Acyclovir

Acyclovir is a guanosine analogue antiviral that interferes with replication of susceptible herpesviruses. Its activity depends both on viral susceptibility and on achieving adequate active-drug concentrations inside infected cells. Veterinary use is therefore much less straightforward than extrapolating a human herpesvirus regimen to another species.

Selected equine, canine and psittacine herpesvirus uses have been described, with important evidence limitations. Poor oral absorption restricts systemic exposure in horses, while feline herpesvirus activates acyclovir inefficiently. Systemic acyclovir is consequently not a suitable routine choice for feline herpesvirus disease.

Group

Antiviral; nucleoside analogue

Mechanism of Action

In susceptible herpesvirus-infected cells, viral thymidine kinase converts acyclovir to its monophosphate form. Host-cell enzymes then add two further phosphate groups to form acyclovir triphosphate. Preferential initial activation in infected cells helps produce antiviral selectivity, although selectivity is not absolute and differs among viruses.

The triphosphate competes with the normal guanosine nucleotide at viral DNA polymerase and can be incorporated into growing viral DNA. Because it lacks the structure needed for continued chain extension, incorporation terminates DNA elongation and inhibits further replication. It acts on replicating virus and does not eliminate latent herpesvirus genomes.

A virus that poorly phosphorylates acyclovir produces little active triphosphate. This, together with low oral bioavailability in some hosts, explains why favorable activity against human herpes simplex virus does not establish useful efficacy against feline or equine herpesvirus in vivo.

Dose Rates

Horses

Use / stage	Dose	Route	Schedule	Instructions
Herpesvirus infection	10 mg/kg	IV	Every 12 h	Do not use in: Compromised renal function, Animals intended for food; Infuse over one hour with appropriate dilution and hydration. Clinical efficacy is uncertain; oral acyclovir does not provide reliable systemic exposure.
Herpesvirus infection	10 mg/kg	PO		Anecdotal outbreak use with uncertain efficacy. Very poor equine oral bioavailability makes benefit unlikely; retained separately from the IV regimen. The source gives five oral administrations per day; evenly spaced timing is not specified.
Herpesvirus infection	20 mg/kg	PO	Every 8 h	Anecdotal outbreak use with uncertain efficacy and poor oral bioavailability; this is not equivalent to the IV regimen.

Dogs

Use / stage	Dose	Route	Schedule	Instructions
Herpesvirus infection	3–10 mg/kg	PO		Up to 10 days; Do not use in: Compromised renal function, Animals intended for food; Historical extrapolated regimen: five administrations daily. Systemic efficacy and an optimal canine dose are not established.
Herpesvirus infection	10–20 mg/kg	IV	Every 8 h	Do not use in: Compromised renal function, Animals intended for food; Historical extrapolated regimen; infuse over one hour. Systemic efficacy is not established.

Birds

Use / stage	Dose	Route	Schedule	Instructions
Pacheco's disease	80 mg/kg	PO	Every 8 h	Up to 14 days; Do not use in: Dehydration, Compromised renal function; Psittacine birds; a 7-14 day course is described. Combine with supportive care and transmission control.
Pacheco's disease	40 mg/kg	IM	Every 8 h	Up to 3 days; Do not use in: Dehydration, Compromised renal function; Highly irritating historical alternative with tissue-necrosis risk; oral treatment is preferable where feasible. Do not continue parenteral treatment beyond 72 hours.
Pacheco's disease	80 mg/kg	PO	Every 24 h	Distinct oral-suspension alternative; the accompanying food/water method is not equivalent to a guaranteed individual intake.
Pacheco's disease	80 mg/kg	PO, IM	Every 12 h	Separate individually administered regimen. IM treatment is highly irritating; do not continue parenteral use beyond 72 hours because injection-site tissue necrosis can occur.
Pacheco's disease prophylaxis	Reference only	IM		Exposed-bird protocol: 25 mg/kg IM once, then 1 mg/mL in drinking water and 400 mg per quart of seed for at least seven days. IM injection is very irritating; subsequent exposure depends on consumption. A separate Quaker-parrot course uses 80 mg/kg by gavage every eight hours for seven days.

