Best Evidence Analyses and Commentary

Tamiflu Expanded Indication
Ketal Patel, PharmD Candidate
01/22/13

Tamiflu® (oseltamavir) is an antiviral agent that is indicated for prophylaxis of influenza and treatment of acute illness caused by influenza A or B viral infection with symptom onset within 48 hours.   As of December 21, 2012 the FDA has expanded the indication of Tamiflu for treatment of influenza infection to include pediatric patients of ages 2 weeks to 1 year.  When the product was originally approved in 1999, it was not indicated for the treatment of children less than 1 year of age, and it is still not indicated for influenza prophylaxis in children less than 1 year of age. The decision to expand the indication was based on data extrapolated from previous studies done in adults and children and two additional, safety and pharmacokinetic studies. 1-3

Two open label trials evaluated the safety and pharmacokinetics of oseltamivir and oseltamivir carboxylate in influenza infected pediatric patients 2 weeks to less than 1 year of age (including premature infants at least 36 weeks post conceptional age). Subjects received oseltamavir at doses ranging from 2 to 3.5 mg/kg twice daily for 5 days depending on subject age. These clinical trials were not designed to evaluate clinical efficacy or virologic response. The trials provided adequate safety data to support the recommended dose selection for the treatment of acute illness in children 2 weeks to 1 year of age of 3 mg/kg twice daily.2-3

Of the 136 subjects under the age of 1 year enrolled and dosed in the trials, the majority of the subjects were male (55%), white (79%), non-Hispanic (74%), full term (76%) and infected with influenza A (80%). Pharmacokinetic data indicated that a dose of 3 mg/kg twice daily in pediatric subjects 2 weeks to less than 1 year of age provided oseltamavir concentrations similar to or higher than those observed in older pediatric subjects and adults receiving the approved dose and, by extrapolation to earlier study results, the FDA has concluded that is expected to provide similar efficacy. 2-3

Current dosing recommendation for the treatment of flu in adults and children older than 2 years of age or those with body weight >40 kg is 75 mg twice daily for 5 days.  The treatment dosing recommendation for oseltamivir for children aged ≥1 year who weigh ≤15 kg is 30 mg twice a day. For children who weigh >15 kg and up to 23 kg, the dose is 45 mg twice a day. For children who weigh >23 kg and up to 40 kg, the dose is 60 mg twice a day. For children less than 1 year of age, dosing is weight based at 3 mg/kg twice daily.4

In conclusion, Tamiflu is indicated for the treatment of flu in children as young as 2 weeks old when time since symptom onset is less than 48 hours. However, it has not been approved for prophylaxis of flu in children less than one year old. Children under the age of 2 years are among those in the highest risk category for developing complications related to influenza infection. As of January 5 2013, The Center for Disease Control (CDC) reports the death of 20 pediatric patients from this season’s flu outbreak.5 This new expanded indication of oseltamivir can become an important part of preventing deaths of pediatric patients.

References

1. FDA News Releases. FDA expands Tamiflu’s use to treat children younger than 1 year. Cited on Jan 8, 2013 at fda.gov.

2. Tamiflu (oseltamivir phosphate) capsules and oral suspension package insert. Roche Laboratories Inc. Jan 2008.  

3. Kimberlin D, Acosta E, Prichard M, Sanchez P, Ampofo K, et al. Oseltamivir Pharmacokinetics, Dosing and Resistance in Children From Birth to Two Years of Age with Influenza. Journal of Infectious Diseases.

4. Seasonal Influenza. Guidance on the Use of Influenza Antiviral Agents. Centers for Disease Control and Prevention. Cited on Jan 9, 2013. Available at CDC.gov.

5. Seasonal Influenza. Flu Activity and Surveillance. Center for Disease Control and Prevention.  Cited on Jan 14, 2013. Available at CDC.gov.

 

 

 

 


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