Aknekutan new packaging. Aknekutan: instructions for use of capsules. Aknekutan instructions for use

Dosage form"type="checkbox">

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

Medicines for treatment acne.

Retinoids for systemic treatment acne rash. Isotretinoin.

ATX code D10BA01

Pharmacological properties"type="checkbox">

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 maximum concentrations in plasma (Cmax) at steady state after taking 80 mg of isotretinoin on an empty stomach was 310 ng / ml (range 188 - 473 ng / ml) and was 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.

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

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, mild and medium degree 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, but it has been found that the improvement clinical picture severe acne is associated with 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 necessary control for their use.

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.

At poor tolerance recommended dose, 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 maximum possible effectiveness in such patients, treatment should be continued at the maximum tolerated dose for the usual duration.

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 Acnecutane 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), intolerance contact lenses, clouding of the cornea, impaired dark adaptation (decrease in twilight visual acuity), keratitis, neuritis optic nerve(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 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 may reduce 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.

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.

Majority side effects Acnecutane is 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

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 sunscreen with high value protective factor (SPF 15 and above).

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 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 possible development 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

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. Must be clinically monitored significant increase triglyceride levels, since their rise above 800 mg / dl may be accompanied by the development 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 (those with diabetes, obesity, alcoholism, or fat metabolism) during treatment with Acnecutane, more frequent laboratory monitoring of glucose and lipid levels may be required. 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 in order to completely exclude the possibility of this blood getting into pregnant patients ( high risk development of teratogenic and embryotoxic effects).

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), thymus anomalies and anomalies parathyroid glands. There was also more high frequency miscarriages.

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

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

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.

Usage contraceptives as stated above, during treatment with Acnecutane, even 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 should be advised.

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. Preferably, the patient should use two additional method contraception, including 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:

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 drive a vehicle or potentially dangerous machinery

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. toxic effect 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

A drug Aknekutan- acne treatment
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 of the duct.
Aknekutan inhibits the proliferation of sebocytes and acts on acne, restoring normal process cell differentiation, stimulates regeneration processes.
In addition, the anti-inflammatory effect of isotretinoin on the skin has been proven.

Pharmacokinetics

Since the kinetics of isotretinoin and its metabolites is linear, its plasma concentrations during therapy can be predicted based on data obtained after a single dose. This property of the drug also suggests that it does not affect the activity of hepatic enzymes involved in the metabolism of drugs.
The high bioavailability of Acnecutane is due to the large proportion of dissolved isotretinoin in the preparation, and may increase if the drug is taken 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 2-4 hours. The concentration of isotretinoin in plasma is 1.7 times higher than in the blood, due to poor penetration of isotretinoin into red blood cells. Communication with plasma proteins (mainly with albumin) - 99.9%.
Equilibrium concentrations of isotretinoin in the blood (Css) in patients with severe forms of 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 (the main metabolite) in these patients were 2.5 times higher than those of isotretinoin.
The concentration of isotretinoin in the epidermis is 2 times lower than in serum.
It is metabolized to form 3 main biologically active metabolites - 4-oxo-isotretinoin (main), tretinoin (all-trans-retinoic acid) and 4-oxo-retinoin, as well as less significant metabolites, including also glucuronides. Since isotretinoin and tretinoin are reversibly converted into each other in vivo, the metabolism of tretinoin is associated with the metabolism of isotretinoin. 20-30% of a dose of isotretinoin is metabolized by isomerization. Enterohepatic circulation may play a significant role in the pharmacokinetics of isotretinoin in humans.
In vitro studies have shown that several CYP enzymes are involved in the conversion of isotretinoin to 4-oxo-isotretinoin and tretinoin. At the same time, none of the isoforms, apparently, plays a dominant role. Isotretinoin and its metabolites do not significantly affect the activity of CYP enzymes.
The terminal phase half-life for isotretinoin averages 19 hours. The terminal phase half-life for 4-oxo-isotretinoin averages 29 hours.
Isotretinoin is excreted by the kidneys and bile in approximately equal amounts.
Refers to natural (physiological) retinoids. Endogenous concentrations of retinoids are restored approximately 2 weeks after the end of the drug.
Pharmacokinetics in special clinical situations
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.

Indications for use

A drug Aknekutan is intended for the treatment of severe forms of acne (nodular-cystic, conglobate, acne with a risk of scarring). Acne unresponsive to other therapies.

Mode of application

Tablets Aknekutan take orally, preferably with meals, 1-2 times a day.
The therapeutic efficacy of Aknekutan and its side effects depend on the dose and vary in different patients. This makes it necessary to individually select the dose during treatment.
The initial dose of Acnecutane is 0.4 mg/kg per day, in some cases up to 0.8 mg/kg per day. At severe forms diseases or with acne of the trunk, a dose of up to 2 mg/kg per day may be required. The optimal course cumulative dose is 100-120 mg/kg. Complete remission usually achieved within 16-24 weeks. If the recommended dose is poorly tolerated, treatment can be continued at a lower dose, but for a longer time.
In most patients, acne disappears completely after a single course of treatment. In case of relapse, it is possible to repeat the course of treatment in the same daily and cumulative dose. A second course is prescribed no earlier than 8 weeks after the first, as the improvement may be delayed.
In severe chronic renal failure, the initial dose should be reduced to 8 mg/day.

Side effects

Majority side effects dose dependent. Usually, side effects are reversible after dose adjustment or drug withdrawal, but some may persist after treatment is stopped.
Symptoms associated with hypervitaminosis A: dry skin, mucous membranes, incl. lips (cheilitis), nasal cavity (bleeding), larynx and pharynx (hoarseness), eyes (conjunctivitis, reversible corneal clouding and intolerance to contact lenses).
Skin and its appendages: peeling of the skin of the palms and soles, rash, itching, facial erythema / dermatitis, sweating, pyogenic granuloma, paronychia, onychodystrophy, increased proliferation of granulation tissue, persistent thinning of the hair, reversible hair loss, fulminant forms of acne, hirsutism, hyperpigmentation, photosensitivity, mild skin injury. At the beginning of treatment, an exacerbation of acne may occur, which persists for several weeks.
Musculoskeletal system: muscle pain with or without elevated serum CPK, joint pain, hyperostosis, arthritis, calcification of ligaments and tendons, tendonitis.
Central nervous system and mental sphere: excessive fatigue, headache, increased intracranial pressure ("pseudotumor of the brain": headache, nausea, vomiting, blurred vision, swelling of the optic nerve), seizures rarely - depression, psychosis, suicidal thoughts.
Sense organs: xerophthalmia, isolated cases of impaired visual acuity, photophobia, impaired dark adaptation (decrease in twilight visual acuity), rarely - impaired color perception (passing after discontinuation of the drug), lenticular cataract, keratitis, blepharitis, conjunctivitis, eye irritation, optic neuritis, swelling of the optic nerve (as a manifestation of intracranial hypertension); hearing loss at certain sound frequencies, difficulty wearing contact lenses.
Gastrointestinal tract: dryness of the oral mucosa, bleeding from the gums, inflammation of the gums, nausea, diarrhea, inflammatory bowel disease (colitis, ileitis), bleeding; pancreatitis (especially with concomitant hypertriglyceridemia above 800 mg / dl). Rare cases of pancreatitis with a fatal outcome have been described. Transient and reversible increase in liver transaminase activity, isolated cases of hepatitis. In many of these cases, the changes did not go beyond the normal range and returned to baseline during treatment, however, in some situations, it became necessary to reduce the dose or cancel Aknekutan.
Respiratory organs: rarely - bronchospasm (more often in patients with a history of bronchial asthma).
Blood system: anemia, decreased hematocrit, leukopenia, neutropenia, increase or decrease in the number of platelets, accelerated ESR.
Laboratory indicators: hypertriglyceridemia, hypercholesterolemia, hyperuricemia, decreased levels of high-density lipoproteins, rarely - hyperglycemia.

