Instructions for use of AKNEKUTAN® capsules

From this article you will learn:

• what is isotretinoin,
• Acnecutane and Roaccutane - instructions, reviews,
• differences between these drugs.

Isotretinoin is a retinoid that is also known as 13-cis-retinoic acid (Figure 1). This chemical compound is an isomer of tretinoin (trans-retinoic acid), which, like isotretinoin, is a structural analogue of vitamin A. Isotretinoin is best known as an oral systemic retinoid that is used to treat severe forms of acne. The latter include, for example, nodular and conglobate forms of acne, as well as forms of acne that are resistant even to oral antibiotics.

Systemic retinoids containing isotretinoin include drugs such as Acnecutane and Roaccutane. As we said above, they are intended for oral administration (available in capsule form). However, there are preparations with isotretinoin for external use that can be used to treat photoaging of facial skin. These drugs include those available on the Russian market - Retasol drugs, as well as retinoic ointment.

Isotretinoin (13-cis-retinoic acid) –

Reviews from dermatologists about Acnecutane and Roaccutane are the most positive, because in fact, these drugs with isotretinoin have made a real revolution in the treatment of severe forms of acne. They have improved the quality of life for many patients, including preventing the formation of scars. Isotretinoin therapy provides complete remission of the disease in almost all patients with acne, and after completion of the course of therapy, remission can last up to several months or even years.

However, therapy with systemic retinoids is associated with the risk of quite severe side effects, which we will discuss in detail below (they occur especially often if the dosage is incorrectly selected). Girls and women should take into account that these drugs have a pronounced teratogenic effect, and therefore they are prohibited both during pregnancy and breastfeeding. In addition, the entire period of use of the drug will require a two-level contraceptive system (both oral contraceptives and condoms).

How much do Roaccutane and Acnecutane cost in pharmacies -

For 2021, the price for Roaccutane will be from 1900 rubles - for a package of 30 capsules of 10 mg. It should be noted that this drug can now not be purchased in every pharmacy, which is apparently due to the current re-registration of the drug on the Russian market. For Acnekutan, the price for a package of 30 capsules of 8 mg will be from 1650 rubles, and for a package of 30 capsules of 16 mg - from 2600 rubles.

Analogs of Roaccutane include such drugs as Sotret (India) and Verocutan (Russia). The first one costs from 1350 rubles per pack of 30 capsules of 10 mg. As for the Russian drug Verokutan, it has currently disappeared from sale.

Roaccutane and Acnecutane (mechanism of action) –

The drug Roaccutane is produced by a pharmaceutical company (Switzerland), and the drug Acnecutane is produced by a pharmaceutical company (Croatia). The drugs contain isotretinoin and are practically equivalent to each other, however, in the production of the drug Acnekutan, the “Lidose” technology is used, which makes it possible to reduce the daily and course doses of isotretinoin, and therefore the risk of side effects during treatment. Lidose technology is a Belgian development.

Indications for use –

• severe forms of acne (nodular, conglobate, fulminant),
• forms of acne with a risk of scarring,
• acne that cannot be treated with topical medications or oral antibiotics.

These are the indications you can find in the official instructions for the drugs Roaccutane and Acnecutane.
However, according to numerous clinical studies and the most authoritative textbook on dermatology in the world, Fitzpatrick's Dermatology (we use the 8th edition), isotretinoin preparations are also very effective for the treatment of gram-negative folliculitis and facial pyoderma. Gram-negative folliculitis is exactly the complication that very often develops in patients with acne after using local and systemic antibacterial drugs. The mechanism of action of isotretinoin for acne -

The mechanism of action of isotretinoin has not been fully studied, but it is known that it quite strongly suppresses the activity of the sebaceous glands. It suppresses both the activity of sebocytes (these are cells in the sebaceous glands that secrete fatty secretions) and their proliferation, i.e. reproduction. Accordingly, as a result of a course of isotretinoin, both the secretion of sebum (secretion of the sebaceous glands) decreases and the sebaceous glands decrease in size.

Studies have shown that after completing the course of treatment with isotretinoin, in most patients the usual activity of the sebaceous glands returns only after 2-4 months, however, in some patients this effect can be expressed even up to 1 year. In addition, isotretinoin helps indirectly reduce the number of P. acnes bacteria, normalizes the processes of follicular keratinization, and also has anti-inflammatory activity.

The latter, however, requires clarification, because at the first stage of drug therapy with Acnecutane or Roaccutane - on the contrary, acne may worsen. This effect usually lasts up to 2 weeks and its appearance does not require discontinuation of the drug, and to reduce the symptoms of acne exacerbation, reduced dosages of isotretinoin are usually used at the first stage of treatment.

Isotretinoin: before and after photos

Important: Keep in mind that it usually takes at least 4 weeks to notice the first positive changes. In addition, during the first 1-2 weeks, your acne may worsen (this is normal with systemic use of isotretinoin). The full course of treatment will last from 16 to 24 weeks.

Acnecutane - interesting cases in everyday practice

About the article

33557

1

Regular issues of "RMZh" No. 22 dated September 17, 2013 p. 1100

Category: Dermatology

Authors: Ustinov M.V. M.V. 1, Sirmais N.S. 1 2nd Central Clinic of the Ministry of Internal Affairs

For quotation:

Ustinov M.V.M.V., Sirmais N.S. Acnecutane – interesting cases in everyday practice. RMJ. 2013;22:1100.

