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 |

clarithromycin

  • clarithromycin is a strong inhibitor of CYP3A.
  • clarithromycin is a moderate inhibitor of CYP2C19.
  • clarithromycin is a weak inhibitor of CYP1A2.
  • CYP1A2CYP2C19CYP3A
    Strong inhibitorsciprofloxacin [1]
    fluvoxamine [2]
    fluconazole [3]
    fluvoxamine [4]
    ticlopidine [5]
    clarithromycin [6]
    erythromycin [7]
    grapefruit juice [8]
    indinavir [a]
    itraconazole [9]
    ketoconazole [9]
    lopinavir/ritonavir [10]
    ritonavir [11]
    saquinavir [12]
    saquinavir/ritonavir [13]
    voriconazole [14]
    Moderate inhibitorsethinyl estradiol [15]
    interferon alpha-2b [16]
    clarithromycin [17]
    fluoxetine [18]
    moclobemide [19]
    voriconazole [20]
    aprepitant [21]
    atazanavir [13]
    atazanavir/ritonavir [13]
    cimetidine [22]
    cyclosporine [23]
    diltiazem [24]
    fluconazole [25]
    fluvoxamine [26]
    imatinib [27]
    posaconazole [a]
    verapamil [24]
    Weak inhibitorscimetidine [28]
    clarithromycin [29]
    diltiazem [30]
    echinacea [31]
    erythromycin [29]
    mexiletine [32]
    moclobemide [19]
    norfloxacin [33]
    propranolol [34]
    roxithromycin [29]
    ticlopidine [35]
    verapamil [36]
    finasteride [37]
    interferon alpha-2b [16]
    ketoconazole [38]
    omeprazole [39]
    oral contraceptives [40]
    roxithromycin [41]
    alprazolam [42]
    amiodarone [43]
    aspirin [44]
    azithromycin [45]
    bicalutamide [46]
    cimetidine [47]
    co-trimoxazole [48]
    cyclosporine [49]
    fluvoxamine [50]
    isoniazid [51]
    maraviroc [52]
    oral contraceptives [53]
    ranitidine [22]
    roxithromycin [54]
    simvastatin [55]

    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/ ).
    1.Granfors MT, Backman JT, Neuvonen M, Neuvonen PJ. Ciprofloxacin greatly increases concentrations and cypotensive effect of tizanidine by inhibiting its cytochrome P450 1A2-mediated presystemic metabolism. Clinical Pharmacology & Therapeutics 2004; 76: 598-606.[PubMed]
    2.Granfors MT, Backman JT, Neuvonen M, Ahonen J, Neuvonen PJ. Fluvoxamine Drastically Increases Concentrations and Effects of Tizanidine: A Potentially Hazardous Interaction. Clinical Pharmacology & Therapeutics 2004; 75: 331-41.[PubMed]
    3.Kang BC, Yang CQ, Cho HK, Suh OK, Shin WG. Influence of fluconazole on the pharmacokinetics of omeprazole in healthy volunteers. Biopharmaceutics & Drug Disposition 2002; 23: 77-81.[PubMed]
    4.Yasui-Furukori N, Takahata T, Nakagami T, Yoshiya G, Inoue Y, Kaneko S, Tateishi T. Different inhibitory effect of fluvoxamine on omeprazole metabolism between CYP2C19 genotypes. British Journal of Clinical Pharmacology 2004; 57: 487-94.[PubMed]
    5.Ieiri I, Kimura M, He S, Urae A, Otsubo K, Ishizaki T. Interaction magnitude, pharmacokinetics and pharmacodynamics of ticlopidine in relation to CYP2C19 genotypic status. Pharmacogenetics and Genomics 2005; 15: 851-59.[PubMed]
    6.Gorski JC, Jones DR, Haehner-Daniels BD, Hamman MA, O'Mara EM, Hall SD. The contribution of intestinal and hepatic CYP3A to the interaction between midazolam and clarithromycin. Clinical Pharmacology & Therapeutics 1998; 64: 133-43.[PubMed]
    7.Kivisto KT, Lamberg TS, Kantola T, Neuvonen PJ. Plasma buspirone concentrations are greatly increased by erythromycin and itraconazole. Clinical Pharmacology & Therapeutics 1997; 62: 348-54.[PubMed]
