Table 1.
Analysis of opioid-related adverse drug reaction reports recorded in the European Medicines Agency (EMA) EudraVigilance (EV) dataset and the Food and Drug Administration (FDA) Adverse Event Reporting System.
| ADR Report Characteristics | Codeine | Dihydrocodeine | Fentanyl | Oxycodone | Pentazocine | Tramadol | ||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|
| EMA | FAERS | EMA | FAERS | EMA | FAERS | EMA | FAERS | EMA | FAERS | EMA | FAERS | |
| Individual cases | 814 | 6764 | 53 | 575 | 5443 | 54,640 | 7441 | 45,672 | 136 | 112 | 2619 | 22,530 |
| Mean age in years (SD) | 38.3 (13.6) | 50.7 (19.6) | 37.9 (12.7) | 43.4 (22.2) | 43.3 (16.0) | 53.2 (19.2) | 38.0 (13.6) | 45.6 (18.2) | 46.3 (16.5) | 51.4 (21.1) | 42.7 (15.7) | 52.8 (20.4) |
| M (%) | 73.8% (540) 26.2% (192) | 32.2% (1983) | 36.2% (17) | 48.2% (244) | 53.0% (2459) | 40.5% (19,354) | 61.4% (3929) | 54.2% (22,504) | 20.7% (28) | 51.9% (54) | 48.9% (1142) | 38.7% (7890) |
| F (%) | 67.8% (4167) | 63.8% (30) | 51.8% (262) | 47.0% (2178) | 59.5% (28,382) | 38.6% (2468) | 45.8% (19,036) | 79.3% (107) | 48.1% (50) | 51.1% (1195) | 61.3% (12,479) | |
| Most common | Drug abuse (1.9%) | Pain (7.2%) | Pain (20.0%) | Pain (12.3%) | Pain (25.0%) | Pain (31.0%) | Drug abuse (15.3%) | Pain (30.5%) | Pain (24.4%) | Pain (17.3%) | Pain (18.9%) | Pain (21.6%) |
| indications recorded for the index opioid when reported (%) | Pain (1.6%) | Rheumatoid arthritis (4.9%) | Procedural pain (10.0%) | Back Pain (5.9%) | Intentional product misuse (7.3%) | Back pain (9.1%) | Pain (13.8%) | Back Pain (5.8%) | Drug abuse (7.7%) | Analgesic therapy (14.3%) | Back pain (7.8%) | Back pain (6.8%) |
| Cough (1.4%) | Cough (2.6%) | Drug dependence (6.7%) | Rheumatoid arthritis (5.4%) | Back pain (4.7%) | Cancer pain (6.2%) | Back pain (4.7%) | Drug abuse (4.0%) | Migraine (3.8%) | Drug abuse (8.2%) | Headache (2.7%) | Depression (6.1%) | |
| ROA (%) | Oral (26.9%) | Oral (32.2%) | Oral (63.0%) | Oral (40.1%) | Transdermal (44.9%) | Transdermal (75.0%) | Oral (56.0%) | Oral (76.1%) | Intravenous (70.0%) | Intramuscular (32.7%) | Oral (86.5%) | Oral (63.9%) |
| Parenteral (9.0%) | Parenteral (2.3%) | Parenteral (0%) | Transplacental (16.5%) | Oral (22.6%) | Intravenous (6.0%) | Intravenous (3.2%) | Intravenous (1.3%) | Intramuscular (19.2%) | Intravenous (32.7%) | Intravenous (0.8%) | Intravenous (2.1%) | |
| Nasal/inhalation (1.8%) | Transplacental (1.3%) | Nasal/inhalation (0%) | Intrauterine (0.6%) | Intravenous (4.6%) | Oral (3.6%) | Nasal/inhalation (2.5%) | Nasal/inhalation (1.0%) | Oral (2.5%) | Oral (7.3%) | Parenteral (0.3%) | Transplacental (1.0%) | |
| Intravenous (0.6%) | Intravenous (0.6%) | Intravenous (0%) | Parenteral (3.7%) | Intrathecal (1.4%) | Parenteral (0.4%) | Transplacental (0.5%) | Parenteral (2.5%) | Parenteral (7.3%) | Oropharyngeal (0.5%) | |||
| Rectal (0.2%) | Nasal/inhalation (0.4%) | Rectal (0%) | Nasal/inhalation (3.1%) | Topical (1.1%) | Rectal (0%) | Parenteral (0.3%) | Subcutaneous (5.5%) | Intramuscular (0.3%) | ||||
| Fatal outcome (%) | 69.50% | 29.70% | 24.50% | 32.70% | 46.80% | 21.00% | 31.30% | 36.90% | 1.50% | 13.40% | 21.70% | 22.40% |
