Dosing
Adult dosing:
Acute retinal necrosis
:
HIV-infected:
10 to 15 mg/kg IV every 8 hours for 10 to 14 days plus ganciclovir 2 mg/0.05 mL intravitreally twice weekly for 1 to 2 doses, followed by valacyclovir 1 g orally 3 times daily for 6 weeks (guideline dosage
)
1500 mg/m(2)/day IV for 7 to 10 days followed by oral acyclovir
for 2 to 4 weeks (off-label dosage
)
Encephalitis due to human herpes simplex
virus:
10 mg
/kg IV (over 1 hour) given every 8 hours for 10 days
Maximum 20 mg
/kg every 8 hours (FDA dosage
)
5 to 10 mg
/kg IV every 8 hours for 21 days (guideline dosage
)
Genital herpes simplex
, severe initial clinical episodes, immunocompetent patients:
5 mg/kg IV over 1 hour every 8 hours for 5 days
Maximum dose, 20 mg
/kg every 8 hours (FDA dosage
)
5 to 10 mg
/kg IV every 8 hours for 2 to 7 days
or until clinical improvement occurs, and then switch to oral therapy to complete at least 10 days of total therapy (guideline dosage
)
Herpes simplex
, Mucosal and cutaneous – Patient immunocompromised:
5 mg/kg IV (over 1 hour) given every 8 hours for 7 days
Maximum 20 mg
/kg every 8 hours (FDA dosage
)
Severe infections in HIV-infected patients:
5 mg/kg IV every 8 hours (guideline dosage
)
Herpes simplex
– Viral hepatitis:
5 to 10 mg
/kg IV every 8 hours for 2 to 7 days
or until clinical improvement occurs, and then switch to oral therapy to complete at least 10 days of total therapy (guideline dosage
)
Herpes zoster
, Shingles – Patient immunocompromised:
10 mg
/kg IV (over 1 hour) given every 8 hours for 7 days
Maximum 20 mg
/kg every 8 hours (FDA dosage
)
Extensive cutaneous or visceral involvement, HIV-infected patients:
10 to 15 mg/kg IV every 8 hours until clinical improvement, then switch to oral therapy for a total duration of 10 to 14 days
Oral options include valacyclovir 1 g 3 times daily, famciclovir 500 mg 3 times daily, or acyclovir
800 mg 5 times daily (guideline dosage
)
HIV infection
– Varicella:
Severe or complicated cases:
10 to 15 mg/kg IV every 8 hours for 7 to 10 days (guideline dosage
)
Pediatric dosing:
Congenital herpes simplex
:
Birth to 3 months of age:
10 mg
/kg IV (over 1 hour) given every 8 hours for 10 days; doses of 15 to 20 mg
/kg IV have been used; Maximum 20 mg
/kg every 8 hours (FDA dosage
)
Infants:
Disseminated and CNS disease: 20 mg
/kg IV every 8 hours for 21 days (guideline dosage
)
Skin and mucous membrane disease: 20 mg
/kg IV every 8 hours for 14 days (guideline dosage
)
Encephalitis due to human herpes simplex
virus:
3 months to 12 years
of age:
20 mg
/kg IV (over 1 hour) given every 8 hours for 10 days
Maximum 20 mg
/kg every 8 hours
12 years
of age and older:
10 mg
/kg IV (over 1 hour) given every 8 hours for 10 days
Maximum 20 mg
/kg every 8 hours
Genital herpes
simplex, severe initial clinical episodes, immunocompetent patients:
12 years
or older:
5 mg/kg IV (over 1 hour) given every 8 hours for 5 days
Maximum 20 mg
/kg every 8 hours
Herpes simplex
, Mucosal and cutaneous – Patient immunocompromised:
Younger than 12 years
:
10 mg
/kg IV (over 1 hour) every 8 hours for 7 days
Maximum 20 mg
/kg every 8 hours (FDA dosage
)
12 years
or older:
5 mg/kg IV (over 1 hour) every 8 hours for 7 days
Maximum 20 mg
/kg every 8 hours (FDA dosage
