Journal Article

Evaluation of the Drug Interaction between Rifabutin and Efavirenz in Patients with HIV Infection and Tuberculosis

Weiner Marc, Debra Benator, Charles A. Peloquin, William Burman, Andrew Vernon, Melissa Engle, Awal Khan and Zhen Zhao

in Clinical Infectious Diseases

Published on behalf of Infectious Diseases Society of America

Volume 41, issue 9, pages 1343-1349
Published in print November 2005 | ISSN: 1058-4838
Published online November 2005 | e-ISSN: 1537-6591 | DOI: http://dx.doi.org/10.1086/496980
Evaluation of the Drug Interaction between Rifabutin and Efavirenz in Patients with HIV Infection and Tuberculosis

More Like This

Show all results sharing these subjects:

  • Infectious Diseases
  • Immunology
  • Public Health and Epidemiology
  • Microbiology

GO

Show Summary Details

Preview

Background. Because of drug-drug interactions mediated by hepatic cytochrome P450, tuberculosis treatment guidelines recommend an increase in rifabutin from 300 mg to 450 or 600 mg when combined with efavirenz-based antiretroviral therapy. To assess this recommendation, rifabutin and efavirenz pharmacokinetic parameters were investigated.

Methods. Plasma concentrations of rifabutin were determined as a baseline control in 15 patients with tuberculosis and human immunodeficiency virus (HIV) infection who were treated with rifabutin 300 mg and isoniazid 15 mg/kg (up to 900 mg) twice weekly. Rifabutin, isoniazid, and efavirenz concentrations were determined after a median of 21 days (interquartile range, 20–34 days) of daily efavirenz-based antiretroviral therapy with twice-weekly rifabutin 600 mg and isoniazid 15 mg/kg.

Results. The mean rifabutin area under the concentration-time curve (AUC0–24) increased 20% from the baseline value (geometric mean, 5.0 vs. 4.2 µg*h/mL; ratio of geometric means, 1.2 [90% confidence interval, 1.0–1.4]). Also, the mean efavirenz AUC0–24 in the 15 patients taking concomitant rifabutin 600 mg twice-weekly was 10% higher than that in 35 historical subjects with HIV infection who were not taking rifabutin. Efavirenz-based antiretroviral therapy was effective; HIV load decreased 2.6 log copies/mL, and the median CD4+ T cell count increased from 141 to 240 cells/mm3 after a median of 21 days of efavirenz-based antiretroviral therapy. No statistically significant differences in isoniazid pharmacokinetic parameters were found.

Conclusions. The rifabutin dose increase from 300 mg to 600 mg was adequate to compensate for the efavirenz drug interaction in most patients, and no drug interaction with isoniazid was detected. Efavirenz therapy administered at a standard 600-mg dose achieved adequate plasma concentrations in patients receiving intermittent rifabutin and isoniazid therapy, was generally well tolerated, and demonstrated potent antiretroviral activity.

Journal Article.  3968 words.  Illustrated.

Subjects: Infectious Diseases ; Immunology ; Public Health and Epidemiology ; Microbiology

Full text: subscription required

How to subscribe Recommend to my Librarian

Users without a subscription are not able to see the full content. Please, subscribe or login to access all content.