Treatment with roaccutane in small doses. Roaccutane® in acne therapy: standard therapy regimens and a new low-dose regimen

Antipyretics for children are prescribed by a pediatrician. But there are emergency situations for fever when the child needs to be given medicine immediately. Then the parents take responsibility and use antipyretic drugs. What is allowed to give to infants? How can you bring down the temperature in older children? What medicines are the safest?

Roaccutane is a drug from the group of systemic retinoids. intended for the treatment of acne. It is available in capsules with the active substance isotretinoin.

The drug is used to treat severe forms of acne.: nodular-cystic, conglobate, as well as flowing with subsequent scarring. It is also prescribed in cases where other methods of therapy are useless.

For every patient the scheme of application of Roaccutane is selected individually. The drug can be taken only as directed by a doctor after a thorough examination, and self-medication is unacceptable.

Mechanism of action

When choosing an acne treatment it is necessary to consider how Roaccutane acts on the body.

The results of the studies showed that the drug causes improvement clinical picture with severe forms of acne. This is due to the fact that it reduces the activity of the sebaceous glands, and also reduces their size.

With increased production of sebum, a favorable environment is created for the reproduction of Propionibacterium acnes. These are the bacteria that lead to the development of severe acne.

Also Isotretionine has been scientifically proven to reduce inflammatory processes skin.

Standard dosing regimen

Before taking the drug you need to be examined by a doctor and take tests for an accurate diagnosis.

After that, the specialist will tell the patient, how to take roaccutane. The dosages given below are indicative and require individual adjustment.

Roaccutane capsules are taken orally 1 or 2 times a day with meals.. The recommended dosage for starters is 0.5-1 mg per 1 kg of body weight. Every month it can be adjusted depending on the result achieved and the severity of side effects.

For the treatment of particularly severe forms of acne or acne on the trunk, it may be necessary to increase the daily dose of the drug to 2 mg / kg.

If the patient does not tolerate the amount of isotretinoin prescribed to him, it is reduced. However, in this case, the treatment is delayed.

First month: (60 mg/day x 30 days) / 70 kg.
Second month: (50 mg/day x 30 days) / 70 kg.
Third month: (40 mg / day x 30 days) / 70 kg.

These are theoretical calculations.. In reality, they should be made only on the basis of the analyzes carried out.

When the cumulative dose reaches 120-150 mg/kg, the likelihood of acne recurrence is greatly reduced. The time when Roaccutane improves is on average 16-24 weeks. During this period, in most cases, it is possible to achieve a stable remission.

Acne usually resolves completely after one treatment. receiving funds. In case of relapse, treatment can be repeated at similar dosages.

However resuming the drug is possible no earlier than after 8 weeks after completing the first course. During this period, as a rule, therapeutic effect.

Contraindications

Contraindications for taking Roaccutane are:

pregnancy and lactation;
kidney failure;
hypersensitivity to the drug or individual components in its composition;
an excess of vitamin A;
severe hyperlipidemia;
simultaneous administration with drugs from the tetracycline group;
age up to 12 years.

With caution, Roaccutane is prescribed for diabetes mellitus, alcoholism, lipid metabolism disorders, obesity and a tendency to depression.

Dosing in special cases

In exceptional cases, the drug is prescribed, even if there are contraindications.

However, the expected benefits of therapy must outweigh the potential health risks.

When prescribing a treatment regimen, the doctor takes into account the results of the patient's examination. During the entire course of taking the funds the patient should be constantly monitored by his doctor.

kidney failure

Patients with severe kidney failure initially prescribed Roaccutane in small doses.

Usually it is 10 mg/day.

If the patient tolerates the treatment well, it is possible to increase the daily dosage, but up to a maximum of 1 mg / kg.

Pregnancy

Pregnancy is an absolute contraindication for taking Roaccutane. If it occurs during treatment or within a month after completion of therapy, there is a high risk of miscarriage or detection in born child severe malformations:

hydrocephalus;
microcephaly;
malformations of the cerebellum;
anomalies of the outer ear;
microphthalmia;
cardiovascular pathologies;
wolf's mouth;
malformations of the thymus and parathyroid glands.

The appointment of Roaccutane to women of childbearing age is possible only with all of the following conditions are met simultaneously:

Even those women who are diagnosed with infertility, amenorrhea, as well as those who inform the doctor about the complete absence of sexual life, should use contraceptives during the period of treatment with Roaccutane. An exception is made for patients who have undergone a hysterectomy.

If during the period of treatment a woman is pregnant, taking Roaccutane is immediately stopped. The patient should consult with a specialist in the field of teratology about the advisability of preserving it.

During lactation, taking Roaccutane is also not recommended.. Isotretinoin is highly lipophilic, so there is a high risk that it will pass into breast milk. This is fraught with side effects for the baby.

special instructions

The drug is intended for the treatment of only severe forms of acne.. With acne vulgaris of mild or moderate course, the use of Roaccutane is not recommended.

During the period of taking the drug, it is necessary to carefully monitor the patient's condition. Also The patient should adhere to the following guidelines:

donate blood to study lipid levels to monitor liver function;
patients who wear contact lenses - use glasses when side effects from the eyes appear;
sick diabetes- more often to monitor the concentration of glucose in the blood;
donors - refuse to donate blood for the entire period of treatment and for 1 month after its completion (to exclude the transfusion of this blood to pregnant women);
when taking the first dose - be extra careful while driving and when performing work associated with risk or requiring increased concentration of attention, quick response;
avoid exposure to ultraviolet radiation (including UV therapy, prolonged exposure to direct sunlight, visits to solariums).

Interaction with other drugs

During treatment with the drug, caution should be exercised when taking other medicines. So, in combination with tetracycline antibiotics, the effectiveness of Roaccutane is reduced.

Simultaneous reception with sulfonamides, thiazide diuretics, tetracyclines increases the risk of sunburn. Tetracyclines are forbidden to be combined with Roaccutane also because of the likelihood of an increase in intracranial pressure.

Side effects

During treatment with Roaccutane, side effects often occur. Dose adjustment sometimes helps to get rid of them, but some persist even after discontinuation of the drug.

On the part of the skin and mucous membranes are possible:

The most likely musculoskeletal side effects are:

muscle and joint pain;
arthritis;
bone changes (including calcification of tendons and ligaments).

From the side of the central nervous system, some patients experience:

There are also isolated cases side effects by the sense organs:

photophobia;
impaired visual acuity and adaptation to the dark;
edema optic nerve;
hearing loss at certain frequencies;
eye irritation;
reversible disturbances in color perception.

From the gastrointestinal tract, the following adverse reactions occur:

nausea;
diarrhea;
colitis;
bleeding.

Described isolated cases of hepatitis in patients receiving Roaccutane. Extremely rarely, the drug provokes the occurrence of pancreatitis with a fatal outcome.

In addition, spasms in the bronchi are possible in patients bronchial asthma, anemia and dysfunction immune system. Cases of primary diabetes mellitus have also been reported.

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Dosage form

Capsules 8 mg and 16 mg

Compound

One capsule contains

active substance - isotretinoin 8.00 mg or 16.00 mg,

excipients: stearoyl macrogolglycerides, refined soybean oil, sorbitol oleate,

composition of gelatin capsules No. 3 (lid and body): gelatin, iron oxide red (E 172), titanium dioxide (E 171),

composition of gelatin capsules No. 1:

cap: gelatin, iron oxide yellow (E 172), indigo carmine (E 132), titanium dioxide (E 171), titanium dioxide (E 171),

body: gelatin, titanium dioxide (E 171).

Description

Gelatin capsules No. 3, with a cap and a body of orange color (for a dosage of 8 mg).

Gelatin capsules No. 1, with a green cap and a white body (for a dosage of 16 mg).

The contents of the capsules are an orange waxy paste.

Pharmacotherapeutic group

Preparations for the treatment of acne.

Retinoids for systemic treatment acne rash. Isotretinoin.

ATX code D10BA01

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Pharmacological properties

Pharmacokinetics

Suction

After oral administration, absorption is variable, the bioavailability of isotretinoin is low and variable - due to the proportion of dissolved isotretinoin in the preparation and may also increase when taking the drug with food.

In patients with acne, the maximum plasma concentrations (Cmax) at steady state after taking 80 mg of isotretinoin on an empty stomach were 310 ng / ml (range 188 - 473 ng / ml) and were reached after 2-3 hours. The concentration of isotretinoin in plasma is 1.7 times higher than in the blood, due to poor penetration into red blood cells.

