This monograph discusses the use of the gentamicin; prednisolone ophthalmic combination product. Clinicians may wish to consult the individual monographs of gentamicin or prednisolone for more information about each specific agent.
Gentamicin; prednisolone is an ophthalmic preparation that combines an aminoglycoside antibiotic with a corticosteroid. The combination is used to treat corticosteroid-responsive inflammatory ocular conditions for which a corticosteroid is indicated and where superficial bacterial ocular infection or a risk of bacterial infection exists. The gentamicin; prednisolone ophthalmic suspension was approved by the FDA in June, 1988 and ophthalmic ointment was approved in December of 1989.
General Administration Information
For storage information, see the specific product information within the How Supplied section.
Route-Specific Administration
Ophthalmic Administration
Ophthalmic Suspension:
-Gentamicin; prednisolone ophthalmic suspension is indicated for topical administration to the eye; do NOT administer parenterally.
-Instruct patient on proper instillation of eye solution and suspension.
-Wash hands before and after use.
-Do not touch the tip of the dropper to the eye, fingertips, or other surface to prevent contamination.
-Shake suspension well prior to use.
-Tilt the head back slightly and pull the lower eyelid down with the index finger to form a pouch. Squeeze the prescribed number of drops into the pouch. Close eyes to spread drops. To avoid excessive systemic absorption, apply finger pressure on the lacrimal sac for 1-2 minutes following application to the eye.
-To avoid contamination or the spread of infection, do not use dropper for more than one person.
Ophthalmic Ointment:
-Instruct patient on proper application of eye ointment.
-Do not touch the tip of the tube to the eye, fingertips, or other surface to prevent contamination.
-Wash hands before and after use.
-Tilt the head back slightly and pull the lower eyelid down with the index finger to form a pouch. Place a small amount (about one-half of an inch) of the ointment into the pouch. Look downward before closing eyes.
-To avoid contamination or the spread of infection, do not use tube for more than one person.
This monograph discusses the use of the gentamicin; prednisolone ophthalmic combination product. Clinicians may wish to consult the individual monographs of gentamicin or prednisolone for more information about each specific agent.
Ocular irritation or discomfort and punctate keratitis are the most frequent reactions with gentamicin; prednisolone. These reactions should resolve upon discontinuation of the medicine. Other adverse events reported include ocular burning, ocular stinging, ocular hyperemia/conjunctival hyperemia, ocular pain, ocular discharge, increased lacrimation, ocular edema, visual impairment, blurred vision, foreign body sensation, and dysgeusia. Sensitivity to topically administered gentamicin may occur in some patients. Patients should be advised to consult a physician if ocular pain, redness, swelling, or irritation worsens or persists. Prolonged use of corticosteroids may result in increased ocular pressure (ocular hypertension) with the possible development of glaucoma, with damage to the optic nerve, defects in visual acuity and fields of vision, and in formation of posterior subcapsular cataracts. Various ocular diseases and long term use of topical corticosteroids have been known to cause corneal and scleral thinking, which may lead to perforation. Administration of prednisolone to the eye may also result in impaired wound healing after ocular surgery or injury and may increase the incidence of bleb formation. In patients receiving prolonged ophthalmic corticosteroid therapy, intraocular pressure should be checked routinely and frequently.
A superinfection may occur during gentamicin; prednisolone treatment. An ocular infection of the cornea resulting from viruses or fungi are particularly prone to develop with prolonged or repeated therapy. Consider the possibility of a fungal infection in patients with persistent corneal ulcerations. Secondary bacterial ocular infections may occur after suppression of host responses due to steroid use.
Hypersensitivity reactions to gentamicin; prednisolone have been reported and include ocular allergy (conjunctivitis), angioedema (tongue edema), and allergic skin reactions such as rash (unspecified) and contact allergy (contact dermatitis).
This monograph discusses the use of the gentamicin; prednisolone ophthalmic combination product. Clinicians may wish to consult the individual monographs of gentamicin or prednisolone for more information about each specific agent.
The use of gentamicin; prednisolone is contraindicated in patients with hypersensitivity to any component of the combination product, including patients with a history of aminoglycoside hypersensitivity or corticosteroid hypersensitivity. If hypersensitivity develops, discontinue use and institute appropriate therapy.