Retinoids are one of the few groups of pharmacological drugs intended almost exclusively for the treatment of skin diseases, incl. tumor, as well as age-related changes, i.e. almost strictly for dermatological and cosmetology practice. Even topical corticosteroids were initially mostly developed as drugs for systemic use in various serious diseases and for emergency care, and only then did they find their niche in dermatology. Retinoids are representatives of both aromatic and non-aromatic compounds, they are both derivatives of vitamin A and substances with other chemical structures, their final mechanism of action is united through RAR and RXR retinoid nuclear receptors of various isoforms [7, 9]. That is why at the present stage they are classified as supersteroids, and their effect is assessed not so much as a “vitamin” itself, but rather as a hormone-like one [3]. Vitamin A derivatives perform many essential and diverse functions in living tissues of the body. They play a vital role in the maintenance of vision, in the differentiation of keratinocytes, promote the growth of bone tissue, suppress neutrophil chemotaxis, sebocyte proliferation and sebum production, increase cell tumor resistance and drive genes that can suppress tumors.

Retinoids are widely used to prevent skin aging, incl. in anti-aging cosmetics. Vitamin A derivatives are involved in the renewal of skin cells, their communication and facilitate their normal functioning, and with age these processes fade away. The anti-aging effect when using retinoids is mainly due to the following mechanisms: – acceleration of cell cycles in the upper layers of the epidermis and the promotion of “young” layers of epithelial tissue, which make the complexion bright and smooth; – stimulation of collagen production, which helps smooth out small wrinkles on the face and even out the skin structure; – narrowing enlarged pores, blocking the sebaceous glands and normalizing sebum regulation; – a decrease in melanin levels, with hyperpigmentation, such as melasma; – protecting the skin from the action of harmful free radicals due to antioxidant activity [9, 11]. Retinoids are usually classified by generation, but behind this distinction lies not only the time of synthesis of the drugs, but also their structure. I generation – non-aromatic retinoids: retinol, tretinoin, isotretinoin, alitretinoin. II generation - monoaromatic retinoids: etritinate, acitretin, motretinide. III generation – polyaromatic retinoids: tazarotene, bexarotene, adapalene. IV generation – molecules under development: for example, Seletinoid G is a substance that well prevents both skin aging itself and its photoaging, while lacking irritating properties [11]. Systemic retinoid preparations are used to treat skin diseases such as psoriasis, various acneiform dermatoses, tylotic eczema, skin lymphomas, actinic keratosis, and to a lesser extent seborrheic keratosis, HIV-associated Kaposi's sarcoma, as well as other diseases with lesions of the follicular apparatus and keratinization disorders . Depending on the specific drug, the set of indications differs, and, nevertheless, when such dermatoses are combined in one patient, a positive effect of the selected derivative is usually observed on all retinoid-sensitive diseases to one degree or another [8–10]. Despite the traditionally high effectiveness of systemic retinoids, their use in our country is limited. The reasons for this are not only the actual contraindications to such therapy, but also the extremely high cost of the course of treatment, the fear of absolute teratogenicity, expected adverse events and the impact on biochemical homeostasis. In this article, we present our observations on the use of isotretinoin in a combination of severe forms of acne and other retinoid-sensitive dermatoses, as well as the experience of its use in acne in combination with metabolic disorders. The appearance on our market of the isotretinoin drug – Acnecutane* – at a more affordable price compared to the original drug, increases the number of potential patients with severe forms of acne who agree to therapy with this drug [1, 2, 5]. And although patients associate most refusals of such treatment not with the price, but with the fear of unwanted and side effects, in practice it turned out that the price is still of leading importance, increasing patient compliance with isotretinoin therapy by approximately 25% or more. We have already mentioned earlier that we allocate time for patients to familiarize themselves with official information, prices and reviews of drugs on Internet resources. This is done, among other things, due to the fact that the time of admission to one patient at the CVD is limited, and the information on drugs is quite voluminous; In addition, this approach for schoolchildren and students involves parents in the treatment process, their financial support and monitoring the implementation of doctor’s prescriptions. As a rule, after such an introduction, according to our latest estimates, only 20–25% of patients agree to therapy (a year ago there were 10–15%). At an outpatient appointment at a medical center, overcoming the problem of disagreement with the proposed use of isotretinoin (essentially, “retinoidophobia”) is always greatly complicated by the time limit for the appointment. Despite the fact that a wide arsenal of methods for overcoming disagreement is available in the literature (for example, K.N. Monakhov and E.S. Svetlova identify 5 psychodermatological models for solving this problem), these models are still applicable mainly in institute clinics and private practice , their implementation in practical healthcare, unfortunately, is limited by significant time costs. The most effective and accessible is the so-called “behavioral” model of overcoming disagreement, which focuses on environmental rewards (self-realization, career growth, etc.), this model increases the number of patients who agreed to therapy by 2–2.5 times [ 6]. Based on our practice, for the age of 15–19 years, we can form a typical average portrait of a patient in Moscow who is highly likely to agree to treatment with isotretinoin: with a 65–75% probability, this will be a young man suffering from severe acne (III–IV degree severity), with manifestations of post-acne, who have completed a course of therapy with various anti-acne drugs, a 10th-11th grade school student or a 1st-2nd year university student, mostly doing well in all subjects, socially adapted, without visible deviations in behavior, career-oriented and with aspirations to success and self-realization. It is likely that in other age categories, in private practice or university clinics, in other geographical areas, such a portrait will not be so obvious, but, nevertheless, we will be glad if our observation is useful in solving the problem of non-consent to isotretinoin treatment in patients with severe forms of acne. In a relatively short period of time since the appearance of the drug Acnecutan on the market, in our practice there have been several interesting cases when patients with severe forms of acne had concomitant skin diseases or metabolic changes according to the results of laboratory examination. The first patient, a 17-year-old boy to whom we prescribed Acnekutan, was on a follow-up follow-up with a diagnosis of “scalp psoriasis” for 6 years at the start of therapy, with an almost continuous wave-like course of the disease. By this time, the patient had tried various medications, dietary supplements, and diets. According to him, medical fasting had the most lasting effect, but it led to asthenia and difficulties in communicating with parents. The patient practically did not pay attention to acne during this period, because... the dominance