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    Peramivir

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    Apr.12.2024

    Peramivir

    Indications/Dosage

    Labeled

    • influenza A virus infection
    • influenza B virus infection

    Seasonal influenza virus:

    • Antiviral treatment with peramivir is recommended for patients with acute uncomplicated influenza infection who are at higher risk for influenza complications (i.e., adults 65 years and older; patients with chronic conditions; immunosuppressed patients; females who are pregnant or postpartum [less than 2 weeks since delivery]; pediatric patients on long-term aspirin therapy; American Indians/Alaska Natives; morbidly obese patients; and residents of long-term care facilities). Treatment may also be considered for previously healthy, symptomatic patients that are not considered high risk based on clinical judgment if treatment can be initiated within 48 hours of symptom onset.
    • Intravenous peramivir is a treatment option for patients who cannot absorb orally or enterally administered oseltamivir or tolerate inhaled zanamivir.[63520][63866]
    • When indicated, antiviral therapy should be started as soon as possible after illness onset, ideally within 48 hours of symptom onset.
    • The 2009 H1N1 influenza virus (swine influenza) is included in seasonal influenza A viruses.[62315][63866]

     

    Novel influenza A viruses associated with severe human disease, including avian influenza virus:

    • Antiviral therapy is recommended as early as possible for patients with suspected or confirmed cases, even if more than 48 hours have elapsed since illness onset. Treatment is also recommended for any patient with recent or close contact with a confirmed or probable case.[62336][62338]

     

    Limitations of Use:

    • Efficacy of peramivir was based on clinical trials in which the predominant influenza virus type was influenza A; a limited number of subjects infected with influenza B were enrolled.
    • Because influenza viruses change over time, influenza drug susceptibility patterns and treatment effects should be considered when deciding whether to use peramivir.
    • Efficacy has not been established in patients with serious influenza requiring hospitalization.[58671]

    Off-Label

    • avian influenza A virus infection
    † Off-label indication

    For the treatment of uncomplicated acute influenza (e.g., influenza A virus infection or influenza B virus infection)

    Intravenous dosage

    Adults

    600 mg IV as a single dose within 48 hours of symptom onset.[58671] [62315] [63866]

    Adolescents

    600 mg IV as a single dose within 48 hours of symptom onset.[58671] [62315] [63866]

    Infants and Children 6 months to 12 years

    12 mg/kg/dose (Max: 600 mg/dose) IV as a single dose within 48 hours of symptom onset.[58671] [62315] [63866]

    For the treatment of novel influenza A viruses associated with severe human disease†, including avian influenza A virus infection†

    Intravenous dosage

    Adult outpatients with uncomplicated, mild-to-moderate illness

    600 mg IV as a single dose within 48 hours of symptom onset.[62336] [62315]

    Hospitalized adults who are unable to tolerate or absorb oseltamivir

    600 mg IV once daily for a minimum of 5 days may be used as an alternative. Consider longer courses (e.g., 10 days) for severely ill hospitalized patients or immunosuppressed patients. Clinical judgement and virologic testing should guide duration assessment.[62336] [62315]

    Adolescent outpatients with uncomplicated, mild-to-moderate illness

    600 mg IV as a single dose within 48 hours of symptom onset.[62336] [62315]

    Hospitalized adolescents who are unable to tolerate or absorb oseltamivir

    600 mg IV once daily for a minimum of 5 days may be used as an alternative. Consider longer courses (e.g., 10 days) for severely ill hospitalized patients or immunosuppressed patients. Clinical judgement and virologic testing should guide duration assessment.[62336] [62315]

    Children 2 to 12 years who are outpatients with uncomplicated, mild-to-moderate illness

    12 mg/kg (Max: 600 mg) IV as a single dose within 48 hours of symptom onset.[62336] [62315]

    Hospitalized children 2 to 12 years who are unable to tolerate or absorb oseltamivir

    12 mg/kg/dose (Max: 600 mg/dose) IV once daily for a minimum of 5 days may be used as an alternative. Consider longer courses (e.g., 10 days) for severely ill hospitalized patients or immunosuppressed patients. Clinical judgement and virologic testing should guide duration assessment.[62336] [62315]

    Therapeutic Drug Monitoring

    Maximum Dosage Limits

    • Adults

      600 mg/day IV.

