Drug – Drug Interactions

Drug A Drug B Type Mechanism Clinical Consequences Management
Amiodarone Phenytoin Pharmacokinetic CYP2C9 inhibition ↑ Phenytoin toxicity Monitor phenytoin levels
Amiodarone Dabigatran Pharmacokinetic P-gp inhibition ↑ Dabigatran levels → bleeding risk Monitor for bleeding; consider dose adjustment
Amphotericin B Digoxin Pharmacodynamic Additive nephrotoxicity Kidney damage Monitor renal function and digoxin levels
Antacids Fluoroquinolones Pharmacokinetic Chelation ↓ absorption ↓ Antibiotic efficacy Separate doses by 2–4 hours
Antacids Isoniazid Pharmacokinetic ↓ absorption due to pH changes ↓ Isoniazid efficacy Separate administration times
Antacids Ketoconazole Pharmacokinetic ↑ gastric pH ↓ absorption ↓ Ketoconazole efficacy Separate administration times
Antipsychotics SSRIs Pharmacodynamic ↑ QT prolongation risk Torsades de pointes ECG monitoring; avoid if high risk
Apixaban Rifampin Pharmacokinetic CYP3A4 induction ↓ Apixaban levels → thrombotic risk Avoid combination or monitor closely
Aspirin Methotrexate Pharmacodynamic ↓ Methotrexate renal clearance ↑ Methotrexate toxicity Monitor renal function and methotrexate levels
Atazanavir Proton pump inhibitors Pharmacokinetic Requires acidic pH for absorption ↓ Atazanavir efficacy Avoid PPIs or use H2 blockers with caution
Atorvastatin Clarithromycin Pharmacokinetic CYP3A4 inhibition Rhabdomyolysis Avoid or reduce statin dose
Azathioprine Allopurinol Pharmacokinetic ↓ Azathioprine metabolism Severe bone marrow suppression Reduce azathioprine dose by 75%
Azithromycin Warfarin Pharmacokinetic Alters metabolism, possible CYP3A4 inhibition ↑ Bleeding risk Monitor INR
Azithromycin Digoxin Pharmacokinetic ↑ Digoxin levels via P-glycoprotein inhibition Digoxin toxicity Monitor digoxin levels
Azithromycin Digoxin Pharmacokinetic P-gp inhibition ↑ Digoxin toxicity Monitor digoxin levels
Baclofen CNS depressants Pharmacodynamic Additive CNS depression Excess sedation Avoid or monitor closely
Beta blockers Calcium channel blockers Pharmacodynamic Additive negative chronotropic and inotropic effects Bradycardia, hypotension Monitor cardiac function
Captopril Spironolactone Pharmacodynamic Additive hyperkalemia Arrhythmia, cardiac arrest Monitor potassium closely
Carbamazepine Oral contraceptives Pharmacokinetic CYP3A4 induction ↓ contraceptive efficacy Use backup contraception
Carbamazepine Phenytoin Pharmacokinetic CYP induction ↓ Phenytoin levels Monitor levels and adjust dose
Carbamazepine Warfarin Pharmacokinetic CYP induction ↓ Warfarin effect, thrombotic risk Monitor INR, adjust warfarin dose
Carbamazepine Doxycycline Pharmacokinetic CYP induction ↓ Doxycycline efficacy Monitor and adjust dose
Carbamazepine Erythromycin Pharmacokinetic CYP3A4 inhibition ↑ Carbamazepine levels Avoid or monitor closely
Chloramphenicol Phenytoin Pharmacokinetic Inhibits phenytoin metabolism ↑ Phenytoin toxicity Monitor levels
Clarithromycin Colchicine Pharmacokinetic CYP3A4 inhibition Colchicine toxicity Avoid or reduce colchicine dose
Clindamycin Neuromuscular blockers Pharmacodynamic Potentiation of neuromuscular blockade Respiratory depression Monitor neuromuscular function
Clopidogrel Omeprazole Pharmacokinetic CYP2C19 inhibition ↓ Clopidogrel activation, ↓ antiplatelet effect Avoid combination if possible
Clopidogrel Omeprazole Pharmacokinetic CYP2C19 inhibition ↓ Clopidogrel activation Use pantoprazole or other alternatives
Clozapine Ciprofloxacin Pharmacokinetic CYP1A2 inhibition ↑ Clozapine levels → seizures, sedation Monitor levels and symptoms
Clozapine Fluoxetine Pharmacokinetic CYP1A2 inhibition ↑ Clozapine toxicity (seizures, sedation) Monitor levels
Clozapine Valproic acid Pharmacokinetic ↓ Clozapine clearance ↑ Clozapine toxicity Monitor levels and side effects
