CLASSES

Ophthalmological Corticosteroid and Anti-infective Combinations
Topical Aminoglycosides, Plain or in Combination

DEA CLASS

Rx

DESCRIPTION

Neomycin and polymyxin B affect primarily gram-negative, aerobic bacteria, while bacitracin is effective against gram-positive organisms; available in ophthalmic and topical forms.

COMMON BRAND NAMES

AK-Spore HC, AK-Spore HC Ophthalmic, Cortisporin, Cortomycin, Neo-Polycin HC, Ocu-Cort

HOW SUPPLIED

AK-Spore HC/AK-Spore HC Ophthalmic/Cortisporin/Cortomycin/Neomycin, Polymyxin B, Bacitracin Zinc, Hydrocortisone/Neo-Polycin HC/Ocu-Cort Ophthalmic Ointment
Cortisporin Topical Ointment

DOSAGE & INDICATIONS

MAXIMUM DOSAGE

8 g or 10 days for ophthalmic ointment then reevaluate before further therapy; 4 applications/day for up to 7 days topically.

8 g or 10 days for ophthalmic ointment then reevaluate before further therapy; 4 applications/day for up to 7 days topically.

Safety and efficacy have not been established.

Safety and efficacy have not been established.

Safety and efficacy have not been established.

DOSING CONSIDERATIONS

No dosage adjustment is needed.

No dosage adjustment is needed; use caution with prolonged therapy under conditions where systemic exposure is possible.

ADMINISTRATION

Apply sparingly in a thin film to the affected area.
Do not cover with an occlusive dressing. A light gauze dressing may be used if required.
To avoid risk of infection, use one open tube per individual patient.

For topical ophthalmic administration only.
Instruct patient on proper instillation of eye ointment.
Patients should not wear contact lenses if they have an ocular infection.
Do not to touch the tip of the applicator to the eye, eyelid, fingertips, or other surface.
Apply directly into the conjunctival sac. In blepharitis all scales and crusts should be carefully removed and the ointment then spread uniformly over the lid margins.
Keep tightly closed when not in use.
To avoid risk of infection, use one open tube per individual patient.

STORAGE

AK-Spore HC :
- Store at controlled room temperature (between 68 and 77 degrees F)
AK-Spore HC Ophthalmic:
- Store at controlled room temperature (between 68 and 77 degrees F)
Cortisporin:
- Store at controlled room temperature (between 68 and 77 degrees F)
Cortomycin :
- Store at controlled room temperature (between 68 and 77 degrees F)
Neo-Polycin HC:
- Store at controlled room temperature (between 68 and 77 degrees F)
Ocu-Cort:
- Store at controlled room temperature (between 68 and 77 degrees F)

CONTRAINDICATIONS / PRECAUTIONS

NOTE: This monograph discusses the use of the bacitracin, hydrocortisone, neomycin, and polymyxin B in combination for inflammatory and infectious conditions of the eyes or skin. Clinicians may wish to consult the individual monographs for more information about the specific contraindications and precautions of each agent.

Bacitracin; hydrocortisone; neomycin; polymyxin B products are contraindicated in patients who are allergic to any of the components including those patients with aminoglycoside hypersensitivity, polymyxin 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 such reactions. Use with caution in patients with a stated corticosteroid hypersensitivity.

Use of bacitracin; hydrocortisone; neomycin; polymyxin B products is contraindicated in the treatment of fungal infection or viral infection including varicella-zoster or other herpes infection (e.g., herpes simplex or vaccinia). Specifically, 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. Further, the topical ointment is contraindicated in cutaneous tuberculosis lesions. Secondary infections, especially of fungi, may occur with prolonged use of bacitracin-hydrocortisone-neomycin-polymyxin B products. In acute purulent conditions of the eye, corticosteroids may mask infection or enhance existing infection. It is recommended that the topical ointment not be used for longer than 7 days and the ophthalmic preparations should not be used for longer than 10 days to avoid development of secondary infections.

Hearing loss is associated with the use of neomycin-containing products, particularly with prolonged use. Systemic absorption of bacitracin and neomycin may occur following topical application to denuded or damaged epithelium. Following systemic absorption of these agents in patients with renal impairment or renal failure, there is a risk of developing ototoxicity (hearing impairment) that is irreversible and progressive even after the therapy is stopped.

Bacitracin; hydrocortisone; neomycin; polymyxin B topical skin ointment is contraindicated for all ocular exposure and is contraindicated for external ear canal application if the eardrum is perforated (tympanic membrane perforation).

