Acitretin – StatPearls – NCBI Bookshelf

Continuing Education Activity

Acitretin belongs to a group of drugs known as retinoids. Retinoids include natural and synthetic compounds that have similar activity to vitamin A. Vitamin A helps regulate the immune system, impacts cellular growth, differentiation, proliferation, and plays a role in embryonic development. Other effects of retinoids include immunologic anti-inflammatory effects, induction of apoptosis, and inhibition of tumor promotion. This activity reviews the indications, contraindications, and adverse events associated with acitretin so that interprofessional team members can work together to manage patients using the medication optimally.

Objectives:

• Identify the indications for acitretin.

• Describe the adverse effects/toxicity with acitretin use.

• Outline the monitoring necessary for patients on acitretin therapy.

• Review interprofessional team strategies for improving care coordination for patients undergoing acitretin therapy to improve patient outcomes.

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Indications

Acitretin belongs to a group of drugs known as retinoids. Retinoids include natural and synthetic compounds that have similar activity to vitamin A. Vitamin A helps regulate the immune system, impacts cellular growth, differentiation, proliferation, and plays a role in embryonic development. Other effects of retinoids include immunologic anti-inflammatory effects, induction of apoptosis, and inhibition of tumor promotion.[1][2][3]

Vitamin A exists as retinol (vitamin A alcohol), retinal (vitamin A aldehyde), and retinoic acid (RA, vitamin A acid). The body cannot synthesize vitamin A; therefore, one must acquire it in the diet through foods such as eggs and milk. Carotenoids are precursors of vitamin A that are synthesized by plants. In the intestines, beta-carotene is converted to retinal then absorbed. Each molecule of beta-carotene converts into two molecules of retinal. Researchers have observed that animals with vitamin A deficiency have epidermal hyperkeratosis, squamous metaplasia of mucous membranes, and precancerous lesions.  

Currently, three generations of synthetic retinoids exist. First-generation retinoids include tretinoin (all-trans RA), isotretinoin (13-cis-retinoic acid), and alitretinoin (9-cis RA). Second-generation retinoids include etretinate and acitretin. Third-generation retinoids include adapalene, tazarotene, and bexarotene. In 1972, Bolag developed two aromatic retinoids: etretinate and acitretin. Acitretin is the retinoic acid metabolite of etretinate. Acitretin is relatively water-soluble in comparison and has a little deposition in adipose tissue. 

FDA-approved Indication

Acitretin is FDA-approved for psoriasis (severe plaque-type psoriasis, pustular psoriasis generalized, pustular psoriasis localized), combination therapy with ultraviolet B (UVB) or psoralen ultraviolet A (PUVA), combination therapy with cyclosporine, combination therapy with biologic therapies. Acitretin is the only systemic retinoid that is FDA-approved for psoriasis and effective as monotherapy.  

Off-labeled Use

Acitretin has been used off-label in dermatology for other uses. In solid organ transplants, acitretin has served as a chemoprevention measure for nonmelanoma skin cancers. Acitretin has also been used for Darier disease, pityriasis rubra pilaris (PRP), and ichthyoses such as lamellar ichthyosis. Additionally, acitretin has been used in Grover disease (transient acantholytic dermatosis), lichen planus, and lupus erythematosus.[4]

Mechanism of Action

Retinoids bind cytosolic retinoic acid-binding protein (CRABP) that acts as the intracellular carrier transporting it to the nucleus. In the nucleus, retinoids impact transcription by binding two families of nuclear receptors: retinoic acid receptors (RARs) and retinoid X receptors (RXR). RAR and RXR families contain three receptor subtypes: alpha, beta, and gamma that are encoded by different genes. RAR can bind with RXR forming a heterodimer. RXR can bind with itself, forming a homodimer, or bind with other nuclear receptors such as thyroid hormone receptor, vitamin D3 receptor, and peripheral peroxidase-activated receptor (PPAR). Dimers of RAR/RXR or RXR/RXR bind to DNA regulatory sequences in the promoter region, retinoid acid response elements (RAREs). Once the ligand binds, it undergoes a conformational change to release co-repressors and recruit co-activators. The retinoid-receptor complex may antagonize the action of other transcription factors, thus working indirectly. Acitretin competes with RA for CRABP. Acitretin can activate but does not bind to multiple RARs.[5][6]

Acitretin has anti-inflammatory and anti-proliferative effects. It normalizes keratinocyte differentiation in the epithelium. It also hinders the expression of proinflammatory cytokines like interleukin-6 (IL-6), migration inhibitory factor-related protein-8 (MRP-8), and interferon-gamma. The agent acts by binding and activating all nuclear subtypes of retinoid X-receptors and retinoic acid receptors.

