It is common practice to administer acyclovir as prophylaxis to patients with hematologic malignancies during neutropenia; however, effective therapy requires frequent dosing, which is difficult in this setting. Valacyclovir has greater oral bioavailability and requires less frequent dosing.
OBJECTIVE:
To evaluate the efficacy and safety of valacyclovir compared with acyclovir.
METHODS:
Patients who had been treated with chemotherapy or stem-cell transplantation were randomized to receive acyclovir 400 mg orally 3 × daily (n = 51), valacyclovir 500 mg orally twice daily (n = 48), or valacyclovir 250 mg orally twice daily (n = 52) during neutropenia.
RESULTS:
Clinical success, defined as the absence of an active herpes simplex virus (HSV) lesion or asymptomatic viral shedding, was similar between the 3 groups (acyclovir 96%, valacyclovir 500 mg 95%, valacyclovir 250 mg 100%). The overall rates of adverse events were similar in the 3 groups.
CONCLUSIONS:
Prophylactic treatment with valacyclovir is an effective and safe alternative to acyclovir for the prevention of HSV reactivation in patients with hematologic malignancies.
KocYMillerKBSchenkeinDPGriffithJAkhtarMDesJardinJVaricella zoster virus infections following allogeneic bone marrow transplantation: Frequency, risk factors, and clinical outcome. Biol Blood Marrow Transplant2000;6: 44–9.
2.
BoeckhMGooleyTABowdenRA. Effect of high-dose acyclovir on survival in allogeneic marrow transplant recipients who received ganciclovir at engraftment or for cytomegalovirus pp65 antigenemia. J Infect Dis1998;178: 1153–7.
3.
RieuxCGautheret-DejeanAChalline-LehmannDKirchCAgutHVernantJP. Human herpesvirus-6 meningoencephalitis in a recipient of an unrelated allogeneic bone marrow transplant. Transplantation1998;65: 1408–11.
4.
Tanaka-TayaKOkadaS. [Human herpesvirus-6 and −7 infection and bone marrow transplantation (BMT)]. Japanese. Nippon Rinsho1998;56: 208–12.
5.
MookerjeeBPVogelsangG. Human herpes virus-6 encephalitis after bone marrow transplantation: Successful treatment with ganciclovir. Bone Marrow Transplant1997;20: 905–6.
6.
SaralRBurnsWHLaskinOLSantosGWLietmanPS. Acyclovir prophylaxis of herpes-simplex-virus infections. N Engl J Med1981;305: 63–7.
7.
SableCADonowitzGR. Infections in bone marrow transplant recipients. Clin Infect Dis1994;18: 273–84.
8.
EpsteinJBRansierASherlockCHSpinelliJJReeceD. Acyclovir prophylaxis of oral herpes virus during bone marrow transplantation. Eur J Cancer B Oral Oncol1996;32B:158–62.
9.
LjungmanPWilczekHGahrtonGGustavssonALundgrenGLonnqvistBLong-term acyclovir prophylaxis in bone marrow transplant recipients and lymphocyte proliferation responses to herpes virus antigens in vitro. Bone Marrow Transplant1986;1: 185–92.
10.
BergmannOJEllermann-EriksenSMogensenSCEllegaardJ. Acyclovir given as prophylaxis against oral ulcers in acute myeloid leukaemia: Randomized, double blind, placebo controlled trial. BMJ1995;310: 1169–72.
11.
SheppDHDandlikerPSFlournoyNMeyersJD. Sequential intravenous and twice daily oral acyclovir for extended prophylaxis of herpes simplex virus infection in marrow transplant patients. Transplantation1987;43: 654–8.
12.
WadeJCNewtonBFlournoyNMeyersJD. Oral acyclovir for prevention of herpes simplex virus reactivation after marrow transplantation. Ann Intern Med1984;100: 823–8.
13.
HannIMPrenticeHGBlacklockHARossMGBrigdenDRoslingAEAcyclovir prophylaxis against herpes virus infections in severely immunocompromised patients: Randomized double blind trial. BMJ1983;287: 384–8.
