- Azelex (azelaic Acid Cream) 20%
- Description
- Clinical Pharmacology
- Indications And Usage
- Contraindications
- Warnings
- Precautions
- Adverse Reactions
- Dosage And Administration
- How Supplied
- Principal Display Panel - Ndc: 16110-869-50 - 50 Gram Tube Label
- Azelex (azelaic Acid Cream) 20%
- Description
- Clinical Pharmacology
- Indications And Usage
- Contraindications
- Warnings
- Precautions
- Adverse Reactions
- Dosage And Administration
- How Supplied
- Azelex (azelaic Acid Cream) 20%
Azelex (azelaic Acid Cream) 20% ⮝
For Dermatologic Use Only
Not for Ophthalmic Use
Description ⮝
AZELEX (azelaic acid cream) 20% contains azelaic acid, a naturally occurring saturated dicarboxylic acid.
Structural Formula: HOOC-(CH2)7-COOH
Chemical Name: 1,7-heptanedicarboxylic acid
Empirical Formula: C9H16O4
Molecular Weight: 188.22
Active Ingredient: Each gram of AZELEX contains azelaic acid......... 0.2 g (20% w/w).
Inactive Ingredients: cetearyl octanoate and isopropyl myristate; glycerin; glyceryl monostearate and PEG-30 stearate; glyceryl stearate and cetearyl alcohol and cetyl palmitate and cocoglycerides; propylene glycol; and purified water. Benzoic acid is present as a preservative.
Clinical Pharmacology ⮝
The exact mechanism of action of azelaic acid is not known. The following in vitro data are available, but their clinical significance is unknown. Azelaic acid has been shown to possess antimicrobial activity against Propionibacterium acnes and Staphylococcus epidermidis. The antimicrobial action may be attributable to inhibition of microbial cellular protein synthesis.
A normalization of keratinization leading to an anticomedonal effect of azelaic acid may also contribute to its clinical activity. Electron microscopic and immunohistochemical evaluation of skin biopsies from human subjects treated with AZELEX cream demonstrated a reduction in the thickness of the stratum corneum, a reduction in number and size of keratohyalin granules, and a reduction in the amount and distribution of filaggrin (a protein component of keratohyalin) in epidermal layers. This is suggestive of the ability to decrease microcomedo formation.
Pharmacokinetics
Following a single application of AZELEX cream to human skin in vitro, azelaic acid penetrates into the stratum corneum (approximately 3 to 5% of the applied dose) and other viable skin layers (up to 10% of the dose is found in the epidermis and dermis). Negligible cutaneous metabolism occurs after topical application. Approximately 4% of the topically applied azelaic acid is systemically absorbed. Azelaic acid is mainly excreted unchanged in the urine but undergoes some -oxidation to shorter chain dicarboxylic acids. The observed half-lives in healthy subjects are approximately 45 minutes after oral dosing and 12 hours after topical dosing, indicating percutaneous absorption rate-limited kinetics.
Azelaic acid is a dietary constituent (whole grain cereals and animal products), and can be formed endogenously from longer-chain dicarboxylic acids, metabolism of oleic acid, and -oxidation of monocarboxylic acids. Endogenous plasma concentration (20 to 80 ng/mL) and daily urinary excretion (4 to 28 mg) of azelaic acid are highly dependent on dietary intake. After topical treatment with AZELEX cream in humans, plasma concentration and urinary excretion of azelaic acid are not significantly different from baseline levels.
Indications And Usage ⮝
AZELEX cream is indicated for the topical treatment of mild-to-moderate inflammatory acne vulgaris.
Contraindications ⮝
AZELEX cream is contraindicated in individuals who have shown hypersensitivity to any of its components.
Warnings ⮝
AZELEX cream is for dermatologic use only and not for ophthalmic use.
There have been isolated reports of hypopigmentation after use of azelaic acid. Since azelaic acid has not been well studied in patients with dark complexions, these patients should be monitored for early signs of hypopigmentation.
Precautions ⮝
General
If sensitivity or severe irritation develop with the use of AZELEX cream, treatment should be discontinued and appropriate therapy instituted.
