Higher dose versus lower dose of antiviral therapy in the treatment of herpes zoster infection in the elderly: a matched retrospective population-based cohort study

Abstract

BackgroundHigher versus lower doses of antiviral drugs used to treat herpes zoster infection may lead to more adverse drug events in older adults, particularly those with chronic kidney disease.MethodsWe conducted a matched retrospective population-based cohort study of older adults (mean 77 years) in Ontario, Canada who initiated in the outpatient setting a higher (n = 23,256) or lower (n = 3,876) dose of one of three oral antivirals for the treatment of herpes zoster between 2002 and 2011. The primary outcome was hospitalization within 30 days with evidence of a computed tomography (CT) scan of the head (a proxy for acute neurotoxicity). The secondary outcome was 30-day all-cause mortality.ResultsA higher compared to lower dose of antiviral drug was not associated with an increased risk of hospitalization with an urgent CT scan of the head (247 [1.06%] events with higher dose versus 43 [1.11%] events with lower dose, relative risk 0.96, 95% confidence interval 0.69 to 1.33, p-value 0.79) and was not associated with a higher risk of all-cause mortality (63 [0.27%] events versus 15 [0.39%] events, relative risk 0.70, 95% confidence interval 0.40 to 1.23, p-value 0.21). Results were consistent in all subgroups, including those with and without chronic kidney disease.ConclusionsInitiating a higher compared to a lower dose of an antiviral drug for the treatment of herpes zoster was not associated with an increased risk of adverse drug events. The findings support the safety of these drugs in older adults as currently prescribed in routine care.

Valacyclovir Non-Oliguric Acute Kidney Injury: a Case Report of 84 Year-Old Female

“…Higher doses of Valacyclovir may be safe as in Meur YL 18 correspondence followed the use of Valacyclovir 6-8 g/day in 6 cases after renal transplantation for prevention of cytomegalovirus and found that after 3 months, there was no increase in the serum creatinine and crystalluria was not detected. Lam NN and team 19 carried out another study, which was a matched retrospective population-based cohort study of older adults (mean 77 years) in Ontario, Canada with the outpatient setting of higher (n = 23,256) or lower (n = 3,876) dose of one of three oral antivirals for the treatment of herpes zoster (acyclovir 4,000 vs 800-3,200 mg/day; Valacyclovir 3,000 vs 500-2,000 mg/day and famvir 1,500 vs 350-1,000 mg/day), and found that a higher dose of the antiviral drug, compared to a lower dose, was not associated with an increased risk of hospitalization with an urgent head CT scan, and was not associated with a higher risk of all-cause mortality. 19 However, Valacyclovir taken 8g/day, which was seen to significantly reduce the risk of cytomegalovirus (CMV), and was found to be associated with earlier mortality in Feinberg JE 20 study (1998).…”

“…Lam NN and team 19 carried out another study, which was a matched retrospective population-based cohort study of older adults (mean 77 years) in Ontario, Canada with the outpatient setting of higher (n = 23,256) or lower (n = 3,876) dose of one of three oral antivirals for the treatment of herpes zoster (acyclovir 4,000 vs 800-3,200 mg/day; Valacyclovir 3,000 vs 500-2,000 mg/day and famvir 1,500 vs 350-1,000 mg/day), and found that a higher dose of the antiviral drug, compared to a lower dose, was not associated with an increased risk of hospitalization with an urgent head CT scan, and was not associated with a higher risk of all-cause mortality. 19 However, Valacyclovir taken 8g/day, which was seen to significantly reduce the risk of cytomegalovirus (CMV), and was found to be associated with earlier mortality in Feinberg JE 20 study (1998). Valacyclovir-related AKI occurred more in the summer as noticed by Inaba I 21 (2019) from the Japanese Adverse Drug Event Report (JADER) database and was assumed to be from dehydration.…”