Azelaic Acid

Azelaic Acid, officially nonanedioic acid, is a white crystalline strong with a melting point of 106.5 ° C. It happens naturally in grains such as wheat, rye, and barley and is produced industrially by ozonolyzing oleic acid. Some plants release azelaic acid as a “distress flare” to signal cells to activate their defenses against assaulting pathogens. [2]

Background

Azelaic acid is a saturated dicarboxylic acid found naturally in wheat, rye, and barley. It is also produced by Malassezia furfur, likewise known as Pityrosporum ovale, which is a types of fungi that is normally discovered on human skin. Azelaic acid is effective versus a number of skin conditions, such as moderate to moderate acne, when used topically in a cream solution of 20%. It operates in part by stopping the development of skin bacteria that cause acne, and by keeping skin pores clear. Azelaic acid’s antimicrobial action may be attributable to inhibition of microbial cellular protein synthesis.

Mechanism of action

The specific mechanism of action of azelaic acid is not known. It is thought that azelaic acid manifests its antibacterial results by preventing the synthesis of cellular protein in anaerobic and aerobic germs, especially Staphylococcus epidermidis and Propionibacterium acnes. In aerobic bacteria, azelaic acid reversibly inhibits a number of oxidoreductive enzymes consisting of tyrosinase, mitochondrial enzymes of the respiratory chain, thioredoxin reductase, 5-alpha-reductase, and DNA polymerases. In anaerobic germs, azelaic acid impedes glycolysis. Along with these actions, azelaic acid also improves acne vulgaris by stabilizing the keratin procedure and decreasing microcomedo development. Azelaic acid might be effective versus both inflamed and noninflamed lesions. Specifically, azelaic acid reduces the density of the stratum corneum, shrinks keratohyalin granules by reducing the quantity and distribution of filaggrin (a component of keratohyalin) in skin layers, and lowers the number of keratohyalin granules. [3]

Metabolism

Primarily excreted unchanged in the urine however undergoes some b-oxidation to much shorter chain dicarboxylic acids.

Path of elimination

Azelaic acid is mainly excreted the same in the urine, however goes through some ß-oxidation to shorter chain dicarboxylic acids.

Half-life

The observed half-lives in healthy topics are around 45 minutes after oral dosing and 12 hours after topical dosing, indicating percutaneous absorption rate-limited kinetics. [3]

Residence

Azelaic acid is soluble in hot water, alcohol and organic solvents.

Azelaic acid is utilized in the manufacture of adhesives and sealant chemicals; lubes and lubricant ingredients; paint and covering ingredients, and plasticizers. [4]

Benefits

A single mechanism of action has not been identified to describe the effects of azelaic acid on the skin. It helps scavenge reactive oxygen types, reduces expression of kallikrein-5 (KLK-5) and pro-inflammatory cathelicidins such as LL-37, as well as hinders toll-like receptor 2 (TLR-2). In addition, it prevents the pigment producing enzyme tyrosinase, has comedolytic residential or commercial properties, and might minimize skin hyperkeratinization. While the 15% gel formula is FDA authorized for the treatment of rosacea, a different 20% cream solution (Azelex, Allergan) is shown for the treatment of acne. Both formulations bring a pregnancy category B score.

Azelaic Acid for Rosacea

The 15% gel solution of azelaic acid is FDA approved to deal with the papules and pustules of moderate to moderate rosacea. While the 15% gel has a lower concentration of azelaic acid compared to the 20% cream, advances in formulation technology give the gel greater cutaneous biovailability. While the sign is for use of azelaic acid 15% gel two times daily, a research study subsequent to its approval demonstrated equivalent effectiveness of when compared to two times daily application.

Current data recommend irregular over-activity of the innate body immune system as a significant factor to the pathophysiology of rosacea. Excess skin antimicrobial peptides (e.g., cathelicidins) and stimulation of TLR-2 both play considerable functions. Cathelicidins are processed by serine proteases (e.g., KLK-5) into pro-inflammatory peptides, such as LL-37. Overactivity of KLK-5 results in a high level of cathelicidin processing into peptides with higher pro-inflammatory residential or commercial properties than antibacterial residential or commercial properties. This imbalance promotes angiogenesis and chronic skin inflammation. Topical application of azelaic acid 15% gel has been shown to minimize skin serine protease activity and aid reverse these modifications.