14.
GluckmanELotsbergJDevergieAZhaoXMMeloRGomez-MoralesMProphylaxis of herpes infections after bone marrow transplantation by oral acyclovir. Lancet1983;2: 706–8.
15.
WagstaffAJFauldsDGoaKL. Aciclovir: A reappraisal of its antiviral activity, pharmacokinetic properties and therapeutic efficacy. Drugs1994;47: 153–205.
16.
WellerSBlumMRDoucetteMBurnetteTCederbergDMde MirandaPPharmacokinetics of the acyclovir pro-drug valaciclovir after escalating single- and multiple-dose administration to normal volunteers. Clin Pharmacol Ther1993;54: 595–605.
17.
Soul-LawtonJSeaberEOnNWoottonRRolanPPosnerJ. Absolute bioavailability and metabolic disposition of valaciclovir, the l-valyl ester of acyclovir, following oral administration to humans. Antimicrob Agents Chemother1995;39: 2759–64.
18.
AcostaEPFletcherCV. Valacyclovir. Ann Pharmacother1997;31: 185–91.
ReitanoMTyringSLangWThomingCWormAMBorelliSValaciclovir for the suppression of recurrent genital herpes simplex virus infection: A large-scale dose range—finding study. J Infect Dis1998;178: 603–10.
21.
FifeKHBarbarashRARudolphTDegregorioBRothR. Valaciclovir versus acyclovir in the treatment of first-episode genital herpes infection. Results of an international, multicenter, double-blind, randomized clinical trial. Sex Transm Dis1997;24: 481–6.
22.
SpruanceSLTyringSKDeGregorioBMillerCBeutnerK. A large-scale, placebo-controlled, dose-ranging trial of peroral valaciclovir for episodic treatment of recurrent herpes genitalis. Arch Intern Med1996;156: 1729–35.
23.
TyringSKDouglasJMJr.CoreyLSpruanceSLEsmannJ. A randomized, placebo-controlled comparison of oral valacyclovir and acyclovir in immunocompetent patients with recurrent genital herpes infections. Arch Dermatol1998;134: 185–91.
24.
PatelRBodsworthNJWoolleyPPetersBVejlsgaardGSaariSValaciclovir for the suppression of recurrent genital HSV infection: A placebo controlled study of once daily therapy. Genitourin Med1997;73: 105–9.
25.
BodsworthNJCrooksRJBorelliSVejlsgaardGPaavonenJWormAMValaciclovir versus aciclovir in patient initiated treatment of recurrent genital herpes: A randomised, double blind clinical trial. Genitourin Med1997;73: 110–6.
26.
LawrenceAGBellAR, and the International Valaciclovir HSV Study Group. Valaciclovir for prevention of recurrent herpes simplex virus infection in HIV-infected individuals — A double-blind, controlled trial (abstract). In: Programs and Abstract of the 8th European Congress of Clinical Microbiology and Infectious Diseases, Lausanne, Switzerland, May 25–28, 1997.
27.
BearmanSIAppelbaumFRBucknerCDPetersenFBFisherLDCliftRARegimen-related toxicity in patients undergoing bone marrow transplantation. J Clin Oncol1988;6: 1562–8.
28.
HallasJ. Drug-related hospital admissions: The role of definitions and intensity of data collection and the possibility of prevention. J Int Med1990;228: 83–9.
29.
LowanceDNeumayerHHLegendreCMSquiffletJPKovarikJBrennanPJValacyclovir for the prevention of cytomegalovirus disease after renal transplantation. N Engl J Med1999;340: 1462–70.
30.
EganJSheikhSWoodcockA. Valacyclovir reduces the incidence of cytomegalovirus infection in heart transplant patients (abstract 151). Presented at: 9th Congress of the European Society for Organ Transplantation, Oslo, Norway, June 19–24, 1999.
31.
LjungmanP. Efficacy and safety of valacyclovir as a prophylaxis against CMV infection and disease in BMT recipients (abstract). J Clin Virol1999;12:G6–02.
