AEGiS-Glasgow [PL5.1] Use of TMC114 in combination with other drugs: guidance from pharmacokinetic studies

Eighth International Congress on Drug Therapy in HIV Infection

Glasgow, UK - 12-16 November 2006

[PL5.1] Use of TMC114 in combination with other drugs: guidance from pharmacokinetic studies

Int Cong Drug Therapy HIV 2006 Nov 12-16;8:Abstract No. PL5.1

D Back, V Sekar, E Lefebvre, M De Pauw, E De Paepe, T Vangeneugden, R Hoetelmans
University of Liverpool, Liverpool, UK; Tibotec Inc., Yardley, USA; Tibotec BVBA, Mechelen, Belgium

PURPOSE OF THE STUDY: Drug interactions (DIs) are a practical concern when treating HIV-infected patients. Pharmacokinetic (PK) interactions between TMC114 (now known as PREZISTA™) with low-dose ritonavir (TMC114/r) and other drugs used in HIV-infected patients are presented.

METHODS: Clinical studies were conducted to assess effects of combining TMC114/r with other drugs based on in-vitro findings and theoretical considerations for potential PK interactions. TMC114/r was studied with atazanavir (ATV), indinavir (IDV), lopinavir/r (LPV/r), saquinavir/r (SQV/r), efavirenz (EFV), nevirapine (NVP), tenofovir disoproxil fumarate (TDF), atorvastatin (AVS), omeprazole (OME), ranitidine (RAN), sildenafil (SIL), clarithromycin (CLA), sertraline (SER), paroxetine (PAR), oral contraceptives (OC) and ketoconazole (KTZ).

SUMMARY OF RESULTS: TMC114/r increased exposure to EFV (21%), NVP (27%), TDF (22%), IDV (23%), LPV (37%), KTZ (212%), CLA (57%), AVS and SIL (4-fold), and decreased exposure to SER (49%), PAR (39%) and ethinyl estradiol (44%). There was no change in ATV or SQV. TMC114 exposure increased by 21%, 24% and 42%, respectively, when combined with TDF, IDV and KTZ, decreased by 13%, 13%, 26% and 53%, respectively, when combined with EFV, CLA, SQV/r and LPV/r, and was unchanged when combined with ATV, NVP, AVS, OME, RAN, SER and PAR.

CONCLUSIONS: TMC114/r can be combined with many drugs with no TMC114/r dose adjustments. Some co-administered drugs may require dose adjustments (SIL, AVS, KTZ and IDV). Combining TMC114/r with LPV/r or SQV/r is not recommended. Additional contraception should be used when OC are combined with TMC114/r. Current evidence shows that DIs between TMC114/r and drugs commonly used in HIV-infected patients are well characterised and manageable.

Plenary Session: Oral Papers

2006-11-12
PL5.1

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