Isotretinoin (Isotroin®/Acnetrent®/Acutein®) oral therapy

Hello, I am a doctor at Smart Skin Clinic, a cosmetic dermatology clinic.

Do you have any of these questions or concerns?

In this article, our cosmetic dermatology clinic will explain these questions and concerns from a professional standpoint in an easy-to-understand manner.

*If you would like to know the rates, you can jump to the table of contents below.

What is isotretinoin?

Isotretinoin is, simply put, an oral treatment for acne. It is classified as a vitamin A derivative.

andThe ultimate weapon in acne treatment."This medication is sometimes referred to as

Briefly on how it works,Atrophy of sebaceous glandsaction, thereby providing a therapeutic effect on acne.

Isotretinoin is the name of the ingredient, and there are several drugs with the trade names Accutane, Isotroin, Roaccutane, and Tretiva.

In Japan, it is not yet covered by insurance,Drugs that have been used for many years in other countrieswill be. Specifically,In Europe and the U.S., for about 35 years now.In the U.S., it was approved in 1982.

For moderate to severe acneAcne Treatment Guidelines" in the U.S. and Europe recommend a high level of oral isotretinoin treatment.Isotretinoin has risks and side effects, and must be prescribed under a physician's consultation.

Some of the actual Western "acne treatment guidelines" are shown below. For "Severe" acne, which may be difficult to understand in English,Isotretinoin" is listed as a "high strength of recommendation" treatment.

(Source.)Nast A et al: European evidence-based (S3) guideline for the treatment of acne - update 2016 - short version. J Eur Acad Dermatol Venereol. 2016, 30, 1261-1268

Please see our Instagram below for a visual explanation, if you prefer to understand visually rather than reading text.

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Case study photographs (Before/After)

Name of treatment	Isotretinoin oral therapy (20 mg)
Treatment	Isotretinoin is used to improve acne and oily skin by taking one tablet once a day.
Length of treatment	Average 6 to 9 months.
Charge	10mg (30 days) 7,980 yen 20mg (30 days) 12,980 yen Tax included, free medical treatment
Risks and Side Effects	Must be sterilized due to teratogenicity Dry skin (especially lips) Changes in liver function, changes in lipid levels, joint and muscle pain, headache, dizziness, visual disturbances, photosensitivity, allergic reactions, changes in bone density

Effects and Mechanisms

Effect

In one case, a patient who had been receiving insurance treatment (oral and topical) for 2 to 3 years but had not improved, showed improvement within 3 months of taking isotroin.

Three mechanisms of effectiveness

Mechanism 1: Decrease in skin oil content

Isotretinoin regulates sebaceous gland function and decreases skin oil secretion.This inhibits the overproduction of sebum, which causes acne, and reduces inflammation and clogged pores.

Isotretinoin also inhibits the activity of lipid synthase enzymes in sebaceous glands. Specifically, it reduces sebum secretion by inhibiting 5α-reductase and decreasing the size of sebaceous glands.

Reduced sebum production may, as a side effect, reduce the appearance of pores.

Mechanism 2: Suppression of inflammation

Isotretinoin also improves the symptoms of inflammatory acne. It exerts an anti-inflammatory effect on factors that cause inflammation, relieving symptoms such as redness and swelling.

It suppresses inflammation by modulating various mechanisms involved in the inflammatory response. Specifically, it reduces the production of inflammatory cytokines (IL-1, IL-6, IL-8, etc.) and alleviates inflammatory responses. It also suppresses T-cell activation and neutrophil migration, thereby reducing inflammation.

Mechanism 3: Improvement of turnover

Isotretinoin decreases pore clogging. This also improves pore-related problems such as powdery and blackheads.

It also improves epidermal cell differentiation and apoptosis (cell death) by regulating gene expression. Thereby,Normalization of skin turnoverThe result is a reduction in pore clogging.

Action to improve keratinization abnormalitiesIt also Reduces pore-clogging and inflammation by promoting normal keratinization and inhibiting excessive keratinization of the stratum corneum.

Because it improves turnover, skin luster may be increased as a side effect.

Concept of Total Amount｜How long should the period of oral administration be?

When undergoing isotretinoin treatment, many peopleHow long do I have to drink it?"You may be asking yourself the question, "What is the best way to do this?

Actually, the answer to this question is."Total AmountThis is closely related to the concept of In this section, we will explain in simple terms the concept of total dosage and how to determine the duration of oral dosage based on this concept.

What is the total volume?

