130
P A R T 2
Chemotherapeutic agents
AGENTS FOR INFLUENZA A AND
RESPIRATORY VIRUSES
Influenza A
and other respiratory viruses, including
influenza B and respiratory syncytial virus (RSV), invade
the respiratory tract and cause the signs and symptoms
of respiratory “flu”. Vaccines have been developed (see
Chapter 18) to stimulate immunity against influenza
A and RSV. Preventing the viral infection is the best
option, but if people do develop a viral infection, some
drug therapies are available. Agents for influenza A and
respiratory viruses include amantadine (
Symmetrel
),
oseltamivir (
Tamiflu
), ribavirin (
Virazide
) and zanam-
ivir (
Relenza
). These drugs are described in detail in
Table 10.1.
Therapeutic actions and indications
The exact mechanism of action of drugs that combat
influenza A and respiratory viruses is not known.
The belief is that these agents prevent shedding of the
viral protein coat and entry of the virus into the cell
(Figure 10.2). This action prevents viral replication,
causing viral death. These agents for influenza A and
respiratory viruses are especially important for health-
care workers and other high-risk individuals and
for reducing the severity of infection if it occurs. See
Table 10.1 for usual indications specific to each antiviral
drug. Oseltamivir is the only antiviral agent that has
been shown to be effective in treating avian flu.
Pharmacokinetics
Amantadine is slowly absorbed from the gastrointesti-
nal (GI) tract, reaching peak levels in 4 hours. Excretion
occurs unchanged through the urine, with a half-life of
15 hours. Oseltamivir is readily absorbed from the GI
tract, extensively metabolised in the urine and excreted
in the urine with a half-life of 6 to 10 hours.
Ribavirin, an inhaled drug, is slowly absorbed
through the respiratory tract. It is metabolised at the
cellular level and is excreted in the faeces and urine
with a half-life of 9.5 hours. It is teratogenic and is rated
pregnancy category X.
Zanamivir must be delivered by a Diskhaler device,
which comes with every prescription. It is absorbed
through the respiratory tract and excreted unchanged in
the urine with a half-life of 2.5 to 5.1 hours.
Contraindications and cautions
Because of its renal clearance, amantadine must be
used at reduced doses and with caution in people who
have any renal impairment
to avoid altered metabolism
and excretion of the drug
. Amantadine is embryotoxic
in animals and crosses into breast milk. Therefore, it
should be used during pregnancy and breastfeeding only
if the benefits clearly outweigh the risks to the fetus or
neonate.
People with renal dysfunction who are taking
oseltamivir require reduced doses and close monitoring
to avoid altered metabolism and excretion of the drug
.
TABLE 10.1
DRUGS IN FOCUS Agents for influenza A and respiratory viruses
Drug name
Dosage/route
Usual indications
amantadine (Symmetrel)
Adult and paediatric >10 years: 100 mg PO b.d.
Paediatric 5–9 years: 100 mg PO daily.
Treatment of Parkinson’s disease;
treatment and prevention of respiratory
virus infections
oseltamivir (Tamiflu)
Adult: 75 mg PO b.d. for 5 days (treatment);
75 mg/day PO for 7 days (prevention)
Paediatric (1–12 years): 30–75 mg b.d. PO for
5 days (treatment); 30–75 mg/day for 7 days
(prevention)
Treatment and prevention of
uncomplicated influenza for person who
is symptomatic for <2 days; only antiviral
agent effective in treatment of avian flu
ribavirin (Rebetol, Virazide)
Adult <65 kg: 800 mg/day PO;
65–85 kg: 1000 mg/day PO;
86–105 kg 1400 mg/day PO;
>105 kg: 1400 mg/day PO
Used in combination with interferon
alfa-2b as an oral drug for the treatment
of chronic hepatitis C in children and
adults who relapse after interferon-alpha
therapy
Treatment of influenza A, respiratory
syncytial virus (RSV), and herpes virus
infections; treatment of children with
RSV; has undergone testing for use in
several other viral conditions
zanamivir (Relenza)
2 inhalations b.d. for 5 days
Approved in 1999 for treatment and
prevention of uncomplicated influenza
infections in adults and in children
>7 years of age who have had symptoms
for <2 days
