Which medications should prompt an offer of naloxone when filling an opioid prescription?

From the Guidelines

Naloxone should be offered to patients filling opioid prescriptions who are taking high-dose opioids, those on concurrent benzodiazepines, or have a history of opioid use disorder, as these factors increase the risk of overdose and respiratory depression. When considering the options provided, the following should prompt an offer of naloxone:

• B Alprazolam + oxycodone, as the combination of opioids with benzodiazepines increases the risk of overdose and respiratory depression 1
• A Oxycodone 30 mg TID x 30 days, as high-dose opioids (≥50 morphine milligram equivalents per day) are associated with an increased risk of overdose 1 The other options do not necessarily require naloxone co-prescribing based on the information provided:
• C Buprenorphine/naloxone 16/4 mg daily already contains naloxone, an opioid antagonist that can reverse opioid-induced overdoses
• D Tramadol 25 mg qid, Tylenol 500 mg qid, Naproxen 440 mg tid does not contain high-dose opioids or benzodiazepines, and therefore does not necessarily require naloxone co-prescribing based on the information provided. It is essential to note that naloxone co-prescribing can be facilitated by clinics or practices with resources to provide naloxone training and by collaborative practice models with pharmacists 1. Patients and their household members should be educated on recognizing overdose signs and proper naloxone administration techniques, as bystander intervention with naloxone can prevent fatal outcomes while emergency services are en route.

From the FDA Drug Label

The risk is increased with concurrent abuse of buprenorphine hydrochloride with alcohol and/or other CNS depressants. Naloxone hydrochloride injection is indicated for the complete or partial reversal of opioid depression, including respiratory depression, induced by natural and synthetic opioids The medications that should prompt an offer of naloxone when filling an opioid prescription are:

• B. Alprazolam + oxycodone: This combination increases the risk of respiratory depression, which can be reversed with naloxone.
• A. Oxycodone 30 mg TID x 30 days: High doses of opioids like oxycodone increase the risk of overdose and respiratory depression, making naloxone a necessary precaution.

The other options do not directly indicate a need for naloxone:

• C. Buprenorphine/naloxone 16/4 mg daily: This combination already includes naloxone, which is intended to reduce the risk of overdose.
• D. Tramadol 25 mg qid, Tylenol 500 mg qid, Naproxen 440 mg tid: While tramadol is an opioid, the dose is relatively low, and the presence of other non-opioid medications does not necessarily increase the risk of overdose to the same extent as other options. 2 3

From the Research

Medications that Prompt Naloxone Offer

The following medications should prompt an offer of naloxone when filling an opioid prescription:

• B. Alprazolam + oxycodone: This combination of a benzodiazepine and an opioid increases the risk of overdose and respiratory depression, making naloxone co-prescription crucial 4.
• D. Tramadol 25 mg qid, Tylenol 500 mg qid, Naproxen 440 mg tid: Although tramadol is considered to have a lower risk of overdose compared to other opioids, its combination with other medications that may increase the risk of overdose, such as benzodiazepines or other opioids, warrants naloxone co-prescription 5, 4.

Medications that Do Not Prompt Naloxone Offer

The following medications do not necessarily prompt an offer of naloxone:

• A. Oxycodone 30 mg TID x 30 days: While oxycodone is an opioid that carries a risk of overdose, the dose and frequency of this prescription do not inherently necessitate naloxone co-prescription without other risk factors being present 6.
• C. Buprenorphine/naloxone 16/4 mg daily: This medication already contains naloxone, an opioid antagonist, which reduces the risk of overdose and may not require additional naloxone co-prescription 7, 8.

Considerations for Naloxone Co-Prescription

When considering naloxone co-prescription, it is essential to evaluate the patient's risk factors for opioid overdose, including:

• High-dose opioid therapy (e.g., morphine-equivalent daily dose ≥100 mg) 6
• Concurrent use of other central nervous system depressants (e.g., benzodiazepines, sleep aids) 4
• History of substance use disorder or opioid misuse 4
• Presence of pulmonary disease or other medical conditions that increase the risk of overdose 6