Antiviral/Antibiotic Suggestions

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 steady- state 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 Adverse Class Drug Dosage Effects Costa

Nucleoside acyclovir HSV gingivostomatitis in children: Not different HSV gingivostomatitis in children: Analogues 15 mg/kg 5 times daily po × 7 days or 600 mg/m2 QID from placebo. po: $$$$$ b Zovirax Cream, Zovirax po × 10 days iv:c $135/day 250 mg/m2 Q8H iv × 5–10 days Oral, generics Recurrent orolabial HSV: Recurrent orolabial HSV: b Treatment, oral: 400 mg 5 times daily × 5 days Treatment, po: $ Treatment, topical: Start within 1 h of onset of signs or Treatment, topical cream: $$$$$ symptoms. Apply the cream 5 times daily during Prophylaxis: $$$ b /30-day supply waking hours × 4 days. Suppression: $$$ b /30-day supply 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 Nucleoside famciclovir Recurrent orolabial HSV: Not different $ Treatment: 750 mg BID po × 1 day or 1500 mg po as a Adverse Class Drug Dosage Effects Costa

Analogues Famvir, generics single dose from placebo.

Nucleoside valacyclovir Recurrent orolabial HSV: Not different Treatment: $ Analogues Treatment: 2 g BID po × 1 day from placebo. Valtrex, generics Suppression: 500 mg once daily po × 4 months Suppression: $$/30-day supply

Table 2: Antivirals for Anogenital HSV Infections

Adverse Class Drug Dosage Effects Costa

Nucleoside acyclovir Genital HSVinfection, first episode: Not different Genital HSV infection, first episode: Analogues 200 mg 5 times daily po × 5–10 days from placebo. Zovirax,generics 5 mg/kg Q8H iv × 5–10 days po: $$ b Recurrent genital HSVinfection: Treatment: 200 mg 5 times daily po × 5–7 days iv:c $400/day or 800 mg TID po × 2 days Suppression:200 mg po up to 5 times daily or400 mg Recurrent genital HSV infection: BID poor 800 mg once daily po × 3–6 months HSV proctitis:400 mg 5 times daily po × 10 days Treatment: $ b

Suppression: $$$ b /30-day supply

HSV proctitis: $$$ b

Nucleoside famciclovir Genital HSVinfection, first episode: Not different Genital HSV infection, first episode: $$ Analogues 250 mg TID po × 10 days from placebo. Famvir,generics Recurrent genital HSVinfection: Recurrent genital HSV infection: Treatment: 125 mg BID po × 5 days or 1000 mg BID po × 1 day Treatment: $ Suppression:250 mg BID po × 3–6 months Suppression: $$$$/30-day supply

Nucleoside valacyclovir Genital HSVinfection, first episode: Not different Genital HSV infection, first episode: $$$ Analogues 1000 mg BID po × 10 days from placebo. Valtrex,generics Recurrent genital HSVinfection: Recurrent genital HSV infection: Treatment: 500 mg BID po × 3–5 days Suppression: Treatment: $ ≤9 recurrences per y: 500 mg once daily po × 3–6 months Suppression: $$/30-day supply >9 recurrences per y: 1000 mg once dailypo × 3–6 months Reduction in genital HSVinfection transmission: Reduction in genital HSV infection 500 mg once daily po transmission: $$/30-day supply

Table 3: Antivirals for Herpesvirus Infections of the Skin

Class Drug Dosage Adverse Effects Costa

Nucleoside Analogues acyclovir Chickenpox: Not different from placebo. Chickenpox: Children: po: Zovirax,generics 5–7 years: 20 mg/kg QID po × 5–7 days Children: $$$$-$$$$$ 8–12 years: 15 mg/kg QID po × 5–7 days Adults $$ b: 13–16 years: 10 mg/kg QID po × 5–7 days c Adults: iv : ~$700/day Class Drug Dosage Adverse Effects Costa

800 mg 5 times daily po × 5 days or Eczema herpeticum: 10 mg/kg Q8H iv × 5 days po: $$ Eczema herpeticum: iv:c 200 mg 5 times daily po × 5 days Children: ~$275/day 5–10 mg/kg Q8H iv × 7 days in patients >12 years 750 mg/m2 TID iv × 7 days in patients <12 years Adults: $400–700/day Herpes zoster: Herpes zoster: $$$ 800 mg 5 times daily po × 7 days Nucleoside Analogues famciclovir Herpes zoster: Not different from placebo. $$$ 500 mg TID po × 7 days Famvir,generics

Nucleoside Analogues valacyclovir Herpes zoster: Not different from placebo. $$$ 1000 mg TID po × 7 days Valtrex,generics

Legend: $ <$15 $$ $15–30 $$$ $30–45 $$$$ $45–60 $$$$-$$$$$ $45–75 $$$$$ $60–75

Infectious Diseases: Herpesvirus Infections, Gerald A. Evans, MD, FRCPC, Date of revision: June 2014

Contraindications Adverse Effects (CI), drug Medication Uses (common and Initial dose; typical dose Monitoring interactions (DI) or severe) cautions Acyclovir antiviral: herpes CI: hypersensitivity headache, nausea, shingles: 800mg every 4-6 zoster to drug vomiting, diarrhea, hours for 7-10 day (shingles), imalaise herpes genitalis, DI: probenecid genital herpes: 200mg recurrent Chronic use requires every 4-6 hours for 10 genital herpes, follow up especially days varicella zoster in immune chronic therapy: 400mg (chicken pox) compromised every 12 hours or 200mg patients every 4-6 hours up to 12 months

chicken pox in children: 20mg/kg every 6 hours for 5 days