Rapivab

Browse PDR's full list of drug information

Rapivab

Classes

Neuraminidase Inhibitor Antivirals

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.

Intravenous Administration

Preparation
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 for Injection, 5% Dextrose for Injection, or Lactated Ringer's.
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.
 
Intermittent IV Infusion
Infuse over 15 to 30 minutes.
Do not mix or administer concurrently with other intravenous medications.

Adverse Reactions
Severe

exfoliative dermatitis / Delayed / 0-1.0
erythema multiforme / Delayed / 0-1.0
Stevens-Johnson syndrome / Delayed / 0-1.0
anaphylactoid reactions / Rapid / Incidence not known

Moderate

neutropenia / Delayed / 8.0-8.0
hyperglycemia / Delayed / 5.0-5.0
constipation / Delayed / 4.0-4.0
proteinuria / Delayed / 3.0-3.0
elevated hepatic enzymes / Delayed / 3.0-3.0
hypertension / Early / 2.0-2.0
psychosis / Early / Incidence not known
delirium / Early / Incidence not known
hallucinations / Early / Incidence not known

Mild

diarrhea / Early / 8.0-8.0
vomiting / Early / 3.0-3.0
insomnia / Early / 3.0-3.0
rash / Early / Incidence not known

Common Brand Names

Rapivab

Dea Class

Rx

Description

Intravenous neuraminidase inhibitor
Used for the treatment of acute uncomplicated influenza in patients 6 months and older
Administer within 48 hours of symptom onset

Dosage And Indications
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.

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.

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.

Adolescent outpatients with uncomplicated, mild-to-moderate illness

600 mg IV as a single dose within 48 hours of symptom onset.

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.

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.

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.

†Indicates off-label use

Dosing Considerations
Hepatic Impairment

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.

Renal Impairment

Adults and Adolescents :
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 :
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.
 
NOTE: Dosage recommendations below for pediatric patients younger than 2 years were included in the Emergency Use Authorization (EUA) of peramivir. These recommendations have not been FDA-approved.
NOTE: In the absence of a measured CrCl, the Schwartz equation may be used to estimate CrCl.
Infants 181 days and older and Children younger than 2 years:
CrCl 50 mL/minute/1.73 m2 or more: No dosage adjustment necessary.
CrCl 31 to 49 mL/minute/1.73 m2: Reduce to 3 mg/kg/dose.
CrCl 10 to 30 mL/minute/1.73 m2: Reduce to 1.9 mg/kg/dose.
CrCl less than 10 mL/minute/1.73 m2 (not on dialysis or CRRT): 1.9 mg/kg IV on day one, then 0.3 mg/kg IV daily. (NOTE: The regimen approved in the EUA was for a 5 to 10 day course.)
 
Infants 91 to 180 days:
CrCl 50 mL/minute/1.73 m2 or more: No dosage adjustment necessary.
CrCl 31 to 49 mL/minute/1.73 m2: Reduce to 2.5 mg/kg/dose.
CrCl 10 to 30 mL/minute/1.73 m2: Reduce to 1.6 mg/kg/dose.
CrCl less than 10 mL/minute/1.73 m2 (not on dialysis or CRRT): 1.6 mg/kg IV on day one, then 0.25 mg/kg IV daily. (NOTE: The regimen approved in the EUA was for a 5 to 10 day course.)
 
Infants 31 to 90 days:
CrCl 50 mL/minute/1.73 m2 or more: No dosage adjustment necessary.
CrCl 31 to 49 mL/minute/1.73 m2: Reduce to 2 mg/kg/dose.
CrCl 10 to 30 mL/minute/1.73 m2: Reduce to 1.3 mg/kg/dose.
CrCl less than 10 mL/minute/1.73 m2 (not on dialysis or CRRT): 1.3 mg/kg IV on day one, then 0.2 mg/kg IV daily. (NOTE: The regimen approved in the EUA was for a 5 to 10 day course.)
 
Neonates:
CrCl 50 mL/minute/1.73 m2 or more: No dosage adjustment necessary.
CrCl 31 to 49 mL/minute/1.73 m2: Reduce to 1.5 mg/kg/dose.
CrCl 10 to 30 mL/minute/1.73 m2: Reduce to 1 mg/kg/dose.
CrCl less than 10 mL/minute/1.73 m2 (not on dialysis or CRRT): 1 mg/kg IV on day one, then 0.15 mg/kg IV daily. (NOTE: The regimen approved in the EUA was for a 5 to 10 day course.)
 
 
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.

Drug Interactions

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.

How Supplied

Rapivab Intravenous Inj Sol: 1mL, 10mg

Maximum Dosage
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

181 days and older: 12 mg/kg/day IV.
31 to 180 days: Safety and efficacy have not been established.

Neonates

Safety and efficacy have not been established.

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. 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.

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.
 
Affected cytochrome P450 isoenzymes and drug transporters: none

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.

Pregnancy And Lactation
Pregnancy

Limited available data with peramivir use in pregnancy are insufficient to determine a drug-associated risk of adverse developmental outcomes. There are risks to the mother and fetus associated with influenza in pregnancy. 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.

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.