Download Suggestion from clinicians

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