In the course of taking Acnecutane, cases of newly diagnosed diabetes mellitus have been reported. In some patients, especially those engaged in intense physical activity, individual cases of increased serum CPK activity are described.
Immune system: local or systemic infections caused by gram-positive pathogens (Staphylococcus aureus).
Other: lymphadenopathy, hematuria, proteinuria, vasculitis (Wegener's granulomatosis, allergic vasculitis), systemic hypersensitivity reactions, glomerulonephritis.
Teratogenic and embryotoxic effects: congenital deformities - hydro- and microcephaly, underdevelopment of the cranial nerves, microphthalmia, malformations of the cardiovascular system, parathyroid glands, skeletal formation disorders - underdevelopment of the digital phalanges, skull, cervical vertebrae, femur, ankles, bones of the forearm, facial skull, cleft palate, low location of the auricles, underdevelopment of the auricles, underdevelopment or complete absence of external ear canal, hernia of the brain and spinal cord, bone adhesions, fusion of fingers and toes, impaired development of the thymus; fetal death in the perinatal period, premature birth, miscarriage), premature closure of the epiphyseal growth zones; in an animal experiment - pheochromocytoma.

Contraindications

Contraindications to the use of the drug Aknekutan are: pregnancy, established and planned (possibly teratogenic and embryotoxic effects), lactation period, liver failure, hypervitaminosis A, severe hyperlipidemia, concomitant tetracycline therapy; hypersensitivity to the drug or its component.
Acnecutane is not recommended for use in children under 12 years of age.
With caution: diabetes mellitus, a history of depression, obesity, lipid metabolism disorders, alcoholism.

Pregnancy

Pregnancy - absolute contraindication for therapy Acnecutane.
If pregnancy occurs, despite warnings, during treatment or within a month after the end of therapy, there is a very high risk of having a child with severe malformations.
Isotretinoin is a drug with a strong teratogenic effect. If pregnancy occurs during the period when a woman takes oral isotretinoin (at any dose and even for a short time), there is a very high risk of having a child with malformations. Acnecutane is contraindicated in women of childbearing age unless the woman's condition satisfies all of the following criteria: - she must have severe acne resistant to conventional methods treatment;
- she must surely understand and follow the instructions of the doctor;
- she must be informed by a doctor about the danger of pregnancy during treatment with Acnecutane, within one month after it and an urgent consultation if pregnancy is suspected;
- she should be warned about the possible ineffectiveness of contraceptives; - she must confirm that she understands the essence of the precautions;
- she must understand the need and continuously use effective methods of contraception for one month before treatment with Acnecutane, during treatment and for a month after its completion (see section "Interaction with other drugs"); Preferably use 2 at the same time. various ways contraception, including barrier;
- she must have received negative result a reliable pregnancy test within 11 days before the start of the drug; a pregnancy test is strongly recommended monthly during treatment and 5 weeks after the end of therapy;
- she should start treatment with Acnecutane only on the 2-3rd day of the next normal menstrual cycle;
- she must understand the need for mandatory visits to the doctor every month;
- when treating for a relapse of the disease, she must constantly use the same effective methods of contraception for one month before the start of treatment with Acnecutane, during treatment and within a month after its completion, as well as undergo the same reliable pregnancy test;
- she must fully understand the need for precautions and confirm her understanding and desire to use reliable methods of contraception, which the doctor has explained to her.
The use of contraceptives as indicated above during treatment with isotretinoin should be recommended even for women who do not normally use contraceptive methods due to infertility (with the exception of patients who have had a hysterectomy), amenorrhea, or who report not being sexually active.
The doctor must be sure that:
- the patient suffers from a severe form of acne (nodular cystic, conglobate acne or acne with a risk of scarring); acne, not amenable to other types of therapy;
- a negative result of a reliable pregnancy test was obtained before the start of the drug, during therapy and 5 weeks after the end of therapy; the dates and results of the pregnancy test should be documented;
- the patient uses at least 1, preferably 2 effective methods contraception, including a barrier method, within one month before the start of treatment with Aknekutan, during treatment and within a month after its completion;
- the patient is able to understand and comply with all of the above requirements for contraception;
- The patient meets all of the above conditions.
Pregnancy test In accordance with current practice, a pregnancy test with a minimum sensitivity of 25 mIU/ml should be performed on the first 3 days of the menstrual cycle:
Before starting therapy:
. To rule out possible pregnancy, the result and date of the initial pregnancy test must be recorded by a doctor before contraception is started. In patients with irregular menstruation The timing of the pregnancy test depends on sexual activity and should be done 3 weeks after unprotected intercourse. The doctor should inform the patient about the methods of contraception.
. A pregnancy test is carried out on the day of the appointment of Aknekutan or 3 days before the patient's visit to the doctor. The specialist should record the test results. The drug can be prescribed only to patients receiving effective contraception for at least 1 month before the start of therapy with Acnecutane.
During therapy:
. The patient must visit the doctor every 28 days. The need for monthly pregnancy testing is determined in accordance with local practice and taking into account sexual activity, previous menstrual irregularities. If indicated, a pregnancy test is carried out on the day of the visit or three days before the visit to the doctor, the test results must be recorded.
End of therapy:
. 5 weeks after the end of therapy, a test is performed to exclude pregnancy.
A prescription for Acnecutane for a woman of childbearing potential can only be issued for 30 days of treatment, continuation of therapy requires a new appointment of the drug by a doctor. It is recommended that a pregnancy test, a prescription, and receiving the drug be carried out on the same day. If, despite the precautions taken, pregnancy still occurs during treatment with Acnecutane or within a month after its termination, there is a high risk of very severe fetal malformations.
If pregnancy occurs, Aknekutan therapy is discontinued. The feasibility of maintaining the pregnancy should be discussed with a doctor specializing in teratology. Since isotretinoin is highly lipophilic, it is highly likely that it enters breast milk. Due to possible side effects, Aknekutan should not be administered to nursing mothers.
For male patients:
Existing data suggest that in women, the exposure of the drug, which came from the semen and seminal fluid of men taking Acnecutane, is not sufficient to cause the teratogenic effects of Acnecutane.
Men should exclude the possibility of taking the drug by other persons, especially women.

