Disease-A-Month
Volume 56, Issue 3 , Pages 163-179 , March 2010

Updates on Cytochrome P450-Mediated Cardiovascular Drug Interactions

  • Judy W.M. Cheng, PharmD, MPH, FCCP, BCPS

      Affiliations

    • Arnold and Marie Schwartz College of Pharmacy and Sciences, Long Island University, Brooklyn, New York, Mt. Sinai Medical Center, New York, New York
    • ,
  • William H. Frishman, MD

      Affiliations

    • Department of Medicine, New York Medical College/Westchester Medical Center, Valhalla, New York
    • ,
  • Wilbert S. Aronow, MD

      Affiliations

    • Department of Medicine, New York Medical College/Westchester Medical Center, Valhalla, New York

References 

  1. Gonzalez FJ. Molecular genetics of the P-450 superfamily. Pharmac Ther. 1990;45:1–38
  2. Slaughter RL, Edwards DJ. Recent advances: the cytochrome P450 enzymes. Ann Pharmacother. 1995;29:619–624
  3. Guengerich FP, Dannan GA, Wright ST, et al. Purification and characterization of liver microsomal cytochrome P450: electrophoretic, spectral, catalytic and immunochemical properties and inducibility of eight isozymes isolated from rats treated with phenobarbital or B-naphthoflavone. Biochemistry. 1982;21:6019–6030
  4. Waxman DJ, Walsh C. Phenobarbital-induced rat liver cytochrome P-450-purification and characterization of two closely related isozymic forms. J Biol Chem. 1982;2257:10446–10457
  5. P450 tables. http://medicine.iupui.edu/flockhart/table.htmAccessed March 25, 2007
  6. Heimark LD, Wienkers L, Dunze K, et al. The mechanism of the interaction between amiodarone and warfarin in humans. Clin Pharmacol Ther. 1992;51:398–407
  7. Williamson KM, Patterson JH, McQueen RH, et al. Effects of erythromycin or rifampin on losartan pharmacokinetics in healthy volunteers. Clin Pharmacol Ther. 1998;63:316–323
  8. Kazierad DJ, Martin DE, Blum RA, et al. Effect of fluconazole on the pharmacokinetics of eprosartan and losartan in healthy male volunteers. Clin Pharmacol Ther. 1997;62:417–425
  9. Slaughter RL, Edwards DJ. Recent advances: the cytochrome P450 enzymes. Ann Pharmacother. 1995;29:619–624
  10. Shinn AF. Clinical relevance of cimetidine drug interactions. Drug Saf. 1992;7;:245–267
  11. Levy RH. Cytochrome P450 isoenzyme and antiepileptic drug interactions. Epilepsia. 1995;36(suppl 5):S8–S13
  12. Venkatesan K. Pharmacokinetic drug interactions with rifampin. Clin Pharmacokinet. 1992;22:47–65
  13. Spinler S, Cheng JWM, Kindwall KE, et al. Possible inhibition of hepatic metabolism of quinidine by erythromycin. Clin Pharmacol Ther. 1995;57:89–94
  14. Nolan PE, Marcus FL, Karol MD, et al. Effect of phenytoin on the clinical pharmacokinetics of amiodarone. J Clin Pharmacol. 1990;30:1112–1119
  15. Gore JM, Haffajee CI, Alpert JS. Interaction of amiodarone and diphenylhydantoin. Am J Cardiol. 1984;54:1145
  16. Marcus FI. Drug interactions with amiodarone. Am Heart J. 1983;106:924–930
  17. Saal AK, Werner JA, Greene HL, et al. Effect of amiodarone on serum quinidine and procainamide levels. Am J Cardiol. 1984;53:1264–1267
  18. DeVane CL, Gill HS, Markowitz JS, et al. Awareness of potential drug interactions may aid avoidance. Ther Drug Monit. 1997;19:366–367
  19. Savi P, Pereillo JM, Uzabiaga MF, et al. Identification and biological activity of the active metabolite of clopidogrel. Thromb Haemost. 2000;84:891–896
  20. Hasegawa M, Sugidachi A, Ogawa T, et al. Stereoselective inhibition of human platelet aggregation by R-138727, the active metabolite of CS-747 (prasugrel, LY640315), a novel P2Y12 receptor inhibitor. Thromb Haemost. 2005;94:593–598
