Azelaic Acid

Azelaic Acid, officially nonanedioic acid, is a white crystalline strong with a melting point of 106.5 ° C. It occurs 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 trigger their defenses against assaulting pathogens. [2]

Background

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

System of action

The precise system of action of azelaic acid is not known. It is believed that azelaic acid manifests its anti-bacterial effects by preventing the synthesis of cellular protein in anaerobic and aerobic bacteria, especially Staphylococcus epidermidis and Propionibacterium acnes. In aerobic bacteria, azelaic acid reversibly hinders a number of oxidoreductive enzymes consisting of tyrosinase, mitochondrial enzymes of the respiratory chain, thioredoxin reductase, 5-alpha-reductase, and DNA polymerases. In anaerobic bacteria, azelaic acid impedes glycolysis. Along with these actions, azelaic acid likewise enhances acne vulgaris by normalizing the keratin procedure and reducing microcomedo formation. Azelaic acid might work against both inflamed and noninflamed sores. Particularly, azelaic acid minimizes the thickness of the stratum corneum, diminishes keratohyalin granules by reducing the amount and distribution of filaggrin (a part of keratohyalin) in epidermal layers, and decreases the number of keratohyalin granules. [3]

Metabolism

Mainly excreted the same in the urine however undergoes some b-oxidation to shorter chain dicarboxylic acids.

Route of elimination

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

Half-life

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

Properties

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

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

Advantages

A single system of action has actually not been identified to describe the effects of azelaic acid on the skin. It assists scavenge reactive oxygen types, lowers expression of kallikrein-5 (KLK-5) and pro-inflammatory cathelicidins such as LL-37, in addition to inhibits toll-like receptor 2 (TLR-2). In addition, it inhibits the pigment producing enzyme tyrosinase, has comedolytic homes, and might reduce epidermal hyperkeratinization. While the 15% gel formulation is FDA approved for the treatment of rosacea, a separate 20% cream solution (Azelex, Allergan) is shown for the treatment of acne. Both formulas bring a pregnancy category B rating.

Azelaic Acid for Rosacea

The 15% gel solution of azelaic acid is FDA approved to deal with the papules and pustules of mild 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 higher cutaneous biovailability. While the indication is for use of azelaic acid 15% gel two times daily, a study subsequent to its approval showed comparable efficacy of when compared to twice everyday application.

Current data recommend abnormal over-activity of the innate body immune system as a major factor to the pathophysiology of rosacea. Excess skin antimicrobial peptides (e.g., cathelicidins) and stimulation of TLR-2 both play substantial roles. Cathelicidins are processed by serine proteases (e.g., KLK-5) into pro-inflammatory peptides, such as LL-37. Overactivity of KLK-5 leads to a high level of cathelicidin processing into peptides with higher pro-inflammatory properties than anti-bacterial properties. This imbalance promotes angiogenesis and chronic skin inflammation. Topical application of azelaic acid 15% gel has actually been shown to minimize skin serine protease activity and help reverse these modifications.

Azelaic Acid for Acne

TLR-2 over-activity contributes in the pathogenesis of acne. Propionibacterium acnes itself has been shown to promote TLR-2 activity, leading to skin inflammation and comedogenesis. Topical retinoids are a staple in treating acne not only because of their ability to normalize follicular hyperkeratinization however likewise due to their anti-inflammatory residential or commercial properties. Comparable to its system of action in treating rosacea, azelaic acid’s ability to prevent TLR-2 activity helps discuss its efficacy in dealing with acne vulgaris. Making use of azelaic acid 15% gel is considered off label for the treatment of acne vulgaris. Many professionals might utilize it off-label for acne as part of a mix treatment for clients who can not endure topical retinoids, those who likewise struggle with hyperpigmentation, and for females who are pregnant or breastfeeding (as it is pregnancy category B).

Azelaic Acid for Hyperpigmentation

Post-inflammatory pigmentation medically manifests as dark areas in locations of skin that previously were inflamed, be it from acne or another inflammatory dermatosis. While not enhanced for this sign, azelaic acid is typically utilized off-label to deal with coloring. One clinical trial showed 15% azelaic acid gel to be both efficacious and safe in dealing with hyperpigmentation connected with acne for 16 weeks. This result might be described by two properties of the drug. First, azelaic acid is known to hinder the enzyme tyrosinase, which is required for the production of melanin.3 2nd, its function as an anti-inflammatory might be useful too. When active acne sores (e.g., papules and pustules) resolve, evidence reveals that the skin in these locations still have subclinical swelling.14 While this has actually been demonstrated in acne scars, the very same might also be true in cases of persistent erythema and coloring. More research study is required to validate this theory, however.

