Drug-drug interactions with raltegravir
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EUROPEAN JOURNAL OF MEDICAL RESEARCH
Eur J Med Res (2009) 14(Suppl. III): 17-21
17 © I. Holzapfel Publishers 2009
DRUG-DRUG INTERACTIONS WITH RALTEGRAVIR David M. Burger
Department of Clinical Pharmacy and Nijmegen Institute for Infection, Inflammation and Immunology (N4i), Radboud University Nijmegen Medical Centre, Nijmegen, the Netherlands
Abstract Objective: To review all currently published drug-drug interaction studies with the HIV-integrase inhibitor raltegravir. Methods: A PubMed search was conducted for all published reports up to August 1, 2009 as well as a review of updated European and US Prescriber’s Information (EMEA & FDA) and abstracts from recent international scientific meetings. Results: A total of 14 drug-drug interaction studies were found. Due to the relatively broad therapeutic range of raltegravir almost all co-administered agents can safely be combined with raltegravir, with the exception of rifampin in which a doubling of the raltegravir dose to 800mg BD is currently recommended. Conclusions: Raltegravir is not without drug-drug interactions but due to the lack of an effect on CYP450 or UGT by raltegravir and the broad therapeutic range of raltegravir itself, this agent can safely combined with almost all tested agents.
INTRODUCTION
Drug-drug interactions remain a major concern in the treatment of HIV-infected patients. This is caused by the treatment and prophylaxis of opportunistic infections, the treatment of malignancies, the high prevalence of use of psycho-active agents in the HIV-infected patient population, the treatment of adverse effects caused by this polypharmacy, etc.. As a result, it is more likely that a drug-drug interaction is present in a particular patient than that it is absent, and any HIV clinician should always be suspecting a drug-drug interaction when prescribing medications to an HIV-infected patient. With the recent introduction of newer antiretroviral agents such as the HIV-integrase inhibitor raltegravir, there is an urgent need for an updated and complete overview of potential drug-drug interactions with this agent, especially when raltegravir is used in patients being treated with multiple recently-developed antiretroviral agents, or as a substitute of other drugs in otherwise virologically stable patients (switch scenario).
PHARMACOKINETICS OF RALTEGRAVIE
The pharmacokinetics of raltegravir after single and multiple doses have been mainly characterized in healthy subjects [1]. The drug is rapidly absorbed with a median tmax in the fasted state of approximately 1 hour. Raltegravir plasma concentration decrease in a
biphasic manner with a rapid initial phase (t 1/2 of approx. 1 hour) and a slower terminal phase (t 1/2 of approx. 7-12 hour). During twice-daily dosing, this terminal elimination half-life is difficult to assess, but it is more apparent after single dosing or multiple QD dosing. Steady-state conditions are already reached after 2 days with only minimal accumulation over time. Raltegravir AUC increases almost proportionally in a single do
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