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Drugs Involved in Significant Pharmacokinetic Drug-Drug Interactions in 2015

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Drugs Involved in Significant Pharmacokinetic Drug-Drug Interactions in 2015 Drugs Involved in Significant Pharmacokinetic Drug-Drug Interactions in 2015 This table lists drugs which are demonstrated (or predicted convincingly) to be involved in pharmacokinetic drug-drug interaction (DDI) at therapeutic doses in human associated with pH change, chelate formation Akihiro Hisakaa, Yoshiyuki Ohnob, Hiroshi Suzukib, Kazuya Maedac, Yuichi Sugiyamad in gastrointestinal tract or with alternations in activity of drug metabolizing enzymes and transporters. Most of drugs selected in this table are approved and frequently used in Japanese market as of Jan 2015. The a pharmacokinetic theory suggests that simultaneous oral intake of drugs(otherwise specified) in this table (such as a substrate and an inhibitor for the same enzyme) will cause significant pharmacokinetic DDI. The selection Clinical Pharmacology and Pharmacometrics, Graduate School of Pharmaceutical Sciences, Chiba University of drugs in this table is based on open information and mostly described in refs 1) and 2) for CYP related DDIs with an analysis of alert classification of DDI in the product labeling. The selection of drugs for transporter b Department of Pharmacy, The University of Tokyo Hospital, Faculty of Medicine, The University of Tokyo related DDIs is described in refs 3) and 4). Please note that classification of drugs in this table is not conclusive and may be incomplete. Drugs which are not listed in this table may also cause serious DDIs, including c Graduate School of Pharmaceutical Sciences, The University of Tokyo pharmacodynamic DDIs. In clinical settings, appropriate cares must be taken for all possible DDIs. d Sugiyama Laboratory, RIKEN Innovation Center, RIKEN Research Cluster for Innovation, RIKEN Mechanism of DDI and Category 1) Victim Drugs of DDI Blood Level Increasing Drugs Blood Level Reducing Drugs Genetic Variation in Japanese Interrupting absorption by pH ★ Antiretrovirals: Atazanavir(ATV), Saquinavir(SQV), Rilpivirine(RPV), Indinavir(IDV), Is DDI avoidable by adjusting timing of dose? Proton-pump inhibitors: Omeprazole, Esomeprazole, Lansoprazole, Rabeprazole elevation Delavirdine Histamine H -antagonists: Famotidine, Ranitidine, Cimetidine, Roxatidine, Nizatidine, DDIs of proton-pump inhibitors are unavoidable due to their durative 2 ★ Antineoplastic agents(oral drug): Gefitinib, Dasatinib, Erlotinib, Pazopanib, Nilotinib Lafutidine Azoles: Itraconazole(except for oral liguid) pharmacological action. For other drugs, longer interval between the Antacids: Aluminium Hydroxide Magnesium Hydroxide preparations ★ doses is better in order to reduce significance of DDI. ・ pH change and chelate formation Interrupting absorption by ★ Antiretrovirals: Dolutegravir Is DDI avoidable by adjusting timing of dose? Antacids(for Cefdinir, blue): Aluminium Hydroxide・Magnesium Hydroxide preparations, in gastrointestinal formation of chelate ★ Quinolones: Ciprofloxacin, Sitafloxacin, Tosufloxacin, Garenoxacin, Moxifloxacin, Sucralfate Hydrate, Dried Aluminium Hydroxide Gel, Levofloxacin When cefdinir needs