Tamiflu Drug Interactions

Information derived from pharmacology and pharmacokinetic studies of oseltamivir phosphate suggest that clinically significant drug interactions are unlikely.
Oseltamivir phosphate is extensively converted to the active compound by esterases, located predominantly in the liver. Drug interactions involving competition for esterases have not been extensively reported in the literature. Low protein binding of oseltamivir and the active metabolite do not suggest the probability of drug displacement interactions.
In vitro studies demonstrated that neither oseltamivir phosphate nor the active metabolite is a good substrate for P450 mixed-function oxidases or for glucuronyl transferases (see Pharmacology: Pharmacokinetics under Actions). There is no mechanistic basis for an interaction with oral contraceptives.
Cimetidine, a non-specific inhibitor of cytochrome P450 isoforms and competitor for renal tubular secretion of basic or cationic drugs has no effect on plasma levels of oseltamivir or its active metabolite.
Clinically important drug interactions involving competition for renal tubular secretion are unlikely due to the known safety margin for most of these drugs, the elimination characteristics of the active metabolite (glomerular filtration and anionic tubular secretion) and the excretion capacity of these pathways. Co-administration of probenecid results in approximate 2-fold increase in exposure to the active metabolite due to a decrease in active tubular secretion in the kidney. However, due to the wide safety margin of the active metabolite, no dose adjustments are required when co-administering with probenecid.
Co-administration with amoxicillin does not alter plasma levels of either compound, indicating that competition for the anionic secretion pathway is weak. Co-administration with paracetamol does not alter plasma levels of oseltamivir, its active metabolite, or paracetamol. No pharmacokinetic interactions between oseltamivir or its major metabolite have been observed when co-administering oseltamivir with paracetamol, acetyl-salicylic acid, cimetidine, antacids (magnesium and aluminium hydroxides and calcium carbonates), warfarin, rimantadine, or amantadine.