    • Geriatric

      600 mg/day IV.

    • Adolescents

      600 mg/day IV.

    • Children

      12 mg/kg/day (Max: 600 mg/day) IV.

    • Infants

      6 months and older: 12 mg/kg/day IV.

      younger than 6 months: Safety and efficacy have not been established.

    • Neonates

      Safety and efficacy have not been established.

    Patients with Hepatic Impairment Dosing

    The pharmacokinetics of peramivir in patients with hepatic impairment have not been studied. Because peramivir is not significantly metabolized by the liver, no dose adjustment is necessary for patients with impaired hepatic function.[58671]

    Patients with Renal Impairment Dosing

    Adults [58671]:

    CrCl 50 mL/minute or more: No dosage adjustment necessary.

    CrCl 30 to 49 mL/minute: 200 mg IV as single dose.

    CrCl 10 to 29 mL/minute: 100 mg IV as single dose.

     

    Adolescents [58671]:

    CrCl 50 mL/minute or more: No dosage adjustment necessary.

    CrCl 30 to 49 mL/minute: 200 mg IV as single dose.

    CrCl 10 to 29 mL/minute: 100 mg IV as single dose.

     

    Children 2 to 12 years [58671]:

    CrCl 50 mL/minute or more: No dosage adjustment is necessary.

    CrCl 30 to 49 mL/minute: 4 mg/kg (Max: 200 mg/dose) IV as single dose.

    CrCl 10 to 29 mL/minute: 2 mg/kg (Max: 100 mg/dose) IV as single dose.

     

    Intermittent Hemodialysis:

    Peramivir is removed by hemodialysis. In patients with chronic renal impairment maintained on hemodialysis, peramivir should be administered after dialysis at a dose adjusted on renal function.[58671]

    † Off-label indication
    Revision Date: 04/12/2024, 12:16:56 PM

    References

    58671 - Rapivab (peramivir injection) package insert. Durham, NC: BioCryst Pharmacetuicals, Inc; 2024 Jun.62315 - Centers for Disease Control and Prevention (CDC). Influenza antiviral medications: Summary for clinicians, 2020-2021. Retrieved November 5, 2020. Available on the World Wide Web at https://www.cdc.gov/flu/professionals/antivirals/summary-clinicians.htm62336 - Centers for Disease Control and Prevention (CDC). Interim guidance on the use of antiviral medications for treatment of human infections with novel influenza A viruses associated with severe human disease. Retrieved May 3, 2022. Available on the World Wide Web at https://www.cdc.gov/flu/avianflu/novel-av-treatment-guidance.htm62338 - Centers for Disease Control and Prevention (CDC). Interim guidance on follow-up of close contacts of persons infected with novel influenza A viruses associated with severe human disease and on the use of antiviral medications for chemoprophylaxis. Retrieved May 4, 2022. Available on the World Wide Web at https://www.cdc.gov/flu/avianflu/novel-av-chemoprophylaxis-guidance.htm63520 - American Academy of Pediatrics Committee on Infectious Diseases. Recommendations for Prevention and Control of Influenza in Children, 2024-2025: Technical report. Pediatrics 2024; 154(4): e2024068508.63866 - Uyeki TM, Bernstein HH, Bradley JS, et al. Clinical Practice Guidelines by the Infectious Diseases Society of America: 2018 Update on Diagnosis, Treatment, Chemoprophylaxis, and Institutional Management of Seasonal Influenza. Clin Infect Dis 2019;68:e1-e47.