What is the total volume?Total dose per kg of body weightrefers to the total amount of the product. In isotretinoin therapy, this cumulative amount is an important indicator.

• Target integrated dose: 120-150 mg/kg
• Calculation method: (daily dose [mg/kg/day]) x (number of treatment days) = cumulative dose [mg/kg]

Why is the total amount important?

Treatment based on the total volume has the following advantages

1. Long-term symptom improvement
2. Reduced risk of recurrence
3. Establishing the optimal treatment period for each individual patient

Estimated duration of oral administration based on the total amount

Duration of oral administration depends on body weight and daily dosagebut here are some general guidelines:

gender	average body weight	Daily dosage	Estimated duration of internal use	Cumulative dose
masculine gender	67 kg	10 mg/day	Approx. 30 months	Approx. 134 mg/kg
		20 mg/day	Approx. 15 months	Approx. 134 mg/kg
female	53 kg	10 mg/day	Approx. 24 months	Approx. 136 mg/kg
		20 mg/day	Approx. 12 months	Approx. 136 mg/kg

This is only a guideline, and the actual treatment period may vary from person to person.

On the choice between low and high doses:

1. Advantages of low doses (10 mg/day):
   • May lower the risk of side effects.
   • Skin dryness and other symptoms may be mild.
2. Benefits of higher doses (20 mg/day):
   • The duration of treatment is shortened, which may lead to early results.
   • Long-term compliance (keeping up with oral medication) may be improved.

Relationship between cumulative dose and treatment effect

Isotretinoin has the following effects on the sebaceous glands

1. Reduces sebaceous gland size and activity
2. Long-term suppression of sebum secretion
3. Normalization of abnormal keratinization of follicular epithelium
4. Suppression of inflammatory cytokine production

By reaching a sufficient cumulative dose, these effects work continuously, improving symptoms and reducing the risk of recurrence.This leads to

Importance of personalized treatment

The total volume is an important indicator, though,We do not provide uniform treatment to all.The following factors are taken into consideration to develop the best treatment plan for each individual patient

• Severity of symptoms
• body weight (usu. one's own)
• Presence and severity of side effects
• Responsiveness to treatment
• lifestyle

For example, the international standard is 0.5mg/kg-1.0mg/kg for 15-20 weeks. However, this is only the global standard, and it is better to adapt it to the characteristics of the Japanese.

Since there are fewer Japanese patients with severe acne compared to those in other countries, it is considered acceptable to start treatment with a lower dose. In many cases, the starting dose for Japanese patients is about 0.3 mg/kg.

Summary of total volume

The concept of totalization in isotretinoin therapy is an important indicator for effective and safe treatment.

However, this is only a guideline, and actual treatment will be adjusted in detail according to the individual patient's condition through periodic examinations.

We carefully evaluate each patient's condition to develop the best treatment plan. If you are considering isotretinoin treatment, please contact us for a consultation.

An example of treatment progress

Before treatment: Before the start of treatment

Name of treatment	Isotretinoin oral therapy (20 mg)
Treatment	Isotretinoin is used to improve acne and oily skin by taking one tablet once a day.
Length of treatment	Average 6 to 9 months.
Charge	10mg (30 days) 7,980 yen 20mg (30 days) 12,980 yen Tax included, free medical treatment
Risks and Side Effects	Must be sterilized due to teratogenicity Dry skin (especially lips) Changes in liver function, changes in lipid levels, joint and muscle pain, headache, dizziness, visual disturbances, photosensitivity, allergic reactions, changes in bone density

1st month: 1 month

The skin, eyes, nose, and especially the lips may experience side effects. This occurs because the mechanism of isotretinoin is to shrink the sebaceous glands and reduce the oil content of the skin.

Some patients may also experience a temporary worsening of acne when isotretinoin is used for the first time. This can beAlso called the "initial flare" or "purging" period, it occurs when the drug expels impurities deep in the skin.It is said.

2nd month: 1

In most cases,Improvement of acne is often recognized at this point.It is. On the other hand, skin dryness and other side effects may persist or possibly worsen. The physician will usually evaluate the patient's response at this stage and adjust the dosage if necessary.

3rd-4th month:.

The majority of patients often show improvement at this point.It is.New outbreaks of acne are virtually eliminated and existing acne is cured.Some people experience side effects, but many patients learn how to manage them or (e.g., applying lip balm, etc.)

5th-6th month:.