Distribution
Isotretinoin is almost completely (99.9%) bound to plasma proteins, mainly to albumin.

Equilibrium concentrations of isotretinoin in the blood of patients with severe acne, who took 40 mg of the drug 2 times a day, ranged from 120 to 200 ng / ml. The concentrations of 4-oxo-isotretinoin in these patients were 2-5 times higher than those of isotretinoin. The concentration of isotretinoin in the epidermis is two times lower than in serum.

Metabolism
Isotretinoin is metabolized to form three major metabolites in plasma: 4-oxo-isotretinoin, tretinoin (all-trans retinoic acid) and 4-oxo-retinoin, as well as less significant metabolites, including also glucuronides. The main metabolite is 4-oxo-isotretinoin, its plasma level in the equilibrium state is 2.5 times higher than the concentration of the parent drug. Several enzymes of the cytochrome system are involved in the conversion of isotretinoin to 4-oxo-isotretinoin and tretinoin: CYP2C8, CYP2C9, CYP2B6 and, probably, CYP3A4, as well as CYP2A6 and CYP2E1. At the same time, none of the isoforms, apparently, plays a dominant role.

Isotretinoin metabolites have a high biological activity. The clinical effects of the drug in patients may be the result of the pharmacological activity of isotretinoin and its metabolites. Enterohepatic circulation may play a significant role in the pharmacokinetics of isotretinoin in humans.

breeding

The terminal phase elimination half-life for unchanged isotretinoin in patients with acne is, on average, 19 hours. The half-life of the terminal phase of 4-oxo-isotretinoin is longer, on average, 29 hours.

Isotretinoin is excreted by the kidneys and bile in approximately equal amounts.

Isotretinoin is a natural (physiological) retinoid. Endogenous concentrations of retinoids are restored approximately 2 weeks after the end of taking Aknekutan.
Pharmacokinetics in special cases

Since data on the pharmacokinetics of the drug in patients with impaired liver function are limited, isotretinoin is contraindicated in this group of patients.

Renal failure of mild to moderate severity does not affect the pharmacokinetics of isotretinoin.

Pharmacodynamics

Isotretinoin is a stereoisomer of all-trans retinoic acid (tretinoin).

The exact mechanism of action of isotretinoin has not yet been identified, however, it has been established that the improvement in the clinical picture of severe forms of acne is associated with the suppression of the activity of the sebaceous glands and a histologically confirmed decrease in their size. Sebum is the main substrate for the growth of Propionibacterium acnes, so reducing sebum production inhibits bacterial colonization in the duct.

The anti-inflammatory effect of isotretinoin on the skin has been proven.

Dosage and administration

Acnecutane should only be prescribed by a physician or used under the supervision of a physician experienced in the use of systemic retinoids for the treatment of severe acne and who understands the risks of Acnecutane therapy and the necessary monitoring of their use.

Therapeutic efficacy of Acnecutane and its side effects dose dependent and vary from patient to patient. Therefore, it is important to individually select doses during treatment.

Capsules are taken with meals, once or twice a day.

The initial dose of Acnecutane is 0.4 mg/kg per day, in some cases up to 0.8 mg/kg of body weight per day.

The optimal course cumulative dose is 100-120 mg/kg. Complete remission of acne is often achieved within 16-24 weeks of treatment.

If the recommended dose is poorly tolerated, treatment can be continued at a lower daily dose, but longer. An increase in the duration of treatment may lead to an increased risk of relapse. To ensure the maximum possible effectiveness in such patients, treatment should be continued at the maximum tolerated dose for the usual time.

In most patients, acne disappears completely after a single course of treatment.

With a clear relapse, a second course of treatment is indicated in the same daily and cumulative dose of Aknekutan as the first. Since improvement may be delayed, up to 8 weeks after discontinuation of the drug, a second course should be prescribed no earlier than after the end of this period.

Dosing in special cases

In patients with severe renal insufficiency, treatment should be initiated at a low dose (eg, 8 mg/day). The dose should then be increased to 0.8 mg/kg/day or the maximum tolerated dose.

Studies involving persons under 18 years of age have not been conducted, so the dosing regimen for this group has not been established.

Side effects

Very common (≥ 1/10)

Anemia, increased erythrocyte sedimentation rate, thrombocytopenia, thrombocytosis

Blepharitis, conjunctivitis, dry eye, eye irritation

Increase in transaminases

Cheilitis, dermatitis, dry skin, peeling of the skin of the palms and soles, itching,

erythematous rash, slight skin injury (risk of injury)

Arthralgia, myalgia, back pain

Hypertriglyceridemia, decreased high-density lipoprotein

Often (≥ 1/100,< 1/10)

Neutropenia

Headache

Epistaxis, dryness of the nasal mucosa, rhinopharyngitis

Alopecia

Hypercholesterolemia, hyperglycemia, hematuria, proteinuria

Rare (≥ 1/10,000,< 1/1 000)

Allergic skin reactions, anaphylactic reactions, hypersensitivity

Depression, worsening depression, aggressive tendencies, anxiety, mood lability

Very rare (≤ 1/10,000)

Gram-positive infections

Lymphadenopathy

Diabetes mellitus, hyperuricemia

Conduct disorder, psychosis, suicidal ideation, suicide attempts, suicide

Drowsiness, increased intracranial pressure, convulsions

Violation of visual acuity, cataracts, impaired color perception (passing after discontinuation of the drug), contact lens intolerance, corneal clouding, impaired dark adaptation (reduced twilight visual acuity), keratitis, optic neuritis (as a sign of intracranial hypertension), photophobia

Hearing loss

Vasculitis (Wegener's granulomatosis, allergic vasculitis)

Bronchospasm (especially in patients with asthma), hoarseness

Colitis, ileitis, dry throat, gastrointestinal bleeding, hemorrhagic diarrhea and inflammatory diseases gastrointestinal tract, nausea, pancreatitis

Hepatitis

Acne fulminans, acne exacerbation, erythema (of the face), exanthema, hair disease, hirsutism, nail dystrophy, paronychia, photosensitivity, pyogenic granuloma, skin hyperpigmentation, sweating

Arthritis, calcification (calcification of ligaments and tendons), premature closure of the growth plate of the epiphysis, exostosis (hyperostosis), decreased bone density, tendinitis

Glomerulonephritis

Enlargement of granulomatous tissues, malaise

Increase in blood creatine phosphokinase

Frequency unknown

Rhabdomyolysis

Contraindications

Hypersensitivity to isotretinoin or auxiliary components of the drug, including soybean oil. The drug is contraindicated in patients with soy allergy.

Concomitant therapy with tetracyclines

Liver failure

Hypervitaminosis A

Hyperlipidemia

Children and adolescents up to 18 years of age

Pregnancy, lactation

Women of childbearing age, if all conditions of the Pregnancy Prevention Program are not met

Carefully

Diabetes

History of depression

Obesity

Lipid metabolism disorder

Alcoholism

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Drug Interactions

Due to the possible increase in the symptoms of hypervitaminosis A, the simultaneous administration of Aknekutan and preparations containing vitamin A should be avoided.

Simultaneous use with other retinoids, incl. acitretin, tretinoin, retinol, tazarotene, adapalene, also increases the risk of hypervitaminosis A.

Since tetracyclines reduce efficacy and can also cause an increase in intracranial pressure, their use in combination with Acnecutane is contraindicated.

Acnecutane can weaken the effectiveness of progesterone preparations, so you should not use contraceptives containing low doses of progesterone.

Simultaneous use with drugs that increase photosensitivity (including sulfonamides, thiazide diuretics) increases the risk of sunburn. Combined use with local keratolytic drugs for the treatment of acne is not recommended due to the possible increase in local irritation.

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special instructions

Acnecutane should only be prescribed by physicians, preferably dermatologists, experienced in the use of systemic retinoids and aware of the risk of teratogenicity of the drug.

Most of the side effects of Acnecutane are dose dependent. Usually, side effects are reversible after dose adjustment or drug withdrawal, but some may persist after treatment is stopped.

Benign intracranial hypertension

Cases of benign intracranial hypertension have been reported, some of which have been associated with concomitant administration of tetracycline antibiotics. Signs and symptoms of benign intracranial hypertension include headache, nausea and vomiting, visual disturbances and swelling of the optic nerve papilla. With the development of benign intracranial hypertension in patients, Aknekutan therapy should be immediately canceled.

