This monograph discusses the use of the neomycin, polymyxin B, and hydrocortisone in combination for inflammatory and infectious conditions of the ear, eyes, or skin.
Neomycin, polymyxin B, and hydrocortisone are used together in otic and ophthalmic preparations to treat otitis externa or ocular inflammation. Topical products are also available for treating corticosteroid-responsive dermatoses with secondary infection. The acidity of the cream helps to restore the acidic pH of the skin. Hydrocortisone is a corticosteroid that exhibits both mineralocorticoid and glucocorticoid activity; it is used in these preparations for its antiinflammatory properties. Neomycin is an aminoglycoside antibiotic derived from cultures of Streptomyces fradiae. Polymyxin B is a polypeptide antibiotic derived from a strain of Bacillus polymyxa. Both of these antibiotics affect primarily gram-negative, aerobic bacteria, but are also effective against Staphylococcus aureus (methicillin-sensitive). The FDA approved neomycin, polymyxin B, and hydrocortisone ophthalmic and otic preparations prior to 1982. The FDA first approved neomycin, polymyxin B, and hydrocortisone topical products in 1985.
General Administration Information
For storage information, see the specific product information within the How Supplied section.
Route-Specific Administration
Topical Administration
Cream/Ointment/Lotion Formulations
-Apply sparingly in a thin film to the affected area. If conditions permit, the cream should be gently rubbed into the affected area.
-Avoid application to eyes.
-To avoid risk of infection, use one open bottle per individual patient.
Ophthalmic Administration
-For topical ophthalmic administration only.
-Instruct patient on proper instillation of eye suspension. Shake well before using.
-Patients should not wear contact lenses if they have an ocular infection.
-Do not to touch the tip of the dropper to the eye, eyelid, fingertips, or other surface.
-Keep the bottle tightly closed when not in use.
-To avoid risk of infection, use one open bottle per individual patient.
Otic Administration
-For use in the ear only. Do not use in eyes.
-Avoid touching the dropper to the ear, fingers, or other objects to preserve the sterility of the solution.
-Keep the bottle tightly closed when not in use.
-To avoid risk of infection, use one open bottle per individual patient.
-Otic suspension: Shake well before using.
-The external auditory canal should be thoroughly cleaned and dried with a sterile cotton applicator.
-Patients should lie with the affected ear upward, and then the drops should be instilled. This position should be maintained for a few minutes to facilitate penetration of the drops into the ear canal. Repeat, if necessary, for the opposite ear.
-If preferred, a cotton wick may be inserted into the external ear canal, and then the cotton may be saturated with the solution. This wick should be kept moist by adding additional solution every 4 hours. The wick should be replaced at least once every 24 hours.
This monograph discusses the use of the neomycin, polymyxin B, and hydrocortisone in combination for inflammatory and infectious conditions of the ear, eyes, or skin. Clinicians may wish to consult the individual monographs for more information about the specific adverse reactions of each agent.
Neomycin has been associated with skin sensitization. Sensitivity is more common with chronic use on inflamed skin. Patients have reported allergic contact hypersensitivity 1% or less of the time. The manifestation of the sensitization to neomycin is usually rash (unspecified), low-grade erythema with swelling, dry scaling, and pruritus, or it may manifest as a failure to heal. Periodic examinations for these symptoms are advisable and the patient should discontinue treatment if they are observed. These symptoms regress quickly upon withdrawing the medication. Neomycin may also cause mast cell degranulation and histamine release. Neomycin; polymyxin B; hydrocortisone otic solution may contain potassium metabisulfite which may cause an allergic-type reaction including anaphylactoid reactions or less severe asthmatic episodes in susceptible patients. The over incidence is unknown, but is likely low.
Neomycin ototoxicity can induce permanent sensorineural hearing loss due to cochlear damage, mainly destruction of hair cells in the organ of Corti. The risk of ototoxicity is greater with prolonged use; therefore, the duration of therapy with neomycin; polymyxin B; hydrocortisone otic preparations should be limited to 10 consecutive days. Topical preparations of neomycin; polymyxin B; hydrocortisone should not be used over a wide area or for extended periods of time. If neomycin; polymyxin B; hydrocortisone otic preparations reach the middle ear, stinging and burning can occur.
