Table 4.
Frequency of clinically relevant DDIs, their pharmacological and clinical classification and potential consequence
| Classification pharmacological | Classification clinical/documentation | Drug combination (frequency) | Potential clinical consequence |
|---|---|---|---|
| 1. Pharmacokinetic interactions (n = 169) | |||
| 1.1 Drug absorption interactions (n = 83) | C3 | Calcium + alendronic acid (13) | Reduction of efficacy of alendronic acid |
| C3 | Calcium + levothyroxine (22) | Reduction of efficacy of levothyroxine | |
| C3 | Calcium + iron (15) | Reduction of efficacy of iron | |
| C0 | Calcium + risedronic acid (2) | Reduction of efficacy of risedronic acid | |
| D3 | Colestyramine + furosemide (1) | Reduction of efficacy of furosemide | |
| C4 | Iron + levothyroxine (8) | Reduction of efficacy of levothyroxine | |
| C3 | Iron + levodopa (2) | Reduction of efficacy of levodopa | |
| C0 | Iron + alendronic acid (2) | Reduction of efficacy of alendronic acid | |
| C0 | Iron + risedronic acid (1) | Reduction of efficacy of risedronic acid | |
| C3 | Iron + aluminium (1) | Reduction of efficacy of iron | |
| C3 | Iron + sodium hydrogen carbonate (13) | Reduction of efficacy of iron | |
| C3 | Magnesium + mycophenolic acid (1) | Reduction of efficacy of mycophenolic acid | |
| C1 | Magnesium + calcium polystyrene sulphonate (1) | Increased risk of systemic metabolic alkalosis | |
| C3 | Omeprazole + levothyroxine (1) | Reduction of efficacy of levothyroxine | |
| 1.2.1 Drug metabolism interactions, enzyme induction (n = 15) | C2 | Azathioprine + warfarin (1) | Reduction in clinical efficacy of warfarin |
| C3 | Carbamazepine + acetaminophen (1) | Increased risk of liver damage | |
| C1 | Carbamazepine + atorvastatin (1) | Reduction in clinical efficacy of atorvastatin | |
| C2 | Carbamazepine + cholecalciferol (2) | Reduction in clinical efficacy of cholecalciferol | |
| C4 | Carbamazepine + citalopram (2) | Reduction in clinical efficacy of citalopram | |
| D0 | Carbamazepine + diazepam (1) | Reduction in clinical efficacy of diazepam | |
| D3 | Carbamazepine + felodipine (1) | Reduction in clinical efficacy of felodipine | |
| C4 | Carbamazepine + olanzapine (1) | Reduction in clinical efficacy of olanzapine | |
| D0 | Carbamazepine + ticagrelor (1) | Reduction in clinical efficacy of ticagrelor | |
| C3 | Phenytoin + acetaminophen (1) | Reduction in clinical efficacy of acetaminophen, increased risk of liver damage | |
| C3 | Phenytoin + mirtazapine (1) | Reduction in clinical efficacy of mirtazapine | |
| C1 | Phenytoin + simvastatin (1) | Reduction in clinical efficacy of simvastatin | |
| C3 | Prednisolone + tacrolimus (1) | Reduction in clinical efficacy of tacrolimus | |
| 1.2.2 Drug metabolism interactions, enzyme inhibition (n = 66) | C3 | Amiodarone + simvastatin (1) | Increased efficacy of simvastatin, risk of myopathy |
| C4 | Amiodarone + metoprolol (2) | Increased risk of hypotension, bradycardia or cardiac arrest | |
| C1 | Atorvastatin + diltiazem (1) | Increased efficacy of atorvastatin, risk of myopathy | |
| D2 | Budesonide + fluconazole (1) | Increased plasma levels of budesonide | |
| C4 | Ciclosporin + felodipine (1) | Increased plasma levels of felodipine | |
| C3 | Ciclosporin + cinacalcet (1) | Increased efficacy of cinacalcet | |
| C0 | Cinacalcet + metoprolol (1) | Increased efficacy of metoprolol | |
| C0 | Clopidogrel + imatinib (1) | Increased efficacy of imatinib | |
| C3 | Darunavir + atorvastatin (1) | Increased efficacy of atorvastatin, risk of myopathy | |
| C0 | Darunavir + budesonide (1) | Increased efficacy of budesonide | |
| D1 | Econazole + warfarin (1) | Increased efficacy of warfarin | |
| C3 | Esomeprazole + clopidogrel (3) | Reduction in clinical efficacy of clopidogrel | |
| C0 | Esomeprazole + escitalopram (1) | Increased plasma levels of escitalopram, risk of QT prolongation | |
| C0 | Esomeprazole + citalopram (2) | Increased plasma levels of citalopram, risk of QT prolongation | |
| C0 | Fluconazole + clopidogrel (1) | Reduction in clinical efficacy of clopidogrel | |
| D2 | Fluconazole + citalopram (1) | Increased plasma levels of citalopram, risk of QT prolongation | |
| C3 | Hydroxychloroquine + metoprolol (1) | Increased efficacy of metoprolol | |
| C0 | Imatinib + atorvastatin (1) | Increased efficacy of atorvastatin, risk of myopathy | |
| C3 | Mirabegron + metoprolol (2) | Increased efficacy of metoprolol, risk of hypotension and bradycardia | |
| C3 | Omeprazole + citalopram (25) | Increased plasma levels of citalopram, risk of QT- prolongation | |
| C3 | Omeprazole + clopidogrel (7) | Reduction in clinical efficacy of clopidogrel | |
| C3 | Omeprazole + escitalopram (4) | Increased plasma levels of escitalopram, risk of QT-prolongation | |
| C2 | Omeprazole + tacrolimus (1) | Increased efficacy of tacrolimus | |
