E-drug: Acyclovir or valazyclovir? (3)
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Dear colleagues, in response to Dr Michel LALOGE.
I only know of one comparative trial (RCT) comparing acyclovir to the
prodrug valacyclovir. (1) The Prescrire international published recently a
review of valacyclovir (2). The advantage of the slightly cheaper
valacyclovir is three times a day dosing. Efficacy is similar to acyclovir
although the serum conc. is significantly higher after valacyclovir. The
effects are mainly on the acute phase although the industry claims effects
on post herpetic neuralgia (it depends heavily on how PHN is defined or
wheather we use zoster associated pain (ZAP) as an endpoint). A major flaw
in many of the RCT's on antivirals for zoster in immunocompetent adults is
that no distinction is made between mild (clinically insignificant in many
cases) and moderate or severe pain. (3) A superb study (3) done a few
years ago showed no effect on PHN in >350 elderly patients. The study has
been eliminated by most reviews or metanalysis on the grounds that all pt.
were not followed for 6 months. My own study on the prognosis of zoster
showed (5) that in patients painfree at 3 months reappearance of pain later
was extremely rare.
Blanket reccommendations that all patients over certain age (>50) are
unfounded. Other clinical parameters should be taken into account. Other
cheap modalities like amitriptyline or nortriptylin are underused as
adjunctive therapy for pain from the start.
Another good review is (6)
(1) Beutner KR, Friedman DJ, Forszpaniak C, Andersen PL, Wood MJ.
Valacyclovir compared with acyclovir for improved therapy for herpes zoster
in immunocompetent adults. Antimicrob Agents Chemother 1995;39:1546-53.
(2) Valaciclovir. Prescrire International 1997;7:72-73 (Rev Prescr March
1997;17(171):156-158.
(3) Dworkin RH, Carrington D, Cunningham A, Kost RG, Levin MJ, Mckendrick
MW, Oxman MN, Rentier B, Schmader KE, Tappeiner G, Wassilew SW, Whitley RJ.
Assessment of pain in herpes zoster: lessors learned from antiviral trials.
Antiviral Research 1997; 33:73-85.
(4)McKendrick MW, McGill JI, Wood MJ. Lack of effect of acyclovir on
postherpetic neuralgia. BMJ 1989;298:431.
(5) Helgason S, Sigurdsson JA, Gudmundsson S. The clinical course of herpes
zoster: a prospective study in primary care. Eur J Gen Pract 1996;2:12-6.
(6) Lancaster T, Silagy C, Gray S. Primary care management of acute herpes
zoster: systematic review of evidence from randomized controlled trials.
British Journal of General Practice 1995;45:39-45.
Sincerely
Sigurdur Helgason MD
Heilsug�slust�din Arbae
Hraunb� 102, Reykjav�k 110
Fax (354)-5671183
Phone (354)-5671500
e-mail sh@centrum.is
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