Superinfection may occur after use of drug-combinations containing corticosteroids and antimicrobials, such as neomycin; polymyxin B; hydrocortisone preparations. Fungal infection and viral infection of the cornea are particularly prone to develop with long-term applications of a corticosteroid. The possibility of fungal invasion must be considered in any persistent corneal ulceration when corticosteroid treatment is being used.
Local adverse reactions have been reported with topical corticosteroids, such as neomycin; polymyxin B; hydrocortisone, especially when the preparation is covered by occlusive dressings: burning, pruritus, skin irritation, xerosis, folliculitis, hypertrichosis, acneiform eruptions, skin hypopigmentation, perioral dermatitis, allergic contact dermatitis, maceration of the skin, skin atrophy, striae, and miliaria.
Adverse reactions to the ocular preparations of neomycin; polymyxin B; hydrocortisone preparations include blurred vision after instillation, ocular irritation including swelling, ocular pruritus, and conjunctival erythema due to allergic reactions to the antibiotic components. Reactions due to the corticosteroid component include elevation of intraocular pressure (IOP) with possible development of glaucoma or ocular hypertension, infrequent optic nerve damage; formation of posterior subcapsular cataracts; and delayed wound healing. Corticosteroid-containing products have also been reported to cause perforation of the globe. Keratitis, conjunctivitis, corneal ulcers/corneal erosion, and conjunctival hyperemia have also been reported.
Nephrotoxicity or renal failure (unspecified) has been reported with the use of neomycin. Combination topical products, such as neomycin; polymixin B; hydrocortisone should not be used over a wide area or for extended periods of time.
This monograph discusses the use of the neomycin, polymyxin B, and hydrocortisone in combination for inflammatory and infectious conditions of the ear, eyes, or skin. Clinicians may wish to consult the individual monographs for more information about the specific contraindications and precautions of each agent.
Neomycin; polymyxin B; hydrocortisone products are contraindicated in patients who are allergic to any of the components including those patients with aminoglycoside hypersensitivity or neomycin hypersensitivity. Patients should be monitored for the development of neomycin hypersensitivity, and the patient should discontinue treatment if symptoms are observed. Long-term use of neomycin products may place the patient at risk to develop neomycin hypersensitivity. Patients should avoid neomycin-containing products after the development of this reaction
The manufacturers recommend that neomycin; polymyxin B; hydrocortisone products not be used in patients with a fungal infection or viral infection including varicella-zoster(e.g., chickenpox) or other herpes infection (e.g., herpes simplex or vaccinia). The ophthalmic preparations are contraindicated in fungal infections of ocular structures, most viral infections of the cornea and conjunctiva, including epithelial herpes simplex keratitis (dendritic keratitis), vaccinia, varicella, and mycobacterial infection of the eye. The topical cream is not recommended in patients with cutaneous tuberculosis. Secondary infections, especially of fungi, may occur with prolonged use of neomycin; polymyxin B; hydrocortisone products. In acute purulent conditions of the eye, corticosteroids may mask infection or enhance existing infection. It is recommended that the topical cream not be used for longer than 7 days and the otic or ophthalmic preparations should not be used for longer than 10 days to avoid development of secondary infections.
Systemic absorption of neomycin may occur following application to denuded or damaged epithelium. Following systemic absorption of neomycin in patients with renal impairment or renal failure, there is a risk of developing ototoxicity that is irreversible and progressive even after the therapy is stopped.
Avoid ocular exposure of neomycin; polymyxin B; hydrocortisone topical cream or otic preparations. The ophthalmic preparations should never be directly introduced into the anterior chamber of the eye.
Neomycin; polymyxin B; hydrocortisone otic products should be avoided in patients with tympanic membrane perforation or with chronic otitis media because of the possibility of ototoxicity. Additionally, the acidity of the neomycin; polymyxin B; hydrocortisone otic solution may cause burning and stinging in patients with perforated tympanic membrane.
