Azelaic Acid

Azelaic Acid, formally nonanedioic acid, is a white crystalline solid 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 launch 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 discovered naturally in wheat, rye, and barley. It is likewise produced by Malassezia furfur, likewise known as Pityrosporum ovale, which is a species 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 applied topically in a cream formulation of 20%. It operates in part by stopping the growth 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 exact system of action of azelaic acid is not known. It is believed that azelaic acid manifests its antibacterial effects by hindering the synthesis of cellular protein in anaerobic and aerobic bacteria, particularly Staphylococcus epidermidis and Propionibacterium acnes. In aerobic germs, azelaic acid reversibly inhibits a number of oxidoreductive enzymes consisting of tyrosinase, mitochondrial enzymes of the breathing chain, thioredoxin reductase, 5-alpha-reductase, and DNA polymerases. In anaerobic bacteria, azelaic acid hinders glycolysis. In addition to these actions, azelaic acid also enhances acne vulgaris by normalizing the keratin process and decreasing microcomedo development. Azelaic acid may work against both inflamed and noninflamed lesions. Particularly, azelaic acid minimizes the density of the stratum corneum, shrinks keratohyalin granules by decreasing the quantity and circulation of filaggrin (an element of keratohyalin) in epidermal layers, and lowers the number of keratohyalin granules. [3]

Metabolism

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

Route of elimination

Azelaic acid is primarily excreted unchanged in the urine, but goes through some ß-oxidation to much 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, suggesting percutaneous absorption rate-limited kinetics. [3]

Characteristic

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

Azelaic acid is utilized in the manufacture of adhesives and sealant chemicals; lubricants and lube ingredients; paint and coating additives, and plasticizers. [4]

Benefits

A single system of action has actually not been determined to explain the impacts of azelaic acid on the skin. It helps scavenge reactive oxygen types, decreases expression of kallikrein-5 (KLK-5) and pro-inflammatory cathelicidins such as LL-37, as well as inhibits toll-like receptor 2 (TLR-2). In addition, it hinders the pigment producing enzyme tyrosinase, has comedolytic properties, and might minimize epidermal hyperkeratinization. While the 15% gel formula is FDA approved for the treatment of rosacea, a different 20% cream formula (Azelex, Allergan) is indicated for the treatment of acne. Both formulations carry a pregnancy category B score.

Azelaic Acid for Rosacea

The 15% gel formulation of azelaic acid is FDA authorized 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 innovation provide the gel higher cutaneous biovailability. While the sign is for use of azelaic acid 15% gel two times daily, a research study subsequent to its approval showed comparable effectiveness of once compared to twice day-to-day application.

Recent data suggest irregular 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 significant 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 greater pro-inflammatory homes than antibacterial properties. This imbalance promotes angiogenesis and persistent skin inflammation. Topical application of azelaic acid 15% gel has actually been demonstrated to reduce 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 shown to stimulate TLR-2 activity, resulting in skin inflammation and comedogenesis. Topical retinoids are a staple in treating acne not just because of their capability to stabilize follicular hyperkeratinization however likewise due to their anti-inflammatory properties. Comparable to its mechanism of action in treating rosacea, azelaic acid’s ability to inhibit TLR-2 activity assists explain its effectiveness in dealing with acne vulgaris. Using azelaic acid 15% gel is considered off label for the treatment of acne vulgaris. Many practitioners might utilize it off-label for acne as part of a combination therapy for clients who can not endure topical retinoids, those who also experience hyperpigmentation, and for females who are pregnant or breastfeeding (as it is pregnancy classification B).

Azelaic Acid for Hyperpigmentation

Post-inflammatory coloring medically manifests as dark spots in locations of skin that formerly were inflamed, be it from acne or another inflammatory dermatosis. While not enhanced for this sign, azelaic acid is commonly used off-label to deal with pigmentation. One medical trial showed 15% azelaic acid gel to be both efficacious and safe in treating hyperpigmentation connected with acne for 16 weeks. This effect might be explained by 2 homes of the drug. Initially, azelaic acid is understood to hinder the enzyme tyrosinase, which is required for the production of melanin.3 Second, its function as an anti-inflammatory may be beneficial also. When active acne sores (e.g., papules and pustules) willpower, proof reveals that the skin in these locations still have subclinical swelling.14 While this has actually been shown in acne scars, the exact same may also hold true in cases of relentless erythema and pigmentation. More research study is needed to substantiate this theory, however.