Interaction with other drugs

Antibiotics of the tetracycline series, GCS reduce the effectiveness.
Simultaneous application Aknekutana with drugs that increase photosensitivity (including sulfonamides, tetracyclines, thiazide diuretics) increases the risk of sunburn.
Simultaneous use with other retinoids (including acitretin, tretinoin, retinol, tazarotene, adapalene) increases the risk of hypervitaminosis A. Isotretinoin can weaken the effectiveness of progesterone preparations, so contraceptives containing low doses of progesterone should not be used.
Combined use with local keratolytic drugs for the treatment of acne is not recommended due to the possible increase in local irritation.
Since tetracyclines increase the risk of increased intracranial pressure, concomitant use with isotretinoin is contraindicated.

Overdose

In case of overdose Acnecutane signs of hypervitaminosis A may appear.
In the first few hours after an overdose, gastric lavage may be necessary.

Storage conditions

In a dry, dark place, out of the reach of children, at a temperature not exceeding 25ºС.

Release form

Aknekutan - capsules 8 mg and 16 mg.
10 or 14 capsules in PVC blister, covered with aluminum foil.
Blisters-10-N2, N3, N5, N6, N9, N10; blisters-14-N1, N2, N4, N7 in a cardboard box along with instructions for use.

Compound

1 capsule Aknekutan 8 mg contains active substances: isotretinoin - 8.0 mg.
Excipients: gelucir 50/13 (a mixture of esters of stearic acid of polyethylene oxide and glycerol) - 96.00 mg; refined soybean oil - 52.00 mg.
Span 80 (sorbitan oleate - mixed esters oleic acid and sorbitol) - 8.00 mg.

1 capsule Aknekutan 16 mg contains active substances: isotretinoin - 16.0 mg.
Excipients: gelucir 50/13 (a mixture of esters of stearic acid of polyethylene oxide and glycerol) - 192.00 mg; refined soybean oil - 104.00 mg.
Span 80 (sorbitan oleate - mixed esters of oleic acid and sorbitol) - 16.00 mg

Capsule composition:
Acnecutane 8 mg: body and lid: gelatin, iron oxide red (E172), titanium dioxide (E171).
Acnecutane 16 mg: body: gelatin, titanium dioxide (E171).
Lid: gelatin, titanium dioxide (E171), iron oxide yellow (E172), indigo carmine (E132).

Additionally

It is recommended to monitor liver function and liver enzymes before treatment, 1 month after its initiation, and then every 3 months or as indicated. A transient and reversible increase in hepatic transaminases was noted, in most cases within normal values. 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 before treatment, 1 month after initiation, and every 3 months thereafter, or as indicated. 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 or 9 mmol/l may be associated with acute pancreatitis, possibly fatal.
With persistent hypertriglyceridemia or symptoms of pancreatitis, Aknekutan should be discontinued. In rare cases, depression, psychotic symptoms, and very rarely 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, the abolition of Aknekutan may not lead to the disappearance of symptoms and further monitoring and treatment by a specialist may be required.
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.
When prescribing the drug, any patient should first carefully evaluate the ratio of possible benefits and risks.
Patients receiving Acnecutane are advised to use a moisturizing ointment or body cream, lip balm to reduce dryness of the skin and mucous membranes at the beginning of therapy. Against the background of taking Acnecutane, pain in the muscles and joints, an increase in serum creatinine phosphokinase, which may be accompanied by a decrease in the tolerance to intense physical activity, are possible.
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 the occurrence of hyper- and hypopigmentation. 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. 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. Conjunctival dryness, corneal opacities, blurred night vision, and keratitis usually resolve after discontinuation of the drug. With dryness of the mucous membrane of the eyes, applications of a moisturizing eye ointment or an artificial tear preparation can be used. It is necessary to observe patients with dryness of the conjunctiva for the possible development of keratitis. Patients presenting with complaints of vision should be referred to an ophthalmologist and consideration should be given to discontinuing Aknekutan. In case of intolerance to contact lenses, glasses should be used during therapy.
Exposure to solar insolation and UV therapy should be limited. If necessary, use a sunscreen with a high protection factor of at least 15 SPF.
Rare cases of the development of benign intracranial hypertension (“pseudotumor of the brain”) have been described, incl. when combined with tetracyclines. In such patients, Aknekutan should be discontinued immediately.
Acnecutane therapy may cause inflammatory bowel disease. In patients with severe hemorrhagic diarrhea, Aknekutan should be discontinued immediately. Rare cases of anaphylactic reactions have been described that occurred only after previous topical use of retinoids. Severe allergic reactions dictate the need to discontinue the drug and carefully monitor the patient.
Patients at high risk (diabetic, obese, chronic alcoholism or disorders of fat metabolism) in the treatment with Acnecutane, more frequent laboratory monitoring of glucose and lipid levels may be required. In the presence of diabetes or suspicion of it, more frequent determination of glycemia is recommended. Patients with diabetes are advised to conduct more frequent monitoring of blood glucose levels.
During the period of treatment, care must be taken when driving vehicles and engaging in other potentially hazardous activities that require increased concentration attention and speed of psychomotor reactions (when taking the first dose).
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).

main parameters

Name:	AKNEKUTAN
ATX code:	D10BA01 -

In modern times, people attach more importance to the problem of acne than ten years ago. attractiveness appearance- this is the first component of success, which has nothing to do with red spots on the face and purulent acne.

Agree that the picture is not pleasant - to admire the inflamed areas of the face of another person. The interlocutor himself, who understands his physical handicap, also feels awkward. But it is not so easy to deal with it, as practice has shown.

many ointments and medical preparations only smooth the situation, but do not radically change it. Acne, acne on the face and body of a person cause not only psychological discomfort, but also physical pain.

Not everyone, of course, faces this problem. But also those who know firsthand what it is inflamed pimples on the face, not so much. And this problem concerns not only adolescence, youth, but also mature people who have crossed the border of forty years.

So the question arises: “What actually causes human body acne that hurts and distorts the attractiveness of the appearance with its inflammation? And the thing is that these phenomena relate to the malfunctioning of the sebaceous glands.

