A Comprehensive Monograph on Fluocinolone Acetonide (DB00591): From Topical Dermatoses to Intravitreal Implants

Overview and Key Findings

Fluocinolone acetonide is a synthetic, fluorinated corticosteroid that has been a cornerstone of anti-inflammatory therapy for over six decades. Identified by DrugBank ID DB00591 and CAS Number 67-73-2, this small molecule has demonstrated remarkable versatility, attributable to its potent intrinsic activity and its adaptability to a wide range of pharmaceutical formulations.[1] This report provides an exhaustive analysis of fluocinolone acetonide, synthesizing data from chemical databases, regulatory filings, clinical trials, and professional pharmacotherapy resources to create a definitive monograph for clinicians and researchers.

The primary mechanism of action for fluocinolone acetonide is its function as a high-affinity agonist of the intracellular glucocorticoid receptor.[1] This interaction initiates a cascade of genomic effects, leading to the upregulation of anti-inflammatory proteins like annexin-1 and the subsequent suppression of key inflammatory mediators, including prostaglandins and leukotrienes.[2] This fundamental activity translates into potent anti-inflammatory, antipruritic, and vasoconstrictive effects, which form the basis of its therapeutic utility.[4]

A defining characteristic of fluocinolone acetonide is the critical role that pharmaceutical formulation plays in dictating its clinical application and safety profile. The same active pharmaceutical ingredient is engineered into a spectrum of products, from low-potency topical creams, oils, and shampoos for the management of dermatological conditions such as atopic dermatitis and psoriasis, to sophisticated, long-acting intravitreal implants for chronic, sight-threatening ocular diseases like diabetic macular edema (DME) and non-infectious posterior uveitis.[2]

Clinical evidence robustly supports its efficacy across these varied indications. In dermatology, it provides effective relief from the inflammatory and pruritic manifestations of corticosteroid-responsive dermatoses.[5] In otology, it is indicated for chronic eczematous external otitis.[2] In ophthalmology, its implantable forms offer sustained, localized drug delivery for up to three years, significantly reducing treatment burden and controlling chronic inflammation.[8]

The safety profile of fluocinolone acetonide is well-characterized and is also highly dependent on the formulation and conditions of use. For topical applications, risks are primarily local (e.g., skin atrophy, striae) and are associated with long-term, occlusive, or high-potency use.[10] Systemic absorption can lead to hypothalamic-pituitary-adrenal (HPA) axis suppression, particularly in pediatric patients or with extensive use.[4] For intravitreal implants, the most significant and frequent adverse events are ocular, namely the development of cataracts in phakic patients and a high incidence of increased intraocular pressure (IOP) that often requires medical or surgical management.[13] This comprehensive review will dissect these aspects in detail, providing a nuanced understanding of fluocinolone acetonide's chemistry, pharmacology, clinical efficacy, and its established place in modern therapeutics.

1.0 Drug Identification and Physicochemical Properties

Establishing the fundamental chemical and physical identity of fluocinolone acetonide is essential for understanding its pharmaceutical behavior, formulation development, and biological activity. This section details its precise nomenclature, unique identifiers across various databases, and core physicochemical characteristics.

1.1 Chemical Identity and Nomenclature

Fluocinolone acetonide is a synthetic corticosteroid belonging to the pregnane class of organic compounds. Its structure is a modification of the hydrocortisone backbone, engineered to enhance potency and lipophilicity.[1]

• Common Name: Fluocinolone acetonide.[1]
• Systematic (IUPAC) Name: The International Union of Pure and Applied Chemistry (IUPAC) name, which unambiguously defines its complex stereochemistry and polycyclic structure, is (1S,2S,4R,8S,9S,11S,12R,13S,19S)-12,19-difluoro-11-hydroxy-8-(2-hydroxyacetyl)-6,6,9,13-tetramethyl-5,7-dioxapentacyclo[10.8.0.0$^{2,9}.0^{4,8}.0^{13,18}$]icosa-14,17-dien-16-one.[1]
• Chemical Formula: The empirical formula for fluocinolone acetonide is C24​H30​F2​O6​.[2]
• Structure: Chemically, it is described as pregna-1,4-diene-3,20-dione, 6,9-difluoro-11,21-dihydroxy-16,17-[(1-methylethylidene)bis(oxy)]-, (6α, 11β, 16α)-.[4] Key structural features include a steroid nucleus with double fluorination at the 6-alpha and 9-alpha positions and a cyclic ketal (acetonide) group formed between the 16-alpha and 17-alpha hydroxyl groups and acetone.[1]

The specific chemical modifications to the hydrocortisone scaffold are directly responsible for the drug's enhanced pharmacological properties. The introduction of a fluorine atom at the 9α position dramatically increases glucocorticoid activity and reduces mineralocorticoid effects. A second fluorine atom at the 6α position further potentiates its anti-inflammatory action. The formation of the 16α,17α-acetonide group significantly increases the molecule's lipophilicity (fat solubility).[1] This high lipophilicity is a critical physicochemical property that enhances the drug's ability to penetrate the stratum corneum of the skin and cross cellular membranes to engage with its intracellular glucocorticoid receptor. Thus, the drug's chemical architecture is causally and inextricably linked to its high potency and its suitability for topical and localized delivery systems.

1.2 Physicochemical Properties

The physical properties of fluocinolone acetonide dictate its appearance, stability, and solubility, which are critical considerations for its formulation into stable and effective dosage forms.

• Molecular Weight: The average molecular weight is approximately 452.49 g/mol, with a more precise monoisotopic mass of 452.201045102 Da.[2]
• Appearance: It exists as a white or practically white, crystalline powder.[1]
• Odor: The compound is odorless.[1]
• Melting Point: Fluocinolone acetonide has a melting point in the range of 266–268 °C, with some sources reporting a value as high as 270 °C with decomposition.[1]
• Solubility: Consistent with its highly lipophilic nature, it is practically insoluble in water. It is soluble in organic solvents such as alcohol, acetone, and methanol, and slightly soluble in chloroform.[3]
• Stability: The compound is noted to be stable in light.[4] Formulated products have demonstrated stability for at least four years under appropriate storage conditions.[3]

A consolidated summary of these key identifiers and properties is presented in Table 1 for ease of reference.

Table 1: Key Chemical and Physical Properties of Fluocinolone Acetonide

Identifier/Property	Value / Description
CAS Number	67-73-2 1
DrugBank ID	DB00591 1
UNII	0CD5FD6S2M 1
IUPAC Name	(1S,2S,4R,8S,9S,11S,12R,13S,19S)-12,19-difluoro-11-hydroxy-8-(2-hydroxyacetyl)-6,6,9,13-tetramethyl-5,7-dioxapentacyclo[10.8.0.0$^{2,9}.0^{4,8}.0^{13,18}$]icosa-14,17-dien-16-one 1
InChIKey	FEBLZLNTKCEFIT-VSXGLTOVSA-N 1
SMILES	C[C@]12CC@@HO
Molecular Formula	C24​H30​F2​O6​
Molecular Weight	~452.49 g/mol
Appearance	White crystalline powder
Odor	Odorless
Melting Point	~266–270 °C (with decomposition)
Solubility	Insoluble in water; soluble in alcohol, acetone, and methanol

2.0 Pharmacology

The therapeutic effects of fluocinolone acetonide are derived from its specific interactions with cellular targets and its subsequent processing by the body. This section details its molecular mechanism of action, its resulting pharmacodynamic effects, and its pharmacokinetic profile across various routes of administration.

2.1 Mechanism of Action

Fluocinolone acetonide is a synthetic anti-inflammatory corticosteroid whose primary molecular activity is as a potent agonist for the glucocorticoid receptor. Its high binding affinity for this intracellular receptor, with a reported half maximal inhibitory concentration (

IC50​) of 2.0 nM, underpins its potent biological effects.

The mechanism follows the classical pathway for steroid hormone action. Upon diffusing across the cell membrane, fluocinolone acetonide binds to the glucocorticoid receptor located in the cytoplasm. This binding event triggers a conformational change in the receptor, leading to the dissociation of chaperone proteins (such as heat shock proteins) and the formation of an activated receptor-ligand complex. This complex then translocates into the cell nucleus, where it acts as a ligand-dependent transcription factor.

