Index of drugs

Severe forms of acne (including nodular acne, acne acne or acne with the risk of permanent scars) resistant to properly conducted standard treatment with antimicrobial agents acting in general and topically applied drugs.

1 soft capsule contains 5 mg, 10 mg, 20 mg or 40 mg isotretinoin. The preparation contains purified soya oil.

Anti-acne drug for general use. It inhibits the activity of sebaceous glands and reduces their size, affecting the inhibition of multiplicationPropionibacterium acnes. Normalizes the process of keratinization as a result of inhibiting the proliferation of sebocytes and probably restores the normal process of cell differentiation. Isotretinoin also exerts anti-inflammatory action. Absorption of the drug from the gastrointestinal tract is variable and linearly dose-dependent within the therapeutic range; food increases absorption (when taken with food, the bioavailability is increased by 2-fold compared to the administration on an empty stomach). It binds plasma proteins in more than 99.9% (mainly albumin). Isotretinoin concentrations in the epidermis are half that of serum concentrations. Following the oral administration, three major metabolites were isolated: 4-oxo-isotretinoin, tretinoin (all-trans-retinoic acid) and 4-oxotretinoin. Several enzymes of the cytochrome CYP system are involved in the metabolism of the drug. It is excreted in urine and faeces. T_0,5 isotretinoin in the final phase of elimination is on average 19 h, and its metabolite (4-oxo-isotretinoin) - an average of 29 h.

Pregnancy and breastfeeding, isotretinoin is contraindicated in women of childbearing age, unless the requirements of the Pregnancy Prevention Program are met. Hypersensitivity to isotretinoin or any of the excipients, peanut allergies or soybean oil. Liver failure. Increased blood lipids. Hypervitaminosis A. Simultaneous use of tetracyclines.

The preparation is contraindicated in women of childbearing age, unless all the requirements of the Pregnancy Prevention Program are met: the patient has severe acne, is aware of the risk of teratogenic effects of the drug, and understands the need to regularly carry out monthly medical checks. The patient understands and accepts the need for effective contraception, continuously, for 1 month before the start of treatment, throughout the treatment period and for 1 month after the end of treatment. The patient should use at least one, preferably two complementary methods of contraception, including a mechanical method. Even if the patient does not have menses, she must follow all recommendations for effective contraception. The patient understands the need to perform pregnancy tests and agrees to carry them out before treatment, during treatment and 5 weeks after the end of treatment. These requirements also apply to women who are not sexually active in the current period, unless the doctor believes that there are reasons to conclude that there is no risk of becoming pregnant. According to local practice, it is recommended that under the supervision of a physician, a pregnancy test with a minimum sensitivity of 25 ml U / ml is performed within the first 3 days of the menstrual cycle, as described below. Before starting treatment in order to rule out that the patient is pregnant, before using contraception, it is recommended to perform a preliminary pregnancy test under the supervision of the doctor and to record the date and the result in the documentation. In patients with irregular menstruation, the date of the test should take into account the sexual activity of the patient and should be carried out approximately 3 weeks after the last sexual intercourse without contraceptive protection. A pregnancy test under the supervision of a physician should also be carried out during a visit during which isotretinoin is prescribed or within 3 days before. If the patient has not used effective methods of contraception for at least 1 month, the date of the doctor's visit and the pregnancy test should be moved accordingly. Control visits should be carried out at 28-day intervals.The necessity to perform pregnancy tests under the supervision of a doctor every month should be determined in accordance with local practice, taking into account the sexual activity of the patient and the course of the menstrual cycle in the recent period (menstrual disorders, delayed menstruation, total lack of menstruation). After 5 weeks after the end of treatment, a final pregnancy test should be performed to ensure that the patient is not pregnant. Isotretinoin for women of childbearing age must be discharged in an amount not exceeding 30 days of treatment. Ideally, the pregnancy test, prescription and purchase of the preparation should take place on the same day. The prescription should be completed within a maximum of 7 days from the date of the doctor's prescription. Available data suggest that the exposure of a pregnant partner to isotretinoin contained in the semen of men treated with isotretinoin is not sufficient to induce a teratogenic effect. Patients should be instructed not to give the preparation to other people, especially women, and to return to the pharmacy all unused capsules after treatment. Patients should not donate blood during treatment and for 1 month after treatment because of the potential risk of fetal damage if blood is transfused to a pregnant woman. The preparation should be used with particular care in patients with a history of depression. All patients should be monitored for symptoms of depression and referred to appropriate treatment if necessary. Exacerbation of acne changes is sometimes observed in the initial period of treatment, usually it disappears within 7-10 days and does not require a change in dosage. Avoid exposure to intense solar radiation and UV radiation. If necessary, protective preparations containing UV filters of at least SPF 15 should be used. Aggressive chemical dermabrasion and laser treatment of the skin during treatment with isotretinoin should be avoided and within 5-6 months after its completion, due to the risk of hypertrophic scars with atypical location and (less frequently) post-inflammatory hyperpigmentation and discoloration in treated areas of the skin. Avoid waxing for at least 6 months after treatment, due to the risk of rupture of the epidermis. The simultaneous use of isotretinoin with topical keratolytic and exfoliating preparations should be avoided, due to the risk of local irritation. Careful observation of patients for severe skin reactions should be made; if severe skin reaction is suspected, treatment with isotretinoin should be discontinued. Patients with symptoms of vision disorders should be referred for ophthalmologic consultation - it may be necessary to discontinue isotretinoin. In patients who develop benign intracranial hypertension, treatment with isotretinoin should be stopped immediately. Unless there are clinical indications for more frequent monitoring, hepatic enzymes should be measured prior to treatment initiation, after 1 month after starting treatment, and then at 3-month intervals. If a clinically significant increase in transaminases persists, a dose reduction or discontinuation of treatment should be considered. The concentration of serum lipids (fasted) should be measured before treatment, after 1 month after initiation of treatment, and then at 3-month intervals, unless more frequent monitoring is indicated. Treatment with isotretinoin should be discontinued if hypertriglyceridemia can not be compensated for or when symptoms of pancreatitis occur. Concentrations in excess of 800 mg / dl or 9 mmol / l may sometimes lead to acute pancreatitis that can cause death. Due to the risk of inflammatory bowel diseases, in the case of severe (hemorrhagic) diarrhea, treatment with isotretinoin should be stopped immediately. If severe allergic reactions occur, discontinuation of treatment and close monitoring of the patient is necessary. In patients with diabetes, obesity, alcohol abuse or lipid metabolism disorders, more frequent monitoring of serum lipids and / or blood Glucose may be necessary. An increase in fasting glucose was reported and new cases of diabetes were diagnosed during treatment with isotretinoin. Isotretinoin is not indicated for the treatment of pre-pubescent acne and is not recommended for children under 12 years of age.

