Dermatología Pediatrica

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Review Article
Marshall, Beth C.; Koch, William C..Antivirals for Cytomegalovirus
Infection in Neonates and Infants: Focus on Pharmacokinetics,
Formulations, Dosing, and Adverse Events. Pediatric Drugs:
1 October 2009 - Volume 11 - Issue 5 - pp 309-321


Abstract
Cytomegalovirus (CMV) infection is very common throughout the world,
and has become more of a pediatric clinical concern given the high
incidence of congenital CMV infections as well as the increasing
numbers of immunocompromised patients. Because of this, the need for
antiviral therapies in infants and neonates is growing.

Currently, there are four antivirals available that are active against
CMV: ganciclovir, valganciclovir, foscarnet, and cidofovir. At this
time, none have approved indications for use in children. Although
there are limited data regarding the dose, pharmacokinetics (PK),
safety, and adverse events for some of these antivirals, ganciclovir,
and its oral prodrug valganciclovir, have been the best studied in the
infant and neonate populations. In general, pharmaceutical PK studies
in young children are limited by the constraints of sampling
difficulties and blood volume requirements; fewer sampling times and
studies may be available for drug evaluation. Given this caveat,
ganciclovir and valganciclovir PK in children thus far appears to
follow a monocompartmental model, contrary to what has been described
in adults. However, when normalized for weight, the volume of
distribution, clearance, and half-life of ganciclovir are similar to
those found in adults. Given the findings that ganciclovir (and thus
valganciclovir) clearance is directly proportionate to renal function,
care must be taken when administering the drug to patients with
impaired renal function. Recent studies evaluating valganciclovir PK
in infants (at a dose of 16 mg/kg every 12 hours) have shown similar
areas under the plasma concentration-time curve (AUCs) to intravenous
ganciclovir (at a dose of 6 mg/kg every 12 hours), and that these AUCs
remain quite stable over a number of weeks. As seen in adults, oral
ganciclovir has a low bioavailability (4.8% in a pediatric analysis)
and is therefore a poor alternative for treating serious CMV
infections.

Neutropenia is the most frequent toxicity associated with ganciclovir
and valganciclovir therapy, whereas significant (and possibly
irreversible) renal toxicity can be seen with cidofovir. Foscarnet
administration can also result in renal toxicity as well as
significant electrolyte imbalances. Several of these drugs have
potential toxicities that are of concern, including carcinogenesis,
teratogenesis, and azospermia (ganciclovir, valganciclovir, and
cidofovir) and deposition into bone or dentition (foscarnet) that may
have significant implications when treating an infant. Given these
potential ill effects, careful consideration of the indications for
the clinical use of these antivirals is necessary before using them
for CMV infection in neonates and infants.