    How Supplied

    Peramivir Solution for injection

    Rapivab 200mg/20mL Solution for Injection (61364-0181) (BioCryst Pharmaceuticals, Inc.) null

    Description/Classification

    Description

    Peramivir is an intravenous neuraminidase inhibitor indicated for the treatment of acute uncomplicated influenza in patients 6 months and older who have been symptomatic for no more than 48 hours. The efficacy is based on clinical trials in which the predominant influenza virus type was influenza A; only a limited number of patients infected with influenza B virus were enrolled.[58671] Peramivir is not a substitute for annual influenza virus vaccination. Instead, antiviral drugs are considered adjuncts to the prevention and control of influenza; annual influenza vaccination remains the main option for reducing the impact of influenza.[62315] [63866] The FDA-approved regimen is a single infusion for patients with uncomplicated influenza. An interim analysis of a phase 3 study failed to show a significant difference in efficacy of peramivir (5-day course) and standard of care vs. placebo and standard of care in patients with serious influenza requiring hospitalization.[58671]

    Classifications

    • General Anti-infectives Systemic
      • Antivirals For Systemic Use
        • Neuraminidase Inhibitor Antivirals
    Revision Date: 04/12/2024, 12:16:56 PM

    References

    58671 - Rapivab (peramivir injection) package insert. Durham, NC: BioCryst Pharmacetuicals, Inc; 2024 Jun.62315 - Centers for Disease Control and Prevention (CDC). Influenza antiviral medications: Summary for clinicians, 2020-2021. Retrieved November 5, 2020. Available on the World Wide Web at https://www.cdc.gov/flu/professionals/antivirals/summary-clinicians.htm63866 - Uyeki TM, Bernstein HH, Bradley JS, et al. Clinical Practice Guidelines by the Infectious Diseases Society of America: 2018 Update on Diagnosis, Treatment, Chemoprophylaxis, and Institutional Management of Seasonal Influenza. Clin Infect Dis 2019;68:e1-e47.

    Administration Information

    General Administration Information

    For storage information, see the specific product information within the How Supplied section.

    Route-Specific Administration

    Injectable Administration

    • For intravenous use only. Do not administer as an intramuscular (IM) injection.
    • Visually inspect parenteral products for particulate matter and discoloration prior to administration whenever solution and container permit. Do not use if seal over the bottle opening is broken or missing.[58671]

    Intravenous Administration

    Dilution

    • Use aseptic technique during the preparation process, as the solution does not contain a preservative or bacteriostatic agent.
    • Dilute the appropriate dose of peramivir 10 mg/mL solution to a final concentration between 1 and 6 mg/mL. Acceptable diluents include 0.9% or 0.45% Sodium Chloride Injection, 5% Dextrose Injection, or Lactated Ringer's Injection.
      • Adults: Dilute to a maximum volume of 100 mL.
      • Pediatric patients weighing more than 20 kg: Dilute to a maximum volume of 100 mL.
      • Pediatric patients weighing 15 to 19 kg: Dilute to a maximum volume of 75 mL.
      • Pediatric patients weighing 10 to 14 kg: Dilute to a maximum volume of 50 mL.
      • Pediatric patients 6 months to 1 year and pediatric patients weighing less than 10 kg: Dilute to a maximum volume of 25 mL.
    • Storage of diluted solution: Administer immediately or store under refrigeration 2 to 8 degrees C (36 to 46 degrees F) for up to 24 hours. If refrigerated, allow solution to reach room temperature prior to administration. Discard any unused diluted solution after 24 hours.[58671]

     

    Intermittent IV Infusion

    • Infuse over 15 to 30 minutes.
    • Do not mix or administer concurrently with other intravenous medications.[58671]

    Clinical Pharmaceutics Information

    From Trissel's 2‚Ñ¢ Clinical Pharmaceutics Database

    Peramivir

    pH Range
    pH 5.5 to 8.5
    ReferencesRapivab (peramivir injection), for intravenous use. Durham, NC. BioCryst Pharmaceuticals, Inc. 2024; Jun
      Revision Date: 04/12/2024, 12:16:56 PMCopyright 2004-2024 by Lawrence A. Trissel. All Rights Reserved.

      References

      58671 - Rapivab (peramivir injection) package insert. Durham, NC: BioCryst Pharmacetuicals, Inc; 2024 Jun.

