PKIS v2.0 A clinical tool for identifying important pharmacokinetic drug-drug interactions
| 1. Accepted major perpetrators | 2. Rejected perpetrators | 3. Unclassifiable | 4. Full table |

imatinib

  • imatinib is a moderate inhibitor of CYP3A.
  • imatinib is a weak inhibitor of CYP2D6.
  • imatinib has not been evaluated in the literature showing its role of altering the activities of CYP2C9.
  • CYP2C9CYP2D6CYP3A
    Moderate inhibitorsfluconazole [1]
    cinacalcet [2]
    doxepin [3]
    duloxetine [4]
    flecainide [5]
    moclobemide [6]
    quinine [7]
    terbinafine [8]
    aprepitant [9]
    atazanavir [10]
    atazanavir/ritonavir [10]
    cimetidine [11]
    cyclosporine [12]
    diltiazem [13]
    fluconazole [14]
    fluvoxamine [15]
    imatinib [16]
    posaconazole [a]
    verapamil [13]
    Weak inhibitorsamiodarone [17]
    cimetidine [18]
    co-trimoxazole [19]
    disulfiram [20]
    echinacea [21]
    fluvastatin [22]
    fluvoxamine [23]
    ketoconazole [24]
    lovastatin [17]
    metronidazole [25]
    sertraline [26]
    simvastatin [17]
    sulfadiazine [27]
    voriconazole [28]
    zafirlukast [a]
    amiodarone [29]
    amitriptyline [30]
    aspirin [31]
    celecoxib [32]
    cimetidine [33]
    darifenacin [b]
    desvenlafaxine [34]
    diltiazem [35]
    diphenhydramine [36]
    escitalopram [37]
    felodipine [38]
    fluvoxamine [39]
    gefitinib [40]
    hydralazine [41]
    imatinib [42]
    interferon alpha-2b [43]
    ketoconazole [44]
    methadone [45]
    metoprolol [46]
    nortriptyline [47]
    oral contraceptives [48]
    oxprenolol [46]
    pindolol [46]
    propranolol [46]
    ranitidine [49]
    risperidone [50]
    ritonavir [51]
    saw palmetto [52]
    sertraline [53]
    timolol [46]
    venlafaxine [54]
    alprazolam [55]
    amiodarone [56]
    aspirin [31]
    azithromycin [57]
    bicalutamide [58]
    cimetidine [59]
    co-trimoxazole [60]
    cyclosporine [61]
    fluvoxamine [62]
    isoniazid [63]
    maraviroc [64]
    oral contraceptives [65]
    ranitidine [11]
    roxithromycin [66]
    simvastatin [67]
    Not evaluated in the literatureatazanavir
    efavirenz
    5-fluorouracil
    fluoxetine
    imatinib
    isoniazid
    leflunomide
    phenobarbitone
    phenytoin
    ritonavir
    teniposide
    artemether/ lumefantrine
    chlorpheniramine
    chlorpromazine
    cocaine
    doxorubicin
    haloperidol
    ibuprofen
    methadone
    metoclopramide
    nilotinib
    ticlopidine
    anastrozole
    atenolol
    atorvastatin
    caffeine
    cyproterone
    ethosuximide
    danazol
    delavirdine [c]
    digoxin
    gemfibrozil
    lapatinib
    metoprolol
    metronidazole
    mifepristone
    norfloxacin
    quinipristin-dalfopristin
    raloxifene
    repaglinide
    valproate

    Footnotes and References

    a.assessment based on product information accessed via the Therapeutic Goods Administration of Australia Product and Consumer Medicines Information website ( https://www.ebs.tga.gov.au/ebs/picmi/picmirepository.nsf/PICMI?OpenForm&t=PI&q=&r=https://www.ebs.tga.gov.au/ ).
    b.systemic preparations not available in Australia or New Zealand.
    c.likely to be a major inhibitor based on subjective evaluation (≥ 2-fold AUC increase or ≥ 50% decrease in clearance of in vivo CYP probe).
