Peramivir (Monograph)

Brand name: Rapivab
Drug class: Neuraminidase Inhibitors
VA class: AM800
Chemical name: 3-[(1S)-1-(Acetylamino)-2-ethylbutyl]-4-[(aminoiminomethyl)amino]-2-hydroxy-cyclopentanecarboxylic acid hydrate
Molecular formula: C₁₅H₂₈N₄O₄ • 3H₂O
CAS number: 1041434-82-5

Medically reviewed by Drugs.com on Sep 24, 2024. Written by ASHP.

Introduction

Antiviral; neuraminidase inhibitor active against influenza A and B viruses.^{1 2 3 120 144}

Uses for Peramivir

Treatment of Seasonal Influenza A and B Virus Infections

Treatment of acute, uncomplicated illness caused by influenza A or B viruses in adults, adolescents, and children ≥6 months of age who have been symptomatic for ≤2 days.^{1 2 3 120}

Has been used for treatment of serious influenza^{† [off-label]} in some patients,^{1 4 120} but efficacy not established in patients with serious influenza requiring hospitalization.¹

Safety and efficacy not established for prevention of influenza virus infection^{† [off-label]};¹ not recommended for prophylaxis of influenza.^{112 120}

For treatment of suspected or confirmed acute, uncomplicated seasonal influenza in otherwise healthy outpatients, CDC, IDSA, and others state that any age-appropriate influenza antiviral (oral oseltamivir, inhaled zanamivir, oral baloxavir marboxil, IV peramivir) can be used if not contraindicated.^{112 116 120} CDC states may consider early empiric antiviral treatment in outpatients with suspected influenza (e.g., influenza-like illness such as fever with either cough or sore throat) based on clinical judgement if such treatment can be initiated within 48 hours of illness onset.¹²⁰

For treatment of suspected or confirmed seasonal influenza in hospitalized patients or outpatients with complications or progressive illness (e.g., pneumonia, exacerbation of underlying chronic medical conditions), oseltamivir is the preferred influenza antiviral because of lack of data regarding use of other influenza antivirals in such patients.¹²⁰ Although data are insufficient regarding use of peramivir for treatment of severe influenza in hospitalized patients or outpatients^{† [off-label]}, CDC states consider use of peramivir in patients who cannot tolerate or absorb oseltamivir administered orally or enterically (e.g., because of suspected or known gastric stasis, malabsorption, or GI bleeding).¹²⁰

Consider that influenza and coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) have overlapping signs and symptoms and coinfection with influenza A or B viruses and SARS-CoV-2 can occur.¹²⁰ Although laboratory testing can help distinguish between influenza virus infection and SARS-CoV-2 infection, CDC recommends initiating empiric influenza treatment in patients with suspected influenza who are hospitalized, have severe, complicated, or progressive illness, or are at high risk for influenza complication without waiting for results of influenza testing, SARS-CoV-2 testing, or multiplex molecular assays that detect influenza A and B viruses and SARS-CoV- 2.¹²⁰

Consider viral surveillance data available from local and state health departments and CDC when selecting an antiviral for treatment of seasonal influenza.^{1 116 120} Strains of circulating influenza viruses and the antiviral susceptibility of these strains constantly evolve, and emergence of resistant strains may decrease effectiveness of influenza antivirals.¹ Although circulating influenza A and B viruses during recent years generally have been susceptible to peramivir ,^{188 192 193 194 195 196 198 199 200 201} consult most recent information on susceptibility of circulating viruses when selecting an antiviral for treatment of influenza.^{1 120}

CDC issues recommendations concerning use of antivirals for treatment of influenza, and these recommendations are updated as needed during each influenza season.¹²⁰ Information regarding influenza surveillance and updated recommendations for treatment of seasonal influenza are available from CDC at [Web].