Doctors-specialists identify three main factors that provoke the development of the disease in question:

Excessive production of fat by the sebaceous ducts;

Overdeveloped stratum corneum of follicles, called in medical practice follicular hyperkeratosis;

Reproduction on the human body of bacteria Propionibacterium acnes along with staphylococcus, fungi and skin mites.

Turning to a competent specialist for help, the patient must undergo a series of tests so that the doctor can prescribe the correct and effective treatment, affecting precisely existing cause the appearance and development of inflamed acne and acne.

One or two pimples on the face is a signal for action, that is, the search for an anti-inflammatory drug, especially if the formations cause pain during touching and not only. Single elements of acne within a few days can turn into a more significant problem and spread throughout the face, arms, back or chest. If many parts of the body can be covered with clothes, then the face cannot be hidden from the views of others. The only way out- visit to a professional doctor for advice and appointment effective treatment. This is what most of those who still dream of having a clean face do in modern times, which does not scare people away, but, on the contrary, disposes them to communicate.

First medical assistance the patient is the appointment of cosmetics that relieve pain and redness. If they don't help, move on to more effective drugs, which relieve the problem, but require a long and correct course of treatment.

Currently, positive patient reviews are very often discussed about the drug "Aknekutan". So we will consider in this article what is a remedy that helps many people get rid of a serious problem with the health of the skin of the face and body.

The composition of the drug "Aknekutan" from acne

This remedy is often prescribed for complex forms of acne, when the face is completely dotted with acne and other drugs do not work. For many patients, the drug "Aknekutan" (reviews confirm this) is the last hope for recovery.

The composition of this remedy includes isotretinoin, the so-called synthetic analogue of vitamin A, as well as mixtures essential oils, sorbitan olean and soy concentrate.

In what form is the drug produced?

The remedy for acne and acne "Aknekutan" (instruction, reviews of many patients note this) is available in the form of capsules. On sale you can find hard gelatin capsules in a dosage of the main active ingredient of 8 mg or 16 mg. The dose of the medicine is always prescribed by the doctor. Self-activity during treatment with this drug is inappropriate and can harm health.

Pharmacological properties of the drug

Assessing a lot of reviews about the Aknekutan drug, one can note the tendency for the patient's condition to improve only a few months after the start of taking the medication as prescribed by the doctor. Who notices the result already in the second month, who is in the fourth, and who needs a period of more than six months to achieve cleanliness of the skin on the face and body.

Today, according to the information that reviews about Aknekutan are filled with, this is one of the most effective medicines that is prescribed in hopeless situations in severe forms of acne under the strict supervision of the attending physician.

What is the effect of the drug in terms of pharmacology? Much of the research on isotretionin is aimed at identifying the exact algorithm of its effects. However, it has not yet been fully explored. Therefore, the reviews of doctors warn about the drug "Aknekutan" to be extremely careful with it. And also in no case should you take an independent initiative in the issue of increasing the dose.

The medicine "Aknekutan" (reviews, photos of patients below confirm) can effectively cleanse the face.

It is it that suppresses the activity of the sebaceous glands, reduces the production of fat, which is a favorable environment for the development of Propionibacterium acnes. Thus, the sebaceous duct gets rid of harmful organisms, due to which it is possible to extinguish the focus of inflammation. With the appointment of the correct therapy, the process of development of skin cells and stimulation of regenerative processes is normalized.

It is a potent anti-inflammatory, antimicrobial, antibacterial, antiseptic drug.

The Aknekutan remedy (reviews, photos before and after taking it prove) relieves acne, pimples, various kinds of rashes, but other methods of struggle are effective from pits and scars. Of course, skin roughness and dents remain, but due to the removal of inflammation, they are less noticeable. A good example of this is shown in the photo below.

Indications for prescribing treatment with Aknekutan

Scars and scars on the skin are the most unwanted result of acne treatment. That is why they rush to get rid of it when its appearance does not cover large areas of the skin. However, it is not always possible to apply effective medicines to eliminate this skin defect in time. Many drugs do not act on too inflamed areas as effectively as Aknekutan. Reviews of many people say that they are treated with this drug only when other drugs have been powerless.

Yes, and the instructions for it insist that the remedy is intended specifically for the treatment of complex forms of acne. Once you see a doctor, you will find out the degree of complexity of your illness, namely: what spoils your appearance so much - nodular cystic acne, either conglobate or forming scars. Depending on the severity of the course of acne, certain dosages of the drug are prescribed.

Contraindications

Numerous reviews of people about the drug "Aknekutan" also say that it is not suitable for treatment for everyone. So, the instruction focuses on several points when it is unacceptable to take this remedy due to the prevention of deterioration in the health of patients.

So, the drug "Aknekutan" is not recommended for the treatment of patients with diabetes mellitus, alcoholism, obesity, liver failure, hypervitaminosis A. Categorically no to taking this medication during pregnancy, breastfeeding, under the age of twelve years, with tetracycline therapy, hypersensitivity to the components of the drug.

Despite the fact that Aknekutan is prescribed for both men and women, more effective result treatment can be achieved precisely by the representatives of the stronger sex. And everything is connected with the fact that it is much easier for a man to follow the instructions of a doctor without worrying about his function of conceiving children and effective contraception.

The thing is that the main active ingredient of this drug has undesirable effects on the health of the fetus and the subsequent development of the fetus. That is why pregnancy is the most important obstacle in the way of taking Aknekutan. Reviews of treated women focus on this. If the treatment is prescribed by a doctor, then the woman follows all the recommendations strictly, without missing the slightest detail. Of course, the main problem during the course of therapy is reliable contraception. Isotretionine significantly reduces the effectiveness of oral contraceptives, along with them, barrier methods of protection should be used.

No competent doctor will undertake to treat a woman with Aknekutan if he is not sure that:

She does suffer from a complex form of acne;

She is not pregnant at the time of the prescription;

She understands the seriousness of the treatment and the possibility of advanced fetal malformations;

She is ready for a monthly doctor visit and a pregnancy test.

Much easier, of course, for women who do not live sexually, and those who have been diagnosed with infertility. But even these persons are always recommended by the doctor reliable contraceptive medications and other effective methods.

What should be focused on?

Many reviews about the Aknekutan drug (after taking it in particular) contain information that a pregnancy test should be carried out monthly to be sure that there is no pregnancy as such. If it does occur, then the patient is recommended its operable interruption (abortion).

Isotretinoin has the property of high lipophilicity, it easily penetrates into breast milk and can harm the health of the baby. You need to know about this and understand all the risks of taking the drug for the treatment of acne.

The drug "Aknekutan", reviews of which are discussed in this article, despite its high efficiency, is not prescribed for teenage acne. To do this, use safer medications in the form of ointments and creams.

