What medication is most commonly involved in prescription opioid overdose deaths?

Most Common Medication in Prescription Opioid Overdose Deaths

Immediate-release oxycodone is involved in the greatest number of opioid-related deaths among prescription opioids. 1

Evidence on Prescription Opioid Overdose Deaths

Prescription opioid overdoses represent a significant public health concern. Based on the available evidence, the medications most commonly involved in prescription opioid overdose deaths can be identified:

• A population-based study examining medication histories of overdose decedents found that immediate-release oxycodone was involved in the greatest number of opioid-related deaths 1
• Of the 221 oxycodone-related deaths examined, 61% of decedents had filled a prescription for oxycodone within 60 days prior to death 1
• Methadone has been associated with disproportionate numbers of overdose deaths relative to the frequency with which it is prescribed for pain 2
• The rank order of commonly misused opioid medications has been documented as: hydrocodone = oxycodone > methadone = buprenorphine = tramadol = fentanyl (prescription form) > morphine > hydromorphone = oxymorphone > tapentadol 3

Risk Factors for Prescription Opioid Overdose

Several factors increase the risk of overdose with prescription opioids:

• High-dose opioid therapy (>80-100 MME/day) is disproportionally associated with overdose deaths 4
• Methadone has complex pharmacokinetics and pharmacodynamics, including a long and variable half-life and peak respiratory depressant effect occurring later and lasting longer than peak analgesic effect 2
• Transdermal fentanyl has complex absorption and pharmacodynamics with gradually increasing serum concentration during the first part of the 72-hour dosing interval 2
• Extended-release/long-acting (ER/LA) opioids present higher risks when prescribed inappropriately, especially to opioid-naive patients 2

Patterns of Prescription Opioid Misuse and Overdose

Important patterns have been observed in prescription opioid overdose deaths:

• Immediate-release formulations are more commonly misused than extended-release formulations 3
• For oxycodone specifically, the most common strength dispensed within 60 days to decedents was 10 mg for immediate-release formulations (72 prescriptions) 1
• A strong increasing linear trend exists between dose strength and proportion of prescriptions dispensed to decedents for immediate-release oxycodone products and extended-release fentanyl products 1
• Multiple drugs are typically involved in fatal overdoses, with concurrent use of benzodiazepines and other CNS depressants significantly increasing risk 4, 3

Prevention Strategies

To reduce prescription opioid overdose deaths:

• Initiate opioid treatment with immediate-release rather than ER/LA opioids 2, 4
• Avoid methadone for pain management when alternatives exist due to its complex pharmacology and disproportionate association with overdose deaths 2, 4
• Implement careful dose titration for all opioids, particularly at doses above 50 MME/day 4
• Avoid co-prescribing benzodiazepines with opioids 4
• Consider naloxone prescriptions for high-risk patients 4
• Utilize Prescription Drug Monitoring Programs (PDMPs) to identify potential doctor shopping 4

Clinical Implications

The evidence suggests that immediate-release oxycodone's prominence in overdose deaths may be related to several factors:

• Its widespread prescription and availability
• High "liking" and "wanting" properties that contribute to its abuse liability 5
• The false initial claim that certain formulations (like OxyContin) were less addictive 5
• The ability to manipulate immediate-release formulations for rapid onset of effects 5

Clinicians should be particularly cautious when prescribing immediate-release oxycodone and other commonly misused opioids, especially at higher doses or in combination with other CNS depressants.