Pharmacokinetics

Absorption: Generally administered with food and reaches peak plasma concentration in 2.7 hours (2-5 hours).

Plasma Protein Binding: 99.9%

Metabolism: The initial metabolism of acitretin involves isomerization; this differs from isotretinoin, where the initial metabolism is oxidation. Acitretin converts to isoacitretin. Acitretin is ultimately eliminated in the bile as beta-glucuronide derivatives or through the kidneys as soluble metabolites. Acitretin can undergo reverse metabolism to etretinate when acitretin is used in combination with alcohol.

Excretion:  Its metabolites, as well as conjugates of acitretin and cis-acitretin, are excreted in the feces (34% to 54%) and urine (16% to 53%).

Terminal Elimination Half-life: Following multiple-dose, acitretin has a half-life of 49 hours, and cis-acitretin has 63 hours.

Administration

Initial: Administer 25 to 50 mg orally daily as a single dose with the main meal.

Maintenance: Administer 25 to 50 mg orally daily after initial response to treatment. The maintenance dose should have its basis in clinical efficacy and tolerability.

Acitretin is available in 10 mg and 25 mg in hard gelatin capsules. In psoriasis treatment with acitretin, improvement is seen approximately at weeks 4 to 6. The maximum benefit may take between 3 to 4 months. Treatment dosing is initiated at 25 mg orally once daily. When the disease is stable, dosing is often reduced to 10 mg orally once daily or 25 mg orally every other day as a maintenance protocol. Treatment with acitretin leads to decreased plaque thickness, scaling, and pruritis. However, there is not much reduction in body surface area (BSA).

In combination with phototherapy, dosing is recommended at 25 mg orally once daily for two weeks before phototherapy, with a need to decrease the initial dose of ultraviolet (UV) light. If a patient is already on a stable dose of UV light and is starting acitretin, reduce the dose by 30% to 50% approximately seven days after initiation of acitretin.

Specific Patients Population 

• Patient with Hepatic Impairment: There is no dose adjustment guidance in the manufacturer label for patients with hepatic impairment. However, the use of acitretin is contraindicated in patients with severe hepatic impairment.

• Patient with Renal Impairment: A 53 % reduction of acitretin plasma concentrations was observed in patients with end-stage renal disease. The drug was not able to be removed by hemodialysis in these subjects.

• Pregnant Women: It is considered a pregnancy category X medicine. As per the box warning, acitretin must not be given to pregnant patients, patients who intend to become pregnant during therapy, or at least three years following discontinuation of treatment. Significant human fetal abnormalities have been reported with the administration of acitretin.

• Breastfeeding Women: Due to the potential for serious adverse reactions to infants, the manufacturer recommends avoiding acitretin in nursing mothers as the drug presents in breast milk.[7]

• Pediatric Patients: The safety and efficacy of acitretin are not established for pediatric patients.

• Geriatric Patients: In a multiple-dose trial, a 2-fold increase in acitretin plasma concentrations were observed in geriatric patients.

Adverse Effects

A high amount of vitamin A produces a wide spectrum of signs and symptoms primarily of the musculoskeletal, mucocutaneous, neuropsychiatric, central nervous systems, and hepatic systems. Many of the adverse reactions reported using acitretin capsules resemble those of the hypervitaminosis A syndrome. Following adverse reactions are reported in clinical trials and post-marketing experience.[8]

Cardiovascular: Flushing, acute myocardial infarction, thromboembolism, stroke

Immune System Disorders: Hypersensitivity, including angioedema and urticaria 

Nervous System: Headache, pain, rigors; myopathy with peripheral neuropathy which improved upon discontinuation of the acitretin.

Psychiatric: Aggressive feelings, depression, insomnia, self-injurious behavior, and/or suicidal thoughts have been reported. Since other factors may have contributed to psychiatric events, it is not known if they are related to acitretin.

