Valaciclovir

Additional information

Valaciclovir is a prodrug to aciclovir.

Pharmacokinetics and dosing

There are some published studies suggesting similar pharmacokinetics in late pregnancy and in the non-pregnant state, albeit no publication of such comparison within one study has been found. Recalculation of some  published data, to allow comparison between studies, shows roughly similar systemic exposures (AUC and Cmax) of aciclovir following oral administration of aciclovir or valaciclovir in late pregnancy (n=15) [1] as compared to other populations [2,3]. In view of the paucity of data, differentiation of dosing regimen by sex or during pregnancy cannot be justified.

Effects

In those few placebo-controlled trials  where sex was included as co-variate in exploratory analyses, no overt differences in terms of efficacy were discernible when aciclovir, or its pro-drug valaciclovir, were given orally to treat recurrent genital herpes [4,5]. Likewise, in a study with topical administration of aciclovir to immuno­compromised patients (37 men, 26 women), no sex differences were discernible [6]. On the other hand, a more pronounced treatment effect was seen in men as compared to women following topical administration of aciclovir to patients with recurrent genital herpes in good health, in two placebo-controlled studies (54 men, 34 women and 63 men, 48 women, respectively) [7,8].

Adverse effects

No studies with a clinically relevant sex analysis regarding adverse effects of aciclovir or valaciclovir have been found.It should be noted that a reduction of dose with decline in renal function is needed, as to avoid toxic side-effects from accumulation of aciclovir or its metabolites. Particularly in elderly, this might call for sex differences in dosing secondary to sex differences in decline of kidney function [9].

Reproductive health issues

Regarding teratogenic aspects, please consult Janusmed Drugs and Birth Defects (in Swedish, Janusmed fosterpåverkan).