NURSING MOTHERS SECTION.

Nursing Mothers. It is not known whether this drug is excreted in human milk. Because many drugs are excreted in human milk, caution should be exercised when polymyxin sulfate and trimethoprim ophthalmic solution is administered to nursing woman.

PACKAGE LABEL.PRINCIPAL DISPLAY PANEL.

Principal Display Panel. NDC24208-315-10 Polymyxin BSulfate andTrimethoprimOphthalmicSolution, USP (Sterile) FOR TOPICALAPPLICATIONIN THE EYERx only10 mLBAUSCH LOMB9534002AB31509. Carton.

PEDIATRIC USE SECTION.

Pediatric Use. Safety and effectiveness in children below the age of months have not been established (see WARNINGS).

PRECAUTIONS SECTION.

PRECAUTIONS. General. As with other antimicrobial preparations, prolonged use may result in overgrowth of nonsusceptible organisms, including fungi. If superinfection occurs, appropriate therapy should be initiated.. Information for Patients. Avoid contaminating the applicator tip with material from the eye, fingers, or other source. This precaution is necessary if the sterility of the drops is to be maintained.If hypersensitivity reactions such as redness, irritation, swelling or pain persists or increases, discontinue use immediately and contact your physician.Patients should be advised not to wear contact lenses if they have signs and symptoms of ocular bacterial infections.. Carcinogenesis, Mutagenesis, Impairment of Fertility. Carcinogenesis:Long-term studies in animals to evaluate carcinogenic potential have not been conducted with polymyxin sulfate or trimethoprim. Mutagenesis:Trimethoprim was demonstrated to be non-mutagenic in the Ames assay. In studies at two laboratories no chromosomal damage was detected in cultured Chinese hamster ovary cells at concentrations approximately 500 times human plasma levels after oral administration; at concentrations approximately 1,000 times human plasma levels after oral administration in these same cells, low level of chromosomal damage was induced at one of the laboratories. Studies to evaluate mutagenic potential have not been conducted with polymyxin sulfate. Impairment of Fertility:Polymyxin sulfate has been reported to impair the motility of equine sperm, but its effects on male or female fertility are unknown. No adverse effects on fertility or general reproductive performance were observed in rats given trimethoprim in oral dosages as high as 70 mg/kg/day for males and 14 mg/kg/day for females.. Pregnancy. Teratogenic Effects. Animal reproduction studies have not been conducted with polymyxin sulfate. It is not known whether polymyxin sulfate can cause fetal harm when administered to pregnant woman or can affect reproduction capacity.Trimethoprim has been shown to be teratogenic in the rat when given in oral doses 40 times the human dose. In some rabbit studies, the overall increase in fetal loss (dead and resorbed and malformed conceptuses) was associated with oral doses times the human therapeutic dose.While there are no large well-controlled studies on the use of trimethoprim in pregnant women, Brumfitt and Pursell, in retrospective study, reported the outcome of 186 pregnancies during which the mother received either placebo or oral trimethoprim in combination with sulfamethoxazole. The incidence of congenital abnormalities was 4.5% (3 of 66) in those who received placebo and 3.3% (4 of 120) in those receiving trimethoprim and sulfamethoxazole. There were no abnormalities in the 10 children whose mothers received the drug during the first trimester. In separate survey, Brumfitt and Pursell also found no congenital abnormalities in 35 children whose mothers had received oral trimethoprim and sulfamethoxazole at the time of conception or shortly thereafter.Because trimethoprim may interfere with folic acid metabolism, trimethoprim should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus.. Nonteratogenic Effects. The oral administration of trimethoprim to rats at dose of 70 mg/kg/day commencing with the last third of gestation and continuing through parturition and lactation caused no deleterious effects on gestation or pup growth and survival.. Nursing Mothers. It is not known whether this drug is excreted in human milk. Because many drugs are excreted in human milk, caution should be exercised when polymyxin sulfate and trimethoprim ophthalmic solution is administered to nursing woman.. Pediatric Use. Safety and effectiveness in children below the age of months have not been established (see WARNINGS). Geriatric Use. No overall differences in safety or effectiveness have been observed between elderly and other adult patients.

NONTERATOGENIC EFFECTS SECTION.

Nonteratogenic Effects. The oral administration of trimethoprim to rats at dose of 70 mg/kg/day commencing with the last third of gestation and continuing through parturition and lactation caused no deleterious effects on gestation or pup growth and survival.

ADVERSE REACTIONS SECTION.

ADVERSE REACTIONS. The most frequent adverse reaction to polymyxin sulfate and trimethoprim ophthalmic solution is local irritation consisting of increased redness, burning, stinging, and/or itching. This may occur on instillation, within 48 hours, or at any time with extended use. There are also multiple reports of hypersensitivity reactions consisting of lid edema, itching, increased redness, tearing, and/or circumocular rash. Stevens-Johnson Syndrome/Toxic Epidermal Necrolysis (SJS/TEN) and anaphylaxis have been reported. Photosensitivity has been reported in patients taking oral trimethoprim.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.

