Label: TRIMETHOPRIM SULFATE AND POLYMYXIN B SULFATE- trimethoprim sulfate and polymyxin b sulfate solution

  • Category: HUMAN PRESCRIPTION DRUG LABEL
  • DEA Schedule: None
  • Marketing Status: Abbreviated New Drug Application

Drug Label Information

Updated 09/11

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  • SPL UNCLASSIFIED SECTION

    Rx only

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  • DESCRIPTION

    Trimethoprim Sulfate and Polymyxin B Sulfate Ophthalmic Solution is a sterile antimicrobial solution for topical ophthalmic use. Trimethoprim sulfate, 2,4-diamino-5-(3,4,5-trimethoxybenzyl)pyrimidine sulfate (2:1), occurs as a white, odorless, crystalline powder with a molecular weight of 678.72. The structural formula is as follows:

    Structural Formula

    Polymyxin B sulfate is the sulfate salt of polymyxin B1 and B2 which 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 as follows:

    Structural Formula

    Each mL contains:

    Actives: Trimethoprim Sulfate equivalent to Trimethoprim 1 mg (0.1%) and Polymyxin B Sulfate 10,000 units. Preservative: Benzalkonium Chloride 0.04 mg (0.004%). Inactives: Sodium Chloride, Sulfuric Acid and Sodium Hydroxide may be added to adjust pH (3.0 to 5.5), and Purified Water USP.

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  • CLINICAL PHARMACOLOGY

    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 very much stronger for the bacterial enzyme than for the corresponding mammalian enzyme. For that reason, trimethoprim selectively interferes with bacterial biosynthesis of nucleic acids and proteins.

    Polymyxin B, a cyclic lipopeptide antibiotic, is rapidly 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.

    When used topically, trimethoprim and polymyxin B absorption through intact skin and mucous membranes is insignificant.

    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 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 aerogenes, and Serratia marcescens.

    Polymyxin B: Pseudomonas aeruginosa, Escherichia coli, Klebsiella pneumoniae, Enterobacter aerogenes and Haemophilus influenzae.

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  • INDICATIONS AND USAGE

    Trimethoprim Sulfate and Polymyxin B Sulfate 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 influenza and Pseudomonas aeruginosa.*

    *Efficacy for this organism in this organ system was studied in fewer than 10 infections.

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  • CONTRAINDICATIONS

    Trimethoprim Sulfate and Polymyxin B Sulfate Ophthalmic Solution is contraindicated in patients with known hypersensitivity to any of its components.

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  • WARNINGS

    NOT FOR INJECTION INTO THE EYE. If a sensitivity reaction to Trimethoprim and Polymyxin B Sulfate Ophthalmic Solution occurs, discontinue use. Trimethoprim Sulfate and Polymyxin B Sulfate Ophthalmic Solution is not indicated for the prophylaxis or treatment of ophthalmic neonatorum.

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  • 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 redness, irritation, swelling or pain persists or increases, discontinue use immediately and contact your physician.

    Carcinogenesis, Mutagenesis, Impairment of Fertility

    Carcinogenesis: Long-term studies in animals to evaluate carcinogenic potential have not been conducted with polymyxin B 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 1000 times human plasma levels after oral administration in these same cells a low level of chromosomal damage was induced at one of the laboratories. Studies to evaluate mutagenic potential have not been conducted with polymyxin B sulfate.

    Impairment of Fertility: Polymyxin B 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

    Pregnancy Category C. Animal reproduction studies have not been conducted with polymyxin B sulfate. It is not known whether polymyxin B sulfate can cause fetal harm when administered to a 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 6 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 a 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 a 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 a 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 Trimethoprim Sulfate and Polymyxin B Sulfate Ophthalmic Solution is administered to a nursing woman.

    Pediatric Use: Safety and effectiveness in pediatric patients below the age of 2 months have not been established (see WARNINGS).

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  • ADVERSE REACTIONS

    The most frequent adverse reaction to Trimethoprim Sulfate and Polymxin B Sulfate 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.

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  • DOSAGE AND ADMINISTRATION

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

    Pediatric Use: Clinical studies have shown Trimethoprim and Polymyxin B Sulfate Ophthalmic Solution to be safe and effective for use in pediatric patients over two months of age. The dosage regimen is the same as for adults.

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  • HOW SUPPLIED

    Trimethoprim Sulfate and Polymyxin B Sulfate Ophthalmic Solution is supplied as a sterile solution in plastic dropper bottles in the following size: 10 mL in a 10 mL bottle NDC 17478-703-11

    STORAGE: Store at 20° to 25°C (68° to 77°F) [see USP Controlled Room Temperature]. Protect from light.

    WARNING – KEEP THIS AND ALL DRUGS OUT OF THE REACH OF CHILDREN.

    Akorn

    Manufactured by: Akorn, Inc.
    Lake Forest, IL 60045

    ATP00N
    Rev. 10/08

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  • PRINCIPAL DISPLAY PANEL

    Principal Display Panel Text for Container Label:

    NDC 17478-703-11

    Trimethoprim Sulfate

    and Polymyxin B

    Sulfate Ophthalmic

    Solution

    10 mL

    For the eye

    Sterile

    Rx only [Akorn Logo]

    Principal Display Panel Text for Container Label
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  • PRINCIPAL DISPLAY PANEL

    Principal Display Panel Text for Carton Label:

    NDC 17478-703-11

    Trimethoprim

    Sulfate and

    Polymyxin B

    Sulfate

    Ophthalmic

    Solution

    For the eye

    10 mL

    Sterile

    Rx only [Akorn Logo]

    Principal Display Panel Text for Carton Label
    Close
  • INGREDIENTS AND APPEARANCE
    TRIMETHOPRIM SULFATE AND POLYMYXIN B SULFATE 
    trimethoprim sulfate and polymyxin b sulfate solution
    Product Information
    Product Type HUMAN PRESCRIPTION DRUG LABEL Item Code (Source) NDC:17478-703
    Route of Administration OPHTHALMIC DEA Schedule     
    Active Ingredient/Active Moiety
    Ingredient Name Basis of Strength Strength
    Trimethoprim sulfate (Trimethoprim) Trimethoprim sulfate 1 mg  in 1 mL
    Polymyxin B sulfate (Polymyxin B) Polymyxin B sulfate 10000 [USP'U]  in 1 mL
    Inactive Ingredients
    Ingredient Name Strength
    benzalkonium chloride  
    sodium chloride  
    sulfuric acid  
    sodium hydroxide  
    water  
    Packaging
    # Item Code Package Description Marketing Start Date Marketing End Date
    1 NDC:17478-703-11 1 in 1 CARTON
    1 10 mL in 1 BOTTLE, DROPPER
    Marketing Information
    Marketing Category Application Number or Monograph Citation Marketing Start Date Marketing End Date
    ANDA ANDA065006 12/17/1998
    Labeler - Akorn, Inc. (062649876)
    Establishment
    Name Address ID/FEI Business Operations
    Akorn, Inc. 155135783 MANUFACTURE, REPACK, ANALYSIS
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