Polymyxin B Sulfate (EENT) (Monograph)

Brand name: Casporyn HC
Drug class: Antibacterials

Introduction

Antibacterial; polymyxin antibiotic.

Uses for Polymyxin B Sulfate (EENT)

Bacterial Ophthalmic Infections

Used in fixed combination with other anti-infectives (i.e., bacitracin; bacitracin and neomycin; neomycin and gramicidin; trimethoprim) for topical treatment of superficial infections of the eye (e.g., conjunctivitis, keratitis, keratoconjunctivitis, blepharitis, blepharoconjunctivitis) caused by susceptible bacteria.

Used subconjunctivally for treatment of infections of the eye caused by susceptible Pseudomonas aeruginosa.

Mild, acute bacterial conjunctivitis often resolves spontaneously without anti-infective treatment. Although topical ophthalmic anti-infectives may shorten time to resolution and reduce severity and risk of complications, avoid indiscriminate use of topical anti-infectives. Treatment of acute bacterial conjunctivitis generally is empiric; use of a broad-spectrum topical ophthalmic antibacterial usually recommended. In vitro staining and/or cultures of conjunctival material may be indicated in management of recurrent, severe, or chronic purulent conjunctivitis or when acute conjunctivitis does not respond to initial empiric topical treatment.

Because bacterial keratitis may be associated with subsequent loss of vision as the result of corneal scarring or topographic irregularities and because untreated or severe bacterial keratitis may result in corneal perforation with potential for endophthalmitis and possible loss of the eye, optimal management involves rapid evaluation and diagnosis, timely initiation of treatment, and appropriate follow-up. Treatment of community-acquired bacterial keratitis generally is empiric; use of a broad-spectrum topical ophthalmic antibacterial usually recommended. Subconjunctival anti-infectives may be necessary if scleral spread or perforation is imminent. In vitro staining and/or cultures of corneal material are indicated in management of keratitis involving corneal infiltrates that are central, large, and extend to the middle to deep stroma; when keratitis is chronic or unresponsive to broad-spectrum topical anti-infective treatment; or when atypical features suggest fungal, amebic, or mycobacterial infection.

Bacterial Otic Infections

Used in fixed combination with neomycin and a corticosteroid (i.e., hydrocortisone) for topical treatment of superficial infections of the external auditory canal (otitis externa) caused by susceptible bacteria. Also used for topical treatment of infections of mastoidectomy and fenestration cavities caused by susceptible bacteria.

Diffuse, uncomplicated acute otitis externa in otherwise healthy patients usually treated initially with topical therapy (e.g., otic anti-infective or antiseptic with or without an otic corticosteroid). Supplement with systemic anti-infective therapy if patient has a medical condition that could impair host defenses (e.g., diabetes mellitus, HIV infection) or if infection has spread into pinna, skin of the neck or face, or into deeper tissues such as occurs with malignant otitis externa. Malignant otitis externa is an invasive, potentially life-threatening infection, especially in immunocompromised patients, and requires prompt diagnosis and treatment with systemic anti-infectives.

Ocular Inflammation

Fixed-combination ophthalmic preparations containing polymyxin B, neomycin, and dexamethasone or fixed-combination ophthalmic preparations containing polymyxin B, neomycin, bacitracin, and hydrocortisone or hydrocortisone acetate are used for topical treatment of corticosteroid-responsive ocular conditions when a corticosteroid is indicated and superficial bacterial ocular infection or risk of such infection exists.

Although manufacturers state that use of fixed-combination ophthalmic preparations containing anti-infectives and a corticosteroid may be indicated in ocular inflammatory conditions when risk of superficial ocular infection is high or when potentially dangerous numbers of bacteria are expected to be present in the eye, experts state avoid use of such preparations in patients with bacterial conjunctivitis because of risk of potentiating the infection.

