Advertisement

Drug Interactions with Cisapride

Clinical Implications

Abstract

Cisapride, a prokinetic agent, has been used for the treatment of a number of gastrointestinal disorders, particularly gastro-oesophageal reflux disease in adults and children. Since 1993, 341 cases of ventricular arrhythmias, including 80 deaths, have been reported to the US Food and Drug Administration. Marketing of the drug has now been discontinued in the US; however, it is still available under a limited-access protocol. Knowledge of the risk factors for cisapride-associated arrhythmias will be essential for its continued use in those patients who meet the eligibility criteria. This review summarises the published literature on the pharmacokinetic and pharmacodynamic interactions of cisapride with concomitantly administered drugs, providing clinicians with practical recommendations for avoiding these potentially fatal events.

Pharmacokinetic interactions with cisapride involve inhibition of cytochrome P450 (CYP) 3A4, the primary mode of elimination of cisapride, thereby increasing plasma concentrations of the drug. The macrolide antibacterials clarithromycin, erythromycin and troleandomycin are inhibitors of CYP3A4 and should not be used in conjunction with cisapride. Azithromycin is an alternative. Similarly, azole antifungal agents such as fluconazole, itraconazole and ketoconazole are CYP3A4 inhibitors and their concomitant use with cisapride should be avoided.

Of the antidepressants nefazodone and fluvoxamine should be avoided with cisapride. Data with fluoxetine is controversial, we favour the avoidance of its use. Citalopram, paroxetine and sertraline are alternatives.

The HIV protease inhibitors amprenavir, indinavir, nelfinavir, ritonavir and saquinavir inhibit CYP3A4. Clinical experience with cisapride is lacking but avoidance with all protease inhibitors is recommended, although saquinavir is thought to have clinically insignificant effects on CYP3A4. Delavirdine is also a CYP3A4 inhibitor and should be avoided with cisapride.

We also recommend avoiding coadministration of cisapride with amiodarone, cimetidine (alternatives are famotidine, nizatidine, ranitidine or one of the proton pump inhibitors), diltiazem and verapamil (the dihydropyridine calcium antagonists are alternatives), grapefruit juice, isoniazid, metronidazole, quinine, quinupristin/dalfopristin and zileuton (montelukast is an alternative).

Pharmacodynamic interactions with cisapride involve drugs that have the potential to have additive effects on the QT interval. We do not recommend use of cisapride with class Ia and III antiarrhythmic drugs or with adenosine, bepridil, cyclobenzaprine, droperidol, haloperidol, nifedipine (immediate release), phenothiazine antipsychotics, tricyclic and tetracyclic antidepressants or vasopressin. Vigilance is advised if anthracyclines, cotrimoxazole (trimethoprim-sulfamethoxazole), enflurane, halothane, isoflurane, pentamidine or probucol are used with cisapride. In addition, uncorrected electrolyte disturbances induced by diuretics may increase the risk of torsade de pointes. Patients receiving cisapride should be promptly treated for electrolyte disturbances.

This is a preview of subscription content, log in to check access.

Table I
Table II

References

  1. 1.

    Wiseman RL, Faulds D. Cisapride: an updated review of its pharmacology and therapeutic efficacy as a prokinetic agent in gastrointestinal motility disorders. Drugs 1994; 47 (1): 116–52.

  2. 2.

    McCallum RW, Prakash C, Campoli-Richards DM, et al. Cisapride: a preliminary review of its pharmacodynamic and pharmacokinetic properties, and therapeutic use as a prokinetic agent in gastrointestinal motility disorders. Drugs 1988; 36: 652–81.

  3. 3.

    Reynolds JC. Influence of pathophysiology, severity, and cost on the medical management of gastroesophageal reflux disease. Am J Health-Syst Pharm 1996; 53 Suppl. 3: S5–12.

  4. 4.

    Briejer MR, Akkermans LMA, Schuurres JAJ. Gastrointestinal prokinetic benzamides: the pharmacology underlying stimulation of motility. Pharmacol Rev 1995; 47: 631–51.

  5. 5.

    Vandenpias Y, Belli D, Benatar A, et al. The role of cisapride in the treatment of pediatric gastroesophagel reflux. J Pediatr Gastroenterol Nutr 1999; 28: 518–28.

  6. 6.

    DeVault KR, Castell D. Guidelines for the diagnosis and treatment of gastroesophageal reflux disease. Arch Intern Med 1995; 155: 2165–73.

  7. 7.

    Janssen Pharmaceutica Inc. Limited-access program announced in United States to ensure appropriate use of Propulsid® (cisapride): product no longer to be promoted in United States [media release, 2 pages]. 2000 Mar 23. Available from: URL: http://www.us.janssen.com/news/cur-rent/propuls lim acc.html [accessed 2000 May 29].

  8. 8.

    Food and Drug Administration. Janssen Pharmaceutica stops marketing cisapride in the US [talk paper, 1 page]. 2000 Mar 23. Available from: http://www.fda.gov/bbs/topics/AN-SWERS/ANS01007.html [accessed 2000 May 30].

  9. 9.

    Meuldermans W, Van Peer A, Hendricks J, et al. Excretion and biotransformation of cisapride in dogs and humans after oral administration. Drug Metab Dispos 1988; 16: 403–9.

  10. 10.

    Corinaldesi R, Stanghellini V, Tosetti C, et al. The effect of different dosage schedules of cisapride on gastric emptying in idiopathic gastroparesis. Eur J Clin Pharmacol 1993; 44: 429–32.

  11. 11.

    Mohammad S, Zhou Z, Gonng Q, et al. Blockage of the HERG human cardiac K+ channel by the gastrointestinal prokinetic agent cisapride. Am J Physiol 1997; 273: 2534–8.

  12. 12.

    Michalets EL. Update: clinically significant cytochrome P450 drug interactions. Pharmacotherapy 1998; 18 (1): 84–112.

  13. 13.

    Slaughter RL, Edwards DJ. Recent advances: the cytochrome P450 enzymes. Ann Pharmacother 1995; 29: 619–24.

  14. 14.

    Rendie S, Di Carlo F. Human cytochrome P450 enzymes: a status report summarizing their reactions, substrates, inducers and inhibitors. Drug Metab Rev 1997; 29: 413–580.

  15. 15.

    Brosen K. Recent developments in hepatic drug oxidation: implications for clinical pharmacokinetics. Clin Pharmacokinet 1990; 18: 220–39.

  16. 16.

    Guengerich FP. Polymorphism of cytochrome P450 in humans. Trends Pharmacol Sci 1989; 10 (3): 107–9.

  17. 17.

    Faber TS, Zehender M, Just H. Drug-induced torsade de pointes: incidence, management and prevention. Drug Saf 1994; 11 (6): 463–76.

  18. 18.

    Lazzara R. Antiarrhythmic drugs and torsade de points. Eur Heart J 1993; 14 Suppl. H: 88–93.

  19. 19.

    Lehmann MH, Hardy S, Archibald D, et al. Sex differences in risk of torsade de pointes with d,l-sotalol. Circulation 1996; 94: 2535–41.

  20. 20.

    Keren A, Tzivoni D, Gavish D. Etiology, warning signs and therapy of torsade de pointes: a study of 10 patients. Circulation 1981; 64: 1167–74.

  21. 21.

    Roden DM. Arrhythmogenic potential of class HI antiarrhythmic agents: comparison with Class I agents. In: Singh BN, editor. Control of cardiac arrhythmias by lengthening repolarization. Mt Kisco: Futura Publishing Co., 1988: 559–77.

  22. 22.

    Kay GN, Plumb VJ, Arciniegas JG, et al. Torsade de pointes: the long-short initiating sequence and clinical features: observations in 32 patients. J Am Coll Cardiol 1983; 2: 806–17.

  23. 23.

    Bateman DN. The action of cisapride on gastric emptying and the pharmacodynamics and pharmacokinetics of oral diazepam. Eur J Clin Pharmacol 1986; 30: 205–8.

  24. 24.

    Francois I, Nutte ND. Nonulcer dyspepsia: effect of the gastrointestinal prokinetic drug cisapride. Curr Ther Res 1987; 41 (6): 891–8.

  25. 25.

    Olsson S, Edwards IR. Tachycardia during cisapride treatment. BMJ 1992; 305: 748–9.

  26. 26.

    Bedu A, Lupoglazoff JM, Faure C. Cisapride high dosage and long QT interval [letter]. J Pediatr 1997; 130: 164.

  27. 27.

    Gray VS. Syncopal episodes associated with cisapride and concurrent drugs. Ann Pharmacother 1998; 32: 648–51.

  28. 28.

    Sakkarje MA. Torsades de pointes in two chronic renal failure patients treated with cisapride and clarithromycin. Am J Kidney Dis 1997; 30 (3): 437–9.

  29. 29.

    Hill, SL, Evangelista JK, Pizzi AM, et al. Proarrhythmias associated with cisapride in children. Pediatrics 1998; 101 (6): 1053–6.

  30. 30.

    Bran S, Murray WA, Hirsch IB, et al. Long QT syndrome during high-dose cisapride. Arch Intern Med 1995; 155: 756–8.

  31. 31.

    Thomas AR, Chan LN, Bauman JL, et al. Prolongation of the QT interval related to cisapride-diltiazem interaction. Pharmacotherapy 1998; 18 (2): 381–5.

  32. 32.

    Khongphatthanayothin A, Lane J, Thomas D, et al. Effects of cisapride on QT interval in children. J Pediatr 1998; 133: 51–6.

  33. 33.

    Lewin MB, Bryant RM, Fenrich AL, et al. Cisapride-induced long QT interval. J Pediatr 1996; 128: 279–81.

  34. 34.

    Pettignano R, Chambliss CR, Darsey E, et al. Cisapride-induced dysrhythmia in a pediatric patient receiving extracorporeal life support. Crit Care Med 1996; 24: 1268–71.

  35. 35.

    Valdes L, Champel V, Olivier C, et al. Syncope with long QT interval in a 39 day-old infant treated with cisapride [in French]. Arch Pediatr 1997; 4 (6): 535–7.

  36. 36.

    Vitola J, Vukanovic J, Roden DM. Cisapride-induced torsades de pointes. J Cardiovasc Electrophysiol 1998; 9: 1109–13.

  37. 37.

    Piquette RK. Torsade de pointes induced by cisapride/clarithromycin interaction. Ann Pharmacotherapy 1999; 33: 22–6.

  38. 38.

    van Haarst AD, van’t Klooster GAE, van Gerven KMA, et al. The influence of cisapride and clarithromycin on QT intervals in healthy volunteers. Clin Pharmacol Ther 1998; 64: 542–6.

  39. 39.

    Jenkins IR, Gibson J. Cisapride, erythromycin and arrhythmia. Anaesth Intens Care 1996; 24 (6): 728.

  40. 40.

    Bernardini S, Semama DS, Heut F, et al. Effects of cisapride on QTc interval in neonates. Arch Dis Child Fetal Neonatal Ed 1997; 77 (3): F241–3.

  41. 41.

    Ahmad SR, Wolfe SM. Cisapride and torsades de pointes [letter]. Lancet 1995; 345: 508.

  42. 42.

    Wysowski DK, Bacsanyi J. Cisapride and fatal arrhythmia. N Engl J Med 1996; 335: 290–1.

  43. 43.

    Tan HL, Hou CJY, Lauer MR, et al. Electrophysiologic mechanisms of the long QT interval syndromes and torsade de points. Ann Intern Med 1995; 122: 701–14.

  44. 44.

    Inman W, Kubota K. Tachycardia during cisapride treatment [abstract]. BMJ 1992; 305: 1019.

  45. 45.

    Tack JT, Janssens F. A risk-benefit assessment of cisapride in the treatment of gastrointestinal disorders. Drug Saf 1995; 12 (6): 384–92.

  46. 46.

    Wager E, Tooley PJH, Pearce GL, et al. A comparison of two cohort studies evaluating the safety of cisapride: prescription-event monitoring and a large phase IV study. Eur J Clin Pharmacol 1997; 52: 87–94.

  47. 47.

    Janssen Pharmaceutica, Inc. Propulsid (cisapride) package insert. Titusville (NJ): Janssen Pharmaceutica, Inc., 2000.

  48. 48.

    Humphrey PPA, Bunce KT. Tachycardia during cisapride treatment [letter]. BMJ 1992; 304: 1019.

  49. 49.

    Drolet B, Khalifa M, Daleau P, et al. Block of the rapid component of the delayed rectifier potassium current by the prokinetic agent cisapride underlies drug-related lengthening of the QT interval. Circulation 1998; 97: 204–10.

  50. 50.

    Carlsson L, Amos G, Andersson B, et al. Electrophysiological characterization of the prokinetic agents cisapride and mosapride in vivo and in vitro: implications for proarrhythmic potential? J Pharmacol Exp Ther 1997; 282: 220–7.

  51. 51.

    Puisieux FL, Adamantidis MM, Dumotier BM, et al. Cisaprideinduced prolongation of cardiac action potential and early afterdepolarizations in rabbit Purkinje fibres. Br J Pharmacol 1996; 117: 1377–9.

  52. 52.

    Periti P, Mazzei T, Mini E, et al. Pharmacokinetic interactions of macrolides. Clin Pharmacokinet 1992; 23: 106–31.

  53. 53.

    Pichard L, Fabre I, Fabre G, et al. Cyclosporin A drug interactions. Screening for inducers and inhibitors of cytochrome P-450 (cyclosporin A oxidase) in primary cultures of human hepatocytes and in liver microsomes. Drug Metab Dispos 1990; 18 (5): 595–606.

  54. 54.

    Jurima-Romet M, Crawford K, Cyr T, et al. Terfenadine metabolism in human liver. In vitro inhibition by macrolide antibiotics and azole antifungals. Drug Metab Dispos 1994; 22 (6): 849–57.

  55. 55.

    Gascon MP, Dayer P. Comparative effects of macrolide antibiotics on liver monoxygenases. Clin Pharmacol Ther 1991; 49: 158.

  56. 56.