Signs and symptoms of exogenous hyperadrenocorticism can occur with the use of topical corticosteroids, including hypothalamic-pituitary-adrenal (HPA) suppression. Systemic absorption of topical steroids, such as neomycin; polymixin B; hydrocortisone, will be increased if an extensive body surface area is treated or if an occlusive dressing is used. In children, sufficient absorption of hydrocortisone may occur during prolonged use, causing growth inhibition, as well as other signs and symptoms of hyperadrenocorticism.
Caution is warranted with the use of neomycin; polymyxin B; hydrocortisone products during pregnancy. Topical corticosteroids have been shown to be teratogenic in animals. There are no adequate and well controlled studies in pregnant women, therefore topical corticosteroid-containing products should only be used during pregnancy if the potential benefit justifies the potential risk to the fetus. Because of the minimal systemic absorption of neomycin; polymyxin B; hydrocortisone after topical otic/ophthalmic administration, there is expected to be minimal risk of maternal and fetal toxicity when administered during pregnancy.
Neomycin; polymyxin B; hydrocortisone otic solutions may contain potassium metabisulfite that may cause allergic-type reactions and life-threatening or severe asthmatic episodes in patients with sulfite hypersensitivity; this product should be avoided in these patients. Although the overall incidence of sulfite sensitivity is low, people with asthma may be at increased risk.
The manufacturer recommends that neomycin; polymyxin B; hydrocortisone products should be used cautiously in women who are breast-feeding. Hydrocortisone appears in breast milk following oral administration and there is a minimal possibility of systemic absorption following topical administration. Trace amounts of endogenous hydrocortisone (cortisol) are excreted in breast milk; however, no reports of exogenous hydrocortisone excretion into breast milk exist. The American Academy of Pediatrics (AAP) states that another steroid, prednisone, is usually compatible with breast-feeding. Another report states that systemic steroids used in asthma patients are compatible with breast-feeding. Topical, otic, and ophthalmic use of neomycin and polymyxin B would result in minimal absorption. 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. Oral ingestion by the nursing infant would also result in minimal absorption. Only water-miscible cream products should be applied to the breast because ointments may expose the infant to high levels of mineral paraffins. Topical creams should not be applied directly to the breast during lactation if breast-feeding. 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.
Ocular corticosteroids should be used with caution in patients with glaucoma. If neomycin; polymyxin B; hydrocortisone ophthalmic products are used for 10 days or longer, intraocular pressure should be routinely monitored due to the risk development of ocular hypertension or glaucoma. The initial prescription and renewal of the medication order beyond 20 ml should be made only after examination of the patient with aid of magnification such as slit lamp biomicroscopy, and where appropriate, fluorescein staining. If signs and symptoms fail to improve after 2 days, the patient should be re-evaluated. Use of neomycin; polymyxin B; hydrocortisone ophthalmic products after cataract surgery may delay healing and increase the incidence of filtering blebs.
Patients who wear contact lenses should avoid wearing them while being treated with neomycin; polymyxin B; hydrocortisone ophthalmic products for an ocular infection.
Geriatric patients are more likely to have damaged skin through aging, and this may increase the risk of side effects from neomycin; polymyxin B; hydrocortisone combination products. Corticosteroid-containing skin preparations should only be used for brief periods and infrequently in older patients. Clinical studies did not include sufficient numbers of subjects aged 65 years and over to determine whether they respond differently from younger subjects. Other reported clinical experience has not identified differences in responses between the elderly and younger patients. In general, dose selection for an elderly patient should be cautious, usually starting at the low end of the dosing range, reflecting the greater frequency of decreased hepatic, renal, or cardiac function, and of concomitant disease or other drug therapy.
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: Enterobacter sp., Escherichia coli, Haemophilus influenzae (beta-lactamase negative), Haemophilus influenzae (beta-lactamase positive), Klebsiella sp., Neisseria sp., Pseudomonas aeruginosa, Staphylococcus aureus (MSSA)
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 bacterial infections of the external auditory canal (i.e., otitis externa) caused by susceptible organisms, and for the treatment of infections of mastoidectomy and fenestration caused by susceptible organisms:
Otic dosage (solution or suspension):
NOTE: If the infection does not improve after 1 week of treatment, cultures and susceptibility tests should be repeated to verify the identity of the organism and to determine whether therapy should be changed.
