Zirgan

1 INDICATIONS AND USAGE ZIRGAN is indicated for the treatment of acute herpetic keratitis (dendritic ulcers) in adults and pediatric patients aged 2 years and older. ZIRGAN is a nucleoside analog antiviral indicated for the treatment of acute herpetic keratitis (dendritic ulcers) in adults and pediatric patients aged 2 years and older.

The recommended dosage is 1 drop in the affected eye 5 times per day (approximately every 3 hours while awake) until the corneal ulcer heals, and then 1 drop 3 times per day for 7 days. Apply 1 drop in the affected eye 5 times per day (approximately every 3 hours while awake) until the corneal ulcer heals, and then 1 drop 3 times per day for 7 days.

5 WARNINGS AND PRECAUTIONS ZIRGAN is indicated for topical ophthalmic use only. Patients should not wear contact lenses if they have signs or symptoms of herpetic keratitis or during the course of therapy with ZIRGAN.

5.1Topical Ophthalmic Use Only

ZIRGAN is indicated for topical ophthalmic use only.

5.2Avoidance 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 ZIRGAN.

5.3Risk of Contamination Do

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.

None. None.

8.1Pregnancy Risk Summary There

are no available human data on use of ZIRGAN or ganciclovir during pregnancy to inform any drug-associated risk. Intravenous administration of ganciclovir to pregnant mice or rabbits during organogenesis or during the pre/postnatal period did not produce adverse embryofetal or offspring effects at clinically relevant doses . The background risk in the U.S. general population of major birth defects is 2 to 4% and the risk of miscarriage is 15 to 20% of clinically recognized pregnancies. Data Animal Data Daily intravenous doses of ganciclovir were administered to pregnant mice [up to 108 mg/kg/day, approximately 1400 times the maximum recommended human ocular dose (RHOD) of 0.375 mg] and rabbits [up to 60 mg/kg/day, approximately 2400 times the maximum RHOD], and also to female mice [up to 90 mg/kg, approximately 1174 times the maximum RHOD] prior to mating, during gestation, and during lactation.

Fetal resorptions were present in at least 85% of rabbits and mice. Additional effects observed in rabbits included fetal growth retardation, embryolethality, teratogenicity, and/or maternal toxicity. Teratogenic changes included cleft palate, anophthalmia/microphthalmia, aplastic organs (kidney and pancreas), hydrocephaly and brachygnathia.

A maternal no observed adverse effect level (NOAEL) was observed at 36 mg/kg/day (approximately 470 times higher than the maximum RHOD, based on body surface area) in mice and at 6 mg/kg/day (approximately 240 times higher than the maximum RHOD, based on body surface area) in rabbits. In pre/postnatal development studies in mice, there were maternal/fetal toxicity and embryolethality which included fetal effects of hypoplasia of the testes and seminal vesicles in the male offspring, as well as pathologic changes in the nonglandular region of the stomach. A maternal no observed adverse effect level (NOAEL) was observed at 20 mg/kg/day (approximately 261 times higher than the maximum RHOD, based on body surface area).

Most common adverse reactions reported in patients were blurred vision (60%), eye irritation (20%), punctate keratitis (5%), and conjunctival hyperemia (5%). Most common adverse reactions were blurred vision (60%), eye irritation (20%), punctate keratitis (5%), and conjunctival hyperemia (5%). To report SUSPECTED ADVERSE REACTIONS, contact Bausch & Lomb Incorporated, at 1-800-553-5340 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.