    Aoki, FY, Yatscoff R, Jeffrey J, et al. Effects of erythromycin on cyclosporin A kinetics in renal transplant patients [abstract]. Clin Pharmacol Ther 1987; 41: 221.

  57. 57.

    Jensen CWB, Flechner SM, Van Buren CT, et al. Exacerbation of cyclosporin toxicity by concomitant administration of erythromycin. Transplantation 1987; 43: 263–70.

  58. 58.

    Honig P, Wortham DC, Zamani K, et al. Effect of erythromycin, clarithromycin and azithromycin on the pharmacokinetic s of terfenadine [abstract]. Clin Pharmacol Ther 1993; 53: 161.

  59. 59.

    Phillips JP, Antal EJ, Smith RB. A pharmacokinetic interaction between erythromycin and triazolam. J Clin Psychopharmacol 1986; 6: 297–9.

  60. 60.

    Warot D, Bergougnan L, Lamiable D, et al. Troleandomycintriazolam interaction in healthy volunteers: pharmacokinetic and psychometric evaluation. Eur J Clin Pharmacol 1987; 32: 389–93.

  61. 61.

    Gillum JG, Israel DS, Polk R. Pharmacokinetic drug interactions with antimicrobial agents. Clin Pharmacokinet 1993; 25 (6): 450–82.

  62. 62.

    Harris S, Hilligoss DM, Colangelo PM, et al. Azithromycin and terfenadine: lack of drug interaction. Clin Pharmacol Ther 1995; 58: 310–15.

  63. 63.

    Hardman JG, Limbird LE, Molinoff PB, et al., editors. Goodman and Gilman’s the pharmacological basis of therapeutics. 9th ed. New York: McGraw-Hill, 1996.

  64. 64.

    Oberg K, Bauman JL. QT interval prolongation and torsades de pointes due to erythromycin lactobionate. Pharmacotherapy 1995; 15: 687–92.

  65. 65.

    Lai D, Brown G, MacDonald I. Clarithromycin-induced prolonged QT syndrome. Can J Hosp Pharm 1996; 49: 33–5.

  66. 66.

    Amsden GW. Macrolides versus azalides: a drug interaction update. Ann Pharmacother 1995; 29: 906–17.

  67. 67.

    Schmeling WT, Warltier DC, McDonald DJ, et al. Prolongation of the QT interval by enflurane, isoflurane, and halothane in humans. Anesth Anal 1991; 72: 137–44.

  68. 68.

    Stratmann HG, Kennedy HL. Torsade de pointes associated with drugs and toxins: recognition and management. Am Heart J 1987; 113 (6): 1470–82.

  69. 69.

    Roden DM, Thompson KA, Hoffman BF, et al. Clinical features and basic mechanisms of quinidine-induced arrhythmias. J Am Coll Cardiol 1986; 8: 73A–78A.

  70. 70.

    Bauman JL, Bauernfeind RA, Hoff JV, et al. Torsade de pointes due to quinidine: observations in 31 patients. Am Heart J 1984; 107: 425–30.

  71. 71.

    Strasberg B, Schlarvosky S, Erdberg A, et al. Procainamide-in-duced polymorphous ventricular tachycardia. Am J Cardiol 1981; 47: 1309–14.

  72. 72.

    Riccioni N, Castiglioni M, Bartolomei C. Disopyramide-in-duced QT prolongation and ventricular tachy arrhythmias. Am Heart J 1983; 105 (5): 870–1.

  73. 73.

    Selzer A, Wray AH. Quinidine syncope. Paroxysmal ventricular fibrillation occurring during treatment of chronic atrial arrhythmias. Circulation 1964; 30: 17–26.

  74. 74.

    Olshanksy B, Martins J, Hunt S. N-acetyl procainamide causing torsade de pointes. Am J Cardiol 1982; 50: 1439–40.

  75. 75.

    Herre JM, Thompson JA. Polymorphic ventricular tachycardia and ventricular fibrillation due to N-acetyl procainamide. Am J Cardiol 1985; 55: 227–8.

  76. 76.

    Stratmann HG, Walter KE, Kennedy HL. Torsade de pointes associated with elevated N-acetylprocainamide levels. Am Heart J 1985; 109:375–7.

  77. 77.

    Lo KS, Gantz KB, Stetson PL, et al. Disopyramide-induced ventricular tachycardia. Arch Intern Med 1980; 140: 413–4.

  78. 78.

    Tzivoni D, Keren A, Stern S, et al. Disopyramide-induced torsade de pointes. Arch Intern Med 1981; 141: 946–7.

  79. 79.

    Neuvovnen PJ, Elonen E, Tanskanen A, et al Sotalol and prolonged Q-Tc interval [letter]. Lancet 1981; II: 426.

  80. 80.

    Hohnloser SH, Arendts W, Quart B. Incidence, type and dose-dependence of proarrhythmic events during sotalol therapy in patients treated for sustained VT/VF [abstract]. Pacing Clin Electrophysiol 1992; 15: 551.

  81. 81.

    Kuck KH, Roewer N, Bleifeld W. Sotalol-induced torsade de pointes. Am Heart J 1984; 107: 179–80.

  82. 82.

    McKibbin JK, Pocock WA, Barlow JB, et al. Sotalol, hypokalemia, syncope, and torsade de pointes. Br Heart J 1984; 51: 157–62.

  83. 83.

    Howard PA. Ibutilide: an antiarrhythmic agent for the treatment of atrial fibrillation or flutter. Ann Pharmacother 1999; 33: 38–47.

  84. 84.

    Kowey PR, Vanderlugt JT. Safety and risk/benefit analysis of ibutilide for acute conversion of atrial fibrillation/flutter. Am J Cardiol 1996; 78(8a Suppl.): 46–52.

  85. 85.

    Laganiere S, Davies RF, Carignan G, et al. Pharmacokinetic and pharmacodynamic interactions between diltiazem and quinidine. Clin Pharmacol Ther 1996; 60: 255–64.

  86. 86.

    Levy RH. Cytochrome P450 isoenzyme and antiepileptic drug interactions. Epilepsia 1995; 36 Suppl. 5: S8–13.

  87. 87.

    Heimark LD, Wienkers L, Kunze K, et al. The mechanism of the interaction between amiodarone and warfarin in humans. Clin Pharmacol Ther 1992; 51: 398–407.

  88. 88.

    Walker DK, Alabaster CT, Congrave GS, et al. Significance of metabolism in the disposition and action of the antidysrhythmic drug, dofetilide: in vitro studies and correlation with in vivo data. Drug Metab Dispos 1996; 24 (4): 447–55.

  89. 89.

    Funck-Brentano C, Becquemont L, Kroemer HK, et al. Variable disposition kinetics and electrocardiographic effects of flecainide during repeated dosing in humans: contribution of genetic factors, dose-dependent clearance, and interaction with amiodarone. Clin Pharmacol Ther 1994; 55 (3): 256–69.

  90. 90.

    Duenas-Laita A, Bary MG, MacMathuna P, et al. Effects of chronic treatment with amiodarone on hepatic demethylation and cytochrome P450. J Pharm Pharmacol 1987; 39 (9): 757–9.