of psoriasis, from his point of view, was obvious. In the 10th grade, during a period of incomplete remission, the patient “suddenly” noticed manifestations of a severe form of acne and, at the next preventive visit, complained of a rash. When examined on the skin of the face and, to a lesser extent, the upper back, there was an abundant inflammatory papulopustular rash, multiple comedones, nodular elements with a total number of more than 20. This psychologically complex patient was offered Acnecutane as a drug that, due to its pharmacological action, could lead to double positive result. To our surprise, the patient easily agreed to therapy; moreover, he helped us convince the parents who did not agree during the first conversation. The prescribed therapy was the maximum dose, both course and daily; the course of treatment took 5.5 months. During the period of initiation of therapy, the patient had a transient increase in transaminases, but he refused our proposed dose reduction, because all other undesirable effects (in particular, the phenomena of cheilitis and retinoid dermatitis) were minimal and in his case were well compensated by cosmeceuticals. The symptoms of psoriasis began to decrease by the end of the first month of therapy and were completely leveled out by 3.5 months. from the start of therapy. By 4 months During the therapy, the manifestations of acne were practically minimized; by the end of the therapy, the skin acquired a matte tint with post-acne elements in the form of single, barely noticeable scars, which did not bother the patient at all. The patient was satisfied with the result of the therapy, but by the time of the next preventive examination, 4 months later. After treatment, he noted the appearance, against the background of stress (final exams), of isolated small, non-infiltrated pinkish spots on the scalp with virtually no peeling, barely visible against the background of healthy skin. The symptoms of the “psoriatic triad” and “psoriatic crown”, identified earlier, were not detected during the follow-up examination. The second patient, also a 17-year-old boy, came with his mother for another examination. This patient has been under follow-up care for psoriasis for 4 years, but his process is hereditary and widespread, with typical manifestations in various anatomical areas and a fairly aggressive course. At the same time, the severity of the acne disease in this patient was slightly lower: only the face is affected, inflammatory papulopustular elements are not so abundant, the number of nodular elements is 11. The prescribed total course dose is the maximum by weight, but the patient did not receive the maximum daily dose by weight (48 mg). I couldn’t afford it financially, but I also couldn’t afford good cosmeceuticals, which worsened the subjective tolerability of the drug. There were no fluctuations in biochemical parameters during monthly monitoring. This led to the decision to reduce the dose to 32 mg and extend the duration of therapy to 7.5 months. The response of acne to therapy in this case was quite rapid: within 2 months. the main elements were resolved, but, having reached the level of resolution of nodular-cystic elements, the positive dynamics for no apparent reason slowed down and sluggishly resolved by the end of therapy, achieving only at the end of the course a result acceptable to us, although a result accepted by the patient as very good was achieved in relation to acne already after 3 months. treatment. Despite the duration of therapy, it was not possible to achieve complete remission of psoriasis, however, the resolution of psoriatic elements reached about 80% both in area and in the degree of infiltration, which, according to the patient himself, was not achieved by other methods of therapy from the very beginning of the disease. At the next appearance for follow-up after 3 months. After the end of treatment, stability of the results achieved for both diseases is noted. After 6 months The patient noted a slow progression of psoriatic rashes, but, having felt the effect of retinoids after isotretinoin therapy, he is determined to undergo a course of treatment with acitretin in case of the next severe exacerbation of psoriasis. The third patient of the same gender and age was registered at the dispensary with a diagnosis of atopic dermatitis; exacerbations of the disease were mainly in winter and had no obvious connection with food or inhaled allergens. The rashes were not abundant with typical localization, dry skin, the main manifestation of the pathological process was lichenification and damage to the hands with dryness, peeling, hyperkeratosis and cracks. At the same time, in general, the disease was not severe and was under pharmacological control using intermittent therapy with a good effect. The patient had acne for 3 years; he constantly underwent cosmetic cleansing, used specialized cosmetics and external preparations. There were no nodular-cystic elements at the start of therapy; inflammatory papulopustular elements involving the face and upper torso were observed. Despite the absence of nodular-cystic elements, the patient developed post-acne in the form of small atrophic scars and persistent pinpoint hyperpigmentation; in addition, none of the methods gave the desired result, and isotretinoin was prescribed at the request of the patient’s parents. During the treatment period, basic therapy for atopic dermatitis was not carried out, and while taking Acnecutan, the phenomena of lichenification in the area of ​​the elbows and extensor surfaces of the shoulders and hips, dryness and peeling of the hands resolved almost completely within a month, despite the time of year when the patient usually experienced an exacerbation diseases. However, the positive effect on the course of atopic dermatitis, having reached a maximum a month after the start of taking isotretinoin, began to gradually decrease after another month, and by 4.5 months. from the start of therapy, the patient again developed noticeable clinical signs of atopic dermatitis in the form of moderate lichenification of the elbow bends. These rashes were less pronounced and gave way to seasonal remission. The patient was transferred to D-registration in the adult office; it was not possible to track long-term results, because he did not show up for the reception. Fourth case: a young man, age 22, has been suffering from isolated Unna-Tost keratoderma of the soles since early childhood. Receives specific treatment in courses 1–2 times a year with keratolytics and Aevit, 1 capsule 2 times a day. for 30 days 2 times a year, without complete and lasting effect, constant mycological control. Acne since the age of 14, severity level II–III, courses of external therapy are irregular with unstable and incomplete effect, citing being busy with school and work, which makes it difficult to use topical agents. The prescribed dose was 32 mg/day. for a period of 9 months. with a patient weight of 74 kg. Acne symptoms were completely relieved in the middle of the course of therapy, plantar hyperkeratosis was almost completely resolved by the end of therapy, local hyperhidrosis was reduced by cosmeceuticals. The result achieved by the patient was assessed as excellent. Acne recurrence after 6 months. there were no observations after the end of therapy; the negative dynamics of the keratoderma clinic were insignificant, incl. and due to the recommended active ongoing management of foot hyperhidrosis. At the moment, the patient has graduated from university and moved to another city. It was not possible to track the long-term effect. Another case, in our opinion, of interest to practicing physicians, demonstrates the possibility of using Acnecutane against the background