Información del artículo
Resumen
Etravirina (ETR) es un fármaco perteneciente a la familia de los inhibidores de la transcriptasa inversa no análogos de nucleósidos (ITINAN), con actividad antiviral en situaciones de resistencia a los ITINAN de primera generación. Las interacciones farmacológicas producidas por ETR se deben a su efecto dual sobre el sistema CYP450. Es inductor de la actividad de CYP3A4 e inhibidor de la de CYP2C9 y CYP2C19. ETR presenta escasas interacciones farmacológicas clínicamente significativas, entre las que destacan los inhibidores de la proteasa sin potenciar, los ITINAN efavirenz y nevirapina, ritonavir a dosis plena y tipranavir/ritonavir. La interacción con fosamprenavir/ritonavir no es clínicamente significativa, aunque hay una escasa variación de sus valores plasmáticos al administrarse de manera conjunta con ETR. No presenta interacciones con darunavir/ritonavir.
Palabras clave:
Etravirina
Interacciones
Abstract
Etravirine (ETR) belongs to the family of non-nucleoside analogue reverse transcriptase inhibitors (NNRTIs), with antiviral activity in patients with resistance to first-generation NNRTIs. The drug interactions caused by ETR are due to its dual effect on the CYP450 system. ETR acts as an inducer of CYP3A4 and inhibitor of CYP2C9 and CYP2C19. This drug shows few clinically significant drug interactions, the most important of which involve the unboosted protease inhibitors, the NNRTIs efavirenz and nevirapine, full-dose ritonavir and tipranavir/ritonavir. Interaction with fosamprenavir/ritonavir is not clinically significant, although their plasma levels vary slightly when used in combination with ETR. ETR shows no interactions with darunavir/ritonavir.
Keywords:
Etravirine
Drug interactions
El Texto completo está disponible en PDF
Bibliografía
[1.]
D.S. Schiller, M. Youssef-Bessler.
Etravirine: a second-generation nonnucleoside reverse transcriptase inhibitor (NNRTI) active against NNRTI-resistant strains of HIV.
Clin Ther, 31 (2009), pp. 692-704
[2.]
Informe público europeo de evaluación (EPAR), Intelence European Medicines Agency (EMEA). Documento EMEA/H/C/900 [consultado 14-7-2009]. Disponible en: http://www.emea.europa.eu
[3.]
M. Schöller-Gyre, A. Raaof, G. Mannens, S. Bollen, T.N. Kakuda, D. Woodfall, et al.
Mass-balance of 14C-labelled TMC125 in healthy volunteers.
8th International Workshop on Clinical Pharmacology of HIV Therapy,
[4.]
P. Baede, S. Piscitelli, N. Graham, G. Van’t Klooster.
Drug interactions with TMC125, a Potent Next Generation NNRTI.
Program and abstracts of the Interscience Conference on Antimicrobial Agents and Chemotherapy,
[5.]
M. Schöller-Gyre, R. Hoetelmans, S. Bollen, K. Vandermeulen, M. Peeters, L. Bastiaanse, et al.
No significant interaction between TMC125 and didanosine in healthy volunteers.
3rd International AIDS Society Conference on HIV Pathogenesis and Treatment,
[6.]
M. Schöller-Güyre, C. Debroye, B. Woodfall, J. Witek, G. De Smedt, R.M. Hoetelmans.
Pharmacokinetic evaluation of the interaction between TMC125 and tenofovir disoproxil fumarate.
46th Interscience Conference on Antimicrobial Agents and Chemotherapy,
[7.]
T. Kakuda, M. Schöller-Gyüre, B. Woodfall, G. De Smedt, M. Peeters, K. Vandermeulen, et al.
TMC125 in combination with other medications: summary of drug-drug interaction studies.
8th International Congress on Drug Therapy in HIV Infection,
[8.]
M. Harris, C. Zala, S. Ramírez, B. Woodfall, M. Peeters, M. Scholler, et al.
Pharmacokinetics and safety of adding TMC125 to stable regimens of saquinavir, lopinavir and ritonavir in HIV+adults.
13th Conference on Retroviruses and Opportunistic Infections,
[9.]
M. Schöller Gyüre, B. Woodffall, T. De Marez, G. De Smedt, M. Peeters, K. Vandermeulen, et al.
Pharmacokinetics of TMC125 with atazanavir and atazanavir/ritonavir.
8th Internacional Congress on Drug Therapy in HIV Infection,
[10.]
M. Schöller, M. Kraft, R. Hoetelmans, V. Vyncke, K. Vandermeulen, M. Peeters, et al.
Significant decrease in TMC125 exposures when co-administered with tipranavir in healthy subjects.
13th Conference on Retroviruses and Opportunistic Infections,
[11.]
M. Schöller-Gyüre, B. Woodfall, S. Bollen, M. Peeters, K. Vandermeulen, R. Hoetelmans.
Pharmacokinetics of amprenavir and TMC125 in HIV infected volunteers receiving TMC125 with fosamprenavir/ritonavir.
46th Interscience Conference on Antimicrobial Agents and Chemotherapy,
[12.]
S.C. Piscitelli, P. Baede, G. Van’t Klooster, N. Graham.
TMC125 does not alter lopinavir/ritonavir pharmacokinetics in healthy volunteers.
42nd Interscience Conference on Antimicrobial Agents and Chemotherapy,
[13.]