  91. 91.

    Bhandari AK, Quock C, Sung RJ. Polymorphous ventricular tachycardia associated with a marked prolongation of the Q-T interval induced by amiodarone. Pacing Clin Electrophysiol 1984; 7: 341–5.

  92. 92.

    Mattioni TA, Zheutlin TA, Sarmiento JJ, et al. Amiodarone in patients with previous drug-mediated torsade de pointes. Ann Intern Med 1989; 111 (7): 574–80.

  93. 93.

    Lazzara R. Amiodarone and torsade de pointes. Ann Intern Med 1989; 111 (7): 549–50.

  94. 94.

    Hii JTY, Wyse DG, Gillis AM, et al. Precordial QT interval dispersion as a marker of torsade de pointes. Disparate effects of class Ia antiarrhythmic drugs and amiodarone. Circulation 1992; 86; 1376–82.

  95. 95.

    Sclarvosky S, Lewin RF, Kracoff O, et al. Amiodarone-induced polymorphous ventricular tachycardia. Am Heart J 1983; 105 (1): 6–12.

  96. 96.

    Wesley RC, Turnquest P. Torsade de pointe after intravenous adenosine in the presence of prolonged QT syndrome. Am Heart J 1992; 123 (3): 794–6.

  97. 97.

    Rubart M, Pressler ML, Pride HP, et al. Electrophysiological mechanisms in a canine model of erythromycin-associated long QT syndrome. Circulation 1993; 88: 1832–44.

  98. 98.

    Freedman RA, Anderson KP, Green LS, et al. Effect of erythromycin on ventricular arrhythmias an ventricular repolarization in idiopathic long QT syndrome. Am J Cardiol 1987; 59: 168–9.

  99. 99.

    Gitler B, Berger LS, Buffa SD. Torsade de pointes induced by erythromycin. Chest 1994; 105: 368–72.

  100. 100.

    Nattel S, Ranger S, Talajic M, et al. Erythromycin-induced long QT syndrome: concordance with quinidine and underlying cellular electrophysiologic mechanism. Am J Med 1990; 89: 235–8.

  101. 101.

    Maurice M, Pichard L, Daujat M, et al. Effects of imidazole derivatives on cytochrome P450 from human hepatocytes in primary culture. FASEB J 1992; 6 (2): 752–8.

  102. 102.

    Spina E, Pisani F, Perucca E. Clinically significant pharmacokinetic drug interactions with carbamazepine: an update. Clin Pharmacokinet 1996; 31 (3): 198–214.

  103. 103.

    Hismanal. FDA Med Bull 1996; 269 (2): 4.

  104. 104.

    Mirghani RA, Hellgren R, Westerberg PA, et al. The roles of cytochrome P450 3A4 and 1A2 in the 3-hydroxylation of quinine in vivo. Clin Pharmacol Ther 1999; 66: 454–60.

  105. 105.

    Cantelli-Forte G, Paolini M, et al. Effects of metronidazole, asanidazole and azathioprine on cytochrome P450 and various monoxygenase activities in hepatic microsome from control and induced mice. Arch Toxicol 1987; 11 Suppl.: 264–9.

  106. 106.

    Cooke CE, Sklar GE, Nappi JM. Possible pharmacokinetic interaction with quinidine: ciprofloxacin or metronidazole? Ann Pharmacother 1996; 30 (4): 365–6.

  107. 107.

    Spinier SA, Cheng JWM, Kindawall KE, et al. Possible inhibition of hepatic metabolism of quinidine by erythromycin. Clin Pharmacol Ther 1995; 57: 89–95.

  108. 108.

    Borcherding SM, Stevens R, Nicholas RA. Quinolones: a practical review of clinical uses, dosing consideration, and drug interactions. J Fam Pract 1996; 42: 69–78.

  109. 109.

    Rubinstein E, Prokocimer P, Talbot GH. Safety and tolerability of quinupristin/dalfapristin: administration guidelines. J Antimicrob Chemother 1999; 44 Suppl. A: 37–46.

  110. 110.

    Ballow C, Chevalier P, Forrest A, et al. Randomized, crossover, phase I study of the interactions between quinupristin/ dalfopristin (Q/D), (RP 59500, Synercid) at steady state and cyclosporine in healthy volunteers [abstract 2313:43]. Twentieth International Congress of Chemotherapy; 1997 Jun 28-Jul 3; Sydney.

  111. 111.

    Lopez JA, Harold JG, Rosenthal MC, et al. QT prolongation and torsade de pontes after administration of trimethoprim-sulfamethoxazole. Am J Cardiol 1987; 376–7.

  112. 112.

    Von Moltke LL, Greenblatt DJ, Cotreau-Bibbo MM, et al. Inhibitors of alprazolam metabolism in vitro: effect of serotonin-reuptake-inhibitor antidepressants, ketoconazole and quinidine. Br J Clin Pharmacol 1994; 38: 23–31.

  113. 113.

    Nemeroff CB, DeVane CL, Pollock BG. Newer antidepressants and the cytochrome P450 system. Am J Psychiatry 1996; 153: 311–20.

  114. 114.

    Mitchell PB. Drug interactions of clinical significance with selective serotonin reuptake inhibitors. Drug Saf 1997; 17 (6): 390–406.

  115. 115.

    DeVane CL. Differential pharmacology of newer antidepressants. J Clin Psychiatry 1998; 59 Suppl. 20: 85–93.

  116. 116.

    Richelson E. Pharmacokinetic drug interactions of new antidepressants: a review of the effects on the metabolism of other drugs. Mayo Clin Proc 1997; 72: 835–47.

  117. 117.

    Fleishaker JC, Hulst LK. A pharmacokinetic and pharmacodynamic evaluation of the combined administration of alprazolam and fluvoxamine. Eur J Pharmacol 1994; 46: 35–9.

  118. 118.

    Bedford TA, Rowbotham DJ. Cisapride: drug interactions of clinical significance. Drug Saf 1996; 15 (3): 167–75.

  119. 119.

    Fritz J, Unsorg B, Lanczik M. Interaction between carbamazepine and fluvoxamine. Acta Psychiatr Scand 1991; 84: 583–4.

  120. 120.

    Martin DE, Zussman B, Everitt DE, et al. No effect of paroxetine on the cardiac safety and pharmacokinetics of terfenadine [abstract]. J Clin Pharmacol 1996; 36: 849.

  121. 121.

    Martin DE, Zussman BD, Everitt DE, et al. Paroxetine does not affect the cardiac safety and pharmacokinetics of terfenadine in healthy adult men. J Clin Psychopharmacol 1997; 17 (6): 451–9.

  122. 122.

    Rapeport WG, Williams SA, Muirhead DC, et al. Absence of a sertraline-mediated effect on the pharmacokinetics and pharmacodynamics of carbamazepine. J Clin Psychiatry 1996; 57 Suppl. 1:20–3.

  123. 123.

    Lasher TA, Fleishaker JC, Steenwyk RC, et al. Pharmacokinetic pharmacodynamic evaluation of the combined administration of alprazolam and fluoxetine. Psychopharmacology 1991; 104: 323–7.