Inside the nucleus, the complex binds to specific DNA sequences known as Glucocorticoid Response Elements (GREs), which are located in the promoter regions of target genes. This binding modulates the transcription of a wide array of genes. The principal anti-inflammatory effect is achieved through the increased transcription of genes encoding anti-inflammatory proteins. Chief among these are the phospholipase A₂ inhibitory proteins, collectively known as lipocortins, particularly annexin-1. These proteins exert control over the biosynthesis of powerful inflammatory mediators, such as prostaglandins and leukotrienes, by inhibiting the enzymatic activity of phospholipase A₂. This enzyme is responsible for releasing arachidonic acid, the common precursor for these inflammatory molecules, from membrane phospholipids. By blocking this initial step, fluocinolone acetonide effectively shuts down a major inflammatory cascade.

Beyond this primary pathway, fluocinolone acetonide has other relevant mechanisms. In the context of its ophthalmic use for diabetic macular edema, it has been shown to inhibit the secretion of vascular endothelial growth factor (VEGF) in a dose-dependent manner, thereby reducing the angiogenesis and vascular permeability that contribute to macular edema. Some research also suggests a role in tissue repair, as it has been observed to promote the proliferation of dental pulp cells and up-regulate signaling molecules like Wnt4.

It is noteworthy that official prescribing information from regulatory bodies sometimes states that the precise mechanism of anti-inflammatory activity is "unclear". This language reflects the high standard of evidence required for regulatory claims and the complexity of fully elucidating every step of a biological cascade in human clinical trials. However, the pathway involving glucocorticoid receptor binding and subsequent induction of lipocortins is the widely accepted scientific consensus based on extensive

in vitro and in vivo research, representing the current and most complete understanding of its molecular action.

2.2 Pharmacodynamics

The molecular actions of fluocinolone acetonide translate into a set of well-defined physiological and clinical effects. The primary pharmacodynamic properties are potent anti-inflammatory, antipruritic (anti-itch), and vasoconstrictive actions.

These properties manifest as the inhibition of the cardinal signs of inflammation. Fluocinolone acetonide suppresses edema (swelling), fibrin deposition, capillary dilation (which reduces erythema or redness), and the migration of inflammatory cells like leukocytes to the site of inflammation. It also curtails the later stages of chronic inflammation by inhibiting capillary and fibroblast proliferation, collagen deposition, and subsequent scar formation. Collectively, these effects lead to the clinical relief of symptoms such as swelling, redness, and itching that characterize inflammatory dermatoses.

The potency of topical corticosteroids is often compared using vasoconstrictor assays, which measure the degree of skin blanching caused by the drug. In these assays, which serve as a surrogate for clinical anti-inflammatory efficacy, fluocinolone acetonide has demonstrated approximately 100 times the activity of hydrocortisone acetate, classifying it as a potent agent.

2.3 Pharmacokinetics

The pharmacokinetic profile of fluocinolone acetonide—its absorption, distribution, metabolism, and excretion (ADME)—is profoundly influenced by its formulation and route of administration. This variability allows the same active molecule to be used for both acute, localized conditions and chronic, deep-tissue diseases.

• Absorption:
• Topical and Otic Administration: When applied to the skin or in the ear, the extent of percutaneous absorption is a critical factor. Absorption is determined by the formulation's vehicle (e.g., ointments are more occlusive and enhance penetration more than creams or solutions), the integrity of the epidermal barrier (absorption is significantly increased through inflamed, diseased, or broken skin), and the use of occlusive dressings (e.g., bandages or plastic wrap), which can substantially increase systemic uptake. Under normal use for localized conditions, systemic absorption is generally minimal.
• Intravitreal Implant: This dosage form is specifically engineered for localized, sustained drug delivery to the posterior segment of the eye. The Iluvien implant, for instance, is a non-bioerodable device that provides a continuous, low-dose release of fluocinolone acetonide for up to 36 months. This design ensures that therapeutic concentrations are maintained at the target site while minimizing systemic exposure. Consequently, plasma concentrations of the drug following implant administration are typically very low, often below the limit of quantitation (0.1 ng/mL).
• Distribution: For topical and intravitreal routes, the concept of systemic distribution is of limited clinical relevance due to the minimal amount of drug that enters the bloodstream. In cases where systemic absorption does occur, corticosteroids are known to bind to plasma proteins, including corticosteroid-binding globulin and albumin, to varying degrees.
• Metabolism: The small fraction of fluocinolone acetonide that is systemically absorbed is metabolized primarily in the liver. This metabolism is mediated, at least in part, by the cytochrome P450 3A4 (CYP3A4) enzyme system.
• Excretion: Following metabolism, the drug and its metabolites are eliminated from the body primarily through renal excretion (in the urine), with a smaller portion also excreted in the bile.
• Half-life: The systemic elimination half-life of fluocinolone acetonide is reported to be short, ranging between 1.3 and 1.7 hours. This indicates that if any drug is absorbed systemically, it is cleared from the circulation relatively quickly.

The distinct pharmacokinetic profiles of the different formulations highlight a key principle of modern pharmaceutical science: the therapeutic application of a drug can be dramatically expanded by innovating its delivery system. The same active molecule, by virtue of its physicochemical properties, can be formulated as a short-acting agent for surface-level skin conditions or as a long-acting implant for chronic internal diseases, demonstrating how formulation science is crucial for optimizing clinical outcomes.

3.0 Clinical Applications and Efficacy

Fluocinolone acetonide is a versatile therapeutic agent with a broad spectrum of approved indications spanning dermatology, otology, and ophthalmology. Its efficacy is supported by a substantial body of clinical evidence from randomized controlled trials and real-world studies.

3.1 Approved and Investigational Indications

The U.S. Food and Drug Administration (FDA) and other regulatory bodies have approved fluocinolone acetonide in various formulations for a range of inflammatory conditions. The specific indication is inextricably linked to the dosage form and strength, as summarized in Table 2.

Table 2: Summary of Approved Indications by Formulation

Formulation	Common Brand Names	Primary Approved Indication(s)	Typical Patient Population
Topical Cream/Ointment/Solution (0.01%, 0.025%)	Synalar	Relief of inflammatory and pruritic manifestations of corticosteroid-responsive dermatoses (e.g., eczema, dermatitis)	Adults and pediatric patients (age limits may apply)
Topical Body Oil (0.01%)	Derma-Smoothe/FS	Atopic dermatitis	Adults; Moderate to severe atopic dermatitis in pediatric patients ≥3 months
Topical Scalp Oil (0.01%)	Derma-Smoothe/FS	Psoriasis of the scalp	Adults
Topical Shampoo (0.01%)	Capex	Seborrheic dermatitis of the scalp	Adults
Otic Drops (0.01%)	Dermotic, Otovel (in combination with ciprofloxacin)	Chronic eczematous external otitis	Adults and pediatric patients ≥2 years
Intravitreal Implant (0.18 mg, 0.19 mg, 0.59 mg)	Yutiq, Iluvien, Retisert	Diabetic macular edema (DME); Chronic non-infectious posterior uveitis (NIU-PS)	Adults

In addition to these primary indications, some reports have suggested its investigational use as a vasoprotective agent and for the treatment of first-degree hemorrhoids.

3.2 Clinical Efficacy in Dermatological Conditions

In dermatology, fluocinolone acetonide is a widely used agent for managing inflammatory skin diseases.

• Corticosteroid-Responsive Dermatoses: It is broadly indicated for the relief of inflammation and itching associated with conditions like atopic dermatitis, psoriasis, seborrheic dermatitis, and various forms of eczema. Its efficacy stems directly from its potent anti-inflammatory and antipruritic properties.
• Atopic Dermatitis: The efficacy of the 0.01% oil formulation has been demonstrated in pediatric populations. A multicenter, double-blind, randomized, vehicle-controlled trial involving children aged 2 to 12 years found that after two weeks of treatment, 81% to 87% of patients treated with fluocinolone acetonide oil showed at least a 50% improvement in their condition. This was significantly superior to the 39% improvement rate observed in the group treated with the vehicle oil alone, confirming that the active ingredient provides substantial therapeutic benefit.
• Scalp Psoriasis: The scalp oil formulation has proven effective for this difficult-to-treat condition. In a vehicle-controlled study involving adults, 60% of patients treated with fluocinolone acetonide 0.01% scalp oil for 21 days achieved an "excellent to cleared" clinical response. In contrast, only 21% of patients using the vehicle base achieved this outcome, highlighting a clear and statistically significant treatment effect.
• Melasma: Fluocinolone acetonide is a key component of a widely used triple-combination cream that also contains the depigmenting agent hydroquinone and the retinoid tretinoin. This combination leverages a synergistic effect, where fluocinolone acetonide mitigates the irritation often caused by tretinoin, thereby improving tolerability and allowing the primary depigmenting agents to work effectively. A randomized, placebo-controlled trial in Chinese patients compared a generic version of this cream to the brand-name product (Tri-Luma) and placebo. The study found that the generic and brand-name products were similarly effective, with efficacy rates of 52.2% and 57.1%, respectively, based on the Melasma Severity Scale. Both active treatments were significantly more effective than placebo. Furthermore, long-term studies lasting up to 12 months have confirmed the safety and efficacy of this combination, with over 90% of patients being assessed by both themselves and their physicians as having their melasma completely or nearly cleared by the end of the study.