Consider that use of fixed-combination ophthalmic preparations containing anti-infectives and a corticosteroid may mask clinical signs of bacterial, fungal, or viral infections; prevent recognition of ineffectiveness of the anti-infective; and/or increase IOP.

Polymyxin B Sulfate (EENT) Dosage and Administration

Administration

Ophthalmic Administration (Topical)

Fixed combination of polymyxin B and bacitracin with or without neomycin: Apply topically to eye as an ophthalmic ointment.

Fixed combination of polymyxin B, neomycin, and gramicidin: Apply topically to eye as an ophthalmic solution.

Fixed combination of polymyxin B and trimethoprim: Apply topically to eye as an ophthalmic solution.

Fixed combination of polymyxin B, other anti-infectives (i.e., neomycin with or without bacitracin), and a corticosteroid (i.e., dexamethasone, hydrocortisone, or hydrocortisone acetate): Apply topically to eye as ophthalmic ointments or suspensions.

For topical ophthalmic use only; do not inject subconjunctivally or directly into anterior chamber of the eye.

Avoid contaminating container tip with material from eye, eyelids, fingers, or other source.

Ophthalmic Administration (Subconjunctival)

Has been administered by subconjunctival injection.

For subconjunctival administration, reconstitute vial containing sterile powder for injection (500,000 units of polymyxin B) by adding 20–50 mL of sterile water for injection or 0.9% sodium chloride injection to provide a solution containing 10,000–25,000 units/mL. Administer appropriate dose of reconstituted solution by subconjunctival injection.

Otic Administration

Fixed combination of polymyxin B, neomycin, and hydrocortisone: Apply topically into ear canal as an otic solution or suspension.

Otic preparations are for topical otic use only; do not use in the eyes.

Clean and dry ear canal prior to administration.

Shake otic suspensions well prior to each use.

Lie with the affected ear upward. Instill appropriate amount of otic solution or suspension into ear; maintain this position for 5 minutes to facilitate penetration into ear canal. Repeat procedure for opposite ear if necessary.

If ear canal is narrow or edematous and there are concerns that drug delivery might be impeded, consider inserting cotton wick into ear canal and saturating it with the otic preparation. Manufacturers state keep wick moist by adding additional otic solution or suspension every 4 hours and replace wick once every 24 hours. Experts state that wick unnecessary after ear canal edema subsides, which may occur within 24 hours or a few days after topical treatment initiated.

Avoid contaminating container tip with material from ear, fingers, or other source.

Dosage

Available as polymyxin B sulfate; potency and dosage expressed in terms of polymyxin B activity (units of polymyxin B).

Pediatric Patients

Bacterial Ophthalmic Infections

Ophthalmic

Polymyxin B and trimethoprim in infants and children ≥2 months of age (ophthalmic solution): Instill 1 drop in affected eye(s) every 3 hours (maximum of 6 doses daily) for 7–10 days.

Usual duration of topical anti-infective treatment for bacterial conjunctivitis is 5–10 days; 5–7 days usually adequate for mild bacterial conjunctivitis.

Bacterial Otic Infections

Otic

Polymyxin B, neomycin, and hydrocortisone in children ≥2 years of age (otic solution or suspension): Instill 3 drops in affected ear(s) 3 or 4 times daily for up to 10 days.

Optimal duration of topical treatment of acute otitis externa not determined, but 7–10 days usually recommended. Appropriate treatment should result in improvement in symptoms (otalgia, pruritus, fullness) within 48–72 hours, although resolution of symptoms may take up to 2 weeks.

Ocular Inflammation

Ophthalmic

Polymyxin B, neomycin, and dexamethasone in children ≥2 years of age (ophthalmic suspension): Instill 1 or 2 drops in conjunctival sac of affected eye(s) up to 4–6 times daily. In severe disease, instill 1 or 2 drops every hour initially, then taper dosage by decreasing frequency of administration as inflammation subsides.

If no improvement after 48 hours, reevaluate patient.