Most patients complete the treatment. The skin is clean and new acne outbreaks are rare. Side effects may persist for some time after discontinuing drug use, but usually resolve with time.

*Please keep in mind that not all patients will show improvement over this course of time.

What happens after quitting? What is the recurrence rate?

Progress after quitting isotretinoin

The first few weeks after the end of the program:.

Skin dryness and other side effects may persist after treatment is completed. However, these side effects gradually diminish.

Months after closing:.

In many cases, acne is completely cleared and new acne outbreaks are controlled. Skin side effects are almost completely eliminated.

More than 6 months after completion:.

 In some patients, acne may reappear after completion of treatment. This is usually not as severe as before and in most cases can be controlled with another isotretinoin treatment or other methods.

recurrence rate

There is no clear recurrence rate data, but it is safe to say that the disease rarely recurs. In a few cases, recurrence does occur, but in the majority of cases, it is not as severe as before.

Why is it unapproved and not covered by insurance in Japan?

In the U.S. and other countries, it has been covered by insurance for more than 30 years, but in Japan it is not.

The reasons involve side effects and difficulty in risk management.

One example is prenatal influences.

Isotretinoin is aPregnancy during or within a short period of time after use may cause serious fetal malformations or developmental disorders.Therefore, women who use them must implement strict pregnancy prevention. Such control and monitoring is difficult, and for this reason is considered unapproved for use in some countries.

Here we will also look at the opinions of physicians in Japan regarding the use of isotretinoin.

(Source.)Hayashi, N., Sasaki, M., Kurokawa, I. et al., A survey on the frequency of patients with acne conglobata and severe acne and dermatologists' attitudes toward oral isotretinoin in Japan, Journal of the Japanese Society of Clinical Dermatology. Journal of the Japanese Society of Clinical Dermatology, Vol. 38, No. 4, p. 629-634, 2021.

In summary,Many physicians see a need for isotretinoin treatment for refractory acneI guess you could say that.

Those who cannot be treated

At what age can it be taken internally?

Acne treatment guidelines in Europe and the United States stateCan be taken internally from age 12.(Conversely, those under 12 years of age are not allowed to take it). (Conversely, it should not be taken by anyone under 12 years of age.)

So, to begin with, "Why should we care about age?" I would like to explain why we need to be concerned about age. It is the "effect on bones," or in other words. may affect height growth (bone growth)."The first time the product is used, it will be from the

This one may be mentioned in theory, though,According to clinical studies (medical papers)Isotretinoin taken internally for as short a period as six months "does not have a significant impact."It is mentioned that

Acne is at risk of remaining as "craters" and "hyperpigmentation" in the long term. Since we are a cosmetic dermatology clinic, we also treat patients suffering from craters and hyperpigmentation, especially craters, which are difficult to improve. Therefore, we believe that there is great merit in treating acne with isotretinoin as early as possible.

Risks and Side Effects

Serious side effects

(1) Fetal malformation, miscarriage, stillbirth, premature birth

(2) Serious mental illness such as depression, psychosis (hallucinations, auditory hallucinations), self-injurious behavior, and suicide attempts

Likely Side Effects

(3) Dry skin and mucous membranes

Isotretinoin shrinks the sebaceous glands, reducing the oil content of the skin and mucous membranes. This causes dry lips, dry nose, dry eyes, and excessively dry skin.

Dryness of the mucous membranes of the nose may cause "nosebleeds".

Other side effects

(4) Changes in liver function

Isotretinoin is taxing on the liver and can cause abnormal liver function in some patients. Therefore, periodic liver function tests are required during treatment.

(5) Fluctuations in lipid levels

Isotretinoin can raise cholesterol and triglyceride levels in the blood. This is especially important for patients at risk for cardiovascular disease.

(6) Joint and muscle pain

Some patients experience joint and muscle pain. This usually improves after treatment is interrupted or completed.

(7) Headache, dizziness, visual disturbance

Some isotretinoin users have been reported to experience headaches, dizziness, or visual disturbances. Changes in visual acuity and reduced night vision, in particular, may affect driving and other aspects of daily life.

(8) Photosensitivity

Isotretinoin users may be more sensitive to sunlight. Therefore, appropriate precautions should be taken to avoid sunburn.

(9) Allergic reaction

Isotretinoin can cause allergic reactions in rare cases. These include skin rashes, hives, severe itching, difficulty breathing, irregular heartbeat, and swelling (especially of the face and throat).

