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VALACYCLOVIR Usual Dose Adult: 1 g TID PO OR 500 mg BID PO (UWHC cost/day $5.92-17.76). Indications 1. Herpes zoster (shingles) in immunocompetent individuals (1 g TID PO x 7 days). Must be started within 72 hours of onset of rash to be effective, except in immunocompromised hosts. 2. Herpes simplex (genital herpes) â acute recurrence (500 mg BID PO x 3- 5 days). 3. Herpes labialis (cold sores) â initiate therapy at first sign of tingling (2 g BID for 1 day). Comments Dose adjustment required for renal impairment. See renal dosing guideline on uconnect. Valacyclovir, a prodrug, is the L-valyl ester of acyclovir. It is metabolized to acyclovir by hepatic enzymes. The oral bioavailability of valacyclovir is 3 to 5 times higher than that of acyclovir, making lower doses and longer dosing intervals possible. An increasing trend toward mortality from thrombotic thrombocytopenic purpura/hemolytic uremic syndrome (TTP/HUS) was seen in one clinical trial with immunocompromised patients at supranormal doses, making its use in this population questionable. The safety and efficacy of valacyclovir in children have not been established. VALGANCICLOVIR Usual Dose Adult: Induction 900 mg BID PO x 21 days (UWHC cost/day 158.16). Maintenance and prophylaxis 900 mg Q24H PO (UWHC cost/day $79.08). Indications 1. Cytomegalovirus (CMV) retinitis, pneumonitis, enterocolitis, esophagitis or bloodstream infections. 2. CMV prophylaxis - oral formulation restricted to prophylaxis of CMV infections in transplant recipients receiving a graft from a seropositive donor or who are seropositive for CMV and in patients receiving anti-rejection therapy. Comments Dose adjustment required for renal impairment. See renal dosing guideline on uconnect. Oral bioavailability is 60%. Patients should be monitored for progression of CMV retinitis and signs and symptoms of adverse effects including granulocytopenia, anemia, thrombocytopenia, seizures, sedation, ataxia, confusion, increased creatinine, diarrhea, nausea, vomiting, fever, headache, insomnia, peripheral neuropathy, paresthesia and retinal detachment. Valganciclovir should not be administered if the absolute neutrophil count is less than 500 cells/mcL, the platelet count is less than 25,000/mcL or the hemoglobin is less than 8 g/dL. The bioavailability of ganciclovir from valganciclovir differs significantly from that of ganciclovir capsules; therefore, valganciclovir tablets cannot be substituted for ganciclovir capsules on a one-to-one basis. Valganciclovir tablets should not be crushed; may use suspension. Patients taking zidovudine and valganciclovir may not be able to tolerate full doses of both drugs because of the myelosuppressive effects of each drug. Drug Interactions Probenecid may increase the area under the curve (AUC) of valganciclovir and thus may increase the likelihood of toxicity from valganciclovir. Valganciclovir may increase the AUC of didanosine and increase the potential for didanosine toxicity.