Having a drug that effectively treats a condition helps us much better understand that condition, as we find the system by which the drug works. Just as biologics have actually shed light on the pathogenesis of psoriasis, research into the system of action of azelaic acid has significantly enhanced our understanding about the pathogenesis of rosacea, particularly the role of an over-active natural body immune system. A greater understanding of the illness translates to better treatment algorithms and client results, and ultimately this helps influence the future of drug advancement. [5]

Blackheads

The antibacterial qualities of azelaic acid aid to prevent the development of both white and blackheads, by eliminating the skin germs that can lead to areas. It also prevents the production of keratin skin cells, which can block pores and sebaceous glands and create oily accumulations (leading to blackheads).

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

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

Listed below, we’ve highlighted the key distinctions in between Finacea Gel and Skinoren cream:.

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

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

Finacea Gel deals with rosacea: it’s a milder treatment, which makes it okay for rosacea.

As both include comparable ingredients, they can cause comparable side effects.

More about Finacea Gel

Finacea Gel is a prescription-only gel used to treat rosacea. It’s 15% azelaic acid, which provides it anti-inflammatory results and permits it to lower the inflammation and swelling of rosacea.

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

More about Skinoren Cream

Skinoren cream also includes the active ingredient of azelaic acid, however 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 combat acne: by minimizing the growth of pore-blocking keratin cells, and by killing the germs connected with acne. A typical skin germs called propionibacterium feeds upon the sebum produced by the skin, developing waste items and fatty acids that aggravate acne symptoms and inflame the skin.

By uncloging pores and glands and eliminating propionibacterium, Skinoren decreases acne and allows your skin to recover naturally.

Although Finacea Gel is usually utilized for rosacea, and Skinoren cream is mostly used for acne, the two treatments can sometimes be prescribed for the other skin conditions. All of it depends on the scenario, however because each item is prescription-only, there should not be any confusion about what to use. [6]

How Do You Use Azelaic Acid?

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

Most skin doctors suggest that whichever form you select, the strength must sit somewhere in the 15% to 20% variety.

Over the counter products containing a smaller dose of azelaic acid are available too, although for best results a prescription is normally needed.

A lot of topical agents need you to apply them twice a day to clean, dry skin (masks containing azelaic acid should be used less often).

Listed below we’ve created a step-by-step skin care regimen to reveal you how to integrate azelaic acid into your routine.

Step One

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

It is essential not to avoid this action due to the fact that the cleaner your skin is, the most likely it is to take in other treatments.

Step 2

Next apply your azelaic acid cream, gel or cream.

If you have delicate skin, we suggest starting with a single application every other day. As your skin adjusts, you can use the item more often.

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

You should also wait about 15 minutes for the product to soak up to prevent smearing. This is particularly essential if you’re using it as an area treatment to fade darker areas.

If you’re using azelaic acid as an area treatment, don’t apply it all over the face. This is since you’ll run the risk of fading the skin in unneeded locations.

Step 3

After letting the azelaic acid take in, apply your moisturizer as usual. It’s likewise important not to skimp on sunscreen.

When utilizing azelaic acid, the skin tends to become more vulnerable to environmental damage.

This suggests that not utilizing sun defense can reverse all of the advantages of azelaic acid, since sun damage can trigger hyperpigmentation and melasma.

Step 4

It’s safe to use makeup after the azelaic acid cream, foam or gel has actually dried completely.

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

When not in use, store your azelaic acid at room temperature and away from direct light.

This is due to the fact that extreme 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 used to deal with skin problem like acne.

The most common kinds of these acids include salicylic acid, glycolic acid, and lactic acid.

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

BHAs are similar to AHAs, except they have antibacterial homes. This is great for dealing with acne due to the fact that it kills harmful germs that can possibly infect blemishes.

Although you’ll see faster outcomes by utilizing BHAs, they are most likely to trigger extreme negative effects like rashes or blistering.

In contrast to AHAs and BHAs, azelaic acid is a gentler treatment with fewer side effects.

However, some skin specialists caution against integrating azelaic acid with salicylic acid or other beta-hydroxy acids due to the fact that it might cause excessive dryness and irritation.

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

Forms of Azelaic Acid

You can get azelaic acid as a:.

• Gel
• Foam
• Cream
• Tablet

Prescription kinds have 15% to 20% azelaic acid, but non-prescription variations have much less. [8]

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

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

Curiously, DHT is also harmful to the development of hair on the scalp. In other words, it has the specific opposite impact on the scalp compared to the rest of the body. This makes it a key molecule in male pattern baldness.