Codeine Fluoxetine Pharmacokinetic CYP2D6 inhibition ↓ Morphine activation from codeine Reduced analgesic effect
Colchicine Clarithromycin Pharmacokinetic CYP3A4 inhibition and P-gp inhibition Colchicine toxicity (neuropathy, myopathy) Avoid or reduce colchicine dose
Cyclosporine Erythromycin Pharmacokinetic CYP3A4 inhibition ↑ Cyclosporine levels, nephrotoxicity Reduce dose and monitor drug levels
Cyclosporine St. John’s Wort Pharmacokinetic CYP3A4 induction ↓ Cyclosporine levels → rejection risk Avoid St. John’s Wort
Cyclosporine St. John’s Wort Pharmacokinetic CYP3A4 induction ↓ Cyclosporine levels → transplant rejection Avoid St. John’s Wort
Dabigatran Ketoconazole Pharmacokinetic P-gp inhibition ↑ Dabigatran levels Avoid combination
Dapsone Rifampin Pharmacokinetic CYP450 induction ↓ Dapsone levels Monitor and adjust dose
Diazepam Cimetidine Pharmacokinetic Inhibits hepatic metabolism ↑ Diazepam levels → sedation Consider dose reduction
Digoxin Verapamil Pharmacokinetic ↓ renal clearance of digoxin Bradycardia, digoxin toxicity Monitor levels; adjust digoxin dose
Digoxin Loop diuretics Pharmacodynamic Hypokalemia increases digoxin toxicity Arrhythmias Monitor potassium and digoxin levels
Digoxin Quinidine Pharmacokinetic ↓ Digoxin clearance Digoxin toxicity Monitor digoxin levels
Diltiazem Statins (e.g., Simvastatin) Pharmacokinetic CYP3A4 inhibition ↑ Statin toxicity → rhabdomyolysis Limit statin dose; consider alternatives
Disulfiram Metronidazole Pharmacodynamic Inhibits acetaldehyde metabolism Disulfiram-like reaction (flushing, nausea) Avoid combination
Disulfiram Metronidazole Pharmacodynamic Disulfiram-like reaction Flushing, nausea, vomiting Avoid combination
Disulfiram Alcohol Pharmacodynamic Aldehyde dehydrogenase inhibition Severe hangover-like symptoms Absolute contraindication
Drug A Drug B Type Mechanism Clinical Consequence Management
Efavirenz Rifampin Pharmacokinetic CYP3A4 induction ↓ Efavirenz levels → therapeutic failure Adjust efavirenz dose or avoid combo
Efavirenz Oral contraceptives Pharmacokinetic CYP3A4 induction ↓ Efficacy of OCPs Use backup contraception
Enalapril Potassium-sparing diuretics Pharmacodynamic Additive hyperkalemia risk Hyperkalemia Monitor potassium levels
Erythromycin Statins Pharmacokinetic CYP3A4 inhibition Rhabdomyolysis risk Avoid combination or monitor closely
Fluconazole Warfarin Pharmacokinetic CYP2C9 inhibition ↑ INR, bleeding risk Monitor INR closely
Fluconazole Phenytoin Pharmacokinetic CYP2C9 inhibition ↑ Phenytoin toxicity Monitor phenytoin levels
Fluconazole Warfarin Pharmacokinetic CYP2C9 inhibition ↑ INR → bleeding Monitor INR closely
Fluoxetine MAO inhibitors Pharmacodynamic ↑ Serotonin levels Serotonin syndrome Avoid combination
Fluoxetine Warfarin Pharmacokinetic CYP2C9 inhibition ↑ INR, bleeding risk Monitor INR
Fluoxetine Tamoxifen Pharmacokinetic CYP2D6 inhibition ↓ Tamoxifen activation → ↓ efficacy Consider alternative SSRI
Fluoxetine Tamoxifen Pharmacokinetic CYP2D6 inhibition ↓ Tamoxifen efficacy Consider alternative antidepressant
Fluoxetine Tramadol Pharmacodynamic ↑ Risk of serotonin syndrome Hyperthermia, tremor, seizures Avoid or monitor closely
Furosemide Digoxin Pharmacodynamic Hypokalemia potentiates digoxin toxicity Arrhythmias Monitor potassium and digoxin levels
Furosemide Aminoglycosides Pharmacodynamic Additive nephrotoxicity Acute kidney injury Avoid combination or monitor renal function
Gabapentin Antacids Pharmacokinetic ↓ Gabapentin absorption ↓ Therapeutic effect Separate doses by 2 hours
Gentamicin Vancomycin Pharmacodynamic Additive nephrotoxicity AKI Monitor renal function
Haloperidol Metoclopramide Pharmacodynamic ↑ Extrapyramidal symptoms Dystonia, Parkinsonism Avoid combination
Hydrochlorothiazide Lithium Pharmacokinetic ↓ Lithium clearance Lithium toxicity Monitor lithium levels