Psychiatric disorders

In rare cases, depression, psychotic symptoms and suicidal attempts have been described in patients treated with Aknekutan. Although their causal relationship with the use of the drug has not been established, special care should be taken in patients with a history of depression and all patients should be observed for depression during treatment with the drug, if necessary, referring them to the appropriate specialist.

However, discontinuation of Acnecutane may not be sufficient to alleviate symptoms and therefore additional psychiatric consultation may be necessary.

Diseases of the skin and subcutaneous tissues

In rare cases, at the beginning of therapy, an exacerbation of acne is noted, which disappears within 7-10 days without adjusting the dose of the drug.

Exposure to solar insolation and UV therapy should be limited. If necessary, use a sunscreen with a high protection factor (SPF 15 or higher).

Deep chemical dermabrasion and laser treatment should be avoided in patients receiving Acnecutane, as well as within 5-6 months after the end of treatment due to the possibility of increased scarring in atypical areas and less often, with the risk of post-inflammatory hyper- or hypopigmentation in the treated areas. During treatment with Acnecutane and for 6 months after it, epilation with wax applications should not be performed due to the risk of epidermal detachment, scarring and dermatitis.

During treatment, the use of local keratolytic or exfoliative anti-acne agents should be avoided, due to the possibility of increasing local irritation.

Diseases of the musculoskeletal system

After the use of Aknekutan in high doses for many years for the treatment of dyskeratosis, bone changes developed, including premature closure of the epiphyseal growth zones, calcification of tendons and ligaments, therefore, when prescribing the drug, the balance of possible benefit and risk should be carefully assessed.

Against the background of taking Acnecutane, pain in the muscles and joints, an increase in the level of creatine phosphokinase in serum, which may be accompanied by a decrease in the tolerance of intense physical activity, are possible.

visual impairment

Dry eyes, corneal opacities, worsening night vision, and keratitis usually resolve after therapy ends. Dry eye symptoms can be alleviated with an eye lubricating ointment or with tear replacement therapy. Contact lens intolerance may occur, which may lead to the need to wear glasses during therapy.

The deterioration of night vision began suddenly in some patients. Patients with visual impairments should be referred for consultation with a specialist ophthalmologist. In some cases, the abolition of Aknekutan may become necessary.

Since some patients may experience a decrease in night vision, which sometimes persists after the end of therapy, patients should be informed of the possibility of this condition, advising them to be careful when driving at night. The state of visual acuity must be carefully monitored.

It is necessary to observe patients with dryness of the conjunctiva for the possible development of keratitis.

Gastrointestinal disorders

Isotretinoin treatment is associated with exacerbations inflammatory diseases gastrointestinal tract, in particular, regional yelitis, in patients without prerequisites for such disorders. In patients with severe hemorrhagic diarrhea, Aknekutan should be discontinued immediately.

Hepatobiliary disorders

It is recommended to monitor liver function 1 month before treatment, 1 month after the start of treatment, and then every 3 months, except for special medical circumstances that warrant more frequent monitoring. If the level of hepatic transaminases exceeds the norm, it is necessary to reduce the dose of the drug or cancel it.

Fasting serum lipid levels should also be determined 1 month before treatment, 1 month after initiation, and then every 3 months, unless there is an indication for more frequent monitoring. Usually, lipid concentrations normalize after dose reduction or discontinuation of the drug, as well as with diet. Clinically significant elevations in triglycerides should be monitored, as elevations above 800 mg/dl may be associated with acute pancreatitis, possibly fatal. With persistent hypertriglyceridemia or symptoms of pancreatitis, Aknekutan should be discontinued.

allergic reactions

Rare cases of anaphylactic reactions have been described, which sometimes occurred after previous external use of retinoids. Dermal allergic reactions are extremely rare. Cases of severe allergic vasculitis, often accompanied by purpura (ecchymosis or petechiae), have been reported. Acute allergic reactions dictate the need to discontinue the drug and carefully monitor the patient.

High risk patients

Patients at high risk (with diabetes mellitus, obesity, alcoholism, or disorders of fat metabolism) may require more frequent laboratory monitoring of glucose and lipid levels during treatment with Acnecutane. During treatment with isotretinoin, an increase in fasting blood glucose levels was observed, as well as cases of the onset of diabetes.

During the period of treatment and within 30 days after its completion, it is necessary to completely exclude blood sampling from potential donors to completely exclude the possibility of this blood getting into pregnant patients (high risk of developing teratogenic and embryotoxic effects).

Both female and male patients need to be given patient information.

Additional Precautions:

Patients should be warned never to transmit this medical preparation to another person, but return unused capsules to their pharmacist at the end of therapy.

Pregnancy and lactation

The drug has a teratogenic effect!

Fetal malformations associated with exposure to Acnecutane include abnormalities of the central nervous system(hydrocephalus, cerebellar malformations/abnormalities, microcephaly), facial dysmorphism, cleft palate, outer ear malformations (absence of the outer ear, small or absent external auditory canals), visual disturbances (microophthalmia), cardiovascular disorders (malformations such as as tetralogy of Fallot, transposition of major vessels, septal defects), abnormalities thymus and anomalies of the parathyroid glands. A higher miscarriage rate was also observed.

If pregnancy occurs in women treated with Acnecutane, the pregnancy should be terminated and the patient should be referred to a specialized physician experienced in teratology for evaluation and recommendations.

Isotretinoin is contraindicated in women childbearing age unless all of the requirements set out in the Pregnancy Prevention Program are met:

The patient has severe acne (such as nodose, nodular, or other acne that leaves significant scarring) that is resistant to classical treatment consisting of systemic antibiotics and topical treatment

She understands the risk of developmental anomalies

She understands the need for regular monthly check-ups

She understands the need for effective continuous contraception, and takes one month before the start of the course of treatment, throughout the course and a month after the end of the course of treatment. It is necessary to use at least one, and preferably two, methods of complete contraception, including mechanical.

Even with amenorrhea, the patient must follow all appropriate measures for effective contraception.

It is necessary to use the contraceptive means that are prescribed to her correctly.

She is informed and understands everything possible consequences possible pregnancy and the need for immediate consultation with a doctor if there are risks of becoming pregnant

She understands and accepts the need for pregnancy testing before, during, and five weeks after treatment.

It confirms the awareness of all the risks and precautions that arise when taking isotretinoin.

These precautions also apply to women who are not having any sexual activity, unless the prescriber makes a good case that there really is no possibility of pregnancy.

The nominee must certify that:

The patient meets the requirements of the Pregnancy Prevention Program listed earlier and, if she has confirmed that she has an adequate level of understanding

The patient is aware of the requirements

The patient used two methods of effective contraception, including mechanical, one month before the start of treatment, during it and one month after

Pregnancy tests must be negative before, during and 5 weeks after the end of treatment. Test results should be recorded in the patient's record.

The use of contraceptives, as indicated above, during treatment with Acnecutane should be recommended even to those women who do not normally use contraceptive methods due to infertility (with the exception of patients who have undergone a hysterectomy) or who report that they are not sexually active.

Information on preventing pregnancy should be given to patients both orally and in writing.

Contraception

Patients should be given full information about pregnancy prevention and should be referred for contraceptive counseling if they are not using effective contraception.

As a minimum requirement, patients at potential risk of pregnancy should use at least one effective method contraception. Preferably, the patient should use two additional method contraception, including the barrier method. The use of contraception should continue for at least 1 month after the end of treatment with Acnecutane, even in patients with amenorrhea.

Pregnancy test

According to the established order medical examination on pregnancy is recommended during the first three days of the menstrual cycle as follows.

Before starting therapy:

To exclude the possibility of pregnancy before starting contraception, it is recommended that an initial pregnancy test be performed under medical supervision and a record of its date and result. In patients without a regular menstrual cycle, the timing of this pregnancy test should depend on the patient's sexual activity; the test should be performed approximately 3 weeks after the last unprotected intercourse. The doctor must provide the patient with complete information about contraception.

A supervised pregnancy test should also be performed at the time of the first isotretinoin prescription, or three days prior to that prescription. The date of this test may be delayed until the patient has been using contraceptives for at least 1 month. The purpose of this test is to confirm that the patient was not pregnant at the start of isotretinoin treatment.

