Increasing nevirapine dose can overcome reduced bioavailability due to rifampicin coadministration

Government of Tamil Nadu, Mathurai, Tamil Nadu, India
JAIDS Journal of Acquired Immune Deficiency Syndromes (Impact Factor: 4.39). 06/2006; 42(1):36-41. DOI: 10.1097/01.qai.0000214808.75594.73
Source: PubMed

ABSTRACT We studied the effect of rifampicin on steady-state pharmacokinetics of nevirapine and the impact of increasing the dose of nevirapine on its peak (Cmax) and trough (Cmin) levels in 13 HIV-infected patients on regular antiretroviral treatment with nevirapine-containing regimens (200 mg twice daily). A baseline pharmacokinetic study was conducted and repeated after 1 week of daily rifampicin (450/600 mg). The study was repeated in 7 of 8 patients who had subtherapeutic Cmin nevirapine levels after increasing nevirapine dose to 300 mg twice daily. Liver function was monitored. Rifampicin caused significant reductions in Cmax (42%), Cmin (53%), and exposure (46%) of nevirapine (P <.01). The Cmin of nevirapine fell below the therapeutic range of 3 microg/ml in 8 of 13 patients. An increase of nevirapine to 300 mg twice daily raised Cmin to therapeutic range in all 7 patients without exceeding the toxic level of 12 microg/mL. There were no clinical or laboratory adverse events. Our findings suggest that decreased bioavailability of nevirapine because of rifampicin coadministration could be overcome by increasing the dose of nevirapine from 200 to 300 mg twice daily without short-term adverse events. Further studies to evaluate the long-term safety of higher dose of nevirapine are required.

Download full-text


Available from: Sikhamani Rajasekaran, Dec 14, 2013
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: ESC 1753 1763 2401 0.60 (0.5-0.8) 0.60 (0.4-0.9) FDN 3148 2920 2702 1.11 (1.0-1.2) 1.08 (0.9-1.3) *P value 0.01 0.08 0.73 AUC 0-12 ng.h/mL ESC 25223 23668 32606 0.72 (0.6-0.9) 0.57 (0.5 -0.7) FDN 43195 44918 41997 1.03 (0.9-1.1) 1.07 ( 1.0-1.1) *P value
  • [Show abstract] [Hide abstract]
    ABSTRACT: This paper presents the asymptotic performance of Hamming and extended Hamming product codes for the binary symmetric channel and the additive white Gaussian noise (AWGN) channel. Simulation results for very low complexity high dimensional single parity check product codes on the AWGN channel are also given
    Communications, 1999. ICC '99. 1999 IEEE International Conference on; 02/1999
  • [Show abstract] [Hide abstract]
    ABSTRACT: HIV and tuberculosis (TB) are leading global causes of mortality and morbidity, and yet effective treatment exists for both conditions. Rifamycin-based antituberculosis therapy can cure HIV-related TB and, where available, the introduction of highly active antiretroviral therapy (HAART) has markedly reduced the incidence of AIDS and death. Optimal treatment regimens for HIV/TB co-infection are not yet clearly defined. Combinations are limited by alterations in the activity of the hepatic cytochrome P450 (CYP) enzyme system, which in particular may produce subtherapeutic plasma concentrations of antiretroviral drugs. For example, protease inhibitors often must be avoided if the potent CYP inducer rifampicin is co-administered. However, an alternative rifamycin, rifabutin, which has similar efficacy to rifampicin, can be used with appropriate dose reduction. Available clinical data suggest that, for the majority of individuals, rifampicin-based regimens can be successfully combined with the non-nucleoside reverse transcriptase inhibitors nevirapine and efavirenz. Most available HAART regimens in areas that have a high burden of TB contain one or the other of these drugs as a backbone. However, significant questions remain as to the optimal dose of either agent required to ensure therapeutic plasma concentrations, especially in relation to particular ethnic groups. The timing of HAART initiation after starting antituberculosis therapy continues to be controversial. Debate centres upon whether early initiation of HAART increases the risk of paradoxical reactions (immune reconstitution-related events) and other adverse events, or whether delay greatly elevates the risk of disease progression. Further prospective clinical data are needed to help inform practice in this area.
    Drugs 02/2006; 66(18):2299-308. DOI:10.2165/00003495-200666180-00003 · 4.13 Impact Factor
Show more