to be used with iron preparations, iron preparations Synthetic Aluminum Silicate, Magnesium Hydroxide, Magnesium Oxide tract should be administered more than 3hr later than dose of cefdinir. ★ Tetracyclines: Doxycycline, Minocycline Iron preparations(for Cefdinir, bold red): Ferrous Citrate, Soluble Ferric pyrophosphate, Cephalosporins: Cefdinir Administration of multivalent cations should be avoided within 4hr Iron(II) Sulfate ★ before and after dose of eltrombopag and it should be administered in Hematopoietic agents: Eltrombopag Phosphate-removing agents(not defined for Cefdinir): Lanthanum Carbonate Hydrate, the fasting state. Other interacting drugs should be administered more Ferric citrate, Calcium Carbonate than 4hr before or 2hr after administration of "victim drugs". In human, 57 genes of cytochrome P450 (CYP) are recognized. Among them, 23 species are belong to CYP1−3 families which are significantly selectivity with P-glycoprotein, a typical efflux transporter. In general, inhibition of CYP potentiates both pharmacological and adverse actions of a involved in drug metabolism. CYP3A4 is the most important drug metabolizing enzyme and mediates metabolism of approximately half of drugs in drug, and induction of CYP reduces them. However, when metabolite(s) are pharmacologically active, the situation may be reversed. Usually, degree the market. CYP3A4 is expressed in the liver and intestine, and other CYPs are expressed predominantly in the liver. CYP3A4 often shares substrate of DDI is more evident when victim drugs are given orally compared with other route of administration. Inhibition and induction of Skeletal muscle relaxants: Tizanidine SSRIs: Fluvoxamine Anticonvulsants: Phenytoin CYP1A2 Melatonin receptor agonists: Ramelteon, Melatonin Quinolones: Ciprofloxacin, Enoxacin, Clinafloxacin Others: smoking intermediate 1% ★ Xanthine derivatives: Caffeine, Theophylline NSAIDs: Rofecoxib extensive 99% SNRIs: Duloxetine Contraceptives: (progesterone and ethinylestradiol) Antifibrotic agents: Pirfenidone Antiarrhythmics: Mexiletine Nonergot-derivative dopamine receptor agonists: Ropinirole Vitiligo therapeutic agents: Methoxsalen Atypical antipsychotics: Clozapine, Olanzapine Muscle relaxant: Idrocilamide 5-HT3 inhibitors: Alosetron, Ramosetron Acetylcholinesterase inhibitors: Tacrine Induction of CYP2B6 DNRIs: Bupropion Antiretrovirals: Efavirenz(EFV) intermediate 21% Antiretrovirals: Efavirenz(EFV) extensive 79% Inhibition of CYP2C8 ★ Antidiabetic agents: Repaglinide, Pioglitazone Antilipemic agents: Gemfibrozil※ Antituberculosis agents: Rifampicin extensive 100% Leukotriene-receptor antagonists: Montelukast Iron chelating agents: Deferasirox Immunosuppressive agents: Cyclosporin Inhibition and induction of ★ Anticoagulants: Warfarin Fluorinated pyrimidine antagonist2): TS-1※, UFT※, Tegafur※, Fluorouracil※, Antituberculosis agents: Rifampicin CYP2C9 ★ Antidiabetic agents: Glimepiride, Tolbutamide, Glibenclamide, Nateglinide Doxifluridine※, Capecitabine※, Carmofur※ Anticonvulsants: Phenobarbital, Carbamazepine intermediate 4% ★ Anticonvulsants: Phenytoin Azoles: Miconazole, Fluconazole Antiemetics: Aprepitant extensive 96% NSAIDs: Diclofenac, Celecoxib, Ibuprofen Sulfonamides: Sulfaphenazole Antilipemic agents: Fluvastatin Antiarrhythmics: Amiodarone Antigout agents: Bucolome Immunosuppressive agents: Cyclosporin Inhibition and induction of ★ Azoles: Voriconazole SSRIs: Fluvoxamine, Fluoxetine Antituberculosis agents: Rifampicin CYP2C19 Proton-pump inhibitors: Omeprazole, Lansoprazole, Esomeprazole, Rabeprazole Platelet-aggregation inhibitors: Ticlopidine※ Antiretrovirals: Ritonavir(RTV) poor 16% ★ Antiepileptic agents: Clobazam, S-Mephenytoin Azoles: Voriconazole, Fluconazole intermediate 48% Benzodiazepines: Diazepam, Etizolam Diuretics: Tienilic acid extensive 36% Platelet-aggregation inhibitors: Clopidogrel3) Antidepressants: Moclobemide SSRIs: Sertraline, Escitalopram Inhibition of CYP2D6 Antitussives: Dextromethorphan SSRIs: Paroxetine※, Fluoxetine, Escitalopram poor 3% Genitourinary smooth muscle relaxants: Tolterodine 5) Allylamine antifungal agents: Terbinafine *10/*10 14%4) Opiate agonists: Tramadol 3) Antiarrhythmics: Quinidine intermediate 35% SNRIs: Atomoxetine Calcium receptor agonists: Cinacalcet extensive 48% ★ Antiarrhythmics: Encainide, Propafenone, Flecainide Genitourinary smooth muscle relaxants: Mirabegron6) Cytochrome 3) P450 (CYP) ★ Antineoplastic agents(oral drug): Tamoxifen SNRIs: Duloxetine Antidepressants: Trimipramine, Desipramine, Nortriptyline, Maprotiline, Venlafaxine, DNRIs: Bupropion Doxepin, Amitriptyline, Imipramine, Clomipramine NSAIDs: Celecoxib β-adrenergic blocking agents: Metoprolol, Nebivolol, Timolol, Propranolol Antineoplastic agents: Dacomitinib Antipsychotics: Perphenazine Antidepressants: Moclobemide 5-HT3 inhibitors: Tropisetron Inhibition and induction of ★ Benzodiazepines: Triazolam, Midazolam, Alprazolam Azoles: Itraconazole, Voriconazole, Ketoconazole, Posaconazole, Antituberculosis agents: Rifampicin, Rifabutin CYP3A7) ★ Immunosuppressive agents: Everolimus, Sirolimus, Tacrolimus Miconazole, Fluconazole Anticonvulsants: Phenobarbital, Phenytoin, Carbamazepine intermediate 2% Antilipemic agents: Simvastatin, Lovastatin, Atorvastatin Antiretrovirals: Ritonavir(RTV)※, Indinavir(IDV)※, Cobicistat, Antiretrovirals: Etravirine(ETR), Efavirenz(EFV) extensive 98% Calcium-channel blocking agents: Nisoldipine, Felodipine, Azelnidipine Nelfinavir(NFV)※, Saquinavir(SQV)※, Atazanavir(ATV)※, Others: St.John's wort Antipsychotics: Blonanserin, Quetiapine, Lurasidone Fosamprenavir(FPV), Amprenavir(APV) Psychostimulants: Modafinil ★ Antipsychotics(Risk of LQTS): Pimozide HCV protease inhibitors: Telaprevir, Boceprevir Endothelin-receptor antagonists: Bosentan PDE-5 inhibitors: Vardenafil, Sildenafil, Tadalafil Macrolides: Troleandomycin※, Clarithromycin※, Erythromycin※ Antidepressants: Buspirone Calcium-channel blocking agents: Diltiazem※, Verapamil※ ★ Antineoplastic agents(oral drug): Dasatinib Antidepressants: Nefazodone※ ★ Antiretrovirals: Maraviroc(MVC), Darunavir(DRV), Indinavir(IDV), Lopinavir(LPV), Fruit juice: Grapefruit juice※ Saquinavir(SQV), Tipranavir(TPV), Rilpivirine(RPV) Antineoplastic agents: Imatinib※, Crizotinib ★ Anticoagulants: Rivaroxaban Antiemetics: Aprepitant, Casopitant Platelet-aggregation inhibitors: Ticagrelor Quinolones: Ciprofloxacin ★ Antiarrhythmics: Dronedarone Immunosuppressive agents: Cyclosporin Vasopressin V2 receptor antagonists: Conivaptan, Tolvaptan Benzodiazepines:
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