      Adverse Reactions

      Moderate

      • constipation
      • delirium
      • elevated hepatic enzymes
      • hallucinations
      • hyperglycemia
      • hypertension
      • neutropenia
      • proteinuria
      • psychosis

      Mild

      • diarrhea
      • insomnia
      • rash
      • vomiting

      Severe

      • anaphylactoid reactions
      • erythema multiforme
      • exfoliative dermatitis
      • Stevens-Johnson syndrome

      Gastrointestinal effects are among the most frequently reported adverse reactions to peramivir in clinical trials. Diarrhea (8% peramivir vs. 7% placebo) was the most common adverse event. Constipation (4% vs. 2% placebo) was reported in a subset of patients (n = 101) with serious influenza requiring hospitalization who were treated with peramivir 600 mg as monotherapy. Vomiting was reported in 3% of pediatric patients (6 months to 17 years of age) receiving peramivir (n = 107) compared with 9% of patients receiving oseltamivir (n = 23) in clinical trials.[58671]

      Anaphylactoid reactions and cases of serious dermatologic adverse events have been reported in clinical trials and international postmarketing experience, including anaphylaxis, Stevens-Johnson syndrome, exfoliative dermatitis, and erythema multiforme. Rash has also been reported. If anaphylaxis or a serious rash develops during treatment, immediately discontinue peramivir and institute appropriate treatment.[58671]

      Neuropsychiatric adverse events, including delirium (psychosis), abnormal behavior, and hallucinations, have been reported with neuraminidase inhibitors, including peramivir. Some cases have been severe; fatalities have been reported. These reactions were primarily reported in pediatric patients and often occurred abruptly and resolved rapidly. Because influenza infection itself can be associated with a variety of neurologic and behavioral symptoms, particularly in children, the relative contribution of neuraminidase inhibitors to these adverse reactions is not known. Regardless, all patients with influenza should be closely monitored for signs of abnormal behavior. Insomnia (3% peramivir vs. 0% placebo) was also reported in a subset of patients (n = 101) with serious influenza requiring hospitalization.[58671]

      Neutropenia (neutrophils less than 1 x 109/L) occurred more frequently in patients receiving peramivir (8%) than placebo (6%) in clinical trials.[58671] Neutropenia was the most frequent laboratory adverse event in a single arm trial of 117 Japanese pediatric patients (aged 28 days to 16 years) with uncomplicated influenza who received a single dose of peramivir 10 mg/kg.[58681] Proteinuria (Grade 2) was reported in 3% of pediatric patients receiving peramivir (n = 107) compared with 0% of patients receiving oseltamivir (n = 23) in clinical trials. Other laboratory abnormalities reported in placebo-controlled trials include the following: creatinine phosphokinase of at least 6 times upper limit of normal (4% peramivir vs. 2% placebo), elevated hepatic enzymes (specifically increased ALT/AST; 3% peramivir vs. 2% placebo), and hyperglycemia (serum glucose more than 160 mg/dL; 5% peramivir vs. 3% placebo).[58671]

      Hypertension was noted in 2% of patients receiving peramivir compared to 0% of placebo patients in a subset of adult patients (n = 101) with serious influenza requiring hospitalization.[58671]

      Revision Date: 04/12/2024, 12:16:56 PM

      References

      58671 - Rapivab (peramivir injection) package insert. Durham, NC: BioCryst Pharmacetuicals, Inc; 2024 Jun.58681 - Sugaya N, Kohno S, Ishibashi T, et al. Efficacy, safety, and pharmacokinetics of intravenous peramivir in children with 2009 pandemia H1N1 influenza A virus infection. Antimicrob Agents Chemother 2012;56:369-377.

      Contraindications/Precautions

      Absolute contraindications are italicized.

