Table 3.
Summary of drug-drug interactions provided in the literature. When available, recommendations for dose adaptation or contraindications by the competent authorities are provided [26–28].
| Molecule | Mechanism | Dabigatran | Rivaroxaban | Apixaban |
|---|---|---|---|---|
| Antiarrhythmics | ||||
| Dronedarone | P-gp and CYP 3A4 inhibitor | AUC: +114% (400 mg: single dose)∗ | Minor effect (use with caution if CrCl 15–50 mL/min)∗∗∗ | No data yet |
| AUC: +136% (400 mg: multiple doses) | ||||
| Quinidine | P-gp competition | AUC: +53% (1,000 mg: single dose)∗∗ | Minor effect (use with caution if CrCl 15–50 mL/min) | No data yet |
| Verapamil | P-gp competition and weak CYP 3A4 inhibitor | AUC: +18% (120 mg IR: single dose taken 2 h after DE intake)∗∗ | Minor effect (use with caution if CrCl 15–50 mL/min) | No data yet |
| AUC: +143% (120 mg IR: single dose, 1 h before DE intake)∗∗ | ||||
| Cmax: +12% (120 mg IR: single dose taken 2 h after DE intake)∗∗ | ||||
| Cmax: +179% (120 mg IR: single dose, 1 h before DE intake)∗∗ | ||||
| Amiodarone | P-gp competition | AUC: +58% (600 mg: single dose)∗∗ | Minor effect (use with caution if CrCl 15–50 mL/min) | No clinically relevant effect |
| Diltiazem | P-gp and CYP 3A4 inhibitor | No effect | Minor effect (use with caution if CrCl 15–50 mL/min) | AUC: +40% |
|
| ||||
| Antianginal/antihypertensive drugs | ||||
| Ranolazine | P-gp and CYP 3A4 inhibitor | No data yet | Minor effect (use with caution if CrCl 15–50 mL/min) | No data yet |
| Felodipine | P-gp and CYP 3A4 inhibitor | No data yet | Minor effect (use with caution if CrCl 15–50 mL/min) | No data yet |
|
| ||||
| Anti-inflammatory | ||||
| Naproxen | P-gp competition | No data yet | AUC: +10% (500 mg) | AUC: +50% |
|
| ||||
| Antihypercholesterolemiant | ||||
| Atorvastatin | P-gp and CYP 3A4 substrate | AUC: +18% | No effect | No PK data yet |
|
| ||||
| Antimycotic | ||||
| Ketoconazole | P-gp and CYP 3A4 inhibitor | AUC: +138% (400 mg: single dose)∗ | Cmax: +72% (400 mg: single dose) | Cmax: +62% (400 mg od) |
| AUC: +153% (400 mg: multiple doses) | AUC: +158% (400 mg: single dose) | AUC: +100% (400 mg od) | ||
| Itraconazole | P-gp and CYP 3A4 inhibitor | No data yet∗ | No data yet, but similar results than ketoconazole are expected | No data yet, but similar results than ketoconazole are expected |
| Voriconazole | P-gp and CYP 3A4 inhibitor | No data yet | ||
| Posaconazole | P-gp and CYP 3A4 inhibitor | No data yet∗∗∗ | No data yet | |
| Fluconazole | CYP 3A4 inhibitor | No data yet Supposed no effect |
Cmax: +28% | No data yet |
| AUC: +42% | ||||
|
| ||||
| Antibacterial | ||||
| Clarithromycin | P-gp and CYP 3A4 inhibitor | Cmax: +49% | No data yet | |
| AUC: +60% | AUC: +54% (500 mg bid) | |||
| Azithromycin | P-gp and CYP 3A4 inhibitor | No data yet | Minor effect (use with caution if CrCl 15–50 mL/min) | No data yet |
| Erythromycin | P-gp and CYP 3A4 inhibitor | No data yet | AUC: +34% (500 mg tid) | No data yet |
|
| ||||
| Protease inhibitors | ||||
| Ritonavir | P-gp and CYP 3A4 inhibitor | No data yet∗∗∗ | Cmax: +55% (600 mg bid) | No PK data but strong increase |
|
| ||||
| AUC: +153% (600 mg bid) | ||||
|
| ||||
| Immunosuppressor | ||||
| Cyclosporine | P-gp competition | No data yet∗ | AUC: +50% | No data yet |
| Tacrolimus | P-gp competition | No data yet∗ | AUC: +50% | No data yet |
*The FDA recommends reducing the dabigatran etexilate at 75 mg bid for stroke prevention in NVAF. No recommendations are given by the FDA for cyclosporine, tacrolimus, and itraconazole.
∗∗The EMA contraindicates concomitant treatment with these drugs. EMA recommends dose reduction from 220 mg od to 150 mg od in major orthopedic surgery and from 150 mg bid to 110 mg bid in stroke prevention in patients with NVAF. No dose recommendation is provided by the FDA.
∗∗∗Not recommended by the EMA.