Clobetasol

D07A - Corticosteroids, plain ATC D07AD01 Small molecule

JFDA label: Cloderm Ointment

Mechanism of Action

Topical corticosteroids have anti-inflammatory, antipruritic, and vasoconstrictive properties. May depress the formation, release, and activity of endogenous chemical mediators of inflammation (kinins, histamine, liposomal enzymes, prostaglandins) through the induction of phospholipase A2 inhibitory proteins (lipocortins) and sequential inhibition of the release of arachidonic acid. Clobetasol has very high range potency.

Indications

Approved

Steroid-responsive dermatoses

Contraindications

Source: Lexicomp

Additional contraindications (not in US labeling): Treatment of rosacea, acne vulgaris, perioral dermatitis, or perianal and genital pruritus Absolute
Hypersensitivity to clobetasol, other corticosteroids, or any component of the formulation Absolute
application to eyes or eyelids Absolute
children Note: Product labels may vary (refer also to product labels) Absolute
primary infections of the scalp (scalp solution only) Absolute
ulcerous wounds Absolute
viral (eg, herpes or varicella) lesions of the skin, bacterial or fungal skin infections, parasitic infections, skin manifestations relating to tuberculosis or syphilis, eruptions following vaccinations 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 (3)

Common headache · Localized burning · numbness of fingers, telangiectasia, eczema, xeroderma, erythema, local irritation, nasopharyngitis, streptococcal pharyngitis

Skin and subcutaneous tissue disorders (2)

Not Known Local acneiform eruptions · urticaria

General disorders and administration site conditions (1)

Not Known Application site edema

Other (1)

Very Common Endocrine & metabolic: HPA-axis suppression

Dosing

Source: Lexicomp

Note: Discontinue when control achieved; if improvement not seen within 2 weeks, reassessment of diagnosis may be necessary. Oral mucosal inflammation (off-label use): Topical: Cream: Apply twice daily for up to 2 weeks (maximum dose: 50 g/week); discontinue application when control is achieved; if no improvement is seen, reassessment of diagnosis may be necessary. Steroid-responsive dermatoses: Topical: Cream (0.05%), emollient cream, foam, gel, lotion, ointment, solution: Apply twice daily for up to 2 weeks (maximum dose: 50 g/week or 50 mL/week). Mild to moderate plaque-type psoriasis of nonscalp areas: Topical: Foam: Apply twice daily for up to 2 weeks (maximum dose: 50 g/week). Moderate to severe plaque-type psoriasis: Topical: Cream (0.025%), emollient cream, lotion: Apply twice daily for up to 2 weeks (cream) or up to 4 weeks if needed (emollient cream, lotion) when application is Spray: Apply by spraying directly onto affected area twice daily and gently rub into skin. Limit treatment to 4 consecutive weeks; treatment beyond 2 weeks should be limited to localized lesions that have not improved sufficiently. Maximum total dose: 50 g/week or 59 mL/week. Do not use more than 26 sprays per application or 52 sprays per day. Scalp psoriasis, moderate to severe: Topical: Foam: Apply twice daily for up to 2 weeks (maximum dose: 50 g/week). Shampoo: Apply thin film to dry scalp once daily (maximum dose: 50 g/week or 50 mL/week); leave in place for 15 minutes, then add water, lather, and rinse thoroughly. Limit treatment to 4 consecutive weeks.

(For additional information see "Clobetasol: Pediatric drug information") Note: Discontinue when control achieved; if improvement not seen within 2 weeks, reassessment of diagnosis may be necessary. Use in children Mild to moderate plaque-type psoriasis of nonscalp areas: Topical: Foam: Children ≥12 years and Adolescents: Refer to adult dosing. Moderate to severe plaque-type psoriasis: Topical: Emollient cream: Adolescents ≥16 years: Refer to adult dosing. Lotion, spray, cream (0.025%): Adolescents ≥18 years: Refer to adult dosing. Scalp psoriasis, moderate to severe: Topical: Foam: Children ≥12 years and Adolescents: Refer to adult dosing. Shampoo: Adolescents ≥18 years: Refer to adult dosing. Steroid-responsive dermatoses: Topical: Cream (0.05%), emollient cream, foam, gel, ointment, solution: Children ≥12 years and Adolescents: Refer to adult dosing. Lotion: Adolescents ≥18 years: Refer to adult dosing. Oral mucosal inflammation (off-label use): Topical: Cream: Children ≥12 years and Adolescents: 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 may 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.

Local effects

Local effects may occur, including folliculitis, acneiform eruptions, hypopigmentation, perioral dermatitis, allergic contact dermatitis, secondary infection, striae, miliaria, skin atrophy, and telangiectasia; local adverse effects may be irreversible.

