Avaclyr

1 INDICATIONS AND USAGE AVACLYR is a sterile topical antiviral indicated for the treatment of acute herpetic keratitis (dendritic ulcers) in patients with herpes simplex (HSV-1 and HSV-2) virus. AVACLYR (acyclovir ophthalmic ointment) 3%, a herpes simplex virus nucleoside analog DNA polymerase inhibitor, is indicated in the treatment of acute herpetic keratitis (dendritic ulcers) in patients with herpes simplex (HSV-1 and HSV-2) virus.

2 DOSAGE AND ADMINISTRATION The recommended dosing regimen is to apply a 1 cm ribbon of ointment in the lower cul-de-sac of the affected eye 5 times per day (approximately every 3 hours while awake) until the corneal ulcer heals and then a 1 cm ribbon 3 times per day for 7 days. Apply a 1 cm ribbon in the lower cul-de-sac of the affected eye 5 times per day until healed then 3 times per day for 7 days. ( 2 )

5 WARNINGS AND PRECAUTIONS AVACLYR is indicated for topical ophthalmic use. ( 5.1 ) Patients should not wear contact lenses if they have signs or symptoms of herpetic keratitis or during the course of therapy with AVACLYR. ( 5.2 ) 5.1 Topical Ophthalmic Use AVACLYR is indicated for topical ophthalmic use. 5.2 Avoidance of Contact Lenses Patients should not wear contact lenses if they have signs or symptoms of herpetic keratitis or during the course of therapy with AVACLYR. 5.3 Risk of Contamination This product is sterile when packaged. Patients should be advised to not allow the tip of the container to touch any surface, as this may contaminate the ointment. If pain develops, or if redness, itching, or inflammation becomes aggravated, the patient should be advised to consult a physician.

4 CONTRAINDICATIONS AVACLYR is contraindicated for patients who develop sensitivity to acyclovir or valacyclovir. AVACLYR is contraindicated in patients with a known hypersensitivity to acyclovir or valacyclovir.

7 DRUG INTERACTIONS No clinically significant interactions have been identified resulting from topical administration of other drugs concomitantly with AVACLYR.

8.1 Pregnancy Risk Summary A prospective epidemiologic registry of acyclovir use from 1984 to 1999 indicated that the occurrence rate of birth defects in women exposed to systemically administered acyclovir during the first trimester of pregnancy (period of organogenesis) approximated that found in the general population. Likewise, oral and subcutaneous administration of acyclovir to pregnant mice, rats, and rabbits during organogenesis did not produce teratogenicity at clinically relevant doses (see Animal Data ) . Data Human Data 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 systemically administered 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. The human maternal plasma level of acyclovir following ocular administration is unknown. Animal Data In published animal reproduction studies, acyclovir was not maternally toxic and did not produce teratogenicity in the mouse at oral doses up to 450 mg/kg/day (1100 times the maximum recommended human ophthalmic dose [RHOD] on a mg/m 2 basis, assuming 100% absorption), or in the rat and rabbit at subcutaneous doses up to 50 mg/kg/day (approximately 250 and 500 times the RHOD, respectively) when administered throughout the period of organogenesis. Administration of acyclovir from postnatal days 3 to 21 did not produce adverse effects in neonatal rats at subcutaneous doses less than or equal to 20 mg/kg/day (100 times the RHOD).

6 ADVERSE REACTIONS The most common adverse reactions (2-10%) reported in patients were eye pain (stinging), punctate keratitis and follicular conjunctivitis. Rare reports of blepharitis and very rare reports of immediate hypersensitivity reactions including angioedema and urticaria have been observed post-marketing in patients taking AVACLYR. The most common adverse reactions (2 to 10%) reported in patients were eye pain (stinging), punctate keratitis and follicular conjunctivitis. ( 6 ) To report SUSPECTED ADVERSE REACTIONS, contact Fera Pharmaceuticals, LLC at (414) 434-6604 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch .