AcneCutan® (Acnecutan®)

Composition Pharmacodynamics Indications Carefully Contraindications Dosing and Administration Side effects Form release / dosage
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Active substanceIsotretinoinIsotretinoin
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    • Dosage form: & nbspcapsules
    Composition:

    COMPOSITION ON 1 CAPSULE

    Capsules 8 mg

    Active substances: Isotretinoin - 8.0 mg

    Excipients:

    Gelucir® 50/13 (mixture of stearic acid esters of polyethylene oxide and glycerol) - 96.00 mg;

    refined soybean oil - 52,00 mg;

    Span 80® (sorbitan oleate - mixed esters of oleic acid and sorbitol) - 8.00 mg.

    Capsules 16 mg

    Active substances: Isotretinoin - 16.0 mg

    Excipients:

    Gelucir® 50/13 (mixture of stearic acid esters of polyethylene oxide and glycerol) - 192.00 mg;

    purified soybean oil - 104,00 mg;

    Span 80® (sorbitan oleate - mixed esters of oleic acid and sorbitol) - 16,00 mg

    COMPOSITION OF CAPSULES

    Acnekutan 8 mg

    body and cover: gelatin, iron oxide red (E172), titanium dioxide (E171);

    Acnecutan 16 mg

    body: gelatin, titanium dioxide (E171),

    cover: gelatin, titanium dioxide (E171), iron oxide yellow dye (E172), indigocarmine (E132).

    Description:

    Capsules 8 mg:

    Hard gelatin capsules No. 3 in brown color. The contents of the capsules are a waxy yellow-orange paste.

    Capsules 16 mg:

    Hard gelatin capsules No. 1, white body, lid green. The contents of the capsules are a waxy yellow-orange paste.

    Pharmacotherapeutic group:Treatment for acne
    ATX: & nbsp

    D.10.B.A.01   Isotretinoin

    Pharmacodynamics:

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

    The exact mechanism of action of isotretinoin has not yet been revealed, but it has been established that the improvement in the clinical picture of severe forms of acne is associated with suppression of sebaceous gland activity and histologically confirmed decrease in their size. Skin fat - the main substrate for growth Propionibacterium acnes, so reducing the formation of sebum suppresses the bacterial colonization of the duct.

    Acnekutan® suppresses the proliferation of sebocytes and acts on acne, restoring the normal process of cell differentiation, stimulates regenerative 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 on the basis of 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 the metabolism of drugs.

    High bioavailability of Accecutane® is caused by a large proportion of dissolved isotretinoin in the drug, and can increase if the drug is taken with food.

    In patients with acne, the maximum plasma concentrations (Cmax) in the equilibrium state after administration of 80 mg of fasting isotretinoin were 310 ng / ml (range 188-473 ng / ml) and were achieved after 2-4 hours. The concentration of isotretinoin in plasma is 1.7 times higher than in blood, due to the poor penetration of isotretinoin into erythrocytes. The connection with plasma proteins (mainly with albumin) is 99.9%.

    Equilibrium concentrations of isotretinoin in the blood (Css) in patients with severe forms of acne, taking 40 mg of the drug twice a day, ranged from 120 to 200 ng / ml. The concentration of 4-oxo-isotretinoin (the main metabolite) in these patients was 2.5 times higher than that of isotretinoin.

    The concentration of isotretinoin in the epidermis is 2 times lower than in serum.

    Metabolized with the formation of 3 major biologically active metabolites - 4-oxo-isotretinoin (chief), tretinoin (fully trans retinoic acid) and 4-oxo-retinoin, as well as less significant metabolites, including glucuronides. Since in vivo isotretinoin and tretinoin reversibly transform into each other, the metabolism of tretinoin is associated with the metabolism of isotretinoin. 20-30% of the dose of isotretinoin is metabolized by isomerization. In the pharmacokinetics of isotretinoin in humans, an important role can be played by intestinal hepatic recirculation.

    In vitro studies have shown that in the conversion of isotretinoin to 4-oxo-isotretinoin and tretinoin Several cytochrome isoenzymes participate P450, while none of the isoforms, apparently, does not play a dominant role. Isotretinoin and its metabolites have no significant effect on the activity of cytochrome isoenzymes P450.

    The half-life of the terminal phase for isotretinoin averages 19 hours. The half-life of the terminal phase for 4-oxo-isotretinoin averages 29 hours.

    Isotretinoin is excreted by the kidneys and with 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 intake.

