Neuraminidase Inhibitors for Treatment of Influenza

Clinical Question

How safe, effective, and tolerable are oseltamivir and zanamivir in the treatment of children with influenza?

Evidence-Based Answer

Oseltamivir and zanamivir reduce the duration of illness by up to one day if taken within 36 hours of symptom onset. Oseltamivir (and, probably, zanamivir) also reduces the likelihood of otitis media as a complication of influenza (number needed to treat, approximately 10). There were no data on the medications’ efficacy in preventing influenza. Both medications are well tolerated and safe.

Practice Pointers

Two neuraminidase inhibitors, oseltamivir and zanamivir, are approved for use in children. Oseltamivir, which is approved for use in children older then one year, is taken twice daily for five days in dosages of 30 mg (in children weighing less than 15 kg), 45 mg (in children 15 to 22 kg), 60 mg (in children 23 to 40 kg) or 75 mg (in children more than 40 kg). Oseltamivir costs $33 to $67 per treatment course, depending on the dosage. (Prices represent estimated cost to the pharmacist based on average wholesale prices in Red book. Montvale, N.J.: Medical Economics Data, 2004. Cost to the patient will be higher, depending on prescription filling fee.)

Zanamivir, an inhaled agent approved for use in children older than seven years, is taken as two puffs every 12 hours for five days and costs $50 per course. Patients must begin taking oseltamivir or zanamivir within 36 hours of symptom onset.

Matheson and colleagues identified three double-blinded, randomized, placebo-controlled trials of 1,500 children with a clinical diagnosis of influenza (i.e., fever and at least two of the following symptoms: cough, headache, myalgia, sore throat, fatigue). In approximately 53 percent of the children, influenza was eventually confirmed by laboratory tests.

In the 1,500 children with clinically diagnosed influenza, oseltamivir reduced symptoms by a mean of 21 hours, and zanamivir reduced symptoms by a mean of 12 hours. In children with laboratory-confirmed influenza, oseltamivir and zanamivir reduced symptoms by 36 and 30 hours, respectively. In children with asthma and laboratory-confirmed influenza, the duration of illness was reduced by only 10 hours (P = NS).

Oseltamivir reduced the likelihood of acute otitis media from 28 to 17 percent (P = .005) and of bronchitis from 21 to 12 percent (P < .05). Zanamivir use was associated with a nonsignificant reduction in the likelihood of otitis media (23 to 16 percent, P = NS).

Although vomiting was more common in children taking zanamivir (15 percent versus 9 percent in children taking oseltamivir), both drugs were well tolerated, with pooled withdrawal rates similar to those of placebo.