Reproductive: Vulvo-vaginitis (due to Candida albicans)

Skin and Appendages: Thinning of the skin, exfoliation of the skin, xeroderma, nail disease, pruritus, erythematous rash, paronychia, particularly on the palms and soles; nail fragility, madarosis, alopecia, paresthesia, hyperesthesia, and exfoliative dermatitis

Vascular Disorders: Capillary leak syndrome

Miscellaneous: xerophthalmia, visual problems, cheilitis, rhinitis, pseudotumor cerebri, tinnitus, and epistaxis, hepatitis

Laboratory Abnormality: Hypercholesterolemia, increased liver enzymes, increased creatinine phosphokinase, hepatotoxicity, hypertriglyceridemia, hyperglycemia, hypoglycemia, reticulocytosis

Contraindications

Absolute Contraindications

• Pregnancy or woman who is likely to become pregnant

• Non-compliance with contraception

• Nursing mothers

Hypersensitivity to drug or components, pregnancy, intent to become pregnant within three years after treatment discontinuation, severe hepatic or renal dysfunction, chronic abnormally elevated blood lipid levels, or concomitant use with methotrexate or tetracyclines.

It is vital that clinicians who prescribe acitretin to women of childbearing age ensure that they do not get pregnant for at least three years after discontinuing the medication. 

United States Boxed Warning

Female patients should abstain from ethanol during therapy and for at least two months after discontinuing treatment.

Caution

• Concomitant administration with methotrexate increases the risk of hepatic adverse effects.

• Concomitant administration with cyclosporine increases the risk of hypertriglyceridemia.

• Acitretin can undergo reverse metabolism to etretinate with acitretin if used in combination with alcohol.[9]

• The use of other vitamin A compounds can lead to hypervitaminosis A-like toxicities.

• The combination of tetracyclines and retinoids can lead to pseudotumor cerebri and should be avoided.

Individuals prescribed acitretin should receive counsel against giving blood donations for at least three years. The drug is known to remain in the blood for a long time, and the risk of genetic defects is high.

Monitoring

• Lipid profile

• Liver function tests[10]

• Complete blood count (CBC)

• Blood glucose in patients with diabetes

• Evaluation of bone abnormalities and visual problems

• Serum pregnancy testing

Toxicity

Acitretin must be withdrawn all at once in case of acute overdosage. Overdose symptoms are similar to acute hypervitaminosis A (headache and vertigo). In both mice and rats, the acute oral toxicity (LD50) of acitretin was only observed at greater than 4,000 mg per kg dose. In one case report of an overdose, a 32-year old adult male patient with Darier’s disease took 525 mg single dose. Later, he has vomited for several hours; however, he did not experience any other ill effects. One case of fulminant hepatic failure following an intentional overdose of 600 mg of acitretin was reported where the patient demonstrated a rapid recovery and did not require liver transplantation. [11] If any female patients of childbearing potential take an overdose of acitretin, a pregnancy test is recommended at the time of overdose and needed to council patient as per box contraindication and warning related to potential birth defects. Also, need to encourage patients to use contraceptives for at least three years’ duration after the overdose.

Enhancing Healthcare Team Outcomes

Acitretin is frequently used to treat several skin disorders, including acne, psoriasis, lichen planus, and discoid lupus. While the drug is effective, it is crucial for interprofessional healthcare team members, including pharmacists, nurse practitioners, PAs, and primary care clinicians, to know its potential adverse effects. Clinicians should never prescribe the drug to a pregnant female because of the risk of teratogenicity. Also, the FDA has issued several boxed warnings about the risk of hepatitis when combining the agent with alcohol or methotrexate. When prescribing acitretin, the patient must understand the potential adverse effects and the importance of avoiding alcohol. [12][13]

Given the warnings, it is apparent that an interprofessional team is the best means to manage acitretin therapy. Once the prescriber has decided to give the patient the drug, nursing can counsel on the patient’s dosing, administration, and the potential teratogenicity if the patient is female. The pharmacist will verify dosing and perform medication reconciliation, alerting the prescriber of any issues. Nursing can also chart the therapeutic progress of the condition treated, so the prescriber can adjust therapy as needed. Through this interprofessional team paradigm, acitretin can deliver maximal benefit with minimal downside, resulting in better patient outcomes. [Level 5]

Review Questions

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References

1.

Ighani A, Partridge ACR, Shear NH, Lynde C, Gulliver WP, Sibbald C, Fleming P. Comparison of Management Guidelines for Moderate-to-Severe Plaque Psoriasis: A Review of Phototherapy, Systemic Therapies, and Biologic Agents. J Cutan Med Surg. 2019 Mar/Apr;23(2):204-221. [PubMed: 30463416]

2.

Skillen LA, Corry A. Combination therapy of sirolimus and acitretin in solid organ transplant recipients: a new cutaneous adverse event. Clin Exp Dermatol. 2019 Jan;44(1):62-63. [PubMed: 30430627]

3.