      • serious rash
      • breast-feeding
      • children
      • dialysis
      • infection
      • pregnancy
      • psychosis
      • renal failure
      • renal impairment

      The use of peramivir has not been shown to provide benefit in patients with serious influenza requiring hospitalization. In a randomized, double-blind, multicenter, placebo-controlled trial of 398 patients with serious influenza requiring hospitalization, peramivir plus standard care did not improve median time to clinical resolution vs. standard of care alone.[58671]

      A serious bacterial infection may begin with influenza-like symptoms or may coexist with or develop as a complication during the course of influenza illness. Patients should be monitored, evaluated, and treated for suspected bacterial infections as clinically warranted while being treated with peramivir.[58671]

      Peramivir is renally eliminated. The dosage of peramivir should be adjusted in patients with renal impairment defined as a creatinine clearance of less than 50 mL/min, renal failure, and in patients receiving hemodialysis (dialysis). Peramivir should be administered after dialysis at a dose adjusted based on renal function. Peramivir has not been studied in patients receiving peritoneal dialysis or continuous renal replacement therapies.[58671]

      Neuropsychiatric adverse reactions of self-injury and delirium (psychosis) have been reported during postmarketing use of peramivir; some cases resulted in fatal outcomes. These reactions were primarily reported in pediatric patients and often occurred abruptly and resolved rapidly.[58671] In a trial of hospitalized adult patients with serious influenza, 11% of patients who received peramivir 200 to 400 mg IV daily (n = 81) experienced psychiatric adverse events compared to 4% of patients who received oseltamivir (n = 41).[37099] Since influenza infection itself is associated with a variety of neurologic and behavioral symptoms (e.g., hallucinations, delirium, abnormal behavior), the role of peramivir in causing these reactions is unclear. Patients with influenza who are receiving peramivir, particularly children and adolescents, should be closely monitored for signs of abnormal behavior. The risks and benefits of continuing peramivir should be evaluated if neuropsychiatric events occur.[58671]

      Pregnant and postpartum patients are at significantly higher risk for serious complications from influenza infection as compared with nonpregnant people; therefore, timely use of antiviral therapy is recommended for the treatment of influenza. The American College of Obstetricians and Gynecologists (ACOG) consider peramivir an alternative antiviral for treatment of influenza in pregnant patients. Limited available data with peramivir use in pregnancy are insufficient to determine a drug-associated risk of adverse developmental outcomes. In animal reproduction studies, no adverse developmental effects were observed in rats when peramivir was given during organogenesis by IV bolus at 600 mg/kg, representing exposures approximately 8-fold that in humans at the recommended dose. However, when peramivir was administered by continuous IV infusion, fetal anomalies of reduced renal papilla and dilated ureters were observed. In rabbits, maternal toxicity and developmental toxicity (abortion or premature delivery) were observed with administration of peramivir during organogenesis at exposures 8-times those in humans.[58671] [70419]

      There are no data on the presence of peramivir in breast milk, the effects on the breast-fed infant, or the effects on milk production. Limited clinical data during breast-feeding preclude a clear determination of the risk of peramivir to a breast-feeding infant. Consider the benefits of breast-feeding along with the mother's clinical need for peramivir and any potential adverse effects on the breast-fed infant from peramivir or the underlying maternal condition. A pharmacokinetic study in rats demonstrated that peramivir is excreted in milk at concentrations below the mother's plasma drug concentrations; the milk to plasma AUC ratio of peramivir was approximately 0.5.[58671]

      Serious rash, including Stevens-Johnson Syndrome (SJS) and erythema multiforme, have been reported during postmarketing use of peramivir.[58671]

      Revision Date: 04/12/2024, 12:16:56 PM

      References

      37099 - Food and Drug Administration Emergency Use Authorization Fact Sheet for Heath Care Providers. Peramivir injection. Retrieved Nov. 20, 2009. Available on the World Wide Web at http://www.fda.gov/downloads/Drugs/DrugSafety/PostmarketDrugSafetyInformationforPatientsandProviders/UCM187811.pdf.58671 - Rapivab (peramivir injection) package insert. Durham, NC: BioCryst Pharmacetuicals, Inc; 2024 Jun.70419 - The American College of Obstetricians and Gynecologists. Influenza in pregnancy: prevention and treatment: ACOG Committee Statement No. 7. Obstet Gynecol 2023 Nov;143(2):e1-e7.

