Fluocinonide

D07A - Corticosteroids, plain ATC D07AC08 Small molecule approved 1971 Topical Black-box warning

JFDA label: Topsym FAPG

⚠ Black-Box Warning

Mechanism of Action

Agonist of Glucocorticoid receptor — Glucocorticoid receptor agonist

Target	Action	Gene / class
Glucocorticoid receptor efficacy	AGONIST	NR3C1

Indications

Approved

Inflammatory and pruritic dermatologic conditions

Contraindications

Source: Lexicomp

Hypersensitivity to fluocinonide or any component of the formulation Absolute

Adverse Reactions

Very Common >10%Common 1–10%Uncommon 0.1–1% Rare 0.01–0.1%Very Rare <0.01%Not Known

Nervous system disorders (2)

Not Known Intracranial hypertension · localized burning

Metabolism and nutrition disorders (5)

Not Known Cushing's syndrome · glycosuria · growth suppression · HPA-axis suppression · hyperglycemia

Skin and subcutaneous tissue disorders (14)

Not Known Acne vulgaris · allergic dermatitis · atrophic striae · contact dermatitis · folliculitis · hypertrichosis · hypopigmentation · maceration of the skin · miliaria · perioral dermatitis · pruritus · skin atrophy · telangiectasia · xeroderma

Infections and infestations (1)

Not Known Secondary infection

General disorders and administration site conditions (1)

Not Known Local irritation

Dosing

Source: Lexicomp

Atopic dermatitis: Topical: Cream, gel, ointment, solution (0.05%): Apply thin layer to affected area 2 to 4 times daily. Cream (0.1%): Apply thin layer to affected areas once daily. Not recommended for use >2 consecutive weeks or >60 g/week total exposure. Therapy should be discontinued when control is achieved; if no improvement is seen within 2 weeks, reassessment of diagnosis may be necessary. Psoriasis: Topical: Cream, gel, ointment, solution (0.05%): Apply thin layer to affected area 2 to 4 times daily. Cream (0.1%): Apply a thin layer once or twice daily to affected areas. Not recommended for use >2 consecutive weeks or >60 g/week total exposure. Therapy should be discontinued when control is achieved; if no improvement is seen within 2 weeks, reassess diagnosis. Other inflammatory and pruritic dermatologic conditions besides atopic dermatitis or psoriasis: Topical: Cream, gel, ointment, solution (0.05%): Apply thin layer to affected area 2 to 4 times daily. Cream (0.1%): Apply thin layer to affected area once or twice daily. Not recommended for use >2 consecutive weeks or >60 g/week total exposure. Therapy should be discontinued when control is achieved; if no improvement is seen within 2 weeks, reassess diagnosis.

(For additional information see "Fluocinonide: Pediatric drug information") Atopic dermatitis, psoriasis, and other inflammatory and pruritic dermatologic conditions: Children and Adolescents: Topical: Cream, gel, ointment, solution (0.05%): Refer to adult dosing. Children ≥12 years and Adolescents: Topical: Cream (0.1%): Refer to adult dosing.

Refer to adult dosing.

There are no dosage adjustments provided in the manufacturer's labeling.

Warnings & Precautions

Source: Lexicomp

Adrenal suppression

May cause hypercortisolism or suppression of hypothalamic-pituitary-adrenal (HPA) axis, particularly in younger children or in patients receiving high doses for prolonged periods. HPA axis suppression may lead to adrenal crisis.

Contact dermatitis

Allergic contact dermatitis can occur, it is usually diagnosed by failure to heal rather than clinical exacerbation.

Kaposi sarcoma

Prolonged treatment with corticosteroids has been associated with the development of Kaposi sarcoma (case reports); if noted, discontinuation of therapy should be considered (Goedert, 2002).

Local effects

Local adverse reactions may occur (eg, skin atrophy, striae, telangiectasias, burning, itching, irritation, dryness, folliculitis, acneiform eruptions, hypopigmentation, perioral dermatitis, allergic contact dermatitis, secondary infection miliaria); may be irreversible. Local adverse reactions are more likely to occur with occlusive and/or prolonged use. If irritation develops, discontinued use and institute appropriate therapy.

Skin infections

Concomitant skin infections may be present or develop during therapy; discontinue if dermatological infection persists despite appropriate antimicrobial therapy.

