peramivir (Rx)

1-10%

Adults

• Diarrhea (8%)
• Neutrophils <1 x 10⁹/L (8%)
• Increased serum glucose (>160 mg/dL) (5%)
• Creatine phosphokinase (≥6 xULN) (5%)
• Constipation (4%)
• Insomnia (3%)
• AST and ALT increased (3%)
• Hypertension (2%)

Aged 6 months to 17 years

• Generally, similar to adults, except for following
• Vomiting (3%)
• Proteinuria (3%)

Postmarketing Reports

Dermatologic: Stevens-Johnson syndrome, exfoliative dermatitis, rash

General disorders and administration site conditions: Anaphylactic/anaphylactoid reactions

Psychiatric: Abnormal behavior, hallucination

Contraindications

Known serious hypersensitivity or anaphylaxis to peramivir or any component of the product; severe allergic reactions have included anaphylaxis, erythema multiforme, and Stevens-Johnson Syndrome

Cautions

Serious skin reactions reported including erythema multiforme and Stevens-Johnson syndrome; discontinue and initiate appropriate treatment

Influenza can be associated with neurologic and behavioral symptoms including hallucinations, delirium, and abnormal behavior, in some cases resulting in fatal outcomes; postmarketing surveillance has reported delirium and abnormal behavior leading to injury in patients receiving neuraminidase inhibitors

Serious bacterial infections may begin with influenza-like symptoms or may coexist with or occur as complications during the course of influenza; peramivir has not been shown to prevent such complications

Drug interaction overview

• Inactivated influenza vaccine: May administered at any time relative to use of peramivir
• Live attenuated influenza vaccine (LAIV; intranasal): Antiviral drugs may inhibit viral replication and reduce vaccine efficacy; avoid LAIV within 2 weeks before or 48 hr after peramivir unless medically indicated

Pregnancy

Limited available data with use in pregnant women 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

Animal studies

• Administered during organogenesis in rats

  • Dose 8 x human recommended dose
  • Single IV bolus injection: No adverse effects observed
  • Continuous IV infusion: Reduced renal papilla and dilated ureters were observed

• Administered in rabits

  • Administration of drug during organogenesis at exposures 8 times those in humans at recommended dose resulted in developmental toxicity (abortion or premature delivery) at a maternally toxic dose

Lactation

There are no data on presence of drug in human milk, effects on breastfed infant, or on milk production; drug is present in rat milk limited clinical data during lactation preclude a clear determination of risk of therapy to an infant during lactation; therefore, developmental and health benefits of breastfeeding should be considered along with mother’s clinical need for therapy and any potential adverse effects on breastfed child from drug or from underlying maternal condition

Pregnancy Categories

A: Generally acceptable. Controlled studies in pregnant women show no evidence of fetal risk.

B: May be acceptable. Either animal studies show no risk but human studies not available or animal studies showed minor risks and human studies done and showed no risk.

C: Use with caution if benefits outweigh risks. Animal studies show risk and human studies not available or neither animal nor human studies done.

D: Use in LIFE-THREATENING emergencies when no safer drug available. Positive evidence of human fetal risk.

X: Do not use in pregnancy. Risks involved outweigh potential benefits. Safer alternatives exist.

NA: Information not available.

Mechanism of Action

Elicits antiviral activity by inhibiting influenza virus neuraminidase, an enzyme that releases viral particles from the plasma membrane of infected cells

Absorption

Peak plasma concentration

• 6 months to <2 years: 38,000 ng/mL
• 2 to <7 years: 47,400 ng/mL
• 7 to <13 years: 61,200 ng/mL
• 13 to <18 years: 51,500 ng/mL
• Adults: 45,700 ng/mL

AUC

• 6 months to <2 years: 46,200 ng⋅h/mL
• 2 to <7 years: 62,700 ng⋅h/mL
• 7 to <13 years: 76,300 ng⋅h/mL
• 13 to <18 years: 65,500 ng⋅h/mL
• Adults: 68,500 ng⋅h/mL

Distribution

Protein bound: <30%

Vd: 12.56 L

Metabolism

Not significantly metabolized

It is not a substrate for CYP enzymes, does not affect glucuronidation, and is not a substrate or inhibitor of P-gp

Elimination

Half-life: 20 hr (single 600-mg IV dose)

Clearance: ~90% (renal)

Excretion: Urine ~90%

IV Compatibilities

0.9% NaCl

0.45% NaCl

D5W

Lactated Ringer solution

Compatible with materials commonly used for administration (eg, PVC bags, PVC-free bags, polypropylene syringes, polyethylene tubing)

IV Preparation

Contains no preservatives or bacteriostatic agents; do not use if seal over vial opening is broken or missing

Visually inspect vial for particulate matter and discoloration

Dilute appropriate dose in 0.9% or 0.45% NaCl, D5W, or lactated Ringer solution to final concentration of 1-6 mg/mL as recommended by age and weight

Maximum infusion volume by age and weight

• Infants aged 6 months to 1 year (any weight): 25 mL

Adults and pediatric patients aged ≥1 yr

• 5 kg to <10 kg: 25 mL
• 10 kg to <15 kg: 50 mL
• 15 kg to <20 kg: 75 mL
• ≥20 kg: 100 mL

IV Administration

Administer IV over 15-30 minutes

Do not mix or infuse with other IV medications

Storage

Unopened vials: Store in original cartons at 20-25°C (68-77°F); excursions permitted to 15-30°C (59-86°F)

Diluted solution: Administer immediately or refrigerate at 2-8°C (36-46°F) for up to 24 hr

If refrigerated, allow diluted solution to reach room temperature then administer immediately