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Evidence summaries

Antiviral Drugs for Preventing Postherpetic Neuralgia

Oralacyclovir might possibly reduce the incidence of postherpetic neuralgia but the evidence is insufficient. Valaciclovir and famciclovir may be better than aciclovir in reducing herpes-zoster-associated pain. Level of evidence: "D"

The quality of evidence is downgraded by study quality (unclear allocation concealment), inconsistency (unexplained variability in results), and imprecise results (few outcome events).

Antivirals are suggested for patients with acute herpes zoster to prevent postherpetic neuralgia.

Rationale: Antiviral drugs are safe and they have a potential to benefit the patient. Values and preferences: Many patient would choose antiviral drug, but some patient would probably not. Resources: Antiviral drugs are cheap.

Summary

A Cochrane review [Abstract] 1 included 6 studies with a total of 1 211 immunocompetent patients. Rash of herpes zoster had been present for 72 hours or less. Five studies evaluated oral acyclovir at a dose of 800 mg 5 times daily for 7 to 21 days and one study (n=419) evaluated oral famciclovir 500 mg; famciclovir 750 mg; or placebo, 3 times daily for 7 days. One study randomised patients to acyclovir, prednisone, both acyclovir and prednisone, or neither acyclovir nor prednisone for 21 days. The follow-up time was 6 months in 5 studies and 5 months in one study. There was no significant difference between the oral acyclovir and control groups on the incidence of postherpetic neuralgia 4 months or 6 months (RR 1.05, 95% CI 0.87 to 1.27; 2 studies, n=476) after the onset of the acute herpetic rash. There was some evidence for a reduction in the incidence of pain 4 weeks after the onset of rash. Famciclovir 500 mg (RR 1.15, 95% CI 0.87 to 1.52; 1 study, n=284) or 750 mg (RR 1.31, 95% CI 1.01 to 1.71; 1 study, n=281) 3 times daily for 7 days did not reduce the incidence of herpetic neuralgia. No studies on valaciclovir were included.

Another review 2 included 12 studies with a total of 7 277 subjects comparing one antiviral to another (aciclovir, valaciclovir, famciclovir or brivudin) for a minimum of 7 days in immunocompetent patients presenting with herpes zoster diagnosed within 72 h of symptom onset. Compared with aciclovir, valaciclovir showed significant reduction in herpes-zoster-associated pain up to 112 days; risk of pain was significantly less with valaciclovir compared to aciclovir for all timepoints between 1 to 112 days (table T1). The difference was not statistically significant between 113 and 170 days.

Famciclovir 250 mg 3 times daily was superior to aciclovir 800 mg 5 times daily with a 46% reduction in risk of pain at 28-30 days (RR 0.54, 95% CI 0.48 to 0.68; 2 studiesn n=328) with number needed to treat to benefit (NNT) of 3 (95% CI 2 to 5). Time to lesion healing and adverse effect profile was comparable.

Valaciclovir 1000 mg 3 x daily versus acyclovir 800 mg 5 x daily for herpes zoster

Outcome: painRR (95% CI)NNT* (95% CI)Participants (studies)
At presentation1.01 (0.99 to 1.03)-927 (3 studies)
1-10 days0.92 (0.88 to 0.97)14 (9 to 50)927 (3 studies)
11-20 days0.91 (0.84 to 0.98)14 (8 to 100)927 (3 studies)
21-30 days0.64 (0.59 to 0.70)3 (2.7 to 3.8)927 (3 studies)
31-60 days0.85 (0.73 to 0.99)14 (8 to 100)870 (2 studies)
61-112 days0.79 (0.63 to 0.98)17 (8 to 100)870 (2 studies)
113-170 days0.81 (0.62 to 1.05)-870 (2 studies)
* NNT = number needed to treat to benefit

References

Primary/Secondary Keywords