    1.Neal JM, Kunze KL, Levy RH, O'Reilly RA, Trager WF. Kiiv, an in vivo parameter for predicting the magnitude of a drug interaction arising from competitive enzyme inhibition. Drug Metabolism and Disposition 2003; 31: 1043-48.[PubMed]
    2.Harris RZ, Salfi M, Posvar E, Hoelscher D, Padhi D. Pharmacokinetics of desipramine HCl when administered with cinacalcet HCl. European Journal of Clinical Pharmacology 2007; 63: 159-63.[PubMed]
    3.Szewczuk-Boguslawska M, Kiejna A, Beszlej JA, Orzechowska-Juzwenko K, Milejski P. Doxepin inhibits CYP2D6 activity in vivo. Polish Journal of Pharmacology 2004; 56: 491-94.[PubMed]
    4.Skinner MH, Kuan HY, Pan A, Sathirakul K, Knadler MP, Gonzales CR, Yeo KP, Reddy S, Lim M, Ayan-Oshodi M, Wise SD. Duloxetine is both an inhibitor and a substrate of cytochrome P4502D6 in healthy volunteers. Clinical Pharmacology & Therapeutics 2003; 73: 170-77.[PubMed]
    5.Haefeli WE, Bargetzi MJ, Follath F, Meyer UA. Potent inhibition of cytochrome P450IID6 (debrisoquin 4-hydroxylase) by flecainide in vitro and in vivo. Journal of Cardiovascular Pharmacology 1990; 15: 776-79.[PubMed]
    6.Härtter S, Dingemanse J, Baier D, Ziegler G, Hiemke C. Inhibition of dextromethorphan metabolism by moclobemide. Psychopharmacology 1998; 135: 22-26.[PubMed]
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    10.Abel S, Russell D, Taylor-Worth RJ, Ridgway CE, Muirhead GJ. Effects of CYP3A4 inhibitors on the pharmacokinetics of maraviroc in healthy volunteers. British Journal of Clinical Pharmacology 2008; 65: 27-37.[PubMed]
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    12.Arnadottir M, Eriksson LO, Thysell H, Karkas JD. Plasma concentration profiles of simvastatin 3-hydroxy-3-methyl-glutaryl-coenzyme A reductase inhibitory activity in kidney transplant recipients with and without ciclosporin. Nephron 1993; 65: 410-13.[PubMed]
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    17.Herman D, Locatelli I, Grabnar I, Peternel P, Stegnar M, Lainscak M, Mrhar A, Breskvar K, Dolzan V. The influence of co-treatment with carbamazepine, amiodarone and statins on warfarin metabolism and maintenance dose. European Journal of Clinical Pharmacology 2006; 62: 291-96.[PubMed]
    18.Back DJ, Tjia J, Monig H, Ohnhaus EE, Park BK. Selective inhibition of drug oxidation after simultaneous administration of two probe drugs, antipyrine and tolbutamide. European Journal of Clinical Pharmacology 1988; 34: 157-63.[PubMed]
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    20.Svendsen TL, Kristensen MB, Hansen JM, Skovsted L. The influence of disulfiram on the half life and metabolic clearance rate of diphenylhydantoin and tolbtamide in man. European Journal of Clinical Pharmacology 1976; 5-6: 439-41.[PubMed]
    21.Gorski JC, Huang SM, Pinto A, Hamman MA, Hilligoss JK, Zaheer NA, Desai M, Miller M, Hall SD. The effect of echinacea (Echinacea purpurea root) on cytochrome P450 activity in vivo. Clinical Pharmacology & Therapeutics 2004; 75: 89-100.[PubMed]
    22.Kim MJ, Nafziger AN, Kashuba ADM, Kirchheiner J, Bauer S, Gaedigk A, Bertino JS. Effects of fluvastatin and cigarette smoking on CYP2C9 activity measured using the probe S-warfarin. European Journal of Clinical Pharmacology 2006; 62: 431-36.[PubMed]
    23.Madsen H, Enggaard TP, Hansen LL, Klitgaard NA, Brosen K. Fluvoxamine inhibits the CYP2C9 catalyzed biotransformation of tolbutamide. Clinical Pharmacology & Therapeutics 2001; 69: 41-47.[PubMed]
    24.Krishnaiah YSR, Satyanarayana S, Visweswaram D. Interaction between tolbutamide and ketoconazole in healthy subjects. British Journal of Clinical Pharmacology 1994; 37: 205-07.[PubMed]
    25.O'Reilly R. The stereoselective interaction of warfarin and metronidazole in man. New England Journal of Medicine 1976; 295: 354-57.[PubMed]
