Pharmacokinetic parameters

Comment

Co-administration of raltegravir HD 1200 mg QD and rifampicin has not been studied.

Ref #2373 : The first part of the study compared the immediate effect of 600 mg of rifampicin over a unique dose of 400 mg of raltegravir. * The second part of the study compared the administration of 600 mg QD of rifampicin and 800 mg BID of raltegravir with regard to the administration of 400 mg BID of raltegravir alone. The authors conclude that doubling the raltegravir dose to 800 mg when coadministrated with rifampicin allows to compensate for the metabolic induction of raltegravir as for the exposure (AUC), but the trough concentrations remains at the lower limit clinically accepted. Coadministration of rifampicin and raltegravir is not contraindicated; however caution should be used.

Ref #2702 : An ANRS study presented at CROI 2013 (Abstract 539) demonstrated that treatment with efavirenz compared to raltegravir 800 mg BID for the treatment of HIV patients co-infected with tuberculosis was comparable to the point of view of efficacy and safety (30% of patients in the two groups have developed adverse reactions of grade 3).

A sub-analysis of drug interactions was published at the same conference CROI 2013. This summary showed the results of a study of drug interactions. Patients were randomized to receive either raltegravir 400 mg twice daily or 800 mg twice daily. The pharmacokinetic results were highly variable, but there was a trend toward lower concentrations of RAL (Cmax, Cmin, AUC) when it was given in 400 mg BID with rifampicin. These effects were lower in the group receiving raltegravir 800 mg BID.

Ref #2936 : † RAL 400 BID for 5 days, then 33 days of RAL (400mg bid) + RIF(900mg thrice weekly), then 5 days of RAL (800mg bid) + RIF as above.
†† Versus RAL 400mg bid without RIF.
Importantly, a significant proportion of subjects taking RAL 400mg bid (4/16) had C12h at/below the upper bound of the lowest quartile from QDMRK, associated with blunted therapeutic response. Similar findings were observed with RAL + daily RIF in patients suggesting RIF induction of RAL is comparable between daily and intermittent RIF. In the absence of definitive clinical efficacy data to suggest otherwise, doses of RAL800mg bid with thriceweekly RIF are well tolerated and yield higher AUCs and comparable C12 compared to RAL alone.

Ref #2962 : In this study, 153 received randomly raltegravir 400 mg twice a day, raltegravir 800 mg twice daily, or efavirenz 600 mg once daily. At week 24, virological suppression was achieved in 39 patients (76%) in the raltegravir 400 mg group, 40 patients (78%) in the raltegravir 800 mg group, and 32 patients (63%) in the efavirenz group. The adverse-event profile was much the same across the three groups. The authors conclude that raltegravir 400 mg twice daily might be an alternative to efavirenz for the treatment of patients co-infected with HIV and tuberculosis.

Comment

Reference

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