Coly-Mycin® S Otic with Neomycin and Hydrocortisone (colistin sulfate—neomycin sulfate—thonzonium bromide—hydrocortisone acetate otic suspension) is a sterile antibacterial and anti-inflammatory aqueous suspension containing in each mL: Colistin base activity, 3 mg (as the sulfate); Neomycin base activity, 3.3 mg (as the sulfate); Hydrocortisone acetate, 10 mg (1%); Thonzonium bromide, 0.5 mg (0.05%); Polysorbate 80, acetic acid, and sodium acetate in a buffered aqueous vehicle. Thimerosal (mercury derivative), 0.002%, is added as a preservative. It is a nonviscous liquid, buffered at pH 5, for instillation into the canal of the external ear or direct application to the affected aural skin.

The structural formulas of colistin sulfate (mixture of Colistin A & B), neomycin sulfate (mixture of neomycin A, B & C), hydrocortisone acetate ((11β)-21-(acety-loxy)-11,17-dihydroxypregn) methyl]-2 pyrimidinylamino] ethyl]-N,N-dimethyl-1-hexadecanaminium, bromide) are represented below:

Coly-Mycin® S Otic is indicated for the treatment of superficial bacterial infections of the external auditory canal, caused by organisms susceptible to the action of the antibiotics; and for the treatment of infections of mastoidectomy and fenestration cavities, caused by organisms susceptible to the antibiotics.

Therapy with this product should be limited to 10 days. (See WARNINGS.)

The external auditory canal should be thoroughly cleansed and dried with a sterile cotton applicator.

When using the calibrated dropper:

For adults, 5 drops of the suspension should be instilled into the affected ear 3 or 4 times daily using the provided dropper. For pediatric patients, 4 drops (using the provided dropper) are suggested because of the smaller capacity of the ear canal.

The patient should lie with the affected ear upward and then the drops should be instilled. This position should be maintained for 5 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 canal and then the cotton may be saturated with the suspension. This wick should be kept moist by adding further solution every 4 hours. The wick should be replaced at least once every 24 hours.

Coly-Mycin® S Otic is supplied as: NDC 64029-3141-1.....................5 mL bottle with dropper

Each mL contains: Colistin sulfate equivalent to 3 mg of colistin base activity, Neomycin sulfate equivalent to 3.3 mg neomycin base activity, Hydrocortisone acetate 10 mg (1%), Thonzonium bromide 0.5 mg (0.05%), and Polysorbate 80 in an aqueous vehicle buffered with acetic acid and sodium acetate. Thimerosal (mercury derivative) 0.002% is added as a preservative.

A sterilized dropper-cap assembly for use on the bottle of suspension is included in the package.

Shake well before using.

Store at 20°–25°C (68°–77°F). (See USP controlled room temperature.)

Manufactured by: Parkedale Pharmaceuticals, Inc., Rochester, MI 48307. Prescribing Information as of March 2002. FDA Rev date: 3/1/2002

Neomycin occasionally causes skin sensitization.

Ototoxicity (see WARNINGS section) and nephrotoxicity have also been reported. Adverse reactions have occurred with topical use of antibiotic combinations. Exact incidence figures are not available since no denominator of treated patients is available. The reaction occurring most often is allergic sensitization. In one clinical study, using a 20% neomycin patch, neomycin-induced allergic skin reactions occurred in two of 2,175 (0.09%) individuals in the general populaton.² In another study the incidence was found to be approximately 1%.³

The following local adverse events have been reported with topical corticosteroids, especially under occlusive dressings: burning, itching, irritation, dryness, folliculi-tis, hypertrichosis, acneiform eruptions, hypopigmentation, perioral dermatitis, allergic contact dermatitis, maceration of the skin, secondary infection, skin atrophy, striae, and miliaria.

No information provided.