Having a drug that efficiently treats a condition assists us much better comprehend that condition, as we discover the mechanism by which the drug works. Just as biologics have shed light on the pathogenesis of psoriasis, research into the mechanism of action of azelaic acid has significantly enhanced our understanding about the pathogenesis of rosacea, specifically the role of an over-active natural immune system. A greater understanding of the disease equates to improved treatment algorithms and patient outcomes, and ultimately this assists influence the future of drug development. [5]

Blackheads

The antibacterial qualities of azelaic acid help to prevent the development of both white and blackheads, by killing the skin germs that can cause areas. It likewise inhibits the production of keratin skin cells, which can block pores and sebaceous glands and produce oily accumulations (leading to blackheads).

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

Finacea Gel and Skinoren Cream are both skin medications. Each is effective at dealing with acne, but there are some differences between the two, with the key one being that Skinoren Cream contains more azelaic acid than Finacea Gel.

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

Skinoren Cream is stronger: 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, that makes it OK for rosacea.

As both include comparable components, they can cause similar side effects.

More about Finacea Gel

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

Finacea likewise minimizes the body’s natural production of keratin cells. This avoids keratin cells from obstructing pores and sebaceous glands (the small glands in your skin which release sebum), easing 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 greater concentration. It’s 20% azelaic acid where Finacea Gel is a weaker 15%.

The potent azelaic acid in Skinoren operates in 2 methods to fight acne: by decreasing the development of pore-blocking keratin cells, and by killing the bacteria associated with acne. A typical skin bacteria called propionibacterium eats the sebum produced by the skin, developing waste products and fatty acids that get worse acne signs and irritate the skin.

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

Although Finacea Gel is generally utilized for rosacea, and Skinoren cream is largely utilized for acne, the two treatments can in some cases be prescribed for the other skin conditions. It all depends on the scenario, but considering that each item is prescription-only, there shouldn’t be any confusion about what to utilize. [6]

How Do You Utilize Azelaic Acid?

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

Most skin specialists advise that whichever form you pick, the strength ought to sit someplace in the 15% to 20% variety.

Over-the-counter products consisting of a smaller sized dose of azelaic acid are available also, although for finest results a prescription is normally required.

The majority of topical representatives need you to use them two times a day to clean, dry skin (masks containing azelaic acid should be utilized less frequently).

Listed below we’ve assembled a detailed skin care routine to reveal you how to include azelaic acid into your routine.

Step One

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

It’s important not to skip this action due to the fact that the cleaner your skin is, the most likely it is to absorb other treatments.

Step 2

Next apply your azelaic acid cream, gel or lotion.

If you have delicate skin, we recommend starting with a single application every other day. As your skin changes, you can use the item more regularly.

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

You ought to also wait about 15 minutes for the item to absorb to avoid smearing. This is especially essential if you’re utilizing it as an area treatment to fade darker areas.

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

Step Three

After letting the azelaic acid soak up, use your moisturizer as usual. It’s also important not to skimp on sunscreen.

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

This indicates that not using 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 dried entirely.

Do not bandage or cover the area unless your dermatologist has instructed you to do so.

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

This is due to the fact that extreme 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 treat skin problem like acne.

The most typical forms of these acids include salicylic acid, glycolic acid, and lactic acid.

AHAs are more aggressive exfoliants than azelaic acid, which makes them more effective in dealing with sun damage and combating indications of aging. They are also a popular option for people wanting to improve their skin’s texture.

BHAs resemble AHAs, except they have antibacterial residential or commercial properties. This is excellent for dealing with acne due to the fact that it eliminates damaging germs that can potentially contaminate blemishes.

Although you’ll see faster outcomes by utilizing BHAs, they are more likely to trigger serious adverse effects like rashes or blistering.

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

However, some skin specialists caution against combining azelaic acid with salicylic acid or other beta-hydroxy acids because 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 particularly effective. [7]

Kinds of Azelaic Acid

You can get azelaic acid as a:.

• Gel
• Foam
• Cream
• Pill

Prescription types have 15% to 20% azelaic acid, however 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 5 times as powerful as testosterone. It plays an essential role in the advancement of guys’s sexual attributes, consisting of the development of hair on the chin, back, and chest.

