Current Transplantation Reports

, Volume 5, Issue 3, pp 220–230 | Cite as

Review of Major Drug-Drug Interactions in Thoracic Transplantation

  • Yu Xie
  • Deanna Dilibero
  • David H. ChangEmail author
Thoracic Transplantation (J Kobashigawa, Section Editor)
Part of the following topical collections:
  1. Topical Collection on Thoracic Transplantation


Purpose of Review

The first human lung transplant surgery in the world was done in 1963, followed by the first heart transplant in 1967, making this year its 50th anniversary. Since then, there has been great advancement in immunotherapy, with the adoption of calcineurin inhibitors (CNI), mycophenolate mofetil, and proliferation signal inhibitors (PSI). However, while these medications are crucial to maintenance of allograft function and prevention of allograft rejection, they have many toxicities and side effects, which make therapeutic dose monitoring and recognition of drug-drug interactions of critical importance.

Recent Findings

Most of drug-drug interactions in transplant medicine can be explained through the mechanism of CYP3A4 and P-glycoprotein.


A large component of the medical management of post-transplant care is in the appropriate utilization of immunosuppression drugs while minimizing side effects and drug-drug interactions.


Drug-drug interaction Thoracic transplant Immunosuppression CYP450 CYP3A4 Herbal supplementation 


Compliance with Ethical Standards

Conflict of Interest

Yu Xie and Deanna Dilibero declare no conflict of interest. David Chang reports stock interest in ABT and ABBV.

Human and Animal Rights and Informed Consent

This article does not contain any studies with human or animal subjects performed by any of the authors.


Papers of particular interest, published recently, have been highlighted as: • Of importance •• Of major Importance