3.3 Clinical Efficacy in Otic Conditions

Fluocinolone acetonide is also formulated for otic use to treat external ear inflammation.

• Chronic Eczematous External Otitis: The efficacy of the 0.025% otic solution was established in a Phase 3, multicenter, randomized, double-blind, placebo-controlled clinical trial involving 135 patients. The results demonstrated a statistically significant superiority of fluocinolone acetonide over placebo. Patients in the active treatment group experienced significantly greater reductions in itching, the primary efficacy endpoint, during both the 7-day treatment phase ( p=0.005) and the subsequent 8-day follow-up period (p<0.001). Similarly, objective otoscopic signs of inflammation, including erythema, edema, and scaling, were significantly reduced in the fluocinolone group compared to the placebo group at both the end of treatment and the end of follow-up (p<0.05).
• Acute Otitis Media with Tympanostomy Tubes (AOMT): Fluocinolone acetonide is available in a combination ear drop with the antibiotic ciprofloxacin (Otovel). In this formulation, its role is to reduce the pain and swelling associated with the middle ear infection, complementing the antibacterial action of ciprofloxacin. Two large clinical studies in pediatric patients with AOMT demonstrated that this combination therapy led to a significantly faster resolution of otorrhea (ear discharge) compared to treatment with ciprofloxacin alone. The median time to cessation of otorrhea was 3.75 to 4.94 days in the combination group, versus 6.83 to 7.69 days in the antibiotic-only group. This highlights a synergistic effect where the rapid reduction of inflammation by fluocinolone acetonide facilitates a faster clinical resolution of the infection.

3.4 Clinical Efficacy in Ophthalmic Conditions (Intravitreal Implant)

The development of sustained-release intravitreal implants has enabled the use of fluocinolone acetonide for chronic, posterior segment eye diseases, where it provides long-term, localized anti-inflammatory action.

• Diabetic Macular Edema (DME): DME is a leading cause of vision loss in diabetic patients, characterized by retinal thickening due to fluid leakage from damaged blood vessels. The 0.19 mg fluocinolone acetonide implant (Iluvien) is indicated for DME in patients who have been previously treated with corticosteroids without a significant rise in IOP. The pivotal FAME (Fluocinolone Acetonide for Diabetic Macular Edema) trials established its efficacy over a 36-month period. A large European real-world study (the IRISS registry) involving 695 eyes followed for up to 5.5 years confirmed these findings, demonstrating a favorable long-term benefit-to-risk profile. In this study, mean visual acuity increased from a baseline of 52.2 letters to 57.1 letters at month 36. A separate 36-month real-world analysis of 148 eyes showed long-term stabilization of visual acuity and macular anatomy, with a significant reduction in the annual frequency of rescue treatments (e.g., anti-VEGF injections) from 4.9 to 1.5 per year after implant administration ( p<.001).
• Non-Infectious Posterior Uveitis (NIU-PS): This chronic inflammatory condition can lead to severe vision loss. The fluocinolone acetonide implant offers a long-term alternative to systemic immunosuppression or frequent local injections. A 3-year, Phase III, randomized, double-masked trial (NCT02746991) provided definitive evidence of its efficacy. The study found that the implant group had a significantly lower rate of uveitis recurrence at 36 months (46.5%) compared to a sham-treated group that received standard of care (75.0%; p=0.001). The median time to the first recurrence was profoundly longer in the implant group (1116 days) than in the sham group (190.5 days), demonstrating sustained disease control.

A critical perspective on long-term outcomes comes from the 7-year follow-up of the Multicenter Uveitis Steroid Treatment (MUST) trial, which compared the fluocinolone acetonide implant to systemic therapy. This landmark study revealed a complex efficacy-safety trade-off. While the implant provided superior control of local inflammation for the first 54 months of the study, the group randomized to systemic therapy ultimately had better mean visual acuity at the 7-year endpoint (a difference of 7.2 letters, favoring systemic therapy). This finding suggests that while the implant is highly effective at suppressing local inflammation, this may not automatically translate into superior long-term preservation of visual function compared to systemic treatment. This forces a nuanced clinical decision, weighing the benefits of avoiding systemic side effects against the potential for better long-term visual outcomes with systemic therapy.

Table 3: Summary of Key Efficacy Data from Clinical Trials

Indication	Trial Design	Key Efficacy Endpoint & Result	Source(s)
Atopic Dermatitis (Pediatric)	Randomized, Vehicle-Controlled	≥50% improvement at 2 weeks: 81-87% with fluocinolone oil vs. 39% with vehicle.
Scalp Psoriasis (Adult)	Vehicle-Controlled	"Excellent to cleared" response at 21 days: 60% with fluocinolone oil vs. 21% with vehicle.
Otic Eczema	Randomized, Placebo-Controlled	Significantly greater reduction in itching vs. placebo at Day 8 (p=0.005) and Day 15 (p<0.001).
AOMT (Pediatric)	Randomized, Active-Controlled	Median time to otorrhea cessation: 3.75-4.94 days with combo vs. 6.83-7.69 days with ciprofloxacin alone.
Non-Infectious Posterior Uveitis	Randomized, Sham-Controlled (36 months)	Uveitis recurrence rate: 46.5% with implant vs. 75.0% with sham (p=0.001).
Diabetic Macular Edema	Real-World Study (36 months)	Mean annual rescue treatments decreased from 4.9 to 1.5 (p<.001).
Melasma	Randomized, Placebo-Controlled	Efficacy (MSS): 52.2% (generic) and 57.1% (brand) vs. 0% (placebo).

4.0 Dosage, Formulations, and Administration

The clinical utility of fluocinolone acetonide is defined by its diverse range of pharmaceutical formulations, each with specific strengths, potencies, and detailed administration guidelines tailored to the target condition and anatomical site. Proper application is critical to maximizing efficacy and minimizing adverse effects.

4.1 Available Formulations and Strengths

Fluocinolone acetonide is available by prescription in numerous dosage forms, allowing for precise application to the skin, scalp, and ear, as well as specialized delivery into the eye.

• Topical Formulations for Skin:
• Cream: Available in 0.01% and 0.025% strengths. Creams are water-based emulsions that are cosmetically elegant and suitable for most skin areas.
• Ointment: Available in a 0.025% strength. Ointments have an oil base, which provides occlusive and emollient effects, making them ideal for dry, scaly, or thickened lesions.
• Solution: Available in a 0.01% strength. Solutions are useful for hairy areas where creams or ointments would be difficult to apply.
• Body Oil: Available as a 0.01% oil (e.g., Derma-Smoothe/FS). The oil vehicle can help with skin hydration and is particularly used for atopic dermatitis.
• Topical Formulations for Scalp:
• Scalp Oil: A 0.01% oil formulation specifically designed for treating scalp psoriasis.
• Shampoo: A 0.01% medicated shampoo (e.g., Capex) for seborrheic dermatitis of the scalp.
• Otic Formulation for Ear:
• Ear Drops: A 0.01% oil-based solution (e.g., DermOtic) for otic administration.
• Ophthalmic Formulation for Eye:
• Intravitreal Implant: A sterile, non-bioerodable, sustained-release implant available in several doses, including 0.18 mg (Yutiq), 0.19 mg (Iluvien), and 0.59 mg (Retisert).

4.2 Potency Classification

Topical corticosteroids are classified by their vasoconstrictive potency, which generally correlates with clinical anti-inflammatory efficacy. Fluocinolone acetonide formulations span the low to medium potency range, making them suitable for a variety of conditions without the higher risks associated with high- or super-potent steroids.

