Zovirax Ointment

DESCRIPTION

ZOVIRAXis the brand name foracyclovir, a synthetic nucleoside analogue active againstherpesviruses. ZOVIRAXOintment5% is a formulation for topical administration. Eachgramof ZOVIRAX Ointment 5% contains 50 mg of acyclovir in a polyethylene glycol (PEG) base.

Acyclovir is a white, crystalline powder with the molecular formula C₈H₁₁N₅O₃and 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]-6H-purin-6-one; it has the following structural formula:

INDICATIONS

ZOVIRAX Ointment 5% is indicated in the management of initial genital herpes and in limited non-lifethreatening mucocutaneous HSV infections inimmunocompromised patients.

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 totallesion 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 applyingZOVIRAX to prevent autoinoculation of other body sites and transmission of infection to other persons.Therapy should be initiated as early as possible followingonset of signs and symptoms.

HOW SUPPLIED

Storage And Handling

Each gram of ZOVIRAX Ointment 5% contains 50 mg acyclovir in a polyethylene glycol base. It is supplied as follows:

30 g tubes -NDC0187-0993-95

Store at 15° to 25°C (59° to 77°F) in a dry place.

Manufactured by: Bausch Health Companies Inc. Laval, Quebec H7L 4A8, Canada. Revised: Oct 2020.

SIDE EFFECTS

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 two of these patients. Local pruritus occurred in 4% of these patients. In all studies, there was no significant difference between the drugand placebo group in the rate or type of reported adverse reactions nor were there any differences in abnormal clinical laboratory findings.

Observed During Clinical Practice

Based on clinical practice experience in patients treated with ZOVIRAX Ointment in the U.S., spontaneously reported adverseevents are uncommon. Data are insufficient to support an estimate of their incidence or to establish causation. These events may also occur as part of the underlyingdisease process. Voluntary reports of adverse events that have been received since market introduction include:

General:Edema and/or pain at the application site.

Skin:Pruritus, rash.

To report SUSPECTED ADVERSE REACTIONS, contact Bausch Health US, LLC at 1-800-321-4576 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.

DRUG INTERACTIONS

Clinical experience has identified no interactions resulting from topical or systemic administration of other drugs concomitantly with ZOVIRAX Ointment 5%.

警告

ZOVIRAX Ointment 5% is intended forcutaneoususe only and should not be used in the eye.

PRECAUTIONS

General

The recommended dosage, frequency of applications, and length of treatment should not be exceeded (seeDOSAGE AND ADMINISTRATION). There areno data to support the use of ZOVIRAX Ointment 5% to prevent transmission of infection to other persons or preventrecurrentinfections when applied in the absenceof signs and symptoms. ZOVIRAX Ointment 5% should not be used for the prevention of recurrent HSV infections. Although clinically significant viral resistanceassociated with the use of ZOVIRAX Ointment 5% has not been observed, this possibility exists.

Carcinogenesis, Mutagenesis, Impairment Of Fertility

Systemic exposure following topical administration of acyclovir is minimal.真皮carcinogenicity studieswere not conducted. Results from the studies of carcinogenesis,mutagenesis, and fertility are not included in the full prescribing information for ZOVIRAX Ointment5% due to the minimal exposures of acyclovir that result from dermal application. Information on these studies is available in the full prescribing information forZOVIRAX Capsules, Tablets, and Suspension and ZOVIRAX for Injection.

Pregnancy

Teratogenic Effects

Acyclovir was notteratogenicin the mouse, rabbit, or rat at exposures greatly in excess of human exposure. There are no adequateand well-controlled studies of systemic acyclovir in pregnant women. Aprospectiveepidemiologic registry of acyclovir use during pregnancy was established in 1984and completed in April 1999. There were 749 pregnancies followed in women exposed tosystemicacyclovir during the first trimester of pregnancy resulting in 756outcomes. The occurrence rate of birth defects approximates that found in the general population. However, the small size of the registry is insufficient to evaluate therisk for less common defects or to permit reliable or definitive conclusions regarding the safety of acyclovir in pregnant women and their developing fetuses. Systemicacyclovir should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus.