The basic rules that patients follow when prescribing treatment with Aknekutan are as follows:

Strict adherence to the dose and regimen of taking capsules;

Refusal to combine the prescribed medication with other means;

Refusal to play sports, reduce physical activity;

Refusal to treat acne with a laser method;

Refusal of epilation;

Vision control through regular visits to the ophthalmologist;

Refusal of contact lenses, replacing them with glasses;

Using sunscreen for the skin and avoiding prolonged exposure to sunlight;

Refusal to donate blood;

Clear monitoring of one's physical well-being, at the moments of its deterioration, there is always a notification of the attending doctor about this;

Use of moisturizers for the skin of the body, face, lips and eyes;

Refusal to drive, especially at night;

Monthly delivery of analyzes for verification purposes normal functioning all internal organs.

Proper Dosage of Acne Remedy

In most of the drug "Aknekutan" reviews after taking are positive. It really helps, but in order to achieve the desired result of skin cleansing, you should be patient and follow all the above recommendations and rules. In particular, we are talking about the dosage prescribed by the doctor.

Capsules are taken one to two times a day. If you meet reviews that inform you that you need to take Aknekutan 3 capsules a day, then you need to understand that this is an individual dose prescribed by a doctor. It can, depending on the effectiveness of the course of treatment and the condition of the patient, both decrease and increase.

The initial dosage is 4 mg of the active active ingredient once a day; in case of complicated forms of acne, the intake can also begin with a dose of 8 mg of isotretinoin.

Since the drug is available in concentrations of 8 mg and 16 mg, this means that the dosage in the most advanced cases can start from 16 mg, but under the strict supervision of a doctor.

The duration of treatment with this remedy for acne and acne is thirty weeks or more. Who observes improvements in the first months of admission, and who only after six months.

More often, the drug Aknekutan (8 mg) is still applicable in medical practice. The reviews of those who are really set on fighting a skin defect are positive, and most prove the effectiveness of the product with photographic materials. This is the best confirmation that the drug is helping.

Constant fulfillment of the doctor's prescriptions leads to a clean face, in many cases it is enough for the patient to permanently solve the problem with acne and acne, having completed one course of treatment. There are also people who need further treatment.

Side effects

As noted above, the drug "Aknekutan" side effects (patient reviews and medication instructions claim this) can manifest in such forms as:

Violation of moisture exchange skin, due to which their peeling, dryness is observed, this defect is very noticeable on the lips, face, palms, feet;

nosebleeds;

Eye diseases - conjunctivitis, corneal clouding, intolerance to bright lighting;

Reactions similar to allergy manifestations - rash, itching, dermatitis;

Periodic headaches;

unexplained nausea, vomiting, abdominal pain, bowel disorders;

Increased appearance of blackheads and acne;

Depressive states, self-doubt, apathy and drowsiness;

Noticeable hair loss

Increased work of sweat glands;

Pain in the joints and muscles, similar to breaking;

Stomatitis;

A sharp decline protective functions organism, a high degree of development of infectious diseases;

Miscarriages, premature labor.

The most common defect is dry skin of the body and lips.

How much does the drug cost?

The product is produced by the Belgian company SMB TECHNOLOGY S.A., so it is not cheap. So, one package of the drug in a dosage of 8 mg capsules (number of blisters - 3 pcs.) On average costs 1200 rubles, 16 mg (number of blisters - 3 pcs.) - 2000 rubles.

The course is quite long, but effective. So, despite the high cost of the drug, it is in great demand and is a real salvation for those who have completely lost faith in a positive solution to their problem.

Drug analogues

So we examined the properties and reviews about the drug "Aknekutan". After undergoing therapy, most patients are satisfied with their results. It is this drug that restores health to the skin. But, as we noted above, it does not affect the resulting tubercles, depressions and scars after acne. The relief of the skin is corrected by other cosmetic techniques, such as laser, peeling, polishing.

The drug "Aknekutan" is not the only effective tool in the fight against inflamed acne. In pharmacies today you can buy analogues of this medicine, such as Zinocap external skin treatment cream, Roaccutane capsules, Friderm zinc shampoo, Retasol skin wiping solution, Pyrithione zinc powder. All of them are used only on the recommendation of a doctor after thorough examination patient.

The closest in form of release, composition and purpose to the drug "Acnecutane" are capsules "Roaccutane". Compared to the one under consideration effective medicine this one is almost half the price, has a longer list of side effects, and is only absorbed with food.

So many still choose the Aknekutan medicine and are satisfied with the result, although it has to wait a long time.

A complex problem always requires time and attention to itself. But the one who does not give up always gets only positive changes in the end. Monthly snapshots help monitor skin improvement. It is they who show the slow, but fairly stable effect of the drug, which ultimately leads to a clean skin.

It is undesirable to interrupt the course of treatment with Aknekutan. Often, the side effects of the drug are easier to survive than inflamed and painful purulent acne.

Another drug for internal use is Aknekutan for acne. This tool appeared in Russia only in 2010 on the market and is an analogue, only with fewer side effects. But Aknekutan is also prescribed only by a dermatologist and if other types of treatment have not helped get rid of acne. Before you start drinking Acnecutane, read the side effects and reconsider whether you are ready to go for it to get rid of acne. After all, only 50% of patients acne goes away forever, the remaining 50% relapse or exacerbate after giving up Acnecutane.

How Acnecutane Works for Acne

The active ingredient in Acnecutane is isotretinoin. This substance regulates the sebaceous glands. It not only suppresses the active secretion of sebum, but also reduces in size sebaceous glands. Also, doctors have proven that isotretinoin has an anti-inflammatory effect that extends to acne bacteria. In connection with long-term use Acnecutane, the sebaceous glands can remain in a reduced form forever, which will lead to getting rid of acne.

Also, the effect of acne treatment with Acnecutane increases due to the thinning of the upper layers of the epidermis with isotretinoin. It is much easier for active substances to penetrate into the bloodstream, visible results appear quickly.

Isotretinoin is a systemic retinoid and is the most effective treatment for acne. But these drugs can only be prescribed by a doctor in an individual dosage, taking into account the weight, age and form of acne. It was revealed that the cause of acne is too active work sebaceous glands and production a large number sebum, which is a favorable environment for the spread of acne bacteria Propionibacterium acnes. Aknekutan successfully fights this process, reducing both the secretion of sebum itself and the sebaceous glands themselves. In addition, Acnecutane restores normal cell regeneration and differentiation, while having an anti-inflammatory effect.

Instructions for use Aknekutan

Take Aknekutan 1-2 times a day orally with meals. Doses are set by the doctor depending on the weight and form of acne. Aknekutan capsules are produced at 8 and 16 mg, 30 pieces per pack. The average duration of the course of treatment with Acnecutane is 4-6 months, the time varies by the doctor up or down depending on the side effects, improvements or worsening of the patient's condition.