Ocular corticosteroids should be used with caution in patients with glaucoma. If bacitracin; hydrocortisone; neomycin; polymyxin B ophthalmic products are used for 10 days or longer, intraocular pressure should be routinely monitored due to the risk development of glaucoma. Prolonged use of corticosteroids may result in ocular hypertension with damage to the optic nerve, defects in visual acuity and fields of vision, and in posterior subcapsular cataracts formation. The initial prescription and renewal of the medication order beyond 8 g should be made only after ophthalmic 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 these ophthalmic products after ocular surgery for cataracts or other corneal procedures may retard wound healing and increase the incidence of filtering blebs. The ophthalmic ointment should never be directly introduced into the anterior chamber of the eye.

Patients who wear contact lenses should avoid wearing them while being treated with bacitracin; hydrocortisone; neomycin; polymyxin B ophthalmic products for an ocular infection.

Bacitracin; hydrocortisone; neomycin; polymyxin B ophthalmic and topical products are classified as FDA pregnancy risk category C. Although systemic exposures of all 4 components are expected to be minimal, use of topical corticosteroids, such as hydrocortisone, have been shown to be teratogenic in animals. No adequate and well-controlled studies have been conducted in pregnant women, therefore this medication should only be used during pregnancy if the potential benefit justifies the potential risk to the fetus.

It is unknown if bacitracin, neomycin, or polymyxin B are excreted in breast milk; however, hydrocortisone does appear in human milk following oral administration. Therefore, bacitracin; hydrocortisone; neomycin; polymyxin B products should be used cautiously in nursing mothers even though systemic absorption following topical and ophthalmic application is negligible. To minimize potential infant exposure, instruct mothers not to apply the topical products directly to the breast during times of breast-feeding. If using the ophthalmic products, instruct patients to apply pressure over the tear duct by the corner of the eye for 1 minute after each 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, health care providers are encouraged to report the adverse effect to the FDA.

Use of topical corticosteroids may result in signs and symptoms of exogenous hyperadrenocorticism; use with caution in patients with pre-existing hypothalamic-pituitary-adrenal (HPA) suppression. Systemic absorption of topical corticosteroids 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 topical use to cause inhibition of growth, as well as other signs and symptoms of hyperadrenocorticism. The safety and efficacy of bacitracin; hydrocortisone; neomycin; polymyxin B topical and ophthalmic formulations have not been established in neonates, infants, or children.

Clinical studies have not identified a difference in response to bacitracin; hydrocortisone; neomycin; polymyxin B products among patients 65 years and older as compared to younger patients. However, geriatric patients are more likely to have damaged skin through aging, and this may increase the risk of side effects following topical use. No age-based precautions are associated with ophthalmic formulations of this medication.

ADVERSE REACTIONS

hearing loss / Delayed / Incidence not known
skin atrophy / Delayed / Incidence not known
ocular hypertension / Delayed / Incidence not known

erythema / Early / 1.0-1.0
superinfection / Delayed / Incidence not known
impaired wound healing / Delayed / Incidence not known
contact dermatitis / Delayed / Incidence not known
cataracts / Delayed / Incidence not known

rash / Early / 1.0-1.0
pruritus / Rapid / 1.0-1.0
skin hypopigmentation / Delayed / Incidence not known
folliculitis / Delayed / Incidence not known
striae / Delayed / Incidence not known
miliaria / Delayed / Incidence not known
acneiform rash / Delayed / Incidence not known
xerosis / Delayed / Incidence not known
hypertrichosis / Delayed / Incidence not known
skin irritation / Early / Incidence not known
ocular pruritus / Rapid / Incidence not known
ocular irritation / Rapid / Incidence not known