Adults: 4 drops in affected ear(s) 3 to 4 times daily. Treatment should not be continued longer than 10 days.
Infants, Children, and Adolescents: 3 drops in affected ear(s) 3 to 4 times daily. Treatment should not be continued longer than 10 days.
For the treatment of corticosteroid-responsive inflammatory ocular conditions and where bacterial ophthalmic infection or a risk of bacterial ophthalmic infection exists (e.g., inflammation of palpebral and bulbar conjunctiva, cornea and anterior segment of the globe where the inherent risk of corticosteroid use in bacterial conjunctivitis is accepted to obtain a decrease in edema and inflammation; also in chronic anterior uveitis and corneal injury from chemical, radiation, or thermal burns, or penetration of foreign objects):
Ophthalmic dosage:
Adults: 1 to 2 drops in affected eye(s) every 3 to 4 hours, depending upon the severity of the infection. The suspension may be used more frequently if necessary. Not more than 20 mL should be prescribed initially and the prescription should not be refilled without further evaluation.
For the treatment of corticosteroid-responsive dermatoses with secondary infection:
Topical dosage (topical cream or ointment):
Adults: Apply as a thin film topically to the affected area 2 to 4 times daily. Therapy should be limited to 7 days.
Maximum Dosage Limits:
-Adults
Maximum dosage information not available.
-Geriatric
Maximum dosage information not available.
-Adolescents
Maximum dosage information not available.
-Children
Maximum dosage information for otic product not available; safety and efficacy of ophthalmic and topical products not established.
-Infants
Maximum dosage information for otic product not available; safety and efficacy of ophthalmic and topical products not established.
Patients with Hepatic Impairment Dosing
No dosage adjustment is needed.
Patients with Renal Impairment Dosing
No dosage adjustment is needed.
*non-FDA-approved indication
There are no drug interactions associated with Neomycin; Polymyxin B; Hydrocortisone products.
Mechanism of Action:-Neomycin: Neomycin is bacteriocidal. It inhibits bacterial protein synthesis through irreversible binding to the 30S ribosomal subunit of susceptible bacteria. Neomycin is actively transported into the bacterial cell where it binds to receptors present on the 30S ribosomal subunit. This binding interferes with the initiation complex between the messenger RNA (mRNA) and the subunit. As a result, abnormal, nonfunctional proteins are formed due to misreading of the bacterial DNA. Eventually, susceptible bacteria die because of the lack of functional proteins. Neomycin may also inhibit DNA polymerase.
-Polymyxin B: Polymyxin B binds to gram-negative bacterial cell membrane phospholipids. 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.
-Hydrocortisone: The antiinflammatory activity of hydrocortisone is thought to involve phospholipase A2 inhibitory proteins, collectively called lipocortins. Lipocortins control the biosynthesis of potent mediators of inflammation, such as prostaglandins and leukotrienes, by inhibiting the release of the precursor molecule arachidonic acid.
Neomycin; polymyxin B; hydrocortisone combination products are applied topically to the ear, eye, or skin. Systemic absorption may occur in some "at risk" individuals. After systemic absorption, neomycin and polymyxin B are excreted by the kidney.
-Route-Specific Pharmacokinetics
Topical Route
Except when applied to large areas or for an extended period of time, systemic absorption of topical neomycin; polymyxin B; hydrocortisone is negligible. Hydrocortisone is metabolized in the skin. Polymyxin B has a high affinity for cell membranes, so there is little systemic absorption even when applied to open wounds. Neomycin may be absorbed systemically if applied to denuded or damaged epithelium.
-Special Populations
Renal Impairment
Patients with renal dysfunction may develop ototoxicity or worsening nephrotoxicity following prolonged systemic exposure to the neomycin or polymyxin B components due to reduced drug elimination.