After a full course of treatment with Acnecutane, there is a possibility of relapse, possibly re-treatment, but not earlier than 2 months after the end of the previous one. This is due to the possibility of delayed treatment, i.e. the result did not appear immediately.

Side effects of Aknekutan

Because Acnecutane contains maximum amount vitamin A, the first side effects will be associated with hypervitaminosis of vitamin A:

dry skin,

Mucous membranes (nose, throat, eyes),

Hands, feet,

Peeling and irritation

Hair loss, brittle nails,

Rash, itching, excessive sweating,

Exacerbation of acne at the beginning of treatment,

Pain in bones and muscles

Headaches, fatigue, depression, blurred vision, abdominal pain, gum disease, nausea, diarrhea.

Side effects of Aknekutan arose on initial stages treatment and returned to normal during treatment. Sometimes you have to reduce the daily dose of the drug, so as not to aggravate the situation.

In connection with such big list side effects of Acnecutane, you should not only take it according to a doctor's prescription, but also take tests every month to monitor the condition of internal organs, blood and prevent side effects.

During the treatment of acne with Aknekutan, girls should not become pregnant before treatment, during treatment and a month after the end of treatment. There is a high risk of having a child with malformations, so girls need to use reliable contraceptives.

In addition to all of the above, within 6 months after the end of treatment, mechanical and laser cleanings, operations, and epilation of any parts of the body should not be used. High risk of scars and scars

How much is Aknekutan

The price of Acnecutane is 2 times cheaper than Roaccutane. Apparently, this is due to a short stay on Russian market and some distrust of the drug, as well as with a more efficient production technology patented in Belgium. Therefore, Aknekutan is about 40% cheaper.

Capsules Aknekutan 8 mg for 30 pcs - 1070 rubles

Capsules Aknekutan 16 mg for 30 pcs - 1800 rubles

How is Acnecutane different from Roaccutane?

Isotretinoin is the active ingredient found in both Roaccutane and Acnecutane. But Aknekutan has two additional substances that allow isotretinoin to work 20% more efficiently. Doctors conducted comparative studies and it was proved that 16 mg of Acnecutane is equal to 20 mg of Roaccutane. This means that the amount of isotretinoin passing through digestive tract twice less, and, therefore, 2 times less side effects.

To give an example, taking a 20 mg capsule of Roaccutane, only 12 mg of isotretinoin enters the bloodstream and acts against acne, the remaining 8 mg passes through the digestive tract without entering the bloodstream. Taking a 16 mg Acnecutane capsule, 12 mg of isotretinoin (the same amount) goes into the blood for acne treatment, and the remaining 4 mg passes through the digestive system. Those. the passage of isotretinoin through the digestive tract is 2 times less, less load on internal organs. This is the main difference.

Another important plus of Acnecutane is that it is easily digested without food intake. Because isotretinoin is an analogue of vitamin A, and it belongs to fat-soluble vitamins, but the drug is more easily absorbed with fatty foods. But the patient will not always be able to take Acnecutane with a meal or a sufficiently fatty meal. In the course of research, it turned out that Acnecutane is 70% absorbed without food, and Roaccutane is only 37%. This means complete confidence in the treatment that the drug, even when taken without food, will be absorbed by the body.

A drug for the treatment of acne. 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 of the duct. Acnecutane inhibits the proliferation of sebocytes and acts on acne, restoring the normal process of cell differentiation, and stimulates regeneration processes. In addition, the anti-inflammatory effect of isotretinoin on the skin has been proven.

Pharmacokinetics

Suction

Since the kinetics of isotretinoin and its metabolites is linear, its plasma concentrations during therapy can be predicted based on data obtained after a single dose. This property of the drug also suggests that it does not affect the activity of microsomal liver enzymes involved in drug metabolism.

The high bioavailability of Acnecutane is due to the large proportion of dissolved isotretinoin in the preparation, and may increase if the drug is taken with food. In patients with acne, Cmax at steady state after taking isotretinoin at a dose of 80 mg on an empty stomach was 310 ng / ml (range 188-473 ng / ml) and was reached after 2-4 hours. The concentration of isotretinoin in plasma is 1.7 times higher than in blood, due to poor penetration of isotretinoin into erythrocytes.

Distribution

Plasma protein binding (mainly albumin) - 99.9%.

C ss of isotretinoin in the blood of patients with severe forms of acne, who took the drug at 40 mg 2 times / day, ranged from 120 ng / ml to 200 ng / ml. The concentrations of 4-oxo-isotretinoin (the main metabolite) in these patients were 2.5 times higher than those. The concentration of isotretinoin in the epidermis is 2 times lower than in serum.

Metabolism

It is metabolized to form 3 main biologically active metabolites - 4-oxo-isotretinoin (the main metabolite), tretinoin (all-trans-retinoic acid) and 4-oxo-retinoin, as well as less significant metabolites, including also glucuronides. Since isotretinoin and tretinoin are reversibly converted into each other in vivo, the metabolism of tretinoin is associated with the metabolism of isotretinoin. 20-30% of a dose of isotretinoin is metabolized by isomerization. Enterohepatic circulation may play a significant role in the pharmacokinetics of isotretinoin in humans.

In vitro studies have shown that several cytochrome P450 enzymes are involved in the conversion of isotretinoin to 4-oxo-isotretinoin and tretinoin. At the same time, none of the isoforms, apparently, plays a dominant role. Isotretinoin and its metabolites do not significantly affect the activity of cytochrome P450 enzymes.

breeding

T 1/2 of the terminal phase for isotretinoin is on average 19 hours. T 1/2 of the terminal phase for 4-oxo-isotretinoin is on average 29 hours.

Isotretinoin is excreted by the kidneys and bile in approximately equal amounts. Refers to natural (physiological) retinoids. Endogenous concentrations of retinoids are restored approximately 2 weeks after the end of the drug.

Pharmacokinetics in special clinical situations

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.

Release form

Capsules hard gelatin, size №3, Brown color; the contents of the capsules are a yellow-orange waxy paste.

	1 caps.
isotretinoin	8 mg

Excipients: Gelucir ® 50/13 (a mixture of polyethylene oxide and glycerol stearic acid esters), purified soybean oil, Span 80 ® (sorbitan oleate - mixed esters of oleic acid and sorbitol).

The composition of the body and cap of the capsule: gelatin, iron dye red oxide (E172), titanium dioxide (E171).

10 pieces. - blisters (2) - packs of cardboard.
10 pieces. - blisters (3) - packs of cardboard.
10 pieces. - blisters (5) - packs of cardboard.
10 pieces. - blisters (6) - packs of cardboard.
10 pieces. - blisters (9) - packs of cardboard.
10 pieces. - blisters (10) - packs of cardboard.
14 pcs. - blisters (1) - packs of cardboard.
14 pcs. - blisters (2) - packs of cardboard.
14 pcs. - blisters (4) - packs of cardboard.
14 pcs. - blisters (7) - packs of cardboard.

