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Antiviral Adverse Events

Guidance on the Use of Influenza Antiviral Agents

What to know

When considering use of influenza antiviral medications, clinicians must consider many factors such as age, weight, renal function, other medical conditions, indications for use, and potential for interaction with other medication.

Background

This page contains excerpts from Antiviral Agents for the Treatment and Chemoprophylaxis of Influenza – Recommendations of the Advisory Committee on Immunization Practices (ACIP). 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.

Influenza Antiviral Medications: Summary for Clinicians
A summary for clinicians regarding using influenza antiviral medications for the current season.
PDF: Antiviral Agents for the Treatment and Chemoprophylaxis of Influenza – Recommendations of the Advisory Committee on Immunization Practices (ACIP)
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When considering use of influenza antiviral medications (i.e., choice of antiviral drug, dosage, and duration of therapy), clinicians must consider the patient's age and weight; renal function and presence of other medical conditions; indications for use (i.e., chemoprophylaxis or therapy); and the potential for interaction with other medications.

Keep Reading: Influenza Antiviral Medications: Summary for Clinicians

Zanamivir

Limited data are available about the safety or efficacy of inhaled zanamivir for persons with underlying respiratory disease or for persons with complications of acute influenza, and inhaled zanamivir is licensed only for use in persons without underlying respiratory or cardiac disease1. In a study of zanamivir treatment of ILI among persons with asthma or chronic obstructive pulmonary disease in which study medication was administered after use of a B2-agonist, 13% of patients receiving inhaled zanamivir and 14% of patients who received placebo (inhaled powdered lactose vehicle) experienced a greater than 20% decline in forced expiratory volume in 1 second (FEV1) after treatment12. However, in a phase-I study of persons with mild or moderate asthma who did not have ILI, one of 13 patients experienced bronchospasm after administration of inhaled zanamivir1. In addition, during postmarketing surveillance, cases of respiratory function deterioration after inhalation of zanamivir have been reported. Because of the risk for serious adverse events and because efficacy has not been demonstrated among this population, inhaled zanamivir is not recommended for treatment of patients with underlying pulmonary disease1. Allergic reactions, including oropharyngeal or facial edema, also have been reported during postmarketing surveillance12.

In clinical treatment studies of persons with uncomplicated influenza, the frequencies of adverse events were similar for persons receiving inhaled zanamivir and for those receiving placebo (i.e., inhaled lactose vehicle alone)345. The most common adverse events reported by both groups were diarrhea, nausea, sinusitis, nasal signs and symptoms, bronchitis, cough, headache, dizziness, and ear, nose, and throat infections. Each of these symptoms was reported by less than 5% of persons in the clinical treatment studies combined1. Inhaled zanamivir does not impair the immunologic response to TIV.6

Oseltamivir

Nausea and vomiting were reported more frequently among adults receiving oral oseltamivir for treatment (nausea without vomiting, approximately 10%; vomiting, approximately 9%) than among persons receiving placebo (nausea without vomiting, approximately 6%; vomiting, approximately 3%)789. Among children treated with oral oseltamivir, 14% had vomiting, compared with 8.5% of placebo recipients. Overall, 1% discontinued the drug secondary to this side effect10, and a limited number of adults who were enrolled in clinical treatment trials of oral oseltamivir discontinued treatment because of these symptoms11. Similar types and rates of adverse events were reported in studies of oseltamivir chemoprophylaxis11. Nausea and vomiting might be less severe if oseltamivir is taken with food11. In several reports based on public health responses to school outbreaks of influenza A(H1N1)pdm09 (2009 H1N1) virus, self-reported nausea and vomiting has been more common than reported in clinical studies, and might reduce compliance with recommended treatment or chemoprophylaxis regimens among children121314. No published studies have assessed whether oral oseltamivir impairs the immunologic response to inactivated influenza vaccines.

Transient neuropsychiatric events (self-injury or delirium) have been reported during post-marketing surveillance among persons taking oral oseltamivir; the majority of reports were among Japanese adolescents and adults15. Several recent analyses and reviews have found that oral oseltamivir is not associated with an increased risk of neuropsychiatric events1617. FDA advises that persons receiving oral oseltamivir be monitored closely for abnormal behavior11.

Limited safety data on oseltamivir treatment for seasonal influenza in children less than one year of age have not demonstrated any age-related safety concerns, but careful attention to dosing is essential18192021. Healthcare providers should be aware of the limited data on safety and dosing when considering oral oseltamivir use for infants, and carefully monitor infants for adverse events. Clinicians and pharmacists should pay careful attention to the potential for dosing errors in young children22.

Reporting of Adverse Events that Occur After Administering Antiviral Medications

Health care professionals should report all serious adverse events (SAE) after antiviral medication use promptly to MedWatch, the FDA's adverse event reporting program for medications. SAE are defined as medical events that involve hospitalization, death, life-threatening illness, disability, or certain other medically important conditions (refer to FDA/MedWatch website).

