Peramivir

(INVESTIGATIONAL)

Pronunciation: per-AM-i-vir
Class: Antiviral agent

Trade Names

Peramivir
- Injection, solution 200 mg per 20 mL

Pharmacology

Inhibition of influenza virus neuraminidase.

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Pharmacokinetics

Elimination

Eliminated via the kidney. Renal Cl of unchanged peramivir accounts for approximately 90% of total Cl. The half-life of peramivir following administration of 0.5 to 8 mg/kg as a single dose or 4 mg/kg twice daily for 1 day ranged from 7.7 to 20.8 h.

Special Populations

Renal Function Impairment

Mean systemic exposure expected to be approximately 24% higher, 3.4-fold higher, and 6-fold higher in mild, moderate, or severe renal function impairment, respectively. Dosage adjustment required.

Hepatic Function Impairment

Peramivir is not significantly metabolized by the liver.

Elderly

46% increase in dose-normalized AUC and, on average, 26% lower Cl than in healthy patients. Dose adjustment not needed.

Children

Pharmacokinetics have not been studied.

Gender

Pharmacokinetics have not been studied.

Race

Pharmacokinetics have not been studied.

Indications and Usage

Investigational drug authorized for emergency use for the treatment of certain hospitalized patients with known or suspected 2009 H1N1 influenza. Peramivir is authorized only for the following patients who are admitted to a hospital and for whom an IV agent is clinically appropriate based upon one of the following reasons: patient is not responding to either oral or inhaled antiviral therapy; or drug delivery by a route other than IV (eg, enteral oseltamivir or inhaled zanamivir) is not expected to be dependable or is not feasible. In adults, peramivir is indicated if the health care provider judges IV therapy to be appropriate because of other circumstances.

Only the CDC is authorized to distribute peramivir to a hospital at the request of the licensed treating clinician. A peramivir IV request must be submitted electronically to the CDC to obtain peramivir via the CDC's Peramivir IV Electronic Request System.

Contraindications

History of severe allergic reaction to any other neuraminidase inhibitors (zanamivir or oseltamivir) or any ingredient of the product.

Dosage and Administration

Adults

IV 600 mg over 30 min once daily for 5 to 10 days.

Children 6 to 17 yr of age

IV 10 mg/kg over 60 min once daily for 5 to 10 days (max, 600 mg/day).

Children 181 days to 5 yr of age

IV 12 mg/kg over 60 min once daily for 5 to 10 days (max, 600 mg/day).

Children 91 to 180 days of age

IV 10 mg/kg over 60 min once daily for 5 to 10 days.

Children 31 to 90 days of age

IV 8 mg/kg over 60 min once daily for 5 to 10 days.

Children up to 30 days of age

IV 6 mg/kg over 60 min once daily for 5 to 10 days.

Renal function impairment
Adults

IV

Moderate renal impairment (CrCl 31 to 49 mL/min)

150 mg once daily for 5 to 10 days.

Severe renal impairment (CrCl 10 to 30 mL/min)

100 mg once daily for 5 to 10 days.

CrCl less than 10 mL/min and not on dialysis or renal replacement therapy

100 mg on day 1 of dosing, followed by 15 mg once daily thereafter for 5 to 10 days.

ESRD on intermittent hemodialysis

100 mg on day 1, then 100 mg given 2 h after each hemodialysis session on dialysis days for 5 to 10 days.

Children 6 to 17 yr of age

IV

CrCl 31 to 49 mL/min per 1.73 m ²

2.5 mg/kg once daily for 5 to 10 days.

CrCl 10 to 30 mL/min per 1.73 m ²

1.6 mg/kg once daily for 5 to 10 days.

CrCl less than 10 mL/min per 1.73 m ² and not on intermittent hemodialysis or continuous renal replacement therapy (CRRT)

1.6 mg/kg on day 1, then 0.25 mg/kg once daily for 5 to 10 days.

ESRD (CrCl less than 10 mL/min per 1.73 m ² ) on intermittent hemodialysis

1.6 mg/kg on day 1, then 1.6 mg/kg given 2 h after each hemodialysis session on dialysis days for 5 to 10 days.

Children 181 days to 5 yr of age

IV

CrCl 31 to 49 mL/min per 1.73 m ²

3 mg/kg once daily for 5 to 10 days.

