ADVERSE REACTIONS SECTION.

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 two 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.. Observed During Clinical Practice: Based on clinical practice experience in patients treated with Acyclovir Ointment in the U.S., spontaneously reported adverse events 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 underlying disease 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 Actavis at 1-888-838-2872 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.

CARCINOGENESIS & MUTAGENESIS & IMPAIRMENT OF FERTILITY SECTION.

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 Acyclovir Ointment 5% 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(R) Capsules, Tablets, and Suspension and ZOVIRAX(R) for Injection.

CLINICAL PHARMACOLOGY SECTION.

CLINICAL PHARMACOLOGY. Two clinical pharmacology studies were performed with acyclovir ointment 5% in immunocompromised adults at risk of developing mucocutaneous HSV infections or with localized varicella zoster infections. These studies were designed to evaluate the dermal tolerance, systemic toxicity, and percutaneous absorption of acyclovir.In one of these studies, which included 16 inpatients, the complete ointment or its vehicle were randomly administered in dose of 1-cm strips (25 mg acyclovir) times day for 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 patients and in the urine of all patients tested. Acyclovir levels in plasma ranged from <0.01 to 0.28 mcg/mL in patients with normal renal function, and from <0.01 to 0.78 mcg/mL in one 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 STUDIES SECTION.

CLINICAL TRIALS. In clinical trials of initial genital herpes infections, Acyclovir Ointment 5% has shown decrease in healing time and, in some cases, decrease in duration of viral shedding and duration of pain. In studies in immunocompromised patients primarily with herpes labialis, there was decrease in duration of viral shedding and 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.

CONTRAINDICATIONS SECTION.

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

DESCRIPTION SECTION.

DESCRIPTION. Acyclovir is synthetic nucleoside analogue active against herpes viruses. Acyclovir Ointment 5% is formulation for topical administration. Each gram of Acyclovir Ointment 5% contains 50 mg of acyclovir in polyethylene glycol (PEG) base.Acyclovir is white to off-white crystalline powder with the molecular formula C8H11N5O3 and molecular weight of 225.20. The maximum solubility in water at 37C is 2.5 mg/mL. The pkas 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:. Chemical Structure.

DOSAGE & ADMINISTRATION SECTION.

DOSAGE AND ADMINISTRATION. Apply sufficient quantity to adequately cover all lesions every hours, times per day for days. The dose size per application will vary depending upon the total lesion area but should approximate one-half inch ribbon of ointment per square inches of surface area. finger cot or rubber glove should be used when applying acyclovir to prevent autoinoculation of other body sites and transmission of infection to other persons. Therapy should be initiated as early as possible following onset of signs and symptoms.

DRUG INTERACTIONS SECTION.

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

GENERAL PRECAUTIONS SECTION.

General: The recommended dosage, frequency of applications, and length of treatment should not be exceeded (see DOSAGE AND ADMINISTRATION). There are no data to support the use of Acyclovir Ointment 5% to prevent transmission of infection to other persons or prevent recurrent infections when applied in the absence of signs and symptoms. Acyclovir Ointment 5% should not be used for the prevention of recurrent HSV infections. Although clinically significant viral resistance associated with the use of Acyclovir Ointment 5% has not been observed, this possibility exists.

GERIATRIC USE SECTION.

Geriatric Use: Clinical studies of Acyclovir Ointment 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).

HOW SUPPLIED SECTION.

HOW SUPPLIED. Each gram of Acyclovir Ointment 5% contains 50 mg acyclovir in polyethylene glycol base. It is supplied as follows: 30 tubes NDC 0591-1159-30. 30 tubes NDC 0591-1159-30. Store at 15 to 25C (59 to 77F) in dry place.

INDICATIONS & USAGE SECTION.

INDICATIONS AND USAGE. Acyclovir Ointment 5% is indicated in the management of initial genital herpes and in limited non-lifethreatening mucocutaneous HSV infections in immunocompromised patients.

NURSING MOTHERS SECTION.

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 Acyclovir, acyclovir concentrations have been documented in breast milk in two women and ranged from 0.6 to 4.1 times the corresponding plasma levels. These concentrations would potentially expose the nursing infant to 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.

OVERDOSAGE SECTION.

OVERDOSAGE. Overdosage by topical application of Acyclovir Ointment 5% is unlikely because of limited transcutaneous absorption (see CLINICAL PHARMACOLOGY).

PACKAGE LABEL.PRINCIPAL DISPLAY PANEL.

PRINCIPAL DISPLAY PANEL 30 Tube Carton. Net Wt. 30 gACYCLOVIR OINTMENT5%FOR CUTANEOUS USE ONLYNDC 0591-1159-30Each gram contains:50 mg acyclovirin polyethyleneglycol base.ActavisRx only. carton30g.

PEDIATRIC USE SECTION.

Pediatric Use: Safety and effectiveness in pediatric patients have not been established.

PRECAUTIONS SECTION.

PRECAUTIONS. General: The recommended dosage, frequency of applications, and length of treatment should not be exceeded (see DOSAGE AND ADMINISTRATION). There are no data to support the use of Acyclovir Ointment 5% to prevent transmission of infection to other persons or prevent recurrent infections when applied in the absence of signs and symptoms. Acyclovir Ointment 5% should not be used for the prevention of recurrent HSV infections. Although clinically significant viral resistance associated with the use of Acyclovir Ointment 5% has not been observed, this possibility exists.. Drug Interactions: Clinical experience has identified no interactions resulting from topical or systemic administration of other drugs concomitantly with Acyclovir Ointment 5%.. 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 Acyclovir Ointment 5% 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(R) Capsules, Tablets, and Suspension and ZOVIRAX(R) for Injection.. Pregnancy: Teratogenic Effects: 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. 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.. 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 Acyclovir, acyclovir concentrations have been documented in breast milk in two women and ranged from 0.6 to 4.1 times the corresponding plasma levels. These concentrations would potentially expose the nursing infant to 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.. Geriatric Use: Clinical studies of Acyclovir Ointment 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).. Pediatric Use: Safety and effectiveness in pediatric patients have not been established.

PREGNANCY SECTION.

Pregnancy: Teratogenic Effects: 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. 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.

SPL UNCLASSIFIED SECTION.

AcyclovirOintment 5%.

STORAGE AND HANDLING SECTION.

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

TERATOGENIC EFFECTS SECTION.

Pregnancy: Teratogenic Effects: 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. 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.

WARNINGS SECTION.

WARNINGS. Acyclovir Ointment 5% is intended for cutaneous use only and should not be used in the eye.