of insulin-dependent diabetes mellitus type 1 (IDDM type 1). Our patient: a young man, 28 years old, using insulin for more than 15 years, his acne can be classified as severity grade III, previous treatment includes most of the external medications used and basic cosmeceuticals, periodically two-week courses of systemic antibiotics (doxycycline monohydrate, erythromycin, josamycin ). The effect of treatment is insignificant, while the patient repeatedly asked to be prescribed isotretinoin, but was previously refused due to the presence of a disabling disease. Having assessed the state of metabolism according to the analyzes performed, we came to the conclusion that the patient was well compensated, the selected doses of insulins of different periods of action were adequate to the course of the disease. Taking into account the metabolic effect of Acnecutane, the drug is prescribed in a daily dose of 50% of the maximum. Monthly biochemical monitoring did not reveal significant fluctuations. The patient took the drug for 9.5 months, eventually achieving a complete cure. A similar successful case of treatment of grade III acne with Acnecutane against the background of type 1 IDDM was carried out at the EuroFemme clinic (chief physician G.N. Makova) with a comparable approach to dosing and observation. We diagnosed another metabolic disorder - obesity - in a 14-year-old girl (height 172 cm, weight 101 kg). Externally, the teenager corresponded to 18–19 years of age, menstruation since 9 years, acne since 10 years, III degree of severity for a year. By the time of our initial examination, she was permanently and without effect taking courses of external treatment; for a long time, the parents refused to take isotretinoin drugs systemically, but, seeing the failure of attempts and the increasing depressive state of their daughter, they agreed to a course of Acnekutan. In this case, the drug was very well tolerated. It should be noted that people with a pronounced layer of subcutaneous fat, according to our observations, tolerate the drug better, the positive effect sometimes occurs a little later, but the effectiveness objectively and subjectively is ultimately better than in people with an asthenic physique. Acnecutane is prescribed at a daily dose of 80% of the maximum; the course of therapy is 7 months. in order to reduce the average monthly cost of treatment. By 4 months treatment, a pronounced positive clinical effect was achieved, no signs of depression were observed, the patient began to lose weight, and by the end of treatment the weight dropped to 89 kg! We can state that the girl was focused on her problems with acne, almost did not leave the house and tried to smooth out her depressive state by getting positive emotions from food (the effect of “eating” depression). Having received a positive effect from the treatment, which was not difficult for her, which increased her emotional background and self-esteem, she increased the number of active walks, reduced her consumption of easily digestible carbohydrates and began to lose weight, believing that this problem could be solved. Recall that one of the described side effects of retinoids is precisely the depression, which is reflected in the instructions for the drugs, but on this example we clearly show the opposite effect, i.e. The presence of depressive states in patients with acne and provoked by this disease is not a contraindication for therapy of isotretinoin. With competent informing about the terms of positive changes in the treatment of retinoids, acne is injudicated depressive conditions often do not need other types of pharmacocorrection. The experience of prescribing the drug with metabolic changes such as hypercholesterolemia and hyperbilirubinemia can be interesting. Treatment of a 16 -year -old girl of normosthenic physique, cholesterol in which is 1.5 times higher than the age norm without a visible organic cause (the entire period of study it ranged at 9.2–9.4 mmol/l), an acne in a daily dose of 50% From maximum did not affect this indicator. Hyperbilirubinemia, especially not exceeding 26 μmol/l (30% of the level from the upper threshold of the norm), is not such a rare diagnostic find when examining adolescents in the CVD, but the diagnosis of benign hyperbilirubinemia with a bilirubin level of about 40-50 μmol/l, we observed two Patients with acne III and IV severity. The results of observing the level of bilirubin against the background of therapy with acnectan can be recognized as paradoxical - it is reduced, and noticeably. Even with a normal initial level of bilirubin against the background of therapy, it decreases by 2-3 points, and in the aforementioned patients, he dropped to normal values ​​by the end of the 5th month. Therapy, the parents of adolescents stated that they could not achieve such a decrease in previously conducted diets and drugs. The mechanism of development of this effect is incomprehensible, because At the same time, the often identified decrease in bilirubin is accompanied by an increase in ALT, AST and GGTP (often within normal values); Such a multidirectional movement of biochemical indicators of the hepatic profile requires further study. This effect is not expressed in the original drug, and we believe that this is how the combination of the active substance with the Lidose matrix, which underlies the “solid solution” technology, which increases its bioavailability. In conclusion, I would like to note that for isolatinoin in general and for acnectan, in particular, to one degree or another, it is characteristic of all systemic retinoids, a positive effect on the course of various acne dermatoses, dermatoses, accompanied by seborrheic background, and dermatoses with hyperkeratosis and proliferative discos . The positive impact is expected not only for the above diseases, but also with chronic folliculitis, ladown-landing keratoderma, tylotic forms of eczema. System retinoids are one of the most promising classes of drugs for dermatology, the development of which gives hope for overcoming the therapeutic resistance of many chronically leaving skin diseases. It is very important that such treatment of chronic dermatoses is available to the general population of our country, so we must welcome the appearance of high -quality generics in our pharmaceutical market. Literature 1. Acne / Ed. A.A. Kubanova. -M.: Dax-Press, 2010. 28 p. 2. Volkova E.N., Esimbieva M.L., Landysheva K.A. and others. Innovation of patients with acne: preliminary treatment results // wedge. Dermatol. And Venerol. 2011. No. 1. P. 59–63. 3. Ryocken M., Shaller M., Zuttler E. and others. Atlas in dermatology. M.: "Medpress-Inform", 2012. 4. Martsov A.V. Acne and acneiform dermatoses. M.: LLC "Yutkom", 2009. 5. Moatov A.V., Statsenko A.V., Volkova S.V. and other issues of efficiency and safety of the use of acne in therapy acne // Bulletin of Dermatol. And Venerol. 2011. No. 2. 6. Svetlova E.S., Monakhov K.N. A psychedermatological approach to the examination and treatment of patients with acne. S.-PB: SPb MAPO. Collection of articles, no. 9. 7. Germain P., Chambon P., Eichele G. et al. International Union of Pharmacology. LX. Retinoic Acid Receptors. Pharmacological. 2006. Vol. 58, No. 4. S. 712–725. 8. Schmitt-Hofmann AH, ROOS B., Sauer J. et al. PHARMACOKINETIKS, Efficacy and Safety of Alitretinoin in Moderate or Severe Chronic Hand Eczema // Clin. and Experiment. Dermatol. 2011. British Association of Dermatologists. Vol. 36 (SUPPL. 2). P. 29–34. 9. Alexander R. Moise. Pharmacology of Retinoid Receptors // ToCris Bioscience Scientific Review Series. 2011. No. 36. 10. Thieme Case Report. 2010. Vol. 2 (2). P. 1–16. Alitretinoin - Case Reports from Clinical Practice. 11. https://www.retinoidsguide.net