)
Moderate to severe gingivostomatitis in HIV-infected patients:
5 to 10 mg
/kg IV 3 times daily (guideline dosage
)
Herpes zoster
, Shingles – Patient immunocompromised:
Severe immunosuppression, trigeminal nerve involvement, or extensive multidermatomal zoster, HIV-infected (younger than 12 years
of age):
10 mg
/kg IV 3 times daily; switch to oral acyclovir
once cutaneous lesions and visceral disease are clearly resolving for a total duration of 10 to 14 days (guideline dosing)
Younger than 12 years
of age:
20 mg
/kg IV (over 1 hour) given every 8 hours for 7 days
Maximum 20 mg
/kg every 8 hours (manufacturer dosing)
12 years
and older:
10 mg
/kg IV (over 1 hour) given every 8 hours for 7 days
Maximum 20 mg
/kg every 8 hours (manufacturer dosing)
HIV infection
– Varicella:
Complicated or severe immunosuppression; CDC immunologic category 3:
10 mg
/kg IV 3 times daily for 7 to 10 days or until no new lesions appear for 48 hours (guideline dosage
)
Indications
FDA-Labeled Indications:
Congenital herpes simplex
Encephalitis due to human herpes simplex
virus
Genital herpes simplex
, severe initial clinical episodes, immunocompetent patients
Herpes simplex
, Mucosal and cutaneous – Patient immunocompromised
Herpes zoster
, Shingles – Patient immunocompromised
Non-FDA Labeled Indications:
Acute retinal necrosis
Chickenpox pneumonia
Herpes simplex
meningitis
Herpes simplex
– Viral
hepatitis
Herpes simplex
– Viral
respiratory infection
Herpes zoster
auricularis
HIV infection
– Varicella
Varicella
Viral
encephalitis
Mechanism of Action
Acyclovir is a synthetic purine nucleoside analogue with in vitro and in vivo inhibitory activity against
herpes simplex
virus types 1 (HSV-1), 2 (HSV-2), and varicella-zoster virus (VZV).
The inhibitory activity of
acyclovir
is highly selective due to its affinity for the enzyme thymidine kinase (TK) encoded by HSV and VZV.
This
viral
enzyme converts
acyclovir
into
acyclovir
monophosphate, a nucleotide analogue.
The monophosphate is further converted into diphosphate by cellular guanylate kinase and into triphosphate by a number of cellular enzymes.
In vitro,
acyclovir
triphosphate stops replication of herpes
viral
DNA.
This is accomplished in 3 ways:
1) Competitive inhibition of
viral
DNA polymerase
,
2) Incorporation into and termination of the growing
viral
DNA chain
3) Inactivation of the
viral
DNA polymerase
.
The greater
antiviral
activity of
acyclovir
against HSV compared to VZV is due to its more efficient phosphorylation by the
viral
TK.
Adverse Effect
Common:
Dermatologic:
Injection site inflammation (approximately 9%)
Gastrointestinal:
Nausea
Vomiting
Renal
:
Serum blood urea nitrogen raised, Transient
Serum creatinine raised, Transient
Serious:
Dermatologic:
Stevens-Johnson syndrome
Toxic epidermal necrolysis
Hematologic:
Thrombotic thrombocytopenic purpura
Neurologic:
Neurotoxicity
Renal:
Hemolytic uremic syndrome
Renal
failure
Contraindication
Hypersensitivity to acyclovir
or valacyclovir
Interaction
Co-administration of probenecid with intravenous acyclovir
has been shown to increase the mean acyclovir
half-life and the area under the concentration-time curve. Urinary excretion and renal
clearance were correspondingly reduced.