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's 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

Use in children Dosage form specific issues:

Emollient cream

Contains imidurea which releases traces of formaldehyde as a breakdown product; formaldehyde may cause allergic sensitization or irritation upon skin contact.

Foam/Spray

The foam and spray are flammable. Avoid fire, flame, or smoking during and immediately following application. Other warnings/precautions:

Appropriate use

Do not use if there is atrophy at the treatment site. Do not use with occlusive dressing. Do not use on the face, axillae, or groin or for the treatment of acne vulgaris, rosacea, or perioral dermatitis.

Pregnancy & Lactation

Pregnancy

FDA category C

Adverse events have been observed in animal reproduction studies. Extensive use in pregnant women is not recommended.

Lactation

Systemic corticosteroids are present in human milk. It is not known if topical application will result in detectable quantities in breast milk. According to the manufacturer, the decision to continue or discontinue breastfeeding during therapy should take into account the risk of infant exposure, the benefits of breastfeeding to the infant, and benefits of treatment to the mother.

Monitoring

Clinical pearl	Adrenal suppression with extensive/prolonged use (ACTH stimulation test, morning plasma cortisol test, urinary free cortisol test); response to treatment

Chemistry & Properties

Formula	C22H28ClFO4
Molecular weight	410.91 g/mol
IUPAC name	(8S,9R,10S,11S,13S,14S,16S,17R)-17-(2-chloroacetyl)-9-fluoro-11,17-dihydroxy-10,13,16-trimethyl-6,7,8,11,12,14,15,16-octahydrocyclopenta[a]phenanthren-3-one
CAS	25122-41-2
PubChem CID	5311051
InChIKey	`FCSHDIVRCWTZOX-DVTGEIKXSA-N`
logP	3.14 (XLogP 2.5)
Polar surface area	74.6 Å²
H-bond acceptors / donors	4 / 2
Drug-likeness (QED)	0.69
Lipinski violations	0

SMILES

C[C@H]1C[C@H]2[C@@H]3CCC4=CC(=O)C=C[C@]4(C)[C@@]3(F)[C@@H](O)C[C@]2(C)[C@@]1(O)C(=O)CCl

Biology & Pharmacokinetics

Pharmacokinetics predicted

Bioavailability	70.0%
Half-life	2.502 h
Volume of distribution	2.99 L/kg
Protein binding	95.4%
BBB penetrant	Yes

Enzyme interactions

Enzyme	Role	Detail
CYP2B6	Inhibitor	—
CYP2C8	Inhibitor	—
CYP3A4	Inhibitor	—
CYP3A4	Substrate	—

Transporters

BCRP (Inhibitor)BSEP (Inhibitor)BSEP (Inhibitor)MRP1 (Inhibitor)OATP1B1 (Inhibitor)OATP1B1 (Inhibitor)OATP1B3 (Inhibitor)OATP1B3 (Inhibitor)OATP2B1 (Inhibitor)P-gp (Inhibitor)P-gp (Substrate)

Registered Products (13)

Brand	Form / strength	Pack	Agent	Citizen (JOD)
Cloderm Cream	Cream 0.05 %	15 g tube pack varies	UNITED PHARM.MFG.CO.LTD(UPM)/JORDAN	0.720
Cloderm Ointment	Ointment 0.05 %	15 g tube pack varies	United Pharmaceutical Manufacturing Co. Ltd.	0.720
Klobederm Ointment	Ointment 0.05 %	15 g tube	Reda Jardaneh Drug Store	0.970
Cloderm Cream	Cream 0.05 %	25 g tube pack varies	UNITED PHARM.MFG.CO.LTD(UPM)/JORDAN	1.200
Cloderm Ointment	Ointment 0.05 %	25 g tube pack varies	UNITED PHARM.MFG.CO.LTD(UPM)/JORDAN	1.200
Klobederm Cream	Cream 0.05 %	15 g tube	Reda Jardaneh Drug Store	1.310
Delor cream	Cream 0.5 mg/1gm	25 g tube	Pharma International Company/ Jordan	1.600
Delor ointment	Ointment 0.05 %	25 g tube	Pharma International Company/ Jordan	1.600
Clobederm Oin	Cream 0.050 % w/w	30 gm	JERASH PHARMACEUTICALS LTD.CO/JORDAN	1.930
Dermovate Cream	Cream 0.05 %w/w	30 g tube	Suleiman Tannous & Sons Co. Ltd	2.020
Dermovate Scalp Application	Lotion 0.5 mg/g	25 ml	Suleiman Tannous & Sons Co. Ltd	2.080
Dermovate Ointment	Ointment 0.05375 %w/w	30 g tube	Suleiman Tannous & Sons Co. Ltd	2.190
Clobex	Solution 500 mcg/1 g	125 ml	IBN CINA DRUG STORE	11.810