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Acnecutane and Roaccutane: instructions for use

The drug Acnekutan is available in capsules (there are 2 forms of release - capsules of 8 and 16 mg). The drug Roaccutane also has 2 release forms - capsules 10 or 20 mg. A very important issue is determining the optimal daily dose in each specific clinical case. Never take these medications without the advice of a dermatologist and laboratory tests. According to the dermatology textbook Fitzpatrick's Dermatology, the recommended daily dose of isotretinoin is in the range of 0.5-1.0 mg/kg/day.

For Acnecutane, the average daily dosage will be slightly lower (than for Roaccutane), which is explained by the use of Lidose technology in its production. By the way, reviews of dermatologists on Acnecutan note that, apparently due to this circumstance, side effects are less likely to occur. At the 1st stage of therapy, it is customary to use slightly lower doses of isotretinoin than during the main period of treatment. For example, for Acnecutane the daily dose will usually be only 0.4 mg/kg/day at the 1st stage of therapy, and in the future we can increase it to 0.8 mg/kg/day. And for Roaccutane at stage 1, the daily dose will already be 0.5 mg/kg/day, and then it will need to be increased to approximately 1.0 mg/kg/day.

In addition to the standard daily dose recommended above in the range of 0.5-1.0 mg/kg/day, studies have described treatment regimens that use even lower daily doses (in the range of 0.1 to 0.4 mg/kg/day). day). It should be noted that such daily doses also show their effectiveness, but you must understand that in these cases the duration of remission after discontinuation of the drug will be shorter.

1) Recommended cumulative doses –

There is also the concept of a cumulative dose, which during the entire course of therapy can be: 1) for Acnecutane - 100-120 mg/per 1 kg of weight, 2) for Roaccutane - 120-150 mg/per 1 kg. Calculation of the cumulative dose per 1 kg of weight is very important for patients whose daily dosages change or there are breaks in treatment. In these cases, achieving the recommended cumulative dose per 1 kg of weight allows for the longest remission of the disease. In patients with severe lesions of the back and chest, the recommended daily dose can reach up to 2 mg/kg/day, because these areas are less sensitive to isotretinoin therapy.

2) Duration of treatment –

Complete remission of acne symptoms can be achieved after 16 to 24 weeks of taking isotretinoin. In each specific case, the duration of the course is individual and can only be determined by a dermatologist. Please note that an improvement in the condition of your acne may be observed, including within 1-2 months after stopping the drug. Therefore, the drug can be discontinued in some cases even before the inflammatory elements of acne completely disappear.

Approximately 10% of patients treated with isotretinoin require a second course of the drug, with the likelihood of repeat therapy increasing in patients younger than 16–17 years. A second course of therapy can be prescribed no earlier than 8 weeks (after the end of the first).

Important: in patients with severe forms of acne (especially granulomatous lesions), isotretinoin therapy often leads to a sharp exacerbation of acne. And in such patients, it is important not only to use lower dosages at the 1st stage of treatment, but also to conduct a short course of treatment with prednisolone (for 1-2 weeks, 40-60 mg/day). But if necessary, the course of prednisolone can be extended, and can cover the first 2 weeks of isotretinoin therapy (24stoma.ru).

