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Low atovaqone levels compromise prophylactic efficacy for PCP

July 10 2017

Atovaquone is one of the alternative drugs that can be used for prophylaxis against Pneumocystis pneumonia (PCP) in immunosuppressed individuals. These alternative regimens though less efficacious than cotrimoxazole (cotrim, Septrin®, Bactrim®, TMP/SMX) which is the gold standard, may be required in a significant number of patients, because of allergy or intolerance.

Christine Robin et al from the Henri Mondor Teaching Hospital in Paris, found low atovaquone levels in 58% of patients assessed. The assayed 82 plasma concentrations of atovaquone from 33 adults on PCP prophylaxis after a steady state had been achieved. Cmin levels (taken 12 hours after administration) and Cmax levels (1-5 hours after administration) were assessed in routine conditions. The Cmin levels were compared to a >15µg/mL threshold determined from a previous study.

The median Cmin of atovaquone was 11.3 μg/mL (6.2–27.8) and was not significantly different from the median Cmax of 13.4 μg/mL (6.0–28.3) [P = 0.073]. More than half the patients (58%) had a Cmin below the threshold. This study demonstrates great inter-individual variability and suboptimal plasma drug levels that may necessitate therapeutic drug monitoring of atovaquone. It is not clear if dose escalation would result in higher plasma concentrations.