Polymyxin B Sulfate and Trimethoprim Ophthalmic Solution, USP (Sterile)

Rx only

FOR TOPICAL APPLICATION IN THE EYE

Polymyxin B sulfate and trimethoprim ophthalmic solution, USP is a 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 a white, odorless, crystalline powder with a molecular weight of 678.72 and the following structural formula:

C ₂₈H ₃₈N ₈O ₁₀S Mol. Wt. 678.72

Polymyxin B sulfate is the sulfate salt of polymyxin B ₁and B ₂which are produced by the growth of Bacillus polymyxa (Prazmowski) Migula (Fam. Bacillaceae). It has a potency of not less than 6,000 polymyxin B units per mg, calculated on an anhydrous basis. The structural formula is:

Each mL contains:Actives: polymyxin B sulfate equal to 10,000 polymyxin B units, trimethoprim sulfate (equivalent to trimethoprim 1 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%

Trimethoprim is a synthetic antibacterial drug active against a 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, a cyclic lipopeptide antibiotic, is bactericidal for a 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, 1 hour and 3 hours following instillation in the eye of 2 drops of ophthalmic solution containing 1 mg trimethoprim and 10,000 units polymyxin B per mL. Peak serum concentrations were approximately 0.03 mcg/mL trimethoprim and 1 unit/mL polymyxin B.

Microbiology
In vitro studies have demonstrated that the anti-infective components of trimethoprim sulfate and polymyxin B 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.

The most frequent adverse reaction to polymyxin B 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. 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 .

In mild to moderate infections, instill one drop in the affected eye(s) every 3 hours (maximum of 6 doses per day) for a period of 7 to 10 days.

Polymyxin B sulfate and trimethoprim ophthalmic solution, USP* containing 10,000 polymyxin B units and 1 mg trimethoprim per mL, is supplied in a plastic bottle with a controlled drop tip and a natural cap in the following size:

NDC: 70518-0271-00

PACKAGING: 1 in 1 CARTON, 10 mL in 1 BOTTLE DROPPER TYPE 0

Storage:

Store at 15°C to 25°C (59°F to 77°F). PROTECT FROM LIGHT.

*Does not meet USP packaging specification for light resistance.

RETAIN IN CARTON UNTIL TIME OF USE.

Repackaged and Distributed By:

Remedy Repack, Inc.

625 Kolter Dr. Suite #4 Indiana, PA 1-724-465-8762

DRUG: Polymyxin B Sulfate and Trimethoprim

GENERIC: Polymyxin B Sulfate and Trimethoprim Sulfate

DOSAGE: SOLUTION/ DROPS

ADMINSTRATION: OPHTHALMIC

NDC: 70518-0271-0

PACKAGING: 10 mL in 1 BOTTLE, DROPPER

OUTER PACKAGING: 1 in 1 CARTON

ACTIVE INGREDIENT(S):

• TRIMETHOPRIM SULFATE 1mg in 1mL
• POLYMYXIN B SULFATE 10000[USP'U] in 1mL

INACTIVE INGREDIENT(S):

• WATER
• SODIUM CHLORIDE
• SULFURIC ACID
• SODIUM HYDROXIDE
• BENZALKONIUM CHLORIDE

MM1