Flu Antiviral Drug Interactions

Guidance on the Use of Influenza Antiviral Agents

This page contains excerpts from Antiviral Agents for the Treatment and Chemoprophylaxis of Influenza – Recommendations of the Advisory Committee on Immunization Practices (ACIP). PDF Version [1 MB, 28 pages]. It provides guidance on the use of influenza antiviral agents, and is provided for historical context, but the text has not been updated from the ACIP document from which it was excerpted to include peramivir. Please see the current summary of recommendations for clinical practice regarding the use of influenza antiviral medications available at Influenza Antiviral Medications: Summary for Clinicians and a list of related references at Antiviral Guide References.

Clinical data are limited regarding drug interactions with inhaled zanamivir. No known drug interactions have been reported, and no clinically critical drug interactions have been predicted on the basis of in vitro and animal study data (Roche Laboratories Inc., 2009; Daniel, 1999).

Limited clinical data are available regarding drug interactions with oral oseltamivir. Because oseltamivir and oseltamivir carboxylate are excreted in the urine by glomerular filtration and tubular secretion via the anionic pathway, a potential exists for interaction with other agents excreted by this pathway. For example, co-administration of oseltamivir and probenecid resulted in reduced clearance of oseltamivir carboxylate by approximately 50% and a corresponding approximate twofold increase in the plasma levels of oseltamivir carboxylate (He, 1999).

Few published data from clinical trials are available concerning the safety or efficacy of using combinations of different classes of influenza antiviral drugs. One study suggested that use of oral oseltamivir plus inhaled zanamivir was less efficacious than monotherapy with either drug alone (Duval, 2010). Another recent study showed that a triple-combination antiviral drug (TCAD) regimen consisting of oral doses of amantadine, oseltamivir, and ribavirin, had similar pharmacokinetics in healthy volunteers to each individual antiviral during monotherapy following a single oral dose, and that TCAD was administered safely in immunocompromised patients (Seo, 2013).

Providers should consult package inserts for more detailed information about potential drug interactions.


Daniel MJ, Barnett JM, Pearson BA. The low potential for drug interactions with zanamivir. Clin Pharmacokinet 1999;36 Suppl 1:41–50.

Duval X, van der Werf S, Blanchon T, et al. Efficacy of oseltamivir-zanamivir combination compared to each monotherapy for seasonal influenza: a randomized placebo-controlled trial. PLoS Med 2010;7:e1000362.

He G, Massarella J, Ward P. Clinical pharmacokinetics of the prodrug oseltamivir and its active metabolite Ro 64-0802. Clin Pharmacokinet 1999;37(6):471-84.

Roche Laboratories Inc. Tamiflu (oseltamivir phosphate) capsules and oral suspension [package insert]. Nutley, NJ: Roche laboratories, Inc.; 2009.

Seo S, Englund JA, Nguyen JT, et al. Combination therapy with amantadine, oseltamivir and ribavirin for influenza A infection: safety and pharmacokinetics. Antiviral Therapy 2013; 18(3): 377-86.