Drug products: Valaciclovir 2care4, Valaciclovir Actavis, Valaciclovir Alternova, Valaciclovir Amneal, Valaciclovir Arrow, Valaciclovir Bluefish, Valaciclovir Mylan, Valaciclovir Orifarm, Valaciclovir Orion, Valaciclovir Sandoz, Valaciclovir Teva, Valaciklovir Ebb, Valavir, Valtrex, Valtrex®
ATC code: J05AB11
Substances: valaciclovir, valaciclovir hydrochloride, valaciclovir hydrochloride anhydrous, valaciclovir hydrochloride hydrate, valaciclovir hydrochloride monohydrate
There are no published trials with the primary objective to assess sex differences in terms of pharmacokinetics, pharmacodynamics or safety of valaciclovir. Scattered data from different small trials do not suggest overt sex differences.
The present evidence regarding differences between men and women is limited and do not give cause to differentiate the treatment between men and women. Since
valaciclovir has renal excretion and the risk of toxicity in patients with impaired renal function should be considered.
Valaciclovir is a prodrug to aciclovir.
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)  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.
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 . 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].
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 .
Regarding teratogenic aspects, please consult the Drugs and Birth Defects Database (in Swedish, Janusmed fosterpåverkan).
Date of litterature search: 2016-01-10
Reviewed by: Mia von Euler
Approved by: Karin Schenck-Gustafsson