Azelaic Acid

Pharmacologic Category

Topical Skin Product, Acne

Dosing: Adult

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.

* See Dosage and Administration in AHFS Essentials for additional information.

Dosing: Geriatric

Refer to adult dosing.

Dosing: Renal Impairment: Adult

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

Dosing: Hepatic Impairment: Adult

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

Dosing: Pediatric

Acne vulgaris: Children ≥12 years and Adolescents: Cream (Azelex 20%): Topical: Apply a thin film to affected area(s) twice daily, in the morning and evening; may reduce to once daily if persistent skin irritation occurs

Dosing: Renal Impairment: Pediatric

There are no dosage adjustments provided in the manufacturer’s labeling; however, dosage adjustment unlikely needed due to low systemic absorption.

Dosing: Hepatic Impairment: Pediatric

There are no dosage adjustments provided in the manufacturer’s labeling; however, dosage adjustment unlikely needed due to low systemic absorption.

Use: Labeled Indications

Acne vulgaris (cream): Treatment of mild to moderate inflammatory acne vulgaris.

Guideline recommendations: The American Association of Dermatology (AAD) acne guidelines support azelaic acid use as an adjunctive treatment option and, in particular, recommend its use in the treatment of postinflammatory dyspigmentation (AAD [Zaenglein 2016]).

Rosacea (foam, gel): Treatment of inflammatory papules and pustules of mild to moderate rosacea.

Limitations of use: Efficacy for treatment of erythema in rosacea in the absence of papules and pustules has not been evaluated.

* See Uses in AHFS Essentials for additional information.

Clinical Practice Guidelines

American Academy of Dermatology, "Guidelines of Care for the Management of Acne Vulgaris," May 2016

Administration: Topical

Apply a thin film and gently massage into to clean, dry skin; wash hands following application. Avoid the use of occlusive dressings or wrappings. For foam and gel formulations, cosmetics may be applied after the foam or gel has dried. Use only mild soaps or soapless cleansing lotion for facial cleansing. Not intended for intravaginal, ophthalmic, or oral use.

Foam: Shake well before use.

Administration: Pediatric

Topical: Apply a thin film and gently massage into to clean, dry skin; wash hands following application. Avoid the use of occlusive dressings or wrappings. For gel and foam formulation, cosmetics may be applied after the gel has dried. Use only mild soaps or soapless cleansing lotion for facial cleansing. For foam formulation, shake well before use. Not intended for intravaginal, ophthalmic, or oral use.

Dietary Considerations

Gel: Foods and beverages that might provoke erythema, flushing, and blushing, such as spicy food, alcoholic beverages, and thermally hot drinks (including hot coffee and tea), should be avoided.

Storage/Stability

Store at 15°C to 30°C (59°F to 86°F); do not freeze. Store cream on its side. Discard the gel pump 8 weeks after opening.

Foam: Store at 25°C (77°F); excursions are permitted between 15°C and 30°C (59°F and 86°F). Flammable; avoid fire, flame, or smoking during and immediately following application. Contents under pressure. Do not puncture or incinerate. Do not expose to heat or store at temperatures above 49°C (120°F). Discard 8 weeks after opening.

Medication Patient Education with HCAHPS Considerations

What is this drug used for?

• It is used to treat pimples (acne).

• It is used to treat rosacea.

Frequently reported side effects of this drug

• Itching

• Burning

• Stinging

Other side effects of this drug: Talk with your doctor right away if you have any of these signs of:

• Shortness of breath

• Severe skin irritation

• Skin discoloration

• Signs of a significant reaction like wheezing; chest tightness; fever; itching; bad cough; blue skin color; seizures; or swelling of face, lips, tongue, or throat.

Note: This is not a comprehensive list of all side effects. Talk to your doctor if you have questions.

Consumer Information Use and Disclaimer: This information should not be used to decide whether or not to take this medicine or any other medicine. Only the healthcare provider has the knowledge and training to decide which medicines are right for a specific patient. This information does not endorse any medicine as safe, effective, or approved for treating any patient or health condition. This is only a brief summary of general information about this medicine. It does NOT include all information about the possible uses, directions, warnings, precautions, interactions, adverse effects, or risks that may apply to this medicine. This information is not specific medical advice and does not replace information you receive from the healthcare provider. You must talk with the healthcare provider for complete information about the risks and benefits of using this medicine.

Contraindications

Cream: Hypersensitivity to azelaic acid or any component of the formulation.

Foam: There are no contraindications listed in the manufacturer's labeling.

Gel: There are no contraindications listed in the US manufacturer's labeling.