Adults

Bacterial Ophthalmic Infections

Ophthalmic (Topical)

Polymyxin B and bacitracin with or without neomycin (ophthalmic ointment): Apply to affected eye(s) every 3 or 4 hours for 7–10 days, depending on severity of infection.

Polymyxin B, neomycin, and gramicidin (ophthalmic solution): Instill 1 or 2 drops in affected eye(s) every 4 hours for 7–10 days. May instill up to 2 drops every hour for severe infections.

Polymyxin B and trimethoprim (ophthalmic solution): Instill 1 drop in affected eye(s) every 3 hours (maximum of 6 doses daily) for 7–10 days.

Usual duration of topical anti-infective treatment for bacterial conjunctivitis is 5–10 days; 5–7 days usually adequate for mild bacterial conjunctivitis.

Ophthalmic (Subconjunctival)

Up to 100,000 units daily using reconstituted solution containing 10,000–25,000 units/mL.

If used in conjunction with topical polymyxin B, total dosage should not exceed 25,000 units/kg daily.

Bacterial Otic Infections

Otic

Polymyxin B, neomycin, and hydrocortisone (otic solution or suspension): Instill 4 drops in affected ear(s) 3 or 4 times daily for up to 10 days.

Ocular Inflammation

Ophthalmic

Polymyxin B, neomycin, and dexamethasone (ophthalmic ointment): Apply approximately 1.25 cm (½ inch) of ointment in conjunctival sac of affected eye(s) up to 3 or 4 times daily.

Polymyxin B, neomycin, and dexamethasone (ophthalmic suspension): Instill 1 or 2 drops in conjunctival sac of affected eye(s) up to 4–6 times daily. In severe disease, instill 1 or 2 drops every hour initially, then taper dosage by decreasing frequency of administration as inflammation subsides.

Polymyxin B, neomycin, bacitracin, and hydrocortisone or hydrocortisone acetate (ophthalmic ointment): Apply to affected eye(s) every 3 or 4 hours, depending on severity of the condition.

If no improvement after 48 hours, reevaluate patient.

Prescribing Limits

Pediatric Patients

Bacterial Ophthalmic Infections

Ophthalmic

Polymyxin B and trimethoprim in infants and children ≥2 months of age (ophthalmic solution): Maximum 6 doses in 24 hours.

Bacterial Otic Infections

Otic

Polymyxin B, neomycin, and hydrocortisone in children ≥2 years of age (otic solution or suspension): Maximum 10 consecutive days of therapy.

Adults

Bacterial Ophthalmic Infections

Ophthalmic

Polymyxin B and trimethoprim (ophthalmic solution): Maximum 6 doses in 24 hours.

Bacterial Otic Infections

Otic

Polymyxin B, neomycin, and hydrocortisone (otic solution or suspension): Maximum 10 consecutive days of therapy.

Special Populations

No special population dosage recommendations.

Cautions for Polymyxin B Sulfate (EENT)

Contraindications

Polymyxin B: Hypersensitivity to polymyxins.
Fixed combinations of polymyxin B and other anti-infectives (ophthalmic): Hypersensitivity to any ingredient in the formulation.
Fixed combinations of polymyxin B, other anti-infectives, and dexamethasone, hydrocortisone, or hydrocortisone acetate (ophthalmic): Hypersensitivity to any ingredient in the formulation. Also, viral diseases of the cornea and conjunctiva (e.g., epithelial herpes simplex keratitis [dendritic keratitis], vaccinia, varicella), mycobacterial infections of the eye, or fungal diseases of ocular structures.
Fixed combinations of polymyxin B, neomycin, and hydrocortisone (otic): Hypersensitivity to any ingredient in the formulation. Also, viral infections of external ear canal (e.g., herpes simplex, vaccinia, varicella zoster).

Warnings/Precautions

Sensitivity Reactions

Hypersensitivity Reactions

Local irritation and allergic reactions reported; more serious hypersensitivity reactions, including anaphylaxis, reported rarely.

