Table 2.
Drugs most frequently involved in actual drug-drug interactions (DDI)*
| Drug (number of DDIs*) | Drug pairs (number of DDI combinations) | Most relevant reported ADRs | Mechanism of interaction |
|---|---|---|---|
| Cyclosporine (15) |
cyclosporine - fluvastatin (6) |
rhabdomyolysis, myopathy |
inhibition of fluvastatin metabolism |
| cyclosporine- amlodipine
(3) |
cyclosporine toxicity |
inhibition of cyclosporine metabolism by amlodipine |
|
| cyclosporine – methylprednisolone
(2) |
cyclosporine toxicity |
decreased metabolism of cyclosporine |
|
| cyclosporine – prednisone (1) |
cyclosporine toxicity |
decreased metabolism of cyclosporine |
|
| cyclosporine- carvedilol
(1) |
cyclosporine toxicity |
inhibition of cyclosporine metabolism |
|
| cyclosporine- simvastatin (1) |
rhabdomyolysis |
inhibition of cytochrome P450-mediated metabolism of simvastatin and transporters |
|
| cyclosporine- ciprofloxacin (1) |
cyclosporine toxicity |
decreased cyclosporine metabolism; pharmacodynamic antagonism |
|
| Warfarin (9) |
warfarin-enoxaparin (2) |
bleeding |
additive anticoagulation |
| warfarin- acetaminophen (1) |
bleeding |
inhibition of warfarin metabolism or interference with clotting factor formation |
|
| warfarin -allopurinol (1) |
bleeding |
inhibition of warfarin metabolism |
|
| warfarin-amoxicillin (1) |
increased INR |
unknown |
|
| warfarin-atenolol (1) |
increased INR |
unknown |
|
| warfarin-fluvastatin (1) |
INR increased and bleeding |
inhibition of warfarin metabolism |
|
| warfarin- methylprednisolone (1) |
anemia |
unknown |
|
| warfarin-simvastatin (1) |
myalgia |
competition for cytochrome P450 3A4-mediated metabolism |
|
| Fluvastatin (8) |
fluvastatin -cyclosporine (6) |
see above |
|
| fluvastatin -diclophenac (1) |
gastrointestinal toxicity |
inhibition of diclophenac metabolism |
|
| fluvastatin -warfarin (1) |
see above |
||
| Paroxetine (8) |
paroxetine - risperidone (4) |
extrapyramidal ADRs, weight increase |
concomitant use of paroxetine (potent CYP2D6 inhibitor) and risperidone (CYP2D6 substrate) has resulted in increased risperidone plasma concentrations and an increased risk of risperidone adverse effects. |
| paroxetine - clozapine (1) |
sedation, hypotension |
decreased clozapine metabolism |
|
| paroxetine- fluphenazine (1) |
extrapyramidal ADRs |
inhibition of cytochrome P450-mediated fluphenazine metabolism by paroxetine |
|
| paroxetine-meloxicam (1) |
hematochezia |
At therapeutic doses SSRIs can block this reuptake of serotonin by platelets, leading to serotonin depletion, impairment of hemostatic function and increase the risk of bleeding |
|
| paroxetine - tramadol (1) |
palpitations, headache, dizziness |
increased concentration of serotonin in the nervous system and periphery; inhibition of the CYP2D6-mediated formation of tramadol active metabolites (-)-M1 and (+)-M1 by paroxetine |
|
| Risperidone (7) |
risperidone- paroxetine (4) |
see above |
see above |
| risperidone- clozapine (1) |
incontinence of urine |
compete for metabolism by the cytochrome P450 isoenzyme CYP2D6 resulting in a reduction in the metabolism of the clozapine |
|
| risperidone - haloperidol (1) |
QT prolongation |
additive effects on QT prolongation |
|
| risperidone - quetiapine (1) |
neuroleptic malignant syndrome |
additive effects |
|
| sertraline (5) |
sertraline - alprazolam (1) |
neonatal respiratory distress syndrome |
inhibition of cytochrome P450 3A-mediated alprazolam metabolism |
| sertraline - amitriptyline (1) |
sedation |
inhibition of amitriptyline metabolism |
|
| sertraline -lithium (1) |
nausea and vomiting |
additive effect |
|
| sertraline - olanzapine (1) |
weight increased |
inhibition of olanzapine mechanism |
|
| sertraline - zolpidem (1) |
hallucinations |
unknown |
|
| Valproic acid (5) |
valproic acid- lamotrigine (4) |
life-threatening rashes |
decreased lamotrigine metabolism |
| valproic acid - amitriptyline (1) |
disorientation, amnesia, hallucinations |
decreased amitriptyline plasma clearance |
|
| Acetylsalicylic acid (5) |
acetylsalicylic acid -clopidogrel (3) |
bleeding |
inhibition of platelet aggregation |
| acetylsalicylic acid -enoxaparin (1) |
bleeding |
decreased platelet function; decreased coagulation |
|
| acetylsalicylic acid - ketoprofen (1) | gastrointestinal toxicity | additive gastrointestinal irritation |
*Abbreviations: INR – International Normalized Ratio; SSRI – Selective Serotonin Reuptake Inhibitors; ADR – adverse drug reaction.