Table 2.
Proportional reporting ratio signal scores regarding abuse/dependence and withdrawal issues for selected opioid drugs (European Medicines Agency EudraVigilance and the Food and Drug Administration (FDA) Adverse Event Reporting System datasets).
| Preferred Term (PT) | Codeine | Dihydrocodeine | Fentanyl | Oxycodone | Pentazocine | Tramadol |
|---|---|---|---|---|---|---|
| PRR (FDR) | PRR (FDR) | PRR (FDR) | PRR (FDR) | PRR (FDR) | PRR (FDR) | |
| Misuse-/Abuse-Related Terms | ||||||
| Drug Abuse | ||||||
| EV | 1.94 (<0.01) | 0.90 (0.44) | 0.93 (0.71) | 0.91 (0.70) | 2.23 (<0.01) | 1.01 (0.02) |
| FAERS | 1.96 (<0.01) | 0.32 (0.41) | 0.40 (0.43) | 2.48 (<0.01) | 1.17 (0.05) | 0.62 (0.43) |
| Drug Abuser | ||||||
| EV | NA | NA | 0.31 (0.68) | 2.52 (<0.01) | NA | 0.65 (0.49) |
| FAERS | 0.17 (0.42) | NA | 0.13 (0.43) | 10.17 (<0.01) | NA | 0.29 (0.43) |
| Drug Diversion | ||||||
| EV | 0.88 (0.26) | NA | 2.30 (<0.01) | 0.72 (0.68) | NA | 0.18 (0.71) |
| FAERS | NA | 2.12 (<0.01) * | 1.70 (<0.01) | 1.17 (<0.01) | NA | 0.25 (0.42) |
| Drug Use Disorder | ||||||
| EV | NA | NA | NA | NA | NA | NA |
| FAERS | NA | NA | 1.25 (0.07) | NA | NA | 2.81 (<0.01) * |
| Intentional Product Misuse | ||||||
| EV | 2.23 (<0.01) | 1.35 (<0.01) * | 2.20 (<0.01) | 0.33 (0.70) | 0.34 (0.68) | 1.24 (<0.01) |
| FAERS | 1.25 (<0.01) | 1.18 (0.03) * | 1.09 (<0.01) | 1.07 (<0.01) | NA | 0.72 (0.42) |
| Substance Abuse | ||||||
| EV | 1.11 (<0.01) * | NA | 0.09 (0.70) | 8.84 (<0.01) | NA | 0.14 (0.70) |
| FAERS | 0.91 (0.23) | 0.70 (0.25) | 0.03 (0.43) | 17.61 (<0.01) | NA | 0.13 (0.43) |
| Substance Use | ||||||
| EV | NA | NA | NA | NA | NA | NA |
| FAERS | NA | NA | 0.53 (0.31) | NA | NA | 3.51 (<0.01) |
| Dependence-Related Terms | ||||||
| Dependence | ||||||
| EV | 0.92 (0.27) | NA | 1.13 (<0.01) | 0.17 (0.70) | NA | 5.38 (<0.01) |
| FAERS | 0.98 (0.14) | NA | 0.92 (0.23) | 0.64 (0.39) | NA | 1.88 (<0.01) |
| Drug Dependence | ||||||
| EV | 0.78 (0.69) | 1.24 (<0.01) * | 0.21 (0.70) | 2.75 (<0.01) | 0.70 (0.52) | 0.99 (0.22) |
| FAERS | 0.24 (0.43) | 0.30 (0.40) | 0.09 (0.43) | 11.53 (<0.01) | 1.56 (<0.01) * | 0.31 (0.43) |
| Substance Dependence | ||||||
| EV | NA | NA | 0.13 (0.70) | 13.19 (<0.01) | NA | NA |
| FAERS | NA | NA | 0.04 (0.42) | 53.88 (<0.01) | NA | NA |
| Withdrawal-Related Terms | ||||||
| Drug Withdrawal Syndrome | ||||||
| EV | 0.22 (0.70) | 0.81 (0.39) | 0.66 (0.70) | 1.92 (<0.01) | 0.57 (0.55) | 0.65 (0.70) |
| FAERS | 0.19 (0.42) | NA | 0.68 (0.43) | 2.82 (<0.01) | NA | 0.32 (0.43) |
| Overdose and Off-Label-Use Terms | ||||||
| Intentional Overdose | ||||||
| EV | 1.68 (<0.01) * | NA | 0.47 (0.71) | 0.53 (0.71) | NA | 4.00 (<0.01) |
| FAERS | 2.03 (<0.01) | 2.39 (<0.01) | 0.14 (0.43) | 1.48 (<0.01) | NA | 2.49 (<0.01) |
| Off-Label Use | ||||||
| EV | 0.88 (0.24) | NA | 4.67 (<0.01) | 0.28 (0.70) | NA | 0.37 (0.71) |
| FAERS | 0.59 (0.40) | 1.70 (<0.01) | 2.74 (<0.01) | 0.44 (0.43) | NA | 0.57 (0.42) |
| Overdose | ||||||
| EV | 0.93 (0.32) | 1.78 (<0.01) * | 1.02 (0.02) | 0.77 (0.70) | NA | 1.55 (<0.01) |
| FAERS | 0.96 (0.23) | 1.53 (<0.01) | 0.51 (0.43) | 2.24 (<0.01) | NA | 0.72 (0.42) |
* PRR is significant, but all four signal measures are not significant. Boldface denotes significant signals based on FDR < 0.05 for all four pharmacovigilance measures; minimum number of events to compute signal statistics is five for all measures. EV, EudraVigilance; FAERS, Food and Drug Administration Adverse Event Reporting System; FDR, false discovery rate; NA, not available (less than five events for this pair); PRR = proportional reporting ratio. Note: The full version of this table, including the reporting odds ratio, information component, and empirical Bayesian geometric mean, can be found in Supplementary Table S2.