Cats

Use / stage	Dose	Route	Schedule	Instructions
Herpesvirus infection	10–25 mg/kg	PO	Every 12 h	Historical regimen conflicts with the other supplied monograph, which describes poor efficacy and serious feline marrow, hepatic and renal toxicity and recommends alternatives. Do not interpret this record as endorsement. The historical account requires diagnostic evaluation and CBC monitoring every 2–3 weeks.

Indications

Selected equine herpesvirus infections; clinical efficacy remains uncertain.
Historical treatment of canine herpesvirus infection using extrapolated regimens; supporting veterinary evidence is limited.
Treatment of Pacheco’s disease in psittacine birds as part of outbreak management and supportive care.

Contraindications

Cats: poor efficacy and risk of marrow, hepatic and renal toxicity.
Avoid in animals with compromised renal function under the regimens listed here.
Do not administer to animals intended for food.
Dehydration increases renal risk. Assess neurologic disease or previous reactions to related antivirals before systemic treatment.
Avian IM administration is highly irritating and can cause tissue necrosis; do not continue the described IM regimen beyond 72 hours.
Pregnancy and lactation data in veterinary species are limited; placental and milk transfer can occur.

Interactions

Other nephrotoxic drugs increase renal risk.
Do not mix injectable acyclovir with blood products or bacteriostatic diluents containing preservatives.
Zidovudine may increase CNS depression.
Reported infusion incompatibilities include dopamine, dobutamine, fludarabine, foscarnet, meperidine and morphine; avoid unverified admixtures.

Adverse effects

Renal injury or crystalluria, especially with dehydration or rapid administration.
Phlebitis at injection sites.
Sweating or muscle tremors during rapid equine infusion.
Myelosuppression, hepatotoxicity and nephrotoxicity in cats.
Gastrointestinal upset and rare neurologic adverse effects during systemic exposure.

Toxicity

Renal injury is the principal systemic concern. Use adequate hydration and slow infusion; monitor urea, creatinine and urine output. Feline toxicity can involve bone marrow, liver and kidneys.

Preparations

Preparation	Form	Strength	Route
Zovirax 200 mg Tablets Store in a tight, light-resistant container at room temperature.	Tablet	200 mg / tablet	PO
Zovirax 400 mg Tablets Store in a tight, light-resistant container at room temperature.	Tablet	400 mg / tablet	PO
Zovirax 800 mg Tablets Store in a tight, light-resistant container at room temperature.	Tablet	800 mg / tablet	PO
Zovirax Oral Suspension 400 mg/5 mL This strength differs from 200 mg/5 mL acyclovir suspensions; confirm the denominator. Store at room temperature.	Oral Liquid	400 mg / 5 mL	PO
Acyclovir Injection USP 50 mg/mL (Fresenius Kabi) Fresenius Kabi USA, LLC Acyclovir sodium expressed as acyclovir. IV infusion only: dilute before use; not an IM preparation. Available as 500 mg/10 mL and 1000 mg/20 mL single-dose vials. Store at 20-25 C and discard unused opened-vial contents.	Injection	50 mg / mL	IV
Acyclovir Ointment USP 5% Cutaneous ointment, 50 mg/g; not an ophthalmic preparation. Do not substitute it for a sterile ophthalmic product.	Other	50 mg / g	TOPICAL
Cyclovir 200 mg Tablets	Tablet	200 mg / tablet	PO
Aciherpin 200 mg Tablets	Tablet	200 mg / tablet	PO

Monitoring and Administration

Poor oral exposure limits its value in horses, and efficacy and systemic dosing in dogs are poorly established. IV use in horses has pharmacokinetic support, but controlled evidence of clinical benefit is limited.

Monitor renal function and hydration during prolonged or IV treatment. Oral exposure in horses is too unreliable to infer efficacy from an oral dose alone.

Reconstitution to 50 mg/mL uses sterile water without benzyl alcohol or parabens. Further dilute the injectable solution to no more than 7 mg/mL under the described instructions and infuse slowly. Do not mix with blood products or bacteriostatic diluents.