Co-prescribing naloxone with opioids


When authorized medical personnel prescribe two or more medications together for the same condition or disease to the same patient, it is known as co-prescribing. When clinicians prescribe the opioid overdose drug naloxone to patients in conjunction with the patient's opioid prescriptions, or to patients at risk for opioid overdose, it is called a naloxone co-prescription. Due, in part, to the opioid epidemic in the United States, there are currently both a state-level and nation-wide movement in the medical and public policy fields to encourage, and sometimes require, naloxone co-prescribing. The U.S. government has issued guidelines recommending co-prescribing naloxone along with opioids. Some co-prescribing, e.g., the practice of co-prescribing benzodiazepines and certain opioid medications to patients, has been cause for concern due to the high risk of opioid overdose.
Co-prescribing naloxone with opioids is supported by the World Health Organization, U.S. CDC, and Substance Abuse and Mental Health Services Administration.

Background

The illegitimate use of opioids in the United States became an “epidemic” in the early 21st century. The Mayo Clinic Proceedings describes the epidemic as “...the most serious and most important public health crisis today.” The consequences of the calamity are not only significant deaths due to opioid overdose, but also a descending trend in health and people's sense of well-being throughout the country. Increased use of naloxone, particularly the nasal spray version, Narcan, along with a growing awareness of the hazards of opioid ingestion, has reduced overdose mortality.
In 2017, the American Medical Association's Opioid Task Force recommended in a guideline that physicians “...consider co-prescribing the drug when clinically appropriate for patients who are at risk for opioid overdose or might be in a position to help someone else at risk.”
In December 2018, Admiral Brett P. Giroir, the U.S. Health and Human Services Assistant Secretary for Health, released federal guidelines related to the prescribing of naloxone to populations at high risk for opioid overdose. The act of prescribing naloxone along with opioid prescriptions is called co-prescribing. HHS guidelines recommend that clinicians co-prescribe naloxone to people on high doses of opioid medications or have other high risk factors.
According to a 2020 article by Health Crisis Alert:
The study, “A Way Forward: How Naloxone Saves Lives from Overdoses” published by CME Outfitters, a continuing medical education organization, suggests that co-prescribing naloxone is not only a life-saving measure for those with opioid use disorder but a way for prescribers to talk to patients about the risk of accidental overdose.

Naloxone co-prescribing

Naloxone comes with a variety of delivery systems, including nasal spray, intravenous infusion, as well as subcutaneous and intramuscular injection. Administering injectable naloxone does require professional training. Administering through the nasal spray, Narcan, and the auto-injectable device, Evizio, is “...easy and suitable for home use.” According to HHS, most health insurance plans cover at least one of these products.

Federal guidelines

In 2018 a Joint Meeting of the FDA's Anesthetic and Analgesic Drug Products Advisory Committee and the Drug Safety and Risk Management Advisory Committee recommended label changes that encouraged the co-prescribing of naloxone along with opioids, making the potential life-saving opioid antagonist more available to patients and the medical community. Branded versions of naloxone include Evizo, an auto-injector and the nasal spray Narcan. Objections to the recommendation included concerns over the cost of the auto-injector at $4,000/dose. It was noted that the FDA’s estimates were inflated. Generic naloxone lists at around $40/dose; Narcan at $125; and that the manufacturer of Evzio had announced a cheaper, generic version of the drug.
U.S. federal guidelines recommend that doctors co-prescribe naloxone for all patients who are prescribed opioids and also meet at least one of the following criteria:
Additionally, the prescribers are encouraged to authorize naloxone outright to patients who are not prescribed opioids if they use illegal street drugs or engage in other high-risk behavior.