• Medium Potency: 0.025% Ointment
• Medium/Low Potency: 0.025% Cream
• Low Potency: 0.01% Cream, 0.01% Body Oil, 0.01% Scalp Oil, 0.01% Solution

This classification is crucial for clinical decision-making, as higher potency steroids are generally reserved for thicker, more resistant lesions and used for shorter durations, while lower potency options are safer for larger areas, thinner skin (e.g., face, intertriginous areas, if directed), and for pediatric patients.

4.3 Dosing and Administration Guidelines

Adherence to specific administration instructions is paramount for the safe and effective use of fluocinolone acetonide. The instructions are tailored to the formulation and indication, reflecting a scientific approach to optimize drug delivery and minimize risk.

• General Topical Application (Cream, Ointment, Solution): For corticosteroid-responsive dermatoses, a thin film of the product should be applied to the affected skin areas two to four times daily and rubbed in gently. Hands should be washed thoroughly before and after application, unless the hands are the treatment area.
• Atopic Dermatitis (Body Oil): For adults, the oil is applied as a thin film three times daily. For pediatric patients (3 months and older), a "soak and seal" technique is recommended: the skin should be moistened first, and then a thin film of oil is applied twice daily for a maximum duration of four weeks. This method enhances skin hydration and improves drug penetration through the compromised epidermal barrier typical of atopic dermatitis.
• Scalp Psoriasis (Scalp Oil): The hair and scalp should be wet or dampened. A thin film of oil is then applied to the affected scalp areas and massaged in well. The scalp must be covered with the supplied shower cap and the oil left on overnight or for a minimum of four hours before being washed out with regular shampoo. The prolonged contact time and occlusion are necessary to enhance penetration through the thick, hyperkeratotic plaques of psoriasis.
• Seborrheic Dermatitis (Shampoo): A maximum of one ounce (approximately 30 mL) of the 0.01% shampoo is applied to the wet scalp once daily. It should be worked into a lather and allowed to remain on the scalp for five minutes before being rinsed thoroughly from the hair and scalp. The shorter, defined contact time is sufficient for this less-scaled condition and minimizes potential for irritation.
• Eczematous External Otitis (Ear Drops): For patients 2 years of age and older, five drops of the 0.01% otic oil are instilled into the affected ear twice daily for seven to fourteen days. The patient should lie down with the affected ear facing up and remain in that position for about a minute to allow the medication to penetrate the ear canal.
• Intravitreal Implant: This is a specialized medical procedure. The implant is administered by a qualified ophthalmologist via an intravitreal injection in a sterile, operating room setting.

The highly specific nature of these instructions underscores the importance of patient counseling. Misapplication, such as washing out the scalp oil immediately or using the shampoo under occlusion, can lead to suboptimal efficacy or increased adverse effects, respectively. A summary of these regimens is provided in Table 4.

Table 4: Recommended Dosing Regimens for Fluocinolone Acetonide

Indication	Formulation	Dosage and Frequency	Key Administration Instructions & Duration
Atopic Dermatitis (Adult)	Body Oil 0.01%	Apply 3 times daily	Apply a thin film to affected areas.
Atopic Dermatitis (Pediatric ≥3 mos)	Body Oil 0.01%	Apply 2 times daily	Moisten skin before applying a thin film. Maximum duration of 4 weeks.
Scalp Psoriasis	Scalp Oil 0.01%	Apply once daily	Wet hair/scalp, apply oil, cover with shower cap overnight or for ≥4 hours before washing.
Seborrheic Dermatitis	Shampoo 0.01%	Apply once daily	Lather into scalp, leave on for 5 minutes, then rinse thoroughly.
Eczematous External Otitis (≥2 yrs)	Ear Drops 0.01%	Instill 5 drops 2 times daily	Instill into affected ear and keep head tilted for ~1 minute. Duration: 7 to 14 days.

5.0 Safety and Tolerability Profile

The safety profile of fluocinolone acetonide is well-established and is critically dependent on the formulation, dosage, duration of use, application site, and patient population. A thorough understanding of its potential adverse effects, contraindications, and necessary precautions is essential for its safe clinical use.

5.1 Adverse Effects

Adverse effects can be categorized as local reactions at the site of application, systemic effects resulting from absorption into the bloodstream, and specialized ocular effects associated with the intravitreal implant.

5.1.1 Local Adverse Reactions (Topical/Otic)

These are the most frequently encountered side effects of topical fluocinolone acetonide.

• Common Reactions: Patients may experience burning, itching (pruritus), irritation, redness (erythema), or dryness at the application site, particularly upon initial use. These reactions are often mild and transient.
• Reactions with Prolonged Use or Occlusion: Long-term or inappropriate use (e.g., under occlusive dressings) significantly increases the risk of more serious and potentially irreversible local effects. These include skin atrophy (thinning of the epidermis and dermis), striae (stretch marks), telangiectasias (visible small blood vessels), acneiform eruptions, folliculitis, hypertrichosis (excessive hair growth), and changes in skin pigmentation (hypopigmentation or hyperpigmentation). The risk of these adverse events is highest on areas with thin skin, such as the face, groin, axillae, and other intertriginous (skin-fold) areas. Secondary skin infections may also occur, as the immunosuppressive effect of the steroid can allow for the overgrowth of bacteria or fungi.

5.1.2 Systemic Adverse Reactions

Systemic side effects occur when a sufficient amount of the drug is absorbed through the skin into the systemic circulation. The risk is directly proportional to the potency of the steroid, the surface area of application, the duration of treatment, the integrity of the skin barrier, and the use of occlusion.

• Hypothalamic-Pituitary-Adrenal (HPA) Axis Suppression: This is a primary concern with systemic corticosteroid absorption. The exogenous steroid can suppress the body's natural production of cortisol, leading to reversible HPA axis suppression. This can result in adrenal insufficiency if the topical steroid is withdrawn abruptly after prolonged use.
• Cushing's Syndrome: Prolonged, high-dose use can lead to iatrogenic Cushing's syndrome, characterized by symptoms such as weight gain (especially central), a "moon face," a "buffalo hump," severe headache, and slow wound healing.
• Metabolic Effects: Systemic absorption can lead to hyperglycemia (high blood sugar) and glucosuria (sugar in the urine), which is a significant consideration for patients with or at risk for diabetes mellitus.
• Pediatric-Specific Systemic Effects: Children are particularly vulnerable to systemic toxicity due to their higher skin surface area-to-body mass ratio. Systemic absorption in children can lead to HPA axis suppression and has been associated with linear growth retardation and delayed weight gain with chronic use.

5.1.3 Ocular Adverse Reactions (Intravitreal Implant)

The intravitreal implant delivers a high local concentration of the drug over a long period, leading to a distinct and significant profile of ocular adverse events.

• Increased Intraocular Pressure (IOP) and Glaucoma: Elevation of IOP is a very common and expected adverse effect. Data from the pivotal FAME trials for the Iluvien implant showed that 38% of treated patients required IOP-lowering medication (compared to 14% in the sham group), and 5% required incisional surgery for glaucoma (compared to 1% in the sham group) over the 36-month study period. Real-world evidence confirms this high incidence, with up to 38.5% of eyes requiring IOP-lowering medication post-implantation.
• Cataract Formation: This is the most frequent adverse reaction in patients who have not previously had cataract surgery (phakic patients). In the FAME trials, 82% of phakic patients receiving the Iluvien implant developed a cataract, with 80% of that group ultimately requiring cataract surgery. This is substantially higher than the rates in the sham group (50% developed cataracts, 27% required surgery).
• Injection-Related Complications: As with any intravitreal injection, there is a risk of serious complications such as endophthalmitis (a severe intraocular infection), eye inflammation, and retinal detachment.
• Implant Migration: In patients where the posterior capsule of the lens is absent or torn (e.g., after complicated cataract surgery), there is a risk that the implant can migrate into the anterior chamber of the eye.

A summary of the most clinically relevant adverse events is provided in Table 5.