Mehrtens SH, de la Hera I, Shankar S. Case of keratoacanthoma centrifugum marginatum treated with acitretin. BMJ Case Rep. 2018 Nov 01;2018 [PMC free article: PMC6214385] [PubMed: 30389737]

4.

Kaushik SB, Lebwohl MG. Review of safety and efficacy of approved systemic psoriasis therapies. Int J Dermatol. 2019 Jun;58(6):649-658. [PubMed: 30246393]

5.

Chen W, Zhang X, Zhang W, Peng C, Zhu W, Chen X. Polymorphisms of SLCO1B1 rs4149056 and SLC22A1 rs2282143 are associated with responsiveness to acitretin in psoriasis patients. Sci Rep. 2018 Sep 04;8(1):13182. [PMC free article: PMC6123456] [PubMed: 30181619]

6.

Guenther LC, Kunynetz R, Lynde CW, Sibbald RG, Toole J, Vender R, Zip C. Acitretin Use in Dermatology. J Cutan Med Surg. 2017 Nov/Dec;21(3_suppl):2S-12S. [PubMed: 28952335]

7.

Drugs and Lactation Database (LactMed®) [Internet]. National Institute of Child Health and Human Development; Bethesda (MD): Mar 17, 2021. Acitretin. [PubMed: 30000426]

8.

Chiricozzi A, Panduri S, Dini V, Tonini A, Gualtieri B, Romanelli M. Optimizing acitretin use in patients with plaque psoriasis. Dermatol Ther. 2017 Mar;30(2) [PubMed: 27998019]

9.

Grønhøj Larsen F, Steinkjer B, Jakobsen P, Hjorter A, Brockhoff PB, Nielsen-Kudsk F. Acitretin is converted to etretinate only during concomitant alcohol intake. Br J Dermatol. 2000 Dec;143(6):1164-9. [PubMed: 11122016]

10.

Sauder MB, Cheung L, Beecker J. Acitretin-induced hepatitis: when to monitor cholestatic enzymes. J Cutan Med Surg. 2015 Mar-Apr;19(2):115-20. [PubMed: 25775629]

11.

Leithead JA, Simpson KJ, MacGilchrist AJ. Fulminant hepatic failure following overdose of the vitamin A metabolite acitretin. Eur J Gastroenterol Hepatol. 2009 Feb;21(2):230-2. [PubMed: 19092674]

12.

Ortiz NE, Nijhawan RI, Weinberg JM. Acitretin. Dermatol Ther. 2013 Sep-Oct;26(5):390-9. [PubMed: 24099069]

13.

Dunn LK, Gaar LR, Yentzer BA, O’Neill JL, Feldman SR. Acitretin in dermatology: a review. J Drugs Dermatol. 2011 Jul;10(7):772-82. [PubMed: 21720660]

Disclosure: Patrick Zito declares no relevant financial relationships with ineligible companies.

Disclosure: Thomas Mazzoni declares no relevant financial relationships with ineligible companies.

Uses, side effects, and interactions

Acitretin is a prescription drug. It is available as an oral capsule. It is used in the treatment of psoriasis.

It is also available as a brand-name drug called Soriatane and as a generic drug.

Share on PinterestAcitretin is an effective treatment for severe psoriasis.

Acitretin belongs to a class of drugs called retinoids. Retinoids relate to retinol, or vitamin A.

Acitretin works by binding to receptors in the body. These receptors help normalize the speed of skin cell growth, reducing the effects of conditions that include psoriasis.

A doctor will likely only prescribe acitretin if other drugs are not effective for a case of psoriasis or if an individual cannot use other psoriasis drugs.

This drug is used on a long-term basis. If prescribed, it is worth calling the pharmacy ahead of time as not all pharmacies stock this item.

The drug is used to treat severe psoriasis.

Psoriasis is a skin condition that causes cells in the outer layer of the skin to grow faster than normal and build upon the surface of the skin. This leads to inflammation and red, thickened areas of skin, often with silvery scales.

Acitretin carries a United States Food and Drug Administration (FDA) black box warning. This is the most serious health warning a drug can carry.

