Supplementary Materials
Table S1. The significant drug pairs in potential DDIs examined by the two databases.
Micromedex Drugs.com List of drugs paired PK-PD Mechanism details 1. Amiodarone— PD Additive QT-interval prolongation Dronedarone 2. Amiodarone— PK CYP3A inhibition by Ketoconazole Ketoconazole 3. Ciprofloxacin— PD Additive QT-interval prolongation Dronedarone 4. Cyclosporine— PK CYP3A inhibition by Cyclosporine Dronedarone 5. Dronedarone— PK CYP3A inhibition by Erythromycin Erythromycin 6. Dronedarone— PD Additive QT-interval prolongation Flecainide 7. Dronedarone— PK CYP3A4 inhibition by Itraconazole Itraconazole 8. Dronedarone— PK Contraindication Major CYP3A inhibition by Ketoconazole Ketoconazole 9. Dronedarone— PD Additive QT-interval prolongation Procainamide PD 10. Dronedarone—Sotalol Additive QT-interval prolongation
11. Felodipine— PK CYP3A inhibition by Itraconazole Itraconazole 12. Felodipine— PK CYP3A inhibition by Ketoconazole Ketoconazole 13. Itraconazole— PK CYP3A inhibition by Itraconazole Nisoldipine 14. Ketoconazole— PK CYP3A inhibition by Ketoconazole Nisoldipine 15. Praziquantel— PK CYP induction by Rifampin Rifampin PD 1. Amikacin—Furosemide Additive or synergistic toxicity
2. Aminophylline— Decreased clearance of PK Ciprofloxacin Theophylline by Ciprofloxacin 3. Aminophylline— PK Decreased hepatic metabolism Mexiletine 4. Amiodarone— PD Additive effects on QT interval Ciprofloxacin 5. Amiodarone—Digoxin PK P-glycoprotein inhibition by Amiodarone 6. Amiodarone— PD, PK Major Major Additive effects on QT Erythromycin prolongation, CYP3A inhibition by
Erythromycin
7. Amiodarone— PD, PK Flecainide Antiarrhythmic inhibition by Amiodarone, CYP2D inhibition by Amiodarone
8. Amiodarone— PK CYP3A inhibition by Itraconazole Itraconazole 9. Amiodarone— PD Antiarrhythmic inhibition by Procainamide Amiodarone
10. Amiodarone— PK CYP induction by Rifampin Rifampin PD Additive effects on refractory 11. Amiodarone—Sotalol potential 12. Amiodarone— PK CYP3A inhibition by Verapamil Verapamil 13. Amiodarone— PK CYP3A inhibition by Diltiazem Diltiazem PK 14. Amlodipine—Rifampin CYP induction by Rifampin
15. Atenolol—Verapamil Additive cardiovascular effects, PD, PK decreased metabolism of some beta-
blockers by Verapamil
16. Atenolol—Diltiazem Additive cardiovascular effects, PD, PK decreased metabolism of some beta-
blockers by Diltiazem
17. Benazepril— Increased potassium retention Spironolactone PD secondary to lowered aldosterone
levels
18. Benazepril— PD Additive effects of hyperkalemia Trimethoprim 19. Carvedilol—Verapamil Additive cardiovascular effects, PD, PK decreased metabolism of some beta-
blockers by Verapamil
20. Carvedilol—Diltiazem Additive cardiovascular effects, PD, PK decreased metabolism of some beta-
blockers by Diltiazem
21. Ciprofloxacin— PD An additive effect of risk for tendon Prednisolone rupture 22. Ciprofloxacin— PD Additive effects on the QT interval Procainamide 23. Ciprofloxacin—Sotalol PD Additive effects on the QT interval 24. Ciprofloxacin— Decreased clearance of Theophylline PK Theophylline, CYP1A inhibition by
Ciprofloxacin
25. Cyclosporine— PK CYP3A inhibition by Itraconazole Itraconazole 26. Cyclosporine— PK Cyclosporine metabolism induction Rifabutin by Rifabutin