  21. Kazui M, Ishizuka T, Yamamura N, et al. Mechanism of production of pharmacologically active metabolites of CS-747, a new pro-drug ADP-receptor antagonist. Thromb Haemost. 2001;12(suppl):P1916
  22. Lau C, L. Waskell LA, Carville D, et al. The antiplatelet activity of clopidogrel is inhibited by atorvastatin but not by pravastatin. Circulation. 2000;102:2086
  23. Lau C, Waskell LA, Watkins PB, et al. Atorvastatin reduces the ability of clopidogrel to inhibit platelet aggregation: a new drug–drug interaction. Circulation. 2003;107:32–37
  24. Suri A, Forbes WP, Bramer SL. Effects of CYP3A inhibition on the metabolism of cilostazil. Clin Pharmacokinet. 1999;37(suppl 2):61–68
  25. Wood AJ. Drug interactions in hypertension. Hypertension. 1988;11:II-1–II-3
  26. Herman RJ, Nakamura K, Wilkinson GR, et al. Induction of propranolol metabolism by rifampicin. Br J Clin Pharmacol. 1983;16:565–569
  27. Ishii Y, Nakamura K, Tsutsumi K, et al. Drug interaction between cimetidine and timolol ophthalmic solution: effect on heart rate and intraocular pressure in healthy Japanese volunteers. J Clin Pharmacol. 2000;40:193–199
  28. Edeki TI, He H, Wood AJ. Pharmacogenetic explanation for excessive beta-blockade following timolol eye drops: potential for oral-ophthalmic drug interaction. JAMA. 1995;274:1611–1613
  29. Fuhr U, Dummert AL. The fate of naringin in humans: a key to grapefruit juice-drug interactions. Clin Pharmacol Ther. 1995;58:364–373
  30. Abramowicz M. Grapefruit juice interactions with drugs. Med Lett Drugs Ther. 1995;37:63–64
  31. Nordine LH. Erythromycin-felodipine interaction [Letter]. Drug Intell Clin Pharm. 1991;25:1007–1008
  32. Jalava KM, Olkkola KT, Neuvonen PJ. Itraconazole greatly increases plasma concentrations and effects of felodipine. Clin Pharmacol Ther. 1997;61:410–415
  33. Smith SR, Kendall MJ, Lobo J, et al. Ranitidine and cimetidine drug interactions with single dose and steady-state nifedipine administration. Br J Clin Pharmacol. 1987;23:311–315
  34. Schwartz JB, Upton RA, Lin ET, et al. Effect of cimetidine or ranitidine administration on nifedipine pharmacokinetics and pharmacodynamics. Clin Pharmacol Ther. 1988;43:673–680
  35. Fromm MF, Busse D, Kroemer HK, et al. Differential induction of prehepatic and hepatic metabolism of verapamil by rifampin. Hepatology. 1996;24:796–801
  36. Chiu SH. The use of in vitro metabolism studies in the understanding of new drugs. J Pharmacol Toxicol Methods. 1993;29:77–83
  37. Jones DR, Gorski JC, Hamman MA, et al. Diltiazem inhibition of cytochrome P-450 3A activity is due to metabolite intermediate complex formation. J Pharmacol Exp Ther. 1999;290:1116–1125
  38. Jones TE, Morris RG, Mathew TH. Diltiazem-cyclosporin pharmacokinetic interaction: dose-response relationship. Br J Clin Pharmacol. 1997;44:499–504
  39. Campana C, Regazzi MB, Buggia I, et al. Clinically significant drug interactions with cyclosporin: an update. Clin Pharmacokinet. 1996;30:141–179
  40. Kantola T, Kivisto KT, Neuvonen PJ. Erythromycin and verapamil considerably increase serum simvastatin and simvastatin acid concentrations. Clin Pharmacol Ther. 1998;64:177–182
  41. Zocor prescribing information. http:// www.zocor.com/zocor/shared/documents/english/pi.pdfAccessed April 24, 2007
  42. Gruer PJ, Vega JM, Mercuri MF, et al. Concomitant use of cytochrome P450 3A4 inhibitors and simvastatin. Am J Cardiol. 1999;84:811–815
