Adverse Events

Guidance on the Use of Influenza Antiviral Agents

(Current for the 2012-2013 Influenza Season)
 

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, weight, and renal function (Table 1); presence of other medical conditions; indications for use (i.e., chemoprophylaxis or therapy); and the potential for interaction with other medications.

Zanamivir

Limited data are available about the safety or efficacy of zanamivir for persons with underlying respiratory disease or for persons with complications of acute influenza, and zanamivir is licensed only for use in persons without underlying respiratory or cardiac disease [153]. 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 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 treatment [153, 216]. 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 zanamivir [153]. 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, zanamivir is not recommended for treatment of patients with underlying pulmonary disease [153]. Allergic reactions, including oropharyngeal or facial edema, also have been reported during postmarketing surveillance [153, 216].

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) [15, 16, 139]. 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 combined [153]. Zanamivir does not impair the immunologic response to TIV [217].

Oseltamivir

Nausea and vomiting were reported more frequently among adults receiving oseltamivir for treatment (nausea without vomiting, approximately 10%; vomiting, approximately 9%) than among persons receiving placebo (nausea without vomiting, approximately 6%; vomiting, approximately 3%) [91, 111, 188]. Among children treated with oseltamivir, 14% had vomiting, compared with 8.5% of placebo recipients. Overall, 1% discontinued the drug secondary to this side effect [21], and a limited number of adults who were enrolled in clinical treatment trials of oseltamivir discontinued treatment because of these symptoms [113]. Similar types and rates of adverse events were reported in studies of oseltamivir chemoprophylaxis [113]. Nausea and vomiting might be less severe if oseltamivir is taken with food [113]. In several reports based on public health responses to school outbreaks of 2009 H1N1, 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 children [155, 189, 190]. No published studies have assessed whether oseltamivir impairs the immunologic response to inactivated influenza vaccines.

Transient neuropsychiatric events (self-injury or delirium) have been reported postmarketing among persons taking oseltamivir; the majority of reports were among Japanese adolescents and adults [218]. Several recent analyses and reviews have found that oseltamivir is not associated with an increased risk of neuropsychiatric events [219, 220]. FDA advises that persons receiving oseltamivir be monitored closely for abnormal behavior [113].

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 essential [193, 221--223]. Healthcare providers should be aware of the limited data on safety and dosing when considering 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 children [224].

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). SAE that follow medications should be reported at FDA/MedWatch - Reporting By Health Professionals.

Review the references cited in this guidance.