| Most important concomitant prescription psychotropic drugs recorded | ||||||||||||
| Antidepressants (%) | 20.90% | 23.40% | 9.40% | 47.10% | 14.30% | 11.10% | 13.70% | 13.20% | 1.50% | 9.80% | 17.60% | 26.60% |
| Antipsychotics (%) | 5.20% | 6.60% | 9.40% | 21.40% | 2.70% | 2.90% | 3.30% | 4.10% | 1.50% | 7.10% | 3.20% | 6.60% |
| Benzodiazepines (%) | 31.20% | 19.60% | 24.50% | 35.10% | 18.20% | 13.60% | 23.00% | 18.80% | 5.10% | 27.70% | 15.40% | 18.20% |
| Gabapentinoids (%) | 2.20% | 9.40% | 1.90% | 20.30% | 5.00% | 5.60% | 3.20% | 6.20% | 0.70% | 1.80% | 4.30% | 12.30% |
| Mood Stabilizers (%) | 2.00% | 5.20% | 0% | 12.30% | 2.20% | 2.20% | 1.60% | 2.50% | 0.70% | 1.80% | 2.40% | 5.40% |
| OTCs (%): | ||||||||||||
| Anticholinergics (%) | 1.40% | 2.50% | 3.40% | 1.60% | 0.70% | 2.20% | 0.40% | 1.20% | 0% | 9.80% | 0.90% | 2.70% |
| Antihistamines (%) | 19.70% | 12.10% | 9.40% | 0% | 6.00% | 3.70% | 8.70% | 5.30% | 5.10% | 33.90% | 5.60% | 9.00% |
| Dextromethorphan (%) | 12.50% | 3.00% | 0% | 0.30% | 0.70% | 0.20% | 1.50% | 0.60% | 0% | 0% | 1.50% | 0.40% |
| Loperamide (%) | 0% | 0.80% | 0% | 0.30% | 0.10% | 0.10% | 0.10% | 0.20% | 0% | 0.90% | 0.20% | 0.50% |
| Paracetamol/Acetaminophen (%) | 14.30% | 17.50% | 3.80% | 25.10% | 3.00% | 2.70% | 5.50% | 5.70% | 2.20% | 8.90% | 5.80% | 14.00% |
| Pseudoephedrine and Pseudoephedrine-Containing Products (%) | 0.40% | 0.90% | 0% | 0% | 0.10% | 0% | 0.30% | 0.20% | 0% | 0% | 0.10% | 0.20% |
| Other Opioids (%) | 67.60% | 39.70% | 20.80% | 37.40% | 21.50% | 43.00% | 31.00% | 22.80% | 5.90% | 14.30% | 16.60% | 16.70% |
| Z-Drugs (%) | 4.20% | 4.10% | 3.80% | 2.40% | 2.70% | 2.10% | 2.50% | 2.90% | 0.70% | 5.40% | 2.60% | 5.60% |
| Most important concomitant recreational drugs recorded | ||||||||||||
| Alcohol (%) | 8.10% | 3.60% | 11.30% | 8.70% | 3.10% | 0.90% | 8.70% | 4.20% | 2.20% | 0.90% | 3.60% | 2.60% |
| Amphetamines and Methamphetamines (%) | 4.50% | 2.80% | 3.40% | 1.90% | 1.70% | 0.40% | 3.80% | 1.70% | 0% | 0% | 1.50% | 0.90% |
| Cannabis and Cannabinoids (%) | 2.70% | 1.00% | 0% | 0.50% | 1.10% | 0.30% | 4.70% | 1.80% | 0.70% | 0.90% | 1.50% | 0.50% |
| Cocaine (%) | 19.30% | 4.40% | 1.90% | 0.70% | 3.50% | 0.80% | 8.80% | 3.20% | 0% | 0% | 2.60% | 0.90% |
| Hallucinogens (%) | 2.00% | 0.60% | 0% | 0.70% | 0.10% | 0.10% | 0.90% | 0.40% | 0% | 0% | 0.70% | 0.20% |
| Heroin (%) | 0% | 9.10% | 0% | 4.00% | 0% | 1.00% | 0% | 1.80% | 0% | 0.90% | 0% | 0.40% |
| Ketamine (%) | 0.40% | 0.10% | 0% | 0.30% | 0.20% | 0.30% | 0.20% | 0.10% | 0% | 0% | 0% | 0.20% |
| NPS (%) | 0% | 0.10% | 0% | 0% | 0% | 0.00% | 0% | 0.00% | 0% | 0% | 0.20% | 0.10% |
Abbreviations: ADR, adverse drug reaction; AE, adverse event; EMA, European Medicines Agency; FAERS, Food and Drug Administration Adverse Event Reporting System; NPS, new psychoactive substances; OTC, over-the-counter drugs; ROA, route of administration; SD, standard deviation; UK, United Kingdom; US, United States. Note: Full descriptive information on ADR reports can be found in Supplementary Table S1.