Azelaic Acid for Acne

TLR-2 over-activity contributes in the pathogenesis of acne. Propionibacterium acnes itself has actually been revealed to stimulate TLR-2 activity, leading to skin inflammation and comedogenesis. Topical retinoids are a staple in dealing with acne not only because of their ability to stabilize follicular hyperkeratinization but likewise due to their anti-inflammatory residential or commercial properties. Similar to its mechanism of action in dealing with rosacea, azelaic acid’s capability to prevent TLR-2 activity assists describe its effectiveness in treating acne vulgaris. Using azelaic acid 15% gel is thought about off label for the treatment of acne vulgaris. Lots of specialists may use it off-label for acne as part of a mix therapy for clients who can not tolerate topical retinoids, those who also struggle with hyperpigmentation, and for ladies who are pregnant or breastfeeding (as it is pregnancy classification B).

Azelaic Acid for Hyperpigmentation

Post-inflammatory coloring medically manifests as dark areas in locations of skin that formerly were inflamed, be it from acne or another inflammatory dermatosis. While not improved for this indicator, azelaic acid is frequently used off-label to treat coloring. One scientific trial demonstrated 15% azelaic acid gel to be both efficacious and safe in dealing with hyperpigmentation connected with acne for 16 weeks. This result might be explained by 2 residential or commercial properties of the drug. Initially, azelaic acid is understood to inhibit the enzyme tyrosinase, which is needed for the production of melanin.3 Second, its role as an anti-inflammatory may be helpful as well. When active acne sores (e.g., papules and pustules) willpower, evidence shows that the skin in these areas still possess subclinical swelling.14 While this has been shown in acne scars, the very same may also be true in cases of relentless erythema and pigmentation. More research is required to validate this theory, however.

Having a drug that effectively deals with a condition helps us much better understand that condition, as we find the mechanism by which the drug works. Just as biologics have clarified the pathogenesis of psoriasis, research study into the system of action of azelaic acid has considerably improved our understanding about the pathogenesis of rosacea, specifically the function of an over-active inherent body immune system. A higher understanding of the disease translates to improved treatment algorithms and patient results, and eventually this helps affect the future of drug development. [5]

Blackheads

The antibacterial qualities of azelaic acid help to prevent the formation of both white and blackheads, by eliminating the skin germs that can cause areas. It likewise prevents the production of keratin skin cells, which can block pores and sebaceous glands and develop oily accumulations (resulting in blackheads).

Finacea Gel vs. Skinoren Cream: What’s the primary difference?

Finacea Gel and Skinoren Cream are both skin medications. Each works at dealing with acne, however there are some differences between the two, with the key one being that Skinoren Cream consists of more azelaic acid than Finacea Gel.

Below, we have actually highlighted the key differences between Finacea Gel and Skinoren cream:.

Skinoren Cream is more powerful: it’s 20% azelaic acid, while Finacea Gel is 15%.

Skinoren Cream treats all acne: Finacea Gel is just for moderate to moderate acne.

Finacea Gel treats rosacea: it’s a milder treatment, which makes it OK for rosacea.

As both include similar ingredients, they can cause similar negative effects.

More about Finacea Gel

Finacea Gel is a prescription-only gel utilized to deal with rosacea. It’s 15% azelaic acid, which gives it anti-inflammatory impacts and allows it to lower the redness and swelling of rosacea.

Finacea likewise lowers the body’s natural production of keratin cells. This prevents keratin cells from blocking pores and sebaceous glands (the small glands in your skin which release sebum), reducing rosacea symptoms such as bumps, spots, papules, and pustules.

More about Skinoren Cream

Skinoren cream also includes the active ingredient of azelaic acid, but in a higher concentration. It’s 20% azelaic acid where Finacea Gel is a weaker 15%.

The powerful azelaic acid in Skinoren operates in two methods to fight acne: by decreasing the growth of pore-blocking keratin cells, and by eliminating the bacteria connected with acne. A common skin bacteria called propionibacterium feeds upon the sebum produced by the skin, developing waste items and fatty acids that get worse acne signs and inflame the skin.

By unblocking pores and glands and killing propionibacterium, Skinoren lowers acne and enables your skin to heal naturally.

Although Finacea Gel is usually utilized for rosacea, and Skinoren cream is mostly utilized for acne, the two treatments can in some cases be prescribed for the other skin conditions. Everything depends on the situation, however given that each item is prescription-only, there shouldn’t be any confusion about what to use. [6]

How Do You Use Azelaic Acid?