CARCINOGENESIS & MUTAGENESIS & IMPAIRMENT OF FERTILITY SECTION.

Carcinogenesis, Mutagenesis, Impairment of Fertility. Carcinogenesis:Long-term studies in animals to evaluate carcinogenic potential have not been conducted with polymyxin sulfate or trimethoprim. Mutagenesis:Trimethoprim was demonstrated to be non-mutagenic in the Ames assay. In studies at two laboratories no chromosomal damage was detected in cultured Chinese hamster ovary cells at concentrations approximately 500 times human plasma levels after oral administration; at concentrations approximately 1,000 times human plasma levels after oral administration in these same cells, low level of chromosomal damage was induced at one of the laboratories. Studies to evaluate mutagenic potential have not been conducted with polymyxin sulfate. Impairment of Fertility:Polymyxin sulfate has been reported to impair the motility of equine sperm, but its effects on male or female fertility are unknown. No adverse effects on fertility or general reproductive performance were observed in rats given trimethoprim in oral dosages as high as 70 mg/kg/day for males and 14 mg/kg/day for females.

CLINICAL PHARMACOLOGY SECTION.

CLINICAL PHARMACOLOGY. Trimethoprim is synthetic antibacterial drug active against wide variety of aerobic gram-positive and gram-negative ophthalmic pathogens. Trimethoprim blocks the production of tetrahydrofolic acid from dihydrofolic acid by binding to and reversibly inhibiting the enzyme dihydrofolate reductase. This binding is stronger for the bacterial enzyme than for the corresponding mammalian enzyme and therefore selectively interferes with bacterial biosynthesis of nucleic acids and proteins.Polymyxin B, cyclic lipopeptide antibiotic, is bactericidal for variety of gram-negative organisms, especially Pseudomonas aeruginosa.It increases the permeability of the bacterial cell membrane by interacting with the phospholipid components of the membrane. Blood samples were obtained from 11 human volunteers at 20 minutes, hour and hours following instillation in the eye of drops of ophthalmic solution containing mg trimethoprim and 10,000 units polymyxin per mL. Peak serum concentrations were approximately 0.03 mcg/mL trimethoprim and unit/mL polymyxin B.MicrobiologyIn vitrostudies have demonstrated that the anti-infective components of trimethoprim sulfate and polymyxin sulfate ophthalmic solution are active against the following bacterial pathogens that are capable of causing external infections of the eye: Trimethoprim:Staphylococcus aureus and Staphylococcus epidermidis, Streptococcus pyogenes, Streptococcus faecalis, Streptococcus pneumoniae, Haemophilus influenzae, Haemophilus aegyptius, Escherichia coli, Klebsiella pneumoniae, Proteus mirabilis(indole-negative) Proteus vulgaris(indole-positive) Enterobacter aerogenesand Serratia marcescens.Polymyxin B:Pseudomonas aeruginosa, Escherichia coli, Klebsiella pneumoniae, Enterobacter aerogenes and Haemophilus influenzae.

CONTRAINDICATIONS SECTION.

CONTRAINDICATIONS. Polymyxin sulfate and trimethoprim ophthalmic solution is contraindicated in patients with known hypersensitivity to any of its components.

DESCRIPTION SECTION.

DESCRIPTION. Polymyxin sulfate and trimethoprim ophthalmic solution, USP is sterile antimicrobial solution for topical ophthalmic use. It has pH of 4.0 to 5.5 and osmolality of 270 to 310 mOsm/kg.Chemical Names: Trimethoprim sulfate, 2,4-diamino-5-(3,4,5-trimethoxybenzyl)pyrimidine sulfate, is white, odorless, crystalline powder with molecular weight of 678.72 and the following structural formula: Polymyxin sulfate is the sulfate salt of polymyxin 1and 2which are produced by the growth of Bacillus polymyxa (Prazmowski) Migula (Fam. Bacillaceae). It has potency of not less than 6,000 polymyxin units per mg, calculated on an anhydrous basis. The structural formulae are: Each mL contains:Actives: polymyxin sulfate equal to 10,000 polymyxin units, trimethoprim sulfate (equivalent to trimethoprim mg); Inactives: purified water, sodium chloride. Sulfuric acid and, if necessary, sodium hydroxide may be added to adjust pH (4.0 5.5). Preservative: benzalkonium chloride 0.004%. Chem structure. chemical structure 2.

DOSAGE & ADMINISTRATION SECTION.

DOSAGE AND ADMINISTRATION. In mild to moderate infections, instill one drop in the affected eye(s) every hours (maximum of doses per day) for period of to 10 days.

GENERAL PRECAUTIONS SECTION.

General. As with other antimicrobial preparations, prolonged use may result in overgrowth of nonsusceptible organisms, including fungi. If superinfection occurs, appropriate therapy should be initiated.

GERIATRIC USE SECTION.

Geriatric Use. No overall differences in safety or effectiveness have been observed between elderly and other adult patients.