  1. 1.
    Chambers DC, Yusen RD, Cherikh WS, Goldfarb SB, Kucheryavaya AY, Khusch K, et al. The Registry of the International Society for Heart and Lung Transplantation: thirty-fourth adult lung and heart-lung transplantation report—2017; focus theme: allograft ischemic time. J Heart Lung Transplant. 2017;36(10):1047–59.PubMedCrossRefGoogle Scholar
  2. 2.
    Lund LH, Khush KK, Cherikh WS, Goldfarb S, Kucheryavaya AY, Levvey BJ, et al. The Registry of the International Society for Heart and Lung Transplantation: thirty-fourth adult heart transplantation report—2017; focus theme: allograft ischemic time. J Heart Lung Transplant. 2017;36(10):1037–46.PubMedCrossRefGoogle Scholar
  3. 3.
    Lazarou J, Pomeranz BH, Corey PN. Incidence of adverse drug reactions in hospitalized patients: a meta-analysis of prospective studies. JAMA. 1998;279(15):1200–5.PubMedCrossRefGoogle Scholar
  4. 4.
    Phillips KA, Veenstra DL, Oren E, Lee JK, Sadee W. Potential role of pharmacogenomics in reducing adverse drug reactions: a systematic review. JAMA. 2001;286(18):2270–9.PubMedCrossRefGoogle Scholar
  5. 5.
    Srinivas TR, Meier-Kriesche HU, Kaplan B. Pharmacokinetic principles of immunosuppressive drugs. Am J Transplant. 2005;5(2):207–17.PubMedCrossRefGoogle Scholar
  6. 6.
    Page RL 2nd, Miller GG, Lindenfeld J. Drug therapy in the heart transplant recipient: part IV: drug-drug interactions. Circulation. 2005;111(2):230–9.PubMedCrossRefGoogle Scholar
  7. 7.
    • Wanwimolruk S, Prachayasittikul V. Cytochrome P450 enzyme mediated herbal drug interactions (part 1). EXCLI J. 2014;13:347–91. Focused review on clinically relavent herbal medications involved in CYP450 pathway. PubMedPubMedCentralGoogle Scholar
  8. 8.
    Lampen A, Zhang Y, Hackbarth I, Benet LZ, Sewing KF, Christians U. Metabolism and transport of the macrolide immunosuppressant sirolimus in the small intestine. J Pharmacol Exp Ther. 1998;285(3):1104–12.PubMedGoogle Scholar
  9. 9.
    Murthy JN, Yatscoff RW, Soldin SJ. Cyclosporine metabolite cross-reactivity in different cyclosporine assays. Clin Biochem. 1998;31(3):159–63.PubMedCrossRefGoogle Scholar
  10. 10.
    Murthy JN, Davis DL, Yatscoff RW, Soldin SJ. Tacrolimus metabolite cross-reactivity in different tacrolimus assays. Clin Biochem. 1998;31(8):613–7.PubMedCrossRefGoogle Scholar
  11. 11.
    Paine MF, Leung LY, Lim HK, Liao K, Oganesian A, Zhang MY, et al. Identification of a novel route of extraction of sirolimus in human small intestine: roles of metabolism and secretion. J Pharmacol Exp Ther. 2002;301(1):174–86.PubMedCrossRefGoogle Scholar
  12. 12.
    Tokunaga Y, Alak AM. FK506 (tacrolimus) and its immunoreactive metabolites in whole blood of liver transplant patients and subjects with mild hepatic dysfunction. Pharm Res. 1996;13(1):137–40.PubMedCrossRefGoogle Scholar
  13. 13.
    Christians U, Jacobsen W, Benet LZ, Lampen A. Mechanisms of clinically relevant drug interactions associated with tacrolimus. Clin Pharmacokinet. 2002;41(11):813–51.PubMedCrossRefGoogle Scholar
  14. 14.
    Christians U, Sewing KF. Alternative cyclosporine metabolic pathways and toxicity. Clin Biochem. 1995;28(6):547–59.PubMedCrossRefGoogle Scholar
  15. 15.
    Kuhn B, Jacobsen W, Christians U, Benet LZ, Kollman PA. Metabolism of sirolimus and its derivative everolimus by cytochrome P450 3A4: insights from docking, molecular dynamics, and quantum chemical calculations. J Med Chem. 2001;44(12):2027–34.PubMedCrossRefGoogle Scholar