Follow-up visits

Subsequent visits must be arranged at intervals of 28 days. The need for repeated pregnancy tests under medical supervision every month should be determined according to the local routine, taking into account the patient's sexual activity and the menstrual cycle (abnormal menstruation, periods of amenorrhea). If indicated, subsequent pregnancy tests should be carried out on the same day of the doctor's appointment during which the drug is prescribed, or 3 days before the doctor's visit.

End of therapy

Five weeks after stopping therapy, women should have a final pregnancy test to rule out pregnancy.

Restrictions on appointment and leave

For women of childbearing age, a course of isotretinoin treatment can be given for no longer than 30 days; continuation of treatment requires a new appointment. Ideally, pregnancy testing, isotretinoin administration, and isotretinoin dispensing should occur on the same day. Isotretinoin should be dispensed within a maximum of 7 days after its administration.

male patients

There is no reason to believe that treatment with isotretinoin can affect potency or other problems in men. However, men should be reminded that they should not share the drug with anyone, especially women.

lactation period

Aknekutan is highly lipophilic, therefore, the passage of isotretinoin into the mother's milk is very likely. Due to the likelihood of adverse events in mother and child, the use of Aknekutan is contraindicated in nursing mothers.

The drug contains sorbitol; patients with fructose intolerance are not recommended to use Aknekutan.

Features of influence medicinal product on the ability to manage vehicle or potentially dangerous mechanisms

Since some patients may experience a decrease in night vision, which sometimes persists after the end of therapy, patients should be informed about the possibility of this condition, advising them to be careful when driving or driving at night.

Overdose

Isotretinoin is a vitamin A derivative. The short-term toxic effects of hypervitaminosis A include severe headache, nausea and vomiting, drowsiness, irritability, and itching. These symptoms are considered reversible and decrease without the need for treatment.

Do not use after the expiry date stated on the package.

Terms of dispensing from pharmacies

On prescription

Manufacturer

SMB Technology S.A., Rue du Parc Industrial 39-6900 Marche-en-Famenne, Belgium

For citation: Lvov A.N., Kirilyuk A.V. Roaccutane® in the treatment of acne: standard regimens and a new low-dose regimen // BC. 2008. No. 23. S. 1541

About 25 years ago, the first reports appeared in the world scientific literature about the possibility of oral use of isotretinoin (13-cis-retinoic acid - Roaccutane®, F. Hoffmann-La Roche Ltd., Switzerland) for the treatment of severe forms of acne. The therapeutic triumph of this technique in complex inflammatory and sclerosing forms of acne, other dermatoses (for example, rosacea) was confirmed by numerous, constantly increasing number of solid publications from year to year, which, from the standpoint of evidence-based medicine, made it possible not only to reliably assess the clinical effectiveness of the drug, but also to objectify it. tolerability, as well as to draw up a clear range of indications and contraindications.

