EVRIOS : Comparative Evaluation of Low Versus High Doses of Rifampicin
Status:
Completed
Trial end date:
2020-12-01
Target enrollment:
Participant gender:
Summary
Rifampicin is an antibiotic usually required to treat susceptible Staphylococcus spp.
osteo-articular infections, most frequently in association with a fluoroquinolone when the
strain is susceptible to both agents. It is the reference treatment for orthopedic infections
with implanted material.
For tuberculosis treatment the dosage of 10 mg/kg/j is usually prescribed, while in the
treatment of Staphylococcus spp. infections the highest dosage of 20 mg/kg/j is proposed by
French experts' recommendations from 2009.
However, there is little evidence in the literature, which could set out arguments to choose
the best dosage of rifampicin, which may vary from 5 to 20 mg/kg.
The issue with rifampicin is side effects, in particular with long-term treatment. Many side
effects may occur in 10 to 20% of patients and sometimes leads to dosage reduction or
treatment interruption.
In the literature, there is little evidence that higher rifampicin dosage is associated with
higher frequency of adverse effects. Depending on the nature of the toxicity, one could say
that hypersensitivity could be independent from dosage, when digestive disorders may be
related. Plasmatic concentrations studies have not given strong arguments to link higher
rifampicin dosages with side effects occurrence rates. After oral absorption, plasmatic peak
occurs after two to five hours and varies among individuals but also in the same patient
overtime. This particular pharmacokinetic profile could explain discrepancy in adverse events
(AEs) frequencies.