Azelaic Acid

D10A - Anti-acne preparations for topical use ATC D10AX03 Small molecule approved 1995 Topical Natural product

JFDA label: Skinoren Cream

Mechanism of Action

— Unknown

Indications

Approved

Acne vulgaris (cream)
Rosacea (foam, gel)

Contraindications

Source: Lexicomp

Cream: Hypersensitivity to azelaic acid or any component of the formulation Foam, gel: There are no contraindications listed in the manufacturer’s labeling Absolute

Adverse Reactions

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

Skin and subcutaneous tissue disorders (8)

Common acne · contact dermatitis · desquamation · erythema · Pruritus · skin irritation · xeroderma · xerosis

General disorders and administration site conditions (2)

Common Application site pain · application site pruritus

Other (3)

Very Common Dermatologic: Burning sensation of skin · stinging of skin · tingling of skin

Dosing

Source: Lexicomp

Acne vulgaris: Topical: Cream 20%: Apply a thin film to the affected area(s) twice daily, in the morning and evening; may reduce to once daily if persistent skin irritation occurs. Improvement in condition is usually seen within 4 weeks. Rosacea: Topical: Gel 15% and foam 15%: Apply a thin layer to the affected area(s) of the face twice daily, in the morning and evening; reassess if no improvement after 12 weeks of therapy.

(For additional information see "Azelaic acid: Pediatric drug information") Acne vulgaris: Children ≥12 years and Adolescents: Refer to adult dosing.

Refer to adult dosing.

There are no dosage adjustments provided in the manufacturer's labeling. However, dosage adjustment unlikely due to low systemic absorption.

Warnings & Precautions

Source: Lexicomp

Hypersensitivity

Hypersensitivity reactions (eg, angioedema, dyspnea, eye swelling, facial swelling, skin reactions, urticaria) have been reported; discontinue use if signs/symptoms occur.

Hypopigmentation

A few cases of hypopigmentation after use have been reported; monitor for changes in skin color, especially in patients with dark complexions.

Skin irritation

Skin irritation (eg, pruritus, burning, stinging) may occur, usually during the first few weeks of therapy. Discontinue use if severe skin irritation or sensitivity occurs. Disease-related concerns:

Asthma

Exacerbation of asthma has been reported. Dosage form specific issues:

Foam

Contains flammable propellants. Avoid fire, flame and smoking during and immediately following use.

Gel

Reassess use if no improvement is seen after 12 weeks of therapy.

Polysorbate 80

Some dosage forms may contain polysorbate 80 (also known as Tweens). Hypersensitivity reactions, usually a delayed reaction, have been reported following exposure to pharmaceutical products containing polysorbate 80 in certain individuals (Isaksson 2002; Lucente 2000; Shelley 1995). Thrombocytopenia, ascites, pulmonary deterioration, and renal and hepatic failure have been reported in premature neonates after receiving parenteral products containing polysorbate 80 (Alade 1986; CDC 1984). See manufacturer’s labeling. Other warnings/precautions:

Appropriate use

For external use only; not for oral, ophthalmic, or vaginal use; avoid contact with the eyes, mouth, and other mucous membranes. Use of occlusive dressings or wrappings should be avoided.

Pregnancy & Lactation

Pregnancy

FDA category B

Adverse events have been observed in animal reproduction studies following oral administration. The amount of azelaic acid available systemically following topical administration is minimal (

Lactation

It is not known if azelaic acid is excreted in breast milk. The amount of azelaic acid available systemically following topical administration is minimal (

Chemistry & Properties

Formula	C9H16O4
Molecular weight	188.22 g/mol
IUPAC name	nonanedioic acid
CAS	123-99-9
PubChem CID	2266
InChIKey	`BDJRBEYXGGNYIS-UHFFFAOYSA-N`
logP	1.89 (XLogP 1.6)
Polar surface area	74.6 Å²
H-bond acceptors / donors	2 / 2
Drug-likeness (QED)	0.57
Lipinski violations	0

SMILES

O=C(O)CCCCCCCC(=O)O

Biology & Pharmacokinetics

Pharmacokinetics

BBB penetrant	No

Enzyme interactions

Enzyme	Role	Detail
CYP2B6	Substrate	—
CYP2C8	Inhibitor	—
CYP2C9	Substrate	—

Transporters

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

Registered Products (3)

Brand	Form / strength	Pack	Agent	Citizen (JOD)
Azelderm Cream	Cream 20 %	30 g tube	AL Rahma Drug Store	4.150
Azeclear Cream	Cream 20 %	30 g tube	United Pharmaceutical Manufacturing Co. Ltd.	5.620
Skinoren Cream	Cream 20 %	30 g tube	Khoury Drug Store	6.340