DRUG INTERACTIONS

Amphotericin B lipid complex (ABLC): (Minor) Additive nephrotoxicity may occur with concurrent use of systemic bacitracin and other nephrotoxic agents, such as amphoteracin B; when possible, avoid concomitant administration. Topical administration of any preparation containing bacitracin, especially when applied to large surface areas, should not be given with other drugs that have a nephrotoxic potential.
Amphotericin B liposomal (LAmB): (Minor) Additive nephrotoxicity may occur with concurrent use of systemic bacitracin and other nephrotoxic agents, such as amphoteracin B; when possible, avoid concomitant administration. Topical administration of any preparation containing bacitracin, especially when applied to large surface areas, should not be given with other drugs that have a nephrotoxic potential.
Amphotericin B: (Minor) Additive nephrotoxicity may occur with concurrent use of systemic bacitracin and other nephrotoxic agents, such as amphoteracin B; when possible, avoid concomitant administration. Topical administration of any preparation containing bacitracin, especially when applied to large surface areas, should not be given with other drugs that have a nephrotoxic potential.
Bumetanide: (Minor) Additive nephrotoxicity may occur with concurrent use of systemic bacitracin and other nephrotoxic agents. When possible, avoid concomitant administration of systemic bacitracin and other nephrotoxic drugs such as loop diuretics. Topical administration of any preparation containing bacitracin, especially when applied to large surface areas, also should not be given with other drugs that have a nephrotoxic potential.
Ethacrynic Acid: (Minor) Additive nephrotoxicity may occur with concurrent use of systemic bacitracin and other nephrotoxic agents. When possible, avoid concomitant administration of systemic bacitracin and other nephrotoxic drugs such as loop diuretics. Topical administration of any preparation containing bacitracin, especially when applied to large surface areas, also should not be given with other drugs that have a nephrotoxic potential.
Furosemide: (Minor) Additive nephrotoxicity may occur with concurrent use of systemic bacitracin and other nephrotoxic agents. When possible, avoid concomitant administration of systemic bacitracin and other nephrotoxic drugs such as loop diuretics. Topical administration of any preparation containing bacitracin, especially when applied to large surface areas, also should not be given with other drugs that have a nephrotoxic potential.
Loop diuretics: (Minor) Additive nephrotoxicity may occur with concurrent use of systemic bacitracin and other nephrotoxic agents. When possible, avoid concomitant administration of systemic bacitracin and other nephrotoxic drugs such as loop diuretics. Topical administration of any preparation containing bacitracin, especially when applied to large surface areas, also should not be given with other drugs that have a nephrotoxic potential.
Torsemide: (Minor) Additive nephrotoxicity may occur with concurrent use of systemic bacitracin and other nephrotoxic agents. When possible, avoid concomitant administration of systemic bacitracin and other nephrotoxic drugs such as loop diuretics. Topical administration of any preparation containing bacitracin, especially when applied to large surface areas, also should not be given with other drugs that have a nephrotoxic potential.

PREGNANCY AND LACTATION

Bacitracin; hydrocortisone; neomycin; polymyxin B ophthalmic and topical products are classified as FDA pregnancy risk category C. Although systemic exposures of all 4 components are expected to be minimal, use of topical corticosteroids, such as hydrocortisone, have been shown to be teratogenic in animals. No adequate and well-controlled studies have been conducted in pregnant women, therefore this medication should only be used during pregnancy if the potential benefit justifies the potential risk to the fetus.

It is unknown if bacitracin, neomycin, or polymyxin B are excreted in breast milk; however, hydrocortisone does appear in human milk following oral administration. Therefore, bacitracin; hydrocortisone; neomycin; polymyxin B products should be used cautiously in nursing mothers even though systemic absorption following topical and ophthalmic application is negligible. To minimize potential infant exposure, instruct mothers not to apply the topical products directly to the breast during times of breast-feeding. If using the ophthalmic products, instruct patients to apply pressure over the tear duct by the corner of the eye for 1 minute after each 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, health care providers are encouraged to report the adverse effect to the FDA.

MECHANISM OF ACTION

•Bacitracin: Bacitracin is primarily bacteriostatic, but may have bacteriocidal activity depending upon the antibiotic concentration and the susceptibility of the organism. Bacitracin inhibits bacterial cell wall formation. Bacitracin inhibits the final dephosphorylation step in the phospholipid carrier cycle, which inhibits mucopeptide transfer to the growing cell wall. Bacitracin is active against many gram-positive organisms and some gram-negative 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: 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.
 
Bacitracin, polymyxin B sulfate, and neomycin sulfate in combination are considered active against the following microorganisms: Enterobacter sp., Escherichia coli, Haemophilus influenzae, Klebsiella sp., Neisseria sp., Pseudomonas aeruginosa, Staphylococcus aureus, and Streptococcus sp., including Streptococcus pneumoniae. These agents do not provide adequate coverage against Serratia marcescens.

PHARMACOKINETICS

Bacitracin; hydrocortisone; neomycin; polymyxin B combination products are applied topically to the eye or skin.