CrCl 10 to 30 mL/min per 1.73 m ²

1.9 mg/kg once daily for 5 to 10 days.

CrCl less than 10 mL/min per 1.73 m ² and not on intermittent hemodialysis or CRRT

1.9 mg/kg on day 1, then 0.3 mg/kg once daily for 5 to 10 days.

ESRD (CrCl less than 10 mL/min per 1.73 m ² ) on intermittent hemodialysis

1.9 mg/kg on day 1, then 1.9 mg/kg given 2 h after each hemodialysis session on dialysis days for 5 to 10 days.

Children 91 to 180 days of age

IV

CrCl 31 to 49 mL/min per 1.73 m ²

2.5 mg/kg once daily for 5 to 10 days.

CrCl 10 to 30 mL/min per 1.73 m ²

1.6 mg/kg once daily for 5 to 10 days.

CrCl less than 10 mL/min per 1.73 m ² and not on intermittent hemodialysis or CRRT

1.6 mg/kg on day 1, then 0.25 mg/kg once daily for 5 to 10 days.

ESRD (CrCl less than 10 mL/min per 1.73 m ² ) on intermittent hemodialysis

1.6 mg/kg on day 1, then 1.6 mg/kg given 2 h after each hemodialysis session on dialysis days for 5 to 10 days.

Children 31 to 90 days of age

IV

CrCl 31 to 49 mL/min per 1.73 m ²

2 mg/kg once daily for 5 to 10 days.

CrCl 10 to 30 mL/min per 1.73 m ²

1.3 mg/kg once daily for 5 to 10 days.

CrCl less than 10 mL/min per 1.73 m ² and not on intermittent hemodialysis or CRRT

1.3 mg/kg on day 1, then 0.2 mg/kg once daily for 5 to 10 days.

ESRD (CrCl less than 10 mL/min per 1.73 m ² ) on intermittent hemodialysis

1.3 mg/kg on day 1, then 1.3 mg/kg given 2 h after each hemodialysis session on dialysis days for 5 to 10 days.

Children up to 30 days of age

IV

CrCl 31 to 49 mL/min per 1.73 m ²

1.5 mg/kg once daily for 5 to 10 days.

CrCl 10 to 30 mL/min per 1.73 m ²

1 mg/kg once daily for 5 to 10 days

CrCl less than 10 mL/min per 1.73 m ² and not on intermittent hemodialysis or CRRT

1 mg/kg on day 1, then 0.15 mg/kg once daily for 5 to 10 days.

ESRD (CrCl less than 10 mL/min per 1.73 m ² ) on intermittent hemodialysis

1 mg/kg on day 1, then 1 mg/kg given 2 h after each hemodialysis session on dialysis days for 5 to 10 days.

Continuous venovenous hemodialysis (CVVHD) or other CRRT

Use previous values, except use the CRRT clearance (CL _CRRT ) instead of CrCl determined with the Cockcroft and Gault equation (adults) or Schwartz equation (children). If patient has any residual renal function while on CRRT, add an estimate of the patient's renal clearance to CL _CRRT in order to estimate clearance before using the values above.

For slow continuous ultrafiltration (SCUF), continuous arteriovenous hemofiltration (CAVH), or CVVH

CL _CRRT = ultrafiltration rate (mL/min).

For continuous arteriovenous hemodialysis or continuous venovenous hemodialysis

CL _CRRT = dialysate flow rate (mL/min).

For continuous arteriovenous hemodiafiltration and continuous venovenous hemodiafiltration

CL _CRRT = ultrafiltration rate (mL/min) + dialysate flow rate (mL/min).

General Advice

• Peramivir is an investigational drug. Maintain adequate records showing receipt, use, and disposition of peramivir. For unused intact vials, maintain adequate records showing use and disposition of peramivir.
• Initial treatment courses are for 5 to 10 days' duration. For adults, treatment beyond 10 days is permitted depending on clinical presentation, such as critical illness (eg, respiratory failure or intensive care unit admission), continued viral shedding, or unresolved clinical influenza illness.
• Do not administer as an IM injection.
• Infusion rates should not exceed 40 mg/min.
• A separate IV line or separate IV lumen in a multilumen catheter is recommended.
• Peramivir must only be diluted in sodium chloride 0.9% or 0.45% injection that does not contain dextrose or other electrolytes. Refer to manufacturer's Fact Sheet for Health Care Providers for directions.
• Do not administer simultaneously with any other medications.
• Before infusion of peramivir via a heparin lock, flush the port with 3 to 5 mL of sterile saline. After the infusion of peramivir is complete, flush the port again with sterile saline and the heparin can be added to maintain the patency of the catheter.
• If other mediations are also administered via a single lumen catheter or a single multilumen catheter, administer at least 10 mL of sterile saline between the infusions.
• Peramivir may be piggybacked into an existing saline infusion line.