  16. 16.
    Sattler M, Guengerich FP, Yun CH, Christians U, Sewing KF. Cytochrome P-450 3A enzymes are responsible for biotransformation of FK506 and rapamycin in man and rat. Drug Metab Dispos. 1992;20(5):753–61.PubMedGoogle Scholar
  17. 17.
    Benet LZ, Izumi T, Zhang Y, Silverman JA, Wacher VJ. Intestinal MDR transport proteins and P-450 enzymes as barriers to oral drug delivery. J Control Release. 1999;62(1–2):25–31.PubMedCrossRefGoogle Scholar
  18. 18.
    Watkins PB. Drug metabolism by cytochromes P450 in the liver and small bowel. Gastroenterol Clin N Am. 1992;21(3):511–26.Google Scholar
  19. 19.
    Watkins PB. The role of cytochromes P-450 in cyclosporine metabolism. J Am Acad Dermatol. 1990;23(6 Pt 2):1301–9. discussion 9-11PubMedCrossRefGoogle Scholar
  20. 20.
    Macphee IA, Fredericks S, Tai T, Syrris P, Carter ND, Johnston A, et al. Tacrolimus pharmacogenetics: polymorphisms associated with expression of cytochrome p4503A5 and P-glycoprotein correlate with dose requirement. Transplantation. 2002;74(11):1486–9.PubMedCrossRefGoogle Scholar
  21. 21.
    MacPhee IA, Fredericks S, Tai T, Syrris P, Carter ND, Johnston A, et al. The influence of pharmacogenetics on the time to achieve target tacrolimus concentrations after kidney transplantation. Am J Transplant. 2004;4(6):914–9.PubMedCrossRefGoogle Scholar
  22. 22.
    Hesselink DA, van Schaik RH, van der Heiden IP, van der Werf M, Gregoor PJ, Lindemans J, et al. Genetic polymorphisms of the CYP3A4, CYP3A5, and MDR-1 genes and pharmacokinetics of the calcineurin inhibitors cyclosporine and tacrolimus. Clin Pharmacol Ther. 2003;74(3):245–54.PubMedCrossRefGoogle Scholar
  23. 23.
    Hustert E, Haberl M, Burk O, Wolbold R, He YQ, Klein K, et al. The genetic determinants of the CYP3A5 polymorphism. Pharmacogenetics. 2001;11(9):773–9.PubMedCrossRefGoogle Scholar
  24. 24.
    Kuehl P, Zhang J, Lin Y, Lamba J, Assem M, Schuetz J, et al. Sequence diversity in CYP3A promoters and characterization of the genetic basis of polymorphic CYP3A5 expression. Nat Genet. 2001;27(4):383–91.PubMedCrossRefGoogle Scholar
  25. 25.
    Lamba JK, Lin YS, Schuetz EG, Thummel KE. Genetic contribution to variable human CYP3A-mediated metabolism. Adv Drug Deliv Rev. 2002;54(10):1271–94.PubMedCrossRefGoogle Scholar
  26. 26.
    Lamba JK, Lin YS, Thummel K, Daly A, Watkins PB, Strom S, et al. Common allelic variants of cytochrome P4503A4 and their prevalence in different populations. Pharmacogenetics. 2002;12(2):121–32.PubMedCrossRefGoogle Scholar
  27. 27.
    Zhou Y, Ingelman-Sundberg M, Lauschke VM. Worldwide distribution of cytochrome P450 alleles: a meta-analysis of population-scale sequencing projects. Clin Pharmacol Ther. 2017;102(4):688–700.PubMedPubMedCentralCrossRefGoogle Scholar
  28. 28.
    Hesselink DA, Bouamar R, Elens L, van Schaik RH, van Gelder T. The role of pharmacogenetics in the disposition of and response to tacrolimus in solid organ transplantation. Clin Pharmacokinet. 2014;53(2):123–39.PubMedCrossRefGoogle Scholar
  29. 29.
    Yates CR, Zhang W, Song P, Li S, Gaber AO, Kotb M, et al. The effect of CYP3A5 and MDR1 polymorphic expression on cyclosporine oral disposition in renal transplant patients. J Clin Pharmacol. 2003;43(6):555–64.PubMedCrossRefGoogle Scholar
