3rd International AIDS Society Conference on HIV Pathogenesis and Treatment Rio de Janeiro - July 24 - 27, 2005

INCREASING NEVIRAPINE DOSE CAN OVERCOME REDUCED BIOAVAILABILITY DUE TO RIFAMPICIN CO-ADMINISTRATION

IAS Conf HIV Pathog Treat 2005 Jul 24-27;3rd: Abstract No. WePe3.3C02

Ramachandran G.¹, Hemanth Kumar A.K.¹, Rajasekaran S.², Padmapriyadarsini C.¹, Narendran G.¹, Sukumar B.¹, Swaminathan S.^1
1Tuberculosis Research Centre, Chennai, India, ²Government Hospital of Thoracic Medicine, Chennai, India

INTRODUCTION: Majority of patients in the developing world who are receiving antiretroviral therapy (ART) are on 3-drug fixed dose combination pills that include nevirapine (NVP). Rifampicin (RMP), an integral part of anti-TB therapy, induces the cytochrome P-450 system, which is involved in the metabolism of NVP. We wanted to study the effect of RMP on steady state pharmacokinetics of NVP and the impact of increasing the dose of NVP on its peak (C_max) and trough (C_min) levels.

METHODS: Thirteen HIV-infected patients, on regular ART (stavudine 30/40 mg + lamivudine 150 mg + nevirapine 200 mg b.i.d.) participated. Patients had been on ART for 1 – 8 months. A baseline pharmacokinetic study was conducted and repeated after one week of daily RMP 450/600 mg. The study was repeated in 7 out of 8 patients who had sub-therapeutic C_min NVP levels, after increasing their NVP dose to 300 mg b.i.d. Liver function was monitored.

RESULTS: Significant reductions in C_max (42 %), C_min (53 %) and exposure (46 %) of NVP were observed when RMP was also administered (p<0.01). The C_min of NVP fell below the therapeutic range of 3.4µg/ml in 8 out of 13 patients. An increase of NVP to 300 mg b.i.d. raised C_min in all the 7 patients tested to above therapeutic levels and did not cross the toxic level of 12µg/ml. There were no clinical or laboratory adverse events.

CONCLUSIONS: Rifampicin significantly reduced the bioavailability of NVP, and the C_min to sub-therapeutic levels in a high proportion (62%) of patients. This could be overcome by increasing the dose of NVP from 200 mg to 300 mg b.i.d., without any short term adverse events. However, this needs to be confirmed on a larger sample size.

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050724
Clinical | WePe3.3C02 | Geetha Ramachandran
Drug Interactions

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