    Pharmacokinetics in special clinical cases

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

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

    Indications:

    Heavy forms of acne (nodular - cystic, conglobata, acne with the risk of scar formation).

    Acne, not amenable to other types of therapy.

    Contraindications:
    Pregnancy, established and planned (possibly teratogenic and embryotoxic action), the period of breastfeeding, liver failure, hypervitaminosis A, severe hyperlipidemia, concomitant tetracycline therapy.

    Hypersensitivity to the drug or its components.

    Acnekutan® not recommended for use in children under 12 years.

    Carefully:

    Diabetes mellitus, a history of depression, obesity, a violation of lipid metabolism, alcoholism.

    Pregnancy and lactation:

    Pregnancy is an absolute contraindication for therapy with Acnecutane®.

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

    Isotretinoin is a drug with a strong teratogenic effect. If pregnancy occurs during the period when a woman orally takes isotretinoin (at any dose and even for a short time), there is a very high risk of a child with developmental defects. Acnekutan® contraindicated in women of childbearing age, unless the condition of a woman meets all of the following criteria:

    · she should have a severe form of acne, resistant to conventional methods of treatment;

    · she must accurately understand and follow the doctor's instructions;

    · she should be informed by the doctor about the dangers of pregnancy during treatment with Acnecutane®, within one month after it and urgent consultation in case of suspected pregnancy;

    · she should be warned about the possible ineffectiveness of contraceptives;

    · she must confirm that she understands the nature of precautions;

    · she must understand the need and continuously use effective contraceptive methods within one month prior to treatment with Acnecutant®, during treatment and for a month after its end (see section "Interaction with other drugs"); It is desirable to use at the same time 2 different methods of contraception, including barrier;

    · she should receive a negative result of a valid pregnancy test within 11 days before the drug is taken; a pregnancy test is strongly recommended to be performed monthly during treatment and 5 weeks after the end of therapy;

    · she must begin treatment with Acnecutane® only on 2-3 day of the next normal menstrual cycle;

    · she must understand the need for a compulsory visit to the doctor every month;

    · when treating for a relapse of the disease, she should constantly use the same effective methods of contraception within one month before the beginning of treatment with Acnecutant®, during treatment and within a month after its completion, and also undergo the same reliable pregnancy test;

    · she must fully understand the need for precautionary measures and confirm her understanding and desire to apply reliable methods of contraception, which the doctor explained to her.

    The use of contraceptives in accordance with the above instructions during treatment with isotretinoin should be recommended even to women who usually do not use contraceptive methods due to infertility (except for patients who underwent a hysterectomy), amenorrhea, or who report that they do not have sex.

    The doctor should be sure that:

    · the patient suffers from severe acne (nodular-cystic, conglobate acne or acne with the risk of scarring); acne, not amenable to other types of therapy;

    · a negative result of a valid pregnancy test was obtained prior to taking the drug, during therapy and 5 weeks after the end of therapy; the dates and results of the pregnancy test must be documented;

    · the patient uses at least one, preferably two, effective methods of contraception, including the barrier method, within one month before initiating treatment with Acnecutant®, during treatment and for a month after its termination;

    · the patient is able to understand and fulfill all of the above requirements for protection from pregnancy;

    · the patient meets all of the above conditions.

    Pregnancy test

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

    Before the start of therapy:

    · To exclude a possible pregnancy before the application of contraception, the result and the date of the initial pregnancy test must be recorded by the doctor. In patients with irregular menstruation, the timing of the pregnancy test depends on sexual activity, it should be performed 3 weeks after unprotected intercourse. The doctor should inform the patient about the methods of contraception.

    · The pregnancy test is carried out on the day of appointment of Acnecutane® or 3 days before the patient's visit to the doctor. The specialist should register the test results. The drug may be prescribed only to patients receiving effective contraception at least 1 month prior to initiating therapy with Acnecutant®.

    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 the sexual activity preceding the menstrual cycle disorders. If there is evidence, a pregnancy test is conducted on the day of the visit or 3 days before the visit to the doctor, the test results must be recorded.

    End of therapy:

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

    Recipe for Accutane® a woman capable of childbearing can be discharged only for 30 days of treatment, continuation of therapy requires a new prescription of the drug by a doctor. It is recommended that a pregnancy test, a prescription and preparation be conducted on the same day.

    If, despite the precautionary measures taken, during treatment with Acnecutane® or within a month after its termination, pregnancy nevertheless has come, there is a high risk of very serious malformations of the fetus.

