The conventional approach to control viral diseases is to develop effective vaccines, but this is not always possible. The objective of antiviral therapy is to eradicate the virus, while minimally impacting the host, and to prevent further viral invasion. However, the method of replication of viruses makes them a greater challenge to treat than bacteria.
Viruses comprise a core genome of nucleic acid surrounded by a protein shell or capsid. Some viruses are further surrounded by a lipoprotein membrane or envelope. Viruses cannot replicate independently and are thus obligate intracellular parasites. The host’s pathways of energy generation, protein synthesis, and DNA or RNA replication provide the means of viral replication.
Viral replication occurs in five sequential steps:
host cell entry
capsid disassembly (uncoating)
control of host protein and nucleic acid synthesis to make viral components
assembly of viral proteins
release of the virus
Drugs that target viral processes must penetrate host cells. Given that viruses often modulate cell division, drugs that negatively affect a virus are also likely to negatively affect normal pathways of the host. For this reason, antiviral drugs have a narrow therapeutic margin, compared with antimicrobial drugs. Nephrotoxicosis is emerging as an adverse reaction to antiviral drugs in human medicine.
Treatment is further complicated by viral latency, the ability of the virus to remain dormant within the host cell (ie, by incorporating its genome into the host genome); reactivation can then lead to clinical signs of infection in the animal even if it has not been reexposed to the virus.
In vitro susceptibility testing depends on cell cultures, which are expensive. More importantly, in vitro inhibitory tests do not necessarily correlate with therapeutic efficacy of antiviral drugs. The discrepancy between in vitro and in vivo testing is due, in part, to the fact that some drugs require activation (metabolism) to be effective.
Only a few antiviral drugs are reasonably safe and effective, against a limited number of viral diseases, and most of these have been developed for use in humans. Few have been studied in animals, and widespread clinical use of antiviral drugs is not common in veterinary medicine. The advent of human immunodeficiency virus (HIV) and the development of the cat as a model of HIV infection has somewhat increased the animal knowledge base.
There are notable concerns that the use of antiviral agents in veterinary medicine, particularly in food-producing animals, leads to the development of resistance to these medications in human pathogens. In 2006, the FDA prohibited the extralabel use of adamantanes and neuraminidase inhibitors in chickens, turkeys, and ducks because of concern about the potential emergence of resistant strains of influenza A, including H5N1 avian influenza virus, in the human population. Resistance to adamantane antivirals has been documented in influenza A strains in both humans and poultry, and some human strains have also demonstrated resistance to neuraminidase inhibitors. Although extralabel drug use (ELDU) is not prohibited in other species, these antivirals should be considered to be reserved classes of drugs to preserve their efficacy in the human population, and they should be used only in instances of documented infection and only when other agents or measures are considered inadequate for patient survival.
Dosages of Antiviral Drugs
Drug | Preparation | Species, Dose, Route, and Frequency | Indication | Notes |
|---|---|---|---|---|
Idoxuridine | 0.1% ophthalmic solution or 0.5% ophthalmic ointment | Cats, dogs, horses: 1 drop or ¼-inch strip in affected eye, every 2–3 h for 48 h, followed by every 4–6 h until one week beyond resolution of clinical signs | Ocular herpesvirus (FHV-1, CHV-1, EHV-2) infection | No longer commercially available in the US but may be prepared by compounding pharmacies Not approved for use in food animals Potential teratogen: caution for use in pregnant animals; women who are pregnant should avoid handling |
Trifluridine | 1% ophthalmic solution | Cats, dogs: 1 drop, OU, every 2 h for 2 days, then 3–8 times daily until 1 week beyond resolution of clinical signs; do not use more than 3 weeks to avoid corneal toxicity | Ocular herpesvirus (FHV-1, CHV-1) | Not approved for use in food animals Caution in patients with glaucoma; may increase intraocular pressure Women who are pregnant should be cautious when handling Less well tolerated in cats due to ocular discomfort (stinging) on administration |
Vidarabine | 3% ophthalmic ointment | 0.4- to 1-cm strip, OU, every 5–6 h until one week beyond resolution of clinical signs | Ocular herpesvirus (FHV-1) | No longer commercially available in the US but may be prepared by compounding pharmacies Not approved for use in food animals |