Hydroxychloroquine QT-prolonging drugs Pharmacodynamic Additive QT prolongation Torsades de pointes ECG monitoring recommended
Indinavir Rifampin Pharmacokinetic CYP3A4 induction ↓ Indinavir levels Avoid combination
Isoniazid Phenytoin Pharmacokinetic CYP inhibition ↑ Phenytoin toxicity Monitor phenytoin levels
Itraconazole Digoxin Pharmacokinetic P-gp inhibition ↑ Digoxin levels Monitor levels and signs of toxicity
Levetiracetam Carbamazepine Pharmacodynamic Antagonistic seizure threshold effect Seizure control loss Monitor for breakthrough seizures
Levodopa Antipsychotics Pharmacodynamic Antagonistic dopamine effects ↓ Levodopa efficacy Adjust doses or change therapy
Linezolid SSRIs Pharmacodynamic MAOI-like activity Risk of serotonin syndrome Avoid or monitor closely
Lithium ACE inhibitors Pharmacokinetic ↓ renal clearance of lithium Lithium toxicity (tremor, confusion) Monitor levels; adjust dose or avoid combo
Lithium Diuretics (thiazides) Pharmacokinetic ↓ renal clearance of lithium Lithium toxicity Monitor lithium levels
Lithium NSAIDs Pharmacokinetic ↓ renal clearance of lithium Lithium toxicity Monitor lithium levels
Lithium ACE inhibitors Pharmacokinetic ↓ renal clearance of lithium Lithium toxicity Monitor lithium levels
Lithium ACE inhibitors Pharmacokinetic ↓ Renal lithium clearance Lithium toxicity Monitor lithium levels
Lopinavir/ritonavir Statins Pharmacokinetic CYP3A4 inhibition ↑ Statin toxicity → rhabdomyolysis Use pravastatin or rosuvastatin
Macrolides QT-prolonging drugs Pharmacodynamic Additive QT prolongation Torsades de Pointes Monitor ECG, avoid in high-risk patients
Macrolides Statins Pharmacokinetic CYP3A4 inhibition Rhabdomyolysis Avoid combination or monitor closely
MAO inhibitors Tyramine-rich foods Pharmacodynamic ↑ NE from MAO inhibition Hypertensive crisis Dietary restrictions required
MAO inhibitors SSRIs Pharmacodynamic ↑ Serotonergic activity Serotonin syndrome Avoid combination
Metformin Iodinated contrast Pharmacokinetic Acute renal failure ↓ metformin excretion Lactic acidosis Hold metformin 48h before/after contrast
Metformin Iodinated contrast Pharmacokinetic Risk of lactic acidosis with renal dysfunction Lactic acidosis Hold metformin before/after contrast use
Methotrexate NSAIDs Pharmacokinetic ↓ renal elimination Methotrexate toxicity Avoid or monitor renal function and MTX level
Methotrexate Penicillin Pharmacokinetic ↓ Methotrexate renal clearance ↑ Methotrexate toxicity Monitor renal function, adjust dose
Methotrexate Trimethoprim Pharmacodynamic Additive bone marrow suppression Pancytopenia Avoid combination or monitor CBC
Metoprolol Verapamil Pharmacodynamic Additive negative inotropic and chronotropic effects Bradycardia, heart block Monitor cardiac function
Metoprolol Verapamil Pharmacodynamic Additive negative chronotropic effects Bradycardia, AV block Monitor ECG and heart rate
Nifedipine Grapefruit juice Pharmacokinetic CYP3A4 inhibition ↑ Nifedipine plasma levels Avoid grapefruit juice
NSAIDs Anticoagulants Pharmacodynamic Additive bleeding risk Increased bleeding risk Monitor coagulation, avoid if possible
NSAIDs Lithium Pharmacokinetic ↓ Lithium clearance Lithium toxicity Monitor lithium levels
NSAIDs SSRIs Pharmacodynamic ↑ GI bleeding risk GI ulcer, bleeding Consider PPI prophylaxis
Omeprazole Clopidogrel Pharmacokinetic CYP2C19 inhibition ↓ Clopidogrel activation Avoid combination or use alternative PPI
Oxcarbazepine Oral contraceptives Pharmacokinetic Induces metabolism ↓ OCP efficacy Use backup contraception
Phenobarbital Warfarin Pharmacokinetic CYP induction ↓ INR → clotting risk Monitor INR and adjust warfarin
Phenytoin Doxycycline Pharmacokinetic ↑ hepatic metabolism of doxycycline ↓ Doxycycline efficacy Monitor clinical response
Phenytoin Warfarin Pharmacokinetic CYP induction ↓ Warfarin effect, clot risk Monitor INR, adjust warfarin dose