  43. Varhe A, Olkkola KT, Neuvonen PJ. Diltiazem enhances the effects of triazolam by inhibiting its metabolism. Clin Pharmacol Ther. 1996;59:369–375
  44. Ahonen J, Olkkola KT, Salmenpera M, et al. Effect of diltiazem on midazolam and alfentanil disposition in patients undergoing coronary artery bypass grafting. Anesthesiology. 1996;85:1246–1252
  45. Varis T, Backman JT, Kivisto KT, et al. Diltiazem and mibefradil increase the plasma concentrations and greatly enhance the adrenal-suppressant effect of oral methyl-prednisolone. Clin Pharmacol Ther. 2000;67:215–221
  46. Cook CS, Berry LM, Burton E. Prediction of in vivo drug interactions with eplerenone in man from in vitro metabolic inhibition data. Xenobiotica. 2004;34:215–228
  47. Bradford RH, Shear CL, Chremos AN, et al. Expanded clinical evaluation of lovastatin (EXCEL) study results. I. Efficacy in modifying plasma lipoproteins and adverse event profile in modifying plasma lipoproteins and adverse event profile in 8245 patients with moderate hypercholesterolemia. Arch Intern Med. 1991;151:43–49
  48. Illingworth DR, Tobert JA. A review of clinical trials comparing HMG-CoA reductase inhibitors. Clin Ther. 1994;16:366–385
  49. Ayanian JZ, Ruchs CS, Stone RM. Lovastatin and rhabdomyolysis. [Letter] Ann Intern Med. 1988;109:682–683
  50. Garnett WR. Interactions with hydroxymethylglutaryl-coenzyme A reductase inhibitor. Am J Health Syst Pharm. 1995;52:1639–1645
  51. Kunze KL, Wienkers LC, Thummel KE, et al. Warfarin-fluconazole (I. Inhibition of human cytochrome P450-dependent metabolism of warfarin by fluconazole: in vitro studies). Drug Metab Dispos. 1996;24:414–421
  52. Black DJ, Kunze KL, Wienkers LC, et al. Warfarin-fluconazole (II. A metabolically based drug interaction: in vitro studies). Drug Metab Dispos. 1996;24:422–428
  53. Gillum JG, Isreal DS, Polk RE. Pharmacokinetic drug interactions with antimicrobial agents. Clin Pharmacokinet. 1993;25:450–482
  54. Oberg KC. Delayed elevation of international normalized ratio with concurrent clarithromycin and warfarin therapy. Pharmacotherapy. 1998;18:386–391
  55. Gugler R, Jensen JC. Omeprazole inhibits oxidative drug metabolism (Studies with diazepam and phenytoin in vivo and 7-ethoxycoumarin in vitro). Gastroenterology. 1985;89:1235–1241
  56. Nemeroff CB, DeVane L, Pollock BG. Newer antidepressants and the cytochrome P450 system. Am J Psychiatry. 1996;153:311–320
  57. Brosen K. Are pharmacokinetic drug interactions with SSRIs an issue?. Int Clin Psychopharmacol. 1996;11(suppl 1):23–27
  58. Monahan BP, Ferguson CL, Killeavy ES, et al. Torsades de pointes occurring in association with terfenidine use. JAMA. 1990;264:2788–2790
  59. Hiemke C, Avi P, Jabarin M, et al. Fluvoxamine augmentation of olanzapine in chronic schizophrenia: pharmacokinetic interactions and clinical effects. J Clin Psychopharmacol. 2002;22:502–506
  60. Honig PK, Woosley RL, Zamani K, et al. Terfenadine-ketoconazole interaction pharmacokinetic and electrocardiographic consequences. JAMA. 1993;269:1513–1518
  61. Kivisto KT, Neuvonen PJ, Klotz U. Inhibition of terfenidine metabolism: pharmacokinetic and pharmacodynamic consequences. Clin Pharmacokinet. 1994;7:1–5
  62. Gillum JG, Isreal DS, Polk RE. Pharmacokinetic drug interactions with antimicrobial agents. Clin Pharmacokinet. 1993;25:450–482
  63. Oberg K, Bauman JL. QT interval prolongation and Torsades de pointes due to erythromycin lactobionate. Pharmacotherapy. 1995;15:687–692