What are the currently well-established principles of systemic acne therapy with Roaccutane and what are possible ways modifications of well-known circuits? Before answering this question, let us turn to the unique cytoregulatory and pharmacokinetic properties of the drug, which, in accordance with modern indications and the individual situation, in most cases immediately consider it as a first-line drug for the initial treatment of acne.
By the beginning of the 70s of the XX century, information began to appear in the specialized literature about the presence of pronounced regulatory properties in relation to the sebaceous glands of animals and humans in one of the cis-derivatives of retinoic acid. A few years later, this drug was introduced into clinical practice under international name isotretinoin (13-cis isomer of retinoic acid), patented as Roaccutane® (F. Hoffmann-La Roche Ltd, Switzerland). A significant number of works all over the world have been devoted to the study of the unique properties of the drug. It has been established that Roaccutane®, interacting with nuclear receptors, affects the processes of differentiation of sebaceous gland cells, which leads to a pronounced decrease in the size of the sebaceous glands, suppression of activity and a sharp decrease in sebum excretion. Depending on the dose and duration of the drug, the sebostatic effect reaches 90% of the initial level. Additionally, Roaccutane® has a moderate immunomodulatory effect and has a mild anti-inflammatory effect. In this regard, Roaccutane® quickly became the world's number one treatment for severe (conglobate, phlegmonous and cystic) forms of acne. Currently, the drug is also prescribed for milder forms of acne (accompanied, in particular, by severe psychoemotional disorders, social maladaptation, as well as a tendency to scarring, etc.), which is due to a significant improvement in the quality of life of patients against the background of effective treatment. The latter is an indirect confirmation of the fact that often the benefits obtained from the use of Roaccutane® in any group of patients significantly exceed possible risk.
It can be stated that due to the study of the mechanisms of action of Roaccutane®, the pathogenesis of acne has largely become clear. As you know, the starting point for acne is genetically determined hyperandrogenism or increased sensitivity of sebocytes to testosterone derivatives. Ultimately, this background determines the leading importance of four factors: follicular hyperkeratosis, hypertrophy of the sebaceous glands with their hypersecretion, microbial hypercolonization and inflammatory response. The pathogenetic validity and effectiveness of the use of Roaccutane® is determined by the fact that this drug affects, to one degree or another, all links in the pathogenesis of acne.
Standard therapy regimens
Treatment usually begins with a dose of 0.5 mg/kg per day. As our more than a decade of experience with Roaccutane® shows, more than 200 patients with moderate (acne severity II-III) and predominantly severe (acne severity IV) forms of acne (n = 213; 133 men, 80 women), optimal the initial dose is 0.75 mg/kg. It provides a faster therapeutic effect with minimal side effects. In young patients, treatment can be started with a dose of 1.0 mg / kg per day, which makes it possible to quickly reach the total course dose. Dose adjustment is usually made 3-5 weeks after the start of therapy, depending on the effect and tolerability of the drug. In most patients, by the end of the 1st - the beginning of the 2nd week of treatment, an exacerbation of the skin process is noted, consisting primarily in an increase in the number of rashes. The latter is not a reason to reduce the daily dose, since this exacerbation soon subsides. After achieving a stable positive therapeutic effect, the daily dose can be adapted to maintenance (0.1-0.3 mg/kg). The duration of treatment with isotretinoin is usually at least 4 months, and usually 6-8 months (with a total course dose of 120-150 mg / kg). The stability of the treatment result and the absence of relapses largely depend on the achievement of the indicated course dose. So, according to our experience, the overall clinical efficacy of treatment of patients with conglobate form of acne (with localization of rashes on the skin of the face and trunk) after 8 months of therapy reached 92%, while in terms of long-term prognosis, a recurrence of the disease was subsequently observed only in 5.6% patients in this subgroup.
It is not uncommon to encounter a situation where dermatologists avoid prescribing Roaccutane® for fear of its allegedly expressed undesirable effects. In our opinion, these fears are exaggerated. The benefits of using Roaccutane far outweigh the risks. You should clearly understand the possible side effects of systemic isotretinoin and be informed about ways to correct them. Our observations show that the inevitable side effects are facial dermatitis and cheilitis. Less commonly observed dryness in the nose, "dry" blepharoconjunctivitis, mild episodic myalgia with physical activity. Deviations in laboratory parameters (primarily in the form of an increase in ALT and AST) are not always noted, they are usually unstable and normalize even without reducing the daily dose of the drug.
Isotretinoin has a strong teratogenic effect. Every woman of childbearing age receiving the drug must use effective contraceptives one month before treatment, during the entire period of treatment, and also within a month after its completion. We do not share the opinion about the unreasonable, in our opinion, prohibition of pregnancy within 2 years after the end of Roaccutane®. The latter, apparently, can be associated with an unjustified, purely mechanical transfer of the specified period (2 years) from the instructions for the use of other retinoids - etretinate and the currently used acitretin. The fact is that the calculation of the period of mandatory contraception recommended after the end of treatment is based on data on the half-life of the retinoid: to remove 99% of the drug from the body, a time equal to 7 half-lives is required. The half-life of etretinate is about 100 days, which leads to mandatory contraception for 2 years. The half-life of acitretin is on average only 2 days, however, it must be taken into account that in the human body acitretin can be esterified with the formation of etretinate. In this regard, a period of time after the end of treatment with acitretin was established, during which pregnancy should be avoided, also for a period of 2 years. The half-life of isotretinoin (Roaccutane®) averages 19 hours, the half-life of its main metabolite 4-oxo-isotretinoin averages 29 hours. Long-term circulating teratogenic substances in the body are not formed, endogenous concentrations of retinoids are restored approximately 2 weeks after the end of Roaccutane®. In this case, a period of obligate contraception lasting 4 weeks after the end of treatment seems reasonably sufficient. Nevertheless, we recommend prolonging the pregnancy ban up to 2 months after the end of therapy, which coincides with the opinion of reputable German dermatologists.
In women, therapy with Roaccutane® should begin on the 2nd-3rd day of the next normal menstrual cycle. Before starting treatment, patients should be informed about the appropriate precautions and possible consequences in writing. If pregnancy occurs while taking isotretinoin or within a month after its withdrawal, there is a significant risk of developing severe malformations of the organs and systems of the fetus (primarily the central nervous system and of cardio-vascular system). Isotretinoin should not be administered to women during lactation.
Other side effects of Roaccutane®, as already noted, are usually mild and dose-dependent, completely regressing at the end of treatment. Nevertheless, in the process of therapy, for the prevention of retinoid cheilitis, retinoid facial dermatitis, retinoid "dry" conjunctivitis, it is advisable for patients to recommend the application of various moisturizing and emollient drugs (hygienic lipstick, emollient creams, moisturizing eye drops by the type of "artificial tear", etc.).
Low-dose regimens
Recently, in connection with the expansion of indications for the use of Roaccutane® in the foreign scientific and practical literature, the issue of the so-called method of "low-dose" and "ultra-low-dose" use of the drug has been actively discussed. It should be noted that with the standard dosing regimen, low doses of the drug (0.1-0.3 mg / kg or 10 mg per day) were used at the final stages of treatment, while the pharmacokinetic properties of the drug (the half-life of the main metabolite - an average of 30 hours) allowed to use it both daily and intermittently, i.e. in one day. As both foreign and our own experience shows, the use of Roaccutane® immediately from low doses is possible in a number of conditions, including severe seborrhea associated with mild acne, diseases from the group of decalvaning folliculitis, excoriated acne, and acne varying degrees severity, subject to the psychological mood of patients for treatment with systemic retinoids.
It should be noted that empirically many dermatologists and cosmetologists around the world use low doses of Roaccutane® in practice, however, there have been practically no reliable clinical studies based on the principles of evidence-based medicine. Fundamentally, in the appointment of low doses in the so-called "problem skin" abroad, the following four approaches are distinguished: 1) the appointment of Roaccutane® at a dose of 10 mg per day, regardless of body weight, for approximately 4 weeks; then 10 mg every 5 days a week; then 10 mg every 3 days per week; then 10 mg every 2 days per week; then 10 mg once a week, while the stepwise dose adjustment is carried out monthly; 2) 5 mg per day, regardless of body weight for a long time; 3) 2.5 mg per day, regardless of body weight for a long time; 4) 2.5 mg per day twice a week for a long time. Of all the proposed schemes, the first method of using low-dose Roaccutane®, developed and tested in practice from 1991 to 2004 by G. Plewig and co-workers, seems to us the most reasonable. According to them, one study included 28 patients with grade III and IV acne who received isotretinoin at a standard dose of 0.5 mg/kg daily for 6 months. In the second study, patients received ultra-low doses of isotretinoin from 10 to 5 mg per day, as well as 2.5 mg 2 times a week for 6 months. In the first group, the effectiveness of the therapy was confirmed: the number of rash elements decreased, the number of follicular elements decreased as an indicator of therapeutic efficacy, the level of P. acne colonization decreased, and sebum excretion decreased. In the second study, the effectiveness was also noted in the main clinical parameters, the level of seborrhea and the amount of P. acne decreased. Thus, the data obtained demonstrate the effectiveness of low doses of isotretinoin for the treatment of seborrhea, persistent acne1, as well as maintenance therapy for patients with severe forms of acne treated with higher doses, as well as for the treatment of patients with various sebaceous hyperplasia. In our experience, we have also good effect from its use in patients with moderate acne (photo 1, 2). At the same time, the course dose when using low-dose Roaccutane® regimens can be 15, 7.5 and even 1 mg/kg of body weight, which completely reduces the current idea of the need to calculate it as a significant benchmark for the clinical effectiveness of Roaccutane® therapy. We fully share the postulate put forward by this authoritative author about the optionality of calculating the course dose in clinical practice.
Combination therapy with low doses of isotretinoin in combination with other systemic or topical acne treatments also seems to be a very tempting target for dermatologists. A group of researchers evaluated the effectiveness of treating patients with acne with low doses of isotretinoin in combination with cyproterone acetate. 27 patients were treated for 12 weeks at 0.05 mg/kg/day. isotretinoin (10 patients) or 50 mg/day. cyproterone acetate (8 patients), or two drugs at the same time in the same doses (9 patients). The study showed that the clinical efficacy in all groups was approximately the same, however, the increase in triglyceride levels caused by isotretinoin was significantly less common during concomitant therapy with an antiandrogen drug.
A promising direction is the use of low doses of Roaccutane® in patients with late persistent acne (acne adultorum). In a study conducted by R. Marks, the effectiveness of treating patients with advanced acne aged 30-60 years with low doses of isotretinoin at a dose of 0.25 mg/kg per day for 6 months was confirmed. Against the background of the therapy, patients noted regression of acne manifestations, stable remission for 36 months after the end of treatment, and very good tolerability of the therapy. In the course of the work, the effectiveness of using low doses of isotretinoin in a group of patients with torpid acne was also noted in comparison with the use of external forms of retinoids and benzyl peroxide. The use of isotretinoin in the standard regimen caused a significantly greater number of side effects (dry skin, cheilitis, changes in biochemical parameters), which was one of the reasons for interrupting isotretinoin therapy in some patients from this group.
One of the key questions when using low doses of Roaccutane® is how long can such therapy be carried out in a safe mode? It is no secret that long-term use of systemic retinoids in standard or high doses can lead to changes in biochemical markers of bone tissue and toxic effects on bone tissue (early closure of growth zones). With regard to the low-dose regimen, this view has been refuted. Trifiro G. and Norbiato G. studied the ratio of markers of various types of collagen, as well as excretory indicators of bone resorption in 10 young people aged 17-19 years who received treatment with low and medium doses of Roaccutane®. Against the background of a good clinical effect, the effect of isotretinoin on skin type I collagen was noted, while no changes were detected in biochemical parameters reflecting the condition of the bones. Given this fact, it can be hypothesized that the treatment of patients with acne with low doses of isotretinoin over a long period of time can contribute not only to the reduction of inflammatory elements of acne, but also to a significant correction of cicatricial changes (post-acne).
Of undoubted interest is the use of low doses of Roaccutane® in psychosomatized forms of acne, the skin process in which does not always correlate with the severity mental disorders. So, in a study by Ng C.H., Schweitzer I. (2003), with a confirmed association of depressive spectrum disorders and acne of varying severity, dynamics was noted during treatment with low doses of Roaccutane® not only from the skin process, but also from psychopathological symptoms.
In this context, we can also refer to priority own data on the inclusion of low doses of systemic isotretinoin in the therapeutic complex for excoriated acne. In all patients with excoriated acne that developed within the framework of the psychopathological symptom complex of overvalued hypochondria of beauty (n=28, 25 women, 3 men, mean age 25.1±2.3 years), self-destruction phenomena prevailed over manifestations of acne vulgaris in the skin status. At the first stage, we prescribed treatment with the use of psychotropic drugs - atypical antipsychotics (risperidone 2-4 mg / day, olanzapine 2.5-10 mg / day, etc., for 6-8 weeks) and antidepressants (SSRIs - fluoxetine 40 mg/day, sertraline up to 100 mg/day, etc., 6-8 weeks). Subsequently, Roaccutane® was prescribed at an initial dose sufficient to stop the minimal manifestations of acne, at the rate of 0.3 mg/kg, subsequently the dose was reduced to 0.15-0.1 mg/kg per day. After achieving a stable clinical improvement, they switched to an intermittent intake of 10 mg of Roaccutane® every other day. The duration of treatment was 4-6 months. In the process of combined treatment, positive dynamics was noted in the form of regression of comedones, papules, pustules, and seborrhea phenomena. Due to the absence of the appearance of new acne elements, as well as the reduction of psychopathological symptoms, the number of self-extractions also decreased (Fig. 1, photo 3.4). The overall clinical efficacy was 78.2%.
Tolerability of low doses of Roaccutane® was good. The phenomena of retinoid dermatitis were significantly less pronounced in comparison with the treatment according to the standard schemes for the use of Roaccutane®. All patients developed symptoms of retinoid dermatitis on the 2nd-3rd day of therapy (the phenomena of cheilitis, dryness and flaking of the skin of the face were especially disturbing), approximately half of the patients experienced moderate dryness of the skin of the hands during 1-2 months of therapy. Thus, isotretinoin, when used systemically in low doses, is sufficient to stop background skin changes in excoriated acne and, in combination with neuroleptic therapy, significantly improves the quality of disease therapy.
Another model for the use of a low-dose regimen can serve as a dermatosis belonging to the group of inverse acne: decalvaning folliculitis of the scalp, considered by some authors as an erased version of abscessing and undermining folliculitis and Hoffmann's perifolliculitis (photo 5). The disease has a pathogenesis similar to acne, is characterized by an extremely torpid course, is resistant to systemic antibiotic therapy and external retinoids, at the same time, the process is often erased, subclinical, and therefore the appointment of standard doses of Roaccutane® is unjustified. There is only a single experience of treating this condition according to the considered innovative scheme.
In conclusion, it should be especially noted that despite the decrease in side effects with low-dose isotretinoin, its teratogenicity and, as a result, obligatory contraception for the entire period of treatment and a month after it remains an unchanged fact. It should be taken into account that the prolongation of the period of taking the drug, even at low doses, leads to an increased risk of pregnancy, even in conditions of adequate contraception.
Thus, based on literature data and numerous own observations, we believe that Roaccutane® is still the most pathogenetically justified operating means for the treatment of moderate and especially severe forms of acne, giving a persistent high therapeutic effect with minimal and well-controlled side effects. The use of low and very low doses of isotretinoin for the treatment of patients with various forms of acne is a new and promising method. This approach allows not only minimizing the possible effects of standard therapy and expanding therapeutic options, but also significantly optimizes pharmacoeconomic indicators in the direction of reducing the cost of treatment with Roaccutane®.