    8.Lilja JJ, Kivisto KT, Backman JT, Lamberg TS, Neuvonen PJ. Grapefruit juice substantially increases plasma concentrations of buspirone. Clinical Pharmacology & Therapeutics 1998; 64: 655-60.[PubMed]
    9.Olkkola KT, Backman JT, Neuvonen PJ. Midazolam should be avoided in patients receiving the systemic antimycotics ketoconazole or itraconazole. Clinical Pharmacology & Therapeutics 1994; 55: 481-85.[PubMed]
    10.Yeh RF, Gaver VE, Patterson KB, Rezk NL, Baxter-Meheux F, Blake MJ, Eron JJJ, Klein CE, Rublein JC, Kashuba ADM. Lopinavir/Ritonavir Induces the Hepatic Activity of Cytochrome P450 Enzymes CYP2C9, CYP2C19, and CYP1A2 But Inhibits the Hepatic and Intestinal Activity of CYP3A as Measured by a Phenotyping Drug Cocktail in Healthy Volunteers. Journal of Acquired Immune Deficiency Syndromes 2006; 42: 52-60.[PubMed]
    11.Culm-Merdek KE, von Moltke LL, Gan L, Horan KA, Reynolds R, Harmatz JS, Court MH, Greenblatt DJ. Effect of extended exposure to grapefruit juice on cytochrome P450 3A activity in humans: Comparison with ritonavir. Clinical Pharmacology & Therapeutics 2006; 79: 243-54.[PubMed]
    12.Palkama VJ, Ahonen J, Neuvonen PJ, Olkkola KT. Effect of saquinavir on the pharmacokinetics and pharmacodynamics of oral and intravenous midazolam. Clinical Pharmacology & Therapeutics 1999; 66: 33-39.[PubMed]
    13.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]
    14.Saari TI, Laine K, Leino K, Valtonen M, Neuvonen PJ, Olkkola KT. Effect of voriconazole on the pharmacokinetics and pharmacodynamics of intravenous and oral midazolam. Clinical Pharmacology & Therapeutics 2006; 79: 362-70.[PubMed]
    15.Granfors MT, Backman JT, Laitila J, Neuvonen PJ. Oral contraceptives containing ethinyl estradiol and gestodene markedly increase plasma concentrations and effects of tizanidine by inhibiting cytochrome P450 1A2[ast]. Clin Pharmacol Ther 2005; 78: 400-11.[PubMed]
    16.Islam M, Frye RF, Richards TJ, Sbeitan I, Donnelly SS, Glue P, Agarwala SS, Kirkwood JM. Differential Effect of IFNalpha-2b on the Cytochrome P450 Enzyme System: A Potential Basis of IFN Toxicity and Its Modulation by Other Drugs. Clinical Cancer Research 2002; 8: 2480-87.[PubMed]
    17.Furuta T, Ohashi K, Kobayashi K, Iida I, Yoshida H, Shirai N, Takashima M, Kosuge K, Hanai H, Chiba K, Ishizaki T, Kaneko E. Effects of clarithromycin on the metabolism of omeprazole in relation to CYP2C19 genotype status in humans. Clinical Pharmacology & Therapeutics 1999; 66: 265-74.[PubMed]
    18.Harvey AT, Preskorn SH. Fluoxetine pharmacokinetics and effect on CYP2C19 in young and elderly volunteers. Journal of Clinical Psychopharmacology 2001; 21: 161-66.[PubMed]
    19.Gram LF, Guentert TW, Grange S, Vistisen K, Brosen K. Moclobemide, a substrate of CYP2C19 and an inhibitor of CYP2C19, CYP2D6, and CYP1A2 - a panel study. Clinical Pharmacology & Therapeutics 1995; 57: 670-77.[PubMed]
    20.Jeu L, Piacenti FJ, Lyakhovetskiy AG, Fung HB. Voriconazole. Clinical Therapeutics 2003; 25: 1321-81.[PubMed]
    21.Majumdar AK, McCrea JB, Panebianco DL, Hesney M, Dru J, Constanzer M, Goldberg MR, Murphy G, Gottesdiener KM, Lines CR, Petty KJ, Blum RA. Effects of aprepitant on cytochrome P450 3A4 activity using midazolam as a probe. Clinical Pharmacology & Therapeutics 2003; 74: 150-56.[PubMed]
    22.Elliott P, Dundee JW, Elwood RJ, Collier PS. The influence of H2 receptor antagonists on the plasma concentrations of midazolam and temazepam. European Journal of Anaesthesiology 1984; 1: 245-51.[PubMed]