  124. 124.

    Greenblatt DJ, Preskorn SH, Cotreau MM, et al. Fluoxetine impairs clearance of alprazolam but not of clonazepam. Clin Pharmacol Ther 1992; 52: 479–86.

  125. 125.

    Swims MR Potential terfenadine-fluoxetine interaction. Ann Pharmacother 1993; 27: 1404–5.

  126. 126.

    Marchiando RJ, Cook MD, Jue SG. Probable terfenadine-fluoxetine-associated cardiac toxicity. Ann Pharmacother 1995; 27: 937–8.

  127. 127.

    Wright CE, Lasher-Sisson TA, Steenwyk RC, et al. A pharmacokinetic evaluation of the combined administration of triazolam and fluoxetine. Pharmacotherapy 1992; 12: 103–6.

  128. 128.

    Strouse TB, Fairbanks LA, Skotzko CE, et al. Fluoxetine and cyclosporine in organ transplantation. Psychosomatics 1996; 37: 23–30.

  129. 129.

    Caccia S. Metabolism of the newer antidepressants: an overview of the pharmacological and pharmacokinetic implications. Clin Pharmacokinet 1998; 34 (4): 281–302.

  130. 130.

    Sommi R, Crismon L, Bowden C. Fluoxetine: a serotonin-specific second generation antidepressant. Pharmacotherapy 1987; 7: 1–15.

  131. 131.

    Bergstrom RF, Goldberg MJ, Cerimele BJ, et al. Assessment of the potential for a pharmacokinetic interaction between fluoxetine and terfenadine. Clin Pharmacol Ther 1997; 62: 643–51.

  132. 132.

    Zhao Q, Zheng M, Wojcik MA, et al. The effect of multiple doses of fluoxetine on the pharmacokinetics and cardiovascular safety of cisapride in healthy volunteers [abstract]. American College of Clinical Pharmacy Annual Meeting; 1999 Oct 24–27; Kansas City, MO.

  133. 133.

    Eli Lilly and Company. Prozac (fluoxetine) package insert. Indianapolis (IN): Eli Lilly and Co., 1997.

  134. 134.

    Ereshefsky L. Drug-drug interactions involving antidepressants: focus on venlafaxine. J Clin Psychopharmacol 1996; 16 Suppl. 2: 37S–50S.

  135. 135.

    Russell JL. Relatively low doses of cisapride in the treatment of nausea in patients treated with venlafaxine for treatment-refractory depression. J Clin Psychopharmacol 1996; 16 (1): 35–7.

  136. 136.

    Kasper S, Praschak-Rieder N, Tauscher J, et al. A risk-benefit assessment of mirtazapine in the treatment of depression. Drug Saf 1997; 17 (4): 251–64.

  137. 137.

    Owen RJ, Nemeroff CB. New antidepressants and the cytochrome P450 system: focus on venlafaxine, nefazodone, and mirtazapine. Depress Anxiety 1998; 7 Suppl. 1: 24–32.

  138. 138.

    Barbhaiya RH, Shukla UA, Kroboth PD, et al. Coadministration of nefazodone and benzodiazepines: I. Pharmacodynamic assessment II. A pharmacokinetic interaction study with triazolam. J Clin Psychopharmacol 1995; 15: 306–26.

  139. 139.

    Solvay Pharmaceuticals. Luvox (fluvoxamine) package insert. Marietta (GA): Solvay Pharmaceuticals, 1998.

  140. 140.

    Bristol Myers Squibb, Co. Serzone (nefazodone) package insert. Princeton (NJ): Bristol Myers Squibb, Co., 1998.

  141. 141.

    Schmider J, Greenblatt DJ, von Moltke LL, et al. Inhibition of cytochrome P450 by nefazodone in vitro: studies of dextromethorphan O- and N-demethylation. Br J Clin Pharmacol 1996; 41 (4): 339–43.

  142. 142.

    Fowler HO, McCall D, Chou TC, et al. Electrocardiographic changes and cardiac arrhythmias in patients receiving psychotropic drugs. Am J Cardiol 1976; 37: 223–30.

  143. 143.

    Marshall JB, Forker AD. Cardiovascular effects of tricyclic antidepressant drugs: therapeutic usage, overdose, and management of complications. Am Heart J 1982; 103 (3): 401–14.

  144. 144.

    Bigger JT, Giardina EGV, Perel JM, et al. Cardiac antiarrhythmic effect of imipramine hydrochloride. N Engl J Med 1977; 296 (4): 206–9.

  145. 145.

    Giardina EGV, Bigger J, Glassman AH, et al. The electrocardiographic and antiarrhythmic effects of imipramine hydrochloride at therapeutic plasma concentrations. Circulation 1979; 60(5): 1045–52.

  146. 146.

    Herrmann HC, Kaplan LM, Bierer BE. Q-T prolongation and torsade de pointes ventricular tachycardia produced by the tetracyclic antidepressant agent maprotiline. Am J Cardiol 1983; 51: 904–6.

  147. 147.

    Burckhardt D, Raeder E, Muller V, et al. Cardiovascular effects of tricyclic and tetracyclic antidepressants. JAMA 1978; 239: 213–6.

  148. 148.

    Back DJ, Tija JE Comparative effects of the antimycotic drugs ketoconazole, fluconazole, itraconazole and terbinafine on the metabolism of cyclosporin by human liver microsomes. Br J Clin Pharmacol 1991; 32 (5): 624–6.

  149. 149.

    Von Moltke LL, Greenblatt DJ, Schmider J, et al. Midazolam hydroxylation by human liver microsomes in vitro: inhibition by fluoxetine, norfluoxetine, and by azole antifungal agents. J Clin Pharmacol 1996; 36 (9): 783–91.

  150. 150.

    Janssen propulsid concomitant use with nizoral contraindicated. FDC Report — Pink Sheet 1995 Mar 13: 14.

  151. 151.

    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 (2): 191–3.

  152. 152.

    Honig PK, Wortham DC, Zamani K, et al. Terfenadine-ketoconazole interactions. Pharmacokinetic and electrocardiographic consequences. JAMA 1993; 269 (12): 1513–8.

  153. 153.

    Monohan BP, Ferguson CL, Killeavy ES, et al. Torsades de pointes occurring in association with terfenadine use. JAMA 1990; 264: 2788–90.

  154. 154.

    Greenblatt DJ, von Moltke LL, Harmatz JS, et al. Interaction of triazolam and ketoconazole [letter]. Lancet 1995; 345: 191.

  155. 155.

    Jalava K-M, Olkkola KT, Neuvomen PJ. Itraconazole greatly increases plasma concentrations and effects of felodipine. Clin Pharmacol Ther 1997; 61: 410–5.

  156. 156.

    Honig PK, Worham DC, Zamani K, et al. The effect of fluconazole on the steady-state pharmacokinetics and electrocardiographic pharmacodynamics of terfenadine in humans. Clin Pharmacol Ther 1993; 53 (6): 630–6.

  157. 157.

    Varhe A, Olkkola KT, Neuvonen PJ. Effect of fluconazole dose on the extent of fluconazole-triazolam interaction. Br J Clin Pharmacol 1996; 42 (4): 465–70.