See Also: FDA/MedWatch – Reporting By Health Professionals.
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National Center for Immunization and Respiratory Diseases (NCIRD)
  1. Glaxo Wellcome Inc. Relenza (zanimivir for inhalation) [Package insert]. Research Triangle Park, NC: Glaxo Wellcome, Inc.; 2009.
  2. Gravenstein S, Johnston SL, Loeschel E, et al. Zanamivir: a review of clinical safety in individuals at high risk of developing influenza-related complications. Drug Saf 2001;24:1113–25.
  3. Hayden FG, Osterhaus AD, Treanor JJ, et al. Efficacy and safety of the neuraminidase inhibitor zanamivir in the treatment of influenzavirus infections. GG167 Influenza Study Group. N Engl J Med 1997;337:874–80.
  4. Monto AS, Fleming DM, Henry D, et al. Efficacy and safety of the neuraminidase inhibitor zanamivir in the treatment of influenza A and B virus infections. J Infect Dis 1999;180:254–61.
  5. MIST (Management of Influenza in the Southern Hemisphere Trialists). Randomised trial of efficacy and safety of inhaled zanamivir in treatment of influenza A and B virus infections. The MIST (Management of Influenza in the Southern Hemisphere Trialists) Study Group. Lancet 1998;352:1877–81.
  6. Webster A, Boyce M, Edmundson S, et al. Coadministration of orally inhaled zanamivir with inactivated trivalent influenza vaccine does not adversely affect the production of antihaemagglutinin antibodies in the serum of healthy volunteers. Clin Pharmacokinet 1999;36 Suppl 1:51–8.
  7. Schmid ML, Kudesia G, Wake S, et al. Prospective comparative study of culture specimens and methods in diagnosing influenza in adults. BMJ 1998;316:275.
  8. Baz M, Abed Y, Papenburg J, et al. Emergence of oseltamivir-resistant pandemic H1N1 virus during prophylaxis. N Engl J Med 2009;361:2296–7.
  9. LaForce C, Man CY, Henderson FW, et al. Efficacy and safety of inhaled zanamivir in the prevention of influenza in community-dwelling, high-risk adult and adolescent subjects: a 28-day, multicenter, randomized, double-blind, placebo-controlled trial. Clin Ther 2007;29:1579–90; discussion 1577–8.
  10. Whitley RJ, Hayden FG, Reisinger KS, et al. Oral oseltamivir treatment of influenza in children. Pediatr Infect Dis J 2001;20:127–33.
  11. Roche Laboratories Inc. Tamiflu (oseltamivir phosphate) capsules and oral suspension [package insert]. Nutley, NJ: Roche laboratories, Inc.; 2009.
  12. Hayden FG, Jennings L, Robson R, et al. Oral oseltamivir in human experimental influenza B infection. Antivir Ther 2000;5:205–13.
  13. Nichols WG, Guthrie KA, Corey L, et al. Influenza infections after hematopoietic stem cell transplantation: risk factors, mortality, and the effect of antiviral therapy. Clin Infect Dis 2004;39:1300–6.
  14. Kitching A, Roche A, Balasegaram S, et al. Oseltamivir adherence and side effects among children in three London schools affected by influenza A(H1N1)v, May 2009—an internet-based cross-sectional survey. Euro Surveill 2009;14:19287.
  15. Anonymous. New concerns about oseltamivir. Lancet 2007;369:1056.
  16. Blumentals WA, Song X. The safety of oseltamivir in patients with influenza: analysis of healthcare claims data from six influenza seasons. MedGenMed 2007;9:23.
  17. Toovey S, Rayner C, Prinssen E, et al. Assessment of neuropsychiatric adverse events in influenza patients treated with oseltamivir: a comprehensive review. Drug Saf 2008;31:1097–114.
  18. Kimberlin DW, Shalabi M, Abzug MJ, et al. Safety of oseltamivir compared with the adamantanes in children less than 12 months of age. Pediatr Infect Dis J 2009;29:195–8.
  19. Tamura D, Miura T, Kikuchi Y. Oseltamivir phosphate in infants under 1 year of age with influenza infection. Pediatr Int 2005;47:484.
  20. Shalabi M, Abughali N, Abzug M, et al., Safety of oseltamivir vs. amantadine of rimantadine in children under 1 year of age [Abstract]. Presented at the 45th annual meeting of the Infectious Diseases Society of America, October 4–7, 2007; San Diego, California.
  21. Okamoto S, Kamiya I, Kishida K, et al. Experience with oseltamivir for infants younger than 1 year old in Japan. Pediatr Infect Dis J 2005;24:575–6.
  22. Budnitz DS, Lewis LL, Shehab N, et al. CDC and FDA response to risk of confusion in dosing Tamiflu oral suspension. N Engl J Med 2009;361:1913–4.