Topical anti-infectives, particularly neomycin, may cause cutaneous sensitization.

During long-term use, periodically examine patient for signs of sensitization.

Ophthalmic preparations: Sensitization may manifest as rash, pruritus, edema of the conjunctiva and eyelid, conjunctival erythema, or failure to heal.

Otic preparations: Sensitization may manifest as swelling, dry scaling, pruritus, or failure to heal.

If signs or symptoms of sensitivity occur, discontinue the drug. Symptoms usually subside quickly after preparation discontinued.

Patients allergic to one fixed-combination preparation should avoid preparations containing any of the component drugs. Cross-allergenicity occurs among the aminoglycosides; patients allergic to fixed-combination preparations containing neomycin may also be allergic to other aminoglycosides (e.g., gentamicin, paromomycin, streptomycin).

Sulfite Sensitivity

Some fixed-combination otic preparations contain potassium metabisulfite, a sulfite that can cause allergic-type reactions (including anaphylaxis and life-threatening or less severe asthmatic episodes) in certain susceptible individuals.

Superinfection

Prolonged use may result in overgrowth of nonsusceptible organisms, including fungi. If superinfection occurs, institute appropriate therapy.

Resistance to polymyxin B or other anti-infectives in fixed-combination preparations may develop.

Precautions Related to Ophthalmic Administration

Bacterial keratitis has developed in patients who inadvertently contaminated the multiple-dose container of their ophthalmic preparation; in most reported cases, concurrent corneal disease or disruption of ocular epithelial surface was present.

Do not wear contact lenses if any signs or symptoms of ocular infection are present.

Manufacturers caution that ophthalmic ointments may delay healing.

Precautions Related to Otic Administration

Do not use fixed-combination otic preparations containing polymyxin B, neomycin, and hydrocortisone in patients with perforated tympanic membrane.

Neomycin, especially with prolonged use, can induce permanent sensorineural hearing loss due to cochlear damage, mainly destruction of hair cells in the organ of Corti. Use otic preparations containing neomycin only under close clinical observation; do not use for longer than 10 consecutive days.

If otic infection not improved after 1 week of treatment, obtain cultures to guide treatment.

Use of Fixed Combinations Containing Corticosteroids

When ophthalmic or otic preparations containing polymyxin B in fixed combination with other anti-infectives and a corticosteroid (i.e., dexamethasone, hydrocortisone, hydrocortisone acetate) are used, consider cautions, precautions, and contraindications associated with EENT corticosteroids.

Provide initial prescriptions for fixed-combination ophthalmic preparations containing a corticosteroid or renewal prescriptions (beyond 8 g of ophthalmic ointment or beyond 20 mL of ophthalmic suspension) only after examining patient with slit lamp microscopy and, when appropriate, fluorescein staining.

Reevaluate patient if eye pain or inflammation persists for >48 hours or becomes aggravated.

Prolonged use of ophthalmic preparations containing a corticosteroid may result in glaucoma, with optic nerve damage, defects in visual acuity and fields of vision, and posterior subcapsular cataract formation. If used for ≥10 days, monitor IOP regularly, even though monitoring may be difficult in children and uncooperative patients. Use with caution in patients with glaucoma; check IOP frequently in such patients.

Use after cataract surgery may delay healing and increase incidence of bleb formation.

Corneal and scleral thinning reported with various ocular diseases and with long-term use of topical ophthalmic corticosteroids. Use in patients with thin corneal and scleral tissue may result in perforation.

Prolonged use may suppress host responses and increase risk of secondary ocular infections. Use in patients with acute purulent conditions of the eye may mask infection or enhance existing infection.

May prolong course and exacerbate severity of many viral infections of the eye (including herpes simplex). Use great caution in patients with herpes simplex; frequent slit lamp microscopy recommended.

Consider possibility of fungal infections of the cornea after prolonged use, especially in those with persistent corneal ulceration. Perform fungal cultures when appropriate.