  158. 158.

    Varhe A, Olkkola KT, Neuvonen PJ. Fluconazole, but not terbinafine, enhances the effects of triazolam by inhibiting its metabolism. Br J Clin Pharmacol 1996; 41 (4): 319–23.

  159. 159.

    Neuvonen PJ, Varhe A, Olkkola T. The effect of ingestion time interval on the interaction between itraconazole and triazolam. Clin Pharmacol Ther 1996; 60: 326–31.

  160. 160.

    Zeneca Pharmaceuticals. Accolate (zafirlukast) package insert. Wilmington (DE): Zeneca Pharmaceuticals, 1998.

  161. 161.

    NHLBI, National Asthma Education and Prevention Program, Expert Panel Report 2. Guidelines for the diagnosis and management of asthma. NIH Publication No. 97–4051. Bethesda (MD): US Department of Health and Human Services, 1997.

  162. 162.

    Granneman GR, Braechman RA, Cavanaugh JH, et al. Effect of zileuton on theophylline pharmacokinetics. Clin Pharmacokinet 1995; 29 Suppl. 2: 77–83.

  163. 163.

    Lau R. Drug interactions with zileuton. Lancet 1997; 349: 1479–80.

  164. 164.

    Marion Merrell Dow. Seldane (terfenadine) package insert. Kansas City (MO): Marion Merrell Dow, 1993.

  165. 165.

    Awni WM, Cavanaugh JH, Leese P. The pharmacokinetic and pharmacodynamic interaction between zileuton and terfenadine. Eur J Clin Pharmacol 1997; 52 (1): 49–54.

  166. 166.

    Abbott Laboratories. Zyflo (Zileuton) package insert. Chicago (IL): Abbott Laboratories, 1997.

  167. 167.

    Van Hecken A, Depre M, Verbesselt R, et al. Effect of montelukast on the pharmacokinetics and pharmacodynamics of warfarin in healthy volunteers. J Clin Pharmacol 1999; 39 (5): 495–500.

  168. 168.

    Malmstrom K, Schwartz J, Reiss TF, et al. Effect of montelukast on single-dose theophylline pharmacokinetics. Am J Ther 1998; 5 (3): 189–95.

  169. 169.

    Sharma ND, Rosman HS, Padhi D, et al. Torsade de pointes associated with intravenous haloperidol in critically ill patients. Am J Cardiol 1998; 81: 239–40.

  170. 170.

    Wilt JL, Minnema AM, Johnson RF, et al. Torsade de pointes associated with use of intravenous haloperidol. Ann Intern Med 1993; 119:391–4.

  171. 171.

    Kriwisky M, Perry GY, Tarchitsky D, et al. Haloperidol-in-duced torsade de pointes. Chest 1990; 98 (2): 482–4.

  172. 172.

    Flugelman MY, Tal A, Pollack S, et al. Psychotropic drugs and long QT syndromes: case reports. J Clin Psychiatry 1985; 46: 290–1.

  173. 173.

    Kemper AJ, Dulap R, Pietro DA. Thioridazine-induced torsade de pointes. Successful therapy with isoproterenol. JAMA 1983; 249 (21): 2931–4.

  174. 174.

    Kitayama H, Kiuchi K, Nejima J, et al. Long-term treatment with antipsychotic drugs in convention doses prolonged QTc dispersion, but did not increase ventricular tachyarrhythmias in patients with schizophrenia in the absence of cardiac disease. Eur J Clin Pharmacol 1999; 55: 259–62.

  175. 175.

    Drici MD, Wang WX, Liu XK, et al. Prolongation of QT interval in isolated feline hearts by antipsychotic drugs. J Clin Psychopharmacol 1998; 18 (6): 477–81.

  176. 176.

    O’Brien JM, Rockwood RP, Suh KI. Haloperidol-induced torsade de pointes. Ann Pharmacother 1999; 33: 1046–50.

  177. 177.

    Roche Pharmaceuticals. Fotovase (saquinavir soft gel caps) package insert. Nutley (NJ): Roche Pharmaceuticals, 1998.

  178. 178.

    Agouron Pharmaceuticals. Viracept (nelfinavir) package insert. La Jolla (CA): Agouron Pharmaceuticals, 1997.

  179. 179.

    Abbott Laboratories. Norvir (ritonavir) package insert. North Chicago (IL): Abbott Laboratories, 1999.

  180. 180.

    Merck and Company, Inc. Crixivan (indinavir) package insert. West Point (PA): Merck and Co., 1998.

  181. 181.

    Amprenavir: a new HIV protease inhibitor. Med Lett 1999; 41 (1057): 64–6.

  182. 182.

    Kumar GN, Rodrigues AD, Buko AM, et al. Cytochrome P450-mediated metabolism of the HIV-1 protease inhibitorritonavir (ABT-538) in human liver microsomes. J Pharmacol Exp Ther 1996; 277 (1): 423–31.

  183. 183.

    Decker CJ, Laithinen LM, Bridson GW, et al. Metabolism of amprenavir in liver microsomes: role of CYP3A4 inhibition for drug interactions. J Pharm Sci 1998; 87 (7): 803–7.

  184. 184.

    Kaul DR, Cinti SK, Carver PL, et al. HIV protease inhibitors: advances in therapy and adverse reactions, including metabolic complications. Pharmacotherapy 1999; 19 (3): 281–98.

  185. 185.

    von Moltke LL, Greenblatt DJ, Grassi JM, et al. Protease inhibitors as inhibitors of human cytochromes P450: high risk associated with ritonavir. J Clin Pharmacol 1998;38(2): 106–11.

  186. 186.

    Iribarne C, Berthou F, Carlhant D, et al. Inhibition of methadone and buprenorphine N-dealkylations by three HIV-1 protease inhibitors. Drug Metab Dispos 1998; 26 (3): 257–60.

  187. 187.

    Eagling VA, Back DJ, Barry MG. Differential inhibition of cytochrome P450 isoforms by the protease inhibitors, ritonavir, saquinavir and indinavir. Br J Clin Pharmacol 1997; 44 (2): 190–4.

  188. 188.

    Chiba M, Hensleigh M, Nishime JA, et al. Role of cytochrome P450 3A4 in human metabolism of MK-639, a potent human immunodeficiency virus protease inhibitor. Drug Metab Dispos 1996; 24 (3): 307–14.

  189. 189.

    Lillibridge JH, Liang BH, Kerr BM, et al. Characterization of the selectivity and mechanism of human cytochrome P450 inhibition by the human immunodeficiency virus-protease inhibitor nelfinavir mesylate. Drug Metab Dispos 1998; 26 (7): 609–16.

  190. 190.

    Barry M, Malcahy F, Merry C, et al. Pharmacokinetics and potential interactions amongst antiretroviral agents used to treat patients with HIV infection. Clin Pharmacokinet 1999; 36 (4): 289–304.

  191. 191.

    Hsu A, Granneman GR, Cao G, et al. Pharmacokinetic interactions between two immunodeficiency virus protease inhibitors, ritonavir and saquinavir. Clin Pharmacol Ther 1998; 63 (4): 453–64.