Azelaic acid is applied topically and it’s available in creams, foams and gels.

Many skin specialists suggest that whichever form you choose, the strength needs to sit someplace in the 15% to 20% range.

Non-prescription items including a smaller sized dose of azelaic acid are readily available as well, although for finest results a prescription is usually needed.

Most topical representatives need you to apply them two times a day to clean, dry skin (masks consisting of azelaic acid needs to be used less often).

Listed below we have actually put together a step-by-step skin care regimen to show you how to integrate azelaic acid into your regimen.

Step One

Wash your face with your everyday cleanser and pat the skin dry. If you use a toner, use it after this primary step.

It’s important not to skip this step since the cleaner your skin is, the more likely it is to soak up other treatments.

Step Two

Next use your azelaic acid cream, gel or lotion.

If you have sensitive skin, we advise starting with a single application every other day. As your skin adjusts, you can use the item more frequently.

Alternatively, perform a patch test on the back of your arm before using your foam, cream, or gel to more delicate areas such as your face or neck, where the skin is thinner.

You must also wait about 15 minutes for the item to absorb to avoid smearing. This is specifically important if you’re using it as an area treatment to fade darker locations.

If you’re utilizing azelaic acid as an area treatment, do not use everything over the face. This is since you’ll run the risk of fading the skin in unneeded locations.

Step Three

After letting the azelaic acid absorb, apply your moisturizer as usual. It’s also essential not to skimp on sunscreen.

When utilizing azelaic acid, the skin tends to end up being more vulnerable to ecological damage.

This indicates that not utilizing sun protection can reverse all of the advantages of azelaic acid, since sun damage can cause hyperpigmentation and melasma.

Step Four

It’s safe to apply makeup after the azelaic acid cream, foam or gel has dried entirely.

Do not bandage or cover the location unless your skin doctor has actually advised you to do so.

When not in use, shop your azelaic acid at space temperature level and away from direct light.

This is due to the fact that excessive direct exposure to light can trigger azelaic acid to destabilize and break down.

A Note about AHA and BHAs

Alpha-hydroxy acids (AHAs) and beta-hydroxy acids (BHAs) are utilized to treat skin problem like acne.

The most typical kinds of these acids consist of salicylic acid, glycolic acid, and lactic acid.

AHAs are more aggressive exfoliants than azelaic acid, that makes them more efficient in treating sun damage and combating signs of aging. They are also a popular choice for people seeking to improve their skin’s texture.

BHAs are similar to AHAs, except they have antibacterial homes. This is terrific for treating acne since it eliminates harmful germs that can possibly contaminate imperfections.

Although you’ll see faster outcomes by using BHAs, they are more likely to trigger extreme side effects like rashes or blistering.

In comparison to AHAs and BHAs, azelaic acid is a gentler treatment with less negative effects.

However, some dermatologists caution against integrating azelaic acid with salicylic acid or other beta-hydroxy acids due to the fact that it might trigger extreme dryness and irritation.

For those who have oily or combination skin, treating your acne with azelaic and salicylic acid can be especially reliable. [7]

Kinds of Azelaic Acid

You can get azelaic acid as a:.

• Gel
• Foam
• Cream
• Pill

Prescription types have 15% to 20% azelaic acid, but over-the-counter versions have much less. [8]

Azelaic Acid’s Role as an Inhibitor of 5α-Reductase Activity

5α-reductase is an enzyme that transforms testosterone into another androgen, dihydrotestosterone (DHT) (5 ). DHT is five times as powerful as testosterone. It plays an essential function in the advancement of men’s sexual characteristics, consisting of the advancement of hair on the chin, back, and chest.

Curiously, DHT is likewise detrimental to the development of hair on the scalp. Simply put, it has the specific opposite impact on the scalp compared to the rest of the body. This makes it an essential particle in male pattern baldness.

DHT is involved in male pattern baldness.

Hence, discovering molecules that inhibit the action of 5α-reductase is of fantastic interest to pharmaceutical companies and skin doctors focusing on hair regrowth.

A 1988 study published in the British Journal of Dermatology used an in vitro assay to evaluate the impacts of zinc and azelaic acid on 5α-reductase activity in human skin.

