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INFECTIOUS
DISEASES
Allana Sucher, Section Advisor
Emergency use of peramivir approved
Key point: FDA has issued an emergency use
authorization for I.V. peramivir, an unapproved investigational
neuraminidase inhibitor, for the treatment of specific adult and
pediatric patients with suspected or laboratory-confirmed H1N1
influenza. Peramivir is authorized for use in patients not responding to
either oral or inhaled antiviral therapy or when drug delivery by a
route other than I.V. is not expected to be dependable or feasible.
Finer points: Peramivir has limited efficacy and
safety data. Only four trials using I.V. peramivir have been
completed—three in patients with acute uncomplicated influenza and
one in hospitalized patients with acute influenza. None of these trials
has been conducted in patients with the H1N1 virus or in pediatric
patients. In a Phase II trial conducted in Japan, patients with
confirmed influenza who were randomized to a single dose of peramivir
300 mg (n = 99) or 600 mg (n = 97) had an approximately 1-day treatment
benefit for time to alleviation of symptoms compared with patients given
placebo (n = 100). In a Phase III trial, patients randomized to a single
dose of peramivir 300 mg (n = 364), peramivir 600 mg (n = 362), or
oseltamivir 75 mg twice daily for 5 days (n = 365) all had a similar
time to alleviation of symptoms (median range 78.0–81.8 hours).
Another trial in patients with poorly controlled diabetes or chronic
respiratory conditions or on immunosuppressive therapy randomized
patients to peramivir 300 mg once daily (n = 18) or 600 mg once daily (n
= 19) for 1 to 5 days. Preliminary results showed that time to
alleviation of symptoms was shorter for the 600-mg group compared with
the 300-mg group and shorter in patients given multiple doses compared
with a single dose.
The trial in hospitalized patients compared peramivir 200 mg once
daily (n = 41), peramivir 400 mg once daily (n = 40), and oseltamivir 75
mg twice daily (n = 41) for 5 days. There was no reported difference
among the three treatment groups for the primary endpoint of time to
clinical stability.
A total of 1,891 adult patients have been exposed to peramivir during
clinical trials. The most common adverse events were diarrhea, nausea,
vomiting, and neutropenia. Peramivir is contraindicated in patients with
a history of serious allergic reaction to any neuraminidase inhibitor.
Although not observed in clinical trials with peramivir, serious
allergic-like reactions and psychiatric adverse events have been
reported with other neuraminidase inhibitors. Peramivir should not be
used for the treatment of seasonal influenza A or B virus infections,
for outpatients with acute uncomplicated H1N1 infection, for
chemoprophylaxis of influenza, or for the treatment of patients with
highly suspected or documented oseltamivir resistance.
What you need to know: Peramivir can only be
obtained from CDC. Clinicians who wish to use the drug must read and
understand the content of the FDA-issued Emergency Use Authorization of
Peramivir I.V.: Fact Sheet for Health Care Providers before initiating a
request to CDC. In addition, clinicians must acknowledge and agree to
all of the terms associated with use of this agent. Some of the terms
include giving the patient/caregiver the fact sheet written for
patients, documenting in the patient’s medical record that the
patient has been informed of alternative therapies and that I.V.
peramivir is an unapproved drug that has been authorized for emergency
use, and completing mandatory FDA MedWatch reporting of all medication
errors and adverse events within 7 days of the onset of the event. A
request for peramivir can be submitted at
http://emergency.cdc.gov/h1n1antivirals/3.asp.
Hospitalized patients should continue to receive therapy with an
available neuraminidase inhibitor such as oseltamivir
(Tamiflu—Roche) or zanamivir (Relenza—GlaxoSmithKline) until
after the first dose of peramivir has been given. The recommended dose
of peramivir for adults with normal renal function is 600 mg I.V.
(diluted in 0.9% or 0.45% sodium chloride) more than 30 minutes once
daily for 5 to 10 days. The recommended dose for pediatric patients is
based on age and weight. Dosage adjustments for patients with impaired
renal function are required. Infusion rates cannot exceed 40 mg per
minute.
What your patients need to know: Patients should be
given the Fact Sheet for Patients and Parents/Caregivers. In addition,
patients should be educated that peramivir is an unapproved,
investigational agent that has been authorized for emergency use in
select patients. Patients should also be informed of any alternative
therapies to peramivir.
Source
Carli Richard (crichard@aphanet.org)
Posted November 11, 2009
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