REFERENCES

2. Leyden JJ, Kligman AM. Contact dermatitis to neomycin sulfate. JAMA1979; 242 (12): 1276–1278.

3. Prystowsky SD, Allen AM, Smith RW, et al. Allergic contact hypersensitivity to nickel, neomycin, ethylenediamine, and benzocaine; relationship between age, sex, history of exposure, and reactivity to standard patch tests and use tests in a general populaton. Arch Dermatol 1979; 115:959–962.

Neomycin can induce permanent sensorineural hearing loss due to cochlear damage, mainly destruction of hair cells in the organ of Corti. The risk is greater with prolonged use. Therapy should be limited to 10 consecutive days. (See PRECAUTIONS - General.) Patients being treated with eardrops containing neomycin should be under close clinical observation. Coly-Mycin® S Otic 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 ususally a low-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.

General

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 the treatment of future infections.

Laboratory Tests

Systemic effects of excessive levels of hydrocortisone may include a reduction in the number of circulating eosinophils and a decrease in urinary excretion of 17-hydroxycorticosteroids.

Carcinogenesis, Mutagenesis, Impairment of Fertility

Long-term animal carcinogenicity studies have not been performed with colistin or neomycin, or Coly-Mycin® S Otic. An increased incidence of chromosome aberrations in human lymphocytes has been reported following in vitro exposure to colistin or neomycin.

Fertility studies have not been performed with neomycin, but reports from the scientific literature suggest that it may decrease spermatogenesis in rats. No adverse effects on fertility were observed in male or female rats given intramuscular doses of colistimethate sodium, the methanesulfonate salt of colistin, up to 20 mg/kg (equivalent to 9.3 mg/kg of colistin base). This is approximately 30 times the clinical daily dose based on body surface area, assuming 100% absorption from the ear; however, significant systemic levels of colistin or neomycin would not be anticipated in humans when Coly-Mycin® S Otic is used as directed.

Long term studies in rodents showed no evidence of carcinogenicity attributable to oral administration of corticosteroids. Mutagenicity studies with hydrocortisone were negative. Studies have not been performed to evaluate the effect on fertility of topical corticosteroids.

Pregnancy-Teratogenic Effects

Pregnancy Category C – There are no adequate and well controlled studies of Coly-Mycin® S Otic in pregnant women. It is not known whether Coly-Mycin® S Otic can cause fetal harm when administered to a pregnant woman.

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) the clinical daily dose based on body suface area and assuming 100% absorption from the ear). Increased resorptions were observed in rabbits at 20 mg/kg, but not 10 mg/kg (equivalent to 4.15 mg/kg of colistin base). Decreased pup survival at weaning was observed in rats at 20 mg/kg, a maternally toxic dose of colistin, but not 10 mg/kg. Colistin has not been shown to have any adverse effects on the developing embryo or fetus at doses relevant to the amount that will be delivered ototopically at the 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 Coly-Mycin® S Otic 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. Coly-Mycin® S Otic should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus.

Nursing Mothers

Hydrocortisone and colistin sulfate appear in human milk following oral administration of the drugs. Since systemic absorption of these drugs may occur when they are used topically, caution should be exercised when Coly-Mycin® S Otic Suspension is used by a nursing woman.

Pediatric Use

See DOSAGE AND ADMINISTRATION.

No information provided.

This product is contraindicated in those individuals who have shown hypersensitivity to any of its components.

This product should not be used if the external auditory canal disorder is suspected or known to be due to cutaneous viral infection (e.g., herpes simplex virus or varicella zoster virus).

Colistin sulfate is a polypeptide antibiotic which penetrates into and disrupts the bacterial cell membrane. Neomycin sulfate is an aminoglycoside antibiotic which inhibits protein synthesis, disrupting the normal cycle of ribosomal function. Hydrocortisone acetate is a corticosteroid hormone which is thought to act by regulating the rate of protein synthesis; it controls inflammation, edema, pruritus and other dermal reactions. Cortiscosteroids suppress the inflammatory response to a variety of agents and they may delay healing. Since corticoids may inhibit the body's defense mechanism against infection, a concomitant antimicrobial drug may be used when this inhibition is considered to be clinically significant in a particular case.