Storage/Stability

Store at ambient temperature (59° to 86°F); however, temperature extremes encountered during shipment and storage (including freezing) would likely not adversely affect the quality of this product. Once a diluted solution has been prepared, administer immediately or store under refrigerated conditions (36° to 46°F). If refrigerated, allow the refrigerated diluted solution to reach room temperature prior to administration. Administer the diluted solution within 24 h following preparation. Discard any unused diluted solution after 24 h. Discard any unused portion of a single-use peramivir injection vial after a diluted solution is prepared.

Drug Interactions

Renally eliminated or nephrotoxic agents

Coadministration with drugs that reduce renal function or compete for active tubular secretion may increase the concentration of peramivir and/or increase the concentrations of other renally eliminated drugs. Use with caution.

Adverse Reactions

Cardiovascular

ECG abnormalities (single case report of prolonged QTc), hypertension.

CNS

Depression, dizziness, feeling agitated, headache, insomnia, nervousness, nightmares, somnolence.

GI

Diarrhea (13%); nausea, vomiting.

Genitourinary

Cystitis, hematuria, proteinuria.

Miscellaneous

Anorexia, hyperbilirubinemia, hyperglycemia, neutrophil count decreased.

Precautions

Monitor Monitor patients for development of diarrhea and administer appropriate evaluation and/or treatment, as indicated, including evaluation for other causes of diarrhea as clinically warranted. Monitor, evaluate, and treat patients for suspected bacterial infections. Closely monitor patients with influenza for signs of abnormal behavior. If neuropsychiatric symptoms occur, evaluate the risks and benefits of continuing treatment for each patient. Upon initiation, day 3 of therapy, and end of therapy, monitor CBC with differential and a basic metabolic profile (eg, glucose, calcium, sodium, potassium, chloride, serum bicarbonate, creatinine, and blood urea nitrogen). Upon initiation and conclusion of therapy and during therapy, if clinically indicated, monitor ALT, AST, alkaline phosphatase, and total and direct bilirubin. Perform urinalysis upon initiation and conclusion of therapy and during therapy, if clinically indicated. If significant proteinuria develops while on therapy, consider appropriate further evaluation, including laboratory testing, 24-h urine collection, and possible nephrology consultation. Monitor body temperature, noninvasive blood pressure, heart rate, respiratory rate, and oxygen saturation daily (at a minimum). Assess serum creatinine prior to initiation of dosing and follow carefully throughout dosing, as clinically appropriate. It is especially important for patients in whom abnormal laboratory values are noted at the time peramivir treatment is initiated to be monitored through the duration of therapy for worsening. Continually assess patients with significant or serious metabolic abnormalities with regard to the risks and potential benefits of continued peramivir therapy. Perform careful follow-up and, at a minimum, repeat assessment within 1 to 2 wk of the conclusion of therapy to assess normalization in patients with abnormal laboratory parameters.

Pregnancy

Category undetermined.

Lactation

Undetermined.

Elderly

Use with caution.

Hypersensitivity

Allergic-like reactions, including oropharyngeal edema, serious skin rashes, and anaphylaxis, have been reported with use of neuraminidase inhibitors.

Renal Function

Dosage adjustment required in all patients with known or suspected renal insufficiency.

Bacterial infections

Serious bacterial infections may begin with influenza-like symptoms or may coexist with or develop as complications during the course of influenza illness.

GI effects

May occur.

Neuropsychiatric events

Neurologic and behavioral symptoms, including hallucinations, delirium, and abnormal behavior, may occur.

Patient Information

• Advise patient that peramivir is an unapproved product. The FDA has authorized the emergency use of peramivir under an Emergency Use Authorization (EUA).
• Advise patients that peramivir is not for the treatment of seasonal influenza A or B, for outpatients with acute uncomplicated 2009 H1N1 virus infection, or for pre- or postexposure prevention of influenza.

Copyright © 2009 Wolters Kluwer Health.