Coprescription of naloxone for acute use in case of overdose may benefit primary care patients taking opioids for chronic pain

Receiving a naloxone prescription corresponded to a 47% reduction in opioid-related ED visits per month 6 months after getting the prescription.


Providing naloxone for acute use in case of overdose to patients receiving opioids in primary care settings may reduce opioid-related adverse events, a new study found.

To evaluate the feasibility and effect of implementing naloxone prescription to patients prescribed opioids for chronic pain, researchers conducted a 2-year nonrandomized intervention study for 1,985 patients receiving long-term opioid therapy at 6 safety-net primary care clinics in San Francisco. Researchers developed a standardized naloxone coprescribing program (Naloxone for Opioid Safety Evaluation, or NOSE), which included training in naloxone prescribing for doctors, advanced practitioners, and staff on the rationale and indications for prescribing naloxone, communicating with patients, and educating patients on naloxone use. The patient education checklist included information on the causes of opioid overdose, how to recognize opioid overdose, what to do if someone overdoses (call 911, administer naloxone, follow 911 dispatchers' instructions), and optional aftercare. The checklist also encouraged patients to tell someone else where their naloxone is kept and how to use it.

The researchers then examined the proportion of patients prescribed naloxone, opioid-related ED visits, and prescribed opioid dose based on chart review. Results were published online June 28 by Annals of Internal Medicine.

Baseline opioid dose ranged from 2 to 4,200 morphine-equivalent daily doses per day (MEQ/d), with a median dose of 53 MEQ/d. Nearly 75% received more than 20 MEQ/d, and nearly 10% received more than 400 MEQ/d. Oxycodone was the most commonly prescribed opioid, followed by hydrocodone and morphine.

During the study period, naloxone was prescribed to 759 pain patients (38.2%) over 2,254 patient-years. Patients who received naloxone accounted for 19 (32.2%) of 59 deaths during the study period and 2 (40%) of 5 opioid poisoning deaths. A logistic regression model of a subset of patients for whom clinician data were available showed that patients who were receiving a higher dose of opioids or who were seen in the county ED for an opioid-related visit in the 12 months were more likely to receive a naloxone prescription.

Older patients had lower odds of being prescribed naloxone. Receiving a naloxone prescription was also dependent on which clinic patients attended, with 3 clinics (including 1 of 2 resident training sites) prescribing naloxone to a substantially lower proportion of patients than the other clinics.

Among the 4,322 ED visits during the study period, 471 were opioid-related and 95 were attributed to opioid-induced oversedation. On average, patients had 6% fewer opioid-related ED visits with each additional month since the receipt of a naloxone prescription (incidence rate ratio [IRR], 0.94; 95% CI, 0.89 to 0.998; P=0.044), after adjustment for all demographic and clinical covariates and secular trends in ED use. This monthly decrease in opioid-related ED visits after the receipt of a naloxone prescription corresponded to a 47% reduction in opioid-related ED visits per month 6 months after receipt of the prescription (IRR, 0.53; 95% CI, 0.34 to 0.83; P=0.005) and a 63% reduction after 1 year (IRR, 0.37; 95% CI, 0.22 to 0.64; P<0.001).

The researchers wrote, “When advised to offer naloxone to all patients receiving long-term opioids, clinicians were more likely to prescribe to those likely to be at higher risk for overdose, including patients taking higher doses of opioids and those who have had opioid-related ED visits in the past. In the absence of guideline-based indications for naloxone coprescribing, these may be reasonable metrics upon which to prioritize prescription of naloxone.”

An editorial noted that this was the first study to demonstrate both the feasibility and the clinical benefit of reduced opioid-related ED visits of coprescribing naloxone.

“These results are encouraging in light of the recognized challenges in the implementation of naloxone prescription at the patient, prescriber, and pharmacy levels,” the editorial stated. “With thorough staff training and ongoing staff support, naloxone prescription rates in the NOSE study were substantial but not universal.”