(10) Change in bone density

Prolonged use of high doses of isotretinoin may cause changes in bone density and arrest of bone growth.

precautions

Please use contraception if you have sexual intercourse during the period of taking the drug and during the month before and after the period of taking the drug.

Do not become pregnant, breastfeed, or donate blood during the period of taking the drug and for one month thereafter.

*Transfusion of blood to a pregnant woman may cause isotretinoin effects in the fetus.

・Please refrain from peeling or waxing during isotretinoin treatment and for 6 months after treatment.

Invasive laser therapy is not available during treatment.

Do not share isotretinoin with others.

Acne may temporarily worsen after treatment begins.

Treatment Flow

Charge

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Efficacy of isotretinoin for "seborrheic dermatitis

Here we introduce the efficacy of isotretinoin for the disease "seborrheic dermatitis".

There are two reasons why we are introducing this program

➊Current status of seborrheic dermatitis｜No curative therapy has been established.

So let's start with "What is seborrheic dermatitis?" What are the causes? What is the current treatment for seborrheic dermatitis? Next, I will provide the evidence that isotretinoin is a good option for seborrheic dermatitis.

First, please see this summary of seborrheic dermatitis from a reliable medical website.

Seborrheic dermatitis is a common inflammatory disease of the skin in areas of high sebaceous gland density (e.g., face, scalp, sternum).Cause unknown.is a yeast-like fungus that is endemic to the skin.Malasseziagenus fungi play an important role. Seborrheic dermatitis occurs with increased frequency in HIV-infected patients and in patients with certain neurological disorders. Seborrheic dermatitis sometimes presents with itching, dandruff, and yellowish, greasy scales on the scalp, hairline, and face. The diagnosis is made on examination.Treatment is with antifungals, topical corticosteroids, tar, and keratolytics.

Seborrheic Dermatitis (MSD Manual Professional Edition)

There are two important points.

What does that mean?Since the root cause of the disease is unknown and no cure has been established, many people have tried various treatments but have been troubled by the lack of improvement."That is to say.

How can you be so sure?" You might think, "Because I was one of them.

In fact, I had been suffering from dandruff for 10 years, but when I took isotretinoin for acne treatment, my seborrheic dermatitis was cured, although I had not expected it.

From there, I researched papers and found some interesting facts. Next, I will introduce the reasons why isotretinoin was effective and the medical evidence.

Mechanism of isotretinoin efficacy in seborrheic dermatitis (hypothesis)

As we have explained, the main actions of isotretinoin are"Retraction of sebaceous glands = reduced sebum secretion."This is the action of the

The causes of seborrheic dermatitis are not clearly understood, but the following mechanisms are thought to be involved

Malassezia, a mold fungus, is medically called a "fungus. Therefore, drugs that kill this fungus are called "antifungal drugs. That is why "antifungal drugs" are listed as one of the treatments for seborrheic dermatitis.

However, if Malassezia is activated by "some mechanism", I think you can see that we have not solved the root of the problem.

In fact, in seborrheic dermatitis,Sebum production is on the rise."It is also said that And Malassezia isSebum is the source of their nutritional needs."There is a story that

In other words, the hypothesis is that the root cause is sebum, which activates Malassezia. In this way of thinking,Isotretinoin, which suppresses sebum secretion, may be the root solution.So.

Now, this is just my hypothesis as a cosmetic dermatologist, so let me show you the actual paper.

The first will be an article published in the medical journal International Journal of Dermatology in June 2023.

Study evaluated patients diagnosed with moderate to severe seborrheic dermatitis and treated with oral isotretinoin between January 2019 and December 2020.

The study concluded that 48 patients with moderate to severe seborrheic dermatitis treated with isotretinoin showed statistically significant improvement in their symptoms.

Given its efficacy and safety, oral isotretinoin can be used to treat patients with moderate to severe seborrheic dermatitis.

Zhang Yanfei, et al. Efficacy and safety of oral isotretinoin in the treatment of moderate to severe seborrheic dermatitis: a retrospective study. Int J Dermatol. 2023 Jun;62(6):759-763.

The second paper was published in a similar medical journal in January 2017.

This study was conducted to determine the efficacy and safety of isotretinoin for the treatment of moderate to severe seborrheic dermatitis of the scalp and face.

Forty-five patients were recruited for the study, half were treated with isotretinoin and half with topical agents.

The results showed that isotretinoin relieved the symptoms of seborrheic dermatitis, leading to the conclusion that isotretinoin may be an effective treatment for seborrheic dermatitis.

