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Ganciclovir Ophthalmic Gel

Dosage Form: ophthalmic gel

Indications and Usage for Ganciclovir Ophthalmic Gel

Ganciclovir Ophthalmic Gel 0.15% is indicated for the treatment of acute herpetic keratitis (dendritic ulcers).

Ganciclovir Ophthalmic Gel Dosage and Administration

The recommended dosing regimen for Ganciclovir Ophthalmic Gel 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.

Dosage Forms and Strengths

Ganciclovir Ophthalmic Gel contains 0.15% of ganciclovir in a sterile preserved topical ophthalmic gel.

Contraindications

None.

Warnings and Precautions

Topical Ophthalmic Use Only

Ganciclovir Ophthalmic Gel is indicated for topical ophthalmic use only.

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 Ganciclovir Ophthalmic Gel.

Adverse Reactions

Most common adverse reactions reported in patients were blurred vision (60%), eye irritation (20%), punctate keratitis (5%), and conjunctival hyperemia (5%).

USE IN SPECIFIC POPULATIONS

Pregnancy

Teratogenic Effects
Pregnancy Category C: Ganciclovir has been shown to be embryotoxic in rabbits and mice following intravenous administration and teratogenic in rabbits. Fetal resorptions were present in at least 85% of rabbits and mice administered 60 mg/kg/day and 108 mg/kg/day (approximately 10,000x and 17,000x the human ocular dose of 6.25 mcg/kg/day), respectively, assuming complete absorption. 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. In mice, effects observed were maternal/fetal toxicity and embryolethality. Daily intravenous doses of 90 mg/kg/day (14,000x the human ocular dose) administered to female mice prior to mating, during gestation, and during lactation caused hypoplasia of the testes and seminal vesicles in the month-old male offspring, as well as pathologic changes in the nonglandular region of the stomach [see Carcinogenesis, Mutagenesis, Impairment of Fertility (13.1)]. There are no adequate and well-controlled studies in pregnant women. Ganciclovir Ophthalmic Gel should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus.

Nursing Mothers

It is not known whether topical ophthalmic ganciclovir administration could result in sufficient systemic absorption to produce detectable quantities in breast milk. Caution should be exercised when Ganciclovir Ophthalmic Gel is administered to nursing mothers.

Pediatric Use

Safety and efficacy in pediatric patients below the age of 2 years have not been established.

Geriatric Use

No overall differences in safety or effectiveness have been observed between elderly and younger patients.

Ganciclovir Ophthalmic Gel Description

Ganciclovir Ophthalmic Gel 0.15% contains a sterile, topical antiviral for ophthalmic use. The chemical name is 9-[[2-hydroxy-1-(hydroxymethyl) ethoxy]methyl]guanine (CAS number 82410-32-0). Ganciclovir is represented by the following structural formula:

Ganciclovir has a molecular weight of 255.23, and the empirical formula is C9H13N5O4.

Each gram of gel contains: ACTIVE: ganciclovir 1.5 mg (0.15%). INACTIVES: Carbomer Homopolymer, water for injection, sodium hydroxide (to adjust the pH to 7.2-7.6), mannitol. PRESERVATIVE: benzalkonium chloride 0.075 mg (0.0075%).

Ganciclovir Ophthalmic Gel - Clinical Pharmacology

Mechanism of Action

Ganciclovir Ophthalmic Gel 0.15% contains the active ingredient, ganciclovir, which is a guanosine derivative that, upon phosphorylation, inhibits DNA replication by herpes simplex viruses (HSV). Ganciclovir is transformed by viral and cellular thymidine kinases (TK) to ganciclovir triphosphate, which works as an antiviral agent by inhibiting the synthesis of viral DNA in 2 ways: competitive inhibition of viral DNA-polymerase and direct incorporation into viral primer strand DNA, resulting in DNA chain termination and prevention of replication.

Pharmacokinetics

The estimated maximum daily dose of ganciclovir administered as 1 drop, 5 times per day is 0.375 mg. Compared to maintenance doses of systemically administered ganciclovir of 900 mg (oral valganciclovir) and 5 mg/kg (IV ganciclovir), the ophthalmically administered daily dose is approximately 0.04% and 0.1% of the oral dose and IV doses, respectively, thus minimal systemic exposure is expected.

Nonclinical Toxicology

Carcinogenesis, Mutagenesis, Impairment of Fertility

Ganciclovir was carcinogenic in the mouse at oral doses of 20 and 1,000 mg/kg/day (approximately 3,000x and 160,000x the human ocular dose of 6.25 mcg/kg/day, assuming complete absorption). At the dose of 1,000 mg/kg/day there was a significant increase in the incidence of tumors of the preputial gland in males, forestomach (nonglandular mucosa) in males and females, and reproductive tissues (ovaries, uterus, mammary gland, clitoral gland, and vagina) and liver in females. At the dose of 20 mg/kg/day, a slightly increased incidence of tumors was noted in the preputial and harderian glands in males, forestomach in males and females, and liver in females. No carcinogenic effect was observed in mice administered ganciclovir at 1 mg/kg/day (160x the human ocular dose). Except for histocytic sarcoma of the liver, ganciclovir-induced tumors were generally of epithelial or vascular origin. Although the preputial and clitoral glands, forestomach and harderian glands of mice do not have human counterparts, ganciclovir should be considered a potential carcinogen in humans. Ganciclovir increased mutations in mouse lymphoma cells and DNA damage in human lymphocytes in vitro at concentrations between 50 to 500 and 250 to 2,000 mcg/mL, respectively.

