Zovirax Information
Zovirax (Acyclovir) Description
Zovirax (Acyclovir) is the brand name for acyclovir, a synthetic nucleoside analogue active against herpes viruses. Zovirax (Acyclovir) Ointment 5% is a formulation for topical administration. Each gram of Zovirax (Acyclovir) Ointment 5% contains 50 mg of acyclovir in a polyethylene glycol (PEG) base.
Acyclovir is a white, crystalline powder with the molecular formula CHNO and a molecular weight of 225. The maximum solubility in water at 37°C is 2.5 mg/mL. The pka’s of acyclovir are 2.27 and 9.25.
The chemical name of acyclovir is 2-amino-1,9-dihydro-9-[(2-hydroxyethoxy)methyl]-6-purin-6-one; it has the following structural formula:
Zovirax (Acyclovir) Virology
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, and 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.
Zovirax (Acyclovir) Clinical Pharmacology
Two clinical pharmacology studies were performed with Zovirax (Acyclovir) Ointment 5% in immunocompromised adults at risk of developing mucocutaneous Herpes simplex virus infections or with localized varicella-zoster infections. These studies were designed to evaluate the dermal tolerance, systemic toxicity, and percutaneous absorption of acyclovir.
In 1 of these studies, which included 16 inpatients, the complete ointment or its vehicle were randomly administered in a dose of 1-cm strips (25 mg acyclovir) 4 times a day for 7 days to an intact skin surface area of 4.5 square inches. No local intolerance, systemic toxicity, or contact dermatitis were observed. In addition, no drug was detected in blood and urine by radioimmunoassay (sensitivity, 0.01 mcg/mL).
The other study included 11 patients with localized varicella-zoster infections. In this uncontrolled study, acyclovir was detected in the blood of 9 patients and in the urine of all patients tested. Acyclovir levels in plasma ranged from
Zovirax (Acyclovir) Clinical Trials
In clinical trials of initial genital herpes infections, Zovirax (Acyclovir) Ointment 5% has shown a decrease in healing time and, in some cases, a decrease in duration of viral shedding and duration of pain. In studies in immunocompromised patients mainly with herpes labialis, there was a decrease in duration of viral shedding and a slight decrease in duration of pain.
In studies of recurrent genital herpes and of herpes labialis in nonimmunocompromised patients, there was no evidence of clinical benefit; there was some decrease in duration of viral shedding.
Zovirax (Acyclovir) Indications And Usage
Zovirax (Acyclovir) Ointment 5% is indicated in the management of initial genital herpes and in limited non-life-threatening mucocutaneous Herpes simplex virus infections in immunocompromised patients.
Zovirax (Acyclovir) Contraindications
Zovirax (Acyclovir) Ointment 5% is contraindicated in patients who develop hypersensitivity to the components of the formulation.
Zovirax (Acyclovir) Warnings
Zovirax (Acyclovir) Ointment 5% is intended for cutaneous use only and should not be used in the eye.
Zovirax (Acyclovir) Adverse Reactions
In the controlled clinical trials, mild pain (including transient burning and stinging) was reported by about 30% of patients in both the active and placebo arms; treatment was discontinued in 2 of these patients. Local pruritus occurred in 4% of these patients. In all studies, there was no significant difference between the drug and placebo group in the rate or type of reported adverse reactions nor were there any differences in abnormal clinical laboratory findings.
Zovirax (Acyclovir) Overdosage
Overdosage by topical application of Zovirax (Acyclovir) Ointment 5% is unlikely because of limited transcutaneous absorption (see CLINICAL PHARMACOLOGY).
Zovirax (Acyclovir) Dosage And Administration
Apply sufficient quantity to adequately cover all lesions every 3 hours, 6 times per day for 7 days. The dose size per application will vary depending upon the total lesion area but should approximate a one-half inch ribbon of ointment per 4 square inches of surface area. A finger cot or rubber glove should be used when applying Zovirax (Acyclovir) to prevent autoinoculation of other body sites and transmission of infection to other persons.
Zovirax (Acyclovir) How Supplied
Each gram of Zovirax (Acyclovir) Ointment 5% contains 50 mg acyclovir in a polyethylene glycol base. It is supplied as follows:
15-g tubes (NDC 64455-993-94)
30-g tubes (NDC 64455-993-95)
Manufactured by
GlaxoSmithKlineResearch Triangle Park, NC 27709
for
BTA Pharmaceuticals, Inc. (subsidiary of Biovail Corporation)Bridgewater, NJ 08807
©2010, GlaxoSmithKline. All rights reserved.
September 2010 ZVO:3PI
Zovirax (Acyclovir)