The medication carries the following warnings:

• Severe warning regarding congenital anomalies: Avoid this drug if you are pregnant or planning to become pregnant within three years after stopping this drug. Acitretin can cause severe congenital anomalies. Women who are able to bear children should use effective birth control while on acitretin.
• Liver problems warning: This drug can cause liver problems, include abnormal liver function test results and inflammation. A doctor will run blood tests before prescribing acitretin. These serve to check liver function before and during acitretin treatment.
• Vision problems: This drug can decrease vision in the dark, causing a condition called night blindness that can onset suddenly. Take extreme caution when driving at night while taking acitretin. This condition usually resolves after the course of treatment has drawn to a close.
• Avoid giving blood: Do not donate blood while taking this drug and for at least 3 years after stopping. The presence of acitretin in the blood can harm an unborn baby if given to a woman who is pregnant.
• Depression: This drug may cause depression or aggressive behavior, including self-harming urges. Call a doctor right away if these urges occur. The doctor may recommend a medication change.

Side effects that can occur when taking acitretin include:

• chapped lips
• peeling fingertips, palms, and soles of the feet
• itching
• scaly skin all over your body
• weak nails
• sticky or fragile skin
• runny or dry nose
• nosebleeds
• dry mouth
• joint pain
• tight muscles
• hair loss
• dry eyes
• high cholesterol
• drowsiness

The drug can also lead to serious complications in people that may already have a predisposition towards them, including:

• liver problems
• heart attack
• stroke
• serious skin conditions
• vision problems
• pancreatitis
• blood vessel issues
• high pressure on the brain
• depression
• abnormal muscle or bone changes
• high blood sugar levels

People with the following conditions should completely avoid this drug:

• severe liver and kidney disease
• high cholesterol
• allergy to retinoids or acitretin

Acitretin can interact with other drugs and chemicals in the body to create adverse effects. It is important to know what to take and avoid when on a course of acitretin.

This drug is known to increase the risk of congenital abnormalities, and alcohol can further enhance the duration of this risk to beyond 3 years after stopping acitretin. Avoid alcohol at all costs while taking acitretin.

There are several types of medication to avoid while taking acitretin, including:

• Tetracycline antibiotics: These increase the risk of dangerous pressure levels in the brain.
• Methotrexate: Taking this drug alongside acitretin can greatly increase the risk of liver problems.
• Progestin-only birth control pills, or minipills: Acitretin can reduce the effectiveness of minipills, and it is vital not to become pregnant while taking acitretin. A doctor may stop the minipill and prescribe a different method of birth control.
• Phenytoin: Acitretin can enhance the side effects of phenytoin, including slurred speech, confusion, and coordination or balance problems.
• Vitamin A supplements and other oral retinoids: Taking these drugs with acitretin may cause nausea, vomiting, loss of balance, and blurry vision.

Acitretin is available in its generic form in 10-milligram (mg) and as the brand-name drug Soriatane in 10-milligram (mg), 17.5-mg, 22.5-mg, and 25-mg capsules.

A typical starting dose is around 25 to 50 mg once per day, to be taken with the largest meal. The doctor who prescribed the drug will monitor the reaction to this dosage and make changes if side effects are becoming disruptive.

There is no dosage recommended for children under 18 years of age, as they should not take the medication. Adults over the age of 65 years will often start on a lower dose.

If a dose is accidentally missed, do not take a double dose next time. It is vital never to miss a dose, as this can reduce or block the effectiveness of the drug.

Here are several extra considerations to bear in mind when transporting, acquiring, or storing acitretin:

• Always take acitretin with food.
• Always carry the medication on your person. When flying, never put it into a checked bag but keep it in the carry-on luggage.
• Airport x-ray machines will not damage the medication.
• Always carry the original prescription-labeled box, as airport security may wish to see this.
• Avoid putting medication in the glove compartment of a vehicle or leaving it in the car. Be sure to avoid doing this in extreme temperatures.
• Many insurers require pre-authorization before approving this treatment. Contact your insurer ahead of time.
• Wear protective clothing in the sun, as acitretin makes the skin more sensitive.
• Prescriptions for acitretin are not refillable.

Retinol: application, effect, tips for use – Ingredients – Blog

We are used to the fact that most of the ingredients in the composition of cosmetics perform one function well: some moisturize, others relieve irritation, others promote renewal. But this rule does not apply to retinol – it masterfully copes with almost any problem, if you find the right approach to it. Anti-aging effect, reduction of pore relief, fight against rashes, lightening pigmentation, stimulation of renewal, increase in elasticity … A solid list, right?

Like other substances with a powerful active effect, it has its own characteristics. To begin with, the first time you use it, the skin condition may visually worsen before you see the first positive results. The most important thing here is not to stop halfway, but to continue the course of treatment / care. In addition, as part of cosmetics, this component is available in various forms and concentrations, so if an undesirable reaction occurs, it is easy to choose another option.

What is retinol?

Retinol is a form of vitamin A (however, the same name is often used as a general term for all vitamin A derivatives – retinoids).