    23.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]
    24.Backman JT, Olkkola KT, Aranko K, Himberg JJ, Neuvonen PJ. Dose of midazolam should be reduced during diltiazem and verapamil treatments. British Journal of Clinical Pharmacology 1994; 37: 221-25.[PubMed]
    25.Olkkola KT, Ahonen J, Neuvonen PJ. The effect of the systemic antimycotics, itraconazole and fluconazole, on the pharmacokinetics and pharmacodynamics of intravenous and oral midazolam. Anesthesia and Analgesia 1996; 82: 511-16.[PubMed]
    26.Lamberg TS, Kivisto KT, Laitila J, Martensson K, Neuvonen PJ. The effect of fluvoxamine on the pharmacokinetics and pharmacodynamics of buspirone. European Journal of Clinical Pharmacology 1998; 54: 761-66.[PubMed]
    27.O'Brien SG, Meinhardt P, Bond E, Beck J, Peng B, Dutreix C, Mehring G, Milosavljev S, Huber C, Capdeville R, Fischer T. Effects of imatinib mesylate (STI571, Glivec) on the pharmacokinetics of simvastatin, a cytochrome P450 3A4 substrate, in patients with chronic myeloid leukaemia. British Journal of Cancer 2003; 89: 1855-59.[PubMed]
    28.Naline E, Sanceaume M, Pays M, Advenier C. Application of theophylline metabolite assays to the exploration of liver microsome oxidative function in man. Fundamental & Clinical Pharmacology 1988; 2: 341-51.[PubMed]
    29.Periti P, Mazzei T, Mini E, Novelli A. Pharmacokinetic drug-interactions of macrolides. Clinical Pharmacokinetics 1992; 23: 106-31.[PubMed]
    30.Soto J, Sacristan JA, Alsar MJ. Diltiazem Treatment Impairs Theophylline Elimination in Patients with Bronchospastic Airway Disease. Therapeutic Drug Monitoring 1994; 16: 49-52.[PubMed]
    31.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]
    32.Hurwitz A, Vacek JL, Botteron GW, Sztern MI, Hughes EM, Jayaraj A. Mexiletine effects on theophylline disposition Clinical Pharmacology & Therapeutics 1991; 50: 299-307.[PubMed]
    33.Ho G, Tierney MG, Dales RE. Evaluation of the effect of norfloxacin on the pharmacokinetics of theophylline. Clinical Pharmacology & Therapeutics 1988; 44: 35-38.[PubMed]
    34.Miners JO, Wing LMH, Lillywhite KJ, Robson RA. Selectivity and dose-dependency of the inhibitory effect of propranolol on theophylline metabolism in man. British Journal of Clinical Pharmacology 1985; 20: 219-23.[PubMed]
    35.Colli A, Buccino G, Cocciolo M, Parravicini R, Elli GM, Scaltrini G. Ticlopidine-theophylline interaction. Clinical Pharmacology & Therapeutics 1987; 41: 358-62.[PubMed]
    36.Stringer KA, Mallet J, Clarke M, Lindenfeld JA. The effect of three different oral doses of verapamil on the disposition of theophylline. European Journal of Clinical Pharmacology 1992; 43: 35-38.[PubMed]
    37.Yasumori T, Narita H, Matsuda T, Takubo T, Ogawa M, Ishii M, Hara K, Ishii Y, Okuyama K, Fujimoto G, Ochiai H, Kano A, Hasegawa S, Sato K, Taniguchi T. Finasteride 1 mg has no inhibitory effect on omeprazole metabolism in extensive and poor metabolizers for CYP2C19 in Japanese. European Journal of Clinical Pharmacology 2006; 62: 939-46.[PubMed]
    38.Bottiger Y, Tybring G, Gotharson E, Bertilsson L. Inhibition of the sulfoxidation of omeprazole by ketoconazole in poor and extensive metabolizers of S-mephenytoin. Clinical Pharmacology & Therapeutics 1997; 62: 384-91.[PubMed]
    39.Caraco Y, Wilkinson GR, Wood AJJ. Differences between white subjects and Chinese subjects in the in vivo inhibition of cytochrome P450s 2C19, 2D6, and 3A by omeprazole. Clinical Pharmacology & Therapeutics 1996; 60: 396-404.[PubMed]
