Comparison of aciclovir, famciclovir and valaciclovir for management of herpes simplex and herpes zoster infections

13 Summary Aciclovir, valaciclovir and famciclovir are all nucleoside analogues active against her- pes simplex virus types 1 and 2, and varicella zoster virus. Valaciclovir is a pro-drug of aciclovir which is absorbed more quickly and therefore has a higher absolute bioavailability; it is therefore dosed less frequently. Famciclovir is a pro-drug of pen- ciclovir, the active form of which is more stable than that of aciclovir, allowing less frequent dosing. Valaciclovir is the only antiviral currently licensed for the reduction of transmission of genital herpes (GH); all three are licensed for the treatment and suppression of GH and the treatment of herpes zoster. Treatment of first episode of GH: Aciclovir, valaciclovir and famciclovir all reduce the severity and duration of episodes when initiated within 72 hours of the onset of lesions; they are probably equally effective but there is more evidence for aciclovir. Treatment of recurrent GH infection: Aciclovir, valaciclovir and famciclovir all re- duce the severity and duration of acute recurrent episodes; there is no evidence for a superior agent out of the three in terms of clinical outcomes. Suppression of recurrent GH infection: There is no evidence to suggest that either famciclovir or valaciclovir is superior to aciclovir when used as suppressive therapy to reduce the frequency of GH recurrences (no comparative data available for famci- clovir vs. aciclovir). Limited data suggest that valaciclovir may have a small advan- tage over famciclovir in terms of virologically-confirmed recurrence; however this was a secondary endpoint and no difference was demonstrated between the two in clini- cally-confirmed recurrence. A small study found that valaciclovir may be superior to famciclovir in terms of viral shedding, but this did not assess clinical consequences and requires confirmation in a larger study. Treatment of herpes zoster: There is some evidence from one RCT to suggest that valaciclovir may reduce the time to complete cessation of pain and the duration of post-herpetic neuralgia (by a median of 13 days; secondary endpoint) when com- pared to aciclovir; although both are similar in terms of resolution of cutaneous mani- festations. There is some evidence that famciclovir is also superior to aciclovir in terms of pain resolution, but this was only significant for the UK licensed dose in a subgroup of patients who were treated within 48 hours of rash onset and who were compliant with treatment - therefore this may not reflect the 'real world' scenario. Aciclovir has been monitored for two decades and has not been associated with sig- nificant adverse effects in this time, even with long-term use. There are less data available for valaciclovir and famciclovir, but these also have low toxicity profiles. No evidence for improved compliance (and/or improved outcomes associated with such) for famciclovir or valaciclovir versus aciclovir were located. Summary: There is currently no good evidence to suggest superiority of either valaciclovir or famciclovir over aciclovir within their licensed indications; due to the cost considerations, aciclovir should be considered as first-line for treat- ment/suppression of GH and treatment of herpes zoster unless compliance or other issues favour the use of an alternative.