Information for Patients
Patients should be told:
- To use AZELEX cream for the full prescribed treatment period.
- To avoid the use of occlusive dressings or wrappings.
- To keep AZELEX cream away from the mouth, eyes and other mucous membranes. If it does come in contact with the eyes, they should wash their eyes with large amounts of water and consult a physician if eye irritation persists.
- If they have dark complexions, to report abnormal changes in skin color to their physician.
- Due in part to the low pH of azelaic acid, temporary skin irritation (pruritus, burning, or stinging) may occur when AZELEX cream is applied to broken or inflamed skin, usually at the start of treatment. However, this irritation commonly subsides if treatment is continued. If it continues, AZELEX
Carcinogenesis, Mutagenesis, Impairment of Fertility
Azelaic acid is a human dietary component of a simple molecular structure that does not suggest carcinogenic potential, and it does not belong to a class of drugs for which there is a concern about carcinogenicity. Therefore, animal studies to evaluate carcinogenic potential with AZELEX cream were not deemed necessary. In a battery of tests (Ames assay, HGPRT test in Chinese hamster ovary cells, human lymphocyte test, dominant lethal assay in mice), azelaic acid was found to be nonmutagenic. Animal studies have shown no adverse effects on fertility.
Pregnancy
Teratogenic Effects
Embryotoxic effects were observed in Segment I and Segment II oral studies with rats receiving 2500 mg/kg/day of azelaic acid. Similar effects were observed in Segment II studies in rabbits given 150 to 500 mg/kg/day and in monkeys given 500 mg/kg/day. The doses at which these effects were noted were all within toxic dose ranges for the dams. No teratogenic effects were observed. There are, however, no adequate and well-controlled studies in pregnant women. Because animal reproduction studies are not always predictive of human response, this drug should be used during pregnancy only if clearly needed.
Nursing Mothers
Equilibrium dialysis was used to assess human milk partitioning in vitro. At an azelaic acid concentration of 25 mcg/mL, the milk/plasma distribution coefficient was 0.7 and the milk/buffer distribution was 1.0, indicating that passage of drug into maternal milk may occur. Since less than 4% of a topically applied dose is systemically absorbed, the uptake of azelaic acid into maternal milk is not expected to cause a significant change from baseline azelaic acid levels in the milk. However, caution should be exercised when AZELEX cream is administered to a nursing mother.
Pediatric Use
Safety and effectiveness in pediatric patients under 12 years of age have not been established.
Geriatric Use
Clinical studies of AZELEX cream did not include sufficient numbers of subjects aged 65 and over to determine whether they respond differently from younger subjects.
Adverse Reactions ⮝
During U.S. clinical trials with AZELEX cream, adverse reactions were generally mild and transient in nature. The most common adverse reactions occurring in approximately 1-5% of patients were pruritus, burning, stinging and tingling. Other adverse reactions such as erythema, dryness, rash, peeling, irritation, dermatitis, and contact dermatitis were reported in less than 1% of subjects. There is the potential for experiencing allergic reactions with use of AZELEX cream.
In patients using azelaic acid formulations, the following additional adverse experiences have been reported rarely: worsening of asthma, vitiligo depigmentation, small depigmented spots, hypertrichosis, reddening (signs of keratosis pilaris), and exacerbation of recurrent herpes labialis.
Dosage And Administration ⮝
After the skin is thoroughly washed and patted dry, a thin film of AZELEX cream should be gently but thoroughly massaged into the affected areas twice daily, in the morning and evening. The hands should be washed following application. The duration of use of AZELEX cream can vary from person to person and depends on the severity of the acne. Improvement of the condition occurs in the majority of patients with inflammatory lesions within four weeks.
How Supplied ⮝
AZELEX cream is supplied in a closed orifice tube with a white, spiked screwcap in the following sizes:
30 g - NDC 16110-869-30
50 g - NDC 16110-869-50Storage: Protect from freezing. Store product on its side. Store at 15 -30 C (59 -86 F).
Revised: 06/2019
Distributed under license by Almirall, LLC, Exton, PA 19341, U.S.A.