Table 5: Summary of Common and Serious Adverse Events

Category	Adverse Event	Incidence/Frequency (if available)	Clinical Significance/Notes
Local (Topical/Otic)	Burning, itching, irritation, redness	Common	Usually mild and transient, especially at the start of therapy.
	Skin atrophy, striae, telangiectasias	Associated with long-term/occlusive use	Potentially irreversible; risk is highest on face, groin, and skin folds.
Systemic (from Absorption)	HPA Axis Suppression	Risk increases with high dose, large area, long duration, occlusion.	Reversible upon discontinuation, but may require tapering.
	Cushing's Syndrome	Rare; associated with high-risk use patterns.	Requires discontinuation of therapy.
	Hyperglycemia	Risk for patients with diabetes.	May require adjustment of antidiabetic medications if significant absorption occurs.
Ocular (Intravitreal Implant)	Increased Intraocular Pressure	Common; ~38% require IOP-lowering medication.	Requires lifelong monitoring and may necessitate medical or surgical intervention.
	Cataract Formation	Very common; >80% of phakic patients require surgery.	A near-certainty in phakic eyes, which must be part of the informed consent process.
	Endophthalmitis	Rare but serious	A risk of the intravitreal injection procedure itself; a medical emergency.

5.2 Contraindications

The use of fluocinolone acetonide is contraindicated in certain situations to prevent harm.

• General: A known history of hypersensitivity to fluocinolone acetonide or any other component in the formulation is an absolute contraindication.
• Topical Formulations: Topical use is contraindicated in the treatment of primary cutaneous infections of bacterial, fungal, or viral origin (e.g., impetigo, tinea, herpes simplex, varicella). It is also contraindicated for treating rosacea, acne vulgaris, and perioral dermatitis, as steroids can exacerbate these conditions. Use for diaper dermatitis (napkin eruptions) is not recommended.
• Intravitreal Implant: The implant is contraindicated in patients with active or suspected ocular or periocular infections. It is also contraindicated in patients with pre-existing glaucoma who have a large cup-to-disc ratio (>0.8), as the risk of further IOP elevation is unacceptably high.

5.3 Warnings and Precautions

Clinicians should be aware of several important warnings and precautions when prescribing fluocinolone acetonide.

• Systemic Absorption: The potential for systemic absorption and subsequent systemic side effects is the most significant warning for topical formulations. Patients should be evaluated for HPA axis suppression if they are receiving high doses, are treated over large surface areas, for prolonged periods, or under occlusion.
• Concomitant Infections: If a concomitant skin infection is present or develops, an appropriate antimicrobial agent must be instituted. If the infection does not respond promptly, the corticosteroid should be discontinued until the infection is adequately controlled, as the steroid can mask the signs of a worsening infection.
• Ocular Toxicity from Topical Use: Patients should be instructed to avoid contact with the eyes. The use of topical corticosteroids on the face or near the eyes has been associated with the development of glaucoma and posterior subcapsular cataracts.
• Peanut Hypersensitivity: Several oil-based formulations (e.g., Derma-Smoothe/FS) contain refined peanut oil. While the refining process is intended to remove allergenic proteins, caution should be exercised when prescribing these products for individuals with a known peanut allergy.

5.4 Use in Specific Populations

• Pediatrics: Children are at an increased risk for systemic toxicity and require special consideration. Use should be limited to the least amount necessary for the shortest possible duration. Chronic use may interfere with growth and development, which should be monitored. The use of topical oil in the diaper area is not recommended, as diapers can act as an occlusive dressing and increase systemic absorption.
• Pregnancy: Fluocinolone acetonide is classified as Pregnancy Category C. Teratogenic effects have been demonstrated in animal studies following dermal application. As there are no adequate and well-controlled studies in pregnant women, the drug should be used during pregnancy only if the potential benefit to the mother justifies the potential risk to the fetus. Extensive use, large amounts, or prolonged periods of therapy should be avoided.
• Lactation: It is not known whether topical application of corticosteroids could result in sufficient systemic absorption to produce detectable quantities in breast milk. Caution should be exercised when administering to a nursing woman. It is advised not to apply topical steroids to the breasts immediately prior to breastfeeding.

The safety profile clearly illustrates a dose-duration-location dependency. The risk of adverse events is not a fixed property of the molecule but exists on a spectrum determined by how it is used. This underscores that the primary tools for ensuring safety are judicious prescribing and comprehensive patient education on the proper application and limitations of therapy.

6.0 Drug and Disease Interactions

The potential for interactions between fluocinolone acetonide and other drugs or underlying diseases is an important clinical consideration, primarily related to the extent of its systemic absorption.

6.1 Drug-Drug Interactions

For topical and otic formulations of fluocinolone acetonide, clinically significant drug-drug interactions are rare when the medication is used as directed for localized conditions, due to minimal systemic absorption. However, the risk of interactions becomes relevant if significant systemic absorption occurs, such as with prolonged use over large surface areas or under occlusion.

• Concurrent Corticosteroids: The most significant interaction risk is with other corticosteroid-containing products. Co-administration of topical fluocinolone with oral corticosteroids (e.g., prednisone) or potent inhaled corticosteroids (e.g., fluticasone) can have an additive effect, increasing the total systemic corticosteroid load. This potentiates the risk of systemic adverse effects, including HPA axis suppression and Cushing's syndrome.
• Antidiabetic Agents: If systemically absorbed, corticosteroids can induce hyperglycemia by antagonizing the action of insulin and promoting gluconeogenesis. This can decrease the effectiveness of oral antidiabetic agents (e.g., metformin, glipizide, glimepiride) and insulin, potentially requiring dose adjustments to maintain glycemic control.
• Immunosuppressants and Vaccines: Systemic corticosteroid activity can be immunosuppressive. If significant absorption occurs, fluocinolone acetonide could have an additive effect with other immunosuppressive drugs (e.g., adalimumab, cyclosporine), potentially increasing the risk of infections. The immune response to live or live-attenuated vaccines may also be diminished.

While extensive lists of theoretical interactions exist in pharmacological databases, their clinical relevance for topical fluocinolone is low and contingent upon substantial systemic exposure. For the intravitreal implant, systemic drug levels are negligible, making systemic drug-drug interactions highly unlikely.

6.2 Drug-Food/Lifestyle Interactions

There are no known clinically significant interactions between topical fluocinolone acetonide and specific foods or beverages. Patients should always be advised to inform their healthcare providers of all prescription and non-prescription medications, vitamins, and herbal supplements they are taking to ensure a comprehensive safety assessment.

6.3 Disease Interactions

The safety and efficacy of fluocinolone acetonide can be significantly influenced by a patient's pre-existing medical conditions.

• Diabetes Mellitus: Patients with diabetes should use fluocinolone acetonide with caution. Systemic absorption, even if minimal, has the potential to elevate blood glucose levels and may complicate glycemic management.
• Cutaneous Infections: The use of topical corticosteroids is contraindicated in primary bacterial, fungal, or viral skin infections. The anti-inflammatory and immunosuppressive properties of fluocinolone can mask the clinical signs of an infection, allowing it to worsen and spread. If a secondary infection develops during treatment, appropriate antimicrobial therapy must be initiated.
• Hyperadrenocorticism (Cushing's Syndrome): Patients with this condition should use corticosteroids with extreme caution, as any systemic absorption can exacerbate the underlying endocrine disorder.
• Ocular Conditions: For the intravitreal implant, pre-existing glaucoma is a contraindication. For topical formulations, application near the eyes should be avoided, as it has been linked to an increased risk of developing glaucoma and cataracts.
• Impaired Skin Barrier: Conditions that compromise the integrity of the skin, such as large sores, severe burns, or broken skin, dramatically increase percutaneous absorption. In these situations, the risk of systemic toxicity is substantially higher, and use should be approached with caution.

Ultimately, the most clinically significant "interaction" for topical fluocinolone is not with another drug, but with the patient's own physiology and behavior. The integrity of the skin barrier, the presence of underlying diseases like diabetes, and the patient's adherence to application instructions (avoiding overuse or improper occlusion) are the dominant factors that determine the drug's safety profile in practice. This shifts the focus of risk management from a simple review of concomitant medications to a holistic assessment of the patient and comprehensive counseling on appropriate use.

7.0 Regulatory Status and History

Fluocinolone acetonide has a long and established history in clinical medicine, evolving from a novel synthetic steroid in the mid-20th century to a versatile agent utilized in advanced drug delivery systems today.

7.1 Discovery and Early Marketing

Fluocinolone acetonide was a product of the intensive steroid chemistry research of the 1950s. It was first synthesized in 1959 at the research facilities of Syntex Laboratories in Mexico City. As a synthetic derivative of hydrocortisone, its structure was intentionally modified with fluorine substitutions at the 6α and 9α positions to dramatically enhance its glucocorticoid and anti-inflammatory activity. Following demonstration of its potent activity, it was first approved for medical use and introduced to the market in 1961 under the brand name Synalar, quickly becoming a widely used topical corticosteroid.

