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Peramivir for Influenza A and B Viral Infections: A Pharmacokinetic Case Series
Jeffrey J Cies1,2,3, Wayne S Moore1, Adela Enache4
1The Center for Pediatric Pharmacotherapy LLC, Pottstown, Philadelphia, Pennsylvania.
Insights
Critically ill children receiving peramivir for influenza showed altered pharmacokinetics, requiring adjusted dosing intervals. These findings suggest peramivir (PRV) may need different regimens in the pediatric intensive care unit (PICU).
Area of Science:
- Pharmacology
- Infectious Diseases
- Critical Care Medicine
Background:
- Influenza infections in critically ill children necessitate effective antiviral treatment.
- Peramivir (PRV) is an antiviral medication used for influenza, but its pharmacokinetic profile in pediatric intensive care unit (PICU) patients is not well-established.
- Understanding PRV pharmacokinetics in this population is crucial for optimizing treatment and patient outcomes.
Purpose of the Study:
- To characterize the pharmacokinetics of peramivir (PRV) in critically ill children treated for influenza A or B viral infections.
- To compare PRV pharmacokinetics in critically ill children to existing data from healthy pediatric and adult populations.
- To inform potential adjustments in peramivir dosing regimens for critically ill pediatric patients.
Main Methods:
- Retrospective review of prospectively collected data from critically ill children treated with peramivir in a PICU.
- Analysis of peramivir samples for therapeutic drug management.
- Comparison of pharmacokinetic parameters (volume of distribution, clearance, half-life) with package insert and previous pediatric trial data.
Main Results:
- Eleven critically ill children (median age 5 years) with influenza were analyzed.
- Patients exhibited larger volume of distribution, increased clearance, and shorter half-life compared to reference data.
- All patients required adjustments to their dosing interval, with most receiving every-12-hour or every-8-hour regimens.
- No adverse events were reported with peramivir treatment.
Conclusions:
- Peramivir pharmacokinetics in critically ill children differ significantly from healthy populations.
- Current peramivir dosing regimens may be inadequate for achieving optimal therapeutic exposures in PICU patients.
- Further research is warranted to confirm these findings and establish evidence-based dosing guidelines for peramivir in critically ill children.
Objective:
To describe the peramivir (PRV) pharmacokinetics in critically ill children treated for influenza A or B viral infections.
Design:
Retrospective electronic medical record review of prospectively collected data from critically ill children receiving peramivir for influenza A or B viral infections in the pediatric intensive care unit (PICU).
Setting:
A 189-bed, freestanding children's tertiary care teaching hospital in Philadelphia, PA.
Patients:
Critically ill children admitted to the PICU who were infected with influenza between January 1, 2016 and March 31, 2018.
Interventions:
None.
Results:
Eleven patients, two females (18%) and nine males (82%), accounted for 24 peramivir samples for therapeutic drug management. The median age was 5 years (interquartile range 1.5-6.5 yrs) with a median weight of 16.4 kg (interquartile range 14-24 kg). Ten (91%) patients demonstrated a larger volume of distribution, 11 (100%) patients demonstrated an increase in clearance, and 11 (100%) patients demonstrated a shorter half-life estimate as compared with the package insert and previous pediatric trial data for peramivir. Eight (73%) patients tested positive for a strain of influenza A and 3 (27%) patients tested positive for influenza B; 4 of 11 (36%) patients tested positive for multiple viruses. All patients had adjustments made to their dosing interval to a more frequent interval. Ten (91%) patients were adjusted to an every-12-hour regimen and 1 (9%) patient was adjusted to an every-8-hour regimen. No adverse events were associated with peramivir treatment.
Conclusion:
The pharmacokinetics of PRV demonstrated in this PICU cohort differs in comparison to healthy pediatric and adult patients, and alterations to dosing regimens may be needed in PICU patients to achieve pharmacodynamic exposures. Additional investigations in the PICU population are needed to confirm these findings.
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