VIRA-A

Clinical safety rating: caution

Comprehensive clinical and safety monograph for VIRA-A (VIRA-A).

How it works

Vidarabine (VIRA-A) is a purine nucleoside analog that inhibits viral DNA polymerase and incorporates into viral DNA, causing chain termination. It also inhibits ribonucleotide reductase, reducing viral DNA synthesis.

What the body does with it

Metabolism	Vidarabine is rapidly deaminated by adenosine deaminase in the liver and peripheral tissues to arabinosylhypoxanthine (ara-Hx), which is less active but has a longer half-life. Hepatic metabolism predominantly.
Excretion	Primarily renal: approximately 40-70% of dose excreted unchanged in urine via glomerular filtration and tubular secretion. A smaller fraction (10-20%) is eliminated as the metabolite hypoxanthine arabinoside. Fecal excretion accounts for <5% of the dose.
Half-life	Vidarabine: 0.17-0.25 hours (rapidly deaminated to arabinosylhypoxanthine). Arabinosylhypoxanthine: 3.5-5.5 hours in adults with normal renal function; prolonged to 15-20 hours in severe renal impairment.
Protein binding	Vidarabine: 15-30% bound to plasma proteins. Arabinosylhypoxanthine: negligible binding (<10%).
Volume of Distribution	Vidarabine: approximately 2.5-4.0 L/kg; extensive tissue distribution including brain and CSF. Arabinosylhypoxanthine: 1.5-2.5 L/kg.
Bioavailability	Intravenous: 100% (only approved systemic route). Ophthalmic ointment: negligible systemic absorption (<1% of ocular dose).
Onset of Action	Intravenous: within 24-48 hours for virologic response in herpes simplex encephalitis. Ophthalmic: within 2-5 days for reduction of viral shedding in herpes keratitis.
Duration of Action	Antiviral effect persists for the duration of detectable plasma levels of arabinosylhypoxanthine (approximately 24 hours after last IV dose). For ophthalmic use, 7-10 days of treatment typical; clinical resolution by 2-3 weeks.

Classification & Brands

Dosing & administration

15 mg/kg/day IV infused over 12-24 hours for 7 days.

Dosage form	OINTMENT
Renal impairment	CrCl <50 mL/min: 10 mg/kg/day; CrCl <10 mL/min: 7.5 mg/kg/day.
Liver impairment	Child-Pugh B or C: reduce dose by 50%. Use with caution in severe hepatic impairment.
Pediatric use	30 mg/kg/day IV divided every 8 hours for 7 days.
Geriatric use	Monitor renal function closely; consider dose reduction based on CrCl.

Use during pregnancy

1st trimester	Consult provider
2nd trimester	Consult provider
3rd trimester	Consult provider

Clinical note

Comprehensive clinical and safety monograph for VIRA-A (VIRA-A).

Breastfeeding	Not recommended. M/P ratio unknown; vidarabine is excreted in breast milk in small quantities. Potential for serious adverse effects in nursing infants (bone marrow suppression, neurotoxicity).
Teratogenic Risk	FDA Pregnancy Category C. First trimester: Potential for teratogenicity based on animal studies (cleft palate, exencephaly); human data insufficient. Second/third trimesters: No well-controlled studies; use only if maternal benefit outweighs fetal risk. Risk of kernicterus in third trimester if administered near delivery due to bilirubin displacement.

Warnings & precautions

■ FDA Black Box Warning

None.

Side Effect Profile

Serious Effects

Absolute Contraindications

["Hypersensitivity to vidarabine or any component of the formulation.","Concurrent use with allopurinol (increased risk of neurotoxicity).","Severe bone marrow suppression (relative)."]

Clinical Precautions

Precautions

["May cause dose-related neurotoxicity including tremors, ataxia, confusion, and seizures, especially in renal impairment.","Renal function monitoring essential due to accumulation of ara-Hx.","Hematologic effects: anemia, leukopenia, thrombocytopenia.","Gastrointestinal: nausea, vomiting, diarrhea.","Hepatotoxicity: elevated liver enzymes.","Carcinogenesis, mutagenesis, impairment of fertility observed in animal studies."]

Clinical Tips & Counseling

Drug interactions

Loading safety data…

VIRA-A

Clinical safety rating: caution

Comprehensive clinical and safety monograph for VIRA-A (VIRA-A).

How it works

What the body does with it

Metabolism	Vidarabine is rapidly deaminated by adenosine deaminase in the liver and peripheral tissues to arabinosylhypoxanthine (ara-Hx), which is less active but has a longer half-life. Hepatic metabolism predominantly.
Excretion	Primarily renal: approximately 40-70% of dose excreted unchanged in urine via glomerular filtration and tubular secretion. A smaller fraction (10-20%) is eliminated as the metabolite hypoxanthine arabinoside. Fecal excretion accounts for <5% of the dose.
Half-life	Vidarabine: 0.17-0.25 hours (rapidly deaminated to arabinosylhypoxanthine). Arabinosylhypoxanthine: 3.5-5.5 hours in adults with normal renal function; prolonged to 15-20 hours in severe renal impairment.
Protein binding	Vidarabine: 15-30% bound to plasma proteins. Arabinosylhypoxanthine: negligible binding (<10%).
Volume of Distribution	Vidarabine: approximately 2.5-4.0 L/kg; extensive tissue distribution including brain and CSF. Arabinosylhypoxanthine: 1.5-2.5 L/kg.
Bioavailability	Intravenous: 100% (only approved systemic route). Ophthalmic ointment: negligible systemic absorption (<1% of ocular dose).
Onset of Action	Intravenous: within 24-48 hours for virologic response in herpes simplex encephalitis. Ophthalmic: within 2-5 days for reduction of viral shedding in herpes keratitis.
Duration of Action	Antiviral effect persists for the duration of detectable plasma levels of arabinosylhypoxanthine (approximately 24 hours after last IV dose). For ophthalmic use, 7-10 days of treatment typical; clinical resolution by 2-3 weeks.

Classification & Brands

Dosing & administration

15 mg/kg/day IV infused over 12-24 hours for 7 days.

Dosage form	OINTMENT
Renal impairment	CrCl <50 mL/min: 10 mg/kg/day; CrCl <10 mL/min: 7.5 mg/kg/day.
Liver impairment	Child-Pugh B or C: reduce dose by 50%. Use with caution in severe hepatic impairment.
Pediatric use	30 mg/kg/day IV divided every 8 hours for 7 days.
Geriatric use	Monitor renal function closely; consider dose reduction based on CrCl.

Use during pregnancy

1st trimester	Consult provider
2nd trimester	Consult provider
3rd trimester	Consult provider

Clinical note

Comprehensive clinical and safety monograph for VIRA-A (VIRA-A).

Breastfeeding	Not recommended. M/P ratio unknown; vidarabine is excreted in breast milk in small quantities. Potential for serious adverse effects in nursing infants (bone marrow suppression, neurotoxicity).
Teratogenic Risk	FDA Pregnancy Category C. First trimester: Potential for teratogenicity based on animal studies (cleft palate, exencephaly); human data insufficient. Second/third trimesters: No well-controlled studies; use only if maternal benefit outweighs fetal risk. Risk of kernicterus in third trimester if administered near delivery due to bilirubin displacement.

Warnings & precautions

■ FDA Black Box Warning

None.

Side Effect Profile

Serious Effects

Absolute Contraindications

["Hypersensitivity to vidarabine or any component of the formulation.","Concurrent use with allopurinol (increased risk of neurotoxicity).","Severe bone marrow suppression (relative)."]