Cidofovir | 0.5% ophthalmic solution (compounded from 75 mg/mL injection) | Cats: 1 drop, OU, every 12 h for 5 days | Ocular herpesvirus (FHV-1) | Not approved for use in food animals Potential teratogen: caution for use in pregnant animals; women who are pregnant should avoid handling or wear protective apparel when handling |
Acyclovir | 200-mg capsules, 400- or 800-mg tablets, 200 mg/5 mL oral suspension; 50 mg/mL injectable solution or powder for reconstitution; 5% topical ointment | Dogs: 10 mg/kg, PO, every 6 h for 5 days (neonatal CHV-1); 20 mg/kg, IV, every 8 h for 5 days (prophylaxis of canine parvovirus infection) Horses: 10 mg/kg, IV slowly over 1 h, every 12 h (EHV) Birds: 80 mg/kg, PO, every 8 h for 7–14 days (Pacheco's disease) Cats: Contraindicated due to risk of myelosuppression and nephrotoxicity | CHV-1, prophylaxis of canine parvovirus, EHV, Pacheco's disease | Not approved for use in food animals Poor oral bioavailability in horses; oral administration not recommended Caution in patients with renal disease and with coadministration potentially nephrotoxic drugs |
Valacyclovir | 1-g and 500-mg tablets | Horses: 27–40 mg/kg, PO, every 8 h for 2 days, then 18–20 mg/kg, PO, every 12 h for 1–2 weeks Cats: Contraindicated due to hepatic, renal, and bone marrow toxicity | EHM, EHV-1, EHV-3 | Not approved for use in food animals Contraindicated in cats Caution in patients with renal disease and with coadministration of nephrotoxic drugs |
Ganciclovir | 500 mg/vial powder, 0.15% ophthalmic solution | Horses: 2.5 mg/kg, as slow IV bolus, every 8 h for 1 day, then 2.5 mg/kg, as slow IV bolus, every 12 h for maintenancea,b Dogs: 1 drop, in affected eye, 5 times daily until ulcer resolution; then 1 drop, in affected eye, 3 times daily for 7 days Cats: 1 drop, in affected eye, every 6 h | Feline herpes keratitis, EHM, ocular CHV-1 | Not approved for use in food animals Potential teratogen: caution for use in pregnant animals; women who are pregnant should avoid handling |
Famciclovir | 125-, 250- and 500- mg tablets | 90 mg/kg, PO, every 8–12 h until 1 week beyond resolution of clinical signsc | FHV-1 | Not approved for use in food animals |
Zidovudine | 10 mg/mL syrup; 10 mg/mL injection; 300-mg tablets; 100-mg capsules | Cats: 5–10 mg/kg, PO or SC, every 12 h | FIV, FeLV | Not approved for use in food animals Caution in animals with bone marrow suppression; monitor for development of anemia in treated animals, and discontinue use if hematocrit is < 20% |
Rimantadine | 100-mg tablets | Horses: 30 mg/kg, PO, every 12 h | Equine influenza | Prohibited for use in poultry in the US Not approved for use in food animals |
Interferon alfa-2 | 3 × 106 IU/vial; 30-60 IU/mL oral solution (compounded from commercially available injectable solution) | Cats: 60 IU/cat, PO or buccally once daily, treated 7 days on, 7 days off | FeLV | No oral formulation commercially available in the US, but may be prepared by compounding pharmacies Not approved for use in food animals Do not vaccinate animals receiving interferon-alfa |
Oseltamivir | 30-, 45-, and 75-mg capsules; 30 mg/5 mL oral suspension reconstituted from powder | Horses: 2 mg/kg, PO, every 12 h for 5 days Dogs: 2 mg/kg, PO, every 12 h for 5 days | Equine influenza, canine parvovirus | Prohibited for use in poultry in the US Not approved for use in food animals |
CRI = constant-rate infusion; EHM = equine herpesvirus myeloencephalopathy; FeLV = feline leukemia virus; FHV-1= feline herpesvirus 1; FIP = feline infectious peritonitis; FIV = feline immunodeficiency virus aMaxwell LK. Antiherpetic drugs in equine medicine. Vet Clin North Am: Equine practice. 2017;33(1):99–125. doi:10.1016/j.cveq.2016.12.002 bCarmichael RJ, Whitfield C, Maxwell LK. Pharmacokinetics of ganciclovir and valganciclovir in the adult horse. J Vet Pharm Ther 36: 441–9. cSebbag L, Thomasy SM, Woodward AP, Knych HK, Maggs DJ. Pharmacokinetic modeling of penciclovir and brl42359 in the plasma and tears of healthy cats to optimize dosage recommendations for oral administration of famciclovir. Am J Vet Res. 2016 Aug 1;77(8):833–45. https://doi.org/10.2460/ajvr.77.8.833 | ||||
Most antiviral drugs interfere with viral nucleic acid synthesis or regulation. Such drugs generally are nucleic acid analogues that interfere with RNA and DNA production. Other mechanisms of action include interference with viral cell binding or interruption of virus uncoating. Some viruses contain unique metabolic pathways that serve as drug targets. Drugs that simply inhibit single steps in the viral replication cycle are virostatic, only temporarily halting viral replication. Thus, optimal activity of some drugs depends on an adequate host immune response. Some antiviral drugs may enhance the immune system of the host. Dosages of Antiviral Drugs lists the dosage rates for some commonly used antiviral drugs.
