Sleeping Beauty

Fatal Forty DDI: fentanyl, ritonavir, CYP3A4


This case discusses the pharmacokinetic interaction between fentanyl and ritonavir, leading to prolonged narcotic action. Fentanyl is a cytochrome P450 3A4 substrate and ritonavir is a 3A4 inhibitor.


Pharmacokinetic Inhibitor Inhibition Fentanyl Opioid CYP3A4 Ritonavir Narcotic HIV Human immunodeficiency virus Cytochrome P450 3A4 


  1. 1.
    Labroo RB, Paine MF, Thummel KE, et al. Fentanyl metabolism by human hepatic and intestinal cytochrome P450 3A4: implications for interindividual variability in disposition, efficacy, and drug interactions. Drug Metab Dispos. 1997;25(9):1072–80.PubMedGoogle Scholar
  2. 2.
    McClain DA, Hug Jr CC. Intravenous fentanyl kinetics. Clin Pharmacol Ther. 1980;28(1):106–14.PubMedCrossRefGoogle Scholar
  3. 3.
    Olkkola KT, Palkama VJ, Neuvonen PJ. Ritonavir’s role in reducing fentanyl clearance and prolonging its half-life. Anesthesiology. 1999;91(3):681–5.PubMedCrossRefGoogle Scholar
  4. 4.
    Kharasch ED, Whittington D, Hoffer C. Minimal influence of hepatic & intestinal CYP3A activity on the acute disposition & effect of oral transmucosal fentanyl (OTFC) [abstract]. Anesthesiology. 2003;99:A515.CrossRefGoogle Scholar
  5. 5.
    Rowland M, Tozer TN. Elimination. In: Clinical pharmacokinetics: concepts and applications. 3rd ed. Baltimore: Williams & Wilkins; 1995. p. 156–83.Google Scholar
  6. 6.
    Feierman DE, Lasker JM. Metabolism of fentanyl, a synthetic opioid analgesic, by human liver microsomes: role of CYP3A4. Drug Metab Dispos. 1996;24(9):932–9.PubMedGoogle Scholar
  7. 7.
    Kharasch ED, Bedynek PS, Walker A, et al. Mechanism of ritonavir changes in methadone pharmacokinetics and pharmacodynamics: II. Ritonavir effects of CYP3A and P-glycoprotein activities. Clin Pharmacol Ther. 2008;84(4):506–12.PubMedPubMedCentralCrossRefGoogle Scholar
  8. 8.
    Piscitelli SC, Kress DR, Bertz RJ, et al. The effect of ritonavir on the pharmacokinetics of meperidine and normeperidine. Pharmacotherapy. 2000;20(5):549–53.PubMedCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media New York 2015

Authors and Affiliations

  1. 1.Department of AnesthesiologyMayo Clinic College of MedicineRochesterUSA
  2. 2.Department of AnesthesiologyMayo ClinicRochesterUSA

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