Strangely enough, DHT is likewise destructive to the development of hair on the scalp. Simply put, it has the specific opposite impact on the scalp compared to the remainder of the body. This makes it a crucial particle in male pattern baldness.

DHT is associated with male pattern baldness.

Thus, finding molecules that inhibit the action of 5α-reductase is of terrific interest to pharmaceutical business and skin specialists specializing in hair regrowth.

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

In the experiment, Dr. Stamatiadis and his research team identified that azelaic acid might entirely inhibit 5α-reductase activity in vitro (in a petri meal). Much more intriguing, when azelaic was integrated with zinc sulfate, the inhibition was even more powerful.

Dr. Stamatiadis concluded that the combination of these 2 compounds could potentially treat androgen-related ailments.

Azelaic Acid and Alopecia Areata

Alopecia Areata (AA) is a kind of loss of hair that is autoimmune in nature. For factors that are unclear, the body’s immune cells assault the roots. The result is distinct, entirely bald patches. These can appear anywhere on the scalp, and often on other parts of the body.

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

Can Azelaic Acid Reward AA?

Alopecia areata is the scientific term for patchy baldness.

In a pilot study concerning azelaic acid’s possible usage in handling spot 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. Till this research came out, however, there were no controlled research studies to assess its effectiveness.

Anthralin is a tested topical treatment for the management of alopecia location. This makes it a great standard to compare the efficiency of novel treatments.

The Research study Protocol

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

The first group applied 20% azelaic acid cream to the afflicted portion of the scalp daily for 12 consecutive weeks.

The 2nd group used 0.5% anthralin cream to the afflicted portion 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 patients could keep their treatment outcomes.

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

Outcomes

At the end of this 20 week period, Dr. Sasmaz and Dr. Arican performed a medical assessment on each individual.

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

Azelaic acid group

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

Anthralin group

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

Therefore, subjects in either treatment arm had broadly comparable results. The Typical Terminal Regrowth Scores were both over 1, revealing total sufficient 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 complete reaction. In addition, topics with a total reaction had no new bald patches develop during the study duration. This recommends the azelaic acid treatment might assist manage the condition outside of the cured location.

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

This study is not without its faults, nevertheless. Dr. Sasmaz and Dr. Arican utilized 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 results of treatment. Some scientists have actually even questioned making use of anthralin as a contrast tool, due to a lack of certainty in its usefulness.

Azelaic Acid and Androgenetic Alopecia?

To date, there is no released research on the effectiveness of azelaic acid against male androgenetic alopecia (AGA). Having said that, the compound inhibits DHT, at least in vitro. This makes it an in theory helpful treatment alternative.

This has not stopped numerous guys with loss of hair from including it into their baldness treatment routine. Many report positive results, while others say it made no distinction in their loss of hair.

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

Usually, users attempt formulations including in between 10-15% azelaic acid.

How to Experiment With Azelaic Acid Yourself

Given that there are appealing results linking azelaic acid to a drop in DHT levels and a reduction of alopecia areata symptoms, it may deserve your while to try this product out for yourself.

It is recommended that you add azelaic acid to your typical routine instead of substituting 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 products you can buy which contain azelaic acid:.

Scalp creams and conditioner for alopecia including azelaic acid.

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

Azelaic acid side effects

Azelaic acid can trigger adverse effects, including:.

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

Less-common side effects consist of:.

• blistering or flaking skin
• inflammation 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 doctor.

It’s constantly essential to wear sun block when you go outside, but be especially mindful to wear SPF items when you’re using azelaic acid. Since it can thin your skin, your skin is more delicate and susceptible to sun damage.

How azelaic acid compares with other treatments

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

• signs
• skin type
• expectations

Considering that it works slowly, azelaic acid is frequently prescribed together with 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 likewise more costly.

Azelaic acid likewise works more gently 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 suggests that while azelaic acid is less most likely to irritate your skin, it likewise needs to be used regularly and offered time to work. [10]

Azelaic acid topical dosing details

Typical Grownup Dosage for Acne:

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

Remarks:

• The affected area( s) should be gently washed and patted dry prior to application.
• This drug must be gently but completely massaged into the affected location( s) in the morning and evening.
• The period of treatment is based upon the patient and the intensity of the acne.
• Enhancement in patients with inflammatory sores typically takes place within 4 weeks.