    40.Laine K, Tybring G, Bertilsson L. No sex-related differences but significant inhibition by oral contraceptives of CYP2C19 activity as measured by the probe drugs mephenytoin and omeprazole in healthy Swedish white subjects. Clinical Pharmacology & Therapeutics 2000; 68: 151-59.[PubMed]
    41.Kees F, Holstege A, Ittner KP, Zimmermann M, Lock G, Scholmerich J, Grobecker H. Pharmacokinetic interaction between proton pump inhibitors and roxithromycin in volunteers. Alimentary Pharmacology & Therapeutics 2000; 14: 407-12.[PubMed]
    42.Buch AB, Van Harken DR, Seidehamel RJ, Barbhaiya RH. A study of pharmacokinetic interaction between buspirone and alprazolam at steady state. Journal of Clinical Pharmacology 1993; 33: 1104-09.[PubMed]
    43.Becquemont L, Neuvonen M, Verstuyft C, Jaillon P, Letierce A, Neuvonen PJ, Funck-Brentano C. Amiodarone interacts with simvastatin but not with pravastatin disposition kinetics. Clinical Pharmacology & Therapeutics 2007; 81: 679-84.[PubMed]
    44.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]
    45.Zimmermann T, Yeates RA, Laufen H, Scharpf F, Leitold M, Wildfeuer A. Influence of the antibiotics erythromycin and azithromycin on the pharmacokinetics and pharmacodynamics of midazolam. Arzneimittel-Forschung/Drug Research 1996; 46: 213-17.[PubMed]
    46.Cockshott ID. Bicalutamide - Clinical pharmacokinetics and metabolism. Clinical Pharmacokinetics 2004; 43: 855-78.[PubMed]
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    48.Abel S, Russell D, Whitlock LA, Ridgway CE, Muirhead GJ. The effects of cotrimoxazole or tenofovir co-administration on the pharmacokinetics of maraviroc in healthy volunteers. British Journal of Clinical Pharmacology 2008; 65: 47-53.[PubMed]
    49.Li G, Treiber G, Meinshausen J, Wolf J, Werringloer J, Klotz U. Is cyclosporin A an inhibitor of drug metabolism? British Journal of Clinical Pharmacology 1990; 30: 71-77.[PubMed]
    50.Lam YWF, Alfaro CL, Ereshefsky L, Miller M. Pharmacokinetic and pharmacodynamic interactions of oral midazolam with ketoconazole, fluoxetine, fluvoxamine, and nefazodone. Journal of Clinical Pharmacology 2003; 43: 1274-82.[PubMed]
    51.Ochs HR, Greenblatt DJ, Knuchel M. Differential effect of isoniazid on triazolam oxidation and oxazepam conjugation. British Journal of Clinical Pharmacology 1983; 16: 743-46.[PubMed]
    52.Abel S, Russell D, Whitlock LA, Ridgway CE, Muirhead GJ. Effect of maraviroc on the pharmacokinetics of midazolam, lamivudine/zidovudine, and ethinyloestradiol/levonorgestrel in healthy volunteers. British Journal of Clinical Pharmacology 2008; 65: 19-26.[PubMed]
    53.Palovaara S, Kivisto KT, Tapanainen P, Manninen P, Neuvonen PJ, Laine K. Effect of an oral contraceptive preparation containing ethinylestradiol and gestodene on CYP3A4 activity as measured by midazolam 1 '-hydroxylation. British Journal of Clinical Pharmacology 2000; 50: 333-37.[PubMed]
    54.Backman JT, Aranko K, Himberg JJ, Olkkola KT. A pharmacokinetic interaction between roxithromycin and midazolam. European Journal of Clinical Pharmacology 1994; 46: 551-55.[PubMed]
    55.Prueksaritanont T, Vega JM, Zhao J, Gagliano K, Kuznetsova O, Musser B, Amin RD, Liu L, Roadcap BA, Dilzer S, Lasseter KC, Rogers JD. Interactions between simvastatin and troglitazone or pioglitazone in healthy subjects. Journal of Clinical Pharmacology 2001; 41: 573-81.[PubMed]
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