The impact of enzyme-inducing antiepileptic drugs on antiretroviral drug levels: A case-control study

Jason F. Okulicz; Greg A. Grandits; Jacqueline A. French; Emilio Perucca; Jomy M. George; Michael L. Landrum; Edward P. Acosta; Gretchen L. Birbeck

doi:10.1016/j.eplepsyres.2012.07.009

The impact of enzyme-inducing antiepileptic drugs on antiretroviral drug levels: A case-control study

Jason F. Okulicz^*, Greg A. Grandits, Jacqueline A. French, Emilio Perucca, Jomy M. George, Michael L. Landrum, Edward P. Acosta, Gretchen L. Birbeck

^*Corresponding author for this work

Research output: Contribution to journal › Article › peer-review

19 Scopus citations

Abstract

Purpose: To evaluate the impact of enzyme-inducing antiepileptic drugs (EI-AEDs) on serum antiretroviral (ARV) levels in patients with HIV. Methods: Data from the U.S. Military HIV Natural History Study were screened to identify participants taking ARVs with EI-AEDs and controls taking ARVs with non enzyme-inducing AEDs (NEI-AEDs). The proportion of serum ARV levels below the recommended minimum concentrations (C_min) was compared between these groups. Results: ARV levels were available for 10 individuals exposed to 16 intervals on combined ARVs/EI-AEDs (phenytoin and carbamazepine) and for 25 controls exposed to 30 overlap intervals on combined ARVs/NEI-AEDs. The percentage of overlap intervals with ≥1 ARV levels below C_min was higher in the EI-AED group than in controls (37.5% vs. 23.3%; p=0.124). After excluding intervals associated with serum levels of EI-AEDs below the reference range (n=6), the proportion of intervals with ≥1 ARV level below C_min was significantly greater among EI-AED recipients (60%) compared to controls (23.3%; p=0.008). Conclusions: ARV levels below C_min were more common in participants receiving EI-AEDs, the difference being statistically significant for intervals associated with EI-AED levels within the reference range. These data suggest that, in agreement with current guidelines, EI-AEDs should be avoided in patients receiving ARV therapy.

Original language	English
Pages (from-to)	245-253
Number of pages	9
Journal	Epilepsy Research
Volume	103
Issue number	2-3
DOIs	https://doi.org/10.1016/j.eplepsyres.2012.07.009
State	Published - Feb 2013
Externally published	Yes

Keywords

AIDS
Drug interactions
Drug resistence
Epilepsy
Pharmacokinetics

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10.1016/j.eplepsyres.2012.07.009

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@article{702b93e40ad941da9ba8814c46b095f1,

title = "The impact of enzyme-inducing antiepileptic drugs on antiretroviral drug levels: A case-control study",

abstract = "Purpose: To evaluate the impact of enzyme-inducing antiepileptic drugs (EI-AEDs) on serum antiretroviral (ARV) levels in patients with HIV. Methods: Data from the U.S. Military HIV Natural History Study were screened to identify participants taking ARVs with EI-AEDs and controls taking ARVs with non enzyme-inducing AEDs (NEI-AEDs). The proportion of serum ARV levels below the recommended minimum concentrations (Cmin) was compared between these groups. Results: ARV levels were available for 10 individuals exposed to 16 intervals on combined ARVs/EI-AEDs (phenytoin and carbamazepine) and for 25 controls exposed to 30 overlap intervals on combined ARVs/NEI-AEDs. The percentage of overlap intervals with ≥1 ARV levels below Cmin was higher in the EI-AED group than in controls (37.5% vs. 23.3%; p=0.124). After excluding intervals associated with serum levels of EI-AEDs below the reference range (n=6), the proportion of intervals with ≥1 ARV level below Cmin was significantly greater among EI-AED recipients (60%) compared to controls (23.3%; p=0.008). Conclusions: ARV levels below Cmin were more common in participants receiving EI-AEDs, the difference being statistically significant for intervals associated with EI-AED levels within the reference range. These data suggest that, in agreement with current guidelines, EI-AEDs should be avoided in patients receiving ARV therapy.",

keywords = "AIDS, Drug interactions, Drug resistence, Epilepsy, Pharmacokinetics",

author = "Okulicz, {Jason F.} and Grandits, {Greg A.} and French, {Jacqueline A.} and Emilio Perucca and George, {Jomy M.} and Landrum, {Michael L.} and Acosta, {Edward P.} and Birbeck, {Gretchen L.}",

note = "Funding Information: Dr. French as also received funding from NINDS, Milken Foundation and the Epilepsy Therapy Project. Funding Information: Gretchen Birbeck receives research funding from the US NIH for projects in Zambia and Malawi related to epilepsy, HIV and cerebral malaria. Funding Information: Emilio Perucca Emilio Perucca received research grants from the European Union, the Italian Medicines Agency, the Italian Ministry of Health, and the Italian Ministry for Education, University and Research. He also received speaker's or consultancy fees and/or research grants from Bial, Eisai, GSK, Novartis, Ortho-McNeil Janssen, Pfizer, SK Life Sciences, Supernus, UCB Pharma, Upsher Smith, Valeant, Vertex. Funding Information: Support for this work (IDCRP-000-03) was provided by the Infectious Disease Clinical Research Program (IDCRP), a Department of Defense (DoD) program executed through the Uniformed Services University of the Health Sciences. This project has been funded in whole, or in part, with federal funds from the National Institute of Allergy and Infectious Diseases, National Institutes of Health (NIH), under Inter-Agency Agreement Y1-AI-5072. ",

year = "2013",

month = feb,

doi = "10.1016/j.eplepsyres.2012.07.009",

language = "English",

volume = "103",

pages = "245--253",

journal = "Epilepsy Research",

issn = "0920-1211",

number = "2-3",

}

TY - JOUR

T1 - The impact of enzyme-inducing antiepileptic drugs on antiretroviral drug levels

T2 - A case-control study

AU - Okulicz, Jason F.

