Dosage Forms
Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Solution, Intravenous [preservative free]:
Rapivab: 200 mg/20 mL (20 mL)
Pharmacology
Mechanism of Action
Peramivir, a cyclopentane analogue, selectively inhibits the influenza virus neuraminidase enzyme, preventing the release of viral particles from infected cells.
Pharmacokinetics/Pharmacodynamics
Distribution
Vd: 12.45 L
Metabolism
Not significantly metabolized
Excretion
Urine (~90% as unchanged drug)
Half-Life Elimination
~20 hours
Protein Binding
<30%
Use in Specific Populations
Special Populations: Renal Function Impairment
AUC increased with increasing degree of renal impairment
Use: Labeled Indications
Influenza: Treatment of acute, uncomplicated influenza in patients ≥2 years of age who have been symptomatic ≤2 days.
Limitations of use: Efficacy is based on clinical trials in which influenza A was the predominant virus; a limited number of subjects with influenza B have been studied.
Use: Off Label
Influenza (hospitalized, high-risk patients)c
Data from a multicenter, double-blind study conducted in Japan suggest that daily dosing of peramivir compared to a single dose may be beneficial (shorter duration of illness) in high-risk hospitalized patients with influenza A or B and moderate to severe symptoms Kohno 2011. During an open-label, randomized study of similar patients with 2009 influenza A (H1N1) in the United States, the use of peramivir was associated with decreases in viral shedding Ison 2014. However, in a subsequent randomized, placebo-controlled, multicenter, multinational trial in patients with influenza and severity of illness requiring hospitalization, the use of peramivir was not associated with decreases in viral shedding and clinical improvement and was terminated for futility due to sample size de Jong 2014. Additional data may be necessary to further define the role of daily peramivir in hospitalized high-risk patients.
Contraindications
Serious hypersensitivity or anaphylaxis to peramivir or any component of the formulation.
Dosage and Administration
Dosing: Adult
Influenza (acute, uncomplicated): IV: 600 mg as a single dose; initiate within 2 days of onset of symptoms of influenza
Influenza (hospitalized, high-risk) (off-label use): IV: 600 mg once daily for up to 5 to 10 days (de Jong 2014; Ison 2014; Kohno 2011).
Note: During the 2009 influenza season, peramivir was given as part of an Emergency Use Authorization in the US for patients with pandemic A (H1N1) 2009 virus at a daily dose of 600 mg for a median duration of 6 days (Yu 2012). Subsequently, the drug has been studied but not approved for use in hospitalized patients and/or patients with complicated influenza because a clinical benefit could not be demonstrated (de Jong 2014). Some clinicians, however, may consider its use in this population, particularly in patients unable to tolerate or absorb oral oseltamivir (Yeh 2017; Yoo 2015; Zachary 2018).
Dosing: Geriatric
Refer to adult dosing.
Dosing: Pediatric
Influenza (acute, uncomplicated), treatment: Note: Administer within 2 days of onset of symptoms of influenza.
Children ≥2 years: IV: 12 mg/kg as a single dose; maximum dose: 600 mg/dose
Adolescents: IV: 600 mg as a single dose
Influenza (hospitalized, high risk, and/or epidemic), treatment: Limited data available; optimal dosing not established. Note: During the 2009 influenza season, peramivir was given as part of an Emergency Use Authorization in the US for patients with pandemic A (H1N1) 2009 virus (FDA 2009). Subsequently, the drug has been studied but is not approved for use in hospitalized patients and/or patients with complicated influenza (de Jong 2014; Sugaya 2012). Infants, Children, and Adolescents: IV:
29 to 30 days of life: 6 mg/kg/dose once daily for 5 to 10 days (FDA 2009; Hata 2014); others have used 10 mg/kg/dose once daily (Komeda 2014; Sugaya 2012)
31 to 90 days of life: 8 mg/kg/dose once daily for 5 to 10 days (FDA 2009; Hata 2014); others have used 10 mg/kg/dose once daily (Komeda 2014; Sugaya 2012)
91 to 180 days of life: 10 mg/kg/dose once daily for 5 to 10 days (FDA 2009; Hata 2014; Komeda 2014)
181 days of life through 5 years: 12 mg/kg/dose once daily for 5 to 10 days (FDA 2009; Hata 2014); others have used 10 mg/kg/dose once daily (Komeda 2014; Sugaya 2012); maximum daily dose: 600 mg/day
6 to 17 years: 10 mg/kg/dose once daily for 5 to 10 days (FDA 2009; Hata, 2014; Komeda 2014); maximum daily dose: 600 mg/day
≥18 years: 600 mg once daily for 5 to 10 days (Hata 2014)
Reconstitution
Dilute solution in D5W, NS, 1/2NS, or LR to a maximum volume of 100 mL; administer immediately. If refrigerated, allow diluted solution to reach room temperature then administer immediately.
Administration
IV: Administer as an IV infusion over 15 to 30 minutes.
Storage
Store intact vials in original carton at 20°C to 25°C (68°F to 77°F); excursions are permitted between 15°C and 30°C (59°F and 86°F). After dilution, administer immediately or store at 2°C to 8°C (36°F to 46°F) for up to 24 hours. Discard unused diluted solution after 24 hours.