2019 Almirall. All right reserved.
marks owned by Almirall, LLC.Made in Italy by LEO Pharma Manufacturing Italy S.r.l., Segrate (Milan), Italy
Principal Display Panel - Ndc: 16110-869-50 - 50 Gram Tube Label ⮝
AZELEX
azelaic acid cream
Product Information Product Type HUMAN PRESCRIPTION DRUG Item Code (Source) NDC:16110-869 Route of Administration CUTANEOUS
Active Ingredient/Active Moiety Ingredient Name Basis of Strength Strength AZELAIC ACID (UNII: F2VW3D43YT) (AZELAIC ACID - UNII:F2VW3D43YT) AZELAIC ACID 0.2 g in 1 g
Inactive Ingredients Ingredient Name Strength CETEARYL ETHYLHEXANOATE (UNII: 9M64UO4C25) ISOPROPYL MYRISTATE (UNII: 0RE8K4LNJS) GLYCERYL MONOSTEARATE (UNII: 230OU9XXE4) PEG-30 STEARATE (UNII: 1U8KB35S20) CETOSTEARYL ALCOHOL (UNII: 2DMT128M1S) CETYL PALMITATE (UNII: 5ZA2S6B08X) COCO-GLYCERIDES (UNII: ISE9I7DNUG) GLYCERIN (UNII: PDC6A3C0OX) PROPYLENE GLYCOL (UNII: 6DC9Q167V3) WATER (UNII: 059QF0KO0R) BENZOIC ACID (UNII: 8SKN0B0MIM)
Packaging # Item Code Package Description Marketing Start Date Marketing End Date 1 NDC:16110-869-30 1 in 1 CARTON 07/12/2019 1 30 g in 1 TUBE; Type 0: Not a Combination Product 2 NDC:16110-869-50 1 in 1 CARTON 07/12/2019 2 50 g in 1 TUBE; Type 0: Not a Combination Product
Marketing Information Marketing Category Application Number or Monograph Citation Marketing Start Date Marketing End Date NDA NDA020428 09/24/2018
Labeler - Almirall, LLC (605425912) Revised: 10/2019 Document Id: 4e21d6b6-e1de-4601-b80e-0e8bd1c859dd Set id: ebdfcaf7-b5d6-47e1-be87-ccaba4b97e75 Version: 2 Effective Time: 20191002 Almirall, LLC
Azelex (azelaic Acid Cream) 20% ⮝
For Dermatologic Use Only
Not for Ophthalmic Use
Description ⮝
AZELEX (azelaic acid cream) 20% contains azelaic acid, a naturally occurring saturated dicarboxylic acid.
Structural Formula: HOOC-(CH2)7-COOH
Chemical Name: 1,7-heptanedicarboxylic acid
Empirical Formula: C9H16O4
Molecular Weight: 188.22
Active Ingredient: Each gram of AZELEX contains azelaic acid......... 0.2 g (20% w/w).
Inactive Ingredients: cetearyl octanoate; glycerin; glyceryl stearate and cetearyl alcohol and cetyl palmitate and cocoglycerides; PEG-5 glyceryl stearate; propylene glycol; and purified water. Benzoic acid is present as a preservative.
Clinical Pharmacology ⮝
The exact mechanism of action of azelaic acid is not known. The following in vitro data are available, but their clinical significance is unknown. Azelaic acid has been shown to possess antimicrobial activity against Propionibacterium acnes and Staphylococcus epidermidis. The antimicrobial action may be attributable to inhibition of microbial cellular protein synthesis.
A normalization of keratinization leading to an anticomedonal effect of azelaic acid may also contribute to its clinical activity. Electron microscopic and immunohistochemical evaluation of skin biopsies from human subjects treated with AZELEX cream demonstrated a reduction in the thickness of the stratum corneum, a reduction in number and size of keratohyalin granules, and a reduction in the amount and distribution of filaggrin (a protein component of keratohyalin) in epidermal layers. This is suggestive of the ability to decrease microcomedo formation.