Increased Cyclosporine clearance 27. Cyclosporine— PK, PD and decreased systemic Rifampin bioavailability by Rifampin PK P-glycoprotein inhibition by 28. Digoxin—Dronedarone Dronedarone 29. Digoxin—Itraconazole PK Digoxin metabolism and clearance inhibition by Itraconazole 30. Enalapril— PD Increased potassium retention Spironolactone secondary to lowered aldosterone levels
31. Enalapril— PD Additive effects of hyperkalemia Trimethoprim 32. Erythromycin— PK CYP3A inhibition by Erythromycin Ketoconazole and Ketoconazole
33. Erythromycin— PK CYP3A inhibition by Erythromycin Procainamide PD 34. Erythromycin—Sotalol Additive effects on QT prolongation
35. Erythromycin— PK CYP3A inhibition by Erythromycin Verapamil 36. Erythromycin— PK CYP3A-mediated inhibition by Diltiazem Diltiazem 37. Esmolol—Verapamil Additive cardiovascular effects, PD, PK decreased metabolism of some beta-
blockers by Verapamil
Additive cardiovascular effects, 38. Esmolol—Diltiazem PD, PK decreased metabolism of some beta-
blockers by Diltiazem 39. Flecainide— PD Additive effects on QT prolongation Procainamide PD Additive effects on refractory 40. Flecainide—Sotalol potential 41. Fluticasone— PK CYP3A-mediated inhibition by Itraconazole Itraconazole
42. Fluticasone— PK CYP3A-mediated inhibition by Ketoconazole Ketoconazole
43. Furosemide— PD Additive or synergistic toxicity Gentamicin 44. Furosemide— PD Additive or synergistic toxicity Kanamycin 45. Furosemide— PD Additive or synergistic toxicity Streptomycin 46. Furosemide— PD Additive or synergistic toxicity Tobramycin 47. Itraconazole— PK CYP3A inhibition by Itraconazole Nifedipine 48. Itraconazole—Rifabutin PK CYP3A induction by Rifabutin,
CYP3A inhibition by Itraconazole
PK CYP3A-mediated induction by 49. Itraconazole—Rifampin Rifampin 50. Itraconazole— PK CYP3A inhibition by Itraconazole Sildenafil 51. Ketoconazole— PD Additive QT-interval prolongation Procainamide 52. Ketoconazole— Rifabutin CYP3A-mediated inhibition by PK Ketoconazole, CYP3A-mediated
induction by Rifabutin
53. Ketoconazole— PK CYP3A-mediated induction by Rifampin Rifampin 54. Ketoconazole— PK CYP3A induction by Rifapentine Rifapentine PD 55. Ketoconazole—Sotalol Additive effects on the QT interval
56. Metoprolol— Verapamil Additive cardiovascular effects, PD, PK decreased metabolism of some beta-
blockers by Verapamil
57. Metoprolol—Diltiazem Additive cardiovascular effects, PD, PK decreased metabolism of some beta-
blockers by Diltiazem
58. Mexiletine— Theophylline PK Decreased hepatic metabolism, CYP1A inhibition by Mexiletine
59. Nifedipine— PK CYP3A induction by Phenobarbital Phenobarbital PK 60. Nifedipine—Phenytoin CYP3A induction by Phenytoin
PK 61. Nifedipine—Rifabutin CYP3A induction by Rifabutin
PK 62. Nifedipine—Rifampin CYP3A induction by Rifampin
63. Nifedipine— PK CYP3A induction by Rifapentine Rifapentine PD Additive effects on refractory 64. Procainamide—Sotalol potential 65. Ramipril— Increased potassium retention Spironolactone PD secondary to lowered aldosterone
levels
66. Ramipril— PD Additive effects of hyperkalemia Trimethoprim 67. Salmeterol— PK CYP3A-mediated inhibition by Itraconazole Itraconazole
68. Salmeterol— PK CYP3A-mediated inhibition by Ketoconazole Ketoconazole
Additive cardiovascular effects, 69. Sotalol—Verapamil PD, PK decreased metabolism of some beta-
blockers by Verapamil Additive cardiovascular effects, 70. Sotalol—Diltiazem PD, PK decreased metabolism of some beta-
blockers by Diltiazem 71. Spironolactone— PD Additive effects of hyperkalemia Trimethoprim