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 |

carbamazepine

  • carbamazepine is a strong inducer of CYP3A.
  • carbamazepine is a weak inducer of CYP1A2, CYP2C9, and CYP2D6.
  • carbamazepine did not meet the criteria of being an inhibitor or inducer of CYP2C19.
  • CYP1A2CYP2C9CYP2C19CYP2D6CYP3A
    Strong inducersphenytoin [1]
    rifampicin [2]
    rifampicin [3]
    lopinavir/ritonavir [4]
    rifampicin [5]
    St. John's wort [6]
    carbamazepine [7]
    modafinil [8]
    phenytoin [9]
    rifampicin [10]
    St. John's wort [11]
    Weak inducerscarbamazepine [1]
    lopinavir/ritonavir [4]
    montelukast [12]
    phenobarbitone [13]
    smoking [14]
    valproate [1]
    aprepitant [a]
    bosentan [a]
    carbamazepine [15]
    lopinavir/ritonavir [4]
    aspirin [16]
    ginko biloba [17]
    carbamazepine [18]
    phenobarbitone [19]
    rifampicin [20]
    aprepitant [21]
    bosentan [22]
    dexamethasone [23]
    ginko biloba [24]
    quinine [b]
    smoking [25]
    terbinafine [26]
    Criteria not metamiodarone [27]
    methoxsalen [28]
    zafirlukast [29]
    capecitabine [30]
    itraconazole [31]
    carbamazepine [32]
    cimetidine [33]
    isoniazid [34]
    lansoprazole [35]
    pantoprazole [36]
    propoxyphene [37]
    rabeprazole [38]
    chloroquine [39]
    citalopram [40]
    clomipramine [41]
    disulfiram [42]
    grapefuit juice [43]
    hydroxychloroquine [44]
    orange juice [43]
    propoxyphene [37]
    verapamil [45]
    amprenavir [c]
    buspirone [c]
    ciprofloxacin [d] [46]
    citalopram [c]
    darifenacin [c]
    darunavir/ritonavir [d] [c]
    dasatinib [c]
    efavirenze
    erlotinib [c]
    fosamprenavir [d] [47]
    nevirapine [c]
    nilotinib [c]
    omeprazole [c]
    oxcarbazepine [c]
    phenobarbitone [e] [48]
    propoxyphene [49]
    rifabutin [c]