Pharmacokinetics
Following a single application of AZELEX cream to human skin in vitro, azelaic acid penetrates into the stratum corneum (approximately 3 to 5% of the applied dose) and other viable skin layers (up to 10% of the dose is found in the epidermis and dermis). Negligible cutaneous metabolism occurs after topical application. Approximately 4% of the topically applied azelaic acid is systemically absorbed. Azelaic acid is mainly excreted unchanged in the urine but undergoes some -oxidation to shorter chain dicarboxylic acids. The observed half-lives in healthy subjects are approximately 45 minutes after oral dosing and 12 hours after topical dosing, indicating percutaneous absorption rate-limited kinetics.
Azelaic acid is a dietary constituent (whole grain cereals and animal products), and can be formed endogenously from longer-chain dicarboxylic acids, metabolism of oleic acid, and -oxidation of monocarboxylic acids. Endogenous plasma concentration (20 to 80 ng/mL) and daily urinary excretion (4 to 28 mg) of azelaic acid are highly dependent on dietary intake. After topical treatment with AZELEX cream in humans, plasma concentration and urinary excretion of azelaic acid are not significantly different from baseline levels.
Indications And Usage ⮝
AZELEX cream is indicated for the topical treatment of mild-to-moderate inflammatory acne vulgaris.
Contraindications ⮝
AZELEX cream is contraindicated in individuals who have shown hypersensitivity to any of its components.
Warnings ⮝
AZELEX cream is for dermatologic use only and not for ophthalmic use.
There have been isolated reports of hypopigmentation after use of azelaic acid. Since azelaic acid has not been well studied in patients with dark complexions, these patients should be monitored for early signs of hypopigmentation.
Precautions ⮝
General
If sensitivity or severe irritation develop with the use of AZELEX cream, treatment should be discontinued and appropriate therapy instituted.
Information for Patients
Patients should be told:
- To use AZELEX cream for the full prescribed treatment period.
- To avoid the use of occlusive dressings or wrappings.
- To keep AZELEX cream away from the mouth, eyes and other mucous membranes. If it does come in contact with the eyes, they should wash their eyes with large amounts of water and consult a physician if eye irritation persists.
- If they have dark complexions, to report abnormal changes in skin color to their physician.
- Due in part to the low pH of azelaic acid, temporary skin irritation (pruritus, burning, or stinging) may occur when AZELEX cream is applied to broken or inflamed skin, usually at the start of treatment. However, this irritation commonly subsides if treatment is continued. If it continues, AZELEX cream should be applied only once-a-day, or the treatment should be stopped until these effects have subsided. If troublesome irritation persists, use should be discontinued, and patients should consult their physician (see ADVERSE REACTIONS).
Carcinogenesis, Mutagenesis, Impairment of Fertility
Azelaic acid is a human dietary component of a simple molecular structure that does not suggest carcinogenic potential, and it does not belong to a class of drugs for which there is a concern about carcinogenicity. Therefore, animal studies to evaluate carcinogenic potential with AZELEX cream were not deemed necessary. In a battery of tests (Ames assay, HGPRT test in Chinese hamster ovary cells, human lymphocyte test, dominant lethal assay in mice), azelaic acid was found to be nonmutagenic. Animal studies have shown no adverse effects on fertility.
Pregnancy
Teratogenic Effects
Embryotoxic effects were observed in Segment I and Segment II oral studies with rats receiving 2500 mg/kg/day of azelaic acid. Similar effects were observed in Segment II studies in rabbits given 150 to 500 mg/kg/day and in monkeys given 500 mg/kg/day. The doses at which these effects were noted were all within toxic dose ranges for the dams. No teratogenic effects were observed. There are, however, no adequate and well-controlled studies in pregnant women. Because animal reproduction studies are not always predictive of human response, this drug should be used during pregnancy only if clearly needed.
Nursing Mothers
Equilibrium dialysis was used to assess human milk partitioning in vitro. At an azelaic acid concentration of 25 mcg/mL, the milk/plasma distribution coefficient was 0.7 and the milk/buffer distribution was 1.0, indicating that passage of drug into maternal milk may occur. Since less than 4% of a topically applied dose is systemically absorbed, the uptake of azelaic acid into maternal milk is not expected to cause a significant change from baseline azelaic acid levels in the milk. However, caution should be exercised when AZELEX cream is administered to a nursing mother.
Pediatric Use
Safety and effectiveness in pediatric patients under 12 years of age have not been established.