→ Roaccutane instructions for use official. (PDF) → Acnecutane official instructions (PDF)

Material and methods

The inclusion criteria for the study were the following: patient age (men and women) from 18 to 38 years; papulopustular acne of mild, moderate and severe severity; duration of the disease from 4 to 15 years; ineffectiveness of previously used methods of therapy; ability to comply with study requirements and provision of written informed consent from the patient.

Exclusion criteria: patient age under 17 years; comedonal form of acne; liver dysfunction; positive pregnancy test, as well as women planning pregnancy while taking Acnecutan

; severe somatic illnesses and the presence of mental disorders.

We observed 70 patients with papulopustular acne of varying severity. Distribution by clinical forms and assessment of the severity of dermatosis were carried out according to the recommendations of the American Academy of Dermatology (2000). In papulopustular acne, the severity level corresponded to the number of inflammatory elements:

- mild degree - up to 10 papulopustules;

- average degree - from 10 to 25 papulopustules in the absence of nodular elements;

- severe degree - from 26 to 50 papulopustules in the presence of nodular elements.

The patients were divided into three groups: group 1 included 20 people with mild; in the 2nd - 47 patients with moderate severity; in the 3rd - 3 patients with severe acne.

Patients of groups 1 and 2 received Acnekutan

in the form of monotherapy at 0.16-0.32 mg per 1 kg of body weight, and patients of the 3rd group took macrolide antibiotics for the first 7-10 days, followed by the appointment, after the acute inflammatory process had reduced, of isotretinoin at a dose of 0.32 mg per 1 kg of body weight.

In all patients, before treatment, and then monthly, biochemical blood parameters (alanine aminotransferase, aspartate aminotransferase, triglycerides, cholesterol, alkaline phosphatase, glucose, creatinine) were examined, and sebum secretion was measured using a Multiscope Monitor Center device (Germany). According to indications, women underwent hormonal testing to exclude hyperandrogenism. An individual chart was compiled for each patient, informed consent for the therapy was obtained from everyone, and women were given a pregnancy test and given a warning about the possible teratogenic effect of the drug.

The effectiveness of treatment was assessed by the relative number of recovered patients, as well as by the period of stable remission of the disease after treatment. Observation period for patients after treatment with Acnecutane

was 36 months.

Treatment results were assessed according to the following criteria:

1) clinical recovery - complete resolution of clinical manifestations;

2) significant improvement - absence of new rashes, reduction in the affected area and number of elements by more than 50%;

3) improvement - a change in the above-mentioned clinical criteria by less than 50%;

4) without dynamics - no improvement in the clinical picture.

Side effects of isotretinoin -

The severity of side effects always depends on the daily dose of isotretinoin. Most of the side effects will be similar to chronic hypervitaminosis syndrome “A” and, accordingly, they will be associated with the skin and mucous membranes. Below you can see statistics on the most common side effects associated with the skin and mucous membranes.

Frequency of side effects (per number of patients) –

• cheilitis (inflammation of the lips) – in 100% of patients,
• facial dermatitis – 46.1%,
• dry nasal mucosa – 24.8%,
• dry skin – 21.4%,
• skin itching – 14.5%,
• increased cholesterol levels – 9.3%,
• dermatitis of the hands – 6.0%,
• dry conjunctiva of the eye – 3.4%,
• bleeding of the nasal mucosa – 2.6%.

This study of side effects was published in the scientific journal “Bulletin of Dermatology and Venereology 2017”. The study was conducted at the Federal State Budgetary Educational Institution of Higher Education "KSMU" of the Ministry of Health of Russia. Considering that Acnecutane was used as a drug with isotretinoin, which is taken in slightly lower doses (compared to Roaccutane), then the statistics of side effects for Roaccutane should therefore be somewhat worse.

Less common side effects –

• hair thinning,
• myalgia (muscle pain),
• from the eyes - xerophthalmia, night blindness, conjunctivitis, keratitis (corneal clouding) and optic neuritis,
• hearing loss (both transient and permanent),
• severe headaches, lethargy, fatigue,
• risk of depression, suicide, psychosis and aggressive behavior,
• from the gastrointestinal tract - nausea, esophagitis, gastritis, colitis, acute pancreatitis, acute hepatitis,
• an increase in cholesterol levels with a decrease in high-density lipoprotein levels - in the first 4 weeks from the start of therapy,
• impaired bone mineralization (with a repeated course of therapy, osteoporosis may be diagnosed and the risk of fractures increases).

Isotretinoin and pregnancy -

All drugs containing isotretinoin have a strong teratogenic effect. Patients should use 2 reliable methods of contraception at once (both oral contraceptives and condoms). Contraception should be started at least 1 month in advance and continued for at least 1 month after completion of isotretinoin therapy. The patient must have a negative pregnancy test result within 11 days before starting the drug, plus regular monthly testing throughout the course. If the drug is taken by a man, then there is no risk to the fetus.

Research results

The effectiveness of treatment with low doses of Acnekutan

was as follows: clinical recovery was achieved in 61 patients
(see figure)
, significant improvement in 8 patients, improvement was observed in 1 patient.

Figure 1. Acne, papular-pustular form before (a) and after (b) treatment.
In the 1st group ( n

=20) clinical recovery was achieved in all patients (100%). Against the background of the therapy, patients noted regression of acne manifestations already in the 1st month of taking isotretinoin. The duration of treatment averaged 4 months. All patients noted good tolerability of the therapy and stable remission for 36 months.