  30. 30.
    Chen YK, Han LZ, Xue F, Shen CH, Lu J, Yang TH, et al. Personalized tacrolimus dose requirement by CYP3A5 but not ABCB1 or ACE genotyping in both recipient and donor after pediatric liver transplantation. PLoS One. 2014;9(10):e109464.PubMedPubMedCentralCrossRefGoogle Scholar
  31. 31.
    Eidens M, Weise A, Klemm M, Fleischer M, Prause S. Development and validation of a rapid and reliable real-time PCR method for CYP3A5 genotyping. Clin Lab. 2015;61(3–4):353–62.PubMedGoogle Scholar
  32. 32.
    MacPhee IA, Holt DW. A pharmacogenetic strategy for immunosuppression based on the CYP3A5 genotype. Transplantation. 2008;85(2):163–5.PubMedCrossRefGoogle Scholar
  33. 33.
    • Birdwell KA, Decker B, Barbarino JM, Peterson JF, Stein CM, Sadee W, et al. Clinical pharmacogenetics implementation consortium (CPIC) guidelines for CYP3A5 genotype and tacrolimus dosing. Clin Pharmacol Ther. 2015;98(1):19–24. Summary of published literature on CYP3A5 expressers and none-expressors and tacrolimus dose recommendations based on genotypes. PubMedPubMedCentralCrossRefGoogle Scholar
  34. 34.
    Shimada T, Yamazaki H, Mimura M, Inui Y, Guengerich FP. Interindividual variations in human liver cytochrome P-450 enzymes involved in the oxidation of drugs, carcinogens and toxic chemicals: studies with liver microsomes of 30 Japanese and 30 Caucasians. J Pharmacol Exp Ther. 1994;270(1):414–23.PubMedGoogle Scholar
  35. 35.
    Watkins PB, Wrighton SA, Schuetz EG, Molowa DT, Guzelian PS. Identification of glucocorticoid-inducible cytochromes P-450 in the intestinal mucosa of rats and man. J Clin Invest. 1987;80(4):1029–36.PubMedPubMedCentralCrossRefGoogle Scholar
  36. 36.
    Stiff DD, Venkataramanan R, Prasad TN. Metabolism of FK 506 in differentially induced rat liver microsomes. Res Commun Chem Pathol Pharmacol. 1992;78(1):121–4.PubMedGoogle Scholar
  37. 37.
    Venkataramanan R, Swaminathan A, Prasad T, Jain A, Zuckerman S, Warty V, et al. Clinical pharmacokinetics of tacrolimus. Clin Pharmacokinet. 1995;29(6):404–30.PubMedCrossRefGoogle Scholar
  38. 38.
    Lin JH, Lu AY. Inhibition and induction of cytochrome P450 and the clinical implications. Clin Pharmacokinet. 1998;35(5):361–90.PubMedCrossRefGoogle Scholar
  39. 39.
    Mahnke CB, Sutton RM, Venkataramanan R, Michaels M, Kurland G, Boyle GJ, et al. Tacrolimus dosage requirements after initiation of azole antifungal therapy in pediatric thoracic organ transplantation. Pediatr Transplant. 2003;7(6):474–8.PubMedCrossRefGoogle Scholar
  40. 40.
    VFEND. Pfizer. 2010.Google Scholar
  41. 41.
    •• Vanhove T, Bouwsma H, Hilbrands L, Swen JJ, Spriet I, Annaert P, et al. Determinants of the magnitude of interaction between tacrolimus and voriconazole/posaconazole in solid organ recipients. Am J Transplant. 2017;17(9):2372–80. Focused on a large lung transplant recipient cohort, evaluating effect of tacrolimus-azole administration on dose-corrected trough concentration. PubMedCrossRefGoogle Scholar
  42. 42.
    Lecefel C, Eloy P, Chauvin B, Wyplosz B, Amilien V, Massias L, et al. Worsening pneumonitis due to a pharmacokinetic drug-drug interaction between everolimus and voriconazole in a renal transplant patient. J Clin Pharm Ther. 2015;40(1):119–20.PubMedCrossRefGoogle Scholar
  43. 43.
