CLASSES

Combinations of Corticosteroids with Antibacterials
Topical Aminoglycosides, Plain or in Combination

DEA CLASS

Rx

DESCRIPTION

Topical combination of antibiotic and corticosteroid
Used for corticosteroid-responsive dermatoses with secondary infection
Not to be used under occlusive dressing due to risk for augmented absorption and associated adverse effects

COMMON BRAND NAMES

Neo-Synalar

HOW SUPPLIED

Neo-Synalar Topical Cream: 3.5-0.025%

DOSAGE & INDICATIONS

MAXIMUM DOSAGE

4 applications/day topically.

4 applications/day topically.

4 applications/day topically.

4 applications/day topically.

Safety and efficacy have not been established.

Safety and efficacy have not been established.

DOSING CONSIDERATIONS

Specific guidelines for dosage adjustments in hepatic impairment are not available; it appears that no dosage adjustments are needed.

Specific guidelines for dosage adjustments in renal impairment are not available; it appears that no dosage adjustments are needed.

ADMINISTRATION

STORAGE

Neo-Synalar:
- Avoid excessive heat (above 104 degrees F)
- Do not freeze
- Store between 59 to 77 degrees F

CONTRAINDICATIONS / PRECAUTIONS

Neomycin; fluocinolone is contraindicated in patients with corticosteroid hypersensitivity, neomycin hypersensitivity, or hypersensitivity to any of the preparation components.

Neomycin, fluocinolone is contraindicated for use in the external auditory canal if there is tympanic membrane perforation.

Because of the concern of nephrotoxicity and ototoxicity associated with neomycin, do not use neomycin; fluocinolone over a wide area or for extended periods.

Do not use neomycin; fluocinolone under an occlusive dressing; occlusive dressings substantially increase the percutaneous absorption of topical corticosteroids. Systemic absorption of topical corticosteroids has produced reversible hypothalamic-pituitary-adrenal (HPA) axis suppression, manifestations of Cushing's syndrome, hyperglycemia, and glucosuria in some patients. Other conditions which augment systemic absorption include the application of the more potent steroids, use over large surface areas, and prolonged use. Therefore, monitor patients receiving a large dose of a potent topical steroid applied to a large surface area periodically for evidence of HPA axis suppression by using the urinary free cortisol and ACTH stimulation tests. If HPA axis suppression is noted, attempt to withdraw the drug, reduce the frequency of application, or substitute a less potent steroid. Recovery of HPA axis function is generally prompt and complete upon discontinuation of the drug. Infrequently, signs and symptoms of steroid withdrawal may occur, requiring supplemental systemic corticosteroids.

Neomycin; fluocinolone is for external use only. It is not for ophthalmic administration. Advise patients to avoid contact with the eyes.

Children, infants, and neonates may demonstrate greater susceptibility to topical corticosteroid-induced hypothalamic-pituitary-adrenal (HPA) axis suppression and Cushing's syndrome than adult patients because of a larger skin surface area to body weight ratio. Limit administration of topical corticosteroids to the least amount compatible with an effective therapeutic regimen. Chronic corticosteroid therapy may interfere with the growth and development of children.

Use topical corticosteroids during pregnancy only if the potential benefit justifies the potential risk to the fetus. Do not use topical corticosteroids extensively on pregnant patients, in large amounts, or for prolonged periods of time. There are no adequate and well-controlled studies in pregnant women on teratogenic effects from topically applied corticosteroids. Topical corticosteroids have been shown to be teratogenic in animals when administered systemically at relatively low dosages.

Use caution when topical corticosteroids are administered to a breast-feeding woman. It is not known whether topical administration of corticosteroids could result in sufficient systemic absorption to produce detectable quantities in breast milk. Systemically administered corticosteroids are secreted into breast milk in quantities not likely to have a deleterious effect on the infant.

ADVERSE REACTIONS

skin atrophy / Delayed / Incidence not known
nephrotoxicity / Delayed / Incidence not known
ototoxicity / Delayed / Incidence not known

contact dermatitis / Delayed / Incidence not known
hyperglycemia / Delayed / Incidence not known
hypothalamic-pituitary-adrenal (HPA) suppression / Delayed / Incidence not known
Cushing's syndrome / Delayed / Incidence not known

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

DRUG INTERACTIONS

Metyrapone: (Major) Medications which affect pituitary or adrenocortical function, including all corticosteroid therapy, should be discontinued prior to and during testing with metyrapone. Patients taking inadvertent doses of corticosteroids on the test day may exhibit abnormally high basal plasma cortisol levels and a decreased response to the test. Although systemic absorption of topical corticosteroids is minimal, temporary discontinuation of these products should be considered if possible to reduce the potential for interference with the test results.
Voriconazole: (Moderate) Monitor for potential adrenal dysfunction with concomitant use of voriconazole and fluocinolone. In patients taking corticosteroids, voriconazole-associated CYP3A4 inhibition of their metabolism may lead to corticosteroid excess and adrenal suppression. Corticosteroid exposure is likely to be increased. Voriconazole is a strong CYP3A4 inhibitor, and fluocinolone is a CYP3A4 substrate.

PREGNANCY AND LACTATION

Use topical corticosteroids during pregnancy only if the potential benefit justifies the potential risk to the fetus. Do not use topical corticosteroids extensively on pregnant patients, in large amounts, or for prolonged periods of time. There are no adequate and well-controlled studies in pregnant women on teratogenic effects from topically applied corticosteroids. Topical corticosteroids have been shown to be teratogenic in animals when administered systemically at relatively low dosages.

Use caution when topical corticosteroids are administered to a breast-feeding woman. It is not known whether topical administration of corticosteroids could result in sufficient systemic absorption to produce detectable quantities in breast milk. Systemically administered corticosteroids are secreted into breast milk in quantities not likely to have a deleterious effect on the infant.

MECHANISM OF ACTION

Neomycin; fluocinolone is a topical antibiotic and corticosteroid combination. Neomycin is an aminoglycoside antibiotic with bactericidal activity against many gram-positive and gram-negative bacteria. It is actively transported into the bacterial cell where it binds to receptors present on the 30S ribosomal subunit of susceptible bacteria. 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 mRNA. Eventually, susceptible bacteria die because of the lack of functional proteins. Fluocinolone is a corticosteroid. Corticosteroids are naturally occurring hormones that bind to specific protein receptors on targeted tissues. This binding induces a response by modifying transcription and, ultimately, protein synthesis to achieve the steroid's intended action. The anti-inflammatory action of fluocinolone results from the inhibition of leukocyte infiltration at the site of inflammation, interference in the function of mediators of inflammatory response, and suppression of humoral immune responses. Topical corticosteroids share anti-inflammatory, anti-pruritic, and vasoconstrictive actions. Various laboratory methods, including vasoconstrictor assays, are used to compare and predict potencies and/or clinical efficacy of the topical corticosteroids. There is some evidence to suggest that a recognizable correlation exists between vasoconstrictor potency and therapeutic efficacy.

PHARMACOKINETICS

Neomycin; fluocinolone is administered topically to the skin. Once absorbed through the skin, topical corticosteroids are handled through pharmacokinetic pathways similar to systemically administered corticosteroids. Corticosteroids are bound to plasma proteins in varying degrees. Corticosteroids are metabolized primarily in the liver and are excreted by the kidneys. Some topical corticosteroids and their metabolites are also excreted into the bile.