    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.reported at Clinical Trials.gov ( http://clinicaltrials.gov/ct2/show/study/NCT00785486?sect=X701&view=results ).
    c.clinical PK interaction studies referred to in product information.
    d.likely to be a major inhibitor based on subjective evaluation (≥ 2-fold AUC increase or ≥ 50% decrease in clearance of in vivo CYP probe).
    e.likely to be a major inducer based on subjective evaluation (≥ 2-fold decrease in AUC or ≥ 50% increase in clearance of in vivo CYP probe).
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    2.Backman JT, Granfors MT, Neuvonen PJ. Rifampicin is only a weak inducer of CYP1A2-mediated presystemic and systemic metabolism: studies with tizanidine and caffeine. European Journal of Clinical Pharmacology 2006; 62: 451-61.[PubMed]
    3.Adams M, Pieniaszek HJ, Gammaitoni AR, Ahdieh H. Oxymorphone extended release does not affect CYP2C9 or CYP3A4 metabolic pathways. Journal of Clinical Pharmacology 2005; 45: 337-45.[PubMed]
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    8.Robertson P, Hellriegel ET, Arora S, Nelson M. Effect of modafinil on the pharmacokinetics of ethinyl estradiol and triazolam in healthy volunteers. Clinical Pharmacology & Therapeutics 2002; 71: 46-56.[PubMed]
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    13.Saccar CL, Danish M, Ragni MC, Rocci ML, Greene J, Yaffe SJ, Mansmann HC. The effect of phenobarbital on theophylline disposition in children with asthma. Journal of Allergy and Clinical Immunology 1985; 75: 716-19.[PubMed]
    14.Backman JT, Schroder MT, Neuvonen PJ. Effects of gender and moderate smoking on the pharmacokinetics and effects of the CYP1A2 substrate tizanidine. European Journal of Clinical Pharmacology 2008; 64: 17-24.[PubMed]
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    17.Yin OQP, Tomlinson B, Waye MMY, Chow AHL, Chow MSS. Pharmacogenetics and herb-drug interactions: experience with Ginkgo biloba and omeprazole. Pharmacogenetics 2004; 14: 841-50.[PubMed]
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    20.Bennett PN, John VA, Whitmarsh VB. Effect of rifampicin on metoprolol and antipyrine kinetics. British Journal of Clinical Pharmacology 1982; 13: 387-91.[PubMed]
    21.Shadle CR, Lee Y, Majumdar AK, Petty KJ, Gargano C, Bradstreet TE, Evans JK, Blu RA. Evaluation of potential inductive effects of aprepitant on cytochrome P450 3A4 and 2C9 activity. Journal of Clinical Pharmacology 2004; 44: 215-23.[PubMed]
    22.Dingemanse J, Schaarschmidt D, van Giersbergen PLM. Investigation of the mutual pharmacokinetic interactions between bosentan, a dual endothelin receptor antagonist, and simvastatin. Clinical Pharmacokinetics 2003; 42: 293-301.[PubMed]
    23.Villikka K, Kivisto KT, Neuvonen PJ. The effect of dexamethasone on the pharmacokinetics of triazolam. Pharmacol Toxicol 1998; 83: 135-38.[PubMed]
    24.Robertson SM, Davey RT, Voell J, Formentini E, Alfaro RM, Penzak SR. Effect of Ginkgo biloba extract on lopinavir, midazolarn and fexofenadine pharmacokinetics in healthy subjects. Current Medical Research and Opinion 2008; 24: 591-99.[PubMed]
    25.Ochs HR, Greenblatt DJ, Burstein ES. Lack of influence of cigarette smoking on triazolam pharmacokinetics. British Journal of Clinical Pharmacology 1987; 23: 759-63.[PubMed]
    26.Ahonen J, Olkkola KT, Neuvonen PJ. Effect of itraconazole and terbinafine on the pharmacokinetics and pharmacodynamics of midazolam in healthy volunteers. British Journal of Clinical Pharmacology 1995; 40: 270-72.[PubMed]
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    29.Katial RK, Stelzle RC, Bonner MW, Marino M, Cantilena LR, Smith LJ. A drug interaction between zafirlukast and theophylline. Archives of Internal Medicine 1998; 158: 1713-15.[PubMed]
    30.Camidge R, Reigner B, Cassidy J, Grange S, Abt M, Weidekamm E, Jodrell D. Significant effect of capecitabine on the pharmacokinetics and pharmacodynamics of warfarin in patients with cancer. Journal of Clinical Oncology 2005; 23: 4719-25.[PubMed]
    31.Kivisto KT, Kantola T, Neuvonen PJ. Different effects of itraconazole on the pharmacokinetics of fluvastatin and lovastatin. British Journal of Clinical Pharmacology 1998; 46: 49-53.[PubMed]
    32.Bertilsson L, Tybring G, Widen J, Chang M, Tomson T. Carbamazepine treatment induces the CYP3A4 catalysed sulphoxidation of omeprazole, but has no or less effect on hydroxylation via CYP2C19. British Journal of Clinical Pharmacology 1997; 44: 186-89.[PubMed]
    33.Gough PA, Curry SH, Araujo OE, Robinson JD, Dallman JJ. Influence of cimetidine on oral diazepam elimination with measurement of subsequent cognitive change. British Journal of Clinical Pharmacology 1982; 14: 739-42.[PubMed]
    34.Ochs HR, Greenblatt DJ, Roberts GM, Dengler HJ. Diazepam interaction with antituberculosis drugs. Clinical Pharmacology & Therapeutics 1981; 29: 671-78.[PubMed]
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    36.Gugler R, Hartmann M, Rudi J, Brod I, Huber R, Steinijans VW, Bliesath H, Wurst W, Klotz U. Lack of pharmacokinetic interaction of pantoprazole with diazepam in man. British Journal of Clinical Pharmacology 1996; 42: 249-52.[PubMed]
    37.Sanz EJ, Bertilsson L. d-Propoxyphene is a potent inhibitor of debrisoquine, but not S-mephenytoin 4-hydroxylation in vivo. Therapeutic Drug Monitoring 1990; 12: 297-99.[PubMed]
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    39.Masimirembwa CM, Gustafsson LL, Dahl ML, Abdi YA, Hasler JA. Lack of effect of chloroquine on the debrisoquine (CYP2D6) and S-mephenytoin (CYP2C19) hydroxylation phenotypes. British Journal of Clinical Pharmacology 1996; 41: 344-46.[PubMed]
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    49.Abernethy DR, Greenblatt DJ, Morse DS, Shader RI. Interaction of propoxyphene with diazepam, alprazolam and lorazepam. British Journal of Clinical Pharmacology 1985; 19: 51-54.[PubMed]
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