    •• Outeda Macias M, Salvador Garrido P, Elberdin Pazos L, Martin Herranz MI. Management of everolimus and voriconazole interaction in lung transplant patients. Ther Drug Monit. 2016;38(3):305–12. Focused on a lung transplant recipient cohort, evaluating effect of everolimus-voriconazole administration on trough concentrations and concentration/dose ratio. PubMedCrossRefGoogle Scholar
  44. 44.
    Gupta SK, Bakran A, Johnson RW, Rowland M. Cyclosporin-erythromycin interaction in renal transplant patients. Br J Clin Pharmacol. 1989;27(4):475–81.PubMedPubMedCentralCrossRefGoogle Scholar
  45. 45.
    Jones TE, Morris RG. Pharmacokinetic interaction between tacrolimus and diltiazem: dose-response relationship in kidney and liver transplant recipients. Clin Pharmacokinet. 2002;41(5):381–8.PubMedCrossRefGoogle Scholar
  46. 46.
    Huisman MT, Smit JW, Schinkel AH. Significance of P-glycoprotein for the pharmacology and clinical use of HIV protease inhibitors. AIDS. 2000;14(3):237–42.PubMedCrossRefGoogle Scholar
  47. 47.
    Izzedine H, Launay-Vacher V, Baumelou A, Deray G. Antiretroviral and immunosuppressive drug-drug interactions: an update. Kidney Int. 2004;66(2):532–41.PubMedCrossRefGoogle Scholar
  48. 48.
    Shapiro LE, Shear NH. Drug interactions: proteins, pumps, and P-450s. J Am Acad Dermatol. 2002;47(4):467–84. quiz 85-8PubMedCrossRefGoogle Scholar
  49. 49.
    Wolking S, Schaeffeler E, Lerche H, Schwab M, Nies AT. Impact of genetic polymorphisms of ABCB1 (MDR1, P-glycoprotein) on drug disposition and potential clinical implications: update of the literature. Clin Pharmacokinet. 2015;54(7):709–35.PubMedCrossRefGoogle Scholar
  50. 50.
    Ogasawara K, Chitnis SD, Gohh RY, Christians U, Akhlaghi F. Multidrug resistance-associated protein 2 (MRP2/ABCC2) haplotypes significantly affect the pharmacokinetics of tacrolimus in kidney transplant recipients. Clin Pharmacokinet. 2013;52(9):751–62.PubMedPubMedCentralCrossRefGoogle Scholar
  51. 51.
    Christians U, Strom T, Zhang YL, Steudel W, Schmitz V, Trump S, et al. Active drug transport of immunosuppressants: new insights for pharmacokinetics and pharmacodynamics. Ther Drug Monit. 2006;28(1):39–44.PubMedCrossRefGoogle Scholar
  52. 52.
    Wu X, Li Q, Xin H, Yu A, Zhong M. Effects of berberine on the blood concentration of cyclosporin A in renal transplanted recipients: clinical and pharmacokinetic study. Eur J Clin Pharmacol. 2005;61(8):567–72.PubMedCrossRefGoogle Scholar
  53. 53.
    Xin HW, Wu XC, Li Q, Yu AR, Zhong MY, Liu YY. The effects of berberine on the pharmacokinetics of cyclosporin A in healthy volunteers. Methods Find Exp Clin Pharmacol. 2006;28(1):25–9.PubMedCrossRefGoogle Scholar
  54. 54.
    Tsukamoto S, Aburatani M, Ohta T. Isolation of CYP3A4 inhibitors from the black cohosh (Cimicifuga racemosa). Evid Based Complement Alternat Med. 2005;2(2):223–6.PubMedPubMedCentralCrossRefGoogle Scholar
  55. 55.
    Tsunoda SM, Harris RZ, Christians U, Velez RL, Freeman RB, Benet LZ, et al. Red wine decreases cyclosporine bioavailability. Clin Pharmacol Ther. 2001;70(5):462–7.PubMedCrossRefGoogle Scholar
  56. 56.
    Jaeger W, Benet LZ, Bornheim LM. Inhibition of cyclosporine and tetrahydrocannabinol metabolism by cannabidiol in mouse and human microsomes. Xenobiotica. 1996;26(3):275–84.PubMedCrossRefGoogle Scholar
  57. 57.