      Mechanism of Action

      Peramivir is a cyclopentane analogue that competitively binds to the active site of the influenza virus neuraminidase. Peramivir inhibits the neuraminidase activity of strains of influenza A and B viruses.[58671] Influenza virus neuraminidase is a surface glycoprotein that catalyzes the cleavage of the linkage between a terminal sialic acid and adjacent sugar residue. This action promotes the spread of virus in the respiratory tract by several mechanisms. Viral neuraminidase promotes the release of virions from infected cells; promotes the penetration of virus into respiratory epithelial cells; prevents the formation of viral aggregates; prevents viral inactivation by respiratory mucus; induces cellular apoptosis by activating transforming growth factor beta; and induces cytokines including interleukin-1 and tumor necrosis factor.

       

      Influenza viruses are classified into 3 distinct types, influenza A, influenza B, and influenza C. Influenza A is further divided into subtypes based on their hemagglutinin (H or HA) and neuraminidase (N or NA) activity. At least 16 distinct HAs (H1 to H16) and 9 NAs (N1 to N9) have been described. Influenza infection may be attributed to either influenza A virus or influenza B virus. Influenza A virus subtypes include H1N1 and H3N2. In 2009, a novel influenza A H1N1 virus (previously referred to as swine influenza) was identified; this virus is included in season influenza A viruses. Human cases of influenza illness from the avian H5N1 virus (commonly known as avian flu) have been reported since 1997. Human infections with avian H7N9, H5N2, H5N8, H9N2, H7N7, and H7N3 viruses have also been described.[36906][62337]

      Revision Date: 04/12/2024, 12:16:56 PM

      References

      36906 - Treanor JJ. Influenza viruses (including avian influenza and swine influenza). In: Mandell GL, Bennett JE, Dolin R, eds. Principles and Practice of Infectious Diseases, 8th ed. New York: Churchhill Livingstone; 2015:2000-2024.58671 - Rapivab (peramivir injection) package insert. Durham, NC: BioCryst Pharmacetuicals, Inc; 2024 Jun.62337 - Centers for Disease Control and Prevention (CDC). Interim guidance on influenza antiviral chemoprophylaxis of persons exposed to birds with avian influenza A viruses associated with severe human disease or with the potential to cause severe human disease. Retrieved May 3, 2022. Available on the World Wide Web at https://www.cdc.gov/flu/avianflu/guidance-exposed-persons.htm

      Pharmacokinetics

      Peramivir is administered intravenously. Protein binding is less than 30%, and the central volume of distribution was found to be 12.56 L in population pharmacokinetic analysis. Peramivir is not significantly metabolized and is eliminated renally with a half-life of approximately 20 hours in adults with normal renal function after a single 600 mg dose. Renal clearance accounts for about 90% of total clearance. Negligible accumulation was observed after multiple dose administration.[58671]

       

      Affected cytochrome P450 isoenzymes and drug transporters: none

      Route-Specific Pharmacokinetics

      Intravenous Route

      The pharmacokinetic parameters after IV administration of peramivir to adult subjects showed a linear relationship between dose and the exposure parameters (Cmax and AUC). After a single IV dose of 600 mg infused over 30 minutes, Cmax was 46,800 ng/mL at the end of the infusion and AUC was 102,700 ng x hour/mL.[58671]

      Special Populations

      Hepatic Impairment

      Although the pharmacokinetics of peramivir have not been specifically studied in patients with hepatic impairment, clinically relevant alterations are not expected.[58671]

      Renal Impairment

      Peramivir pharmacokinetics have been studied in otherwise healthy adult subjects with various degrees of renal impairment. When compared to a concurrent cohort with normal renal function, no change in mean Cmax was observed (6 subjects per cohort). However, the mean AUC after a single 2 mg/kg IV dose was increased by 28%, 302%, and 412% in patients with creatinine clearance 50 to 79, 30 to 49, and 10 to 29 mL/minute, respectively. The pharmacokinetics of peramivir have not been evaluated in pediatric patients with renal impairment.[58671]

       

      Hemodialysis is effective in reducing systemic exposure of peramivir by 73% to 81%.[58671]

       

