colistin/hydrocortisone/neomycin/thonzonium otic (Rx)

Frequency Not Defined

To report suspected adverse reactions, contact Endo Pharmaceuticals Inc. at 1-800-462-3636 or MEDWATCH at 1-800-FDA-1088 or http://www.fda.gov/medwatch/

Neomycin

• Skin sensitization
• Ototoxicity
• Nephrotoxicity

Hydrocortisone

• Burning
• Itching
• Irritation
• Dryness
• Folliculitis
• Hypertrichosis
• Acneiform eruptions
• Hypopigmentation
• Perioral dermatitis
• Allergic contact dermatitis
• Skin maceration
• Secondary infection
• Skin atrophy
• Striae
• Miliaria

Contraindications

Hypersensitivity

Do not use if external auditory canal disorder is suspected or known to be due to cutaneous viral infection (eg, herpes simplex virus, varicella-zoster virus)

Cautions

For otic use only

Neomycin can induce permanent sensorineural hearing loss due to cochlear damage, mainly destruction of hair cells in organ of Corti; the risk is greater with prolonged use

Therapy should be limited to 10 consecutive days; patients being treated with eardrops containing neomycin should be under close clinical observation

Should be used cautiously in any patient with a perforated tympanic membrane

Neomycin sulfate may cause cutaneous sensitization; a precise incidence of hypersensitivity reactions (primarily skin rash) due to topical neomycin is not known; discontinue promptly if sensitivity or irritation occurs

When using neomycin-containing products to control secondary infection in the chronic dermatoses, such as chronic otitis externa or stasis dermatitis, it should be borne in mind that the skin in these conditions is more liable than is normal skin to become sensitized to many substances, including neomycin

The manifestation of sensitization to neomycin is usually alow-grade reddening with swelling, dry scaling, and itching; it may be manifest simply as a failure to heal

Periodic examination for such signs is advisable, and the patient should be told to discontinue the product if they are observed; these symptoms regress quickly on withdrawing the medication; neomycin containing applications should be avoided for the patient thereafter

As with any other antibiotic preparation, prolonged treatment may result in overgrowth of nonsusceptible organisms and fungi; if the infection is not improved after one week, cultures should be repeated to verify the identity of the organism and to determine whether therapy should be changed

Treatment should not be continued for longer than ten days

Allergic cross-reactions may occur which could prevent the use of any or all of the aminoglycoside antibiotics for treatment of future infections

Not for use in eyes

Pregnancy

There are no adequate and well-controlled studies of this drug in pregnant women; not known whether therapy can cause fetal harm when administered to a pregnant woman

Administer during pregnancy only if potential benefit justifies potential risk to the fetus

Colistimethate sodium, the methanesulfonate salt of colistin, was not teratogenic in rats or rabbits given intramuscular doses up to 20 mg/kg (equivalent to 9.3 mg/kg of colisitin base, approximately 30 times (rats) or 55 times (rabbits) clinical daily dose based on body surface area and assuming 100% absorption from the ear)

Colistin has not been shown to have any adverse effects on developing embryo or fetus at doses relevant to amount that will be delivered ototopically at recommended clinical doses

Although aminoglycosides can cause congenital deafness in humans if administered during pregnancy, significant systemic levels of neomycin would not be anticipated when the drug is used as directed

Corticosteroids are generally teratogenic in laboratory animals when administered systemically at relatively low dosage levels; the more potent corticosteroids have been shown to be teratogenic after dermal application in laboratory animals

Lactation

Hydrocortisone and colistin sulfate appears in human milk following oral administration of the drugs; since systemic absorption of these drugs may occur when they are used topically, use caution when drug is used by a nursing woman

Pregnancy Categories

A: Generally acceptable. Controlled studies in pregnant women show no evidence of fetal risk.

B: May be acceptable. Either animal studies show no risk but human studies not available or animal studies showed minor risks and human studies done and showed no risk.

C: Use with caution if benefits outweigh risks. Animal studies show risk and human studies not available or neither animal nor human studies done.

D: Use in LIFE-THREATENING emergencies when no safer drug available. Positive evidence of human fetal risk.

X: Do not use in pregnancy. Risks involved outweigh potential benefits. Safer alternatives exist.

NA: Information not available.

Mechanism of Action

Colistin: Polypeptide antibiotic; penetrates into and disrupts the bacterial cell membrane

Hydrocortisone: Corticosteroid; thought to act by regulating the rate of protein synthesis; it controls inflammation, edema, pruritus, and other dermal reactions

Neomycin: Aminoglycoside antibiotic; inhibits protein synthesis, disrupting the normal cycle of ribosomal function

Thonzonium: Surface-active agent that promotes tissue contact by dispersion and penetration of cellular debris and exudate

Microbiology

• Together, colistin and neomycin elicit bactericidal activity against most strains of the following organisms in vitro
• Aerobic gram-positive microorganisms: Staphylococcus aureus
• Aerobic gram-negative microorganisms: Enterobacter aerogenes, Escherichia coli, Klebsiella pneumoniae, Pseudomonas aeruginosa