Systemic effects

Topical corticosteroids may be absorbed percutaneously. Absorption of topical corticosteroids may cause manifestations of Cushing syndrome, hyperglycemia, or glycosuria. Absorption is increased by the use of occlusive dressings, application to denuded skin, or application to large surface areas. Special populations:

Pediatric

Children may absorb proportionally larger amounts after topical application and may be more prone to systemic effects. HPA axis suppression, intracranial hypertension, and Cushing syndrome have been reported in children receiving topical corticosteroids. Prolonged use may affect growth velocity; growth should be routinely monitored in pediatric patients. Other warnings/precautions:

Application site

Lower-strength formulations (0.05%) may be used cautiously on face or opposing skin surfaces that may rub or touch (eg, skin folds of the groin, axilla, and breasts); higher-strength (0.1%) should not be used on the face, groin, or axillae.

Appropriate use

0.1% cream: Treatment beyond 2 consecutive weeks is not recommended and the total dosage should not exceed 60 g per week. Therapy should be discontinued when control of the disease is achieved. If no improvement is seen within 2 weeks, reassess diagnosis. Do not use more than half of the 120 g tube per week. Should not be used in the treatment of rosacea or perioral dermatitis.

Pregnancy & Lactation

Pregnancy

FDA category C

Adverse events have been observed with corticosteroids in animal reproduction studies. Topical corticosteroids are preferred over systemic for treating conditions, such as psoriasis or atopic dermatitis in pregnant women; high-potency corticosteroids are not recommended during the first trimester. Topical products are not recommended for extensive use, in large quantities, or for long periods of time in pregnant women (Bae 2011; Koutroulis 2011; Leachman 2006). Information specific to the use of fluocinonide during pregnancy is limited (Valkova 2006).

Lactation

Systemic corticosteroids are excreted in human milk. It is not known if sufficient quantities of fluocinonide are absorbed following topical administration to produce detectable amounts in breast milk. Do not apply topical corticosteroids to nipples; hypertension was noted in a breast-feeding infant exposed to a topical corticosteroid while breast-feeding (Leachman 2006). The manufacturer recommends that caution be exercised when administering fluocinonide 0.05% to nursing women. Because mater

Monitoring

Clinical pearl	HPA axis suppression (ACTH stimulation test, AM plasma cortisol test, urinary free cortisol test); signs of bacterial or fungal infections.

Chemistry & Properties

Formula	C26H32F2O7
Molecular weight	494.53 g/mol
IUPAC name	[2-[(1S,2S,4R,8S,9S,11S,12R,13S,19S)-12,19-difluoro-11-hydroxy-6,6,9,13-tetramethyl-16-oxo-5,7-dioxapentacyclo[10.8.0.02,9.04,8.013,18]icosa-14,17-dien-8-yl]-2-oxoethyl] acetate
CAS	356-12-7
PubChem CID	9642
InChIKey	`WJOHZNCJWYWUJD-IUGZLZTKSA-N`
logP	2.94 (XLogP 3.2)
Polar surface area	99.13 Å²
H-bond acceptors / donors	7 / 1
Drug-likeness (QED)	0.60
Lipinski violations	0

SMILES

CC(=O)OCC(=O)[C@@]12OC(C)(C)O[C@@H]1C[C@H]1[C@@H]3C[C@H](F)C4=CC(=O)C=C[C@]4(C)[C@@]3(F)[C@@H](O)C[C@@]12C

Biology & Pharmacokinetics

Pharmacokinetics

BBB penetrant	Yes

Enzyme interactions

Enzyme	Role	Detail
CYP2C8	Inhibitor	—
CYP3A4	Substrate	—

Receptor binding (top 1)

Target	Action	Affinity
Glucocorticoid receptor (NR3C1)	Agonist	pIC50 8.3

Transporters

BCRP (Inhibitor)BSEP (Inhibitor)MRP1 (Inhibitor)OATP1B1 (Inhibitor)OATP1B1 (Inhibitor)OATP1B3 (Inhibitor)OATP1B3 (Inhibitor)P-gp (Inhibitor)P-gp (Substrate)

Registered Products (1)

Brand	Form / strength	Pack	Agent	Citizen (JOD)
Topsym FAPG	Cream 0.05 %	15 g tube	Nabulsi Drug Store	4.350