What is the recommended treatment protocol for influenza A in newborns?

Treatment Protocol for Influenza A in Newborns

For newborns (0-3 months) with influenza A, treat with oral oseltamivir at 3 mg/kg per dose twice daily for 5 days, initiated as soon as possible after symptom onset. 1

Dosing by Age and Weight

Term Newborns (0-8 months)

• 3 mg/kg per dose orally twice daily for 5 days 1, 2
• This weight-based dosing is preferred over fixed-dose regimens in this age group 1
• Treatment should be initiated within 48 hours of symptom onset for maximum efficacy, though benefit may still occur if started later in hospitalized or high-risk infants 1

Preterm Infants (Dosing Based on Postmenstrual Age)

The American Academy of Pediatrics recommends postmenstrual age-based dosing for preterm infants: 1

• <38 weeks postmenstrual age: 1.0 mg/kg per dose twice daily for 5 days 1
• 38-40 weeks postmenstrual age: 1.5 mg/kg per dose twice daily for 5 days 1
• >40 weeks postmenstrual age: 3.0 mg/kg per dose twice daily for 5 days 1

Extremely Preterm Infants (<28 weeks)

• Consultation with a pediatric infectious diseases physician is mandatory 1
• Limited pharmacokinetic and safety data exist for this population 1

Formulation and Administration

Oseltamivir is available as an oral suspension (6 mg/mL concentration when reconstituted) and capsules (30 mg, 45 mg, 75 mg). 1, 2

• The oral suspension is the preferred formulation for newborns 1
• Can be administered with or without food, though giving with food may reduce gastrointestinal side effects 1, 2
• If commercial suspension is unavailable, capsules can be compounded by pharmacies to achieve 6 mg/mL concentration 1

Indications for Treatment in Newborns

Treatment should be initiated for: 1

• Any hospitalized newborn with clinically suspected or confirmed influenza, regardless of symptom duration 1
• Any newborn with severe, complicated, or progressive illness attributable to influenza 1
• Newborns at high risk of complications (including all infants <6 months of age, who are inherently high-risk) 1

Safety Considerations and Monitoring

Critical safety points for newborn treatment: 1

• Initial concerns about oseltamivir safety in infants <1 year were based on animal data using exposures several-fold higher than therapeutic levels; current consensus strongly supports use in this age group 1
• Infants should be carefully monitored for adverse events, most commonly vomiting and diarrhea 1, 3
• Research data demonstrate that doses of 2-3 mg/kg are well tolerated and achieve therapeutic drug exposures 3, 4
• In a prospective study of 65 infants, on-treatment adverse events occurred in 49% of patients, most frequently vomiting and diarrhea, with no deaths and no treatment withdrawals 3

Renal Impairment Adjustments

For newborns with creatinine clearance 10-30 mL/min: 1

• Reduce treatment dose to once daily (rather than twice daily) 1
• Oseltamivir is not recommended for end-stage renal disease not undergoing dialysis 5

Chemoprophylaxis in Newborns

Prophylaxis dosing for exposed newborns (0-8 months): 1

• 3 mg/kg per dose once daily for 7 days after last exposure 1
• For infants <3 months: prophylaxis is NOT recommended unless the situation is judged critical due to limited safety and efficacy data 1
• Prophylaxis should only be initiated within 48 hours of exposure 1

Clinical Effectiveness Evidence

Research demonstrates substantial clinical benefit in young infants: 6, 7

• In a prospective study of 23 infants with influenza A, oseltamivir treatment reduced mean illness duration from 253.5 hours (untreated) to 82.1 hours (treated), a reduction of 171.4 hours (P = 0.0003) 6
• Viral load in nasopharyngeal secretions declined rapidly within 1-2 days after initiating treatment 6
• Treatment started within 24 hours of symptom onset in children 1-3 years shortened illness duration by 3.5 days and reduced parental work absenteeism by 3 days 7
• Clinical effectiveness appears greater against influenza A than influenza B infections 6, 7

Resistance Monitoring

Oseltamivir resistance considerations: 1, 3, 4

• Current influenza A (H3N2) and most pH1N1 viruses remain sensitive to oseltamivir 1
• Resistance mutations can emerge during treatment (detected in 8 of 65 infants in one study and 3 of 87 subjects in another) 3, 4
• Amantadine and rimantadine should NOT be used due to high resistance rates 1

Common Pitfalls to Avoid

• Do not delay treatment waiting for laboratory confirmation in hospitalized newborns with suspected influenza when virus is circulating in the community 1
• Do not use age-based fixed dosing (e.g., 12 mg twice daily for <3 months) when actual weight is available; weight-based dosing (3 mg/kg) is preferred 1
• Do not withhold treatment in infants <3 months due to limited data; the benefits outweigh theoretical risks in seriously ill infants 1
• Do not use zanamivir in newborns; it is only approved for children ≥7 years for treatment and ≥5 years for prophylaxis 1

Consultation Requirements

Pediatric infectious diseases consultation is strongly advised when treating newborns and young infants with oseltamivir, particularly those <3 months of age, preterm infants, or those with serious illness. 1