  64. Honig PK, Woosley RL, Zamani K, et al. Changes in the pharmacokinetics and electrocardiographic pharmacodynamics of terfenidine with concomitant administration of erythromycin. Clin Pharmacol Ther. 1992;52:213–218
  65. Amsden GW. Macrolides versus azalides: a drug interaction update. Ann Pharmacother. 1995;29:906–917
  66. Inman W, Kubota K. Tachycardia during cisapride treatment. BMJ. 1992;305:748–749
  67. Arizona Center for Education and Research on Therapeutics. Drugs with risk of Torsades de Pointes. http://www.arizonacert.org/medical-pros/drug-lists/ drug-lists.htmAccessed March 25, 2007
  68. Ray WA, Murray KT, Meredith S, et al. Oral erythromycin and the risk of sudden death from cardiac causes. N Engl J Med. 2004;351:1089–1096
  69. Dorsey ST, Biblo LA. Prolonged QT interval and torsades de pointes caused by the combination of fluconazole and amitriptyline. Am J Emerg Med. 2000;18:227–229
  70. Hoover CA, Carmichael JK, Nolan PE, et al. Cardiac arrest associated with combination cisapride and itraconazole therapy. J Cardiovasc Pharmacol Ther. 1996;1:255–258
  71. Khazan M, Mathis AS. Probable case of torsades de pointes induced by fluconazole. Pharmacotherapy. 2002;22:1632–1637
  72. Pohjola-Sintonen S, Viitasalo M, Toivonen L, et al. Itraconazole prevents terfenadine metabolism and increases risk of torsades de pointes ventricular tachycardia. Eur J Clin Pharmacol. 1993;45:191–193
  73. Zimmermann M, Duruz H, Guinand O, et al. Torsades de pointes after treatment with terfenadine and ketoconazole. Eur Heart J. 1992;13:1002–1003
  74. Smith J, Safdar N, Knasinski V, et al. Voriconazole therapeutic drug monitoring. Antimicrob Agents Chemother. 2006;50:1570–1572
  75. Bran S, Murray W, Hirsch IB, et al. Long QT syndrome during high dose cisapride. Arch Intern Med. 1995;155:765–768
  76. Wysowski DK, Bacsanyi J. Cisapride and fatal arrhythmia. N Engl J Med. 1996;335:290–291
  77. Zechnich AD, Hedges JR, Eiselt-Proteau D, et al. Possible interactions with terfenidine or astemizole. West J Med. 1994;160:321–325
  78. Janssen Pharmaceutica stops marking Cisapride in the US. http://www.fda.gov/bbs/topics/ANSWERS/ANS01007.htmlAccessed March 29, 2007
  79. Flockhart DA. Drug interactions, cardiac toxicity, and terfenadine: from bench to clinic?. J Clin Psychopharmacol. 1996;16:101–103
  80. Merkel U, Sigusch H, Hoffman A. Grapefruit juice inhibits 7-hydroxylation of coumarin in healthy volunteers. Eur J Clin Pharmacol. 1994;46:175–177
  81. Pearson EC, Woosley RL. QT prolongation and torsades de pointes among methadone users: reports to the FDA spontaneous reporting system. Pharmacoepidemiol Drug Saf. 2005;14:747–753
  82. Krantz MJ, Lewkowiez L, Hays H, et al. Torsade de pointes associated with very high dose methadone. Ann Intern Med. 2002;137:501–504
  83. Justo D, Gal-Oz A, Paran Y, et al. Methadone associated Torsades de Pointes (polymorphic ventricular tachycardia) in opioid-dependent patients. Addiction. 2006;101:1333–1338
  84. Opie LH. Cardiovascular drug interactions. In:  Frishman WH,  Sonnenblick EH,  Sica DA editor. Cardiovascular pharmacotherapeutics. ed 2. McGraw Hill: New York; 2003;p. 875–891

 Reprinted with permission from Cheng JWM, Frishman WH, Aronow WS. Updates on Cytochrome P450-Mediated Cardiovascular Drug Interactions. Am J Ther 2009;16:155-63.

PII: S0011-5029(09)00159-X

doi: 10.1016/j.disamonth.2009.12.011

Disease-A-Month
Volume 56, Issue 3 , Pages 163-179 , March 2010

Article Tools