ConclusionLow-dose oral isotretinoin may be a therapeutic modality for moderate to severe seborrhea and seborrheic dermatitis.

Cristhine de Souza Leão Kamamoto. et al. Low-dose oral isotretinoin for moderate to severe seborrhea and seborrheic dermatitis: a randomized comparative trial. Int J Dermatol. 2017 Jan;56(1):80-85.

To summarize the above,

If you have persistent problems with seborrheic dermatitis, please contact Smart Skin Clinic.

FAQ

I am afraid of isotretinoin because I am worried about side effects, is it safe?

If you are doing a lot of research, you may be worried about side effects. Since there are many side effects listed, you may think that any of them will surely occur, but those with a non-zero probability are listed because they need to be listed, so there is no need to be worried about all of them.

The important thing is to carefully consider the effects and the side effects/risks. Effectiveness means that if using isotretinoin improves your acne, it could have a significant impact on your quality of life.

The side effects of isotretinoin are varied, but the most serious one teratogenicity. As stated in the precautions, "Always use contraception if you are sexually active during the period of taking isotretinoin and the month before and after." The risk of side effects can be lowered by taking the following risk management precautions.

In addition, there will be periodic doctor's visits, so if side effects occur, we will discuss and address them together.

When will it take effect?

Although there are individual differences, in most cases, the effects are realized in about two months.

Do the effects persist after the end of oral administration?

It will persist. Note, however, that some sebaceous glands may return to their original state, so not all patients can be prevented from recurrence. Even in cases where recurrence does occur after discontinuation of the drug, the symptoms are usually less severe than before taking the drug.

What should I do if my acne recurs?

Basically, at the time of recurrence, the disease is usually milder than before. Treatment often includes topical (topical) therapy (ointment) or oral antibiotics, which were used before isotretinoin therapy was initiated.

Can I undergo other cosmetic procedures while taking medication? Is it ok to do things like hair removal?

Basically, there is no problem. On the other hand, hair removal is recommended after discontinuation of isotretinoin. Recent studies have shown that it is safe to undergo laser hair removal while taking isotretinoin, but medical hair removal is risky because of its high power output.

What should I do if I forget to take it?

If you miss a dose for one day, skip it and resume taking one tablet per day on the following day. Be careful not to take two tablets the next day.

Does it work for back acne, etc. other than on the face?

There are. It acts on the whole body.

References and Bibliography

・Alert regarding ACCUTANE (a drug for the treatment of intractable acne not approved in Japan) (Ministry of Health, Labour and Welfare)

・Hayashi, N., Sasaki, M., Kurokawa, I. et al., A survey on the frequency of patients with acne conglobata and severe acne and dermatologists' attitudes toward oral isotretinoin in Japan, Journal of the Japanese Society of Clinical Dermatology. Journal of the Japanese Society of Clinical Dermatology, Vol. 38, No. 4, p. 629-634, 2021.

・Nast A et al: European evidence-based (S3) guideline for the treatment of acne - update 2016 - short version. J Eur Acad Dermatol Venereol. 2016, 30, 1261-1268

Smart Skin Clinic

Smart Skin Clinic

The concept of the clinic is to "make cosmetic medicine more accessible and smart.

The clinic's concept is to make cosmetic medicine more accessible and smart.

The clinic has eliminated gaudy interior design to reduce interior costs, and instead of introducing equipment in the dark, it carefully selects the equipment it needs and reduces the cost of the equipment.

We aim to "make cosmetic medicine more accessible to as many people as possible.

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Address: 8F EX Kanda Nishiki-cho Building, 3-16-1 Kanda Nishiki-cho, Chiyoda-ku, Tokyo
Specialty: Cosmetic Dermatology (aesthetic dermatology, medical hair removal, medical slimming)

Address: 8F EX Kanda Nishiki-cho Building, 3-16-1 Kanda Nishiki-cho, Chiyoda-ku, Tokyo
Specialty: Cosmetic Dermatology (aesthetic dermatology, medical hair removal, medical slimming)

About the physician supervision of this site

About the physician supervision of this site

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This site is operated under the supervision of the Smart Skin Clinic supervising physicians.

This page is produced under the supervision of our supervising physician, who also operates the website as a medical institution in accordance with the Medical Advertising Guidelines, which were revised and enforced in June 2018.

This page is produced under the supervision of our supervising physician, who also operates the website as a medical institution in accordance with the Medical Advertising Guidelines, which were revised and enforced in June 2018.