Avian Influenza A Virus Infections

Used or recommended for treatment or prevention of infections caused by susceptible avian influenza A viruses^{† [off-label]}.^{50 104 178 179 180 187}

For treatment of uncomplicated avian influenza A infections in outpatients, CDC states that oral oseltamivir, IV peramivir, or inhaled zanamivir may be used.¹⁷⁸

For treatment of severe, complicated, or progressive avian influenza A infections in hospitalized patients or outpatients, including infections caused by avian influenza A (H5N1), avian influenza A (H7N9), or novel avian influenza A H5 viruses, CDC recommends oseltamivir as antiviral of choice.¹⁷⁸ In those with severe avian influenza A infection who cannot tolerate or absorb oseltamivir administered orally or enterically (e.g., because of suspected or known gastric stasis, malabsorption, or GI bleeding), CDC states use of IV peramivir may be considered.¹⁷⁸

When antiviral prophylaxis is indicated in close contacts of individuals with confirmed or probable infection with avian influenza A viruses that have caused or potentially may cause severe disease or indicated in individuals who have been exposed to birds infected with such avian influenza A viruses, CDC recommends oral oseltamivir or inhaled zanamivir.^{179 180}

Information regarding treatment and prevention of avian influenza A infections is available from CDC at [Web] and WHO at [Web].

Pandemic Influenza

Alternative for treatment of pandemic influenza^{† [off-label]} caused by susceptible strains of influenza virus.^{5 9 52 104 151}

Influenza viruses can cause pandemics, during which rates of illness and death from influenza-related complications can increase dramatically worldwide.^{52 104 166}

Most recent influenza pandemic occurred during 2009 and was related to a novel influenza A (H1N1) strain, influenza A (H1N1)pdm09.^{52 135 144 151 166} In the US, the 2009 influenza A (H1N1)pdm09 pandemic was characterized by a substantial increase in influenza activity that peaked in late October and early November 2009 and returned to seasonal baseline levels by January 2010.^{123 166} At that time, ≥99% of influenza viruses circulating in the US were influenza A (H1N1)pdm09.^{123 135 166} After the pandemic, influenza A (H1N1)pdm09 became a seasonal influenza virus and continues to circulate with other seasonal viruses.^{135 192 194 195 198 199 200 201}

The spread of the highly pathogenic Asian strain of avian influenza A (H5N1) in poultry in Asia and other countries that has been occurring since 2003 and has caused human infections represents a potential future pandemic threat.^{50 52 54 55 56 104 147} The novel avian influenza A (H7N9) virus first identified in China in March 2013 that has been causing sporadic human infections also has pandemic potential.^{50 104 182 183 187}

Information on pandemic influenza, including planning and preparedness resources if an influenza pandemic occurs, is available from CDC at [Web] and WHO at [Web].

Peramivir Dosage and Administration

Administration

IV Administration

For solution compatibility information, see Compatibility under Stability.

Administer by IV infusion.¹

Commercially available injection concentrate containing 10 mg/mL must be diluted prior to administration.¹

Do not mix with or administer simultaneously with other drugs.¹

Compatible with materials commonly used for administration (e.g., polyvinyl chloride and polyvinyl chloride-free infusion bags, polypropylene syringes, polyethylene tubing).¹

Vials contain no preservatives or bacteriostatic agents and are for single use only.¹

Dilution

Withdraw appropriate dose of peramivir injection concentrate containing 10 mg/mL and dilute in 0.9 or 0.45% sodium chloride injection, 5% dextrose injection, or lactated Ringer's injection to provide a solution for IV infusion containing 1–6 mg/mL of the drug.¹ The maximum recommended total infusion volume depends on the patient's age and weight.¹ (See Table 1.)

Administer immediately after dilution.¹ If not used immediately, diluted solution may be stored for ≤24 hours at 2–8°C.¹ Allow refrigerated solution to reach room temperature and administer immediately.¹

Discard unused portions of diluted solution 24 hours after dilution.¹

Rate of Administration

Administer by IV infusion over 15–30 minutes.¹

Dosage

Pediatric Patients

Treatment of Seasonal Influenza A and B Virus Infections

Acute, Uncomplicated Seasonal Influenza A or B Virus Infections

IV

Children 6 months to 12 years of age: Single dose of 12 mg/kg (up to 600 mg) given within 2 days of symptom onset.¹

Adolescents ≥13 years of age: Single 600-mg dose given within 2 days of symptom onset.¹

Treatment of Avian Influenza A Virus Infections†

Avian Influenza A (H7N9), Avian Influenza A (H5N1), and Novel Avian Influenza A H5 Viruses†