In the experiment, Dr. Stamatiadis and his research group determined that azelaic acid might completely hinder 5α-reductase activity in vitro (in a petri dish). A lot more fascinating, when azelaic was integrated with zinc sulfate, the inhibition was much more powerful.

Dr. Stamatiadis concluded that the combination of these two compounds might potentially treat androgen-related disorders.

Azelaic Acid and Alopecia Areata

Alopecia Areata (AA) is a type of loss of hair that is autoimmune in nature. For factors that are unclear, the body’s immune cells assault the hair follicles. The outcome is well-defined, completely bald patches. These can appear anywhere on the scalp, and often on other parts of the body.

The FDA has actually not presently approved any medications for AA. As a result, medical professionals recommend numerous medications off-label.

Can Azelaic Acid Treat AA?

Alopecia areata is the scientific term for patchy baldness.

In a pilot research study worrying azelaic acid’s possible use in managing spot baldness, Dr. Sasmaz and Dr. Arican carried out an experiment comparing azelaic acid to anthralin.

Azelaic acid has been used to treat this condition in the past. Till this research came out, however, there were no regulated studies to evaluate its efficiency.

Anthralin is a tested topical treatment for the management of alopecia location. This makes it a good standard to compare the effectiveness of unique treatments.

The Study Procedure

In the experiment, Dr. Sasmaz and Dr. Arican recruited 31 topics with irregular alopecia areata. None of these topics had utilized any alopecia treatments within a minimum of the past month. The researchers then arbitrarily assigned the clients into one of two groups.

The very first group used 20% azelaic acid cream to the affected portion of the scalp daily for 12 successive weeks.

The 2nd group applied 0.5% anthralin cream to the affected part of the scalp daily for 12 successive weeks. Later, there was an 8-week follow-up throughout which patients applied no cream. The goal of this follow-up was to see whether the patients could maintain their treatment results.

All research study participants finished the experiment as advised. There were no serious negative effects.

Outcomes

At the end of this 20 week period, Dr. Sasmaz and Dr. Arican performed a clinical evaluation on each participant.

Throughout this assessment, each of the subject’s scalps was awarded a Terminal Hair Regrowth Rating on a scale from 0 to 2. On this scale, a 0 suggested an insufficient response, a 1 a partial action, and a 2 a complete reaction. At week 20, the Average Terminal Hair Re-growth Ratings were as follows:.

Azelaic acid group

1.27 (Margin of Mistake: +/- 0.9).

Anthralin group

1.37 (Margin of Error: +/- 0.8).

Hence, topics in either treatment arm had broadly comparable results. The Typical Terminal Regrowth Scores were both over 1, revealing overall sufficient action to treatment.

In fact, 53.3% of cases in the azelaic acid cream group and 56.2% of cases in the anthralin group had a complete action. In addition, subjects with a total action had no new bald spots develop during the research study period. This suggests the azelaic acid treatment might help manage the condition outside of the cured area.

Dr. Sasmaz and Dr. Arican concluded that azelaic acid could be a reliable topical treatment for patchy alopecia areata.

This research study is not without its faults, nevertheless. Dr. Sasmaz and Dr. Arican used a fairly little sample size in their experiment. In addition, there was no reported follow-up for the study to evaluate the long-lasting results of treatment. Some scientists have actually even questioned making use of anthralin as a comparison tool, due to an absence of certainty in its usefulness.

Azelaic Acid and Androgenetic Alopecia?

To date, there is no published research study on the efficiency of azelaic acid against male androgenetic alopecia (AGA). Having stated that, the compound prevents DHT, at least in vitro. This makes it an in theory useful treatment alternative.

This has actually not stopped numerous males with loss of hair from incorporating it into their baldness treatment program. Many report favorable outcomes, while others say it made no difference in their hair loss.

The lack of standardized treatment regimens is a problem. There are no standards on what strength to utilize, how frequently, or in mix with what other active components.

Usually, users attempt formulas containing between 10-15% azelaic acid.

How to Experiment With Azelaic Acid Yourself

Given that there are promising outcomes connecting azelaic acid to a drop in DHT levels and a decrease of alopecia areata symptoms, it may deserve your while to try this product out for yourself.

It is advised that you add azelaic acid to your normal program rather than replacing it as a treatment. This is the case particularly if you are utilizing an FDA-approved hair product such as Minoxidil or Propecia. There are a variety of topical items you can buy which contain azelaic acid:.