Phenytoin Theophylline Pharmacokinetic CYP induction ↓ Theophylline levels Monitor theophylline levels
Phenytoin Oral contraceptives Pharmacokinetic CYP induction ↓ Contraceptive efficacy Use backup contraception
Prednisone NSAIDs Pharmacodynamic Additive GI toxicity GI ulcer, bleeding Use gastroprotection
Probenecid Penicillins Pharmacokinetic ↓ Renal tubular secretion ↑ Penicillin levels Adjust dose as necessary
Rifampin Oral contraceptives Pharmacokinetic CYP3A4 induction ↓ contraceptive efficacy Use backup contraception
Rifampin Warfarin Pharmacokinetic CYP induction ↓ Warfarin levels → clot risk Monitor INR, adjust warfarin dose
Rifampin Oral contraceptives Pharmacokinetic CYP induction ↓ Contraceptive efficacy Use backup contraception
Ritonavir Rifampin Pharmacokinetic Rifampin induces CYP → ↓ Ritonavir HIV treatment failure Contraindicated
Sildenafil Nitrates Pharmacodynamic Synergistic vasodilation Severe hypotension Contraindicated
Sildenafil Alpha blockers Pharmacodynamic Additive hypotension Severe hypotension Start alpha blockers at low dose, monitor blood pressure
Sildenafil Nitrates Pharmacodynamic Additive vasodilation Severe hypotension Contraindicated
Simvastatin Clarithromycin Pharmacokinetic CYP3A4 inhibition Rhabdomyolysis, elevated CK Avoid combination; consider statin switch
SSRIs (e.g., fluoxetine) Tramadol Pharmacodynamic ↑ serotonergic activity Serotonin syndrome Avoid combination if possible
Sulfamethoxazole Warfarin Pharmacokinetic CYP2C9 inhibition ↑ INR → bleeding risk Monitor INR closely
Tacrolimus Fluconazole Pharmacokinetic CYP3A4 inhibition ↑ Tacrolimus levels, nephrotoxicity Reduce dose and monitor levels
Tacrolimus Macrolides Pharmacokinetic CYP3A4 inhibition ↑ Tacrolimus toxicity Reduce dose and monitor levels
Tamoxifen Paroxetine Pharmacokinetic CYP2D6 inhibition ↓ Tamoxifen activation Use venlafaxine instead
Theophylline Ciprofloxacin Pharmacokinetic CYP1A2 inhibition Theophylline toxicity Monitor levels, consider dose reduction
Theophylline Ciprofloxacin Pharmacokinetic CYP1A2 inhibition ↑ Theophylline toxicity Monitor levels, dose adjustment
Theophylline Ciprofloxacin Pharmacokinetic CYP1A2 inhibition ↑ Theophylline toxicity Monitor levels and adjust dose
Theophylline Smoking (tobacco) Pharmacokinetic CYP1A2 induction ↓ Theophylline levels Adjust dose based on smoking status
Tramadol SSRIs/SNRIs Pharmacodynamic ↑ Serotonin syndrome risk Agitation, confusion, tremors Avoid or monitor
Valproic acid Lamotrigine Pharmacokinetic Inhibits lamotrigine metabolism Severe rash (SJS/TEN) Start with lower lamotrigine dose
Valproic acid Aspirin Pharmacokinetic Displacement from protein binding ↑ Free valproic acid levels Monitor levels, caution with dosing
Valproic acid Lamotrigine Pharmacokinetic Inhibits lamotrigine metabolism ↑ Risk of severe rash (SJS/TEN) Start with low lamotrigine dose
Verapamil Digoxin Pharmacokinetic ↓ Renal clearance Digoxin toxicity Monitor digoxin levels
Warfarin NSAIDs Pharmacodynamic Increased bleeding risk GI bleeding, bruising Avoid if possible; monitor INR closely
Warfarin Amiodarone Pharmacokinetic CYP2C9 inhibition ↑ INR, bleeding risk Reduce warfarin dose; monitor INR
Warfarin Fluconazole Pharmacokinetic CYP2C9 inhibition ↑ INR, bleeding risk Monitor INR closely
Warfarin Metronidazole Pharmacokinetic CYP2C9 inhibition ↑ INR, bleeding risk Monitor INR closely
Warfarin Amiodarone Pharmacokinetic CYP2C9 inhibition ↑ INR and bleeding risk Reduce warfarin dose; monitor INR
Warfarin Metronidazole Pharmacokinetic CYP2C9 inhibition ↑ INR and bleeding risk Monitor INR closely
Warfarin Sulfamethoxazole Pharmacokinetic CYP2C9 inhibition ↑ INR Reduce warfarin dose and monitor INR
Zidovudine Ganciclovir Pharmacodynamic Additive bone marrow suppression Neutropenia, anemia Monitor CBC closely
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