This component has long been successfully used in cosmetics designed to correct age-related changes:

• wrinkles;
• tissue density reduction;
• age spots;
• uneven terrain;
• roughness and roughness;
• dullness, loss of radiance.

In addition, it is used in the treatment of acne and to get rid of post-acne marks.

What effect does it have on the skin?

• Smoothes the texture. Research shows that the natural process of skin cell renewal slows down after age 25. Retinol brings it back to optimal levels, helping to restore freshness, smoothness and even tone.
• Fights wrinkles. Retinol stimulates the production of collagen and elastin, which, in turn, fill wrinkles, smooth creases and restore elasticity.
• Clears pores. On oily and problematic skin, retinol will show itself as an effective assistant in the fight against rashes. It balances sebum production, preventing clogged pores and inflammation.

How does it work?

Penetrating deep into the skin, retinol stimulates the formation of new cells and restores connective tissues. Using it for the first time, you will most likely go through a process called retination, characterized by redness and intense flaking. By applying a product with retinol to your face, you force the cells to reorganize to work in a new mode, which implies accelerated renewal. This happens gradually, adaptation can take some time – usually up to 4 weeks.

In general, flaking and redness on first use is completely normal. If they are not accompanied by itching and burning, you should not immediately abandon the new care, just wait until the body “gets used” to it. However, if the symptoms do not disappear after 28 days of use, this is a reason to contact a cosmetologist or dermatologist in order to select an alternative form or dosage of the ingredient.

How to use it correctly?

In order to make the adaptation process comfortable, in the case of this active ingredient, the rule of “less is more” should be followed.

1. For the first acquaintance, it is recommended to choose a product with a low concentration.
2. Apply a small amount of product (pea size) at night a couple of times a week to see how tolerant you are. The action of retinoids persists for 72 hours.
3. If the skin reacts positively to the new ingredient, you can gradually increase the frequency of use and concentration. In case of severe irritation, on the contrary, it is recommended to reduce it – for example, by mixing it with a fat cream.

There is a concept of “retinol ladder”, which implies a gradual increase in regularity:

• 1-2 weeks – every three days,
• 3-4 weeks – every two days,
• From 5 weeks – every day.

Retinol can be applied all over the face, however it is recommended to avoid the lash line when used around the eyes.

What kind of skin is it suitable for?

Due to its broad spectrum of action, this ingredient is suitable for all skin types, however, the degree of sensitivity must be taken into account: skin prone to irritation requires special care in terms of frequency of use and concentration.

You can start using retinol to fight the first age-related changes (and prevent them) as early as 25 years old.

When will the result be noticeable?

It depends on the concentration, frequency of application and individual characteristics. The first improvements can be seen after just a few applications: at the end of the retinization period, the face becomes smoother, the tone evens out, and the pores are cleared.

If you have chosen this component for skin rejuvenation, keep in mind that the process will be quite lengthy. However, patience pays off: with regular, long-term use, retinol significantly increases the level of collagen in the skin, improving its density in deep layers and preventing the appearance of new wrinkles.

Studies show that wrinkle reduction is observed in most patients after 3 months, and with longer use, the condition continues to improve. So, after 6 months, a sufficient amount of collagen and elastin accumulates in the skin in order to gradually begin to fill in existing wrinkles, and dark spots lighten due to accelerated renewal.

Types and uses

Depending on the molecular structure and time of the first synthesis, retinoids are divided into generations. Substances similar in structure to the vitamin A molecule, called non-aromatic, got into the first generation, monoaromatic compounds into the second, polyaromatic compounds into the third, and, finally, the fourth generation combined pyranones.

Topical retinoids

Topical retinoids are included in topical formulations. Most often, first-generation retinoids are found in this format – the most studied and “predictable”.

To be effective on the skin, any form of vitamin A must be converted to retinoic acid (tretinoin) by its enzymes. So, the closer the molecule of the active substance in structure to the tretinoin molecule, the stronger the effect.

Consider the form of vitamin A, retinyl palmitate: under the influence of enzymes, it is first converted to retinol, then to retinaldehyde, and only then to tretinoin. The effect of a drug with retinyl palmitate will be less active than, for example, a drug with tretinoin that does not require conversion.

On the other hand, the more active the substance, the greater the likelihood of side effects. When choosing between different ingredients, the level of skin sensitivity should be taken into account: in many cases, a long transducer chain is more of a plus than a minus. Yes, the result will not be so fast, but with a high probability the retinization process will go smoothly and smoothly.