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

Typical Adult Dose for Acne Rosacea:

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

Remarks:

• The afflicted location( s) ought to be carefully cleaned and dried prior to application with a very moderate soap or soapless cleaning lotion.
• This drug should be gently but completely massaged into the impacted areas in the morning and night.
• Clients may use cosmetics once the treatment has dried.
• Clients must be reassessed if improvement is not observed after finishing 12 weeks of treatment.
• For clients using foam solutions, the tiniest quantity of foam must be used to sufficiently cover the affected area( s) with a thin layer.

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

Usual Pediatric Dose for Acne:

12 years and older:

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

Comments:

• The afflicted location( s) must be carefully washed and patted dry before application.
• This drug should be carefully but completely massaged into the afflicted area( s) in the morning and night.
• Improvement in clients with inflammatory sores normally takes place within 4 weeks.

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

What other drugs engage with azelaic acid?

If your medical professional has actually directed you to use this medication, your medical professional or pharmacist might currently understand any possible drug interactions and might be monitoring you for them. Do not begin, stop, or change the dose of any medication prior to checking with your doctor, health care supplier or pharmacist first.

• Azelaic Acid has no known serious interactions with other drugs.
• Azelaic acid has no known major 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 document does not consist of all possible interactions. Therefore, before utilizing this product, inform your doctor or pharmacist of all the items you utilize. Keep a list of all your medications with you, and share the list with your doctor and pharmacist. Check with your doctor if you have health concerns or issues. [12]

FAQs

Who Should Use Azelaic Acid and Who Should Not?

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

Who could gain from azelaic acid?

Azelaic acid is particularly useful for those with blemished skin and/or those with uneven tone and bumpy texture. It can also be used to calm sensitivity.

Who should stay away from azelaic acid?

Unfavorable reactions and side effects to azelaic acid are not common, but as with any skin care component, if you experience indications of irritation, stop usage or experiment with applying 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 similarities, but likewise some fascinating distinctions. Although azelaic acid can exfoliate skin when properly formulated, it does not exfoliate the same way or with the very same level of efficiency as active ingredients like glycolic acid and lactic acid (AHAs) or salicylic acid (BHA).

On the other hand, azelaic acid offers fringe benefits that AHA and BHA components do not offer, specifically when it comes to enhancing a significantly irregular complexion and skin sensitivity problems.

Can you use them together? Yes, in fact, this combination can be perfect for attending to the appearance of multiple skin issues, from bumps to unequal complexion to age-related issues you may be battling with.

Can I Use Vitamin C and Azelaic Acid Together?

Yes, you can use vitamin C and azelaic acid items together– these active ingredients complement one another. Utilizing them together might speed up the outcomes for night complexion and fading marks by targeting the concern through numerous paths.

What Should You Not Combine With Azelaic Acid?

Azelaic acid items can be utilized together with all sort of skin care items, and there isn’t research revealing it’s a problem to utilize alongside other powerhouse components. Obviously, if you’re using a prescription version, talk to your doctor on how to work it into your skin care regimen. [13]

Safety measures

It is extremely crucial that your doctor examine your progress at regular check outs for any unwanted effects that may be caused by this medication.

If your acne does not improve within 4 weeks, or if it worsens, check with your physician.

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

Hypopigmentation might happen while you are utilizing this medication. Talk to your physician right now if your skin color is lighter in the treated areas, particularly if you have dark skin.

This medication might cause allergies, including angioedema, which can be lethal and need immediate medical attention. Consult your physician right away if you have itching skin, difficulty breathing, or large, hive-like swelling on face, eyelids, lips, tongue, throat, hands, legs, feet, or sex organs after using this medicine.

This medicine may cause skin reactions. Consult your doctor immediately if you have a skin rash, burning, dryness, redness, peeling, stinging, swelling, or inflammation on the skin. [14]

The bottom line

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

While the results of treatment with azelaic acid may not be obvious right now, there is research that points to this component as effective.

Acne, unequal complexion, rosacea, and inflammatory skin problem have all been shown to be successfully treated with azelaic acid. As with any medication, follow the dosing and application instructions from your medical professional closely. [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