HOW SUPPLIED SECTION.

HOW SUPPLIED. Polymyxin sulfate and trimethoprim ophthalmic solution, USP is supplied in plastic bottle with controlled drop tip in the following size:NDC 24208-315-10 10 mLStorage:Store at 15C to 25C (59F to 77F). PROTECT FROM LIGHT.Does not meet USP packaging specification for light resistance.RETAIN IN CARTON UNTIL TIME OF USE.Distributed by: Bausch Lomb Americas Inc. Bridgewater, NJ 08807 USA Manufactured by: Bausch Lomb Incorporated Tampa, FL 33637 USA (C) 2025 Bausch Lomb Incorporated or its affiliates Revised: October 20259117805 (Folded) 9117905 (Flat) do not use.

INDICATIONS & USAGE SECTION.

INDICATIONS AND USAGE. Polymyxin sulfate and trimethoprim ophthalmic solution is indicated in the treatment of surface ocular bacterial infections, including acute bacterial conjunctivitis, and blepharoconjunctivitis, caused by susceptible strains of the following microorganisms: Staphylococcus aureus, Staphylococcus epidermidis, Streptococcus pneumoniae, Streptococcus viridans, Haemophilus influenzaeand Pseudomonas aeruginosa. 1Efficacy for this organism in this organ system was studied in fewer than 10 infections.

INFORMATION FOR PATIENTS SECTION.

Information for Patients. Avoid contaminating the applicator tip with material from the eye, fingers, or other source. This precaution is necessary if the sterility of the drops is to be maintained.If hypersensitivity reactions such as redness, irritation, swelling or pain persists or increases, discontinue use immediately and contact your physician.Patients should be advised not to wear contact lenses if they have signs and symptoms of ocular bacterial infections.

PREGNANCY SECTION.

Pregnancy. Teratogenic Effects. Animal reproduction studies have not been conducted with polymyxin sulfate. It is not known whether polymyxin sulfate can cause fetal harm when administered to pregnant woman or can affect reproduction capacity.Trimethoprim has been shown to be teratogenic in the rat when given in oral doses 40 times the human dose. In some rabbit studies, the overall increase in fetal loss (dead and resorbed and malformed conceptuses) was associated with oral doses times the human therapeutic dose.While there are no large well-controlled studies on the use of trimethoprim in pregnant women, Brumfitt and Pursell, in retrospective study, reported the outcome of 186 pregnancies during which the mother received either placebo or oral trimethoprim in combination with sulfamethoxazole. The incidence of congenital abnormalities was 4.5% (3 of 66) in those who received placebo and 3.3% (4 of 120) in those receiving trimethoprim and sulfamethoxazole. There were no abnormalities in the 10 children whose mothers received the drug during the first trimester. In separate survey, Brumfitt and Pursell also found no congenital abnormalities in 35 children whose mothers had received oral trimethoprim and sulfamethoxazole at the time of conception or shortly thereafter.Because trimethoprim may interfere with folic acid metabolism, trimethoprim should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus.. Nonteratogenic Effects. The oral administration of trimethoprim to rats at dose of 70 mg/kg/day commencing with the last third of gestation and continuing through parturition and lactation caused no deleterious effects on gestation or pup growth and survival.

SPL UNCLASSIFIED SECTION.

Rx onlyFOR TOPICAL APPLICATION IN THE EYE.

TERATOGENIC EFFECTS SECTION.

Teratogenic Effects. Animal reproduction studies have not been conducted with polymyxin sulfate. It is not known whether polymyxin sulfate can cause fetal harm when administered to pregnant woman or can affect reproduction capacity.Trimethoprim has been shown to be teratogenic in the rat when given in oral doses 40 times the human dose. In some rabbit studies, the overall increase in fetal loss (dead and resorbed and malformed conceptuses) was associated with oral doses times the human therapeutic dose.While there are no large well-controlled studies on the use of trimethoprim in pregnant women, Brumfitt and Pursell, in retrospective study, reported the outcome of 186 pregnancies during which the mother received either placebo or oral trimethoprim in combination with sulfamethoxazole. The incidence of congenital abnormalities was 4.5% (3 of 66) in those who received placebo and 3.3% (4 of 120) in those receiving trimethoprim and sulfamethoxazole. There were no abnormalities in the 10 children whose mothers received the drug during the first trimester. In separate survey, Brumfitt and Pursell also found no congenital abnormalities in 35 children whose mothers had received oral trimethoprim and sulfamethoxazole at the time of conception or shortly thereafter.Because trimethoprim may interfere with folic acid metabolism, trimethoprim should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus.

WARNINGS SECTION.

WARNINGS. NOT FOR INJECTION INTO THE EYE.If hypersensitivity reaction to polymyxin sulfate and trimethoprim ophthalmic solution occurs, discontinue use.Polymyxin sulfate and trimethoprim ophthalmic solution is not indicated for the prophylaxis or treatment of ophthalmia neonatorum.