A potentially significant interaction between efavirenz and phenytoin: a case report and review of the literature.

Although it has not been demonstrated yet, phenytoin is expected to reduce efavirenz exposure through coinduction of cytochrome P450 (CYP) 3A4 and CYP2B6. Conversely, efavirenz has been shown in vitro to inhibit the enzymes responsible for phenytoin metabolism, CYP2C9 and CYP2C19. We report a case in which a potential bidirectional drug interaction between phenytoin and efavirenz resulted in lower-than-expected efavirenz concentrations and elevated phenytoin levels. Therapeutic drug monitoring was used in this case to ensure adequate efavirenz exposure.

[1]  Catia Marzolini,et al.  Pharmacogenetics of efavirenz and central nervous system side effects: an Adult AIDS Clinical Trials Group study , 2004, AIDS.

[2]  A. Gaedigk,et al.  Coadministration of Lopinavir/Ritonavir and Phenytoin Results in Two-Way Drug Interaction Through Cytochrome P-450 Induction , 2004, Journal of acquired immune deficiency syndromes.

[3]  S. Oka,et al.  Homozygous CYP2B6 *6 (Q172H and K262R) correlates with high plasma efavirenz concentrations in HIV-1 patients treated with standard efavirenz-containing regimens. , 2004, Biochemical and Biophysical Research Communications - BBRC.

[4]  A. Sönnerborg,et al.  Efavirenz Plasma Concentrations in HIV-Infected Patients: Inter- and Intraindividual Variability and Clinical Effects , 2004, Therapeutic drug monitoring.

[5]  Geraldine A Hamilton,et al.  Regulation of CYP2B6 in primary human hepatocytes by prototypical inducers. , 2004, Drug metabolism and disposition: the biological fate of chemicals.

[6]  David A. Flockhart,et al.  The Cytochrome P450 2B6 (CYP2B6) Is the Main Catalyst of Efavirenz Primary and Secondary Metabolism: Implication for HIV/AIDS Therapy and Utility of Efavirenz as a Substrate Marker of CYP2B6 Catalytic Activity , 2003, Journal of Pharmacology and Experimental Therapeutics.

[7]  Jacques Fellay,et al.  Population pharmacokinetics and effects of efavirenz in patients with human immunodeficiency virus infection , 2003, Clinical pharmacology and therapeutics.

[8]  R. Kim,et al.  CYP2C9 allelic variants: ethnic distribution and functional significance. , 2002, Advanced drug delivery reviews.

[9]  Sean Kim,et al.  CYP3A4 induction by drugs: correlation between a pregnane X receptor reporter gene assay and CYP3A4 expression in human hepatocytes. , 2002, Drug metabolism and disposition: the biological fate of chemicals.

[10]  V. Soriano,et al.  Higher efavirenz plasma levels correlate with development of insomnia. , 2001, Journal of acquired immune deficiency syndromes.

[11]  L. Moore,et al.  Regulation of the human CYP2B6 gene by the nuclear pregnane X receptor. , 2001, Molecular pharmacology.

[12]  J. Weide,et al.  The effect of genetic polymorphism of cytochrome P450 CYP2C9 on phenytoin dose requirement. , 2001, Pharmacogenetics.

[13]  A. Telenti,et al.  Efavirenz Plasma Levels Can Predict Treatment Failure and Central Nervous System Side Effects in Hiv-1-infected Patients , 2022 .

[14]  Patrick F. Smith,et al.  Clinical Pharmacokinetics of Non-Nucleoside Reverse Transcriptase Inhibitors , 2001, Clinical pharmacokinetics.

[15]  Paavo Honkakoski,et al.  The Repressed Nuclear Receptor CAR Responds to Phenobarbital in Activating the Human CYP2B6 Gene* , 1999, The Journal of Biological Chemistry.

[16]  K. Siersbaek-Nielsen,et al.  The effect of different sulfonamides on phenytoin metabolism in man. , 2009, Acta medica Scandinavica. Supplementum.

[17]  F. Wollheim,et al.  Plasma salicylate levels in rheumatoid arthritis: a comparison between micro-encapsulated and conventional aspirin. , 1979, Scandinavian journal of rheumatology.