Dosage

Inside, preferably during meals, 1-2 times / day.

The therapeutic efficacy of Aknekutan and its side effects depend on the dose and vary in different patients. This makes it necessary to individually select the dose during treatment.

The initial dose of Aknekutan is 400 mcg / kg / day, in some cases up to 800 mcg / kg / day. In severe forms of the disease or with acne of the trunk, a dose of up to 2 mg / kg / day may be required.

The optimal course cumulative dose is 100-120 mg/kg. Complete remission is usually achieved within 16-24 weeks. If the recommended dose is poorly tolerated, treatment can be continued at a lower dose, but for a longer time. In most patients, acne disappears completely after a single course of treatment.

In case of relapse, it is possible to repeat the course of treatment in the same daily and cumulative dose. A second course is prescribed no earlier than 8 weeks after the first, because. improvement may be delayed.

Overdose

In case of an overdose, signs of hypervitaminosis A may appear.

In the first few hours after an overdose, gastric lavage may be necessary.

Interaction

Antibiotics of the tetracycline series, GCS reduce the effectiveness of Acnecutane.

Simultaneous use with drugs that increase photosensitivity (including sulfonamides, tetracyclines, thiazide diuretics) increases the risk of sunburn.

Simultaneous use with other retinoids (including acitretin, tretinoin, retinol, tazarotene, adapalene) increases the risk of hypervitaminosis A.

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

Combined use with local keratolytic drugs for the treatment of acne is not recommended due to the possible increase in local irritation.

Since tetracyclines increase the risk of increased intracranial pressure, concomitant use with isotretinoin is contraindicated.

Side effects

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

Symptoms associated with hypervitaminosis A: dry skin, mucous membranes, incl. lips (cheilitis), nasal cavity (bleeding), larynx and pharynx (hoarseness), eyes (conjunctivitis, reversible corneal clouding and intolerance to contact lenses).

Dermatological reactions: peeling of the skin of the palms and soles, rash, itching, facial erythema / dermatitis, sweating, pyogenic granuloma, paronychia, onychodystrophy, increased growth of granulation tissue, persistent hair thinning, reversible hair loss, fulminant forms of acne, hirsutism, hyperpigmentation, photosensitivity, mild skin injury. At the beginning of treatment, an exacerbation of acne may occur, which persists for several weeks.

From the musculoskeletal system: muscle pain with or without elevated serum CPK levels, joint pain, hyperostosis, arthritis, calcification of ligaments and tendons, tendinitis.

From the side of the central nervous system: excessive fatigue, headache, increased intracranial pressure (pseudotumor of the brain: headache, nausea, vomiting, blurred vision, swelling of the optic nerve), convulsive seizures; rarely - depression, psychosis, suicidal thoughts.

From the senses: xerophthalmia, isolated cases of impaired visual acuity, photophobia, impaired dark adaptation (decrease in twilight visual acuity); rarely - a violation of color perception (passing after discontinuation of the drug), lenticular cataract, keratitis, blepharitis, conjunctivitis, eye irritation, optic neuritis, optic nerve edema (as a manifestation of intracranial hypertension); hearing loss at certain sound frequencies, difficulty wearing contact lenses.

From the digestive system: dryness of the oral mucosa, bleeding from the gums, inflammation of the gums, nausea, diarrhea, inflammatory bowel disease (colitis, ileitis), bleeding; pancreatitis (especially with concomitant hypertriglyceridemia above 800 mg / dl). Rare cases of pancreatitis with a fatal outcome have been described. There was a transient and reversible increase in the activity of hepatic transaminases, some cases of hepatitis. In many of these cases, the changes did not go beyond the normal range and returned to baseline during treatment, however, in some situations, it became necessary to reduce the dose or cancel Aknekutan.

From the side respiratory system: rarely - bronchospasm (more often in patients with a history of bronchial asthma).

On the part of the hematopoietic system: anemia, a decrease in hematocrit, leukopenia, neutropenia, an increase or decrease in the number of platelets, an acceleration of ESR.

Laboratory indicators: hypertriglyceridemia, hypercholesterolemia, hyperuricemia, decreased HDL levels; rarely - hyperglycemia. In the course of taking Acnecutane, cases of newly diagnosed diabetes mellitus have been reported. In some patients, especially those engaged in intense physical activity, individual cases of increased serum CPK activity are described.

Infections: local or systemic infections caused by gram-positive pathogens (Staphylococcus aureus).

Other: lymphadenopathy, hematuria, proteinuria, vasculitis (Wegener's granulomatosis, allergic vasculitis), systemic hypersensitivity reactions, glomerulonephritis.

Teratogenic and embryotoxic effects: congenital malformations - hydro- and microcephaly, underdevelopment of cranial nerves, microphthalmia, malformations of cardio-vascular system, parathyroid glands, violations of the formation of the skeleton (underdevelopment of the digital phalanges, skull, cervical vertebrae, femur, ankles, bones of the forearm, facial skull, cleft palate), low location of the auricles, underdevelopment of the auricles, underdevelopment or complete absence of the external auditory canal, hernia brain and spinal cord, bone fusion, fusion of fingers and toes, developmental disorders of the thymus gland; fetal death in the perinatal period, premature birth, miscarriage, premature closure of the epiphyseal growth zones; in an animal experiment - pheochromocytoma.

Indications

• severe forms of acne (nodular cystic, conglobate, acne with a risk of scarring);
• acne, not amenable to other types of therapy.

Contraindications

• pregnancy, established and planned (possibly teratogenic and embryotoxic effects);
• breastfeeding period;
• liver failure;
• hypervitaminosis A;
• severe hyperlipidemia;
• concomitant therapy with tetracyclines;
• hypersensitivity to the drug or its components.

With caution, the drug should be prescribed for diabetes mellitus, a history of depression, obesity, lipid metabolism disorders, and alcoholism.

Application features

Use during pregnancy and lactation

Pregnancy is an absolute contraindication for Acnecutane therapy.

If pregnancy occurs, despite warnings, during treatment or within a month after the end of therapy, there is a very high risk of having a child with severe malformations.

Isotretinoin is a drug with a strong teratogenic effect. If pregnancy occurs during the period when a woman takes oral isotretinoin (at any dose and even for a short time), there is a very high risk of having a child with malformations.

