Risk of Opioid Overdose Associated with Concomitant Use of Methadone and Statins

Area of Science:

• Pharmacology and Toxicology
• Pharmacoepidemiology
• Drug Safety

Background:

• Methadone, a medication for opioid use disorder, has a high potential for drug-drug interactions.
• P-glycoprotein (P-gp) plays a role in methadone transport, and statins can inhibit P-gp.
• Limited evidence exists on the magnitude of overdose risk from methadone-statin interactions.

Purpose of the Study:

• To investigate the association between concomitant use of methadone and P-gp-inhibiting statins and the risk of opioid overdose.
• To determine if specific statins (simvastatin, atorvastatin, lovastatin) that inhibit P-gp increase methadone plasma concentrations and subsequent overdose risk.

Main Methods:

• A cohort study using Medicaid claims data from 2003 to 2020.
• Inclusion of new concomitant users of methadone and statins.
• Comparison of opioid overdose rates between users of P-gp-inhibiting statins (simvastatin, atorvastatin, lovastatin) and a negative control (rosuvastatin), with adjusted hazard ratios.

Main Results:

• A total of 69,263 individuals were included in the study.
• The overall incidence rate of opioid overdose was 26.0 per 1,000 person-years.
• Adjusted hazard ratios showed no association between methadone and P-gp-inhibiting statins (simvastatin, atorvastatin) and opioid overdose risk compared to rosuvastatin.

Conclusions:

• Concomitant use of methadone with simvastatin, atorvastatin, or lovastatin is not associated with an increased risk of opioid overdose.
• Findings were consistent across sensitivity analyses and stratified analyses.
• The study provides evidence against a significant drug-drug interaction risk for these specific methadone-statin combinations regarding overdose.