  192. 192.

    Rana KZ, Dudley MN. Human immunodeficiency virus protease inhibitors. Pharmacotherapy 1999; 19(1): 35–59.

  193. 193.

    Barry M, Gibbons S, Back D, et al. Protease inhibitors in patients with HIV disease: clinically important pharmacokinetic considerations. Clin Pharmacokinet 1997; 32 (3): 194–209.

  194. 194.

    Hsu A, Granneman GR, Bertz R. Ritonavir: clinical pharmacokinetics and interactions with other anti-HIV agents. Clin Pharmacokinet 1998; 35 (4): 275–91.

  195. 195.

    Piscitelli S, Flexner C, Minor JR, et al. Drug interactions in patients infected with human immunodeficiency virus. Clin Infect Dis 1996; 23: 685–93.

  196. 196.

    Ouellet D, Hsu A, Granneman GR, et al. Pharmacokinetic interaction between ritonavir and clarithromycin. Clin Pharmacol Ther 1998; 64 (4): 355–62.

  197. 197.

    Cato A, Cavanaugh JH, Shi H, et al. The effect of multiple doses of ritonavir on the pharmacokinetics of rifabutin. Clin Pharmacol Ther 1998; 63 (4): 414–21.

  198. 198.

    Kakuda TN, Struble KA, Piscitelli S. Protease inhibitors for the treatment of human immunodeficiency virus infection. Am J Health-Syst Pharm 1998; 55: 233–54.

  199. 199.

    Cheng CL, Smith DE, Carver PL. Steady-state pharmacokinetics of delavirdine in HIV-positive patients: effect on erythromycin breath test. Clin Pharmacol Ther 1997; 61 (5): 531–43.

  200. 200.

    Ferry JJ, Herman BD, Carel BJ, et al. Pharmacokinetic drugdrug interaction study of delavirdine and indinavir in healthy volunteers. J Acquir Immune Defic Syndr Hum Retrovirol 1998; 18 (3): 252–9.

  201. 201.

    Pharmacia and Upjohn. Rescriptor (delaviradine) package insert. Bridgewater (NJ): Pharmacia and Upjohn, 1998.

  202. 202.

    Murray M, Butler AM. Enhanced inhibition of microsomal cytochrome P340 3A2 in rat liver diltiazem biotransformation. J Pharmacol Exp Ther 1996; 279 (2): 1447–52.

  203. 203.

    Jacolot F, Simon I, Dreano Y, et al. Identification of the cytochrome P450 IIIA family as the enzymes involved in the N-demethylation of tamoxifen in human liver microsomes. Biochem Pharmacol 1991; 41 (12): 1911–9.

  204. 204.

    McDonald P, Keough A, Connell J, et al. Diltiazem co-administration reduces cyclosporine toxicity after heart transplantation: a prospective randomized study. Transplant Proc 1992; 24: 2259–62.

  205. 205.

    Campana C, Regazzi MB, Buggia I, et al. Clinically significant drug interactions with cyclosporine: an update. Clin Pharmacokinet 1996; 30: 141–79.

  206. 206.

    Varhe A, Olkkola KT, Neuvonen PJ. Diltiazem enhances the effects of triazolam by inhibiting its metabolism. Clin Pharmacol Ther 1996; 59 (4): 369–75.

  207. 207.

    Azie NE, Brater DC, Becker PA, et al. The interaction of diltiazem with lovastatin and pravastatin. Clin Pharmacol Ther 1998; 64 (4): 369–77.

  208. 208.

    Dickenson TH, Egan JM, Abernethy DR. Effects of nifedipine on hepatic drug oxidation. Pharmacology 1988; 36 (6): 405–10.

  209. 209.

    Kantola T, Kivisto KT, Neuvonen PJ. Erythromycin and verapamil considerably increase serum simvastatin and simvastatin acid concentrations. Clin Pharmacol Ther 1998; 64: 177–82.

  210. 210.

    Backman JT, Aranko K, Luurila H, et al. Dose of midazolam should be reduced during diltiazem and verapamil treatments. Br J Clin Pharmacol 1994; 37: 221–5.

  211. 211.

    Grayson HA, Kennedy JD. Torsade de pointes and nifedipine. Ann Intern Med 1982; 97 (1): 144–5.

  212. 212.

    Alderman MH, Cohen H, Roque R, et al. Effect of long-acting and short-acting calcium antagonists on cardiovascular outcomes in hypertensive patients. Lancet 1997; 349 (9052): 594–8.

  213. 213.

    Prystowsky E. Effects of bepridil on cardiac electrophysiologic properties. Am J Cardiol 1992; 69: 63D–67D.

  214. 214.

    Martinez C, Albet C, Agundez JA, et al. Comparative in vitro and in vivo inhibition of cytochrome P450 CYP1A2, CYP2D6, and CYP3A by H2- receptor antagonists. Clin Pharmacol Ther 1999; 65 (4): 369–76.

  215. 215.

    Kirch W, Janisch HD, Ohnhaus EE, et al. Cisapride-cimetidine interaction: enhanced cisapride bioavailability and accelerated cimetidine absorption. Ther Drug Monit 1989; 11 (4): 411–4.

  216. 216.

    Ng PW, Chan WK, Chan TV. Torsade de pointes during the concomitant use of terfenadine and cimetidine. Aust NZ Med 1996; 26(1): 120–1.

  217. 217.

    Milligan KA, McHugh P. Effects of concomitant administration of cisapride and ranitidine on plasma concentrations in volunteers [abstract]. Br J Anaesth 1989; 63: 628P.

  218. 218.

    Humphries TJ. Famotidine: a notable lack of drug interactions. Scand J Gastroenterol 1987; 134 Suppl.: 55–60.

  219. 219.

    Huber R, Bliesath H, Hartmann M, et al. Pantoprazole does not interact with the pharmacokinetics of carbamazepine. Int J Clin Pharmacol Ther 1998; 36 (10): 521–4.

  220. 220.

    Shinn AF. Clinical relevance of cimetidine drug interactions. Drug Saf 1992; 7: 245–67.

  221. 221.

    Steinijans VW, Huber R, Harmann M, et al. Lack of pantoprazole drug interactions in man: an updated review. Int J Clin Pharmacol Ther 1996; 34 (6): 243–62.

  222. 222.

    Curi-Pedrosa R, Daujat M, Pichard L, et al. Omeprazole and lansoprazole are mixed inducers of CYP1A and CYP3A in human hepatocytes in primary culture. J Pharmacol Exp Ther 1994; 269 (1): 384–92.

  223. 223.

    Blum RA. Lansoprazole and omeprazole in the treatment of acid peptic disorders. Am J Health-Syst Pharm 1996; 53: 1401–15.

  224. 224.

    Gugler R, Jensen JC. Omeprazole inhibits oxidative drug metabolism: studies with diazepam and phenytoin in vivo and 7-ethoxycoumarin in vitro. Gastroenterology 1985; 89: 1235–41.

  225. 225.

    Shan K, Lincoff AM, Young JB. Anthracycline-induced cardiotoxicity. Ann Intern Med 1996; 125: 47–58.