1 Plewig also considers the treatment of severe, conglobate-
forms of acne with low doses of isotretinoin: the first
Oral corticosteroids 1 mg/kg body weight are used for 7-14 days
body, then within 7-10 days - antibiotics from the macrolide group,
subsequently, after a decrease in the acute inflammatory process
treatment with isotretinoin at a dose of 0.2 to 0.4 mg / kg of body weight is prescribed
body. This scheme allows to achieve faster clinical
effect than isotretinoin monotherapy.

Literature
1. Samgin M.A., Gromova S.A., Kolesnikov Yu.Yu. // Vestn dermatol venerol, 1989; 56-60
2. Samgin M.A., Lvov A.N., Potekaev N.S. and others // Ross Journal of Skin Veins Bol 2002, 3, 60-65
3. Lvov A.N., Samgin M.A. Excoriated acne: the first experience of treatment with low-dose roaccutane // Abstracts of the X Russian National Congress "Man and Medicine". - Moscow, 7-11 April 2003 52
4. Skripkin Yu.K., Kubanova A.A., Samsonov V.A. and others // Vestn dermatol venerol, 1994; 2:3-6
5. Miner I.Ya., Pokryshkin V.I., Pisarenko M.F. // Vestn dermatol 1984; 3:26-31
6 Chu A; Cunliffe WJ // J Eur Acad Dermatol Venereol, 1999 May, 12:3, 263
7 Geiger JM; Saurat JH // Dermatol Clin, 1993 Jan, 11:1, 117-29
8. Kindmark A, et al // Acta Derm Venereol, 1998, Jul 7: 24-9
9. Leyden JJ // J Am Acad Dermatol 1998 Aug, 39:2 Pt 3, S45-9
10. Orfanos CE // Dermatology, 1998, 196:1, 140-7
11. Plewig G., Jansen T. Isotretinoin. // In: Fortschritte der praktischen Dermatologie und Venerologie - Springer - Berlin, 1994; pp. 280-284
12. Wessels F. // S Afr Med J, 1999 Jul, 89:7 Pt 2, 780-4
13. Wiegand UW. // J Am Acad Dermatol, 1998 Aug, 39:2 Pt 3, 8-12
14. Amichai B, Shemer A, Grunwald MH. Low-dose isotretinoin in the treatment of acne vulgaris. //J Am Acad Dermatol. 2006 Apr;54(4):644-6.
15. Benifla JL, Ville Y, Imbert MC, Frydman R, Thomas A, Pons JC. Fetal tissue dosages of retinoids. Experimental study concerning a case of isotretinoin (Roaccutan) administration and pregnancy. // Fetal Diagn. Ther. 1995 May-Jun;10(3):189-91
16. Dreno B, Daniel F, Allaert FA, Aube I. Acne: evolution of the clinical practice and therapeutic management of acne between 1996 and 2000. // Eur J Dermatol. 2003 Mar-Apr;13(2):166-70.
17. Lvov A.N., Samgin M.A. Low doses of systemic isotretinoin for acne excoriee: the first experience of treatment // JEADV, Abstr. of the 12th Congress of the EADV, 15-15 Oct. 2003 Barcelona. Spain - p.168
18. Marks R. Acne and its management beyond the age of 35 years. //Am J Clin Dermatol. 2004;5(6):459-62.
19. Marsden JR, Laker MF, Ford GP, Shuster S. Effect of low dose cyproterone acetate on the response of acne to isotretinoin. // Br J Dermatol. 1984 Jun;110(6):697-702
20. Ng CH, Schweitzer I The association between depression and isotretinoin use in acne. //Aust N Z J Psychiatry. 2003 Feb;37(1):78-84.
21. Plewig G, Hennes R, Maas B, Mack-Hennes A. Remission behavior following low-dose 13-cis-retinoic acid in papulopustular acne // Z Hautkr. 1986 Sep 1;61(17):1205-10.
22. Plewig G. Isotretinoin Therapie: Wann, was, wie? // In: Fortschritte der praktischen Dermatologie und venerologie 2004 (Hrsg. G. Plewig, P. Kaudewitz, C.A. Sander) - Springer Berlin Heidelberg - 2005, p. 245-258
23. Trifiro G, Norbiato G. Type I collagen N-telopeptide variation in adolescents receiving oral isotretinoin for severe acne. // J Pediatr Endocrinol Metab. 2002 Jan;15(1):35-9.
24. Zouboulis CC. Exploration of retinoid activity and the role of inflammation in acne: issues affecting future directions for acne therapy. // J Eur Acad Dermatol Venereol. 2001;15 Suppl 3:63-7.

Roaccutane is a powerful internal acne treatment for severe acne only. It can be drunk exclusively as directed by a dermatologist strictly at the indicated doses. Roaccutane for acne may be prescribed initially if other treatments have not helped, and the form of acne is extremely severe. The drug has a lot of side effects and only 50% of acne is completely cured when taking Roaccutane.

How Roaccutane Treats Acne

Until the end, the principle of operation of Roaccutane has not been established, but doctors attribute this to the suppression of sebum production and the reduction in the size of comedones using the main active substance isotretinoin. Isotretinoin has been shown to have an antiseptic effect.

Isotretinoin also thins the stratum corneum of the epidermis in order to more easily penetrate deep into the affected area. Due to the fact that Roaccutane suppresses the secretion of sebum by reducing the sebaceous glands themselves, this reduces the migration of bacteria in the ducts. And due to the fact that the stratum corneum is thinned, sebum has an outlet to the outside, from which there is no blockage of the pore and, as a result, a pimple.

Roaccutane for acne, we repeat once again, is prescribed only by a doctor and, preferably, a dermatologist. For mild to moderate acne, do not immediately start with Roaccutane. Its effectiveness is not always justified: the number of side effects exceeds the ability to have a clean face. Only half of those treated for acne with Roaccutane completely got rid of them. The rest did not get rid of at all or after stopping the use of the drug received an aggressive relapse.

We will not prescribe doses here, because. they can only be prescribed by a doctor specifically for your condition. But it is sold in pharmacies in a dosage of 10 mg and 20 mg. On average, acne treatment with Roaccutane lasts from 4 months to 6 months. Long-term use of the drug is not recommended. All the time of treatment should be controlled by your doctor. Often in the first days of treatment, there is a sharp exacerbation of acne, and after stopping treatment, the skin condition may not improve. Roaccutane is taken in capsule form with meals. Must be submitted monthly general analysis blood and other tests prescribed by a doctor. If you experience any side effects, tell your doctor right away.