Let’s take a closer look at common forms:

Tretinoin. Used in pharmaceutical and professional products to combat acne, hyperpigmentation and hyperkeratosis.

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Triple Power Overnight Cream, 50 ml

Effectively restores the protective barriers of the skin

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Triple Power Brightening Serum, 30 ml

Evens tone, stimulates metabolic processes

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Retinaldehyde (Retinal). Popular in cosmetics. In the chain of transformations, it is one step ahead of tretinoin. It has good efficiency already at a concentration of 0.025-0.05%, but due to possible instability it is somewhat less common in cosmetic products than other forms.

Anti-aging cream-gel, 50 ml

Prevents the appearance of wrinkles, improves skin firmness and elasticity

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-10%
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Anti-aging serum, 30 ml

Models the oval of the face, has a moisturizing and revitalizing effect

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-10%
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Retinol Lift wrinkle smoothing capsules, 10 pcs

INTENSIVE REJUVENATING ANTI-AGE CARE

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Retinol. The most common retinoid, relatively inexpensive, but effective. For stabilization, it is often found in an encapsulated form: the molecules of the active substance are enclosed in capsules that prevent contact with other components in the composition of the product and are absorbed only when passing through the lipid layer.

Retinol Pure Serum, 30 ml

Powerful regenerating and lifting effect

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Intense Concentrated Anti-Aging Eye Care, 15 ml

AGAINST WRINKLES, BAGS AND DARK CIRCLES UNDER THE EYES

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-20%
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Restoring Cream, 50 ml

INTENSIVE RESTORATION AND RENEWAL OF THE EPIDERMIS

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-10%
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Retinyl Palmitate. Ester of retinoic acid, which has a very gentle effect. In cosmetics, this component is most often found as an antioxidant at a concentration of about 0.5-2%, and for a pronounced effect (at the level of retinol) a sufficiently high concentration is required.

Multi-Action Serum, 150 ml

intensive care for aging skin

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Intensive anti-deep wrinkle serum, to even out complexion and skin texture B3, 30 ml

Intensive anti-ageing serum

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-20%
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Systemic retinoids

Systemic retinoids are used for internal use in the complex therapy of skin diseases. The most common ones are:

Isotretinoin. It is used to combat moderate to severe acne (as part of such medical products as Roaccutane, Accutane and Acnecutane) and is considered the only drug that cures acne. It affects all the factors that cause the disease: the production of sebum, clogged pores and the growth of bacteria.

As with topical retinoids, isotretinoin often causes skin deterioration in the first weeks of treatment followed by gradual recovery. In addition to the period of exacerbation, isotretinoin has other possible side effects (for example, the development of depression, inflammatory bowel disease), so treatment should be carried out strictly under the supervision of a physician. During pregnancy, use is strictly prohibited.

It is important to follow the dosage prescribed by the medical specialist and continue the prescribed course of treatment even after the disappearance of external imperfections.

Acitretin and Etretinate. Retinoids of the second generation are prescribed for various types of psoriasis, impaired keratinization (as part of Tigazon and Neotigazon preparations). They inhibit the growth of cells in the outer layers of the skin and stabilize its cellular structure, helping to cope with peeling.

As in the case of isotretinoin, treatment should be carried out strictly under the supervision of a physician and is strictly not allowed during pregnancy.

Retinol can be a powerful help in solving many problems: from acne and enlarged pores to wrinkles, loss of elasticity and age spots. Although its action is well studied, it can behave completely differently on different skin, so the selection of a suitable remedy must be left to specialists, especially when it comes to systemic use.

Contact a cosmetologist or dermatologist to draw up a system and schedule of care: based on your needs and needs, the doctor will be able to choose a convenient form and give recommendations for use – you just have to observe the pleasant changes and enjoy the effect!

Author – Marina Kanukhina

Local and systemic retinoids – Professor Svyatenko Medical Center

Retinoids are substances that are derivatives of natural vitamin A, as well as synthetic analogues that are similar in pharmacological action.

General principles, classification and structure

Natural and synthetic

Natural (retinol, retinaldehyde, retinyl esters) enter the human body with food, where they are transformed into active molecules of retinoic acid and its isomers. These substances may also be used medicinally.

Synthetic (etretinate, acitretin, adapalene, tazarotene) are analogues that are synthesized for specific therapeutic purposes to minimize side effects and optimize their action.

Local and systemic

Local retinoids – retinol, retinaldehyde, isotretinoin, adapalene, tazarotene. Currently, only isotretinoin is prescribed in dermatology, both orally and systemically.