7.2 FDA Approval History

The regulatory journey of fluocinolone acetonide in the United States reflects its evolution from a single compound to a component of numerous products and delivery systems.

• Early Topical Approvals: The drug has been available in the U.S. for decades. For example, an Abbreviated New Drug Application (ANDA) for Fluocinolone Acetonide Topical Solution, 0.01% was approved by the FDA as early as June 15, 1982.
• Generic Formulations: As patents expired, numerous generic versions entered the market. The ANDAs for generic versions of the 0.01% topical oil (Body Oil and Scalp Oil), bioequivalent to the reference product Derma-Smoothe/FS, were approved by the FDA on October 17, 2011.
• Intravitreal Implants: The modern era of fluocinolone acetonide has been defined by its incorporation into long-acting ophthalmic implants.
• An implantable device containing fluocinolone acetonide was approved by the FDA in May 2016.
• The Yutiq (0.18 mg) intravitreal implant received FDA approval on October 15, 2018, for the treatment of chronic non-infectious uveitis affecting the posterior segment of the eye.
• The Iluvien (0.19 mg) implant is approved for the treatment of diabetic macular edema.

This regulatory timeline illustrates a classic pharmaceutical lifecycle. The initial discovery of a potent molecule led to decades of widespread use in conventional topical formulations. In the 21st century, the drug experienced a revitalization through the application of advanced drug delivery technology, creating novel, high-value products for specialized indications. This demonstrates how a mature, well-understood active pharmaceutical ingredient can gain new therapeutic applications and market longevity through innovations in formulation science that target unmet medical needs.

7.3 Brand Names

Reflecting its long history and global use, fluocinolone acetonide is marketed under a multitude of brand names, both as a single agent and in combination products.

• Topical Formulations: Synalar, Capex, Derma-Smoothe/FS, Flac, Fluoderm, Fluonex.
• Otic Formulations: DermOtic, Flac.
• Ophthalmic Formulations (Implants): Iluvien, Retisert, Yutiq.
• Combination Products:
• Neo-Synalar: with the antibiotic neomycin.
• Otovel: with the antibiotic ciprofloxacin.
• Tri-Luma: with the depigmenting agent hydroquinone and the retinoid tretinoin.

8.0 Expert Analysis and Recommendations

This comprehensive review of fluocinolone acetonide reveals a mature, potent, and remarkably versatile corticosteroid whose clinical role is defined by a nuanced interplay between its intrinsic pharmacological activity and its diverse pharmaceutical formulations. A synthesis of the available evidence allows for a clear delineation of its risk-benefit profile and its appropriate place in modern therapy.

8.1 Synthesis of Risk-Benefit Profile

The risk-benefit profile of fluocinolone acetonide is not monolithic; it exists on a spectrum that is highly dependent on the chosen formulation and the clinical context.

• Topical and Otic Formulations: For the short-term management of acute or subacute, localized, corticosteroid-responsive inflammatory conditions of the skin and ear, the risk-benefit profile is overwhelmingly favorable. Its efficacy in reducing inflammation and pruritus is well-established, and its low-to-medium potency provides a sufficient therapeutic effect for many common dermatoses without incurring the higher risks associated with more potent steroids. The primary risks—local skin atrophy and systemic HPA axis suppression—are almost entirely preventable and are directly linked to improper use. Factors that shift the balance toward risk include treatment duration beyond the recommended 2-4 weeks, application to large surface areas, use on sensitive or thin-skinned areas (face, groin, axillae), and the application of occlusive dressings. Therefore, the key to maintaining a favorable risk-benefit profile lies in strict adherence to prescribing guidelines and, most importantly, robust patient education.
• Intravitreal Implants: In ophthalmology, the risk-benefit calculation is far more complex and is reserved for patients with chronic, severe, and often refractory posterior segment inflammatory diseases. The principal benefit is profound: sustained, localized, long-term (up to 3 years) control of inflammation from a single administration. This can significantly reduce the substantial treatment burden associated with frequent intravitreal injections and may allow patients to avoid or reduce their need for systemic immunosuppressive therapy and its associated toxicities. However, this benefit is counterbalanced by a high probability of significant local adverse events. The development of cataracts in phakic patients is a near certainty, and a substantial proportion of all patients will develop elevated intraocular pressure requiring long-term medical or surgical management. The 7-year data from the MUST trial introduces a critical layer of nuance, suggesting that while the implant provides superior local inflammation control for years, it may not result in better long-term visual acuity compared to systemic therapy. This finding complicates the risk-benefit analysis, forcing a difficult discussion with the patient about treatment goals: is the primary aim to control inflammation and reduce treatment burden, or is it to maximize the probability of long-term vision preservation, even if it requires systemic treatment?

8.2 Place in Therapy

• Dermatology and Otology: Fluocinolone acetonide remains a foundational, workhorse agent. Its availability in multiple formulations (cream, ointment, oil, shampoo, solution) allows clinicians to tailor therapy to the specific type of lesion and anatomical location (e.g., scalp oil for psoriatic plaques, cream for weeping eczema). It is an indispensable tool for the management of mild-to-moderate inflammatory skin and ear conditions.
• Ophthalmology: The intravitreal implant is a specialized, second- or third-line therapy. It is not a first-line treatment for DME or uveitis. Its use is most appropriate for patients with chronic or recurrent disease who have failed or are intolerant to other therapies, or for whom the burden of frequent anti-VEGF or other injections is unsustainable. The FDA's indication for DME, which specifies use in patients who have previously been treated with a course of corticosteroids without a clinically significant rise in IOP, is a clear regulatory effort to guide patient selection toward those less likely to experience the most common and problematic adverse event, thereby optimizing its place in therapy.

8.3 Recommendations for Clinical Practice

1. Prioritize Patient Education for Topical Use: The single most effective strategy for ensuring the safe use of topical fluocinolone acetonide is comprehensive patient education. Clinicians and pharmacists should emphasize the principles of using the least potent formulation for the shortest duration necessary to achieve control. Counseling should explicitly address the risks associated with overuse, occlusion, and application to sensitive areas like the face, groin, and axillae.
2. Meticulous Patient Selection for Intravitreal Implants: The decision to use a fluocinolone acetonide implant requires a thorough discussion of the expected benefits and the high probability of adverse events. The ideal candidate is a well-informed patient with chronic, difficult-to-control posterior segment inflammation in whom the benefits of long-term local control are deemed to outweigh the near-certainty of cataract surgery (if phakic) and the high risk of manageable IOP elevation. The findings of the MUST trial should be discussed, framing the choice between implant and systemic therapy as a long-term strategic decision.
3. Implement Proactive Monitoring: Regular follow-up is essential. For patients on long-term or extensive topical therapy, particularly children, clinicians should monitor for signs of skin atrophy and systemic effects (e.g., by tracking growth parameters). For all patients receiving an intravitreal implant, lifelong, regular monitoring of intraocular pressure is mandatory.

8.4 Future Research Directions

While fluocinolone acetonide is a well-established drug, several areas warrant further investigation.

• Long-Term Topical Safety in Chronic Disease: While long-term safety data exist for combination creams in melasma, more prospective, long-term data on the safety of fluocinolone acetonide monotherapy in chronic pediatric and adult dermatoses, such as atopic dermatitis, would be valuable to better define the cumulative risk of skin atrophy.
• Optimizing Ophthalmic Use: Head-to-head clinical trials comparing the fluocinolone acetonide implant to modern biologic agents for non-infectious uveitis are needed to better position it in the treatment algorithm. Further research to identify predictive biomarkers for both efficacy and the development of severe IOP elevation would help refine patient selection.
• Novel Formulations: Research into novel topical delivery systems (e.g., nanoformulations) that could enhance epidermal retention while minimizing dermal penetration and systemic absorption could potentially improve the long-term safety profile for chronic dermatological use.