    Lee M, Min DI, Ku YM, Flanigan M. Effect of grapefruit juice on pharmacokinetics of microemulsion cyclosporine in African American subjects compared with Caucasian subjects: does ethnic difference matter? J Clin Pharmacol. 2001;41(3):317–23.PubMedCrossRefGoogle Scholar
  58. 58.
    Edwards DJ, Fitzsimmons ME, Schuetz EG, Yasuda K, Ducharme MP, Warbasse LH, et al. 6′,7′-Dihydroxybergamottin in grapefruit juice and Seville orange juice: effects on cyclosporine disposition, enterocyte CYP3A4, and P-glycoprotein. Clin Pharmacol Ther. 1999;65(3):237–44.PubMedCrossRefGoogle Scholar
  59. 59.
    Chiang HM, Chao PD, Hsiu SL, Wen KC, Tsai SY, Hou YC. Ginger significantly decreased the oral bioavailability of cyclosporine in rats. Am J Chin Med. 2006;34(5):845–55.PubMedCrossRefGoogle Scholar
  60. 60.
    Vischini G, Niscola P, Stefoni A, Farneti F. Increased plasma levels of tacrolimus after ingestion of green tea. Am J Kidney Dis. 2011;58(2):329.PubMedCrossRefGoogle Scholar
  61. 61.
    Hou YC, Lin SP, Chao PD. Liquorice reduced cyclosporine bioavailability by activating P-glycoprotein and CYP 3A. Food Chem. 2012;135(4):2307–12.PubMedCrossRefGoogle Scholar
  62. 62.
    Fildes JE, Yonan N, Keevil BG. Melatonin—a pleiotropic molecule involved in pathophysiological processes following organ transplantation. Immunology. 2009;127(4):443–9.PubMedPubMedCentralCrossRefGoogle Scholar
  63. 63.
    Khuu T, Hickey A, Deng MC. Pomegranate-containing products and tacrolimus: a potential interaction. J Heart Lung Transplant. 2013;32(2):272–4.PubMedCrossRefGoogle Scholar
  64. 64.
    Yu CP, Wu PP, Hou YC, Lin SP, Tsai SY, Chen CT, et al. Quercetin and rutin reduced the bioavailability of cyclosporine from Neoral, an immunosuppressant, through activating P-glycoprotein and CYP 3A4. J Agric Food Chem. 2011;59(9):4644–8.PubMedCrossRefGoogle Scholar
  65. 65.
    Lai MY, Hsiu SL, Hou YC, Tsai SY, Chao PD. Significant decrease of cyclosporine bioavailability in rats caused by a decoction of the roots of Scutellaria baicalensis. Planta Med. 2004;70(2):132–7.PubMedCrossRefGoogle Scholar
  66. 66.
    Hebert MF, Park JM, Chen YL, Akhtar S, Larson AM. Effects of St. John’s wort (Hypericum perforatum) on tacrolimus pharmacokinetics in healthy volunteers. J Clin Pharmacol. 2004;44(1):89–94.PubMedCrossRefGoogle Scholar
  67. 67.
    Mai I, Stormer E, Bauer S, Kruger H, Budde K, Roots I. Impact of St John’s wort treatment on the pharmacokinetics of tacrolimus and mycophenolic acid in renal transplant patients. Nephrol Dial Transplant. 2003;18(4):819–22.PubMedCrossRefGoogle Scholar
  68. 68.
    Lampen A, Christians U, Guengerich FP, Watkins PB, Kolars JC, Bader A, et al. Metabolism of the immunosuppressant tacrolimus in the small intestine: cytochrome P450, drug interactions and interindividual variability. Drug Metab Dispos. 1995;23(12):1315–24.PubMedGoogle Scholar
  69. 69.
    Saeki T, Ueda K, Tanigawara Y, Hori R, Komano T. Human P-glycoprotein transports cyclosporin A and FK506. J Biol Chem. 1993;268(9):6077–80.PubMedGoogle Scholar
  70. 70.
    Dean PG, Lund WJ, Larson TS, Prieto M, Nyberg SL, Ishitani MB, et al. Wound-healing complications after kidney transplantation: a prospective, randomized comparison of sirolimus and tacrolimus. Transplantation. 2004;77(10):1555–61.PubMedCrossRefGoogle Scholar
  71. 71.