Canadian labeling: Hypersensitivity to azelaic acid or any component of the formulation.

Warnings/Precautions

Concerns related to adverse effects:

• 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.

* See Cautions in AHFS Essentials for additional information.

Warnings: Additional Pediatric Considerations

Some dosage forms may contain propylene glycol; in neonates large amounts of propylene glycol delivered orally, intravenously (eg, >3,000 mg/day), or topically have been associated with potentially fatal toxicities which can include metabolic acidosis, seizures, renal failure, and CNS depression; toxicities have also been reported in children and adults including hyperosmolality, lactic acidosis, seizures and respiratory depression; use caution (AAP 1997; Shehab 2009).

Pregnancy Risk Factor

B

Pregnancy Considerations

Adverse events have been observed in animal reproduction studies following oral administration. The amount of azelaic acid available systemically following topical administration is minimal (<4%).

Breast-Feeding Considerations

It is not known if azelaic acid is excreted in breast milk. The amount of azelaic acid available systemically following topical administration is minimal (<4%); a significant change from baseline azelaic acid levels in the milk is not expected. The manufacturer of the cream recommends that caution be exercised when administering azelaic acid to nursing women. The manufacturers of the gel and foam recommend a decision be made whether to discontinue nursing or to discontinue the drug, taking into account the importance of treatment to the mother.

Adverse Reactions

>10%: Dermatologic: Burning sensation of skin (≤16%), stinging of skin (≤16%), tingling of skin (≤16%)

1% to 10%:

Dermatologic: Pruritus (1% to 6%), erythema (≤2%), skin irritation (≤2%), acne (gel: ≤1%), contact dermatitis (≤1%), desquamation (≤1%), xeroderma (≤1%), xerosis (≤1%)

Local: Application site pain (6%), application site pruritus (3%)

<1%, postmarketing, and/or case reports: Angioedema, application site erythema, dermatitis, dyspnea, edema, exacerbation of asthma, exacerbation of herpes labialis, facial edema, hypersensitivity reaction, hypertrichosis, hypopigmentation, iridocyclitis, local dryness, skin depigmentation (small spots), skin rash, swelling of eye, urticaria, vitiligo, wheezing

* See Cautions in AHFS Essentials for additional information.

Allergy and Idiosyncratic Reactions

• Azelaic Acid Allergy

Metabolism/Transport Effects

None known.

Drug Interactions Open Interactions

There are no known significant interactions.

Advanced Practitioners Physical Assessment/Monitoring

Monitor for sensitivity, severe irritation, and hypopigmentation in dark skinned patients at regular intervals during therapy.

Nursing Physical Assessment/Monitoring

Monitor for sensitivity, severe irritation, or hypopigmentation in dark skinned patients at regular intervals during therapy.

Dosage Forms: US

Excipient information presented when available (limited, particularly for generics); consult specific product labeling. [DSC] = Discontinued product

Cream, External:

Azelex: 20% (30 g, 50 g [DSC])

Azelex: 20% (30 g, 50 g) [contains benzoic acid, cetearyl alcohol, propylene glycol]

Foam, External:

Finacea: 15% (50 g) [contains benzoic acid, cetostearyl alcohol, polysorbate 80, propylene glycol]

Gel, External:

Finacea: 15% (50 g) [contains benzoic acid, disodium edta, polysorbate 80, propylene glycol]

Generic: 15% (50 g)

Dosage Forms: Canada

Excipient information presented when available (limited, particularly for generics); consult specific product labeling.

Gel, External:

Finacea: 15% (5 g, 50 g) [contains benzoic acid, disodium edta, polysorbate 80, propylene glycol]

Anatomic Therapeutic Chemical (ATC) Classification

• D10AX03

Generic Available (US)

May be product dependent

Pricing: US

Cream (Azelex External)

20% (per gram): $18.57

Foam (Finacea External)

15% (per gram): $8.77

Gel (Azelaic Acid External)

15% (per gram): $7.36 - $7.45

Gel (Finacea External)

15% (per gram): $8.69

Disclaimer: A representative AWP (Average Wholesale Price) price or price range is provided as reference price only. A range is provided when more than one manufacturer's AWP price is available and uses the low and high price reported by the manufacturers to determine the range. The pricing data should be used for benchmarking purposes only, and as such should not be used alone to set or adjudicate any prices for reimbursement or purchasing functions or considered to be an exact price for a single product and/or manufacturer. Medi-Span expressly disclaims all warranties of any kind or nature, whether express or implied, and assumes no liability with respect to accuracy of price or price range data published in its solutions. In no event shall Medi-Span be liable for special, indirect, incidental, or consequential damages arising from use of price or price range data. Pricing data is updated monthly.

