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Valaciclovir

Classification: B

Drug products: Valaciclovir 2care4, Valaciclovir Abacus Medicine, Valaciclovir Actavis, Valaciclovir Alternova, Valaciclovir Aristo, Valaciclovir Arrow, Valaciclovir Bluefish, Valaciclovir CC Pharma, 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

Summary

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. Since valaciclovir has renal excretion and the risk of toxicity in patients with impaired renal function should be considered.

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).

Updated: 2020-08-28

Date of litterature search: 2016-01-10

References

  1. Kimberlin DF, Weller S, Whitley RJ, Andrews WW, Hauth JC, Lakeman F et al. Pharmacokinetics of oral valacyclovir and acyclovir in late pregnancy. Am J Obstet Gynecol. 1998;179:846-51. PubMed
  2. Vergin H, Kikuta C, Mascher H, Metz R. Pharmacokinetics and bioavailability of different formulations of aciclovir. Arzneimittelforschung. 1995;45:508-15. PubMed
  3. Weller S, Blum MR, Doucette M, Burnette T, Cederberg DM, de Miranda P et al. Pharmacokinetics of the acyclovir pro-drug valaciclovir after escalating single- and multiple-dose administration to normal volunteers. Clin Pharmacol Ther. 1993;54:595-605. PubMed
  4. Tyring SK, Douglas JM, Corey L, Spruance SL, Esmann J. A randomized, placebo-controlled comparison of oral valacyclovir and acyclovir in immunocompetent patients with recurrent genital herpes infections The Valaciclovir International Study Group. Arch Dermatol. 1998;134:185-91. PubMed
  5. Spruance SL, Tyring SK, DeGregorio B, Miller C, Beutner K. A large-scale, placebo-controlled, dose-ranging trial of peroral valaciclovir for episodic treatment of recurrent herpes genitalis Valaciclovir HSV Study Group. Arch Intern Med. 1996;156:1729-35. PubMed
  6. Whitley RJ, Levin M, Barton N, Hershey BJ, Davis G, Keeney RE et al. Infections caused by herpes simplex virus in the immunocompromised host: natural history and topical acyclovir therapy. J Infect Dis. 1984;150:323-9. PubMed
  7. Reichman RC, Badger GJ, Guinan ME, Nahmias AJ, Keeney RE, Davis LG et al. Topically administered acyclovir in the treatment of recurrent herpes simplex genitalis: a controlled trial. J Infect Dis. 1983;147:336-40. PubMed
  8. Corey L, Nahmias AJ, Guinan ME, Benedetti JK, Critchlow CW, Holmes KK. A trial of topical acyclovir in genital herpes simplex virus infections. N Engl J Med. 1982;306:1313-9. PubMed
  9. Xu R, Zhang LX, Zhang PH, Wang F, Zuo L, Wang HY. Gender differences in age-related decline in glomerular filtration rates in healthy people and chronic kidney disease patients. BMC Nephrol. 2010;11:20. PubMed
  10. Läkemedelsstatistik. Stockholm: Socialstyrelsen. 2015 [cited 2016-04-05.] länk

Authors: Olof Breuer, Desirée Loikas

Reviewed by: Mia von Euler

Approved by: Karin Schenck-Gustafsson