    King-Biggs MB, Dunitz JM, Park SJ, Kay Savik S, Hertz MI. Airway anastomotic dehiscence associated with use of sirolimus immediately after lung transplantation. Transplantation. 2003;75(9):1437–43.PubMedCrossRefGoogle Scholar
  72. 72.
    Andreassen AK, Andersson B, Gustafsson F, Eiskjaer H, Radegran G, Gude E, et al. Everolimus initiation and early calcineurin inhibitor withdrawal in heart transplant recipients: a randomized trial. Am J Transplant. 2014;14(8):1828–38.PubMedCrossRefGoogle Scholar
  73. 73.
    Lindenfeld J, Page RL 2nd, Zolty R, Shakar SF, Levi M, Lowes B, et al. Drug therapy in the heart transplant recipient: part III: common medical problems. Circulation. 2005;111(1):113–7.PubMedCrossRefGoogle Scholar
  74. 74.
    Gavalda J, Meije Y, Fortun J, Roilides E, Saliba F, Lortholary O, et al. Invasive fungal infections in solid organ transplant recipients. Clin Microbiol Infect. 2014;20(Suppl 7):27–48.PubMedCrossRefGoogle Scholar
  75. 75.
    Shoham S. Emerging fungal infections in solid organ transplant recipients. Infect Dis Clin N Am. 2013;27(2):305–16.CrossRefGoogle Scholar
  76. 76.
    Back DJ, Tjia JF. 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.PubMedPubMedCentralCrossRefGoogle Scholar
  77. 77.
    Niwa T, Shiraga T, Takagi A. Effect of antifungal drugs on cytochrome P450 (CYP) 2C9, CYP2C19, and CYP3A4 activities in human liver microsomes. Biol Pharm Bull. 2005;28(9):1805–8.PubMedCrossRefGoogle Scholar
  78. 78.
    Wexler D, Courtney R, Richards W, Banfield C, Lim J, Laughlin M. Effect of posaconazole on cytochrome P450 enzymes: a randomized, open-label, two-way crossover study. Eur J Pharm Sci. 2004;21(5):645–53.PubMedCrossRefGoogle Scholar
  79. 79.
    Vasquez E, Pollak R, Benedetti E. Clotrimazole increases tacrolimus blood levels: a drug interaction in kidney transplant patients. Clin Transpl. 2001;15(2):95–9.CrossRefGoogle Scholar
  80. 80.
    Page RL 2nd, Mueller SW, Levi ME, Lindenfeld J. Pharmacokinetic drug-drug interactions between calcineurin inhibitors and proliferation signal inhibitors with anti-microbial agents: implications for therapeutic drug monitoring. J Heart Lung Transplant. 2011;30(2):124–35.PubMedCrossRefGoogle Scholar
  81. 81.
    Martin JE, Daoud AJ, Schroeder TJ, First MR. The clinical and economic potential of cyclosporin drug interactions. PharmacoEconomics. 1999;15(4):317–37.PubMedCrossRefGoogle Scholar
  82. 82.
    Soto Alvarez J, Sacristan Del Castillo JA, Alsar Ortiz MJ. Interaction between ciclosporin and ceftriaxone. Nephron. 1991;59(4):681–2.PubMedCrossRefGoogle Scholar
  83. 83.
    Huwyler J, Wright MB, Gutmann H, Drewe J. Induction of cytochrome P450 3A4 and P-glycoprotein by the isoxazolyl-penicillin antibiotic flucloxacillin. Curr Drug Metab. 2006;7(2):119–26.PubMedCrossRefGoogle Scholar
  84. 84.
    Lang CC, Jamal SK, Mohamed Z, Mustafa MR, Mustafa AM, Lee TC. Evidence of an interaction between nifedipine and nafcillin in humans. Br J Clin Pharmacol. 2003;55(6):588–90.PubMedPubMedCentralCrossRefGoogle Scholar
  85. 85.
    Borras-Blasco J, Conesa-Garcia V, Navarro-Ruiz A, Marin-Jimenez F, Gonzalez-Delgado M, Gomez-Corrons A. Ciprofloxacin, but not levofloxacin, affects cyclosporine blood levels in a patient with pure red blood cell aplasia. Am J Med Sci. 2005;330(3):144–6.PubMedCrossRefGoogle Scholar
  86. 86.
    Nasir M, Rotellar C, Hand M, Kulczycki L, Alijani MR, Winchester JF. Interaction between ciclosporin and ciprofloxacin. Nephron. 1991;57(2):245–6.PubMedCrossRefGoogle Scholar
