Are atazanavir levels reduced by antacids?

Levels of the protease inhibitor atazanavir (Reyataz) might not be lowered by taking antacid drugs, according to the results of a French pharmacokinetic study in HIV-positive patients. The study’s results were published in the 4^th November edition of AIDS.

In December 2004, the European Medicines Agency issued a warning that atazanavir and the ‘proton pump inhibitor’ antacid called omeprazole (Losec) should not be taken together. This was based on observations of low blood atazanavir levels in studies of HIV-negative volunteers also taking omperazole, possibly due to reduced stomach acid levels reducing the absorption of atazanavir.

This interaction was of particular concern as many antacids are available without prescription and patients may be unaware of their ability to lower atazanavir levels

To examine the effects of co-administration of atazanavir with proton pump inhibitors in HIV-positive patients, a group of researchers from two clinics in Paris compared blood levels of the drug in 13 patients taking either omprazole or rabeprazole (Pariet) to 79 who were not taking a proton pump inhibitor. All 92 patients were taking a stable antiretroviral drug regimen including ritonavir (Norvir)-boosted atazanavir.

In contrast to the observations in HIV-negative subjects, the minimal blood concentrations of atazanavir did not differ significantly between the two groups of patients: those taking a proton pump inhibitor had a median of 551ng/ml, compared to 496ng/ml in those who were not (p = 0.86). Three patients who had measurements taken before and after starting a course of proton pump inhibitors also showed no difference in atazanavir concentrations at the two time points.

“In clinical practice, proton pump inhibitors appear to be compatible with boosted atazanavir therapy,” the investigators conclude.

The researchers argue that their study failed to show an effect of concomitant antacid administration on atazanavir levels, since previous studies tended to examine higher doses of omperazole of 40mg per day. In this study, eight of the nine patients taking omperazole were taking a lower dose of 20mg per day.

They also suggest that HIV-positive patients may have lower levels of stomach acid, possibly removing the effect of antacids observed in HIV-negative subjects. “Our results show that the results of pharmacological studies in healthy subjects must be systematically confirmed in the target population,” they write.

However, the small sample size in this study limits the reliability of its findings. “It may nonetheless be prudent to monitor atazanavir drug concentrations,” the investigators acknowledge.