Adverse Effects Contraindications and Drug Interactions

The adverse effects of valacyclovir and acyclovir are similar. Toxicity is generally minimal, consisting largely of headache, nausea, and diarrhea. Less frequently observed are skin rash, fatigue, fever, hair loss, and depression. Reversible renal dysfunction (azotemia) and neurotoxicity (tremor, seizure, delirium) are dose-limiting toxicities of intravenous acyclovir. Adequate hydration and slow drug infusion can minimize the risk of renal toxicity.

Aside from drug hypersensitivity, there are no absolute contraindications to the use of acyclovir and valacyclovir. Adjustment of drug dosage is required in patients with renal impairment. A potentially fatal disorder, thrombotic thrombocytopenic purpura-hemolytic uremic syndrome (TTP-HUS), has been reported in immunocompromised individuals. Animal studies have demonstrated no teratogenic or embryo-toxic effects of valacyclovir and acyclovir. Although there are no large, controlled studies of the safety of these drugs in pregnant women, a prospective epidemi-ological registry of acyclovir use during pregnancy showed no increase in the incidence of common birth defects.

The potential for drug interactions, particularly with other drugs that are actively secreted by the proximal tubules, should be considered. Probenecid has been shown to inhibit the renal clearance of acyclovir. Cyclosporine and other nephrotoxic agents may increase the risk of renal toxicity of acyclovir.

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