Probenecid inhibits renal secretion of active metabolite of oseltamivir and markedly raises its plasma levels, but this is notclinically relevant because of wide safety margin of oseltamivir. There was no pharmacokinetic interaction between amoxicillin and oseltamivir,and cimetidine did not alter oseltamivir pharmacokinetics.
In a study in healthy subjects,oseltamivir 75mg twice daily for 4.5 days had no effect on pharmacokinetics of a single 500mg dose of amoxicillin given with last dose of oseltamivir. Similarly, amoxicillin had no effect on pharmacokinetics of active metabolite of oseltamivir (See reference number 1).
In a crossover study in 18 healthy subjects cimetidine 400mg every 6 hrs for 4 days had no effect on pharmacokinetics of a single 150mg dose of oseltamivir given on day 2 (See reference number 1)
In a crossover study in 18 healthy subjects probenecid 500mg every 6 hrs for 4 days approximately halved renal clearance of active metabolite of oseltamivir, and increased its AUC by about 2.5-fold when a single 150mg dose of oseltamivir was given on day 2 (See reference number 1).
Probenecid appears to completely inhibit renal tubular secretion of active metabolite of oseltamivir via anionic renal transporter process. Oseltamivir does not alter amoxicillin pharmacokinetics, suggesting minimal potential to inhibit renal anionic transport process (See reference number 1). Cimetidine, which inhibits renal tubular secretion of drugs via cationic secretion transport process, had no effect on oseltamivir.
Probenecid markedly increased AUC of active metabolite of oseltamivir, but because of large safety margin of oseltamivir, this increase is not considered to be clinically relevant (See reference number 1-3). Oseltamivir did not alter amoxicillin pharmacokinetics,and is therefore unlikely to interact with other renally secreted organic acids. Other drugs that are involved in active anionic tubular secretion mechanism are also unlikely to interact. Cimetidine does not interact with oseltamivir, and other drugs that are inhibitors of renal cationic secretion transport process are unlikely to interact (See reference number 1).
Although UK manufacturer does state that clinically important drug interactions involving competition for renal tubular secretion are unlikely, they recommend care should be taken when prescribing oseltamivir to patients taking other similarly excreted drugs with a narrow therapeutic margin, and they give chlorpropamide, methotrexate, and phenylbutazone as examples (See reference number 2).
1. Hill G,Cihlar T, Oo C, Ho ES, Prior K, Wiltshire H, Barrett J, Liu B, Ward P. The anti-influenza drug oseltamivir exhibits low potential to induce pharmacokinetic drug interactions viarenal secretion–correlation of in vivo and in vitro studies. Drug Metab Dispos (2002) 30, 13–
19.
Tamiflu (Oseltamivir phosphate). Roche Products Ltd. UK Summary of product characteristics,March 2007.
Tamiflu (Oseltamivir phosphate). Roche Pharmaceuticals. US Prescribing information,July2007.