In the 2nd group ( n

=47) clinical recovery was recorded in 40 (85%) patients, significant improvement in 7 (15%) people. The average duration of drug use was 6 months. A decrease in acne manifestations was observed by the 2nd month of therapy. No recurrence of rashes after treatment - for 36 months. Female patients reported premenstrual rashes after treatment.

In the 3rd group ( n

=3) clinical recovery occurred in 1 (33%) person; 1 (33%) patient showed significant improvement, and the effect of therapy in 1 (33%) patient was assessed as improvement. All patients received isotretinoin at a dose of 0.32 mg per 1 kg of body weight per day for 6 months. Everyone noted that the drug was well tolerated. Two of the three patients returned again a year later, but the rash corresponded to a mild severity of the disease.

One of the objectives of this work was to analyze the side effects of taking a systemic retinoid. Tolerance of low doses of Acnekutan

was good. The phenomena of retinoid dermatitis were significantly less pronounced compared to treatment according to standard regimens. All patients developed symptoms of retinoid dermatitis on the 2-3rd day of therapy (cheilitis, dryness and flaking of the facial skin were especially disturbing); approximately half of the patients experienced moderate dry skin of the hands during the 1-3rd month of therapy.

The use of isotretinoin for the correction of wrinkles –

But the retinoid isotretinoin can be used not only systemically (orally).
There are a small number of drugs with isotretinoin for external use, which were initially used exclusively for the treatment of acne and pimples, but later these drugs began to be used to correct the symptoms of photoaging. As in the case of the retinoid tretinoin, preparations with isotretinoin also help to increase skin elasticity and reduce the depth of wrinkles. What effects do external forms of isotretinoin cause in the skin:

• Peeling effect - the thickness of the superficial stratum corneum of the epidermis decreases (due to exfoliation of dead skin cells). This evens out skin tone and texture, leaving skin looking more youthful and radiant—like you've had a few superficial chemical peels.
• Increasing the thickness of the deep layers of the epidermis - isotretinoin affects stem keratinocytes located at the basement membrane, increasing the rate of their division and differentiation. This leads to an increase in the thickness of the deep layers of the epidermis, consisting of living keratinocytes. As a result, the hydrophobicity of the epidermis increases, which contributes to less evaporation of moisture from the surface of the skin. In addition, it prevents skin photoaging.
• Stimulation of the production of collagen and hyaluronic acid - isotretinoin affects not only the epidermis, but also the dermis. It promotes the proliferation (reproduction) of fibroblasts, and also significantly stimulates their activity, which leads to an increase in their production of collagen, elastin and endogenous hyaluronic acid. This leads to an increase in the thickness of the dermis, a decrease in the depth of wrinkles, and an increase in skin elasticity. It is known that thicker skin is less susceptible to the aging process.

Optimal concentrations of external forms of Isotretinoin –

There are a number of clinical studies where scientists have determined the optimal concentration of isotretinoin for the treatment of photoaging.

1) “Armstrong RB, Lesiewicz J, Harvey G et al. Clinical panel assessment of photodamaged skin treated with isotretinoin using photographs. Arch Dermatol 1992; 128:352–6.” 2) “Sendagorta E, Lesiewicz J, Armstrong RB. Topical isotretinoin for photodamaged skin. J Am Acad Dermatol 1992; 27:S15–18.”

In these studies, the concentration of Isotretinoin was increased from 0.05% at the beginning of the study to 0.1% at the end of the study. Despite the increase in concentration, the drug was well tolerated by patients without causing significant skin irritation. As a result of the treatment of photoaging skin with 0.1% Isotretinoin, the skin condition gradually improved throughout the 36-week treatment, and a decrease in the depth of wrinkles and fine lines was achieved.

3) The study “Maddin S, Lauharanta J, Agache P et al. Isotretinoin improves the appearance of photodamaged skin: results of a 36-week, multicenter, double-blind, placebo-controlled trial. J Am Acad Dermatol 2000; 42:56–63.” In this study, a combination of 0.05% Isotretinoin plus SPF sunscreen was used to treat photoaging. The result was that the condition of skin with visible photodamage was significantly improved, which was recorded using profilometry.

Conclusions: if you are interested in preventing skin photoaging, it is best to use a 0.05% concentration in combination with sunscreen. If you want to achieve an increase in skin elasticity and a decrease in the depth of wrinkles, then the main treatment should be carried out using a 0.1% concentration (it is better to use a 0.05% concentration for the first month so that the skin gets used to retinoids).

Isotretinoin has a delayed effect - it will take at least 8-12 weeks before you notice any positive changes, although the first positive effect associated with improved skin tone and texture will be noticeable after 4-6 weeks. It must be admitted that abroad isotretinoin is used for the correction of photoaging much less frequently than other types of retinoids - tretinoin or pure retinol.

Preparations with isotretinoin for external use –

• “Retinoic ointment” (Fig. 8) – is available with an isotretinoin concentration of 0.05% or 0.1%. The cost will be from 300 rubles for a 15 g tube. About a tenth of the volume is ethyl alcohol, so you should not use this drug if you have dry and/or sensitive skin. In principle, the manufacturer writes in this regard that this drug is intended for the treatment of acne in patients with oily skin.

• "Retasol" (Fig. 9) - is a solution for external use, with an isotretinoin concentration of 0.025%. But keep in mind that this drug also contains alcohol, but in less quantity than retinoic ointment. In addition, the drug contains propylene glycol, which may cause irritation in patients with sensitive skin. Cost from 400 rubles per 50 ml bottle.

