C H A P T E R 1 0
Antiviral agents
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Pharmacokinetics
Most of the agents for herpes and cytomegalovirus are
readily absorbed in the body and excreted in the urine.
Although cidofovir has been proven to be embryotoxic
in animals, no adequate studies have been completed for
the other agents.
Aciclovir, which can be given orally and paren-
terally or applied topically, reaches peak levels within
1 hour and has a half-life of 2.5 to 5 hours. It is excreted
unchanged in the urine. It crosses into breast milk,
which exposes the neonate to high levels of the drug.
Cidofovir, which is given by intravenous (IV)
infusion, reaches peak levels at the end of the infusion
and in studies was cleared from the system within
15 minutes after the infusion. It is excreted unchanged
in the urine and must be given with probenecid to
increase renal clearance of the drug. The dose must be
titrated according to renal function and creatinine clear-
ance; renal function tests must be done before each dose
and the dose planned accordingly.
Famciclovir, an oral drug, is well absorbed from the
GI tract, reaching peak levels in 2 to 3 hours. Famciclo-
vir is metabolised in the liver and excreted in the urine
and faeces. It has a half-life of 2 hours and is known to
cross the placenta.
Foscarnet is available in IV form only. It reaches
peak levels at the end of the infusion and has a half-
life of 4 hours. About 90% of foscarnet is excreted
unchanged in the urine, making it highly toxic to the
kidneys. Use caution and at reduced dose in individuals
with renal impairment.
Ganciclovir is available in IV and oral forms. It has
a slow onset and reaches peak levels at 1 hour if given
IV and 2 to 4 hours if given orally. This drug is primar-
ily excreted unchanged in the faeces with some urinary
excretion, with a half-life of 2 to 4 hours.
Valaciclovir is an oral agent and is rapidly absorbed
from the GI tract and metabolised in the liver to aci-
clovir. Excretion occurs through the urine, so caution
should be used in individuals with renal impairment.
Valganciclovir is the oral prodrug, that is, it is imme-
diately converted to ganciclovir once it is in the body. It
is rapidly absorbed and reaches peak levels in 3 hours.
It is primarily excreted unchanged in the faeces with
some urinary excretion, with a half-life of 2.5 to 3 hours.
Contraindications and cautions
Drugs indicated for the treatment of herpes and CMV
are highly toxic and should not be used during preg-
nancy or breastfeeding
to prevent adverse effects
on the fetus or infant
; use only if the benefits clearly
outweigh the potential risks to the fetus or infant. Avoid
use in people with known allergies to antiviral agents
to prevent serious hypersensitivity reactions
; in indi-
viduals with renal disease,
which could interfere with
excretion of the drug
; or in people with severe CNS
disorders
because the drug can affect the CNS, causing
headache, neuropathy, paraesthesias, confusion and
hallucinations.
Cidofovir has been proven to be embryotoxic in
animals. Use cidofovir with caution in children with
AIDS because of the potential carcinogenic effects and
effects on fertility. If no other treatment option is avail
able, monitor the child very closely.
For famciclovir, safety of use in children younger
than 18 years of age has not been established.
Foscarnet has been shown to affect bone develop-
ment and growth. Foscarnet, as well as ganciclovir and
valganciclovir, should not be used in children unless the
benefit clearly outweighs the risk and the child is moni-
tored very closely.
Adverse effects
The adverse effects most commonly associated with these
antiviral agents include nausea and vomiting, headache,
depression, paraesthesias, neuropathy, rash and hair
loss. Rash, inflammation and burning often occur
at sites of IV injection and topical application. Renal
dysfunction and renal failure also have been reported.
Cidofovir is associated with severe renal toxicity and
granulocytopenia. Ganciclovir and valganciclovir have
been associated with bone marrow suppression. Fos-
carnet has been associated with seizures, especially in
individuals with electrolyte imbalance.
Clinically important drug–drug interactions
The risk of nephrotoxicity increases when agents indi-
cated for the treatment of herpes and CMV are used in
Prototype summary: Aciclovir
Indications:
Treatment of herpes simplex virus (HSV)
1 and 2 infections; treatment of severe genital HSV
infections; treatment of HSV encephalitis; acute
treatment of shingles and chickenpox; ointment for
the treatment of genital herpes infections; cream
for the treatment of cold sores (herpes labialis).
Actions:
Inhibits viral DNA replication.
Pharmacokinetics:
Route Onset
Peak
Duration
Oral
Varies
1.5–2 hours Not known
IV Immediate 1 hour
8 hour
Topical Not generally absorbed systemically
T
1/2
:
2.5–5 hours; excreted unchanged in the urine.
Adverse effects:
Headache, vertigo, tremors, nausea,
vomiting, rash.
