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. 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 Solco Healthcare US, LLC at 1-866-257-2597 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch .

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

DESCRIPTION Acyclovir is a synthetic nucleoside analogue active against herpes viruses. Acyclovir ointment, USP 5% is a formulation for topical administration. Each gram of acyclovir ointment 5% contains 50 mg of acyclovir, USP in a polyethylene glycol (PEG) base. Acyclovir is a white to off-white, crystalline powder with the molecular formula C 8 H 11 N 5 O 3 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 H -purin-6-one; it has the following structural formula: structural formula

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 acyclovir ointment 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.

INDICATIONS AND USAGE Acyclovir ointment 5% is indicated in the management of initial genital herpes and in limited nonlifethreatening mucocutaneous HSV infections in immune compromised patients.

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

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

CLINICAL PHARMACOLOGY Two clinical pharmacology studies were performed with acyclovir ointment 5% in immune compromised 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 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 <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.

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1

ACYCLOVIR acyclovir ACYCLOVIR ACYCLOVIR POLYETHYLENE GLYCOL 1450 POLYETHYLENE GLYCOL 300

ANDA212202

ACYCLOVIR

acyclovir

43547-499

HUMAN PRESCRIPTION DRUG

TOPICAL

Package/Label Display Panel Carton Label-15 g Rx only NDC 43547-499-42 Acyclovir Ointment, USP 5% 15 g Each gram contains acyclovir, USP 50 mg in a polyethylene glycol base. USUAL DOSAGE: Apply 6 times a day (every 3 hours) for 7 days. See prescribing information for dosage information. Store at 15°C to 25°C (59°F to 77°F) in a dry place. Manufactured by: UBI Pharma Inc. No. 45, Guangfu N. Rd., Hukou, Hsinchu 303036, Taiwan (TWN) Distributed by: Solco Healthcare US, LLC Somerset, NJ 08873, USA Rev.: 09/2019 Container Label 15 g

Acyclovir Ointment 5% R X only

HOW SUPPLIED Each gram of acyclovir ointment, USP 5% contains 50 mg acyclovir, USP in a polyethylene glycol base. Acyclovir ointment, USP 5% is a white to off white ointment, free of foreign matters, free of lumps, translucent, homogeneous, and no phase separation. It is supplied as follows: 15 g tubes NDC 43547-499-42 30 g tubes NDC 43547-499-41 Store at 15° to 25°C (59° to 77°F) in a dry place. Manufactured by: UBI Pharma Inc. No. 45, Guangfu N. Rd., Hukou, Hsinchu 30351, Taiwan (TWN) Distributed by: Solco Healthcare US, LLC Somerset, NJ 08873, USA Rev.: 09/2019 L187-01

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 acyclovir capsules, tablets, and oral suspension and acyclovir 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. 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. 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 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. 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.