Acute herpes zoster, including herpes zoster ophthalmicus
800 mg every 4 hours, 5 times daily, for 7 to 10 days.
Started within 72 hours of rash onset it reduces keratitis and uveitis but not postherpetic neuralgia.
OFF-LABELNot in the FDA label for this product
Long-term suppression of recurrent ocular HSV disease
400 mg twice daily for 12 months.
RCT · n=703
Herpetic Eye Disease Study Acyclovir Prevention Trial, a randomized double-masked placebo-controlled multicenter trial in 703 immunocompetent patients who had had ocular HSV disease within the preceding year: cumulative probability of a recurrence of any type of ocular HSV disease over the 12-month treatment period was 19% on acyclovir versus 32% on placebo (P<0.001), and among the 337 patients with a history of stromal keratitis, recurrent stromal keratitis was 14% versus 28% (P=0.005); nonocular, primarily orofacial, recurrence was also lower at 19% versus 36% (P<0.001), and there was no rebound in the rate of HSV disease in the 6 months after treatment stopped. A further analysis of the same trial gave rate ratios of 0.62 (95% CI 0.39 to 0.97) for preventing epithelial keratitis and 0.57 (95% CI 0.36 to 0.89) for preventing stromal keratitis, with the absolute benefit greatest in patients with the most prior episodes, and the authors report that the benefit in preventing stromal keratitis was seen solely among patients with a history of stromal keratitis.
Randomized double-blind trial in 60 patients with simple dendritic corneal ulceration comparing acyclovir 400 mg tablets 5 times daily against acyclovir ophthalmic ointment 5 times daily: 88.9% healed on the oral drug versus 96.6% on the ointment, a difference that was not significant, with a median healing time of 5 days in both groups and trough tear concentrations within or above the range of mean in vitro ID50 levels for HSV-1. A Cochrane review of 137 studies in 8333 eyes reports that in a limited number of studies oral acyclovir alone (RR 0.92, 95% CI 0.79 to 1.07) or combined with a topical antiviral (RR 1.36, 95% CI 0.68 to 2.74) appeared as effective as a single topical antiviral agent.
HSV stromal keratitis, added to topical corticosteroid plus topical antiviral
400 mg 5 times daily for 10 weeks.
RCT · n=104 · no benefit
Herpetic Eye Disease Study, a randomized double-masked placebo-controlled multicenter trial in 104 patients with HSV stromal keratitis without accompanying epithelial keratitis, all of whom also received topical prednisolone phosphate and trifluridine: median time to treatment failure was 84 days (95% CI 69 to 93) on acyclovir versus 62 days (95% CI 57 to 90) on placebo, and by 16 weeks 75% versus 74% had failed, neither difference significant. The authors concluded there was no statistically or clinically significant beneficial effect on time to treatment failure, proportion failing, proportion resolving, time to resolution, or 6-month best-corrected visual acuity, while also reporting that visual acuity improved over 6 months in more patients on acyclovir than on placebo.
Demonstrated clinically significant hypersensitivity reaction, such as anaphylaxis or a severe cutaneous adverse reaction, to acyclovir, valacyclovir, or any component of the formulation.
Available Forms
400 mg and 800 mg tablets
Mechanism of Action
Synthetic guanosine nucleoside analog; viral thymidine kinase carries out the first phosphorylation inside herpes-infected cells and host kinases complete conversion to acyclovir triphosphate, which inhibits viral DNA polymerase and incorporates into elongating viral DNA to terminate the chain. That dependence confines activity to infected cells and also drives resistance, which is thymidine kinase deficiency in roughly 95% of resistant isolates.
Warnings & Precautions
Renal failure: Reported with therapy and fatal in some cases; adjust the dose in renal impairment and maintain adequate hydration.
Thrombotic microangiopathy: TTP/HUS, which has resulted in death, has occurred in immunocompromised patients receiving therapy.
Severe cutaneous adverse reactions: AGEP, DRESS, Stevens-Johnson syndrome, toxic epidermal necrolysis and erythema multiforme have been reported; discontinue immediately for a painful rash with mucosal involvement or a progressive severe rash, and do not rechallenge.
Nephrotoxic agents: Concurrent administration may increase the risk of renal dysfunction and of the reversible CNS symptoms reported with intravenous acyclovir.
Probenecid interaction: Coadministration with the intravenous form increased mean half-life and AUC and correspondingly reduced urinary excretion and renal clearance.
Elderly patients: Plasma concentrations are higher, duration of pain after healing was longer in patients 65 and over, and somnolence, hallucinations, confusion and coma were reported more frequently; dose reduction may be required.
Treatment window: There are no data on treatment initiated more than 72 hours after onset of the zoster rash.
Common Side Effects
Ocular: Visual abnormalities; postmarketing, frequency not estimable.
Herpes zoster dosing: Malaise 11.5% versus 11.1% on placebo across 3 trials of 800 mg 5 times daily for 7 to 10 days (n=323).
Suppressive dosing: Nausea 4.8% and diarrhea 2.4% over 1 year of 400 mg twice daily (n=586).
Neurologic: Agitation, aggressive behavior, ataxia, confusion, delirium, dizziness, encephalopathy, hallucinations, paresthesia, psychosis, seizure, somnolence, tremors, coma; postmarketing, and may be marked in older adults or in renal impairment.
Renal: Renal failure, renal pain, elevated BUN and creatinine, hematuria; postmarketing.
Pregnancy: Category B. Not teratogenic in mice, rabbits or rats at plasma levels 9 to 106 times human levels, and a prospective registry of 749 first-trimester systemic exposures yielding 756 outcomes found a birth defect rate approximating the general population, though the registry was too small for reliable or definitive conclusions. There are no adequate and well-controlled studies in pregnant women; use only if the potential benefit justifies the potential risk to the fetus.
Lactation: Breast milk concentrations documented in 2 women ranged from 0.6 to 4.1 times corresponding plasma levels, potentially exposing a nursing infant to up to 0.3 mg/kg/day; administer to a nursing mother with caution and only when indicated.
Pediatric Use
Safety and effectiveness of oral formulations are not established below 2 years of age.
Available Forms
Mechanism of Action
Pregnancy & Lactation
Pediatric Use