    When pregnancy occurs, Acnecutane therapy® terminate. We should discuss the expediency of maintaining a pregnancy with a doctor specializing in teratology.

    Because the isotretinoin has a high lipophilicity, it is very likely that it enters the breast milk. Because of possible side effects of Acnecutane® can not be given to nursing mothers.

    To male patients:

    Existing evidence suggests that in women exposure to the drug that came from the semen and semen of men taking Acnecutane®, is not sufficient for the appearance of teratogenic effects of Acnecutane®.

    Men should be excluded from the possibility of taking the drug by other people, especially women.

    Dosing and Administration:

    Inside, preferably with food, 1-2 times a day.

    Therapeutic efficacy of Acnecutane® and its side effects depend on the dose and vary in different patients. This makes it necessary to select the individual dose in the course of treatment.

    Initial dose of Acnecutane® - 0.4 mg / kg per day, in some cases up to 0.8 mg / kg per day. In severe cases or with acne, 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 is usually achieved in 16-24 weeks. With poor tolerability of the recommended dose, treatment can be continued at a lower dose, but longer.

    In most patients, acne completely disappears 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. The repeated course is prescribed not 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:

    Most side effects depend on the dose. Usually, side effects are reversible after dose adjustment or drug withdrawal, but some may persist after discontinuation of treatment.

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

    Skin and its appendages: peeling of the skin of the palms and soles, rashes, itching, face erythema / dermatitis, sweating, pyogenic granuloma, paronychia, onychodystrophy, increased granulation tissue proliferation, persistent thinning of hair, reversible hair loss, fulminant forms of acne, hirsutism, hyperpigmentation, photosensitivity, slight trauma of the skin .At the beginning of treatment, there may be an exacerbation of acne, which lasts for several weeks.

    Musculoskeletal system: muscle pain with or without elevated serum CK, joint pain, hyperostosis, arthritis, calcification of ligaments and tendons, tendonitis.

    Central nervous system and psychic sphere: excessive fatigue, headache, increased intracranial pressure ("pseudotumor brain": headache, nausea, vomiting, impaired vision, edema of the optic nerve), seizures, rarely - depression, psychosis, suicidal thoughts.

    Sense organs: xerophthalmia, individual cases of visual acuity, photophobia, disturbance of dark adaptation (diminishing of twilight vision), rarely - violation of color perception (passing after drug withdrawal), lenticular cataract, keratitis, blepharitis, conjunctivitis, eye irritation, optic neuritis, optic nerve edema (as a manifestation of intracranial hypertension); hearing impairment at certain sound frequencies, difficulties in 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 lethal outcome are described. Transient and reversible increase in hepatic transaminase activity, isolated cases of hepatitis. In many of these cases, the changes did not go beyond the limits of the norm and returned to the baseline during treatment, however, in some situations, it was necessary to reduce the dose or cancel Acne®.

    Respiratory system: rarely - bronchospasm (more often in patients with bronchial asthma in the anamnesis).

    Blood 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, a decrease in the level of high-density lipoproteins, and rarely hyperglycemia. During the reception of Acnecutane® cases of newly diagnosed diabetes mellitus were registered. In some patients, especially those engaged in intensive physical activity, individual cases of increased activity of CK in the serum are described.

    The 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 malformation - hydrophilic and microcephaly, hypoplasia of the cranial nerves, microphthalmia, developmental defects of the CCC, parathyroid glands, skeletal malformation - underdevelopment of finger phalanges, skull, cervical vertebrae, femur, ankles, forearm bones, facial skull, wolf mouth, shells, underdevelopment of the auricles, underdevelopment or complete absence of the external auditory canal, hernia of the brain and spinal cord, bone fusion, fusion of the fingers and toes, dysplasia of the thymus gland; fetal death in the perinatal period, premature birth, miscarriage), premature closure of epiphyseal growth zones; in an experiment on animals - pheochromocytoma.

    Overdose:

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

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

    Interaction:

    Antibiotics of the tetracycline series, GCS reduce the effectiveness.

    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, adapalen) increases the risk of hypervitaminosis A.

    Isotretinoin may impair the effectiveness of progesterone preparations, so do not use contraceptives containing small doses of progesterone.