Geriatric Use
Clinical studies of AZELEX cream did not include sufficient numbers of subjects aged 65 and over to determine whether they respond differently from younger subjects.
Adverse Reactions ⮝
During U.S. clinical trials with AZELEX cream, adverse reactions were generally mild and transient in nature. The most common adverse reactions occurring in approximately 1-5% of patients were pruritus, burning, stinging and tingling. Other adverse reactions such as erythema, dryness, rash, peeling, irritation, dermatitis, and contact dermatitis were reported in less than 1% of subjects. There is the potential for experiencing allergic reactions with use of AZELEX cream.
In patients using azelaic acid formulations, the following additional adverse experiences have been reported rarely: worsening of asthma, vitiligo depigmentation, small depigmented spots, hypertrichosis, reddening (signs of keratosis pilaris), and exacerbation of recurrent herpes labialis.
Dosage And Administration ⮝
After the skin is thoroughly washed and patted dry, a thin film of AZELEX cream should be gently but thoroughly massaged into the affected areas twice daily, in the morning and evening. The hands should be washed following application. The duration of use of AZELEX cream can vary from person to person and depends on the severity of the acne. Improvement of the condition occurs in the majority of patients with inflammatory lesions within four weeks.
How Supplied ⮝
AZELEX cream is supplied in a closed orifice tube with a white, spiked screwcap in the following sizes:
30 g - NDC 0023-8694-30
50 g - NDC 0023-8694-50Storage: Protect from freezing. Store product on its side. Store at 15 -30 C (59 -86 F).
Revised: 09/2015
Distributed under license by Allergan, Inc., Irvine, CA 92612, U.S.A.
2015 Allergan. All right reserved.
marks owned by Allergan, Inc.Made in Italy by Bayer HealthCare Manufacturing S.r.l., Segrate (Milan), Italy
70896US17
NDC 0023-8694-50
ALLERGAN
AZELEX
(azelaic acid cream) 20%
For Dermatologic Use Only
Not for Ophthalmic Use
Rx only 50 grams
AZELEX
azelaic acid cream
Product Information Product Type HUMAN PRESCRIPTION DRUG Item Code (Source) NDC:0023-8694 Route of Administration CUTANEOUS
Active Ingredient/Active Moiety Ingredient Name Basis of Strength Strength azelaic acid (UNII: F2VW3D43YT) (azelaic acid - UNII:F2VW3D43YT) azelaic acid 0.2 g in 1 g
Inactive Ingredients Ingredient Name Strength cetearyl ethylhexanoate (UNII: 9M64UO4C25) glycerin (UNII: PDC6A3C0OX) cetostearyl alcohol (UNII: 2DMT128M1S) cetyl palmitate (UNII: 5ZA2S6B08X) propylene glycol (UNII: 6DC9Q167V3) water (UNII: 059QF0KO0R) glyceryl monostearate (UNII: 230OU9XXE4) coco-glycerides (UNII: ISE9I7DNUG) benzoic acid (UNII: 8SKN0B0MIM)
Packaging # Item Code Package Description Marketing Start Date Marketing End Date 1 NDC:0023-8694-30 1 in 1 CARTON 03/21/1996 1 30 g in 1 TUBE; Type 0: Not a Combination Product 2 NDC:0023-8694-50 1 in 1 CARTON 03/21/1996 2 50 g in 1 TUBE; Type 0: Not a Combination Product
Marketing Information Marketing Category Application Number or Monograph Citation Marketing Start Date Marketing End Date NDA NDA020428 03/21/1996
Labeler - Allergan, Inc. (144796497)
Establishment Name Address ID/FEI Business Operations Bayer Healthcare Manufacturing Srl 434765750 MANUFACTURE(0023-8694) Revised: 3/2017 Document Id: d7a96fba-04c1-4af1-9e4b-6e22d4e1fdd0 Set id: b086c825-401e-48e7-a6dd-2ad7423e86a0 Version: 6 Effective Time: 20170306 Allergan, Inc.
Azelex (azelaic Acid Cream) 20% ⮝
For Dermatologic Use Only
Not for Ophthalmic Use