  226. 226.

    Spiller HA, Winter ML, Mann KV, et al. Five-year multicenter retrospective review of cyclobenzaprine toxicity. J Emerg Med 1995; 13 (6): 781–5.

  227. 227.

    Michalets EL, Smith LK, Van Tassel ED. Torsade de pointes resulting from the addition of droperidol to an existing cytochrome P450 drug interaction. Ann Pharmacother 1998; 32: 761–4.

  228. 228.

    Lischke V, Behne M, Doelken P, et al. Droperidol causes a dose-dependent prolongation of the QT interval. Anesth Analg 1994; 79: 983–6.

  229. 229.

    Edwards DJ, Bernier SM. Naringin and naringenin are not the primary CYP3A4 inhibitors in grapefruit juice. Life Sci 1996; 59: 1025–30.

  230. 230.

    Edwards DJ, Bellevue FH, Woster PM. Identification of 6,7-dihydroxybergamottin, a cytochrome P450 inhibitor, in grapefruit juice. Drug Metab Dispos 1996; 24: 1287–90.

  231. 231.

    Bailey DG, Arnold MO, Strong A, et al. Effect of grapefruit juice naringin on nisoldipine phannacokinetics. Clin Pharmacol Ther 1993; 54: 589–94.

  232. 232.

    Bailey DG, Spence JD, Numoz C, et al. Interaction of citrus juice with felodipine and nifedipine. Lancet 1991; 337: 268–9.

  233. 233.

    Brunner LJ, Munar MY, Vallian J, et al. Interaction between cyclosporine and grapefruit juice requires long-term ingestion in stable renal transplant recipients. Pharmacotherapy 1998; 18(1): 23–9.

  234. 234.

    Ameer B, Wintraub RA. Drug interactions with grapefruit juice. Clin Pharmacokinet 1997; 33 (2): 103–21.

  235. 235.

    Kupferschmidt HHT, Ha RH, Ziegler WH, et al. Interaction between grapefruit juice and midazolam in humans. Clin Pharmacol Ther 1995; 58: 20–8.

  236. 236.

    Benton RE, Honig PK, Zamani K, et al. Grapefruit juice alters terfenadine phannacokinetics, resulting in prolongation of repolarization on the electrocardiogram. Clin Phannacol Ther 1996; 59: 383–8.

  237. 237.

    Bailey DG, Malcolm J, Arnold O, et al. Grapefruit juice-drug interactions. Br J Clin Phannacol 1998; 46 (2): 101–10.

  238. 238.

    Spence JD. Drug interactions with grapefruit: whose responsibility is it to warn the public? Clin Phannacol Ther 1997; 61 (4): 395–400.

  239. 239.

    Gross AS, Goh YD, Addison RS, et al. Influence of grapefruit juice on cisapride phannacokinetics. Clin Pharmacol Ther 1999; 65: 395–401.

  240. 240.

    Kivisto KT, Lilja JJ, Backman JT, et al. Repeated consumption of grapefruit juice considerably increases plasma concentrations of cisapride. Clin Pharmacol Ther 1999; 66: 448–53.

  241. 241.

    Block SH, Carbamazepine-isoniazid interaction. Pediatrics 1982; 69: 494–5.

  242. 242.

    Fleenor ME, Harden JW, Curtis G. Interaction between carbamazepine and antituberculosis agents [letter]. Chest 1991; 99 (6): 1554.

  243. 243.

    Ochs HR, Greenblatt DJ, Knuckel M, et al. Differential effect of isoniazid on triazolam oxidation and oxazepam conjugation. Br J Clin Pharmacol 1983; 16: 743–6.

  244. 244.

    Gonzalez A, Sager PT, Akil B, et al. Pentamidine-induced torsade de pointes. Am Heart J 1991; 122: 1489–92.

  245. 245.

    Gohn DC, Simmons TW. Polymorphic ventricular tachycardia (torsade de pointes) associated with the use of probucol. New Engl J Med 1991; 326: 1435–6.

  246. 246.

    Bangchang KN, Karbwang J, Back DJ. Mefloquine metabolism by human liver microsomes. Effect of other antimalarial drugs. Biochem Pharmacol 1992; 43 (9): 1957–61.

  247. 247.

    Bangchang KN, Karbwang J, Back DJ. Primaquinine metabolism by human liver microsomes: effect of other antimalarial drugs. Biochem Pharmacol 1992; 44 (3): 587–90.

  248. 248.

    Zhao XJ, Yokoyama H, Chiba K, et al. Identification of human cytochrome P450 isoforms involved in the 3-hydroxylation of quinine by human liver microsomes and nine recombinant human cytochromes P450. J Pharmacol Exp Ther 1996; 279 (3): 1327–34.

  249. 249.

    Stein LB, Dabezies MA, Silverman M, et al. Fatal torsade de pointes occurring in a patient receiving intravenous vasopressin an nitroglycerin. J Clin Gastroenterol 1992; 15 (2): 171–4.

  250. 250.

    Kelly KJ, Stang JM, Mekhjian HS. Vasopressin provocation of ventricular dysrhythmias. Ann Intern Med 1980; 92 (2): 205–7.

  251. 251.

    Minami T, Nishibayashi H, Shinomura Y, et al. Effects of erythromycin in chronic idiopathic intestinal pseudo-obstruction. J Gastroenterol 1996; 31: 855–9.

  252. 252.

    Hendeles L, Scheife RT, editors. New frontiers in asthma therapy: leukotriene receptor antagonists and 5-lipoxygenase inhibitors. Pharmacotherapy 1997; 17 Suppl.: 1–54S.

  253. 253.

    Loft S, Otton SV, Lennard MS. Characterization of metronidazole metabolism by human liver microsomes. Biochem Pharmacol 1991; 41 (8): 1127–34.

  254. 254.

    Brouwers JR. Drug interactions with quinolone antibacterials. Drug Saf 1992; 7 (4): 268–81.

  255. 255.

    McLellan RA, Drobitch RK, Monshouwer M, et al. Fluoroquinolones antibiotics inhibit cytochrome P450-mediated microsomal drug metabolism in rat and human. Drug Metab Dispos 1996; 24 (10): 1134–8.

  256. 256.

    Yamamoto I, Watanabe K, Marimatsu S, et al. Recent advances in the metabolism of cannabinoids. Int J Biochem Cell Biol 1995; 27 (8): 741–6.

  257. 257.

    El-Sherif N, Zeiler RH, Carelius W, et al. QTU prolongation and polymorphic ventricular tachycardia due to bradycardia-de-pendent early afterdepolarizations. Circ Res 1988; 63: 286–305.

Download references

Author information

Correspondence to Dr Elizabeth Landrum Michalets.

Rights and permissions

Reprints and Permissions

About this article

Cite this article

Landrum Michalets, E., Williams, C.R. Drug Interactions with Cisapride. Clin Pharmacokinet 39, 49–75 (2000). https://doi.org/10.2165/00003088-200039010-00004

Download citation

Keywords

  • Fluoxetine
  • Cisapride
  • Terfenadine
  • Saquinavir
  • Droperidol