Acnecutane is contraindicated in women of childbearing age unless the woman's condition satisfies all of the following criteria:

• severe acne resistant to conventional treatments;
• the patient must understand and follow the instructions of the doctor;
• the patient should be informed by the doctor about the danger of pregnancy during treatment with Acnecutane, within one month after it and an urgent consultation if pregnancy is suspected;
• the patient should be warned about the possible ineffectiveness of contraceptives;
• the patient must confirm that she understands the essence of the precautions;
• the patient must understand the need and continuously use effective methods of contraception for one month before treatment with Acnecutane, during treatment and for a month after its completion; it is desirable to use 2 different methods of contraception at the same time, including a barrier;
• the patient must have obtained a negative result of a reliable pregnancy test within 11 days before starting the drug; a pregnancy test is strongly recommended monthly during treatment and 5 weeks after the end of therapy;
• the patient should start treatment with Acnecutane only on the 2-3rd day of the next normal menstrual cycle;
• the patient must understand the need for a mandatory visit to the doctor every month;
• when treating for a relapse of the disease, the patient must constantly use the same effective methods of contraception for one month before the start of treatment with Acnecutane, during treatment and within a month after its completion, and also undergo the same reliable pregnancy test;
• the patient must fully understand the need for precautions and confirm her understanding and desire to use reliable methods of contraception, which were explained to her by the doctor.

The use of contraceptives as indicated above during treatment with isotretinoin should be recommended even for women who do not normally use contraceptive methods due to infertility (with the exception of patients who have had a hysterectomy), amenorrhea, or who report not being sexually active.

The doctor must be sure that:

• the patient suffers from a severe form of acne (nodular cystic, conglobate acne or acne with a risk of scarring); acne, not amenable to other types of therapy;
• a negative result of a reliable pregnancy test was obtained before the start of the drug, during therapy and 5 weeks after the end of therapy; the dates and results of the pregnancy test should be documented;
• the patient uses at least one, preferably two effective methods of contraception, including a barrier method, within one month before the start of treatment with Acnecutane, during treatment and within a month after its completion;
• the patient is able to understand and comply with all of the above requirements for contraception;
• The patient meets all of the above conditions.

Pregnancy test

In accordance with current practice, a pregnancy test with a minimum sensitivity of 25 mIU/ml should be performed on the first 3 days of the menstrual cycle:

Before starting therapy

To rule out possible pregnancy, the result and date of the initial pregnancy test must be recorded by a doctor before contraception is started. In women with irregular periods, the timing of the pregnancy test depends on sexual activity and should be performed 3 weeks after unprotected intercourse. The doctor should inform the patient about the methods of contraception.

A pregnancy test is carried out on the day of the appointment of Aknekutan or 3 days before the patient's visit to the doctor. The specialist should record the test results. The drug can be prescribed only to patients receiving effective contraception for at least 1 month before the start of therapy with Acnecutane.

During therapy

The patient must visit the doctor every 28 days. The need for monthly pregnancy testing is determined in accordance with local practice and taking into account sexual activity, previous menstrual irregularities. If indicated, a pregnancy test is carried out on the day of the visit or 3 days before the visit to the doctor, the test results must be recorded.

End of therapy

5 weeks after the end of therapy, a test is performed to exclude pregnancy.

A prescription for Acnecutane for a woman of childbearing potential can only be issued for 30 days of treatment, continuation of therapy requires a new appointment of the drug by a doctor. It is recommended that a pregnancy test, a prescription, and receiving the drug be carried out on the same day.

If, despite the precautions taken, pregnancy still occurs during treatment with Acnecutane or within a month after its termination, there is a high risk of very severe fetal malformations.

If pregnancy occurs, Aknekutan therapy is discontinued. The feasibility of maintaining the pregnancy should be discussed with a doctor specializing in teratology.

Because isotretinoin is highly lipophilic, it is highly likely that it passes into breast milk. Due to possible side effects, Aknekutan should not be administered to nursing mothers.

male patients

Existing data suggest that in women, the exposure of the drug, which came from the semen and seminal fluid of men taking Acnecutane, is not sufficient to cause the teratogenic effects of Acnecutane. Men should exclude the possibility of taking the drug by other persons, especially women.

Application for violations of liver function

Application for violations of kidney function

In severe chronic renal failure, the initial dose should be reduced to 8 mg / day.

Use in children

Acnecutane is not indicated for the treatment of puberty acne and is not recommended for use in children under 12 years of age.

special instructions

It is recommended to monitor liver function and liver enzymes before treatment, 1 month after its initiation, and then every 3 months or as indicated. A transient and reversible increase in hepatic transaminases was noted, in most cases within normal limits. 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 measured before treatment, 1 month after initiation, and then every 3 months or as indicated. 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 or 9 mmol/l may be associated with acute pancreatitis, possibly fatal. With persistent hypertriglyceridemia or symptoms of pancreatitis, Aknekutan should be discontinued.

In rare cases, depression, psychotic symptoms, and very rarely 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, the abolition of Aknekutan may not lead to the disappearance of symptoms and further monitoring and treatment by a specialist may be required.

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.

When prescribing the drug, any patient should first carefully evaluate the ratio of possible benefits and risks.

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

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 the occurrence of hyper- and hypopigmentation. 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.

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. Conjunctival dryness, corneal opacities, blurred night vision, and keratitis usually resolve after discontinuation of the drug. With dryness of the mucous membrane of the eyes, applications of a moisturizing eye ointment or an artificial tear preparation can be used. It is necessary to observe patients with dryness of the conjunctiva for the possible development of keratitis. Patients presenting with complaints of vision should be referred to an ophthalmologist and consideration should be given to discontinuing Aknekutan. In case of intolerance to contact lenses, glasses should be used during therapy.

Exposure to solar insolation and UV therapy should be limited. If necessary, use a sunscreen with a high protection factor of at least 15 SPF.

Rare cases of the development of benign intracranial hypertension (pseudotumor of the brain) have been described, incl. when combined with tetracyclines. In such patients, Aknekutan should be discontinued immediately.

Acnecutane therapy may cause inflammatory bowel disease. In patients with severe hemorrhagic diarrhea, Aknekutan should be discontinued immediately.

Rare cases of anaphylactic reactions have been described that occurred only after previous topical use of retinoids. Severe allergic reactions dictate the need to discontinue the drug and carefully monitor the patient.

Patients at high risk (with diabetes mellitus, obesity, chronic alcoholism or disorders of fat metabolism) may require more frequent laboratory monitoring of glucose and lipid levels during treatment with Acnecutane. In the presence of diabetes or suspicion of it, more frequent determination of glycemia is recommended. Patients with diabetes are advised to conduct more frequent monitoring of blood glucose levels.

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).

Influence on the ability to drive vehicles and control mechanisms

During the period of treatment, care must be taken when driving vehicles and engaging in other potentially hazardous activities that require an increased concentration of attention and speed of psychomotor reactions (when taking the first dose).