Works cited

1. Fluocinolone Acetonide | C24H30F2O6 | CID 6215 - PubChem, accessed August 20, 2025, https://pubchem.ncbi.nlm.nih.gov/compound/Fluocinolone-Acetonide
2. Fluocinolone acetonide: Uses, Interactions, Mechanism of Action | DrugBank Online, accessed August 20, 2025, https://go.drugbank.com/drugs/DB00591
3. Fluocinolone acetonide (NSC 92339, CAS Number: 67-73-2) | Cayman Chemical, accessed August 20, 2025, https://www.caymanchem.com/product/23027/fluocinolone-acetonide
4. Fluocinolone Acetonide Oil, 0.01% Ear Drops For Otic ... - Amazon S3, accessed August 20, 2025, https://s3-us-west-2.amazonaws.com/drugbank/fda_labels/DB00591.pdf?1265922803
5. Label: FLUOCINOLONE ACETONIDE cream FLUOCINOLONE ACETONIDE ointment - DailyMed, accessed August 20, 2025, https://dailymed.nlm.nih.gov/dailymed/lookup.cfm?setid=de5b78ab-ff79-3e0f-cad4-ecab11ebbdcd
6. Fluocinolone (intraocular route) - Side effects & uses - Mayo Clinic, accessed August 20, 2025, https://www.mayoclinic.org/drugs-supplements/fluocinolone-intraocular-route/description/drg-20122646
7. Fluocinolone Acetonide Cream USP, 0.01%, 0.025% - DailyMed, accessed August 20, 2025, https://dailymed.nlm.nih.gov/dailymed/fda/fdaDrugXsl.cfm?setid=da65dffd-a017-46dd-8a5b-a4e4574c4abc
8. Full article: Efficacy and Safety of Fluocinolone Acetonide 0.19 mg Intravitreal Implant for the Treatment of Non-Infectious Uveitis: A Systematic Review of Real-World Evidence - Taylor & Francis Online, accessed August 20, 2025, https://www.tandfonline.com/doi/full/10.1080/09273948.2024.2435472
9. Efficacy and Safety of Fluocinolone Acetonide Implant in Diabetic Macular Edema: Practical Guidelines from Reference Center - MDPI, accessed August 20, 2025, https://www.mdpi.com/1999-4923/16/9/1183
10. HIGHLIGHTS OF PRESCRIBING INFORMATION These highlights ..., accessed August 20, 2025, https://dailymed.nlm.nih.gov/dailymed/getFile.cfm?setid=64586ff9-941a-418a-a870-ffb5dafbe24b&type=pdf
11. Fluocinolone Acetonide (Topical) Monograph for Professionals - Drugs.com, accessed August 20, 2025, https://www.drugs.com/monograph/fluocinolone-acetonide-topical.html
12. Fluocinolone topical: Uses, Side Effects, Interactions, Pictures, Warnings & Dosing - WebMD, accessed August 20, 2025, https://www.webmd.com/drugs/2/drug-1447-9021/fluocinolone-topical/fluocinolone-eczema-oil-topical/details
13. Untitled - accessdata.fda.gov, accessed August 20, 2025, https://www.accessdata.fda.gov/drugsatfda_docs/label/2017/201923s002lbl.pdf
14. Fluocinolone acetonide - Wikipedia, accessed August 20, 2025, https://en.wikipedia.org/wiki/Fluocinolone_acetonide
15. CAS 67-73-2 Fluocinolone acetonide - Alfa Chemistry, accessed August 20, 2025, https://www.alfa-chemistry.com/fluocinolone-acetonide-cas-67-73-2-item-99341.htm
16. Fluocinolone Acetonide | CAS 67-73-2 - LGC Standards, accessed August 20, 2025, https://www.lgcstandards.com/AG/en/p/TRC-F455800
17. Topical corticosteroids in dermatology, accessed August 20, 2025, https://ijdvl.com/topical-corticosteroids-in-dermatology/
18. CAS Number 67-73-2 | Fluocinolone Acetonide, accessed August 20, 2025, https://www.spectrumrx.com/cas/67-73-2
19. Fluocinolone (Acetonide) | Glucocorticoid Receptor Agonist | MedChemExpress, accessed August 20, 2025, https://www.medchemexpress.com/Fluocinolone-Acetonide.html
20. Fluocinonide Topical: MedlinePlus Drug Information, accessed August 20, 2025, https://medlineplus.gov/druginfo/meds/a601054.html
21. Fluocinolone (topical application route) - Side effects & dosage - Mayo Clinic, accessed August 20, 2025, https://www.mayoclinic.org/drugs-supplements/fluocinolone-topical-application-route/description/drg-20073886
22. medlineplus.gov, accessed August 20, 2025, https://medlineplus.gov/druginfo/meds/a682271.html#:~:text=Fluocinolone%20is%20in%20a%20class,swelling%2C%20redness%2C%20and%20itching.
23. PRODUCT MONOGRAPH INCLUDING PATIENT MEDICATION INFORMATION PrSYNALAR® Fluocinolone Acetonide Ointment 0.025% w/w Topical Cortic, accessed August 20, 2025, https://pdf.hres.ca/dpd_pm/00061939.PDF
24. Skin Inflammation of the ear | DrugBank Online, accessed August 20, 2025, https://go.drugbank.com/indications/DBCOND0135822
25. Fluocinolone: uses, dosing, warnings, adverse events, interactions - MedCentral, accessed August 20, 2025, https://www.medcentral.com/drugs/monograph/1447-382271/fluocinolone-topical
26. Fluocinolone: Side Effects, Dosage, Uses and More - Healthline, accessed August 20, 2025, https://www.healthline.com/health/drugs/fluocinolone-topical-cream
27. Synalar, Capex (fluocinolone) dosing, indications, interactions, adverse effects, and more, accessed August 20, 2025, https://reference.medscape.com/drug/capex-derma-smooth-fs-fluocinolone-343518
28. Fluocinolone - brand name list from Drugs.com, accessed August 20, 2025, https://www.drugs.com/ingredient/fluocinolone.html
29. Fluocinolone Oil: Package Insert / Prescribing Information - Drugs.com, accessed August 20, 2025, https://www.drugs.com/pro/fluocinolone-oil.html
30. Introduction - Clinical Review Report: Fluocinolone Acetonide Intravitreal Implant (Iluvien), accessed August 20, 2025, https://www.ncbi.nlm.nih.gov/books/NBK551990/
31. Fluocinolone acetonide 0.01% in peanut oil: therapy for childhood atopic dermatitis, even in patients who are peanut sensitive - PubMed, accessed August 20, 2025, https://pubmed.ncbi.nlm.nih.gov/12664021/
32. Label: FLUOCINOLONE ACETONIDE OIL - DailyMed, accessed August 20, 2025, https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=0ff97af2-04d6-478e-8abe-ca5a0c675708&audience=consumer
33. (PDF) Efficacy and Safety of Generic Fluocinolone Acetonide ..., accessed August 20, 2025, https://www.researchgate.net/publication/391270213_Efficacy_and_Safety_of_Generic_Fluocinolone_Acetonide_Hydroquinone_and_Tretinoin_Cream_Compared_With_TRI-LUMA_for_the_Treatment_of_Moderate-To-Severe_Melasma_in_Chinese_Patients_A_Randomized_Single-Ce
34. Efficacy and Safety of Generic Fluocinolone Acetonide, Hydroquinone, and Tretinoin Cream Compared With TRI‐LUMA for the Treatment of Moderate‐To‐Severe Melasma in Chinese Patients: A Randomized, Single‐Center, Placebo‐Controlled Trial - PMC - PubMed Central, accessed August 20, 2025, https://pmc.ncbi.nlm.nih.gov/articles/PMC12038315/
35. Hydroquinone 4%, tretinoin 0.05%, fluocinolone acetonide 0.01%: A safe and efficacious 12-month treatment for melasma - ResearchGate, accessed August 20, 2025, https://www.researchgate.net/publication/8002123_Hydroquinone_4_tretinoin_005_fluocinolone_acetonide_001_A_safe_and_efficacious_12-month_treatment_for_melasma
36. Hydroquinone 4%, tretinoin 0.05%, fluocinolone acetonide 0.01%: A safe and efficacious 12-month treatment for melasma - Oregon Health & Science University, accessed August 20, 2025, https://ohsu.elsevierpure.com/en/publications/hydroquinone-4-tretinoin-005-fluocinolone-acetonide-001-a-safe-an
37. Efficacy and safety of fluocinolone acetonide 0.025% otic solution in patients with otic eczema: a randomized, double-blind, placebo-controlled clinical trial - PMC, accessed August 20, 2025, https://pmc.ncbi.nlm.nih.gov/articles/PMC6166331/
