ACYCLOVIR

By | 2010-06-12

Chemistry

An antiviral agent, acyclovir (also known as ACV or acycloguanosine), occurs as a white, crystalline powder. 1.3 mg is soluble in one ml of water. Acyclovir sodium has a solubility of greater than 100 mg/ml in water. However, at a pH of 7.4 at 37°C it is practically all unionized and has a solubility of only 2.5 mg/ml in water. There is 4.2 mEq of sodium in each gram of acyclovir sodium.

Storage – Stability – Compatibility

Acyclovir ointment should be stored in a dry place at room temperature. Acyclovir capsules and tablets should be stored in tight, light resistant containers at room temperature. Acyclovir suspension and sodium sterile powder should be stored at room temperature.

When reconstituting acyclovir sodium do not use bacteriostatic water with parabens as precipitation may occur. The manufacturer does not recommend using bacteriostatic water for injection with benzyl alcohol because of the potential toxicity in neonates. After reconstitution with 50-100 ml of a standard electrolyte or dextrose solution, the resulting solution is stable at 25°C for 24 hours. Acyclovir is reportedly incompatible with biologic or colloidial products (e.g., blood products or protein containing solutions). It is also incompatible with dopamine HC1, dobutamine, fludarabine phosphate, foscarnet sodium, meperidine and morphine sulfate. Many other drugs have been shown to be compatible in specific situations. Compatibility is dependent upon factors such as pH, concentration, temperature and diluents used. It is suggested to consult specialized references (e.g., Handbook on Injectable Drugs by Trissel; see bibliography) for more specific information.

Pharmacology

Acyclovir has antiviral activity against a variety of viruses including herpes simplex (types I and II), cytomegalovirus, Epstein-Barr, and varicella-Zoster. It is preferentially taken up by these viruses, converted into the active triphosphate form where it inhibits viral DNA replication.

Uses – Indications

Acyclovir may be useful in treating herpes infections in a variety of avian species and in cats with corneal and/or conjunctival herpes infections. Its use in veterinary medicine is not well established however, and it should be used with caution.

Pharmacokinetics

Acyclovir is poorly absorbed after oral administration (approx. 20%) and absorption is not significantly affected by the presence of food. It is widely distributed throughout body tissues and fluids, including the brain, semen, and CSF. It has low protein binding and crosses the placenta. Acyclovir is primarily hepatically metabolized and has a half life of about 3 hours in humans. Renal disease does not significantly alter half life unless anuria is present.

Contraindications – Precautions – Reproductive Safety

Acyclovir is potentially contraindicated (assess risk-benefit) during dehydrated states, pre-existing renal function impairment, hypersensitivity to it or other related antivirals, neurologic deficits, or previous neurologic reactions to other cytotoxic drugs.

Acyclovir crosses the placenta, but rodent studies have not demonstrated any teratogenic effects thus far. Acyclovir crosses into maternal milk, but associated adverse effects have not been noted.

Adverse Effects – Warnings

With parenteral therapy, potential adverse effects include thrombophlebitis, acute renal failure, and ecephalopathologic changes (rare). GI disturbances may occur with either oral or parenteral therapy.

Preliminary effects noted in cats, include leukopenia and anemias, that are apparently reversible with discontinuation of therapy.

Overdosage – Acute Toxicity

Oral overdose is unlikely to cause significant toxicity. It is recommended to contact a poison control center for further information should an overdose situation present itself.

Drug Interactions

Concomitant administration of IV acyclovir with nephrotoxic medications may increase the potential for nephrotoxicity occurring. Amphotericin B may potentiate the antiviral effects of acyclovir (but it also increases chances for development of nephrotoxicity).

Doses for birds:

For treatment of Pacheco’s Disease:

a)    80 mg/kg PO q8h or 40 mg/kg q8h IM (do not use parenterally for greater than 72 hours as it can cause tissue necrosis at site of injection)

b)

b) 80 mg/kg in oral suspension once daily PO; mix suspension with peanut butter or add to drinking water 50 mg in 4 oz of water for 7-14 days.

Doses for cats:

In cases of confirmed feline herpes virus infection (corneal and/or conjunctival) in which resolution is not achieved with time, time + antiviral topical agents: One 200 mg capsule PO qid. Mixed results have been achieved. It is important to monitor the CBC of cats. Leukopenia and a mild non regenerative anemia which reversed with cessation of treatment have been noted in some cats.

Monitoring Parameters

1) Renal function tests (BUN, Serum Cr) with prolonged or IV therapy; 2) Cats: CBC

Dosage Forms – Preparations – FDA Approval Status – Withholding Times

Veterinary-Approved Products:

None

Human-Approved Products:

Acyclovir Tablets: 400 mg, 800 mg; Zovirax ®, (Glaxo Wellcome); generic (Rx)

Acyclovir Capsules 200 mg, 400 mg and 800 mg tablets; Zovirax® (Glaxo Wellcome); generic (Rx)

Acyclovir Suspension: 200 mg/5 ml; Zovirax ® (Glaxo Wellcome) (Rx)

Acyclovir Sodium Parenteral Injection (for IV infusion Only), 500 mg/vial (as sodium) in 10 ml vials; 1000 mg/vial (as sodium) in 20 ml vials; Zovirax®{Glaxo Wellcome); (Rx)

Acyclovir is also available in a topical ointment.