E-DRUG: Acyclovir or valazyclovir? (4)
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Here is a reprint of an article on this topic that appeared in the
Therapeutic Letter which is a product of the Therapeutic Initiative in
British Columbia. Basically, there is no evidence that any one of the
three drugs (acyclovir, famciclovir or valacyclovir) is superior.
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Famciclovir (Famvirr) and Valacyclovir (Valtrexr)
Both are new antiherpesviral prodrugs (in the same class as acyclovir).
Indication: Acute herpes zoster in the immunocompetent host. (Their role in
genital herpes will be discussed in a future Therapeutics Letter).
Mechanism of Action: Reduce viral replication by inhibiting viral DNA
polymerase.
Pharmacokinetics: Valacyclovir is a prodrug of, and metabolized to
acyclovir; the oral bioavailability of acyclovir from valacyclovir is 54%
as compared to 15-30% for acyclovir. Famciclovir is a prodrug for the
active metabolite penciclovir; the mean oral bioavailability of penciclovir
from famciclovir is 77%. Penciclovir plus acyclovir are primarily
eliminated unchanged by the kidneys and have mean half-lives of 2.5 hours.
Evidence of efficacy: If given within 72 hours of the first herpes zoster
lesion, famciclovir(1) and valacyclovir(2) (like acyclovir(3)) provide
modest decreases in the time to full crusting (e.g. median 5.5 days for
famciclovir, 7 days for placebo(1)), healing and cessation of pain . The
benefit is greatest in patients with the most severe infections (many
lesions and severe pain)(1),(3),(4). At present the evidence is
inconclusive as to whether any antiviral or other therapy has an effect on
the overall clinical impact of post-herpetic neuralgia.(4) The new prodrugs
have not been studied in children or immunocompromised hosts.
Major adverse effects: These drugs, like acyclovir, produce a low incidence
(similar to placebo) of minor adverse effects, including diarrhea, nausea
and headache.
Dose and Cost: Acute herpes zoster: famciclovir, 500 mg TID for 7 days
($155.61), valacyclovir, 1 g TID for 7 days ($126.84), acyclovir, 800 mg 5
times daily for 7 days ($138.60). Longer durations of therapy are not more
effective; shorter courses have not been tested.
Conclusions: Anti-viral drugs have a modest beneficial effect if given
early (rash <72 hr) to immunocompetent patients (>50 yr) with moderate to
severe rash or pain associated with acute herpes zoster (shingles).
References:
1.Tyring S, Barbarash RA, Nahlik JE, et al. Famciclovir for the treatment
of acute herpes zoster: effects on acute disease and postherpetic
neuralgia. A randomized, double-blind, placebo-controlled trial.
Collaborative
Famciclovir Herpes Zoster Study Group. Annals of Internal Medicine. 1995
July 15; 123(2):89-96.
2.Beutner KR, Friedman DJ,Forszpaniak C, et al. Valaciclovir compared with
acyclovir for improved therapy for herpes zoster in immunocompetent adults.
Antimicrob Agents Chemother. 1996;39:1546-53.
3.Whitley RJ, Weiss H, Gnann JW, et al. Acyclovir with and without
prednisone for the treatment of Herpes Zoster. A placebo-controlled trial.
Ann Intern Med. 1996; 125:376-383.
4.Kost RG, Straus SE. Postherpetic neuralgia - pathogenesis, treatment, and
prevention. NEJM. 1996 July 4; 335:32-42.
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Joel Lexchin
Joel Lexchin MD
121 Walmer Rd.
Toronto, Ontario
CANADA M5R 2X8
Phone: (416)-964-7186
Fax: (416)-923-9515
e mail: joel.lexchin@utoronto.ca
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