Peramivir for Influenza A and B Viral Infections: A Pharmacokinetic Case Series

Abstract

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.

Oxygenator impact on peramivir in extra-corporeal membrane oxygenation circuits

“…While our preliminary data in this report suggests no significant alterations in PRV relating to the ECMO circuitry, dedicated studies of peramivir use with in-vivo advanced forms of life support, including CRRT, will provide valuable information for the care of critically ill adult and pediatric patients, considering PK data for critically ill pediatric patients already exists. 17 Several factors can affect drug PK with ECMO including the composition and configuration of the circuit, the individual drug, and the clinical status of patient, including organ function. 18 The Quadrox-i oxygenators are composed of a polymethylpentene microporous fiber material and a polyurethane heat exchanger with a large surface-area-to-size ratio that may impact the amount of drug sequestration.…”

“…While our preliminary data in this report suggests no significant alterations in PRV relating to the ECMO circuitry, dedicated studies of peramivir use with in-vivo advanced forms of life support, including CRRT, will provide valuable information for the care of critically ill adult and pediatric patients, considering PK data for critically ill pediatric patients already exists. 17…”

Antiviral Drugs in Influenza

“…Acute, subacute, and chronic toxicity studies have demonstrated a high margin of safety for oseltamivir and no oncogenic and mutagenic effects [ 93 , 94 ]. Overall, the drug is well tolerated, and the most common adverse effects are headache and digestive system disorders [ 12 , 59 , 67 , 68 , 69 ].…”

“…Intravenous peramivir is approved for the treatment of acute uncomplicated influenza in adults and children over 2 years of age [ 94 ]. The recommended period from the onset of symptoms to initiation of treatment is 48 h, the same as for other NAIs [ 73 , 94 ], but there are some reports of benefits from later peramivir use [ 71 ]. The drug is available as a colorless solution of 1% peramivir (200 mg in 20 mL).…”

“…The drug is available as a colorless solution of 1% peramivir (200 mg in 20 mL). The intravenous peramivir dose is 600 mg once in adults and adolescents and 12 mg/kg of body weight in children from 2 to 12 years of age [ 94 ]. Patients with renal impairment require adjustment of the dose to the level of creatinine clearance.…”