Table 3.
Clopidogrel DDI signals* of potential clinical concern given statistically significantly increased rates of serious bleeding, by therapeutic class of precipitant drug.
| Precipitant used concomitantly with clopidogrel | Ratio of rate ratios for clopidogrel to pravastatin | 95% confidence interval | Putative mechanism(s) of interaction with clopidogrel** |
|---|---|---|---|
| Anti-infective | |||
| demeclocycline | 3.06 | 1.10–8.49 | unknown |
| Cardiovascular | |||
| bisoprolol | 1.75 | 1.09–2.81 | unknown |
| gemfibrozil | 1.64 | 1.12–2.42 | induction of CYP3A4 |
| Central nervous system | |||
| diazepam | 1.85 | 1.26–2.73 | unknown |
| eszopiclone | 1.99 | 1.12–3.55 | unknown |
| hydromorphone | 2.00 | 1.06–3.77 | unknown |
| pramipexole | 2.57 | 1.54–4.29 | unknown |
| primidone | 2.08 | 1.14–3.78 | induction of CYP2C19, 2C9, 3A4, 1A2, 2B6 |
| prochlorperazine | 2.27 | 1.23–4.18 | unknown |
| quetiapine | 1.47 | 1.06–2.05 | unknown |
| tramadol | 1.26 | 1.05–1.51 | unknown |
| Endocrine and metabolic | |||
| megestrol | 1.46 | 1.02–2.09 | unknown |
| pioglitazone | 1.47 | 1.05–2.05 | induction of CYP3A4 |
| Gastrointestinal | |||
| ursodiol | 2.82 | 1.24–6.43 | unknown |
| Nutritional | |||
| potassium chloride | 1.13 | 1.01–1.26 | unknown |
CYP = cytochrome P450; DDI = drug-drug interaction
*
operational definition of a signal: statistically significantly elevated ratio of rate ratios for serious bleeding, excluding instances in which the rate ratio for the precipitant drug was not statistically significantly elevated in users of clopidogrel but statistically significantly protective in users of pravastatin
**
per DrugBank version 5.1.1 (The Metabolomics Innovation Centre: Edmonton, Alberta, Canada) enzyme, carrier, and transporter pathways