Nursing Mothers

It is not known whether topically applied acyclovir is excreted in breast milk. Systemic exposure followingtopicaladministration is minimal. Afteroraladministration of ZOVIRAX, acyclovir concentrations have been documented in breast milk in two women and ranged from 0.6 to 4.1 times the correspondingplasma levels. These concentrations would potentially expose the nursing infant to a dose of acyclovir up to 0.3 mg/kg/day. Nursing mothers who have active herpeticlesions near or on the breast should avoid nursing.

Geriatric Use

Clinical studies of ZOVIRAX Ointment did not include sufficient numbers of subjects aged 65 and over to determine whether they respond differentlyfrom younger subjects. Other reported clinical experience has not identified differences in responses between the elderly and younger patients. Systemic absorption ofacyclovir after topical administration is minimal (seeCLINICAL PHARMACOLOGY).

体育diatric Use

Safety and effectiveness in pediatric patients have not been established.

OVERDOSE

Overdosage by topical application of ZOVIRAX Ointment 5% is unlikely because of limited transcutaneous absorption (seeCLINICAL PHARMACOLOGY).

CONTRAINDICATIONS

ZOVIRAX Ointment 5% is contraindicated in patients who develop hypersensitivity to the components of the formulation.

CLINICAL PHARMACOLOGY

Virology

Mechanism Of Antiviral Action

Acyclovir is a syntheticpurinenucleoside analogue within vitroandin vivoinhibitory activity against herpes simplex virus types 1 (HSV-1), 2 (HSV-2), andvaricella-zoster virus (VZV).

The inhibitory activity of acyclovir is highly selective due to itsaffinityfor the enzyme thymidine kinase (TK) encoded by HSV and VZV. This viral enzyme converts acyclovir into acyclovir monophosphate, a核苷酸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 viralDNA polymerase, 2) incorporation into and termination of the growing viral DNA chain, and 3) inactivation of the viral DNA polymerase. The greaterantiviralactivity of acyclovir against HSV compared to VZV is due to its more efficientphosphorylationby the viral TK.

Antiviral Activities

Thequantitativerelationship between thein vitrosusceptibility of herpes viruses to antivirals and the clinical response to therapy has not been established in humans, and virus sensitivity testing has not been standardized. Sensitivity testing results, expressed as the concentration of drug required to inhibit by 50% the growth of virus in cell culture (IC50), vary greatly depending upon a number of factors. Using plaque-reduction assays, the IC50 against herpes simplex virus isolates ranges from 0.02 to 13.5 mcg/mL for HSV-1 and from 0.01 to 9.9 mcg/mL for HSV-2. The IC50 for acyclovir against most laboratory strains and clinical isolates of VZV ranges from 0.12 to 10.8 mcg/mL. Acyclovir also demonstrates activity against the Oka vaccine strain of VZV with a mean IC50 of 1.35 mcg/mL.

Drug Resistance

Resistance of HSV and VZV to acyclovir can result fromqualitativeand quantitative changes in the viral TK and/or DNA polymerase. Clinical isolates of HSV and VZV with reduced susceptibility to acyclovir have been recovered fromimmunocompromisedpatients, especially with advancedHIVinfection. While most of the acyclovir-resistant mutants isolated thus far from immunocompromised patients have been found to be TK-deficient mutants, other mutants involving the viral TK gene (TK partial and TK altered) and DNA polymerase have been isolated. TK-negative mutants may cause severe disease in infants and immunocompromised adults. The possibility of viral resistance to acyclovir should be considered in patients who show poor clinical response during therapy.

Two clinicalpharmacologystudies were performed with ZOVIRAX 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, andpercutaneousabsorption of acyclovir.

In 1 of these studies, which included 16 inpatients, the complete ointment or its vehicle wererandomlyadministered 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接触性皮炎were observed. In addition, no drug was detected in blood and urine byradioimmunoassay(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 < 0.01 to 0.28 mcg/mL in 8 patients with normal renal function, and from < 0.01 to 0.78 mcg/mL in 1 patient with impaired renal function. Acyclovir excreted in the urine ranged from < 0.02% to 9.4% of the daily dose. Therefore, systemic absorption of acyclovir after topical application is minimal.

Clinical Trials

In clinical trials of initialgenital herpesinfections, ZOVIRAX 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 recurrentgenitalherpes and of herpes labialis in nonimmunocompromised patients, there was no evidence of clinical benefit; there was some decrease in duration of viral shedding.

PATIENT INFORMATION

No information provided. Please refer to the警告andPRECAUTIONSsections.