In the mouse micronucleus assay, ganciclovir was clastogenic at doses of 150 and 500 mg/kg (IV) (24,000x to 80,000x human ocular dose) but not 50 mg/kg (8,000x human ocular dose). Ganciclovir was not mutagenic in the Ames Salmonella assay at concentrations of 500 to 5,000 mcg/mL.

Ganciclovir caused decreased mating behavior, decreased fertility, and an increased incidence of embryolethality in female mice following intravenous doses of 90 mg/kg/day (approximately 14,000x the human ocular dose of 6.25 mcg/kg/day). Ganciclovir caused decreased fertility in male mice and hypospermatogenesis in mice and dogs following daily oral or intravenous administration of doses ranging from 0.2 to 10 mg/kg (30x to 1,600x the human ocular dose).

Clinical Studies

In one open-label, randomized, controlled, multicenter clinical trial which enrolled 164 patients with herpetic keratitis, Ganciclovir Ophthalmic Gel was non-inferior to acyclovir ophthalmic ointment, 3% in patients with dendritic ulcers. Clinical resolution (healed ulcers) at Day 7 was achieved in 77% (55/71) for Ganciclovir Ophthalmic Gel versus 72% (48/67) for acyclovir 3% (difference 5.8%, 95% CI - 9.6%-18.3%). In three randomized, single-masked, controlled, multicenter clinical trials which enrolled 213 total patients, Ganciclovir Ophthalmic Gel was noninferior to acyclovir ophthalmic ointment 3% in patients with dendritic ulcers. Clinical resolution at Day 7 was achieved in 72% (41/57) for Ganciclovir Ophthalmic Gel versus 69% (34/49) for acyclovir (difference 2.5%, 95% CI - 15.6%-20.9%).

How Supplied/Storage and Handling

Ganciclovir Ophthalmic Gel is supplied as 5 grams of a sterile, preserved, clear, colorless, topical ophthalmic gel containing 0.15% of ganciclovir in a polycoated aluminum tube with a white polyethylene tip and cap and protective band (NDC 69292-015-35).

Storage

Store at 15°C-25°C (59°F-77°F). Do not freeze.

Patient Counseling Information

This product is sterile when packaged. Patients should be advised not to allow the dropper tip to touch any surface, as this may contaminate the gel. If pain develops, or if redness, itching, or inflammation becomes aggravated, the patient should be advised to consult a physician. Patients should be advised not to wear contact lenses when using Ganciclovir Ophthalmic Gel.

Manufactured for:
Amici Pharmaceuticals
Melville, NY 11747 USA

Manufactured by:
Bausch & Lomb Incorporated
Tampa, FL 33637 USA

©Bausch & Lomb Incorporated

9575100 (flat)

9575200 (folded)

PACKAGE LABEL - PRINCIPAL DISPLAY PANEL

NDC 69292-015-35

Ganciclovir
Ophthalmic
Gel
0.15%

Sterile

FOR OPHTHALMIC
USE ONLY

Rx only

5 g

amici
pharmaceuticals

GANCICLOVIR 
ganciclovir gel
Product Information
Product Type HUMAN PRESCRIPTION DRUG LABEL Item Code (Source) NDC:69292-015
Route of Administration OPHTHALMIC DEA Schedule     
Active Ingredient/Active Moiety
Ingredient Name Basis of Strength Strength
GANCICLOVIR (GANCICLOVIR) GANCICLOVIR 1.5 mg  in 1 g
Inactive Ingredients
Ingredient Name Strength
CARBOMER HOMOPOLYMER TYPE B (ALLYL PENTAERYTHRITOL CROSSLINKED)  
WATER  
SODIUM HYDROXIDE  
MANNITOL  
BENZALKONIUM CHLORIDE  
Packaging
# Item Code Package Description
1 NDC:69292-015-35 1 TUBE, WITH APPLICATOR in 1 CARTON
1 5 g in 1 TUBE, WITH APPLICATOR
Marketing Information
Marketing Category Application Number or Monograph Citation Marketing Start Date Marketing End Date
NDA authorized generic NDA022211 09/08/2017
Labeler - Amici Pharmaceuticals LLC (079536824)
Establishment
Name Address ID/FEI Operations
Bausch & Lomb Incorporated 079587625 MANUFACTURE(69292-015), PACK(69292-015)
Revised: 11/2016
 
Amici Pharmaceuticals LLC
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