Polymyxin B and trimethoprim are combined in an ophthalmic preparation for the treatment of acute bacterial ocular infections. Polymyxin B is a polypeptide antibiotic derived from a strain of Bacillus polymyxa. Trimethoprim is a synthetic antiinfective agent. Polymyxin B has activity against gram-negative aerobic bacteria, including Pseudomonas aeruginosa, while trimethoprim is effective against both gram-positive and gram-negative organisms. The FDA approved this combination eye product in October 1988.
General Administration Information
For storage information, see specific product information within the How Supplied section.
Route-Specific Administration
Ophthalmic Administration
-For topical ophthalmic administration only; do not use as an ocular injection.
-Wash hands before and after use.
-Care should be taken to avoid contamination. Do not touch the tip of the container to the eye, fingertips, or other surface. Do not share bottles between patients.
-Tilt head back slightly and pull the lower eyelid down with the index finger to form a pouch. Squeeze the prescribed number of drops into the pouch and gently close eyes for 1-2 minutes. Do not blink.
The most frequent adverse reaction reported with polymyxin B and trimethoprim ophthalmic preparations is ocular irritation consisting of increased redness (erythema), burning, stinging, and/or ocular pruritus. 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, pruritus, increased redness (erythema), epiphora (tearing), and/or circumocular rash (unspecified).
Polymyxin B and trimethoprim can cause the overgrowth of non susceptible organisms, especially fungi, resulting in superinfection. Susceptibility tests should be performed if the infection does not improve.
Polymyxin B; trimethoprim combination products are not for intraocular injection. Polymyxin B; trimethoprim are contraindicated in patients hypersensitive to any of the components of the product (e.g., patients with polymyxin hypersensitivity or trimethoprim hypersensitivity). If a hypersensitivity reaction occurs, discontinue use of the product.
Polymyxin B; trimethoprim can cause the overgrowth of nonsusceptible organisms, resulting in superinfection. Susceptibility tests should be performed if the infection does not improve.
Patients who wear contact lenses should avoid wearing them while being treated with polymyxin B; trimethoprim for an ocular infection.
The effectiveness of polymyxin B; trimethoprim in neonates and infants < 2 months has not been established. Polymyxin B; trimethoprim products are not indicated for the treatment or prophylaxis of ophthalmia neonatorum.
Polymyxin B; trimethoprim ophthalmic products have not been studied in pregnant women. It is not known if polymyxin B can cause fetal harm. Trimethoprim has been shown to be teratogenic in animals when given in high systemic doses. Trimethoprim may interfere with folic acid metabolism and therefore, should only be used during pregnancy if the potential benefit justifies the risk. However, minimal systemic absorption occurs from topical ophthalmic administration.
It is not known if polymyxin B; trimethoprim, when given for ocular infections, is excreted in breast milk. The manufacturer recommends caution should be exercised if this combination is given to a woman who is nursing her infant. However, in 11 volunteers, peak serum concentrations were approximately 0.03 microg/mL trimethoprim and 1 unit/mL polymyxin B after 2 drops of the ophthalmic solution were administered. Oral absorption of any polymyxin by the nursing infant would me minimal. Additionally, trimethoprim is considered usually compatible by the American Academy of Pediatrics (AAP). To minimize the amount of drug that reaches the systemic circulation and breast milk, apply pressure over the tear duct by the corner of the eye for 1 minute after ophthalmic administration. Consider the benefits of breast-feeding, the risk of potential infant drug exposure, and the risk of an untreated or inadequately treated condition. If a breast-feeding infant experiences an adverse effect related to a maternally administered drug, healthcare providers are encouraged to report the adverse effect to the FDA.
Per the manufacturer, this drug has been shown to be active against most strains of the following microorganisms either in vitro and/or in clinical infections: Escherichia coli, Haemophilus aegyptius, Haemophilus influenzae (beta-lactamase negative), Haemophilus influenzae (beta-lactamase positive), Klebsiella aerogenes, Klebsiella pneumoniae, Proteus mirabilis, Proteus vulgaris, Pseudomonas aeruginosa, Serratia marcescens, Staphylococcus aureus (MSSA), Staphylococcus epidermidis, Streptococcus pneumoniae, Streptococcus pyogenes (group A beta-hemolytic streptococci), Viridans streptococci
NOTE: The safety and effectiveness in treating clinical infections due to organisms with in vitro data only have not been established in adequate and well-controlled clinical trials.
For the treatment of superficial ophthalmic infection, including bacterial conjunctivitis, blepharoconjunctivitis, and corneal abrasion*:
-for the treatment of bacterial conjunctivitis and blepharoconjunctivitis:
Ophthalmic dosage:
Adults: 1 drop in the affected eye(s) every 3 hours, up to 6 times daily, for 7 to 10 days.
Infants, Children, and Adolescents 2 months to 17 years: 1 drop in the affected eye(s) every 3 hours, up to 6 times daily, for 7 to 10 days.
-for the treatment of corneal abrasion*:
Ophthalmic dosage:
Adults: 1 drop in the affected eye(s) 4 times daily for 3 to 5 days.
Infants, Children, and Adolescents 2 months to 17 years: 1 drop in the affected eye(s) 4 times daily for 3 to 5 days.
Maximum Dosage Limits:
-Adults
6 drops/day.
-Elderly
6 drops/day.
-Adolescents
6 drops/day.
-Children
6 drops/day.
-Infants
>= 2 months: 6 drops/day.
< 2 months: Use not established.
Patients with Hepatic Impairment Dosing
No dosage adjustments are needed for ophthalmic topical application.
Patients with Renal Impairment Dosing
No dosage adjustments are needed for ophthalmic topical application.
*non-FDA-approved indication
There are no drug interactions associated with Polymyxin B; Trimethoprim products.
Mechanism of Action:
-Polymyxin B: Polymyxin B binds to phospholipids in the gram-negative bacterial cell membrane. This binding destroys bacterial membranes with a surface detergent-like mechanism and increases the permeability of the cell membrane, which results in loss of metabolites essential to bacterial existence. Polymyxin B is bactericidal against most gram-negative bacilli; however, some Proteus and Serratia species may be resistant. Polymyxin B has no in vitro activity against gram-positive organisms.
-Trimethoprim: Trimethoprim interferes with folate synthesis in susceptible bacteria. Trimethoprim blocks the production of tetrahydrofolic acid from dihydrofolic acid by binding to and reversibly inhibiting dihydrofolate reductase. Trimethoprim selectively binds to the bacterial enzyme over the corresponding mammalian enzyme.
Pharmacokinetics:
Polymyxin B and trimethoprim combinations are applied topically to the eye.
-Route-Specific Pharmacokinetics
Other Route(s)
Ophthalmic Route
Blood samples following instillation of 2 drops of polymyxin B 10,000 units/ml and trimethoprim 1 mg/ml in the eye resulted in peak plasma concentrations of polymyxin B and trimethoprim of 1 unit/ml and 0.03 mcg/ml, respectively. Polymyxin B does not penetrate significantly into the aqueous humor of the eye even when inflammation is present.