  87. 87.
    Ibrahim RB, Abella EM, Chandrasekar PH. Tacrolimus-clarithromycin interaction in a patient receiving bone marrow transplantation. Ann Pharmacother. 2002;36(12):1971–2.PubMedCrossRefGoogle Scholar
  88. 88.
    Kunicki PK, Sobieszczanska-Malek M. Pharmacokinetic interaction between tacrolimus and clarithromycin in a heart transplant patient. Ther Drug Monit. 2005;27(1):107–8.PubMedCrossRefGoogle Scholar
  89. 89.
    Sketris IS, Wright MR, West ML. Possible role of the intestinal P-450 enzyme system in a cyclosporine-clarithromycin interaction. Pharmacotherapy. 1996;16(2):301–5.PubMedGoogle Scholar
  90. 90.
    Flexner C. HIV-protease inhibitors. N Engl J Med. 1998;338(18):1281–92.PubMedCrossRefGoogle Scholar
  91. 91.
    Kuo PC, Stock PG. Transplantation in the HIV+ patient. Am J Transplant. 2001;1(1):13–7.PubMedCrossRefGoogle Scholar
  92. 92.
    Euvrard S, Morelon E, Rostaing L, Goffin E, Brocard A, Tromme I, et al. Sirolimus and secondary skin-cancer prevention in kidney transplantation. N Engl J Med. 2012;367(4):329–39.PubMedCrossRefGoogle Scholar
  93. 93.
    Vadnerkar A, Nguyen MH, Mitsani D, Crespo M, Pilewski J, Toyoda Y, et al. Voriconazole exposure and geographic location are independent risk factors for squamous cell carcinoma of the skin among lung transplant recipients. J Heart Lung Transplant. 2010;29(11):1240–4.PubMedCrossRefGoogle Scholar
  94. 94.
    Ibrahim SF, Singer JP, Arron ST. Catastrophic squamous cell carcinoma in lung transplant patients treated with voriconazole. Dermatol Surg. 2010;36(11):1752–5.PubMedPubMedCentralCrossRefGoogle Scholar
  95. 95.
    Miller DD, Cowen EW, Nguyen JC, McCalmont TH, Fox LP. Melanoma associated with long-term voriconazole therapy: a new manifestation of chronic photosensitivity. Arch Dermatol. 2010;146(3):300–4.PubMedCrossRefGoogle Scholar
  96. 96.
    Cowen EW, Nguyen JC, Miller DD, McShane D, Arron ST, Prose NS, et al. Chronic phototoxicity and aggressive squamous cell carcinoma of the skin in children and adults during treatment with voriconazole. J Am Acad Dermatol. 2010;62(1):31–7.PubMedCrossRefGoogle Scholar
  97. 97.
    McCarthy KL, Playford EG, Looke DF, Whitby M. Severe photosensitivity causing multifocal squamous cell carcinomas secondary to prolonged voriconazole therapy. Clin Infect Dis. 2007;44(5):e55–6.PubMedCrossRefGoogle Scholar
  98. 98.
    Epaulard O, Saint-Raymond C, Villier C, Charles J, Roch N, Beani JC, et al. Multiple aggressive squamous cell carcinomas associated with prolonged voriconazole therapy in four immunocompromised patients. Clin Microbiol Infect. 2010;16(9):1362–4.PubMedCrossRefGoogle Scholar
  99. 99.
    Clancy CJ, Nguyen MH. Long-term voriconazole and skin cancer: is there cause for concern? Curr Infect Dis Rep. 2011;13(6):536–43.PubMedCrossRefGoogle Scholar
  100. 100.
    Stallone G, Schena A, Infante B, Di Paolo S, Loverre A, Maggio G, et al. Sirolimus for Kaposi’s sarcoma in renal-transplant recipients. N Engl J Med. 2005;352(13):1317–23.PubMedCrossRefGoogle Scholar

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© Springer International Publishing AG, part of Springer Nature 2018

Authors and Affiliations

  1. 1.Cedars-Sinai Medical CenterLos AngelesUSA

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