38. Why Otovel, accessed August 20, 2025, https://www.otovel.com/why-otovel.html
39. ILUVIEN® (Fluocinolone Acetonide Intravitreal Implant) - Point32Health, accessed August 20, 2025, https://www.point32health.org/provider/wp-content/uploads/sites/2/2024/01/Iluvien-COM-QHP-RIT-MAT-MDMNG.pdf
40. Real-World Outcomes of the 0.19 mg Fluocinolone Acetonide Intravitreal Implant for Diabetic Macular Edema - PMC - PubMed Central, accessed August 20, 2025, https://pmc.ncbi.nlm.nih.gov/articles/PMC11323504/
41. Safety and effectiveness of the fluocinolone acetonide intravitreal implant (ILUVIEN): 3-year results from the European IRISS registry study | British Journal of Ophthalmology, accessed August 20, 2025, https://bjo.bmj.com/content/107/10/1502
42. The 0.2-μg/day Fluocinolone Acetonide Intravitreal Implant in ..., accessed August 20, 2025, https://pmc.ncbi.nlm.nih.gov/articles/PMC10630780/
43. Association Between Long-Lasting Intravitreous Fluocinolone ..., accessed August 20, 2025, https://pubmed.ncbi.nlm.nih.gov/28477440/
44. fluocinolone topical: Dosing, contraindications, side effects, and pill pictures - Epocrates, accessed August 20, 2025, https://www.epocrates.com/online/drugs/27/fluocinolone-topical
45. Fluocinolone Topical: MedlinePlus Drug Information, accessed August 20, 2025, https://medlineplus.gov/druginfo/meds/a682271.html
46. DermOtic (fluocinolone acetonide, otic) dosing, indications, interactions, adverse effects, and more - Medscape Reference, accessed August 20, 2025, https://reference.medscape.com/drug/dermotic-fluocinolone-acetonide-otic-999303
47. Fluocinonide (topical application route) - Side effects & dosage - Mayo Clinic, accessed August 20, 2025, https://www.mayoclinic.org/drugs-supplements/fluocinonide-topical-application-route/description/drg-20073636
48. Fluocinolone Acetonide Topical Solution USP, 0.01% Rx Only - DailyMed, accessed August 20, 2025, https://dailymed.nlm.nih.gov/dailymed/fda/fdaDrugXsl.cfm?setid=3fb00d90-6a5b-4e95-ab6b-f5b102ff0f36&type=display
49. SYNALAR® (fluocinolone acetonide) Ointment 0.025% - accessdata.fda.gov, accessed August 20, 2025, https://www.accessdata.fda.gov/drugsatfda_docs/label/2013/012787s071lbl.pdf
50. Fluocinolone (Topical | Memorial Sloan Kettering Cancer Center, accessed August 20, 2025, https://www.mskcc.org/cancer-care/patient-education/medications/adult/fluocinolone-topical
51. Derma-Smoothe/FS® (fluocinolone acetonide) Topical Oil, 0.01% (Body Oil) - accessdata.fda.gov, accessed August 20, 2025, https://www.accessdata.fda.gov/drugsatfda_docs/label/2017/019452s024lbl.pdf
52. Fluocinolone Topical Dosage Guide + Max Dose, Adjustments - Drugs.com, accessed August 20, 2025, https://www.drugs.com/dosage/fluocinolone-topical.html
53. Fluocinolone (Topical: Pediatric Medication | Memorial Sloan Kettering Cancer Center, accessed August 20, 2025, https://www.mskcc.org/cancer-care/patient-education/medications/pediatric/fluocinolone-topical
54. Fluocinolone Ear Drops: Package Insert / Prescribing Info - Drugs.com, accessed August 20, 2025, https://www.drugs.com/pro/fluocinolone-ear-drops.html
55. fluocinolone 0.01 % topical body oil - Kaiser Permanente, accessed August 20, 2025, https://healthy.kaiserpermanente.org/health-wellness/drug-encyclopedia/drug.fluocinolone-0-01-topical-body-oil.255079
56. Fluocinolone: Uses, Side Effects, FAQs & More - GoodRx, accessed August 20, 2025, https://www.goodrx.com/synalar/what-is
57. FLUOCINOLONE ACETONIDE OINTMENT, USP, 0.025% - DailyMed, accessed August 20, 2025, https://dailymed.nlm.nih.gov/dailymed/fda/fdaDrugXsl.cfm?setid=49552e29-7813-4726-b15d-63bd975b6588
58. Label: FLUOCINOLONE ACETONIDE oil - DailyMed, accessed August 20, 2025, https://dailymed.nlm.nih.gov/dailymed/lookup.cfm?setid=4790bdfa-c964-4c3e-9d01-c2fb23a0172e
59. Fluocinonide Ointment - accessdata.fda.gov, accessed August 20, 2025, https://www.accessdata.fda.gov/drugsatfda_docs/label/2016/016909s053lbl.pdf
60. Fluocinolone Cream and other topical products - Drugs.com, accessed August 20, 2025, https://www.drugs.com/fluocinolone-topical.html
61. Fluocinonide topical: Uses, Side Effects, Interactions, Pictures, Warnings & Dosing - WebMD, accessed August 20, 2025, https://www.webmd.com/drugs/2/drug-96/fluocinonide-topical/details
62. Real-World Data Suggest Safety, Efficacy of Fluocinolone Acetonide for NIU-PS - HCPLive, accessed August 20, 2025, https://www.hcplive.com/view/real-world-data-suggest-safety-efficacy-fluocinolone-acetonide-niu-ps
63. dailymed.nlm.nih.gov, accessed August 20, 2025, https://dailymed.nlm.nih.gov/dailymed/fda/fdaDrugXsl.cfm?setid=49552e29-7813-4726-b15d-63bd975b6588#:~:text=CONTRAINDICATIONS%3A,the%20components%20of%20the%20preparation.
64. Fluocinolone, 0.025 % ointment - Arpimed, accessed August 20, 2025, https://arpimed.am/fluocinolone-0-025-ointment/
65. Fluocinolone Acetonide Topical Oil, 0.01% (Scalp Oil) Rx only - DailyMed, accessed August 20, 2025, https://dailymed.nlm.nih.gov/dailymed/fda/fdaDrugXsl.cfm?setid=47de7132-c692-4c77-8160-ab0c1f501a7c
66. Fluocinolone Acetonide Side Effects, Uses, Interactions, Pictures, Warnings & Dosing, accessed August 20, 2025, https://www.wellrx.com/fluocinolone-acetonide/drug-information/
67. Fluocinolone topical Use During Pregnancy - Drugs.com, accessed August 20, 2025, https://www.drugs.com/pregnancy/fluocinolone-topical.html
68. What is Fluocinolone Acetonide used for? - Patsnap Synapse, accessed August 20, 2025, https://synapse.patsnap.com/article/what-is-fluocinolone-acetonide-used-for
69. Fluocinolone topical Interactions - Drugs.com, accessed August 20, 2025, https://www.drugs.com/drug-interactions/fluocinolone-topical.html
70. Fluocinonide topical Interactions - Drugs.com, accessed August 20, 2025, https://www.drugs.com/drug-interactions/fluocinonide-topical.html
71. Drug Interactions for Derma-Smoothe FS - 284 Major Interactions - PrescriberPoint, accessed August 20, 2025, https://prescriberpoint.com/therapies/fluocinolone-acetonide-bfcc00c/interactions
72. Fluocinonide: Uses, Interactions, Mechanism of Action | DrugBank ..., accessed August 20, 2025, https://go.drugbank.com/drugs/DB01047
73. Fluocinolone topical Disease Interactions - Drugs.com, accessed August 20, 2025, https://www.drugs.com/disease-interactions/fluocinolone-topical.html?professional=1
74. center for drug evaluation and research - accessdata.fda.gov, accessed August 20, 2025, https://www.accessdata.fda.gov/drugsatfda_docs/nda/pre96/087159.PDF
75. Approval Package for: ANDA 201764 - accessdata.fda.gov, accessed August 20, 2025, https://www.accessdata.fda.gov/drugsatfda_docs/bla/2011/201764Orig1s000.pdf
76. Approval Package for: ANDA 201759 - accessdata.fda.gov, accessed August 20, 2025, https://www.accessdata.fda.gov/drugsatfda_docs/bla/2011/201759Orig1s000.pdf
77. DermOtic Oil (Fluocinolone): Uses, Side Effects, Dosage & More - GoodRx, accessed August 20, 2025, https://www.goodrx.com/dermotic/what-is