DHT is associated with male pattern baldness.

Hence, finding particles that inhibit the action of 5α-reductase is of fantastic interest to pharmaceutical companies and skin doctors specializing in hair regrowth.

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

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

Dr. Stamatiadis concluded that the mix of these two compounds could potentially deal with androgen-related disorders.

Azelaic Acid and Alopecia Areata

Alopecia Areata (AA) is a kind of hair loss that is autoimmune in nature. For factors that are unclear, the body’s immune cells assault the follicles. The result is well-defined, entirely 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, doctors prescribe various medications off-label.

Can Azelaic Acid Treat AA?

Alopecia areata is the clinical term for irregular baldness.

In a pilot study concerning azelaic acid’s possible use in handling area baldness, Dr. Sasmaz and Dr. Arican carried out an experiment comparing azelaic acid to anthralin.

Azelaic acid has actually been utilized to treat this condition in the past. Up until this research study came out, however, there were no regulated studies to evaluate its efficiency.

Anthralin is a proven topical treatment for the management of alopecia areata. This makes it a great standard to compare the effectiveness of unique treatments.

The Research study Procedure

In the experiment, Dr. Sasmaz and Dr. Arican hired 31 subjects 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 applied 20% azelaic acid cream to the afflicted part of the scalp daily for 12 successive weeks.

The second group used 0.5% anthralin cream to the afflicted part of the scalp daily for 12 successive weeks. Afterward, there was an 8-week follow-up throughout which patients used no cream. The goal of this follow-up was to see whether the clients could preserve their treatment outcomes.

All research study participants finished the experiment as instructed. There were no major side effects.

Outcomes

At the end of this 20 week duration, Dr. Sasmaz and Dr. Arican carried out a scientific evaluation on each participant.

Throughout this evaluation, each of the topic’s scalps was granted a Terminal Hair Regrowth Score on a scale from 0 to 2. On this scale, a 0 showed an inadequate response, a 1 a partial action, and a 2 a complete action. 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 Ratings were both over 1, revealing total adequate response 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 total action. In addition, subjects with a total action had no brand-new bald spots develop throughout the research study duration. This suggests the azelaic acid treatment might help manage the condition outside of the cured location.

Dr. Sasmaz and Dr. Arican concluded that azelaic acid could be an effective topical treatment for irregular alopecia areata.

This study is not without its faults, nevertheless. Dr. Sasmaz and Dr. Arican used a fairly small sample size in their experiment. In addition, there was no reported follow-up for the research study to evaluate the long-lasting effects of treatment. Some scientists have even questioned the use of anthralin as a contrast tool, due to a lack of certainty in its effectiveness.

Azelaic Acid and Androgenetic Alopecia?

To date, there is no released research study on the effectiveness of azelaic acid against male androgenetic alopecia (AGA). Having said that, the substance hinders DHT, at least in vitro. This makes it a theoretically beneficial treatment alternative.

This has not stopped lots of men with hair loss from integrating it into their baldness treatment regimen. Numerous report favorable results, while others state it made no distinction in their hair loss.

The lack of standardized treatment programs is an issue. There are no standards on what strength to utilize, how often, or in mix with what other active ingredients.

Typically, users try formulas including between 10-15% azelaic acid.

How to Check Out Azelaic Acid Yourself

Since there are appealing outcomes linking azelaic acid to a drop in DHT levels and a decrease of alopecia areata symptoms, it may deserve your while to attempt this product out on your own.

It is recommended that you include azelaic acid to your normal program instead of replacing it as a treatment. This holds true especially if you are using an FDA-approved hair product such as Minoxidil or Propecia. There are a range of topical products you can buy which consist of azelaic acid:.

Scalp creams and conditioner for alopecia consisting of azelaic acid.

• The FDA-approved acne creams mentioned earlier
• Shops offering natural supplements frequently have vials including azelaic acid
• Use the cream or other topical option daily for the best results. [9]

Azelaic acid negative effects

Azelaic acid can cause adverse effects, consisting of:.

• burning or tingling on your skin
• peeling skin at the site of application
• skin dryness or redness

Less-common side effects include:.

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

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

It’s always important to wear sun block when you go outside, however be especially mindful to wear SPF items when you’re using azelaic acid. Because it can thin your skin, your skin is more delicate and prone to sun damage.

How azelaic acid compares with other treatments

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

• symptoms
• skin type
• expectations

Considering that it works gradually, azelaic acid is typically prescribed along with other forms of acne treatment.

