Clinical evidence,mechanism, importance and management
A 31-year-old woman was given intravenous rifampicin 300mg every 8 hrs and linezolid 600mg every 12 hrs for an MRSA infection. During rifampicin treatment her linezolid peak and trough levels were 7.29 and 2.04 micrograms/mL,respectively. However, when rifampicin was stopped linezolid peak and trough levels were higher, at
12.46 and 5.03 micrograms/mL,respectively (See reference number 1).
In an earlier study,healthy subjects were given a single 600mg dose of intravenous linezolid either alone or with a single 600mg dose of intravenous rifampicin. This study also found that rifampicin reduced serum levels of linezolid by 10%, 20 % and 35 % at 6, 9 and 12 hours, respectively.
Linezolid is not metabolised by cytochrome P450 enzyme system so reduction in levels is unlikely to be due to increased metabolism associated with rifampicin enzyme induction. The reduction in linezolid serum levels may be attributable to induction of P-glycoprotein by rifampicin, resulting in increased excretion of linezolid (See reference number 1,2).
The clinical significance of this interaction is unclear and concurrent use of rifampicin and linezolid is not established. The available evidence suggests that,where possible, linezolid levels should be monitored if both drugs are given. If this is not possible it would seem prudent to monitor concurrent use closely to ensure that antibacterial treatment is effective.
Gebhart BC,Barker BC, Markewitz BA. Decreased serum linezolid levels in a critically ill patient receiving concomitant linezolid and rifampin. Pharmacotherapy (2007) 27, 476–9.
Egle H,Trittler R, Kümmerer K, Lemmen SW. Linezolid and rifampicin: drug interaction contrary to expectations? Clin Pharmacol Ther (2005) 77,451–3.