Table 3.
Most frequently used drugs associated with pulmonary toxicity in the group using drugs metabolized by an affected CYP iso-enzyme with at least one polymorphism in CYP2D6, CYP2C9, and/or CYP2C19 (n = 369), stratified by gender [29, 30]
| Drug | Total, n = 369 |
Male, n = 265 (71.8) |
Female, n = 104 (28.2) |
p value | CYP 2D6/2C9/2C19 SUB and/or INH |
Pneumo- toxa [29] | SmPCb [30] +/− |
|---|---|---|---|---|---|---|---|
| Statins | 233 (63.1) | 184 (69.4) | 49 (47.1) | < 0.0001 | 2D6/2C9/2C19 | 5 | + |
| Simvastatin | 143 (38.8) | 113 (42.6) | 30 (28.8) | 0.014 | 2D6/2C9/2C19 | 2 | + |
| Atorvastatin | 54 (14.6) | 42 (15.8) | 12 (11.5) | 0.29 | 2D6/2C9/2C19 | 1 | + |
| Rosuvastatin | 36 (9.8) | 29 (10.9) | 7 (6.7) | 0.22 | 2C9 | 1 | + |
| Metoprolol | 109 (29.5) | 84 (31.7) | 25 (24.0) | 0.15 | 2D6 | 1 | − |
| Carbasalate calcium | 95 (25.7) | 75 (28.3) | 20 (19.2) | 0.07 | 2C9 | 5 | − |
| Acenocoumarol | 80 (21.7) | 62 (23.4) | 18 (17.3) | 0.20 | 2C9/2C19 | 5 | − |
| Omeprazole | 62 (16.8) | 40 (15.1) | 22 (21.2) | 0.16 | 2D6/2C9/2C19 | 1 | − |
| Amlodopine | 49 (13.3) | 35 (13.2) | 14 (13.5) | 0.95 | 2D6/2C9/2C19 | 2 | − |
| Tamsulosinc | 43 (11.7) | 43 (16.2) | 0 | NA | 2D6 | 1 | − |
| Nitrofurantoin | 66 (17.9) | 12 (4.5) | 54 (51.9) | < 0.00001 | NA | 5 | + |
Data are expressed as absolute numbers, with percentage in parentheses
CYP cytochrome P450, INH inhibitor, NA not applicable, Pneumotox.com (Drug-Induced Respiratory Disease Website) [29], SmPC Summary of Product Characteristics, SUB substrate
Bold values indicate statistical significance
aNumber indicates the frequency of drug-induced pulmonary toxicity, from: 1 rare (< 10 cases); 2 (10–50 cases); to 5 very common (> 200 cases)
bDrug-induced interstitial lung disease is mentioned in the SmPC
cTamsulosin is not prescribed to women