No significant interaction reported between etravirine (TMC125) and raltegravir (MK-0518)

Tibotec have contacted doctors in the UK to notify them of results from a drug interaction study in HIV-negative volunteers that supports use of both etravirine (TMC-125) and raltegravir (MK-0518) in the same combination.

Previously, etravirine was the only antiretroviral excluded from the raltegravir expanded access programme.

Preliminary raltegravir pharmacokinetic data showed a modest effect of etravirine on raltegravir pharmacokinetics. They report a mean decrease of approximately -10%, -11% and -34% in the AUC, Cmax and C12 hr respectively.

The letter from Tibotec states that the overall decrease in raltegravir 200 mg to 600 mg in treatment-experienced patients.

Preliminary etravirine pharmacokinetic data showed essentially no meaningful effect of raltegravir on etravirine pharmacokinetics (approximately 4 to 17% mean increase in etravirine pharmacokinetic parameter values).

It also states that Tibotec and Merck have jointly reviewed the available pharmacokinetic data on TMC125 and raltegravir and concluded that co-administration of etravirine and raltegravir may be allowed for patients in the etravirine Named Patient Supply. This assessment is based upon data collected from a drug-drug interaction pharmacokinetic study in healthy volunteers to evaluate the potential interaction of the two compounds.

Merck commented that the phase II dose ranging studies for raltegravir provide a wide margin for efficacy with potent efficacy observed with doses as low as 100 mg bid in naive pts and 200 mg bid in experienced patients. The modest decrease of raltegravir level in the presence of etravirine is not expected to affect the efficacy, so no dose adjustment is needed for raltegravir.

For further details please contact Dr Perry Mohammed, Senior Medical Advisor-Virology on 01494 568313 or by email at: pmohamme@jacgb.jnj.com