Assessment of drug-drug interactions between tenofovir disoproxil fumarate and the nonnucleoside reverse transcriptase inhibitors nevirapine and efavirenz in HIV-infected patients.
BACKGROUND
Tenofovir disoproxil fumarate (DF) has been studied in combination with efavirenz in healthy volunteers and no interaction was found. No data are available on the possible interaction of tenofovir DF with nevirapine and efavirenz in HIV-infected patients. In this study the combination of nevirapine 200 mg twice daily with tenofovir DF 300 mg once daily and nevirapine 400 mg once daily with tenofovir DF 300 mg once daily were compared with nevirapine twice daily or once daily without tenofovir DF in HIV-infected patients. Furthermore, the combination of efavirenz 600 mg and tenofovir DF 300 mg once daily was compared with use of efavirenz 600 mg once daily only.


METHODS
Data were retrospectively collected from routine therapeutic drug monitoring plasma samples. Nevirapine, efavirenz, and tenofovir plasma levels and tenofovir concentration ratios were analyzed. The concentration ratio represents the measured plasma concentration compared with the time-adjusted average concentration, as measured in a reference population. Six different groups were studied: 200 mg nevirapine twice daily, 400 mg nevirapine once daily, 600 mg efavirenz once daily, all without tenofovir DF (groups 1, 2, and 3, respectively), and the same groups with the drugs combined with tenofovir 300 mg once daily (groups 4, 5, and 6, respectively).


RESULTS
Plasma samples were evaluable for 272, 18, 126, 32, 94, and 118 patients in the groups 1-6, respectively. No differences were found in plasma levels for tenofovir, nevirapine, and efavirenz for either of the combinations studied. Addition of tenofovir DF to efavirenz or nevirapine in HIV-infected patients does not influence the plasma levels of nevirapine or efavirenz. Furthermore, nevirapine and efavirenz have no effect on tenofovir plasma levels or tenofovir concentration ratios.


CONCLUSIONS
Efavirenz or nevirapine can be coadministered with tenofovir DF in HIV-infected patients without dose modifications.
Droste
Jacqueline A H
JA
Department of Clinical Pharmacy, Radboud University, Nijmegen Medical Centre, The Netherlands. J.Droste@akf.umcn.nl
Kearney
Brian P
BP
Hekster
Yechiel A
YA
Burger
David M
DM
D000225:Adenine / Q000031:analogs & derivatives* / Q000097:blood / Q000493:pharmacokinetics / Q000627:therapeutic use; D000284:Administration, Oral; D000480:Alkynes; D048588:Benzoxazines; D003521:Cyclopropanes; D004334:Drug Administration Schedule; D004347:Drug Interactions; D004359:Drug Therapy, Combination; D005260:Female; D015658:HIV Infections / Q000097:blood / Q000188:drug therapy*; D006801:Humans; D008297:Male; D019829:Nevirapine / Q000097:blood / Q000493:pharmacokinetics / Q000627:therapeutic use*; D063065:Organophosphonates / Q000097:blood / Q000493:pharmacokinetics / Q000627:therapeutic use*; D010078:Oxazines / Q000097:blood / Q000493:pharmacokinetics / Q000627:therapeutic use*; D012189:Retrospective Studies; D018894:Reverse Transcriptase Inhibitors / Q000097:blood / Q000493:pharmacokinetics / Q000627:therapeutic use; D000068698:Tenofovir
D000480:Alkynes; D048588:Benzoxazines; D003521:Cyclopropanes; D063065:Organophosphonates; D010078:Oxazines; D018894:Reverse Transcriptase Inhibitors; D019829:Nevirapine; D000068698:Tenofovir; D000225:Adenine; C098320:efavirenz