Interactions of Roaccutane with other drugs and procedures

Roaccutane should not be combined with vitamin A, hypervitaminosis A may occur. Should not be used with tetracyclines and contraceptives containing progesterone.

Due to the thinning of the stratum corneum, you can not stay in the sun or use sunscreens with a high SPF level. During treatment and for 1 year after treatment, hair removal procedures, surgical and cosmetic interventions, laser interventions, dermabrasion are prohibited. This is associated with a high risk of scarring and age spots.

In no case should pregnant women and breastfeeding women treat acne with Roaccutane, because. it directly affects the fetus. Before prescribing treatment, the doctor makes you do a pregnancy test twice. During treatment with Roaccutane, contraceptives must be strictly adhered to, otherwise the child may not be born.

Side effects of Roaccutane

Roaccutane for acne has many horrendous side effects that can occur with the use of the drug. They are described in detail in the instructions for the drug, and here we will describe the most common ones.

Bone pain, dry skin, mucous membranes, headache, fever, nausea, rash, itching, nosebleeds, intolerance to contact lenses - observed in most patients, tk. it is associated with hypervitaminosis A.
swelling, numbness of the limbs, abdominal pain, insomnia and, conversely, excessive sleepiness, sensitivity to light, facial dermatitis, rash, sweating - in about 10%
aggressive or withdrawn behavior, depression, suicidal state, convulsions, intracranial pressure, internal bleeding, bowel disease, and more.

There is another similar drug Aknekutan. It appeared on the Russian market quite recently since 2010 and has fewer side effects, although it is also based on isotretinoin, but less isotretinoin passes through the blood, and the amount of active ingredients is the same as with Roaccutane. But we have a separate article about this drug.

How much is Roaccutane

Roaccutane, in addition to all its dangerous side effects, also has a high price, depending on the dosage, from 1300 to 2900 rubles per pack of 30 capsules.

10 mg each - about 1500 rubles
20 mg each - about 2600 rubles

Roaccutane Reviews

I was in a very dangerous state - my whole face was full of potholes and inflammation, nothing helped: neither a beautician, nor a dermatologist, nor vitamins, injections, blood transfusions, etc. The dermatologist prescribed Roaccutane and, lo and behold, a week later the face became even worse than before. I came to her in a rage, but she reassured me that many people react this way at first with an aggravation, then it gets easier. Dear capsules, 1 pack was enough for me for a month. I was treated for half a year. The face became noticeably better, no longer as scary as before, but the acne did not completely go away, the potholes remained, there were spots and inflammation too. Now I have a break in treatment, the dermatologist wants me to take the course again in 2 months and says that after the end of the treatment, there will either be a new relapse or improve.

I was suggested immediately by a dermatologist to start with Roaccutane. I read the instructions and was shocked. After it, you can’t give birth for at least 2 more years and, sorry, but I’m not ready to sacrifice my health and my child for the sake of some ghostly improvements. I refused treatment with Roaccutane, I’d rather just drink vitamin A. By the way, when I got pregnant, my acne went away on its own and they weren’t very scary, like in the pictures.

After suffering for a long time in decisions, he nevertheless decided on Roaccutane. A lot of abscesses all over the face, every day 2-3 got out, a lot of subcutaneous ones. External medicines and antibiotics did not help. I started taking Roaccutane, for the first 2 weeks it got even worse, but then it calmed down and my face began to clean up quietly, BUT a terrible depression came almost to the end, my liver hurt badly and I constantly wanted to sleep. But I went through the whole course, survived and now I walk with a clean face and happy. Thank you all, Roaccutane saved me, although it made me feel its terrible power.

33 comments on Roaccutane for acne:

INN: Isotretinoin

Manufacturer: SMB Technology S.A.

Anatomical-therapeutic-chemical classification: Isotretinoin

Registration number in the Republic of Kazakhstan: No. RK-LS-5 No. 021046

Registration period: 24.12.2014 - 24.12.2019

Instruction

Tradename

Aknekutan

International non-proprietary name

Isotretinoin

Dosage form

Capsules 8 mg and 16 mg

Compound

One capsule contains

active substance- isotretinoin 8.00 mg or 16.00 mg,

Excipients: stearoyl macrogolglycerides, refined soybean oil, sorbitol oleate,

composition of gelatin capsules No. 3 (lid and body): gelatin, iron oxide red (E 172), titanium dioxide (E 171),

composition of gelatin capsules No. 1:

lid: gelatin, iron oxide yellow (E 172), indigo carmine (E 132), titanium dioxide (E 171), titanium dioxide (E 171),

frame: gelatin, titanium dioxide (E 171).

Description

Gelatin capsules No. 3, with a cap and a body of orange color (for a dosage of 8 mg).

Gelatin capsules No. 1, with a green cap and a white body (for a dosage of 16 mg).

The contents of the capsules are an orange waxy paste.

Pharmacotherapeutic group

Preparations for the treatment of acne.

Retinoids for systemic treatment of acne. Isotretinoin.

ATX code D10BA01

Pharmacological properties

Pharmacokinetics

Suction

Distribution Isotretinoin is almost completely (99.9%) bound to plasma proteins, mainly to albumin.

Metabolism Isotretinoin is metabolized to form three major metabolites in plasma: 4-oxo-isotretinoin, tretinoin (all-trans retinoic acid) and 4-oxo-retinoin, as well as less significant metabolites, including also glucuronides. The main metabolite is 4-oxo-isotretinoin, its plasma level in the equilibrium state is 2.5 times higher than the concentration of the parent drug. Several enzymes of the cytochrome system are involved in the conversion of isotretinoin to 4-oxo-isotretinoin and tretinoin: CYP2C8, CYP2C9, CYP2B6 and, probably, CYP3A4, as well as CYP2A6 and CYP2E1. At the same time, none of the isoforms, apparently, plays a dominant role.

Metabolites of isotretinoin have high biological activity. The clinical effects of the drug in patients may be the result of the pharmacological activity of isotretinoin and its metabolites. Enterohepatic circulation may play a significant role in the pharmacokinetics of isotretinoin in humans.

breeding

Isotretinoin is excreted by the kidneys and bile in approximately equal amounts.

Isotretinoin refers to natural (physiological) retinoids. Endogenous concentrations of retinoids are restored approximately 2 weeks after the end of taking Aknekutan. Pharmacokinetics in special cases

Since data on the pharmacokinetics of the drug in patients with impaired liver function are limited, isotretinoin is contraindicated in this group of patients.

Renal failure of mild to moderate severity does not affect the pharmacokinetics of isotretinoin.

Pharmacodynamics

Isotretinoin is a stereoisomer of all-trans retinoic acid (tretinoin).

The exact mechanism of action of isotretinoin has not yet been identified, however, it has been established that the improvement in the clinical picture of severe forms of acne is associated with the suppression of the activity of the sebaceous glands and a histologically confirmed decrease in their size. Sebum is the main substrate for growth propionibaWithterium acnes therefore, reducing sebum production inhibits bacterial colonization in the duct.

The anti-inflammatory effect of isotretinoin on the skin has been proven.

Indications for use

severe forms of acne (nodular cystic, conglobate, or acne with a risk of scarring) refractory to appropriate courses of standard systemic antibiotic and topical therapy

Dosage and administration

The therapeutic efficacy of Aknekutan and its side effects depend on the dose and vary in different patients. Therefore, it is important to individually select doses during treatment.

Capsules are taken with meals, once or twice a day.

The initial dose of Acnecutane is 0.4 mg/kg per day, in some cases up to 0.8 mg/kg of body weight per day.

The optimal course cumulative dose is 100-120 mg/kg. Complete remission of acne is often achieved within 16-24 weeks of treatment.

In most patients, acne disappears completely after a single course of treatment.

Dosing in special cases

In patients with severe renal insufficiency, treatment should be initiated at a low dose (eg, 8 mg/day). The dose should then be increased to 0.8 mg/kg/day or the maximum tolerated dose.

Studies involving persons under 18 years of age have not been conducted, so the dosing regimen for this group has not been established.