The use of gentamicin; prednisolone ophthalmic products has been associated with ocular irritation and punctate keratitis. Also, various ocular diseases and long term use of topical steroids have been known to cause corneal and scleral thinning; therefore, the use of gentamicin; prednisolone in the presence of thin corneal or scleral tissue may lead to perforation. If inflammation or pain persists longer than 48 hours or becomes aggravated, the patient should be advised to discontinue the use of the medication and consult a physician.
The use of gentamicin; prednisolone is contraindicated for use in patients with most types of viral infection of the cornea and conjunctiva, including herpes simplex virus epithelial keratitis, vaccinia, and varicella; in patients with mycobacterial infection of the eye; or with fungal infection of the ocular structures. The use of ocular steroids may prolong the course and may exacerbate the severity of many viral infections of the eye; therefore, use in patients with a history of herpes simplex requires caution and frequent slit lamp microscopy is recommended. Fungal infections of the cornea are prone to develop coincidentally with the long-term application of steroids; therefore, fungal invasion should be suspected in any persistent corneal ulceration where a steroid has been used or is in use. Acute purulent infections of the eye may be masked or enhanced by the use of steroids. Prolonged use of steroids may suppress the host infection response and may increase the risk of secondary ocular infections.
Prolonged steroid use may result in increased intraocular pressure with damage to the optic nerve, defects in visual acuity and fields of vision, and in the formation of posterior subcapsular cataracts. Steroids should be used with caution in the presence of pre-existing glaucoma. If gentamicin; prednisolone ophthalmic products are used for 10 days or longer, intraocular pressure should be routinely monitored. The use of gentamicin; prednisolone ophthalmic products after cataract surgery (ocular surgery) may delay healing and increase the incidence of bleb formation.
Gentamicin; prednisolone ophthalmic products are only indicated for topical administration to the eyes. Take measures to prevent intravenous administration and intramuscular administration. The gentamicin; prednisolone ophthalmic suspension should not be injected subconjunctivally, nor should it be directly introduced into the anterior chamber of the eye.
Avoid abrupt discontinuation of gentamicin; prednisolone to prevent corticosteroid withdrawal and rebound inflammation. Discontinuation of therapy is achieved by gradual tapering as the inflammation subsides.
The safety and efficacy of gentamicin; prednisolone ophthalmic products have not been established in neonates, infants, children, or adolescents.
The manufacturer of gentamicin; prednisolone ophthalmic preparations suggests that gentamicin; prednisolone should be used in pregnancy only if the potential benefit to the mother outweighs the risk to the fetus. In animal studies, ophthalmic administration of corticosteroids have been shown to be teratogenic in rabbits and mice. In mice, corticosteroids resulted in fetal resorption and an increased incidence of cleft palate; rabbits receiving corticosteroids experienced fetal resorption and abnormalities involving the head, ears, limbs, and palate. No adequate studies in pregnant women are available.
The manufacturer states that due to the potential serious adverse reactions in breast-feeding infants, a decision should be made to either discontinue nursing while gentamicin; prednisolone is administered or to discontinue the medication. It is not known if ophthalmic administered prednisolone is detectable in human milk; however, systemically administered corticosteroids do appear in human milk and may suppress infant growth and endogenous corticosteroid production. Gentamicin is poorly absorbed orally, so whatever minor systemic exposure may occur maternally would be unlikely to cause infant harm during nursing. Limited dosage and duration of use is recommended if the use of this combination is necessary. Short term use of usual moderate ocular doses for milder eye conditions probably poses little risk to the nursing infant. 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.
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: Escherichia coli, Haemophilus influenzae (beta-lactamase negative), Haemophilus influenzae (beta-lactamase positive), Klebsiella aerogenes, Klebsiella pneumoniae, Neisseria gonorrhoeae, Pseudomonas aeruginosa, Serratia marcescens, Staphylococcus aureus (MRSA), Staphylococcus aureus (MSSA), Streptococcus pneumoniae, Streptococcus pyogenes (group A beta-hemolytic streptococci)
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 steroid-responsive inflammatory ocular inflammation conditions (e.g., uveitis, bacterial conjunctivitis, corneal abrasion) for which a corticosteroid is indicated and where bacterial infection or a risk of bacterial ocular/ophthalmic infection exists:
NOTE: Ocular steroids are indicated in inflammatory conditions of the palpebral and bulbar conjunctiva, cornea, and anterior segment of the globe where the inherent risk of steroid use in certain infective conjunctivitides is accepted to obtain a diminution in edema and inflammation. They are also indicated in chronic anterior uveitis and corneal injury from chemical, radiation or thermal burns; or penetration of foreign bodies.