Isotretinoin: instructions for use

These instructions for using the drug are equally suitable for the treatment of acne and for facial skin rejuvenation techniques, for which information will be given below.

1) Wash your face thoroughly with a mild cleanser. 2) It is advisable to wait 20-30 minutes for the skin to dry thoroughly. 3) Squeeze out a pea-sized amount of the preparation and rub evenly. 4) Avoid contact of the drug with the mucous membranes of the eyes, lips, and nose. 5) After applying the drug, wash your hands thoroughly. 6) Use Isotretinoin 1 time per day (before bed). 7) Be patient - you will see the first results after 4 weeks when treating acne, and after 8-12 weeks for skin rejuvenation. The average treatment duration is 16-24 weeks for acne, and up to 36 weeks for improving the appearance and firmness of the skin.

Features of application –

Do not use more of the drug than recommended or more often than prescribed, because This will not speed up the effect, but will cause more redness, peeling and itching. In addition, isotretinoin should not be used if the skin in the area of ​​application is damaged. During the treatment period, it is necessary to avoid exposure to sunlight, especially during periods of high solar activity (otherwise you may get hyperpigmentation of the treated skin areas).

Always apply sunscreen with SPF 50 before going outside. In summer, wear wide-brimmed hats to shield your face from the sun.

Side effects of topical forms of isotretinoin -

It should be noted that isotretinoin may affect different people differently. In most patients they are completely absent or mild. The most common side effects are redness, dryness, flaking, itching and burning of the skin, and increased sensitivity to sunlight. You can see the side effects from the use of retinoids in Fig. 10-11.

We hope that our article: Acnecutane and Roaccutane reviews was useful to you!

Sources:

1. Textbook of dermatology “Fitzpatrick's Dermatology” (8th edition), 2. American Academy of Dermatology (USA), 3. “Isotretinoin in the treatment of acne” (Tlish M., Shavilova M.), 4. “Cosmetic dermatology” (Bauman L.).

Reviews of systemic isotretinoin preparations for acne therapy (Acnecutane®, Roaccutane®, Sotret®)

During adolescence, everything was fine with my face. At 19 they began to appear. I tried absolutely everything for 3 years: I tested for demodex (subcutaneous mites), drank Unidox salutab in combination with ointments such as baziron, metrogil, zenirit, dalacin, took yeast, took birth control, did intravenous laser therapy, took tests for hormones, checked liver, was checked by a gynecologist, went to my grandmother, fasted for 2 months (0 results), was in the best dermatological complex in Moscow, changed 3 dermatologists, and when I realized that I could already consult a dermatologist myself, I decided to try Roaccutane. I decided so late because none of the doctors told me about it until I found out about it myself and demanded that it be prescribed to me in the correct doses. Started receiving treatment on October 25, 2011. Now at the final stage. For 4 months I took 40 mg per day i.e. 20 mg in the morning and 20 mg in the evening. Then my dermatologist began to reduce the dose: 10 mg. in the morning and 20 mg. evening = 30 mg per day. Then 20 mg per day. In 10 days my course of treatment will be completed. In total, I took it for about 5-6 months. After the first 2 months of taking it, everything went away. In addition to scars and red spots that were a result of acne and squeezing. Now I don’t have a single pimple, not even a black one. These red spots were very confusing. I was prescribed 10 sessions of creotherapy (liquid nitrogen). I can say that the spots are half as bright as they were. In addition to the fact that absolutely all acne disappeared, all this time my skin on my face did not shine, all the skin on my body became velvety (it contains an analogue of vitamin A), my head did not get dirty at all. I even forgot when I washed it. Now I am finishing the course and will see what happens next. Maybe I'll take another 10 mg pack. For absolutely complete completion. But my skin has suffered through all the years while I was choosing the right product, so I’m waiting for the fall to do peeling. And the color will become better and I will get rid of scars. These were the advantages. Now the cons. During all this time, I only had a dry nose (it could bleed when you blow your nose), dry lips and dry hands. Nothing else. I drank quite a bit of alcohol. How evil are all the holidays, dr. new year, etc. I had my liver checked every month. Everything is fine. You need to check it again after completion. Perhaps many will like my review, but still everyone has an individual approach. The dose is selected by weight. The doctor asks what you were sick with, whether you had jaundice. I read in the anatomy for the pills that it affects vision. I have it good and I don’t have our lenses. The doctor also recommends an additional barrier in addition to condoms. For 6 months I took the contraceptive Yarina (which, by the way, is also aimed at the skin). And the last thing I would like to say: girls and men who suffer from acne as I suffered, if baziron did not help you, do not try anything else, take Roaccutane if you are healthy and do not plan to have children in the next year or two. Do not waste time on all the ways to get rid of acne if you have been suffering with them for so long. I’m 22 now and I wish I didn’t know about them at 19. Then my skin would be without scars and various spots. Believe me, I know how acne interferes with life. Every morning, apply layers of foundation and powder; walk with your hair down to cover at least some of it; be embarrassed to remove makeup if you spend the night with friends or a boyfriend; You can’t go to the beach in powder, so you have to get over yourself; you can’t quickly leave the house or go to the store; It’s terrible when night or bad light is your salvation; and constantly look in the mirror at this?; and to hear from everyone “your face is fucked up” - “damn seriously! and you think I don’t see or don’t go to the mirror.” I used to look at problematic faces on the subway and think, “why don’t they do anything?” It turns out they do, but damn, our 21st century cures cancer, but cannot understand what to do with acne. I wish everyone good luck. If you have any questions, write to me by email, I will be happy to answer [email protected]