Specific Populations

Pregnancy

Not known whether ophthalmic preparations containing polymyxin B can cause fetal harm when administered to pregnant women.

Polymyxin B and bacitracin with or without neomycin (ophthalmic): Use during pregnancy only if clearly needed.

Polymyxin B, neomycin, and gramicidin (ophthalmic): Use during pregnancy only if clearly needed.

Polymyxin B and trimethoprim (ophthalmic): Use during pregnancy only if potential benefits justify potential risks to fetus; trimethoprim may interfere with folic acid metabolism.

Polymyxin B, other anti-infectives, and dexamethasone, hydrocortisone, or hydrocortisone acetate (ophthalmic): Use during pregnancy only if potential benefits justify potential risks to fetus.

Polymyxin B, neomycin, and hydrocortisone (otic): Use during pregnancy only if potential benefits justify potential risks to fetus.

Lactation

Polymyxin B and other anti-infectives (ophthalmic): Use with caution.

Polymyxin B, neomycin, and dexamethasone (ophthalmic): Use with caution.

Polymyxin B, neomycin, bacitracin, and hydrocortisone or hydrocortisone acetate (ophthalmic): Discontinue nursing or the drug, taking into account importance of the drug to the woman.

Polymyxin B, neomycin, and hydrocortisone (otic): Use with caution.

Pediatric Use

Polymyxin B and bacitracin with or without neomycin (ophthalmic): Safety and efficacy not established in pediatric patients.

Polymyxin B, neomycin, and gramicidin (ophthalmic): Safety and efficacy not established in pediatric patients.

Polymyxin B and trimethoprim (ophthalmic): Safety and efficacy not established in infants <2 months of age.

Polymyxin B, neomycin, and dexamethasone (ophthalmic): Safety and efficacy of the suspension not established in children <2 years of age; safety and efficacy of the ointment not established in pediatric patients.

Polymyxin B, neomycin, bacitracin, and hydrocortisone or hydrocortisone acetate (ophthalmic): Safety and efficacy not established in pediatric patients.

Polymyxin B, neomycin, and hydrocortisone (otic): Most manufacturers state safety and efficacy not established in children <2 years of age because of insufficient data. One manufacturer states safety and efficacy have been established in pediatric patients and does not specify an age range.

Geriatric Use

Polymyxin B, neomycin, and gramicidin (ophthalmic): Clinical data insufficient to determine whether geriatric patients respond differently than younger adults.

Polymyxin B and trimethoprim (ophthalmic): No overall differences in safety or efficacy relative to younger adults.

Polymyxin B, neomycin, and dexamethasone (ophthalmic): No overall differences in safety or efficacy relative to younger patients.

Polymyxin B, neomycin, bacitracin, and hydrocortisone acetate (ophthalmic): No overall differences in safety or efficacy relative to younger adults.

Polymyxin B, neomycin, and hydrocortisone (otic): Clinical data insufficient to determine whether geriatric patients respond differently than younger patients; other clinician experience has not identified differences in response.

Common Adverse Effects

Local irritation and allergic reactions.

Polymyxin B Sulfate (EENT) Pharmacokinetics

Absorption

Bioavailability

Minimal or no absorption from intact or denuded skin or from mucous membranes.

Stability

Storage

Ophthalmic

Ointment

Polymyxin B and bacitracin: 15–25°C.

Polymyxin B, neomycin, and bacitracin: 15–25°C.

Polymyxin B, neomycin, and dexamethasone: 2–25°C. Contains methylparaben and propylparaben as preservatives.

Polymyxin B, neomycin, bacitracin, and hydrocortisone or hydrocortisone acetate: 15–25°C.

Solution

Polymyxin B, neomycin, and gramicidin: 15–25°C; protect from light. Contains thimerosal as a preservative.

Polymyxin B and trimethoprim: 15–25°C; protect from light. Contains benzalkonium chloride as a preservative.