AU - Grandits, Greg A.

AU - French, Jacqueline A.

AU - Perucca, Emilio

AU - George, Jomy M.

AU - Landrum, Michael L.

AU - Acosta, Edward P.

AU - Birbeck, Gretchen L.

N1 - Funding Information: Dr. French as also received funding from NINDS, Milken Foundation and the Epilepsy Therapy Project. Funding Information: Gretchen Birbeck receives research funding from the US NIH for projects in Zambia and Malawi related to epilepsy, HIV and cerebral malaria. Funding Information: Emilio Perucca Emilio Perucca received research grants from the European Union, the Italian Medicines Agency, the Italian Ministry of Health, and the Italian Ministry for Education, University and Research. He also received speaker's or consultancy fees and/or research grants from Bial, Eisai, GSK, Novartis, Ortho-McNeil Janssen, Pfizer, SK Life Sciences, Supernus, UCB Pharma, Upsher Smith, Valeant, Vertex. Funding Information: Support for this work (IDCRP-000-03) was provided by the Infectious Disease Clinical Research Program (IDCRP), a Department of Defense (DoD) program executed through the Uniformed Services University of the Health Sciences. This project has been funded in whole, or in part, with federal funds from the National Institute of Allergy and Infectious Diseases, National Institutes of Health (NIH), under Inter-Agency Agreement Y1-AI-5072.

PY - 2013/2

Y1 - 2013/2

N2 - Purpose: To evaluate the impact of enzyme-inducing antiepileptic drugs (EI-AEDs) on serum antiretroviral (ARV) levels in patients with HIV. Methods: Data from the U.S. Military HIV Natural History Study were screened to identify participants taking ARVs with EI-AEDs and controls taking ARVs with non enzyme-inducing AEDs (NEI-AEDs). The proportion of serum ARV levels below the recommended minimum concentrations (Cmin) was compared between these groups. Results: ARV levels were available for 10 individuals exposed to 16 intervals on combined ARVs/EI-AEDs (phenytoin and carbamazepine) and for 25 controls exposed to 30 overlap intervals on combined ARVs/NEI-AEDs. The percentage of overlap intervals with ≥1 ARV levels below Cmin was higher in the EI-AED group than in controls (37.5% vs. 23.3%; p=0.124). After excluding intervals associated with serum levels of EI-AEDs below the reference range (n=6), the proportion of intervals with ≥1 ARV level below Cmin was significantly greater among EI-AED recipients (60%) compared to controls (23.3%; p=0.008). Conclusions: ARV levels below Cmin were more common in participants receiving EI-AEDs, the difference being statistically significant for intervals associated with EI-AED levels within the reference range. These data suggest that, in agreement with current guidelines, EI-AEDs should be avoided in patients receiving ARV therapy.

AB - Purpose: To evaluate the impact of enzyme-inducing antiepileptic drugs (EI-AEDs) on serum antiretroviral (ARV) levels in patients with HIV. Methods: Data from the U.S. Military HIV Natural History Study were screened to identify participants taking ARVs with EI-AEDs and controls taking ARVs with non enzyme-inducing AEDs (NEI-AEDs). The proportion of serum ARV levels below the recommended minimum concentrations (Cmin) was compared between these groups. Results: ARV levels were available for 10 individuals exposed to 16 intervals on combined ARVs/EI-AEDs (phenytoin and carbamazepine) and for 25 controls exposed to 30 overlap intervals on combined ARVs/NEI-AEDs. The percentage of overlap intervals with ≥1 ARV levels below Cmin was higher in the EI-AED group than in controls (37.5% vs. 23.3%; p=0.124). After excluding intervals associated with serum levels of EI-AEDs below the reference range (n=6), the proportion of intervals with ≥1 ARV level below Cmin was significantly greater among EI-AED recipients (60%) compared to controls (23.3%; p=0.008). Conclusions: ARV levels below Cmin were more common in participants receiving EI-AEDs, the difference being statistically significant for intervals associated with EI-AED levels within the reference range. These data suggest that, in agreement with current guidelines, EI-AEDs should be avoided in patients receiving ARV therapy.

KW - AIDS

KW - Drug interactions

KW - Drug resistence

KW - Epilepsy

KW - Pharmacokinetics

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U2 - 10.1016/j.eplepsyres.2012.07.009

DO - 10.1016/j.eplepsyres.2012.07.009

M3 - Article

C2 - 22835761

AN - SCOPUS:84873078874

SN - 0920-1211

VL - 103

SP - 245

EP - 253

JO - Epilepsy Research

JF - Epilepsy Research

IS - 2-3

ER -

The impact of enzyme-inducing antiepileptic drugs on antiretroviral drug levels: A case-control study

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