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

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

    Special instructions:

    It is recommended to monitor liver function and hepatic enzymes before treatment, 1 month after its onset, and then every 3 months or according to indications.There was a transient and reversible increase in hepatic transaminases, 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 to cancel it. The level of serum lipids in the fasting serum should be determined before the treatment, 1 month after the start, and then every 3 months or according to the indications. Usually lipid concentrations are normalized after dose reduction or drug withdrawal, as well as dieting. It is necessary to monitor a clinically significant increase in triglyceride levels, since their elevation above 800 mg / dl or 9 mmol / l may be accompanied by the development of acute pancreatitis, possibly fatal.

    With persistent hypertriglyceridemia or symptoms of pancreatitis, Acnekutan® should be canceled. In rare cases in patients receiving Acnecutane®, described depression, psychotic symptoms and very rarely - suicidal attempts. Although their causal relationship with the use of the drug is not established, special care should be taken in patients with a history of depression and observe all patients for depression during treatment with the drug, if necessary referring them to the appropriate specialist. However, the cancellation of Acnecutane® can not lead to the disappearance of symptoms and may require further observation and treatment with a specialist.

    In rare cases, at the beginning of therapy, there is an exacerbation of acne, which occurs within 7-10 days without correction of the dose of the drug.

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

    Patients receiving AcneCutan®, it is recommended to use 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 Adenecutane® possible pain in the muscles and joints, an increase in serum creatinine phosphokinase, which may be accompanied by a decrease in the tolerance of intense physical activity.

    It is necessary to avoid carrying out deep chemical dermoabrasion and laser treatment in patients receiving Acnecutane®, and also within 5-6 months after the end of treatment because of the possibility of increased scarring in atypical sites and the appearance of hyper- and hypopigmentation. During treatment with Acnecutane® and within 6 months after it can not be epilated using wax applications due to the risk of detachment of the epidermis, the development of scarring and dermatitis.Since some patients may have a decrease in visual acuity, which sometimes persists after the end of therapy, patients should be informed about the possibility of this condition, recommending them to use caution when driving a car at night. The state of visual acuity needs to be carefully monitored. Dryness of the conjunctiva of the eyes, opacity of the cornea, worsening of night vision and keratitis usually pass after drug withdrawal. With dry eye mucosa, you can use moisturizing ointment applications or artificial tears. It is necessary to observe patients with dryness of the conjunctiva for possible development of keratitis. Patients presenting complaints of vision should be referred to an ophthalmologist and consider whether it is advisable to cancel Acnecutane®. If intolerance of contact lenses for the duration of therapy should be used glasses.

    The effects of solar insolation and UV therapy should be limited. If necessary, use a sunscreen with a high protective factor of at least 15 SPF.

    Rare cases of development of benign intracranial hypertension ("pseudotumor brain"),in t.ch. when combined with tetracyclines. Such patients should immediately abolish Acnecutane®.

    With therapy with Acnecutane® possibly the onset of inflammatory bowel disease. In patients with severe hemorrhagic diarrhea, it is necessary to immediately cancel Acne®.

    Rare cases of anaphylactic reactions, which occurred only after the previous external application of retinoids, are described. Severe allergic reactions dictate the need to discontinue the drug and carefully monitor the patient.

    Patients in the high-risk group (with diabetes, obesity, 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 suspected of it, a more frequent definition of glycemia is recommended.

    Patients with diabetes are encouraged to conduct more frequent monitoring of blood glucose.

    During the treatment period and within 30 days after it is completed, it is necessary to completely exclude blood from potential donors forcompletely excluding the possibility of getting this blood to pregnant patients (high risk of teratogenic and embryotoxic action).

    Effect on the ability to drive transp. cf. and fur:

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

    Form release / dosage:
    Capsules 8 mg and 16 mg.
    Packaging:

    For 10 or 14 capsules in a PVC blister, covered with aluminum foil.

    Blisters-10-N2, N3, N5, N6, N9, N10; blisters-14-N1, N2, N4, N7 in a cardboard box together with instructions for use.

    Storage conditions:

    In a dry place, protected from light, out of reach of children, at a temperature not exceeding 25 ° C.

    Shelf life:

    2 years. Do not use after expiry date.

    Terms of leave from pharmacies:On prescription
    Registration number:LSR-004782/09
    Date of registration:16.06.2009 / 19.04.2017
    Expiration Date:Unlimited
    The owner of the registration certificate:Yadran Galensky Laboratories a.o.Yadran Galensky Laboratories a.o. Croatia
    Manufacturer: & nbsp
    Representation: & nbspYadran Galen Laboratory as.Yadran Galen Laboratory as.Croatia
    Information update date: & nbsp25.05.2017
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