxone. “Patients prescribed naloxone had an average of 47% fewer opioid-related emergency department visits in the first year after receiving the prescription compared to those not prescribed naloxone,” adds Dr. Coffin. There was no net change over time in opioid dose among those who received naloxone and those who did not.

Dr. Coffin says results of the analysis were observational and that more research is needed to determine if the findings are generalizable beyond safety-net settings. “However, our data indicate that naloxone can be co-prescribed to primary care patients who are given opioids for pain,” he says. Additional papers in press have demonstrated favorable responses to the practice by patients and providers. The CDC’s recently-released opioid prescribing guidelines now provide criteria for offering naloxone; these include receipt of 50 mg or more morphine equivalents per day of opioids, concurrent use of benzodiazepines, or a history of a substance use disorder. This treatment practice may have ancillary benefits, such as reducing opioid-related adverse events, as suggested by this study.

Phillip O. Coffin, MD, has indicated to Physician’s Weekly that he has led studies that have received donated extended-release naltrexone from Alkermes for a methamphetamine study. He is also currently leading a study that receives donated ledipasvir-sofosbuvir for hepatitis C treatment from Gilead.



Coffin PO, Behar E, Rowe C, et al. Nonrandomized intervention study of naloxone coprescription for primary care patients receiving long-term opioid therapy for pain: naloxone coprescribing in primary care clinics. Ann Intern Med. 2016 Jun 28 [Epub ahead of print]. Available at: http://annals.org/article.aspx?articleid=2531366.

Rowe C, Santos GM, Behar E, Coffin PO. Correlates of overdose risk perception among illicit opioid users. Drug Alcohol Depend. 2016;159:234-239.

Behar E, Santos GM, Wheeler E, Rowe C, Coffin PO. Brief overdose education is sufficient for naloxone distribution to opioid users. Drug Alcohol Depend. 2015;148:209-212.