The relative potency of corticosteroids depends on the molecular structure, concentration, and release from the vehicle.

Thonzonium bromide is a surface-active agent that promotes tissue contact by dispersion and penetration of the cellular debris and exudate.

Microbiology

Together, colistin sulfate and neomycin sulfate have bactericidal activity against most strains of the following microorganisms, both in vitro and in clinical infections as described in the INDICATIONS section.

Aerobic gram-positive microorganisms:

Staphylococcus aureus.

Aerobic gram-negative microorganisms:

Enterobacter aerogenes
Escherichia coli
Klebsiella pneumoniae
Pseudomonas aeruginosa.

Susceptibility Tests

It is not recommended that colistin sulfate or neomycin sulfate be routinely tested and reported by clinical microbiology laboratories.¹

REFERENCES

1. National Committee for Clinical Laboratory Standards, Suggested Groupings of U.S. FDA Approved Antimicrobial Agents That Should be Considered for Routine Testing and Reporting on Nonfastidious Organisms by Clinical Microbiology Laboratories, Table 1-M2-A6 (M100-S7), NCCLS Vol. 17, No. 1, Wayne, PA, 1997.

Avoid contaminating the dropper with material from the ear, fingers, or other source. This caution is necessary if the sterility of the drops is to be preserved. If sensitization or irritation occurs, discontinue use immediately and contact your physician.

Do not use in the eyes.

If you prefer to warm the medication before using it, do not heat the suspension above body temperature in order to avoid loss of potency.

SHAKE WELL BEFORE USING.

IMPORTANT NOTE: This is a summary and does not contain all possible information about this product. For complete information about this product or your specific health needs, ask your health care professional. Always seek the advice of your health care professional if you have any questions about this product or your medical condition. This information is not intended as individual medical advice and does not substitute for the knowledge and judgment of your health care professional. This information does not contain any assurances that this product is safe, effective, or appropriate for you.

NEOMYCIN/COLISTIN/HYDROCORTISONE/THONZONIUM SUSPENSION - OTIC

(nee-oh-MY-sin/koh-LIH-stin/hi-dro-KOR-tih-sown/thon-ZHO-nee-um)

COMMON BRAND NAME(S): Cortisporin-TC

USES: This ear drop is used to treat outer ear infections caused by bacteria (also known as swimmer's ear). This product contains neomycin and colistin, which are antibiotics that work by stopping the growth of bacteria. It also contains hydrocortisone, which is an anti-inflammatory corticosteroid that works by reducing ear swelling and discomfort, and thonzonium, which helps this medication pass through dead cells and pus inside the ear.

This medication treats only bacterial ear infections. It will not work for other types of ear infections. Unnecessary use or overuse of any antibiotic can lead to its decreased effectiveness.

HOW TO USE: This medication is usually used 3 or 4 times a day or as directed by your doctor. The ear canal should be clean and dry before using this medication.

For accuracy and to avoid contamination, have another person insert the drops if possible. Before using, hold the container in your hand for a few minutes in order to warm it. This will minimize dizziness.

To apply ear drops, wash your hands first. To avoid contamination, do not touch the dropper tip or let it touch your ear or any other surface. Shake the container well before using.

Lie on your side with the treated ear upward. Hold the dropper directly over the ear and place the prescribed number of drops into the ear canal. To help the drops roll into the ear of an adult, hold the earlobe up and back. For children, hold the earlobe down and back. Keep the head tilted with the treated ear upward for 5 minutes or insert a soft cotton plug if so directed. Another way to give this medication is to place a cotton wick in the ear canal and moisten it with the prescribed number of drops as often as directed. The wick should be replaced at least once a day.

Repeat the above steps for the other ear if so directed. Do not rinse the dropper. Replace the cap after use.