| C0 | Paroxetine + timolol (1) | Increased efficacy of timolol | |
| C3 | Phenytoin + losartan (1) | Reduction in clinical efficacy of losartan | |
| C4 | Ritonavir + atorvastatin (1) | Increased efficacy of atorvastatin, risk of myopathy | |
| C2 | Ritonavir + budesonide (1) | Increased efficacy of budesonide | |
| D4 | Warfarin + sulfamethoxazolea (1) | Increased risk of bleeding | |
| 1.3 Drug excretion interactions (n = 5) | C3 | Spironolactone + digoxin (4) | Increased plasma levels of digoxin, risk of digoxin toxicity |
| C1 | Furosemide + lithium (1) | Decreased urinary excretion of lithium, risk of lithium toxicity | |
| 2. Pharmacodynamic interactions (n = 187) | |||
| 2.1 Additive or synergistic interactions (n = 185) | C0 | Acetylsalicylic acid + venlafaxine (2) | Increased risk of bleeding |
| C4 | Acetylsalicylic acid + sertraline (9) | Increased risk of bleeding | |
| C4 | Acetylsalicylic acid + escitalopram (2) | Increased risk of bleeding | |
| C4 | Acetylsalicylic acid + citalopram (32) | Increased risk of bleeding | |
| C3 | Acetylsalicylic acid + ibuprofen (1) | Increased risk of bleeding, reduced cardioprotective efficacy | |
| C0 | Clopidogrel + citalopram (8) | Increased risk of bleeding | |
| C0 | Clopidogrel + escitalopram (2) | Increased risk of bleeding | |
| C0 | Clopidogrel + paroxetine (1) | Increased risk of bleeding | |
| C0 | Clopidogrel + sertraline (6) | Increased risk of bleeding | |
| C0 | Clopidogrel + tramadol (1) | Increased risk of bleeding | |
| C0 | Clopidogrel + venlafaxine (1) | Increased risk of bleeding | |
| C0 | Dalteparin + escitalopram (1) | Increased risk of bleeding | |
| C0 | Dalteparin + citalopram (1) | Increased risk of bleeding | |
| C0 | Dalteparin + sertraline (1) | Increased risk of bleeding | |
| C0 | Dipyridamole + citalopram (3) | Increased risk of bleeding | |
| C4 | Ibuprofen + citalopram (1) | Increased risk of bleeding | |
| C0 | Fondaparinux + citalopram (1) | Increased risk of bleeding | |
| D4 | Warfarin + diclofenac (1) | Increased risk of bleeding | |
| C3 | Warfarin + levothyroxine (10) | Increased risk of bleeding | |
| C4 | Warfarin + citalopram (11) | Increased risk of bleeding | |
| C1 | Warfarin + prednisolone (7) | Increased risk of bleeding | |
| C2 | Warfarin + sertraline (1) | Increased risk of bleeding | |
| C2 | Bendroflumethiazide + citalopram (3) | Increased risk of hyponatraemia | |
| C2 | Furosemide + escitalopram (1) | Increased risk of hyponatremia | |
| C2 | Furosemide + citalopram (35) | Increased risk of hyponatraemia | |
| C2 | Furosemide + sertraline (9) | Increased risk of hyponatraemia | |
| C3 | Hydrochlorothiazide + citalopram (2) | Increased risk of hyponatraemia | |
| C4 | Amiloride + enalapril (1) | Increased risk of hyperkalaemia | |
| C4 | Spironolactone + candesartan (1) | Increased risk of hyperkalaemia | |
| C4 | Spironolactone + enalapril (11) | Increased risk of hyperkalaemia | |
| C4 | Spironolactone + losartan (7) | Increased risk of hyperkalaemia | |
| C3 | Spironolactone + potassium (1) | Increased risk of hyperkalaemia | |
| C4 | Spironolactone + ramipril (2) | Increased risk of hyperkalaemia | |
| D0 | Ciprofloxacin + escitalopram (1) | Increased risk of QT- prolongation | |
| D0 | Ciprofloxacin + citalopram (1) | Increased risk of QT- prolongation | |
| D0 | Citalopram + donepezil (2) | Increased risk of QT- prolongation | |
| D1 | Citalopram + haloperidol (1) | Increased risk of QT- prolongation | |
| D0 | Diltiazem + timolol (1) | Increased risk of hypotension, bradycardia or cardiac arrest | |
| D0 | Verapamil + timolol (1) | Increased risk of hypotension, bradycardia or cardiac arrest | |
| C3 | Methotrexate + sulfamethoxazolea (1) | Additive, antagonistic effect on folic acid synthesis | |
| C3 | Methotrexate + trimethoprima (1) | Additive, antagonistic effect on folic acid synthesis | |
| 2.2 Antagonistic or opposing interactions (n = 2) | C4 | Furosemide + diclofenac (1) | Decreased effect of loop diuretics leading to decreased diuresis and worsening of heart failure |
| C0 | Diclofenac + carvedilol (1) | Decreased effect of beta-blocking agents | |
| 3. Classification uncertain (n = 45) | |||
| C4 | Ciclosporin + pravastatin (1) | Increased efficacy of pravastatin, risk of myopathy | |
| C4 | Warfarin + acetaminophen (26) | Increased risk of bleeding | |
| C3 | Morphine + gabapentin (1) | Increased risk of CNS-symptoms | |
| C0 | Ramipril + darbepoetin alfa (1) | Decreased responsiveness to darbepoetin alfa | |
| C4 | Warfarin + simvastatin (16) | Increased efficacy of warfarin, risk of bleeding | |
C = interaction which may require dose adjustment
D = interaction which should be avoided
0–4 = level of documentation according to Table 1
aCombined formulation: trimethoprim/sulfamethoxazole