According to older research, azelaic acid cream may be as effective 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 also works more gently than alpha hydroxy acid, glycolic acid, and salicylic acid.

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

Azelaic acid topical dosing information

Typical Adult Dose for Acne:

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

Comments:

• The afflicted area( s) need to be carefully cleaned and patted dry before application.
• This drug must be gently however thoroughly massaged into the affected location( s) in the morning and night.
• The period of treatment is based upon the client and the seriousness of the acne.
• Improvement in clients with inflammatory lesions typically takes place within 4 weeks.

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

Normal Grownup Dosage for Acne Rosacea:

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

Remarks:

• The affected area( s) should be gently washed and dried before application with a very moderate soap or soapless cleaning lotion.
• This drug should be carefully but thoroughly rubbed into the impacted locations in the morning and evening.
• Patients may use cosmetics when the treatment has actually dried.
• Patients must be reassessed if enhancement is not observed after completing 12 weeks of treatment.
• For patients using foam solutions, the tiniest amount of foam need to be used to adequately cover the afflicted area( s) with a thin layer.

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

Typical Pediatric Dosage for Acne:

12 years and older:

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

Comments:

• The afflicted location( s) should be gently washed and patted dry before application.
• This drug should be carefully however completely rubbed into the affected area( s) in the early morning and evening.
• 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 interact with azelaic acid?

If your physician has actually directed you to use this medication, your doctor or pharmacist may already understand any possible drug interactions and might be monitoring you for them. Do not start, stop, or change the dose of any medication before checking with your doctor, healthcare service provider or pharmacist initially.

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

This file does not include all possible interactions. For that reason, prior to using this item, tell your doctor or pharmacist of all the products you utilize. Keep a list of all your medications with you, and share the list with your medical professional and pharmacist. Contact your physician if you have health concerns 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 sensitive skin.

Who could take advantage of azelaic acid?

Azelaic acid is especially useful for those with blemished skin and/or those with unequal tone and rough texture. It can also be utilized to relax sensitivity.

Who should stay away from azelaic acid?

Unfavorable responses and negative effects to azelaic acid are not typical, however as with any skin care ingredient, if you experience signs of irritation, stop usage or try out using less often (when 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 resemblances, however likewise some interesting distinctions. Although azelaic acid can exfoliate skin when properly formulated, it does not exfoliate the same way or with the exact same level of effectiveness as ingredients like glycolic acid and lactic acid (AHAs) or salicylic acid (BHA).

On the other hand, azelaic acid uses additional benefits that AHA and BHA components don’t supply, particularly when it pertains to improving a significantly uneven skin tone and skin level of sensitivity problems.

Can you use them together? Yes, in fact, this combination can be ideal for resolving the look of numerous skin concerns, from bumps to irregular skin tone to age-related concerns you may be struggling with.

Can I Utilize Vitamin C and Azelaic Acid Together?

Yes, you can utilize vitamin C and azelaic acid items together– these active ingredients complement one another. Utilizing them together may speed up the results for night skin tone and fading marks by targeting the issue through several paths.

What Should You Not Mix with Azelaic Acid?

Azelaic acid items can be utilized together with all kinds of skin care products, and there isn’t research revealing it’s a problem to use alongside other powerhouse active ingredients. Naturally, if you’re utilizing a prescription version, consult with your physician on how to work it into your skin care regimen. [13]

Precautions

It is extremely crucial that your doctor check your progress at regular check outs for any undesirable impacts that might be brought on by this medication.

If your acne does not enhance within 4 weeks, or if it becomes worse, talk to your medical professional.

If your rosacea does not enhance within 12 weeks, or if it worsens, talk to your doctor.

Hypopigmentation might occur while you are utilizing this medication. Check with your doctor right now if your skin color is lighter in the treated locations, especially if you have dark skin.

This medicine might trigger allergic reactions, consisting of angioedema, which can be deadly and require immediate medical attention. Talk to your doctor right away if you have itching skin, problem breathing, or big, hive-like swelling on face, eyelids, lips, tongue, throat, hands, legs, feet, or sex organs after using this medicine.

This medication may trigger skin reactions. Talk to your medical professional immediately if you have a skin rash, burning, dryness, soreness, 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 outcomes of treatment with azelaic acid may not be obvious immediately, there is research study that indicates this active ingredient as effective.

Acne, unequal complexion, rosacea, and inflammatory skin problem have actually all been revealed to be successfully treated with azelaic acid. Similar to any medication, follow the dosing and application directions from your physician carefully. [15]

References

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