Use this medication regularly in order to get the most benefit from it. To help you remember, use it at the same times each day. Continue using it for the full time prescribed, even if symptoms disappear after a few days. Stopping this medication too early may allow bacteria to continue to grow, which may result in a relapse of the infection.

Do not use this medication more often than prescribed or continue to use it for longer than 10 days.

Inform your doctor if your condition persists or worsens.

Do not use in the eye.

SIDE EFFECTS: This medication may temporarily sting or burn your ear for a minute or two when applied. If these effects persist or worsen, notify your doctor or pharmacist promptly.

Remember that your doctor has prescribed this medication because he or she has judged that the benefit to you is greater than the risk of side effects. Many people using this medication do not have serious side effects.

Tell your doctor immediately if this rare but very serious side effect occurs: hearing problems (e.g., hearing loss).

Use of this medication for prolonged or repeated periods may result in a new fungal ear infection. Do not use it for longer than prescribed. Contact your doctor if you notice new or worsening symptoms.

A very serious allergic reaction to this drug is unlikely, but seek immediate medical attention if it occurs. Symptoms of a serious allergic reaction may include: rash, itching, swelling, redness of the ears, severe dizziness, trouble breathing.

This is not a complete list of possible side effects. If you notice other effects not listed above, contact your doctor or pharmacist.

Contact your doctor for medical advice about side effects. The following numbers do not provide medical advice, but in the US you may report side effects to the Food and Drug Administration (FDA) at 1-800-FDA-1088. In Canada, you may call Health Canada at 1-866-234-2345.

PRECAUTIONS: Before using this medication, tell your doctor or pharmacist if you are allergic to neomycin, colistin, hydrocortisone, or thonzonium; or to aminoglycoside antibiotics (e.g., gentamicin, tobramycin), or to corticosteroids (e.g., dexamethasone, prednisone), or to the preservative thimerosal; or if you have any other allergies.

This medication should not be used if you have certain medical conditions. Before using this medicine, consult your doctor or pharmacist if you have: other ear problems (e.g., a hole in your eardrum, middle ear infection), an ear infection caused by a virus (e.g., herpes simplex, varicella).

Before using this medication, tell your doctor or pharmacist your medical history.

This medication should be used only if clearly needed during pregnancy. Discuss the risks and benefits with your doctor.

It is not known whether this medication passes into breast milk. Consult your doctor before breast-feeding.

DRUG INTERACTIONS: Your healthcare professionals (e.g., doctor or pharmacist) may already be aware of any possible drug interactions and may be monitoring you for it. Do not start, stop or change the dosage of any medicine before checking with them first.

Before using this medication, tell your doctor or pharmacist of all prescription and nonprescription/herbal products you may use.

Keep a list of all your medications with you, and share the list with your doctor and pharmacist.

OVERDOSE: If overdose is suspected, contact your local poison control center or emergency room immediately. US residents can call the US national poison hotline at 1-800-222-1222. Canadian residents should call their local poison control center directly. This medicine may be harmful if swallowed.

NOTES: Do not share this medication with others.

This medication has been prescribed for your current condition only. Do not use it later for another infection unless told to do so by your doctor. A different medication may be necessary in those cases.

It is important to keep the infected ear(s) clean and dry. Try not to get the infected ear(s) wet when bathing. Avoid swimming unless your doctor tells you otherwise.

MISSED DOSE: If you miss a dose, use it as soon as you remember. If it is near the time of the next dose, skip the missed dose and resume your usual dosing schedule. Do not double the dose to catch up.

STORAGE: Store at room temperature between 68-77 degrees F (20-25 degrees C) away from heat and light. Do not store in the bathroom. Keep all medicines away from children and pets.

Do not flush medications down the toilet or pour them into a drain unless instructed to do so. Properly discard this product when it is expired or no longer needed. Consult your pharmacist or local waste disposal company for more details about how to safely discard your product.

Information last revised July 2008 Copyright(c) 2008 First DataBank, Inc.