IV

Children: 10 mg/kg (up to 600 mg) once daily for ≥5 days.¹⁷⁸ Only limited data available regarding use for these infections;¹⁷⁸ single-dose regimen not recommended.¹⁷⁸

Adults

Treatment of Seasonal Influenza A and B Virus Infections

Acute, Uncomplicated Seasonal Influenza A or B Virus Infections

IV

Single 600-mg dose given within 2 days of symptom onset.¹

Treatment of Avian Influenza A Virus Infections†

Avian Influenza A (H7N9), Avian Influenza A (H5N1), and Novel Avian Influenza A H5 Viruses†

IV

600 mg once daily for ≥5 days.¹⁷⁸ Only limited data available regarding use for these infections;¹⁷⁸ single-dose regimen not recommended.¹⁷⁸

Special Populations

Hepatic Impairment

Not studied in patients with hepatic impairment;¹ clinically important alterations in pharmacokinetics not expected.¹

Renal Impairment

Treatment of Acute, Uncomplicated Seasonal Influenza A or B Virus Infection

IV

Decrease dosage in adults and pediatric patients ≥2 years of age with Cl_cr of <50 mL/minute.¹ (See Table 2.)

Pediatric patients 6 months to 2 years of age: Data not available to inform a recommendation for dosage adjustment in those with Cl_cr of <50 mL/minute.¹

Chronic renal disease maintained on hemodialysis: Adjust dosage based on renal function;¹ give dose after dialysis.¹

Geriatric Patients

Dosage adjustments based solely on age not needed.¹

Cautions for Peramivir

Contraindications

• Known serious hypersensitivity (e.g., anaphylaxis, erythema multiforme, Stevens-Johnson syndrome) to peramivir or any ingredient in the formulation.¹

Warnings/Precautions

Sensitivity Reactions

Hypersensitivity Reactions

Serious dermatologic reactions (Stevens-Johnson syndrome, erythema multiforme) reported.¹

Anaphylactic/anaphylactoid reactions, exfoliative dermatitis, and rash also reported.¹

If anaphylaxis or serious skin reaction occurs or is suspected, discontinue peramivir and initiate appropriate treatment.¹

Neuropsychiatric and CNS Effects

Postmarketing cases of delirium and abnormal behavior leading to injury reported in patients with influenza receiving neuraminidase inhibitors, including peramivir.¹ Most cases involved pediatric patients and generally had abrupt onset and rapid resolution.¹ Role of peramivir not established.¹

Influenza itself can be associated with a variety of neurologic and behavioral symptoms (e.g., hallucinations, delirium, abnormal behavior) that sometimes result in fatalities.¹ Although such events may occur in the setting of encephalitis or encephalopathy, they can occur in patients with uncomplicated influenza.¹

Closely monitor patients with influenza for signs of abnormal behavior.¹

Differential Diagnosis

When making treatment decisions in patients with suspected influenza, consider possibility of primary or concomitant bacterial infections for which peramivir would be ineffective.¹

Serious bacterial infections may begin with influenza-like symptoms or may coexist with or occur as complications of influenza.¹ No evidence that peramivir prevents such complications.¹

No evidence that peramivir is effective for illness caused by any organisms other than influenza A or B.¹

Influenza Vaccination

Influenza antivirals are not a substitute for annual vaccination with a seasonal influenza vaccine (influenza virus vaccine inactivated, influenza vaccine recombinant, influenza vaccine live intranasal).^{112 116 144}

Although influenza antivirals, including peramivir, may be used concomitantly with or any time before or after influenza virus vaccine inactivated or influenza vaccine recombinant,^{1 100 134} influenza antivirals may inhibit the vaccine virus contained in influenza vaccine live intranasal and decrease efficacy of the live vaccine.^{1 100} (See Specific Drugs under Interactions.)

