Peramivir (Rapivab) is an antiviral drug. It is a neuraminidase inhibitor that is used in the treatment of patients with influenza.

Peramivir (Rapivab)  Uses:

• 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.

• Off Label Use of Peramivir in Adults:

  • High-risk patients or hospitalized patients with Influenza.

Peramivir (Rapivab) Dose in Adults

Peramivir (Rapivab) Dose in the treatment of acute uncomplicated Influenza:

• IV: 600 mg as a single dose; initiate within 2 days of onset of symptoms of influenza

Peramivir (Rapivab) Dose in the treatment of hospitalized or high-risk patients with Influenza:

• IV: 600 mg once a day for up to 5 to 10 days.

Note:

• During the 2009 influenza season, peramivir was prescribed as part of an Emergency Use Authorization in the US for patients with pandemic A (H1N1) 2009 virus at 24 hourly doses of 600 mg for a median duration of 6 days.
• Subsequently, the drug has been studied but was not approved for use in hospitalized patients and/or patients with complicated influenza because a clinical benefit could not be demonstrated.
• Some clinicians, however, may consider its use in this population, particularly in patients unable to tolerate or absorb oral oseltamivir.

Peramivir (Rapivab) Dose in Children

Peramivir (Rapivab) Dose in the treatment of acute uncomplicated Influenza:

• Note: Administer within 2 days of onset of symptoms of influenza.

• Children ≥2 years:

  • IV: 12 mg/kg in a single dose;
  • maximum dose: 600 mg/dose

• Adolescents:

  • IV: 600 mg as a single dose

Peramivir (Rapivab) Dose in the treatment of hospitalized, high-risk patients with Influenza and/or during an epidemic:

• Note:
  • During the 2009 influenza season, peramivir was prescribed as part of an Emergency Use Authorization in the US for patients with pandemic A (H1N1) 2009 virus.
  • Subsequently, the drug has been studied but is not approved for use in hospitalized patients and/or patients with complicated influenza.

• Infants, Children, and Adolescents:

Intravenous:

• 29 to 30 days of life:
  • 6 mg/kg/dose once a day for 5 to 10 days.
  • others have used 10 mg/kg/dose once a day.

• 31 to 90 days of life:

  • 8 mg/kg/dose once a day for 5 to 10 days.
  • others have used 10 mg/kg/dose once a day

• 91 to 180 days of life:

  • 10 mg/kg/dose once a day for 5 to 10 days.

• 181 days of life through 5 years:

  • 12 mg/kg/dose once a day for 5 to 10 days.
  • others have used 10 mg/kg/dose once a day,
  • The maximum daily dose: 600 mg/day

• 6 to 17 years:

  • 10 mg/kg/dose once a day for 5 to 10 days;
  • The maximum daily dose is 600 mg/day

• ≥18 years:

  • 600 mg once a day for 5 to 10 days.

Pregnancy Risk Category: Not assigned

• Peramivir use during pregnancy is not well-documented.
• According to one case, peramivir's pharmacokinetics may change with pregnancy.
• Untreated influenza infection can lead to serious complications and even death for the mother.
• For the treatment or prevention of influenza in pregnancy, and for women who are pregnant up to 2 weeks after giving birth, neuraminidase inhibitors should be used.
• However, other agents than peramivir are recommended.

Peramivir use during breastfeeding:

• Peramivir may be present in breastmilk, but it is unknown.
• According to the drug manufacturer the decision to discontinue or continue breastfeeding should be based on the risks to infants, the benefits to the mother and the benefits to the mother.

Peramivir  Dose in Kidney Disease:

• Note: Renal function may be estimated using the Cockcroft-Gault formula.

• Uncomplicated influenza:

  • CrCl ≥50 mL/minute:

    • No dosage adjustment is necessary.