      Very limited information on peramivir in the setting of continuous veno-venous hemofiltration (CVVH) and continuous veno-venous hemodialysis (CVVHD) in adults indicates that peramivir is efficiently cleared by CRRT. The pharmacokinetic sampling was sparse (2 to 4 samples/patient) and the timing of the samples is not well documented. No information is provided regarding filter type, flow rate, or duration of renal replacement therapy. Ultrafiltrate concentrations from a single adult patient on CVVH revealed a high sieving coefficient (about 80%), which is consistent with peramivir's low protein binding. There is no information available specific to patients receiving extracorporeal membrane oxygenation (ECMO) on peramivir exposure or pharmacokinetics.[37099]

      Pediatrics

      The pharmacokinetics of peramivir were evaluated in a study of 107 pediatric patients (6 months to 17 years) with acute uncomplicated influenza who received a single IV dose of peramivir 12 mg/kg/dose (children 6 months to 12 years) or 600 mg (adolescents). The pharmacokinetics of peramivir in children 2 to 6 years (Cmax 47,400 ng/mL and AUC 62,700 ng x hour/mL), children 7 to 12 years (Cmax 61,200 ng/mL and AUC 76,300 ng x hour/mL), and adolescents (Cmax 51,500 ng/mL and AUC 65,500 ng x hour/mL) were similar to those seen in healthy adults administered a single 600 mg dose (Cmax 45,700 ng/mL and AUC 68,500 ng x hour/mL). The pharmacokinetics of peramivir in children 6 months to younger than 2 years (Cmax 38,000 ng/mL and AUC 46,200 ng x hour/mL) were lower than that of healthy adults, with geometric mean ratios of 0.68 (0.52 to 0.88) for AUC and 0.83 (0.59 to 1.18) for Cmax; however, the difference in exposure was not considered to be clinically significant.[58671]

       

      In another small pharmacokinetic study in 11 critically ill pediatric patients (9 months to 12 years) receiving peramivir (9.8 to 12.7 mg/kg/dose IV every 24 hours) for influenza infections, peramivir pharmacokinetics differed significantly compared with previous pediatric studies and product labeling data in healthy patients. The Vd of peramivir was larger in 10 patients (median 0.58 L/kg; interquartile range, 0.35 to 1.47) and all 11 patients demonstrated an increase in clearance (median 5.1 mL/minute/kg; interquartile range, 2.5 to 11.2 mL/minute/kg) and shorter elimination half-life (median 1.7 hours; interquartile range, 1.25 to 1.95). This compares with previous data in healthy pediatric patients of an elimination half-life of 20 hours, Vd of 0.18 L/kg, and clearance of 0.1 mL/minute/kg. All patients required dosing adjustments to a more frequent dosing interval to attain AUC targets; 10 patients required an every 12-hour regimen and 1 patient required an every 8-hour regimen.[64737]

      Geriatric

      Peramivir pharmacokinetics in geriatric patients were similar to younger patients. Peak concentrations of peramivir after a single 4 mg/kg IV dose were approximately 10% higher in geriatric patients compared to young adults. Additionally, geriatric patients have an approximately 34% increase in dose-normalized AUC. Dose adjustments are not required for geriatric patients without reduced renal function.[58671]

      Gender Differences

      Peramivir pharmacokinetics were similar in male and female subjects.[58671]

      Ethnic Differences

      Peramivir pharmacokinetics were primarily evaluated in Caucasian and Asian patients. Based on a population pharmacokinetic analysis including race as a covariate, volume of distribution was dependent on weight and Asian race. No dosage adjustment is required based on weight or Asian race.[58671]

      Revision Date: 04/12/2024, 12:16:56 PM

      References

      37099 - Food and Drug Administration Emergency Use Authorization Fact Sheet for Heath Care Providers. Peramivir injection. Retrieved Nov. 20, 2009. Available on the World Wide Web at http://www.fda.gov/downloads/Drugs/DrugSafety/PostmarketDrugSafetyInformationforPatientsandProviders/UCM187811.pdf.58671 - Rapivab (peramivir injection) package insert. Durham, NC: BioCryst Pharmacetuicals, Inc; 2024 Jun.64737 - Cies JJ, Moore WS, Enache A, et al. Peramivir for influenza A and B viral infections: A pharmacokinetic case series. Pharmacotherapy 2019 Sept 12; doi: 10.1002/phar.2330. [Epub ahead of print]