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    27.Hansen JM, Kampmann JP, Siersbaeknielsen K, Lumholtz IB, Arroe M, Abildgaard U, Skovsted L. The effect of different sulfonamides on phenytoin metabolism in man. Acta Medica Scandinavica 1979: 106-10.[PubMed]
    28.Purkins L, Wood N, Ghahramani P, Love ER, Eve MD, Fielding A. Coadministration of voriconazole and phenytoin: pharmacokinetic interaction, safety, and toleration. British Journal of Clinical Pharmacology 2003; 56: 37-44.[PubMed]
    29.Fukumoto K, Kobayashi T, Tachibana K, Kat R, Tanaka K, Komamura K, Kamakura S, Kitakaze M, Ueno K. Effect of amiodarone on the serum concentration/dose ratio of metoprolol in patients with cardiac arrhythmia. Drug Metab Pharmacokinet 2006; 21: 501-05.[PubMed]
    30.Baumann P, Meyer JW, Amey M, Baettig D, Bryois C, Jonzierperey M, Koeb L, Monney C, Woggon B. Dextromethorphan and mephenytoin phenotyping of patients treated with thioridazine or amitriptyline. Therapeutic Drug Monitoring 1992; 14: 1-8.[PubMed]
    31.Chen XP, Tan ZR, Huang SL, Huang Z, Ou-Yang DS, Zhou HH. Isozyme-specific induction of low-dose aspirin on cytochrome P450 in healthy subjects. Clinical Pharmacology & Therapeutics 2003; 73: 264-71.[PubMed]
    32.Werner U, Werner D, Rau T, Fromm MF, Hinz B, Brune K. Celecoxib inhibits metabolism of cytochrome P450 2D6 substrate metoprolol in humans. Clinical Pharmacology & Therapeutics 2003; 74: 130-37.[PubMed]
    33.Steiner E, Spina E. Differences in the inhibitory effect of cimetidine on desipramine metabolism between rapid and slow debrisoquin hydroxylators. Clinical Pharmacology & Therapeutics 1987; 42: 278-82.[PubMed]
    34.Patroneva A, Connolly SM, Fatato P, Pedersen R, Jiang Q, Paul J, Guico-Pabia C, Isler JA, Burczynski ME, Nichols AI. An Assessment of Drug-Drug Interactions: The Effect of Desvenlafaxine and Duloxetine on the Pharmacokinetics of the CYP2D6 Probe Desipramine in Healthy Subjects. Drug Metabolism and Disposition 2008; 36: 2484-91.[PubMed]
    35.Tateishi T, Nakashima H, Shitou T, Kumagai Y, Ohashi K, Hosoda S, Ebihara A. Effect of diltiazem on the pharmacokinetics of propranolol, metoprolol and atenolol. European Journal of Clinical Pharmacology 1989; 36: 67-70.[PubMed]
    36.Sharma A, Pibarot P, Pilote S, Dumesnil JG, Arsenault M, Belanger PM, Meibohm B, Hamelin BA. Modulation of metoprolol pharmacokinetics and hemodynamics by diphenhydramine coadministration during exercise testing in healthy premenopausal women. Journal of Pharmacology and Experimental Therapeutics 2005; 313: 1172-81.[PubMed]
    37.Preskorn SH, Greenblatt DJ, Flockhart D, Luo Y, Perloff ES, Harmatz JS, Baker B, Klick-Davis A, Desta Z, Burt T. Comparison of duloxetine, escitalopram, and sertraline effects on cytochrome P450 2D6 function in healthy volunteers. Journal of Clinical Psychopharmacology 2007; 27: 28-34.[PubMed]
    38.Smith SR, Wilkins MR, Jack DB, Kendall MJ, Laugher S. Pharmacokinetic interactions between felodipine and metoprolol. European Journal of Clinical Pharmacology 1987; 31: 575-78.[PubMed]
    39.Alfaro CL, Lam YWF, Simpson J, Ereshefsky L. CYP2D6 status of extensive metabolizers after multiple-dose fluoxetine, fluvoxamine, paroxetine, or sertraline. Journal of Clinical Psychopharmacology 1999; 19: 155-63.[PubMed]
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    48.Kendall MJ, Quarterman CP, Jack DB, Beeley L. Metoprolol pharmacokinetics and the oral contraceptive pill. British Journal of Clinical Pharmacology 1982; 14: 120-22.[PubMed]
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    50.Eap CB, Bondolfi G, Zullino D, Bryois C, Fuciec M, Savary L, Jonzier-Perey M, Baumann P. Pharmacokinetic drug interaction potential of risperidone with cytochrome P450 isozymes as assessed by the dextromethorphan, the caffeine, and the mephenytoin test. Therapeutic Drug Monitoring 2001; 23: 228-31.[PubMed]
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