Specific Populations

Pregnancy

Data regarding use of peramivir in pregnant women are insufficient to determine whether there is a risk of adverse developmental outcomes.¹

In pregnant rats, no adverse embryofetal effects observed when peramivir was given by IV injection once daily at maximum feasible dosage; however, fetal abnormalities (reduced renal papilla, dilated ureters) observed when administered to rats by continuous IV infusion.¹ In rabbits, developmental toxicity (abortion or premature delivery) observed when peramivir given by IV injection once daily at maternally toxic doses.¹

Pregnant women are at increased risk for severe complications from influenza,^{1 142} which may lead to adverse pregnancy and/or fetal outcomes including maternal death, stillbirths, birth defects, preterm delivery, low birthweight, and small size for gestational age.¹

CDC states that only limited data available regarding use of peramivir for treatment of influenza in pregnant women.¹⁴² Oseltamivir is the preferred antiviral for treatment of suspected or confirmed influenza in women who are pregnant or ≤2 weeks postpartum.^{116 120 142}

Lactation

Not known whether peramivir distributes into human milk, affects milk production, or has any effects on breast-fed infants.¹ Distributed into milk in rats.¹

Consider benefits of breast-feeding and importance of peramivir to the woman; also consider potential adverse effects on breast-fed child from the drug or underlying maternal condition.¹

Pediatric Use

Safety and efficacy not established in pediatric patients <6 months of age.¹

Safety and efficacy for treatment of acute, uncomplicated influenza in pediatric patients 6 months to 17 years of age established and supported by evidence from adequate and well-controlled trials of the drug in adults and additional data from a randomized, open-label, active-controlled trial in pediatric patients in this age group.¹

Safety profile in pediatric patients 6 months to 17 years of age generally similar to that reported in adults.¹ Adverse effects reported in ≥2% of pediatric patients and not reported in adults include vomiting and proteinuria.¹

Geriatric Use

Insufficient experience in patients ≥65 years of age to determine whether geriatric patients respond differently than younger adults.¹

Pharmacokinetics in geriatric adults are similar to pharmacokinetics reported in younger adults.¹

Hepatic Impairment

Not studied in patients with hepatic impairment;¹ clinically important alterations in pharmacokinetics not expected since the drug does not undergo clinically important metabolism.¹ (See Elimination under Pharmacokinetics.)

Renal Impairment

Increased AUC.¹ Reduce dosage in adults and pediatric patients ≥2 years of age with Cl_cr <50 mL/minute.¹ (See Renal Impairment under Dosage and Administration.)

Common Adverse Effects

Diarrhea, vomiting, constipation, insomnia, hypertension.

Drug Interactions

Not metabolized by and does not induce or inhibit CYP isoenzymes.¹ Drug interactions with drugs that are substrates or inhibitors of these enzymes unlikely.¹

Not a substrate for and does not inhibit P-glycoprotein (P-gp).¹

Specific Drugs

Peramivir Pharmacokinetics

Absorption

Bioavailability

Following IV infusion over 30 minutes, peak serum concentrations attained at end of the infusion.¹ Negligible accumulation following multiple doses for up to 10 days.¹

Linear relationship between dose and exposure parameters (peak plasma concentrations, AUC).¹

Distribution

Extent

Well distributed within extracellular fluid spaces, including nose and throat, following IV administration.⁶

Not known whether distributed into human milk.¹ Distributed into milk in rats¹ (peak milk concentrations attained 0.75 hours after an IV dose and milk to plasma AUC ratio approximately 0.5).¹

Plasma Protein Binding

<30%.¹

Elimination

Metabolism

Does not undergo clinically important metabolism.¹

Not a substrate for and does not affect CYP isoenzymes.¹

Elimination Route

Following IV administration, approximately 90% of dose eliminated unchanged in urine, principally by glomerular filtration.¹

Removed by hemodialysis.¹

Half-life

Adults: Approximately 20 hours following single 600-mg IV dose.¹

Special Populations

Infants 6 months to <2 years of age: Geometric mean peak plasma concentrations and AUCs are lower than those reported in healthy adults; not considered clinically important.¹

Children 2–12 years of age: Pharmacokinetics following single 12-mg/kg IV dose similar to pharmacokinetics reported in adults following single 600-mg IV dose.¹

Adolescents 13–17 years of age: Pharmacokinetics following single 600-mg IV dose similar to pharmacokinetics reported in adults following single 600-mg IV dose.¹