      Pregnancy/Breast-feeding

      pregnancy

      Pregnant and postpartum patients are at significantly higher risk for serious complications from influenza infection as compared with nonpregnant people; therefore, timely use of antiviral therapy is recommended for the treatment of influenza. The American College of Obstetricians and Gynecologists (ACOG) consider peramivir an alternative antiviral for treatment of influenza in pregnant patients. Limited available data with peramivir use in pregnancy are insufficient to determine a drug-associated risk of adverse developmental outcomes. In animal reproduction studies, no adverse developmental effects were observed in rats when peramivir was given during organogenesis by IV bolus at 600 mg/kg, representing exposures approximately 8-fold that in humans at the recommended dose. However, when peramivir was administered by continuous IV infusion, fetal anomalies of reduced renal papilla and dilated ureters were observed. In rabbits, maternal toxicity and developmental toxicity (abortion or premature delivery) were observed with administration of peramivir during organogenesis at exposures 8-times those in humans.[58671] [70419]

      breast-feeding

      There are no data on the presence of peramivir in breast milk, the effects on the breast-fed infant, or the effects on milk production. Limited clinical data during breast-feeding preclude a clear determination of the risk of peramivir to a breast-feeding infant. Consider the benefits of breast-feeding along with the mother's clinical need for peramivir and any potential adverse effects on the breast-fed infant from peramivir or the underlying maternal condition. A pharmacokinetic study in rats demonstrated that peramivir is excreted in milk at concentrations below the mother's plasma drug concentrations; the milk to plasma AUC ratio of peramivir was approximately 0.5.[58671]

      Revision Date: 04/12/2024, 12:16:56 PM

      References

      58671 - Rapivab (peramivir injection) package insert. Durham, NC: BioCryst Pharmacetuicals, Inc; 2024 Jun.70419 - The American College of Obstetricians and Gynecologists. Influenza in pregnancy: prevention and treatment: ACOG Committee Statement No. 7. Obstet Gynecol 2023 Nov;143(2):e1-e7.

      Interactions

      Level 2 (Major)

      • Intranasal Influenza Vaccine
      • Live Attenuated Influenza Vaccine (intranasal)
      Intranasal Influenza Vaccine: (Major) Do not administer the intranasal live attenuated influenza vaccine (LAIV) 2 weeks before or 5 days after administration of peramivir, unless medically indicated. Inactivated influenza vaccines may be used, as appropriate. Because of its antiviral properties, peramivir may interfere with the efficacy of live attenuated influenza vaccines. Therefore, live influenza virus vaccines are not recommended during treatment with peramivir. Consult currently recommended guidance on the use of antiviral drugs against influenza. [58671] [63436] Live Attenuated Influenza Vaccine (intranasal): (Major) Do not administer the intranasal live attenuated influenza vaccine (LAIV) 2 weeks before or 5 days after administration of peramivir, unless medically indicated. Inactivated influenza vaccines may be used, as appropriate. Because of its antiviral properties, peramivir may interfere with the efficacy of live attenuated influenza vaccines. Therefore, live influenza virus vaccines are not recommended during treatment with peramivir. Consult currently recommended guidance on the use of antiviral drugs against influenza. [58671] [63436]
      Revision Date: 04/12/2024, 12:16:56 PM

      References

      58671 - Rapivab (peramivir injection) package insert. Durham, NC: BioCryst Pharmacetuicals, Inc; 2024 Jun.63436 - Grohskopf LA, Ferdinands JM, Blanton LH, et al. Prevention and Control of Seasonal Influenza with Vaccines: Recommendations of the Advisory Committee on Immunization Practices - United States, 2024-2025 Influenza Season. MMWR 2024;73(No. RR-5):1-25.

      Monitoring Parameters

      • CBC
      • LFTs
      • serum creatinine/BUN
      • urinalysis

      US Drug Names

      • Rapivab
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