ZOVIRAX Cream should be applied 5 times per day for 4 days. Therapy should be initiated as early as possible following onset of signs and symptoms (i.e., during the prodrome or when lesions appear). For adolescents 12 years of age and older, the dosage is the same as in adults.
ZOVIRAX is the brand name for acyclovir, a synthetic nucleoside analogue active against herpesviruses. ZOVIRAX Cream 5% is a formulation for topical administration. Each gram of ZOVIRAX Cream 5% contains 50 mg of acyclovir and the following inactive ingredients: cetostearyl alcohol, mineral oil, poloxamer 407, propylene glycol, sodium lauryl sulfate, water, and white petrolatum. Acyclovir is a white, crystalline powder with the molecular formula CHNOand 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:
Pharmacokinetics:<br/>Adults: A clinical pharmacology study was performed with ZOVIRAX Cream in adult volunteers to evaluate the percutaneous absorption of acyclovir. In this study, which included 6 male volunteers, the cream was applied to an area of 710 cmon the backs of the volunteers 5 times daily at intervals of 2 hours for a total of 4 days. The weight of cream applied and urinary excretion of acyclovir were measured daily. Plasma concentration of acyclovir was assayed 1 hour after the final application. The average daily urinary excretion of acyclovir was approximately 0.04% of the daily applied dose. Plasma acyclovir concentrations were below the limit of detection (0.01��M) in 5 subjects and barely detectable (0.014��M) in 1 subject. Systemic absorption of acyclovir from ZOVIRAX Cream is minimal in adults.<br/>Pediatric Patients: The systemic absorption of acyclovir following topical application of cream has not been evaluated in patients<18 years of age.
ZOVIRAX Cream is contraindicated in patients with known hypersensitivity to acyclovir, valacyclovir, or any component of the formulation.
Each gram of ZOVIRAX Cream 5% contains 50 mg acyclovir in an aqueous cream base. ZOVIRAX Cream is supplied as follows: 2-g tubes (NDC 64455-994-42). 5-g tubes (NDC 64455-994-45). Store at or below 25��C (77��F); excursions permitted to 15��to 30��C (59��to 86��F) (see USP Controlled Room Temperature). Manufactured by GlaxoSmithKline Research Triangle Park, NC 27709 for Bridgewater, NJ 08807 ��2004, GlaxoSmithKline. All rights reserved. January 2004 RL-2061
General: ZOVIRAX Cream is intended for cutaneous use only and should not be used in the eye or inside the mouth or nose. ZOVIRAX Cream should only be used on herpes labialis on the affected external aspects of the lips and face. Because no data are available, application to human mucous membranes is not recommended. ZOVIRAX Cream has a potential for irritation and contact sensitization (see ADVERSE REACTIONS). The effect of ZOVIRAX Cream has not been established in immunocompromised patients.<br/>Information for Patients: Please see Patient Information About ZOVIRAX Cream.<br/>Drug Interactions: Clinical experience has identified no interactions resulting from topical or systemic administration of other drugs concomitantly with ZOVIRAX Cream.<br/>Carcinogenesis, Mutagenesis, Impairment of Fertility: Systemic exposure following topical administration of acyclovir is minimal. Dermal carcinogenicity studies were not conducted. Results from the studies of carcinogenesis, mutagenesis and fertility are not included in the full prescribing information for ZOVIRAX Cream due to the minimal exposures of acyclovir that result from dermal application. Information on these studies is available in the full prescribing information for ZOVIRAX Capsules, Tablets, and Suspension and ZOVIRAX for Injection.<br/>Pregnancy:<br/>Teratogenic Effects: Pregnancy Category B. Acyclovir was not teratogenic in the mouse, rabbit, or rat at exposures greatly in excess of human exposure. There are no adequate and well-controlled studies of systemic acyclovir in pregnant women. A prospective epidemiologic registry of acyclovir use during pregnancy was established in 1984 and completed in April 1999. There were 749 pregnancies followed in women exposed to systemic acyclovir during the first trimester of pregnancy resulting in 756 outcomes. The occurrence rate of birth defects approximates that found in the general population. However, the small size of the registry is insufficient to evaluate the risk for less common defects or to permit reliable or definitive conclusions regarding the safety of acyclovir in pregnant women and their developing fetuses. Systemic acyclovir should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus.<br/>Nursing Mothers: It is not known whether topically applied acyclovir is excreted in breast milk. Systemic exposure following topical administration is minimal. After oral administration of ZOVIRAX, acyclovir concentrations have been documented in breast milk in 2 women and ranged from 0.6 to 4.1 times the corresponding plasma 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 herpetic lesions near or on the breast should avoid nursing.<br/>Geriatric Use: Clinical studies of acyclovir cream did not include sufficient numbers of subjects aged 65 and over to determine whether they respond differently from younger subjects. Other reported clinical experience has not identified differences in responses between the elderly and younger patients. Systemic absorption of acyclovir after topical administration is minimal (see CLINICAL PHARMACOLOGY).<br/>Pediatric Use: Safety and effectiveness in pediatric patients less than 12 years of age have not been established.
Overdosage by topical application of ZOVIRAX Cream is unlikely because of minimal systemic exposure (see CLINICAL PHARMACOLOGY).
In 5 double-blind, placebo-controlled trials, 1,124 patients were treated with ZOVIRAX Cream and 1,161 with placebo (vehicle) cream. ZOVIRAX Cream was well tolerated; 5% of patients on ZOVIRAX Cream and 4% of patients on placebo reported local application site reactions. The most common adverse reactions at the site of topical application were dry lips, desquamation, dryness of skin, cracked lips, burning skin, pruritus, flakiness of skin, and stinging on skin; each event occurred in less than 1% of patients receiving ZOVIRAX Cream and vehicle. Three patients on ZOVIRAX Cream and 1 patient on placebo discontinued treatment due to an adverse event. An additional study, enrolling 22 healthy adults, was conducted to evaluate the dermal tolerance of ZOVIRAX Cream compared with vehicle using single occluded and semi-occluded patch testing methodology. Both ZOVIRAX Cream and vehicle showed a high and cumulative irritation potential. Another study, enrolling 251 healthy adults, was conducted to evaluate the contact sensitization potential of ZOVIRAX Cream using repeat insult patch testing methodology. Of 202 evaluable subjects, possiblecutaneous sensitization reactions were observed in the same 4 (2%) subjects with both ZOVIRAX Cream and vehicle, and these reactions to both ZOVIRAX Cream and vehicle were confirmed in 3 subjects upon rechallenge. The sensitizing ingredient(s) has not been identified. The safety profile in patients 12 to 17 years of age was similar to that observed in adults.<br/>Observed During Clinical Practice: In addition to adverse events reported from clinical trials, the following events have been identified during post-approval use of acyclovir cream. Because they are reported voluntarily from a population of unknown size, estimates of frequency cannot be made. These events have been chosen for inclusion due to a combination of their seriousness, frequency of reporting, or potential causalconnection to acyclovir cream.<br/>General: Angioedema, anaphylaxis.<br/>Skin: Contact dermatitis, eczema, application site reactions including signs and symptoms of inflammation.
ZOVIRAX Cream is indicated for the treatment of recurrent herpes labialis (cold sores) in adults and adolescents (12 years of age and older).