M. Schöller-Gyüre, T.N. Kakuda, S.H. Akuma, I. De Clero, G. De Smedt, K. Spittaels, et al.
Pharmacokinetic interaction between etravirine and lopinavir/ritonavir.
49th Interscience Conference on Antimicrobial Agents and Chemotherapy (ICAAC),
[14.]
A. Lazzarin, T. Campbell, B. Clotet, M. Johnson, C. Katlama, A. Moll, et al.
Efficacy and safety of TMC125 (etravirine) in treatment-experienced HIV-1-infected patients in DUET-2: 24-week results from a randomised, double-blind, placebo-controlled trial.
Lancet, 370 (2007), pp. 39-48
[15.]
J.V. Madruga, P. Cahn, B. Grinsztejn, R. Haubrich, J. Lalezari, A. Mills, et al.
Efficacy and safety of TMC125 (etravirine) in treatment-experienced HIV-1-infected patients in DUET-1: 24-week results from a randomised, double-blind, placebo-controlled trial.
Lancet, 370 (2007), pp. 29-38
[16.]
M. Schöller-Gyüre, T.N. Kakuda, V. Sekar, B. Woodfall, G. De Smedt, E. Lefebvre, et al.
Pharmacokinetics of darunavir/ritonavir and TMC125 alone and coadministered in HIV-negative volunteers.
Antivir Ther, 12 (2007), pp. 789-796
[17.]
J. Lalezari, E. DeJesus, O. Osiyemi, P. Ruane, Z. Haigney, R. Ryan, et al.
Pharmacokinetics of once-daily etravirine (ETR) without and with once-daily darunavir/ritonavir (DRV/r) in antiretroviral-naïve HIV-1 infected adults.
9th International Congress on Drug Therapy in HIV Infection,
[18.]
J. Davis, M. Schöller-Gyre, T.N. Kakuda, C. Ridgway, S. Tweedy, N. Ndongo, et al.
An open, randomized, two period, crossover study in 2 cohorts to investigate the effect of steady state TMC125 and the combination of TMC/darunavir/ritonavir on the steady state pharmacokinetics of oral maraviroc in healthy subjects.
11th European AIDS Conference,
[19.]
A. Menard, C. Solas, S. Mokthari, S. Bregigeon, M.P. Drogoul, C. Tamalet, et al.
Etravirine-raltegravir, a marked interaction in HIV-1 infected patients: about four cases.
AIDS, 23 (2009), pp. 869-871
[20.]
M.S. Anderson, T.N. Kakuda, W. Hanley, J. Miller, J.T. Kost, R. Stoltz, et al.
Minimal pharmacokinetic interaction between the human immunodeficiency virus non-nucleoside reverse transcriptase inhibitor etravirine and the integrase inhibitor raltegravir in healthy subjects.
Antimicrob Agents Chemother, 52 (2008), pp. 4228-4232
[21.]
L. Wittkop, D. Breilh, D. Da Silva, P. Duffau, P. Mercié, I. Raymond, et al.
Virological and immunological response in HIV-1-infected patients with multiple treatment failures receiving raltegravir and optimized background therapy, ANRS CO3 Aquitaine Cohort.
J Antimicrob Chemother, 63 (2009), pp. 1251-1255
[22.]
S. Ramanathan, T.N. Kakuda, R. Mack, S. West, B.P. Kearney.
Pharmacokinetics of elvitegravir and etravirine following coadministration of ritonavir-boosted elvitegravir and etravirine.
Antivir Ther, 13 (2008), pp. 1011-1017
[23.]
M. Schöller-Gyüre, B. Woodfall, C. Debroye, T. De Marez, M. Peeters, K. Vandermeulen, et al.
Pharmacokinetic interaction between TMC125 and rifabutin.
44th Annual Meeting of the Infectious Diseases Society of America,
[24.]
Etravirine interactions chart [consultado 14-7-2009]. Disponible en: http://www.hiv-druginteractions.org
[25.]
M. Schöller-Gyüre, W. Van den Brink, T.N. Kakuda, B. Woodfall, G. De Smedt, H. Vanaken, et al.
Pharmacokinetic and pharmacodynamic study of the concomitant administration of methadone and TMC125 in HIV-negative volunteers.
J Clin Pharmacol, 48 (2008), pp. 322-329
[26.]
M. Schöller-Gyüre, T.N. Kakuda, G. De Smedt, B. Woodfall, S. Bollen, M. Peeters, et al.
Pharmacokinetic interaction between the non-nucleoside reverse transcriptase inhibitor TMC125 and atorvastatin in HIV-negative volunteers.
4th International AIDS Society Conference on HIV Pathogenesis, Treatment and Prevention,
[28.]
M. Schöller-Gyüre, T.N. Kakuda, G. De Smedt, H. Vanaken, M.P. Bouche, M. Peeters, et al.
A pharmacokinetic study of etravirine (TMC125) co-administered with ranitidine and omeprazole in HIV-negative volunteers.
Br J Pharmacol, 66 (2008), pp. 508-516
[29.]
T. Kakuda, M. Schöller-Gyüre, B. Woodfall, G. De Smedt, M. Peeters, K. Vandermeulen, et al.
TMC125 in combination with other medications: summary of drug-drug interaction studies.
8th International Congress on Drug Therapy in HIV Infection,
Copyright © 2009. Elsevier España S.L.. Todos los derechos reservados
