Clinical Inquiries

How well do antivirals shorten genital herpes pain duration?

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Oral and intravenous (IV) acyclovir each shorten the duration of pain for a first primary outbreak of herpes by about 50%; topical acyclovir shortens it by about 25% (strength of recommendation [SOR]: B, small randomized controlled trials [RCTs] with some methodological flaws).

Oral valacyclovir and famciclovir are equivalent to oral acyclovir. Adding topical acyclovir to oral acyclovir doesn’t produce additional benefit (SOR: B, RCTs).

Patients with severe disease may require IV acyclovir (SOR: C, expert opinion).

General treatment measures that may improve patient comfort include keeping lesions clean and dry, avoiding tight clothing, taking analgesics, and using ice packs or taking warm baths (SOR: C, expert opinion).

Evidence for using complementary and alternative medicine to treat genital herpes is lacking or conflicting [SOR: C, narrative review of clinical trials].


A review of 3 double-blind, placebo-controlled RCTs compared topical, oral, and IV acyclovir in patients with a first episode of genital herpes.1 Researchers recruited a total of 138 patients and randomized them to receive either placebo or one of the following: oral acyclovir (200 mg 5 times daily for 10 days), IV acyclovir (5 mg/kg dose, 3 times daily for 5 days), or 5% topical acyclovir in polyethylene glycol (4 times daily for 6 days).

All treatments shortened duration of pain compared with placebo: oral (3 days vs 7 days, P<.01), IV (5 days vs 9 days, P<.05), and topical (5 days vs 7 days, P<.05).

A subsequent RCT with 50 patients found that adding topical acyclovir to oral acyclovir was no more effective than oral acyclovir alone.2

Oral acyclovir, valacyclovir, and famciclovir work equally well

Head-to-head trials comparing acyclovir with valacyclovir or famciclovir show no difference in decreased duration of pain caused by primary genital herpes. An RCT of 643 adults found valacyclovir (1000 mg twice daily for 10 days) to be as effective and well-tolerated as acyclovir (200 mg 5 times daily for 10 days).3 An RCT of 951 adults demonstrated that famciclovir (250 mg 3 times daily for either 5 or 10 days) worked as well as acyclovir (200 mg 5 times daily for 10 days).4


Evidence-based answers from the Family Physicians Inquiries Network

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