Mechanism of Action

Azelaic acid is a dietary constituent normally found in whole grain cereals; can be formed endogenously. Exact mechanism is not known. In vitro, azelaic acid possesses antimicrobial activity against Cutibacterium acnes and Staphylococcus epidermidis. May decrease microcomedo formation.

Pharmacodynamics/Kinetics

Onset of action (cream): Within 4 weeks

Absorption: Cream: ~3% to 5% penetrates stratum corneum; up to 10% found in epidermis and dermis; 4% systemic

Metabolism: Negligible after topical application; some beta-oxidation to shorter chain dicarboxylic acids

Half-life elimination: Topical: Healthy subjects: 12 hours

Excretion: Urine (primarily as unchanged drug)

Local Anesthetic/Vasoconstrictor Precautions

No information available to require special precautions

Effects on Dental Treatment

No significant effects or complications reported

Effects on Bleeding

No information available to require special precautions

Index Terms

Anchoic Acid; Lepargylic Acid

FDA Approval Date

September 13, 1995

References

Alade SL, Brown RE, Paquet A. Polysorbate 80 and E-Ferol toxicity. Pediatrics. 1986;77(4):593-597.[PubMed 3960626]

American Academy of Pediatrics Committee on Drugs. "Inactive" ingredients in pharmaceutical products: update (subject review). Pediatrics. 1997;99(2):268-278.[PubMed 9024461]

Azelex (azelaic acid) [prescribing information]. Exton, PA: Almirall, LLC; June 2019.

Centers for Disease Control (CDC). Unusual syndrome with fatalities among premature infants: association with a new intravenous vitamin E product. MMWR Morb Mortal Wkly Rep. 1984;33(14):198-199. http://www.cdc.gov/mmwr/preview/mmwrhtml/00000319.htm[PubMed 6423951]

Finacea (azelaic acid) foam [prescribing information]. Whippany, NJ: Bayer HealthCare Pharmaceuticals Inc; July 2019.

Finacea (azelaic acid) gel [prescribing information]. Whippany, NJ: Bayer HealthCare Pharmaceuticals; August 2018.

Finacea (azelaic acid) gel [product monograph]. Thornhill, Ontario, Canada: LEO Pharma Inc; September 2019.

Isaksson M, Jansson L. Contact allergy to Tween 80 in an inhalation suspension. Contact Dermatitis. 2002;47(5):312-313.[PubMed 12534540]

Lucente P, Iorizzo M, Pazzaglia M. Contact sensitivity to Tween 80 in a child. Contact Dermatitis. 2000;43(3):172.[PubMed 10985636]

Shehab N, Lewis CL, Streetman DD, Donn SM. Exposure to the pharmaceutical excipients benzyl alcohol and propylene glycol among critically ill neonates. Pediatr Crit Care Med. 2009;10(2):256-259.[PubMed 19188870]

Shelley WB, Talanin N, Shelley ED. Polysorbate 80 hypersensitivity. Lancet. 1995;345(8980):1312-1313.[PubMed 7746084]

Zaenglein AL, Pathy AL, Schlosser BJ, et al. Guidelines of care for the management of acne vulgaris. J Am Acad Dermatol. 2016;74(5):945-973.e33. http://www.jaad.org/article/S0190-9622(15)02614-6/pdf. Accessed May 17, 2016.[PubMed 26897386]

Brand Names: International

Acne Foundation (ID); Acnean (TW); Acnederm (AE, SA); Acnederm Medicated Lotion (SG); Acnestop (UA); Acnezac (BD); Ami (TW); Anzela (VN); Av F Aza Acne Foundation (ID); Azaderm (EG); Azalea (KR); Azclear (BH); Azeclear (EG, HK, JO); Azel (TW); Azelan (BR); Azelderm (JO); Azelec (BD); Azelin (VN); Aziderm (IN); Azogel (UA); Cutacelan (AR, CO, EC, PE, VE); Ezalic (EG); Finacea (AU, BG, FR, GB, IE, MX, SE); Scene (VN); Skinoren (AE, AT, BE, BH, CH, CY, CZ, DE, DK, EE, EG, ES, FI, GB, GR, HK, HR, IE, IQ, IR, IS, IT, JO, KW, LB, LT, LU, LV, LY, MT, MY, NO, NZ, OM, PH, PK, PL, PT, QA, RO, RU, SA, SE, SI, SK, SY, TH, TR, TW, UA, YE, ZA); ZA (TW); Zelface (ID); Zeliris (ID)

Last Updated 4/18/20