State laws

States have taken the lead on this issue. In Tennessee, the combination of the co-prescription of naloxone with opioid medications and telehealth access have helped the state battle its own opioid epidemic. During the 2020 coronavirus pandemic, Tennessee saw an increase in fatal opioid overdoses. The state responded by incorporating recommendations from the Commissioner's Committee on Chronic Pain Guidelines that support co-prescribing naloxone to certain high-risk populations.
Vermont required co-prescribing naloxone to patients who take at least 90 MME/d or who also take benzodiazepines with opioids. In Virginia, doctors are required to co-prescribe for patients at 120 MME/d or greater or for individuals who also take benzodiazepines. As a result, these two states have the highest co-prescription rates in all of the United States.
In New Jersey in June 2020, the state's attorney general issued a policy that requires, for the duration of the coronavirus pandemic, prescribers to prescribe naloxone to patients who take higher doses of opioids or who take opioids with anti-anxiety benzodiazepines. The urgency of the pandemic, according to the news site North New Jersey, led the state to issue the new requirements when it did.
According to the National Institute on Drug Abuse, most pharmacies across the U.S. dispense naloxone without a physician's prescription. Data presented by the Prescription Drug Abuse Policy System indicates that, in 49 states, pharmacists are allowed to dispense naloxone without a "patient-specific prescription from another medical professional."
According to the U.S. Centers for Disease Control and Prevention, the number of prescriptions for naloxone doubled in just a single year. However, for every 70 "high-dose opioid" prescription, only one naloxone prescription is dispensed.
A research project from the University of Kentucky’s Institute for Pharmaceutical Outcomes and Policy at the College of Pharmacy studied the association between legally mandated naloxone co-prescription and dispensing the drug to patients across the United States. 88 prescriptions per 100,000 were distributed in Virginia; 111/100,000 were dispensed in Vermont during the first month the law was in effect. In contrast, 16 prescriptions per 100,000 were dispensed in the ten states with the country’s highest overdose rates and six per/100,000 were distributed in the remaining 38 states. The researchers concluded that statutes requiring naloxone prescriptions for individuals at risk for opioid overdose and those people actually receiving naloxone resulted in “...further reduction of opioid-related harm.”

State legislation

Legislators in several U.S. states have pushed changes to state laws regarding naloxone co-prescribing. Examples include:
Within the Indian Health Service, co-prescribing is on the rise. The Gallup Indian Medical Center, a 99-bed hospital in Gallup, New Mexico, on the border of the Navajo Reservation, started co-prescribing naloxone with opioids in May 2015.

Issues

Access

One contemporary issue for 2020 is addressing the opioid use disorder crisis in the midst of the coronavirus global pandemic. According to the academic journal Health Affairs, "... we are living in a time when only 7 percent of doctors can effectively treat opioid use disorder..."
Forty-two percent of counties in the United States have no buprenorphine prescribers. "Access is almost non-existent," according to Health Affairs.

Physician legal concerns

In a 2016 article in Substance Abuse, a peer-reviewed medical journal, the authors concluded that although some medical providers have concerns about legal risks concerning co-prescribing naloxone to pain patients, "such concerns are unfounded" and that the legal risk is no higher than it is with any other medication. Most states have laws that give explicit protection from legal liability for providers who prescribe or dispense naloxone. According to the article, "Where a prescriber determines, in his or her clinical judgment, that a patient is at risk of overdose, co-prescribing naloxone is a reasonable and prudent clinical and legal decision. No clinician should fail or refuse to issue such a prescription based on liability concerns."

State legislation

In 2018, only one naloxone prescription was dispensed for each 70 "high-dose" opioid prescriptions in the U.S., according to the Centers for Disease Control and Prevention. In South Carolina, a bill was introduced in the state House that would require doctors and other medical professionals who can prescribe medication to prescribe Narcan to patients who have ever overdosed on opioids, have a history of drug abuse, or who are being prescribed any benzodiazepines while on opioids.
Currently, Americans under the age of 50 are more likely to die from a narcotic overdose than from any other cause. While many pharmacies will dispense Narcan or naloxone without a prescription, a prescription is usually required for health insurance reimbursement.

Opioid co-prescribing with benzodiazepine

Between 2014 and 2016, U.S. clinicians prescribed benzodiazepines at 66 million office visits each year. In 35 percent of those cases, the patient being prescribed benzodiazepines was also currently on an opioid prescription. A Stanford University researcher said in January 2020 that benzodiazepines are "implicated in a third of opioid overdoses" because they can increase the negative effects of opioids on the respiratory system. The CDC's guidelines for opioid prescriptions for chronic pain recommends against co-prescribing both benzodiazepines and opioids together because of the high level of that risk. In 2016, the Food and Drug Administration issued a black-box warning against co-prescribing benzodiazepines and opioids, including cough medicines containing opiates.
A 2019 study in PLOS Medicine recommends that doctors avoid co-prescribing benzodiazepines to opioid dependent patients who are being treated with methadone or buprenorphine. According to a University of Bristol study, patients in that population have a "three-fold increase in risk of overdose death." According to the study, one reason doctors might be ignoring clinical guidelines against co-prescribing the two types of medication together is because many opioid dependent patients have high levels of anxiety.