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Antiviral/Antibiotic Suggestions Acyclovir vs. Famcyclovir vs. Valacyclovir Replacement to the List Peer Feedback: “Use famciclovir or valacyclovir because there are water solube and much better excreted by the kidney. No renal tubule crysalization problems.” “Too frequent dosing for acute indications supports noncompliance - consider Famcyclovir - less frequent dose, ends up being about the same price but more effective for better compliance” Note: only oral doses included on CLEAN Meds list Literature Review Question: What are the comparative rates of renal tubule crystallization and other kidney related adverse effects? What are the dosing schedules of acyclovir, famciclovir and valacyclovir? Literature Search: eCPS – Infectious Diseases: Herpesvirus Infections PubMed - (Systemic antiviral nucleoside analogues OR (aciclovir AND valaciclovir AND famciclovir)) AND renal tubule crystalization Risk of AKI from acyclovir (2013) Between 60% and 90% of acyclovir is eliminated unchanged by the kidney through glomerular filtration and renal tubular secretion.31 Acyclovir has a maximum solubility of only 2.5 mg/mL, making it prone to precipitation in the renal tubules.32 Thus, there are many reasons why AKI is more frequent with IV acyclovir than its oral formulation. Rapid infusion of high-dose IV acyclovir may lead to high levels in the tubular lumen. Conversely, only 10%-30% of oral acyclovir is absorbed intestinally, resulting in lower serum (and renal tubule) concentrations.10 In pharmacokinetic studies, IV dosages of acyclovir (5-10 mg/kg every 8 hours) result in steadystate peak plasma concentrations of 10-20 g/mL, whereas the value is only 0.6-1.6 g/mL after multiple oral doses (of 200-800 mg).35,36 Measures to prevent IV acyclovir–induced nephrotoxicity include slowing the rate of IV infusion (over 1-2 hours), dose reductions in the presence of chronic kidney disease, avoidance of concurrent nephrotoxic medications, and adequate hydration to ensure high urinary flow (100-150 mL/h).31,32 In this population-based study of more than 160,000 older patients, we found no association between AKI and treatment with oral acyclovir or valacyclovir compared to famciclovir. Our results provide important safety reassurances about the use of these commonly prescribed oral antivirals in routine practice. The choice of antiviral therapy for the treatment of herpes should depend on other factors, such as microbial efficacy, patient tolerability, and cost, because the risk of AKI does not appear to be a meaningful consideration. Lam, Ngan N., et al. "Risk of acute kidney injury from oral acyclovir: a population-based study." American Journal of Kidney Diseases 61.5 (2013): 723-729. eCPS (2014) Table 1: Antivirals for Orolabial and Mouth HSV Infections Class Nucleoside Analogues Drug Dosage acyclovir HSV gingivostomatitis in children: 15 mg/kg 5 times daily po × 7 days or 600 mg/m2 QID po × 10 days 250 mg/m2 Q8H iv × 5–10 days Recurrent orolabial HSV: Treatment, oral: 400 mg 5 times daily × 5 days Treatment, topical: Start within 1 h of onset of signs or symptoms. Apply the cream 5 times daily during waking hours × 4 days. Prophylaxis: 400 mg BID po 12 h prior to sun exposure × duration of exposure Suppression: 200 mg QID po or 400 mg BID po for up to 4 months Zovirax Cream, Zovirax Oral, generics Adverse Effects Not different from placebo. Costa HSV gingivostomatitis in children: po:$$$$$b iv:c $135/day Recurrent orolabial HSV: Treatment, po:$b Treatment, topical cream: $$$$$ Prophylaxis:$$$b /30-day supply Suppression:$$$b /30-day supply Class Nucleoside Analogues Nucleoside Analogues Adverse Effects Costa Drug Dosage famciclovir Not different from placebo. $ Famvir, generics Recurrent orolabial HSV: Treatment: 750 mg BID po × 1 day or 1500 mg po as a single dose Not different from placebo. Treatment: $ valacyclovir Recurrent orolabial HSV: Treatment: 2 g BID po × 1 day Suppression: 500 mg once daily po × 4 months Suppression: $$/30-day supply Valtrex, generics Table 2: Antivirals for Anogenital HSV Infections Class Nucleoside Analogues Drug Dosage Genital HSVinfection, first episode: 200 mg 5 times daily po × 5–10 days Zovirax,generics 5 mg/kg Q8H iv × 5–10 days Recurrent genital HSVinfection: Treatment: 200 mg 5 times daily po × 5–7 days or 800 mg TID po × 2 days Suppression:200 mg po up to 5 times daily or400 mg BID poor 800 mg once daily po × 3–6 months HSV proctitis:400 mg 5 times daily po × 10 days acyclovir Adverse Effects Not different from placebo. Costa Genital HSV infection, first episode: po:$$b iv:c $400/day Recurrent genital HSV infection: Treatment:$b Suppression:$$$b /30-day supply HSV proctitis:$$$b Nucleoside Analogues famciclovir Famvir,generics Genital HSVinfection, first episode: 250 mg TID po × 10 days Recurrent genital HSVinfection: Treatment: 125 mg BID po × 5 days or 1000 mg BID po × 1 day Suppression:250 mg BID po × 3–6 months Not different from placebo. Genital HSV infection, first episode: $$ Recurrent genital HSV infection: Treatment: $ Suppression: $$$$/30-day supply Nucleoside Analogues valacyclovir Valtrex,generics Genital HSVinfection, first episode: 1000 mg BID po × 10 days Recurrent genital HSVinfection: Treatment: 500 mg BID po × 3–5 days Suppression: ≤9 recurrences per y: 500 mg once daily po × 3–6 months >9 recurrences per y: 1000 mg once dailypo × 3–6 months Reduction in genital HSVinfection transmission: 500 mg once daily po Not different from placebo. Genital HSV infection, first episode: $$$ Recurrent genital HSV infection: Treatment: $ Suppression: $$/30-day supply Reduction in genital HSV infection transmission: $$/30-day supply Table 3: Antivirals for Herpesvirus Infections of the Skin Class Nucleoside Analogues Drug Dosage Adverse Effects Costa acyclovir Chickenpox: Children: 5–7 years: 20 mg/kg QID po × 5–7 days 8–12 years: 15 mg/kg QID po × 5–7 days 13–16 years: 10 mg/kg QID po × 5–7 days Adults: 800 mg 5 times daily po × 5 days or 10 mg/kg Q8H iv × 5 days Eczema herpeticum: 200 mg 5 times daily po × 5 days 5–10 mg/kg Q8H iv × 7 days in patients >12 years 750 mg/m2 TID iv × 7 days in patients <12 years Herpes zoster: 800 mg 5 times daily po × 7 days Not different from placebo. Chickenpox: po: Children: $$$$-$$$$$ Adults$$b: ivc: ~$700/day Eczema herpeticum: po: $$ iv:c Children: ~$275/day Adults: $400–700/day Herpes zoster: $$$ Herpes zoster: 500 mg TID po × 7 days Not different from placebo. $$$ Herpes zoster: 1000 mg TID po × 7 days Not different from placebo. $$$ Zovirax,generics Nucleoside Analogues famciclovir Famvir,generics Nucleoside Analogues valacyclovir Valtrex,generics Legend: 75 $ <$15 $$ $15–30 $$$ $30–45 $$$$ $45–60 $$$$-$$$$$ $45–75 $$$$$ $60– Infectious Diseases: Herpesvirus Infections, Gerald A. Evans, MD, FRCPC, Date of revision: June 2014 Medication Acyclovir Uses antiviral: herpes zoster (shingles), herpes genitalis, recurrent genital herpes, varicella zoster (chicken pox) Contraindications (CI), drug interactions (DI) or cautions CI: hypersensitivity to drug DI: probenecid Chronic use requires follow up especially in immune compromised patients Adverse Effects (common and severe) headache, nausea, vomiting, diarrhea, imalaise Initial dose; typical dose shingles: 800mg every 4-6 hours for 7-10 day genital herpes: 200mg every 4-6 hours for 10 days chronic therapy: 400mg every 12 hours or 200mg every 4-6 hours up to 12 months chicken pox in children: 20mg/kg every 6 hours for 5 days Monitoring