Side effects

ABOUThenyhourthen (≥ 1/10)

- anemia, increased erythrocyte sedimentation rate, thrombocytopenia, thrombocytosis

Blepharitis, conjunctivitis, dry eye, eye irritation

Increase in transaminases

Cheilitis, dermatitis, dry skin, peeling of the skin of the palms and soles, itching,

erythematous rash, slight skin injury (risk of injury)

Arthralgia, myalgia, back pain

Hypertriglyceridemia, decreased high-density lipoprotein

Often (≥ 1/100, < 1/10)

Neutropenia

Headache

Epistaxis, dryness of the nasal mucosa, rhinopharyngitis

Alopecia

Hypercholesterolemia, hyperglycemia, hematuria, proteinuria

Redko (≥1 /10 000, < 1/1 000)

Allergic skin reactions, anaphylactic reactions, hypersensitivity

Depression, worsening depression, aggressive tendencies, anxiety, mood lability

Very rarely(≤ 1/10 000)

Gram-positive infections

Lymphadenopathy

Diabetes mellitus, hyperuricemia

Conduct disorder, psychosis, suicidal ideation, suicide attempts, suicide

Drowsiness, increased intracranial pressure, convulsions

Hearing loss

Vasculitis (Wegener's granulomatosis, allergic vasculitis)

Bronchospasm (especially in patients with asthma), hoarseness

Colitis, ileitis, dry throat, gastrointestinal bleeding, hemorrhagic diarrhea and inflammatory diseases of the gastrointestinal tract, nausea, pancreatitis

Hepatitis

Acne fulminans, acne exacerbation, erythema (of the face), exanthema, hair disease, hirsutism, nail dystrophy, paronychia, photosensitivity, pyogenic granuloma, skin hyperpigmentation, sweating

Arthritis, calcification (calcification of ligaments and tendons), premature closure of the growth plate of the epiphysis, exostosis (hyperostosis), decreased bone density, tendinitis

Glomerulonephritis

Enlargement of granulomatous tissues, malaise

Increase in blood creatine phosphokinase

Frequency unknown

Rhabdomyolysis

Contraindications

hypersensitivity to isotretinoin or auxiliary components of the drug, including soybean oil. The drug is contraindicated in patients with soy allergy.

concomitant therapy with tetracyclines

liver failure

hypervitaminosis A

hyperlipidemia

children and adolescents up to 18 years of age

pregnancy, lactation

women of childbearing age, if all conditions of the Pregnancy Prevention Program are not met

Carefully

diabetes

history of depression

obesity

lipid metabolism disorder

alcoholism

Drug Interactions

Due to the possible increase in the symptoms of hypervitaminosis A, the simultaneous administration of Aknekutan and preparations containing vitamin A should be avoided.

Simultaneous use with other retinoids, incl. acitretin, tretinoin, retinol, tazarotene, adapalene, also increases the risk of hypervitaminosis A.

Since tetracyclines reduce efficacy and can also cause an increase in intracranial pressure, their use in combination with Acnecutane is contraindicated.

Acnecutane can weaken the effectiveness of progesterone preparations, so you should not use contraceptives containing low doses of progesterone.

special instructions

Acnecutane should only be prescribed by physicians, preferably dermatologists, experienced in the use of systemic retinoids and aware of the risk of teratogenicity of the drug.

Most of the side effects of Acnecutane are dose dependent. Usually, side effects are reversible after dose adjustment or drug withdrawal, but some may persist after treatment is stopped.

Benign intracranial hypertension

Cases of benign intracranial hypertension have been reported, some of which have been associated with concomitant administration of tetracycline antibiotics. Signs and symptoms of benign intracranial hypertension include headache, nausea and vomiting, visual disturbances, and papilledema. With the development of benign intracranial hypertension in patients, Aknekutan therapy should be immediately canceled.

Psychiatric disorders

However, discontinuation of Acnecutane may not be sufficient to alleviate symptoms and therefore additional psychiatric consultation may be necessary.

Diseases of the skin and subcutaneous tissues

In rare cases, at the beginning of therapy, an exacerbation of acne is noted, which disappears within 7-10 days without adjusting the dose of the drug.

Exposure to solar insolation and UV therapy should be limited. If necessary, use a sunscreen with a high protection factor (SPF 15 or higher).

During treatment, the use of local keratolytic or exfoliative anti-acne agents should be avoided, due to the possibility of increasing local irritation.

Diseases of the musculoskeletal system

visual impairment

It is necessary to observe patients with dryness of the conjunctiva for the possible development of keratitis.

Gastrointestinal disorders

Treatment with isotretinoin is associated with exacerbations of inflammatory diseases of the gastrointestinal tract, in particular, regional yelitis, in patients without prerequisites for such disorders. In patients with severe hemorrhagic diarrhea, Aknekutan should be discontinued immediately.

Hepatobiliary disorders

allergic reactions

Rare cases of anaphylactic reactions have been described, which sometimes occurred after previous external use of retinoids. Skin allergic reactions are extremely rare. Cases of severe allergic vasculitis, often accompanied by purpura (ecchymosis or petechiae), have been reported. Acute allergic reactions dictate the need to discontinue the drug and carefully monitor the patient.

High risk patients

Both female and male patients need to be given patient information.

Additional Precautions:

Patients should be warned never to pass this medicinal product to another person, but to return unused capsules to their pharmacist at the end of therapy.

Pregnancy and lactation

The drug has a teratogenic effect!

Fetal malformations associated with exposure to Acnecutane include central nervous system abnormalities (hydrocephalus, cerebellar malformations/abnormalities, microcephaly), facial dysmorphism, cleft palate, external ear malformations (lack of the external ear, small or absent external auditory canals), disorders of the organ of vision (microophthalmia), cardiovascular disorders (malformations such as tetralogy of Fallot, transposition of the main vessels, septal defects), anomalies of the thymus gland and anomalies of the parathyroid glands. A higher miscarriage rate was also observed.

Isotretinoin is contraindicated in women of childbearing age unless all of the requirements outlined in the Pregnancy Prevention Program are met:

The patient has severe acne (such as nodose, nodular, or other acne that leaves significant scarring) that is resistant to classical treatment consisting of systemic antibiotics and topical treatment

She understands the risk of developmental anomalies

She understands the need for regular monthly check-ups

Even with amenorrhea, the patient must follow all appropriate measures for effective contraception.

It is necessary to use the contraceptive means that are prescribed to her correctly.

She is informed and understands all the possible consequences of a possible pregnancy and the need for immediate consultation with a doctor if there are risks of becoming pregnant

She understands and accepts the need for pregnancy testing before, during, and five weeks after treatment.

It confirms the awareness of all the risks and precautions that arise when taking isotretinoin.

These precautions also apply to women who are not having any sexual activity, unless the prescriber makes a good case that there really is no possibility of pregnancy.

The nominee must certify that:

The patient meets the requirements of the Pregnancy Prevention Program listed earlier and, if she has confirmed that she has an adequate level of understanding

The patient is aware of the requirements

The patient used two methods of effective contraception, including mechanical, one month before the start of treatment, during it and one month after

Pregnancy tests must be negative before, during and 5 weeks after the end of treatment. Test results should be recorded in the patient's record.

Information on preventing pregnancy should be given to patients both orally and in writing.

Contraception

Patients should be given full information about pregnancy prevention and should be referred for contraceptive counseling if they are not using effective contraception.

As a minimum requirement, patients at potential risk of pregnancy must use at least one effective method of contraception. It is desirable that the patient use two additional methods of contraception, including a barrier method. The use of contraception should continue for at least 1 month after the end of treatment with Acnecutane, even in patients with amenorrhea.

Pregnancy test

According to the established procedure, a medical examination for pregnancy is recommended during the first three days of the menstrual cycle as follows.

Before starting therapy:

Follow-up visits

End of therapy

Five weeks after stopping therapy, women should have a final pregnancy test to rule out pregnancy.

Restrictions on appointment and leave

male patients

lactation period

The drug contains sorbitol; patients with fructose intolerance are not recommended to use Aknekutan.

Features of the influence of the drug on the ability to drive a vehicle or potentially dangerous mechanisms

Mechanism of action

Standard dosing regimen

Contraindications

Dosing in special cases

kidney failure

Pregnancy

special instructions

Interaction with other drugs

Side effects

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Dosage and administration

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special instructions

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Overdose

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How Roaccutane Treats Acne

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Roaccutane Reviews

33 comments on Roaccutane for acne:

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