Suspension

Polymyxin B, neomycin, and dexamethasone: 8–25°C; store upright. Contains benzalkonium chloride as a preservative.

Powder for Injection

Polymyxin B: 20–25°C; protect from light.

After reconstitution, store at 2–8°C; discard unused portions after 72 hours.

Otic

Solution or Suspension

Polymyxin B, neomycin, and hydrocortisone: 15–25°C. Solutions contain potassium meta bisulfite as a preservative; suspensions contain thimerosal as a preservative.

Actions and Spectrum

Polymyxin antibiotic derived from Bacillus polymyxa.
Usually bactericidal. Increases permeability of the bacterial cell wall membrane by interacting with phospholipid components of the cell membrane.
Polymyxin B: Spectrum of activity includes many aerobic gram-negative bacteria. Inactive against gram-positive bacteria and fungi.
Polymyxin B in fixed combination with neomycin: Active against Staphylococcus aureus, Escherichia coli, Haemophilus influenzae, Enterobacter, Klebsiella, Neisseria, and Pseudomonas aeruginosa. Does not provide coverage against streptococci (including Streptococcus pneumoniae) or Serratia marcescens.
Polymyxin B in fixed combination with bacitracin with or without neomycin: Active against S. aureus, streptococci (including S. pneumoniae), E. coli, H. influenzae, Enterobacter, Klebsiella, Neisseria, and Ps. aeruginosa. Does not provide coverage against S. marcescens.
Polymyxin B in fixed combination with neomycin and gramicidin: Active against S. pneumoniae, E. coli, H. influenzae, Enterobacter, Klebsiella, Neisseria, and Ps. aeruginosa. Does not provide coverage against S. marcescens.
Polymyxin B in fixed combination with trimethoprim: Active against S. aureus, S. epidermidis, S. pneumoniae, viridans streptococci, H. influenzae, and Ps. aeruginosa.
Bacteria resistant to polymyxin B may emerge in patients receiving topical preparations containing the drug.
Complete cross-resistance occurs between polymyxin B and colistin.

Advice to Patients

Advise patients to avoid contaminating container tip with material from eye, eyelid, ears, fingers, or other source. Importance of not sharing ophthalmic or otic preparations with others
Inform patients that serious eye damage and subsequent vision loss may occur if ophthalmic preparations are handled improperly and become contaminated by common bacteria known to cause ocular infections.
Inform patients that their vision may be temporarily blurred after administration of topical ophthalmic preparations; take care in operating machinery or driving a motor vehicle.
Importance of not wearing contact lenses if any signs or symptoms of eye infection are present.
Advise patients to immediately discontinue therapy and contact a clinician if any signs of sensitivity or allergic reaction (e.g., rash, pruritus, swelling, redness) occur or if the condition worsens or does not improve.
Advise patients using fixed-combination ophthalmic preparations containing a corticosteroid to discontinue the drug and contact a clinician if inflammation or pain persists for >48 hours or becomes aggravated.
Importance of informing clinicians of existing or contemplated concomitant therapy, including prescription and OTC drugs, as well as any concomitant illnesses.
Importance of women informing clinicians if they are or plan to become pregnant or plan to breast-feed.
Importance of informing patients of other important precautionary information.

Additional Information

The American Society of Health-System Pharmacists, Inc. represents that the information provided in the accompanying monograph was formulated with a reasonable standard of care, and in conformity with professional standards in the field. Readers are advised that decisions regarding use of drugs are complex medical decisions requiring the independent, informed decision of an appropriate health care professional, and that the information contained in the monograph is provided for informational purposes only. The manufacturer’s labeling should be consulted for more detailed information. The American Society of Health-System Pharmacists, Inc. does not endorse or recommend the use of any drug. The information contained in the monograph is not a substitute for medical care.

Preparations

Excipients in commercially available drug preparations may have clinically important effects in some individuals; consult specific product labeling for details.

Please refer to the ASHP Drug Shortages Resource Center for information on shortages of one or more of these preparations.