Major:
Foscarnet (theoretical)
Tolvaptan (theoretical)
Moderate:
Fosphenytoin (probable)
Phenytoin (probable)
Valproic Acid (probable)
Phamacokinetics
Distribution:
Plasma Protein binding: 9% to 33%
Volume of Distribution (Vd):
Adults: 48 L/m (2) (range 37 to 57 L/m(2))
Birth to 3 months: 1.08 +/- 0.35 L/kg
3 months to 16 years: 1.01 +/- 0.28 L/kg
Metabolism:
Metabolites:
9-carboxymethyl methylguanine: inactive
Excretion:
Renal
: 62% to 91% unchanged
Fecal: 2%
Dialyzable:
Hemodialysis: Yes, 60% decrease in plasma concentrations following 6 hours dialysis period
Peritoneal dialysis: No, less than 10% is removed
Other extracorporeal:
Plasmapheresis: No
Exchange transfusion: No
Hemofiltration: No
Elimination:
Adults: 2.5 hours to 3.5 hours
Anuric adults: 19.5 hours
Pediatrics: 2.36 hours to 3.8 hours
Precaution
Hematologic:
Thrombotic thrombocytopenic purpura and hemolytic uremic syndrome
, including fatal cases, has been reported in immunocompromised patients.
Neurologic:
Encephalopathic changes (e.g., lethargy, obtundation, tremors, confusion, hallucinations, agitation, seizures, or coma) have been reported; use
with caution in patients with underlying neurologic abnormalities, significant hypoxia, or serious renal
, hepatic, or electrolyte abnormalities.
Renal
:
Impaired renal
function may occur and is dependent upon rate of administration; risk is increased in patients with pre-existing renal
disease and dehydration, and with concomitant use
of other nephrotoxic drugs.
Precipitation of acyclovir
crystals in renal
tubules may occur and can result in acute renal failure; accompany administration with adequate hydration.
Renal
failure, including fatal cases, has been reported.
Pregnancy Category
B (FDA)
B3 (AUS)
Breast Feeding
AAP: Maternal medication usually compatible with breastfeeding.
Monitoring
Genital herpes
:
Reduction in the duration of viral
excretion, new lesion formation, duration of vesicle presence, and promotion of lesion healing are indicative of efficacy.
Herpes simplex encephalitis:
Reduction in signs or symptoms of
herpes simplex
encephalitis is indicative of efficacy.
herpes simplex
in immunocompromised patients:
Decreased viral
excretion, reduced pain, and healing of lesions is indicative of efficacy.
Neonatal herpes simplex
:
Improvement in signs and symptoms of
herpes simplex
is indicative of efficacy.
Varicella zoster in immunocompromised patients:
Reductions in cutaneous and visceral dissemination are indicative of efficacy.
Renal
function in elderly patients
How to Take or Administration
General Information:
Injection:
Do not administer as a subcutaneous or IM injection
Intravenous:
Do not use
as a rapid or bolus injection; administer only as an IV infusion
Reconstitute with sterile water for injection and use
within 12 hours; do not use
bacteriostatic water for injection containing benzyl alcohol or parabens
Infusion:
After reconstitution, dilute the appropriate dose in D5W or NS to a concentration of 7 mg/mL or less and infuse over 1 hour; biologic or colloidal fluids are not recommended for dilution
Dosage Form
Intravenous Powder for Solution:
500 MG
1000 MG
Intravenous Solution:
50 MG/1 ML
Treatment
Management of Mild to Moderate Toxicity:
Patients generally do well with supportive care. Nausea and vomiting should be treated with antiemetics. Rashes should be treated with supportive care, discontinuation of the offending agent, and consideration of antihistamines and corticosteroids. With massive overdose, hydrate patients and monitor renal
function.
Management of Severe Toxicity:
Supportive care remains the mainstay of care in severe toxicity. Seizures should be treated with benzodiazepines as first line therapy, followed by barbiturates or propofol, if seizures persist. Hydrate patients and monitor urine output and renal
function. Airway protection should be employed as need for patients with coma.
Toxicology
A toxic dose has not been established for these agents.
Patient Counselling or Clinical Teaching
Advise patient to maintain adequate hydration to prevent
renal
toxicity.
Drug may cause nausea, vomiting, itching, and rash, hives, or injection site inflammation or phlebitis.
Instruct patient to report signs or
symptoms of
encephalopathic changes (e.g., lethargy, obtundation, tremors, confusion, hallucinations, agitation, or seizures).
Category of Acyclovir Sodium :