Scalp creams and conditioner for alopecia including azelaic acid.

• The FDA-approved acne creams pointed out earlier
• Shops selling natural supplements typically have vials containing azelaic acid
• Apply the cream or other topical solution daily for the best results. [9]

Azelaic acid negative effects

Azelaic acid can cause adverse effects, including:.

• burning or tingling on your skin
• peeling skin at the website of application
• skin dryness or soreness

Less-common adverse effects consist of:.

• blistering or flaking skin
• irritation and swelling
• tightness or discomfort in your joints
• hives and itching
• fever
• problem breathing

If you experience any of these adverse effects, stop utilizing azelaic acid and see a physician.

It’s constantly crucial to wear sun block when you go outside, but be particularly conscious to wear SPF products when you’re utilizing azelaic acid. Given that it can thin your skin, your skin is more sensitive and prone to sun damage.

How azelaic acid compares to other treatments

Azelaic acid isn’t for everyone. The efficiency of the treatment may depend upon your:.

• symptoms
• skin type
• expectations

Because it works slowly, azelaic acid is frequently prescribed in addition to other kinds of acne treatment.

According to older research, azelaic acid cream might be as efficient as benzoyl peroxide and tretinoin (Retin-A) for the treatment of acne. While azelaic acid outcomes are similar to those of benzoyl peroxide, it’s also more expensive.

Azelaic acid likewise works more carefully than alpha hydroxy acid, glycolic acid, and salicylic acid.

While these other acids are strong enough to be utilized on their own in chemical peels, azelaic acid isn’t. This indicates that while azelaic acid is less most likely to aggravate your skin, it likewise needs to be used regularly and offered time to work. [10]

Azelaic acid topical dosing details

Normal Adult Dosage for Acne:

20% Cream Formulations: Use a thin layer to the afflicted location( s) 2 times a day

Comments:

• The affected location( s) must be carefully cleaned and patted dry before application.
• This drug must be carefully however thoroughly massaged into the afflicted location( s) in the early morning and evening.
• The period of treatment is based upon the client and the intensity of the acne.
• Enhancement in clients with inflammatory lesions generally occurs within 4 weeks.

Usage: Topical treatment of mild-to-moderate inflammatory acne vulgaris

Normal Grownup Dose for Acne Rosacea:

15% Gel/Foam Formulations: Apply a thin layer to the affected area( s) 2 times a day

Remarks:

• The afflicted area( s) should be gently washed and dried prior to application with an extremely mild soap or soapless cleaning cream.
• This drug should be carefully however thoroughly massaged into the impacted areas in the morning and night.
• Patients may apply cosmetics as soon as the treatment has actually dried.
• Clients must be reassessed if enhancement is not observed after completing 12 weeks of treatment.
• For patients utilizing foam formulations, the tiniest amount of foam ought to be utilized to properly cover the afflicted location( s) with a thin layer.

Usage: Topical treatment of the inflammatory papules and pustules of moderate to moderate rosacea

Typical Pediatric Dose for Acne:

12 years and older:

20% Cream Solutions: Apply a thin layer to the affected area( s) 2 times a day

Comments:

• The affected location( s) ought to be gently washed and patted dry prior to application.
• This drug must be gently however thoroughly massaged into the affected location( s) in the morning and night.
• Enhancement in clients with inflammatory sores usually happens within 4 weeks.

Use: Topical treatment of mild-to-moderate inflammatory acne vulgaris [11]

What other drugs connect with azelaic acid?

If your medical professional has actually directed you to utilize this medication, your doctor or pharmacist may already know any possible drug interactions and might be monitoring you for them. Do not begin, stop, or change the dosage of any medicine prior to talking to your physician, healthcare supplier or pharmacist first.

• Azelaic Acid has no recognized extreme interactions with other drugs.
• Azelaic acid has no known severe interactions with other drugs.
• Azelaic acid has no known moderate interactions with other drugs.
• Azelaic acid has no recognized mild interactions with other drugs.

This file does not include all possible interactions. Therefore, prior to utilizing this product, tell your doctor or pharmacist of all the items you use. Keep a list of all your medications with you, and share the list with your physician and pharmacist. Talk to your doctor if you have health questions or concerns. [12]

Frequently asked questions

Who Should Utilize Azelaic Acid and Who Should Not?

Azelaic acid is a safe skin care ingredient that has widespread compatibility with all skin types, and is normally well-tolerated, even by those with delicate skin.