Systemic Retinoids may be given orally to treat skin disorders that involve a large area of ​​the skin and do not respond to topical retinoids. Currently available oral isotretinoin for the treatment of severe acne, acitretin and etretinate for the treatment of psoriasis and hereditary keratinization disorders.

Mechanism of action

Retinoids are fundamental in embryogenesis, reproduction, vision and control of cell growth, differentiation of many mature tissues. It is the latter two activities that are associated with their use in dermatology for psoriasis, hereditary keratinization disorders, topical acne treatment and skin aging .

One of the most pronounced pharmacological actions of retinoids is the inhibition of the secretion of the sebaceous glands. This effect is very specific for systemic isotretinoin, while topical isotretinoin does not inhibit the secretion of the sebaceous glands.

Indications

Topical retinoids

The main indications for topical retinoids are acne and photoaging of the skin .

Topical retinoids are prescribed for mild acne in combination with antibacterial drugs, because they act only comedolytically and have neither a sebosuppressive effect nor an effect against Propionibacterium acnes.

Currently topical retinoids are used to treat actinic keratosis, epidermal melasma (preferably in combination with hydroquinone). Other indications include various conditions of hyperkeratosis, rosacea, and treatment of atrophy caused by topical steroids.

Retinoid products

Retinol is available in Europe at 0.075% for the treatment of skin aging.

Retinaldehyde – at a concentration of 0.05% for the treatment of photoaging of the skin, as well as adjuvant therapy for mild acne, rosacea, prevention of atrophy due to the use of topical steroids and seborrheic dermatitis.

Retinoic Acid – Available in 0.025, 0.05 and 0.1% to treat acne and photoaging (0.05%).

Isotretinoin (13-cis-retinoic acid) – at a concentration of 0.05% for the treatment of acne, at a concentration of 0.1% in the form of a gel. With mild acne, the drug is similar in activity to retinoic acid 0. 025% and causes less irritation.

Tazarotene – 0.05% gel for the treatment of mild psoriasis.

Systemic retinoids

13-cis-retinoic acid (isotretinoin, roaccutane, accutane) was introduced into practice more than 15 years ago and today remains the only drug that cures acne by acting on all etiofactors that cause the disease: products sebum, comedogenesis and P.acnes colonization.

The drug can be used to treat rosacea, cellulitis dissecans of the scalp, confluent and reticular papillomatosis, generalized granuloma annulare, O’Brien.

Acetretin and etretinate are prescribed for various types of psoriasis, impaired keratinization, pre-malignant skin lesions, cutaneous T-cell lymphomas. These drugs are considered the first choice therapy for palmoplantar and generalized pustular psoriasis. The plaque preparation reacts differently to both drugs. The maximum effect is observed not earlier than after 3 months. taking retinoids as monotherapy.

Complete remission

Complete remission requires additional treatment: topical corticosteroids, anthralin (dithranol), UVA phototherapy (PUVA), UVB phototherapy, or topical calcinotriol.

Among the various types of ichthyosis, congenital nebulous ichthyosis (erythro- and non-erythrodermic lamellar ichthyosis) has the best results. In severe forms of Darier’s disease, therapy is prescribed cautiously with very low doses to prevent worsening of the disease.

Etretinate and acetretin are effective in the treatment of premalignant skin lesions, including tumors induced by human popillomaviruses and actenic keratoses. With basal cell nevus syndrome and xeroderma pigmentosum, these drugs dramatically reduce the number of malignant foci.

Treatment of with etretinate may result in clinical improvement in cutaneous T-cell lymphomas (mycosis fungoides or Cesari syndrome) without visceral involvement. A more pronounced effect is obtained in combination with PUVA therapy or interferon-α.

Side effects. Contraindications

Teratogenic risk

Women of childbearing potential must provide a negative pregnancy test and effective contraception during systemic retinoid therapy. Teratogenic risk for topical retinoids has not been established, but their use during pregnancy is not recommended.

Side effects on the skin and mucous membranes have individual differences and are associated with the dose of the drug, observed with systemic administration of etretinate, acetretin, isotretinoin.

Topical retinoids cause burning, erythema, flaking.

Systemic retinoids are not prescribed for patients taking hepatotoxic drugs.

Dosing schedules

Topical retinoids are taken once daily per day, usually at night. Irritation may occur at the beginning of treatment and is minimized when the drugs are taken every other day.

Systemic Retinoids – Start at ¼ of the recommended dose and increase progressively to avoid skin and mucosal side effects.