Are atazanavir levels reduced by antacids?

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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 4th 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

Glossary

proton-pump inhibitor

A drug for the treatment of heartburn and acid reflux, which works by blocking the enzyme system in the stomach that produces acid.

boosting agent

Booster drugs are used to ‘boost’ the effects of protease inhibitors and some other antiretrovirals. Adding a small dose of a booster drug to an antiretroviral makes the liver break down the primary drug more slowly, which means that it stays in the body for longer times or at higher levels. Without the boosting agent, the prescribed dose of the primary drug would be ineffective.

drug interaction

A risky combination of drugs, when drug A interferes with the functioning of drug B. Blood levels of the drug may be lowered or raised, potentially interfering with effectiveness or making side-effects worse. Also known as a drug-drug interaction.

sample size

A study has adequate statistical power if it can reliably detect a clinically important difference (i.e. between two treatments) if a difference actually exists. If a study is under-powered, there are not enough people taking part and the study may not tell us whether one treatment is better than the other.

sample

Studies aim to give information that will be applicable to a large group of people (e.g. adults with diagnosed HIV in the UK). Because it is impractical to conduct a study with such a large group, only a sub-group (a sample) takes part in a study. This isn’t a problem as long as the characteristics of the sample are similar to those of the wider group (e.g. in terms of age, gender, CD4 count and years since diagnosis).

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.

References

Guiard-Schmid JB et al. Proton pump inhibitors do not reduce atazanavir concentrations in HIV-infected patients treated with ritonavir-boosted atazanavir. AIDS 19: 1937-1938, 2005.