Who could take advantage of azelaic acid?

Azelaic acid is especially advantageous for those with blemished skin and/or those with uneven tone and rough texture. It can also be used to relax sensitivity.

Who should keep away from azelaic acid?

Unfavorable responses and side effects to azelaic acid are not common, however just like any skin care component, if you experience signs of irritation, stop usage or explore using less frequently (once every other day, for example).

How Does Azelaic Acid Compare to Alpha Hydroxy Acids (AHAs) or Salicylic Acid (BHA)?

AHA, BHA, and azelaic acid share similarities, however also some fascinating distinctions. Although azelaic acid can exfoliate skin when appropriately formulated, it doesn’t exfoliate the same way or with the exact same level of efficiency as components like glycolic acid and lactic acid (AHAs) or salicylic acid (BHA).

On the other hand, azelaic acid offers additional benefits that AHA and BHA ingredients do not offer, especially when it concerns enhancing a markedly unequal skin tone and skin level of sensitivity issues.

Can you use them together? Yes, in fact, this combination can be ideal for attending to the appearance of multiple skin concerns, from bumps to uneven skin tone to age-related concerns you might be having problem with.

Can I Utilize Vitamin C and Azelaic Acid Together?

Yes, you can use vitamin C and azelaic acid products together– these components complement one another. Utilizing them together might accelerate the outcomes for night skin tone and fading marks by targeting the problem through multiple pathways.

What Should You Not Blend With Azelaic Acid?

Azelaic acid items can be used together with all type of skin care items, and there isn’t research revealing it’s an issue to use alongside other powerhouse active ingredients. Naturally, if you’re using a prescription version, seek advice from your doctor on how to work it into your skin care routine. [13]

Precautions

It is really crucial that your medical professional examine your progress at routine visits for any undesirable results that might be triggered by this medication.

If your acne does not improve within 4 weeks, or if it becomes worse, check with your doctor.

If your rosacea does not enhance within 12 weeks, or if it becomes worse, check with your physician.

Hypopigmentation may take place while you are utilizing this medicine. Talk to your physician immediately if your skin color is lighter in the dealt with locations, particularly if you have dark skin.

This medication may cause allergies, including angioedema, which can be deadly and require immediate medical attention. Contact your doctor immediately if you have itching skin, trouble breathing, or big, hive-like swelling on face, eyelids, lips, tongue, throat, hands, legs, feet, or sex organs after utilizing this medicine.

This medicine may trigger skin responses. Contact your doctor immediately if you have a skin rash, burning, dryness, redness, peeling, stinging, swelling, or irritation on the skin. [14]

The bottom line

Azelaic acid is a naturally happening acid that’s milder than some more popular acids used to deal with acne.

While the results of treatment with azelaic acid might not be obvious right now, there is research that indicates this component as efficient.

Acne, unequal skin tone, rosacea, and inflammatory skin problem have all been revealed to be efficiently treated with azelaic acid. Similar to any medication, follow the dosing and application instructions from your doctor closely. [15]

Recommendations

1. https://www.merriam-webster.com/medical/azelaic%20acid
2. https://www.acs.org/content/acs/en/molecule-of-the-week/archive/a/azelaic-acid.html
3. https://go.drugbank.com/drugs/DB00548
4. https://thechemco.com/chemical/azelaic-acid/
5. https://practicaldermatology.com/articles/2013-mar/new-insights-into-azelaic-acid
6. https://www.theindependentpharmacy.co.uk/rosacea/guides/azelaic-acid-benefits
7. https://navamd.com/face-forward-blog/all-about-azelaic-acid
8. https://www.webmd.com/skin-problems-and-treatments/what-to-know-about-azelaic-acid-skin
9. https://www.hairguard.com/azelaic-acid/
10. https://www.healthline.com/health/azelaic-acid-acne#alternative-treatments
11. https://www.drugs.com/mtm/azelaic-acid-topical.html
12. https://www.rxlist.com/consumer__azelaic_acid_azelex_finacea/drugs-condition.htm
13. https://www.paulaschoice.com/expert-advice/skincare-advice/ingredient-spotlight/azelaic-acid-for-skin.html
14. https://www.mayoclinic.org/drugs-supplements/azelaic-acid-topical-route/precautions/drg-20062084
15. https://www.healthline.com/health/azelaic-acid-acne