Drug Interactions
Influenza Virus Vaccine (Live/Attenuated): Antiviral Agents (Influenza A and B) may diminish the therapeutic effect of Influenza Virus Vaccine (Live/Attenuated). Management: Avoid anti-influenza antivirals during the period beginning 48 hours prior to and ending 2 weeks after live influenza virus vaccine administration. Consider therapy modification
Adverse Reactions
1% to 10%:
Cardiovascular: Hypertension (2%)
Central nervous system: Insomnia (3%)
Endocrine: Increased serum glucose (>160 mg/dL: 5%)
Gastrointestinal: Diarrhea (8%), constipation (4%), vomiting (children & adolescents: 3%)
Genitourinary: Proteinuria (children & adolescents: 3%)
Hematologic and oncologic: Neutropenia (<1 x 109/L: 8%)
Hepatic: Increased serum ALT (>2.5 x ULN: 3%), increased serum AST (3%)
Neuromuscular & skeletal: Increased creatine phosphokinase (≥6 x ULN: 4%)
Miscellaneous: Fever (children & adolescents: 2%)
<1%, postmarketing, and/or case reports: Abnormal behavior, anaphylactoid reaction, anaphylaxis, delirium, erythema multiforme, exfoliative dermatitis, hallucination, skin rash, Stevens-Johnson syndrome
Warnings/Precautions
Concerns related to adverse effects:
- Dermatologic reactions: Rare serious skin reactions (eg, erythema multiforme, Stevens-Johnson syndrome) have been reported. If skin reactions are suspected or occur, discontinue infusion immediately and institute appropriate supportive treatment.
- Hypersensitivity reactions: Serious hypersensitivity reactions (eg, anaphylaxis) have been reported. Discontinue infusion immediately and institute appropriate supportive treatment.
- Neuropsychiatric events: Rare occurrences of neuropsychiatric events (including abnormal behavior, delirium, and hallucinations), including fatalities have been reported, primarily among pediatric patients. Onset is often abrupt and subsequent resolution is rapid. These events may occur in patients with encephalitis, encephalopathy, or in uncomplicated influenza. Closely monitor for signs of abnormal behavior.
Disease-related concerns:
- Renal impairment: Elimination is primarily renal; dosage adjustment is required in patients with CrCl <50 mL/minute.
Concurrent drug therapy issues:
- Drug-drug interactions: Potentially significant interactions may exist, requiring dose or frequency adjustment, additional monitoring, and/or selection of alternative therapy. Consult drug interactions database for more detailed information.
Other warnings/precautions:
- Appropriate use: Emergence of resistance substitutions or other factors (eg, viral virulence) could decrease drug effectiveness. Consider available information on influenza drug susceptibility patterns/treatment effects when using; efficacy in patients with serious influenza requiring hospitalization has not been established. Has not been shown to prevent secondary serious bacterial infections occurring during influenza course; if bacterial infections occur, treat with antibiotics as appropriate.
Monitoring Parameters
Baseline BUN and serum creatinine, neurologic abnormalities (eg, abnormal behavior), rash after administration.
Pregnancy
Pregnancy Considerations
Information related to the use of peramivir in pregnancy is limited (Hernandez 2011; Sorbello 2012). Based on information from one case, the pharmacokinetics of peramivir may be changed with pregnancy (Clay 2011).
Untreated influenza infection is associated with an increased risk of adverse events to the fetus and an increased risk of complications or death to the mother. Neuraminidase inhibitors are currently recommended for the treatment or prophylaxis of influenza in pregnant women and women up to 2 weeks' postpartum, however agents other than peramivir are preferred (ACOG 2018; CDC 60[1], 2011).
Patient Education
What is this drug used for?
- It is used to treat the flu.
Frequently reported side effects of this drug
- Diarrhea
Other side effects of this drug: Talk with your doctor right away if you have any of these signs of:
- Stevens-Johnson syndrome/toxic epidermal necrolysis like red, swollen, blistered, or peeling skin (with or without fever); red or irritated eyes; or sores in mouth, throat, nose, or eyes.
- Confusion
- Behavioral changes
- Altered speech
- Tremors
- Seizures
- Sensing things that seem real but are not
- Signs of a significant reaction like wheezing; chest tightness; fever; itching; bad cough; blue skin color; seizures; or swelling of face, lips, tongue, or throat.
Note: This is not a comprehensive list of all side effects. Talk to your doctor if you have questions.
Consumer Information Use and Disclaimer: This information should not be used to decide whether or not to take this medicine or any other medicine. Only the healthcare provider has the knowledge and training to decide which medicines are right for a specific patient. This information does not endorse any medicine as safe, effective, or approved for treating any patient or health condition. This is only a brief summary of general information about this medicine. It does NOT include all information about the possible uses, directions, warnings, precautions, interactions, adverse effects, or risks that may apply to this medicine. This information is not specific medical advice and does not replace information you receive from the healthcare provider. You must talk with the healthcare provider for complete information about the risks and benefits of using this medicine.