  • CrCl 30 to 49 mL/minute:

    • 200 mg as a single dose

  • CrCl 10 to 29 mL/minute:

    • 100 mg as a single dose

  • ESRD requiring intermittent hemodialysis (IHD):

    • 100 mg as a single dose, administered after dialysis

• Hospitalized (high-risk) patients with influenza (FDA 2009):

  • CrCl ≥50 mL/minute:

    • 600 mg once a day

  • CrCl 31 to 49 mL/minute:

    • 150 mg once a day

  • CrCl 10 to 30 mL/minute:

    • 100 mg once a day

  • CrCl <10 mL/minute (not on renal replacement therapy):

    • 100 mg once a day on day 1, then 15 mg once daily beginning on day 2

  • ESRD requiring intermittent hemodialysis (IHD):

    • 100 mg on day 1, then 100 mg given 2 hours after each dialysis session.

  • Continuous renal replacement therapy (CRRT):

    • Pharmacokinetic data indicate that peramivir is efficiently cleared by CRRT due to the high sieving coefficient and low protein binding.
    • One suggested method for determining the dose of peramivir while on CRRT, assuming a sieving coefficient of 100% and negligible protein binding, is to estimate the patient’s total clearance based on the following equation and refer to the above renal dosage adjustments for dose selection (FDA 2009):
      • Total clearance = Residual renal function (mL/minute) + CRRT clearance (CL ) (mL/minute)

    • CL can be determined as follows:

      • CVVH/Continuous arteriovenous hemofiltration (CAVH)/Slow continuous ultrafiltration (SCUF):

        • Use ultrafiltration rate (mL/minute)

      • CAVHD/CVVHD:

        • Use dialysate flow rate (mL/minute)

      • Continuous arteriovenous hemodialysis (CAVHDF)/CVVHDF:

        • Use a total of ultrafiltration rate and dialysate flow rate (mL/minute)

Peramivir Dose in Liver Disease:

• There are no dosage adjustments provided in the drug manufacturer’s labeling (has not been studied);
• however, not significantly metabolized hepatically.

Side Effects of Peramivir (Rapivab):

• Cardiovascular:

  • Hypertension

• Central Nervous System:

  • Insomnia

• Endocrine:

  • Increased Serum Glucose

• Gastrointestinal:

  • Diarrhea
  • Constipation
  • Vomiting

• Genitourinary:

  • Proteinuria

• Hematologic And Oncologic:

  • Neutropenia

• Hepatic:

  • Increased Serum ALT
  • Increased Serum AST

• Neuromuscular & Skeletal:

  • Increased Creatine Phosphokinase

• Miscellaneous:

  • Fever

Contraindications to Peramivir:

• Serious hypersensitivity/anaphylaxis to peramivir or any component of the formulation.

Warnings and precautions

• Dermatologic reactions

  • Rarely, severe skin reactions, such as Stevens-Johnson syndrome or erythema multiforme have been reported.
  • If you suspect or experience skin reactions, stop infusion immediately and seek supportive treatment.

• Hypersensitivity reactions

  • There have been reports of severe hypersensitivity reactions (eg anaphylaxis).
  • Stop infusion immediately and start supportive treatment.

• Events in neuropsychiatrics:

  • A few rare cases of neuropsychiatric events, including delirium, abnormal behavior, hallucinations, and delirium, have been reported, mostly among pediatric patients.
  • The initial shock is not uncommon and the resolution is quick.
  • These events can occur in patients with encephalitis or encephalopathy as well as in those who have uncomplicated influenza.
  • Pay attention to any signs of abnormal behavior.

• Renal impairment

  • Elimination is primarily a renal process.
  • Patients with CrCl >50 mL/minute will need to adjust their dosage.

Peramivir: Drug Interaction

Monitoring Parameters:

• Baseline BUN and serum creatinine,
• neurologic abnormalities (eg, abnormal behavior),
• rash after administration.

How to administer Peramivir (Rapivab)?

• IV: Administer as an IV infusion over 15 to 30 minutes.

Mechanism of action of Peramivir (Rapivab):

• Peramivir is a cyclopentane analogue that selectively inhibits influenza virus neuraminidase enzyme. This prevents infected cells from releasing viral particles.

Protein binding:

• <30%

Metabolism:

• Not significantly metabolized

Bioavailability:

• Oral: Low (investigational agent)

Half-life elimination:

• ~20 hours

Excretion:

• Urine (~90% as unchanged drug)

International Brands of Peramivir:

• Rapivab
• Alpivab
• Peramiflu
• Rapiacta

Peramivir Brand Names in Pakistan:

No Brands Available in Pakistan.