Drug Mechanism of action Clinical outcome Omeprazole x benzodiazepines Omeprazole inhibits hepatic metabolism of benzodiazepines Enhances valium efficacy Phenytoin x dexamethasone Dexamethasone inhibits hepatic metabolism of phenytoin High phenytoin blood levels trigger toxicity Dexamethasone x aripitant Aripitant inhibits hepatic metabolism of dexamethasone Increases hormonal effects Warfarin x fluconazole, tramadol, paracetamol, amitriptyline Decreases hepatic metabolism of warfarin Increased risk of bleeding Warfarin x carbamazepine, phenobarbital Increased hepatic metabolism of warfarin Decreased anticoagulant effect Rifampin, morphine Rifampin increases AUC of morphine Decreased analgesic effect Ketoconazole x omeprazole Alkaline environment detrimental to ketoconazole absorption Decreased efficacy of ketoconazole Pharmacokinetic interactions between chemotherapeutic and non-chemotherapeutic agents Drug Mechanism of action Clinical outcome Irinotecan x antiepileptics Phenytoin increases Irinotecan metabolism Irinotecan exposure decreased Paclitaxel x antiepileptics Antiepileptics inhibited hepatic metabolism of paclitaxel Paclitaxel exposure increased Irinotecan x ketoconazole Ketoconazole inhibited hepatic metabolism of irinotecan Irinotecan exposure increased Phenytoin x carmustine or cisplatin Cisplatin or carmustine interfered with hepatic metabolism of phenytoin Phenytoin blood levels decreased Cimetidine x epirubicin, 5-FU, carmustine, or mar Frank Cimetidine inhibits hepatic metabolism of these drugs Increased systemic exposure to these drugs 6-MP x allopurinol Allopurinol inhibits the first-pass effect of 6-MP Increased exposure to 6-MP Etoposide x antiepileptics Antiepileptics inhibit clearance of etoposide Increased systemic exposure to etoposide Warfarin x 5-FU, oxaliplatin, tamoxifen, isocyclophosphamide Decreased hepatic metabolism of warfarin Increased bleeding Increased systemic exposure to methotrexate Methotrexate x NSAIDs NSAIDs decrease renal clearance of methotrexate Increased toxicity of methotrexate Platinum x aminoglycosides Aminoglycosides decrease renal clearance of platinum Increased ototoxicity of gefitinib x ketoconazole Ketoconazole inhibits hepatic metabolism of gefitinib Increased hepatic metabolism of gefitinib Erlotinib x rifampin Rifampin increases hepatic metabolism of erlotinib Erlotinib’s effect is diminished 5-FU and capecitabine x phenytoin Fluoropyrimidine decreases metabolism of phenytoin Phenytoin shows toxic blood levels Docetaxel x ketoconazole Ketoconazole inhibits hepatic metabolism of docetaxel Increased exposure to cyclophosphamide x allopurinol Allopurinol inhibits metabolism of cyclophosphamide Prolonged half-life of cyclophosphamide Ondansetron × cyclophosphamide or cisplatin Unknown Decreased exposure to cyclophosphamide and cisplatin Warfarin × fluoropyrimidine, oxaliplatin, tamoxifen, isocyclophosphamide Decreased hepatic metabolism of warfarin Increased risk of hemorrhage Fluconazole × cyclosporine Increased uptake of cyclosporine by fluconazole Increased systemic exposure to cyclosporine Pharmacokinetic interactions between chemotherapeutic agents Drug Mechanism of action Clinical Effect Cisplatin x paclitaxel Cisplatin first reduces clearance of paclitaxel Enhanced toxicity Paclitaxel x anthracyclines Paclitaxel first reduces clearance of anthracyclines Enhanced anthracycline effect 5-FU x irinotecan 5-FU first reduces clearance of irinotecan Increased exposure to irinotecan 5-FU x gemcitabine Gemcitabine reduces clearance of 5-FU, increases half-life Increased exposure to 5-FU Gemcitabine x paclitaxel Paclitaxel decreases clearance of gemcitabine Increased exposure to gemcitabine Cyclophosphamide x Bactrim Cyclophosphamide less than 24 h after Bactrim decreases clearance of Bactrim Increased exposure to Bactrim Pharmacological interactions in oncology therapy Drug Mechanism of action Clinical outcomes Benzodiazepines x Opioids Benzodiazepines activate GABA receptors and antagonize opioid analgesia Decreased analgesia Tramadol x 5-hydroxytryptamine reuptake inhibitors 5-Hydroxytryptamine reuptake inhibitor 5-Hydroxytryptamine release additive 5-Hydroxytryptamine syndrome risk Trastuzumab x Anthracyclines Unknown Increased cardiotoxicity Rifampin x Morphine Rifampin increases morphine metabolism Diminished analgesia 5-FU x Folinic acid Folinic acid promotes 5-FU biotransformation Enhanced antitumor Methotrexate x Folinic acid Folinic acid supplements methotrexate-induced folate deficiency Reduced methotrexate toxicity Methotrexate x Methotrexate x methotrexate Folate inhibition additive Megaloblastic anemia Opioids x phenothiazines, barbiturates, or gastrodiazepines Additive central effects Sedation, respiratory depression Morphine x nimodipine Nimodipine modulates morphine tolerance Morphine daily dose reduction Morphine x methylphenidate Additive central effects Analgesic enhancement of opioids Alpha-interferon x zidovudine Unknown Additive myelosuppressive toxicity Gastrodiazepine x 5-hydroxytryptamine reuptake Inhibitors Increased 5-hydroxytryptamine release and decreased dopamine release 5-hydroxytryptophanergic and dystonic syndrome