Pediatric patients with renal impairment: Pharmacokinetics not evaluated.¹

Adults with renal Impairment: AUC increased by 28, 302, or 412% in patients with Cl_cr of 50–79, 30–49, or <30 mL/minute, respectively, compared with those with normal renal function.¹ Systemic exposure decreased by 73–81% in patients undergoing hemodialysis.¹

Hepatic impairment: Pharmacokinetics not studied, but substantial alterations not expected since the drug does not undergo clinically important metabolism.¹

Geriatric individuals: Pharmacokinetics similar to that in younger adults.¹

Stability

Storage

Parenteral

Solution for IV Use

20–25°C (may be exposed to 15–30°C).¹

Following dilution, use immediately or store for ≤24 hours at 2–8°C.¹ Discard unused portions 24 hours after dilution.¹

Compatibility

Parenteral

Solution Compatibility1 10

Actions and Spectrum

• Peramivir is a neuraminidase inhibitor antiviral^{1 2 5 6} pharmacologically related to other neuraminidase inhibitors (e.g., oseltamivir, zanamivir).¹²⁰

• Potent selective competitive inhibitor of influenza virus neuraminidase, an enzyme essential for viral replication; possibly alters virus particle aggregation and release.^{1 2 3 6 9}

• Active in vitro in cell culture against both influenza A and B viruses.^{1 2 3 6 120} Viral surveillance data indicate majority of seasonal influenza A (H1N1)pdm09, influenza A (H3N2), and influenza B viruses circulating worldwide, including in the US, during recent influenza seasons have been susceptible to peramivir in vitro.^{188 192 193 194 195 198 199 200 201}

• Active in vitro in cell culture against some avian influenza A viruses, including some strains of avian influenza A (H5N1) and (H7N9).^{6 181}

• Influenza A and B viruses with decreased susceptibility to peramivir have been produced in vitro^{1 6} and observed rarely in clinical isolates of seasonal influenza A and B viruses.^{1 181 188 192 193 195 198 199 200} Clinical importance of decreased in vitro susceptibility in these strains unknown.¹

• Major mechanisms of resistance to neuraminidase inhibitors are viral neuraminidase mutations that affect ability of the drugs to inhibit the enzyme and hemagglutinin mutations that reduce viral dependence on neuraminidase activity.^{1 6 14}

• Amino acid substitutions that conferred reduced susceptibility to peramivir reported in some clinical isolates of avian influenza A (H5N1) and (H7N9).¹ Clinical importance of reduced in vitro susceptibility to peramivir in these avian influenza A viruses not known; effects of specific substitutions on susceptibility may be strain-dependent.¹

• Cross-resistance between peramivir and other neuraminidase inhibitors (e.g., oseltamivir, zanamivir) reported in influenza A and B viruses.^{1 6 14 120 172 173 175 181 192 193 195} However, because oseltamivir, peramivir, and zanamivir bind to different sites on the neuraminidase enzyme or interact differently with binding sites, cross-resistance among the drugs is variable.^{173 175}

• Cross-resistance between peramivir and baloxavir (a polymerase acidic [PA] endonuclease inhibitor antiviral) not expected since the drugs have different mechanisms of action against influenza viruses.²² However, influenza viruses with substitutions that confer resistance to neuraminidase inhibitors may also have amino acid substitutions in the PA protein that confer resistance to baloxavir.²²

Advice to Patients

• Advise patients of the risk of severe allergic reactions (including anaphylaxis) or serious skin reactions with peramivir and importance of immediately seeking medical attention if an allergic-like reaction occurs or is suspected.¹

• Advise patients of the risk of neuropsychiatric reactions in patients with influenza and importance of immediately contacting a clinician if they experience signs of abnormal behavior after receiving peramivir.¹

• Importance of informing clinicians of existing or contemplated concomitant therapy, including prescription and OTC drugs, as well as any concomitant illnesses.¹

• Importance of women informing clinicians if they are or plan to become pregnant or plan to breast-feed.¹

• Importance of informing patients of other important precautionary information.¹ (See Cautions.)

Preparations

Excipients in commercially available drug preparations may have clinically important effects in some individuals; consult specific product labeling for details.

Please refer to the ASHP Drug Shortages Resource Center for information on shortages of one or more of these preparations.

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