GRAMICIDIN
DESCRIPTION:
NEOSPORIN Ophthalmic Solution (neomycin and polymyxin B sulfates and gramicidin
ophthalmic solution) is a sterile antimicrobial solution for ophthalmic use.
Each mL contains: neomycin sulfate equivalent to 1.75 mg neomycin base,
polymyxin B sulfate equivalent to 10,000 polymyxin B units, and gramicidin 0.025
mg. The vehicle contains alcohol 0.5%, thimerosal 0.001% (added as a
preservative), and the inactive ingredients propylene glycol, polyoxyethylene
polyoxypropylene compound, sodium chloride, and Water for Injection.
Neomycin sulfate is the sulfate salt of neomycin B and C, which are produced by
the growth of Streptomyces Fradiae Waksman (Fam. Streptomycetaceae). It has a
potency equivalent of not less than 600 mg of neomycin standard per mg,
calculated on an anhydrous basis.
Polymyxin B sulfate is the sulfate salt of polymyxin B1 and B2 which are
produced by the growth of Bacillus Polymyxa (Prazmowski) Migula (Fam.
Bacillaceae). It has a potency of not less than 6,000 polymyxin B units per mg,
calculated on an anhydrous basis.
Gramicidin (also called Gramicidin D) is a mixture of three pairs of
antibacterial substances (Gramicidin A, B, and C) produced by the growth of
Bacillus Brevis Dubos (Fam. Bacillaceae). It has a potency of not less than 900
mcgm of standard gramicidin per mg.
ACTIONS/CLINICAL PHARMACOLOGY:
A wide range of antibacterial action is provided by the overlapping spectra of
neomycin, polymyxin B sulfate, and gramicidin.
Neomycin is bactericidal for many gram-positive and gram-negative organisms. It
is an aminoglycoside antibiotic which inhibits protein synthesis by binding with
ribosomal RNA and causing misreading of the bacterial genetic code.
Polymyxin B is bactericidal for a variety of gram-negative organisms. It
increases the permeability of the bacterial cell membrane by interacting with
the phospholipid components of the membrane.
Gramicidin is bactericidal for a variety of gram- positive organisms. It
increases the permeability of the bacterial cell membrane to inorganic cations
by forming a network of channels through the normal lipid bilayer of the
membrane.
Microbiology: Neomycin sulfate, polymyxin B sulfate, and gramicidin together
are considered active against the following microorganisms: Staphylococcus
Aureus, streptococci, including Streptococcus Pneumoniae, Escherichia Coli,
Haemophilus Influenzae, Klebsiella Enterobacter species, Neisseria species and
Pseudomonas Aeruginosa. The product does not provide adequate coverage against
Serratia Marcescens.
INDICATIONS AND USAGE:
NEOSPORIN Ophthalmic Solution is indicated for the topical treatment of
superficial infections of the external eye and its adnexa caused by susceptible
bacteria. Such infections encompass conjunctivitis, keratitis and
keratoconjunctivitis, blepharitis and blepharoconjunctivitis.
CONTRAINDICATIONS:
NEOSPORIN Ophthalmic Solution is contraindicated in individuals who have shown
hypersensitivity to any of its components.
WARNINGS:
NOT FOR INJECTION INTO THE EYE. NEOSPORIN Ophthalmic Solution should never be
directly introduced into the anterior chamber of the eye or injected
subconjunctivally.
Topical antibiotics, particularly neomycin sulfate, may cause cutaneous
sensitization. A precise incidence of hypersensitivity reactions (primarily skin
rash) due to topical antibiotics is not known. The manifestations of
sensitization to topical antibiotics are usually itching, reddening, and edema
of the conjunctiva and eyelid. A sensitization reaction may manifest simply as a
failure to heal. During long-term use of topical antibiotic products, periodic
examination for such signs is advisable, and the patient should be told to
discontinue the product if they are observed. Symptoms usually subside quickly
on withdrawing the medication. Application of products containing these
ingredients should be avoided for the patient thereafter (see PRECAUTIONS:
General).
PRECAUTIONS:
GENERAL: As with other antibiotic preparations, prolonged use of NEOSPORIN
Ophthalmic Solution may result in overgrowth of nonsusceptible organisms
including fungi. If superinfection occurs, appropriate measures should be
initiated.
Bacterial resistance to NEOSPORIN Ophthalmic Solution may also develop. If
purulent discharge, inflammation, or pain becomes aggravated, the patient should
discontinue use of the medication and consult a physician.
There have been reports of bacterial keratitis associated with the use of
topical ophthalmic products in multiple-dose containers which have been
inadvertently contaminated by patients, most of whom had a concurrent corneal
disease or a disruption of the ocular epithelial surface (see PRECAUTIONS:
Information for Patients).
Allergic cross-reactions may occur which could prevent the use of any or all of
the following antibiotics for the treatment of future infections: kanamycin,
paromomycin, streptomycin, and possibly gentamicin.
INFORMATION FOR PATIENTS: Patients should be instructed to avoid allowing the
tip of the dispensing container to contact the eye, eyelid, fingers, or any
other surface. The use of this product by more than one person may spread
infection.
Patients should also be instructed that ocular products, if handled improperly,
can become contaminated by common bacteria known to cause ocular infections.
Serious damage to the eye and subsequent loss of vision may result from using
contaminated products (see PRECAUTIONS: General).
If the condition persists or gets worse, or if a rash or other allergic reaction
develops, the patient should be advised to stop use and consult a physician. Do
not use this product if you are allergic to any of the listed ingredients.
Keep tightly closed when not in use. Keep out of reach of children.
CARCINOGENESIS, MUTAGENESIS, IMPAIRMENT OF FERTILITY: Long-term studies in
animals to evaluate carcinogenic or mutagenic potential have not been conducted
with polymyxin B sulfate or gramicidin. Treatment of cultured human lymphocytes
in vitro with neomycin increased the frequency of chromosome aberrations at the
highest concentration (80 mcgm/mL) tested. However, the effects of neomycin on
carcinogenesis and mutagenesis in humans are unknown.
Polymyxin B has been reported to impair the motility of equine sperm, but its
effects on male or female fertility are unknown.
PREGNANCY: TERATOGENIC EFFECTS: Pregnancy Category C. Animal reproduction
studies have not been conducted with neomycin sulfate, polymyxin B sulfate, or
gramicidin. It is also not known whether NEOSPORIN Ophthalmic Solution can cause
fetal harm when administered to a pregnant woman or can affect reproduction
capacity. NEOSPORIN Ophthalmic Solution should be given to a pregnant woman only
if clearly needed.
NURSING MOTHERS: It is not known whether this drug is excreted in human milk.
Because many drugs are excreted in human milk, caution should be exercised when
NEOSPORIN Ophthalmic Solution is administered to a nursing woman.
PEDIATRIC USE: Safety and effectiveness in pediatric patients have not been
established.
ADVERSE REACTIONS:
Adverse reactions have occurred with the anti- infective components of NEOSPORIN
Ophthalmic Solution. The exact incidence is not known. Reactions occurring most
often are allergic sensitization reactions including itching, swelling, and
conjunctival erythema (see WARNINGS). More serious hypersensitivity reactions,
including anaphylaxis, have been reported rarely.
Local irritation on instillation has also been reported.
DOSAGE AND ADMINISTRATION:
Instill one or two drops into the affected eye every 4 hours for 7 to 10 days.
In severe infections, dosage may be increased to as much as two drops every
hour.
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