Ophthalmic dosage (ointment):
Adults and Geriatric: Apply a small strip of ointment (approximately 1/2 inch) into the conjunctival sac of the affected eye(s) 1-3 times daily. NOTE: No more than 8 g should be prescribed initially and the prescription should not be refilled without further evaluation.
Neonates, Infants, Children, and Adolescents: Safety and efficacy have not been established.
Ophthalmic dosage (suspension):
Adults: Instill 1 drop into the conjunctival sac 2-4 times daily. During the initial 24-48 hours, the dosing frequency may be increased to up to 1 drop every hour. NOTE: No more than 20 mL should be prescribed initially and the prescription should not be refilled without further evaluation.
Neonates, Infants, Children, and Adolescents: Safety and efficacy have not been established.
Maximum Dosage Limits:
-Adults
24 drops/day per affected eye of the suspension (dispense no more than 20 ml without re-evaluation); 1/2 inch ointment per affected eye up to three times daily (dispense no more than 8 grams without re-evaluation).
-Geriatric
24 drops/day per affected eye of the suspension (dispense no more than 20 ml without re-evaluation); 1/2 inch ointment per affected eye up to three times daily (dispense no more than 8 grams without re-evaluation).
-Adolescents
Safety and efficacy have not been established.
-Children
Safety and efficacy have not been established.
-Infants
Safety and efficacy have not been established.
-Neonates
Safety and efficacy have not been established.
Patients with Hepatic Impairment Dosing
No dosage adjustments are needed.
Patients with Renal Impairment Dosing
No dosage adjustments are needed.
*non-FDA-approved indication
There are no drug interactions associated with Gentamicin; Prednisolone products.
Since steroids may inhibit the body's defense mechanism against infection, a concomitant antimicrobial agent may be used when this inhibition is considered to be clinically significant.
-Gentamicin: Gentamicin is bactericidal in action. Similar to other aminoglycosides, it works by inhibiting bacterial protein synthesis through irreversible binding to the 30 S ribosomal subunit of susceptible bacteria. Gentamicin is actively transported into the bacterial cell where it binds to receptors present on the 30 S ribosomal subunit. This binding interferes with messenger RNA (mRNA). 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. One aspect essential to aminoglycoside lethality is the need to achieve intracellular concentrations in excess of extracellular. Anaerobic bacteria are not susceptible to aminoglycosides due, at least in part, to a lack of an active transport mechanism for aminoglycoside uptake. Gentamicin exhibits post-antibiotic effect (PAE), and, resistance to aminoglycosides can occur (see Gentamicin monograph for more information).
-Prednisolone: Glucocorticoids are naturally occurring hormones that prevent or suppress inflammation and immune responses when administered at pharmacological doses. At a molecular level, unbound glucocorticoids readily cross cell membranes and bind with high affinity to specific cytoplasmic receptors. This binding induces a response by modifying transcription and, ultimately, protein synthesis to achieve the steroid's intended action. Such actions can include: inhibition of leukocyte infiltration at the site of inflammation, interference in the function of mediators of inflammatory response, and suppression of humoral immune responses. Some of the net effects include reduction in edema or scar tissue as well as a general suppression of immune response. The degree of clinical effect is normally related to the dose administered. The antiinflammatory actions of corticosteroids are thought to involve phospholipase A2 inhibitory proteins, collectively called lipocortins. Lipocortins, in turn, control the biosynthesis of potent mediators of inflammation such as prostaglandins and leukotrienes by inhibiting the release of the precursor molecule arachidonic acid. Likewise, the numerous adverse effects related to corticosteroid use are usually related to the dose administered and the duration of therapy.
The combination of gentamicin and prednisolone is administered via the ophthalmic route as a suspension or an ointment. The pharmacokinetics of these ophthalmic administered drug combinations have not been studied; systemic absorption is expected to be negligible. See individual drug monographs for additional information.