The drug is strictly contraindicated during pregnancy. If the patient becomes pregnant despite the necessary precautions being taken during treatment with isotretinoin or during the month following its completion, there is a significant risk of very serious malformations in the fetus. Fetal malformations associated with the use of isotretinoin include the disadvantages of o.u.n. (hydrocephalus, cerebellar developmental defects, microcephaly), facial deformities, cleft palate, external ear abnormalities (lack of external ear, small external auditory tubes or lack thereof), eye defects (minor), cardiovascular defects (malformations of the joint arterial trunk, such as: tetralogy of Fallot, translation of large vessels, damage to the septum), thymic and parathyroid disorders. Spontaneous abortions are more common. If a woman becomes pregnant during treatment with isotretinoin, treatment should be discontinued and the patient referred for consultation with a physician experienced in the field of teratology in order to seek and seek advice. The use of isotretinoin in women during breastfeeding is contraindicated.

Very common: red lips inflammation, dermatitis, dry skin, local epidermal exfoliation, pruritus, erythematous rash, hypersensitivity of the skin (risk of frictional injury), blepharitis, conjunctivitis, dry eyes, eye irritation, muscle and joint pain, pain back pain (especially in adolescents), anemia, accelerated ESR, thrombocytopenia, thrombocytopenia, increased transaminases, increased triglycerides in the blood, decreased high-density lipoprotein. Common: headache, neutropenia, nosebleeds, dry nose, nasopharyngeal inflammation, increased cholesterol in the blood, increased blood Glucose, hematuria, proteinuria. Rarely: depression, aggravation of depressive symptoms, tendency to aggression, anxiety, mood changes, baldness, hypersensitivity reactions (skin allergic reactions, anaphylactic reactions). Very rare: behavioral disorders, psychotic disorders, suicidal thoughts, suicide attempts, suicide, benign intracranial hypertension, convulsions, drowsiness, blurred vision, blurred vision, cataracts, color blindness (lack of color vision), contact lens intolerance, corneal opacity , worsening vision in the dark, keratitis, congestive disc (a symptom of benign intracranial hypertension), photophobia, impaired hearing, vasculitis (eg, Wegener's granulomatous disease, allergic vasculitis), bronchospasm (especially in patients with asthma), hoarseness, inflammation colon, ileitis, dry throat, gastrointestinal haemorrhage, haemorrhagic diarrhea, inflammatory bowel disease, nausea, pancreatitis, hepatitis, glomerulonephritis, diabetes, hyperuricemia, fulminant acne, exacerbation of acne (relapse), facial erythema, knot, hair disorder, hirsutism, nausea dystrophy, allergic reactions, photosensitivity reactions, pyogenic granuloma, hyperpigmentation of the skin, increased sweating, arthritis, calcification (calcification of ligaments and tendons), premature growth of long bones, bone spurs (hyperostosis), reduction bone density, tendinitis, lymphadenopathy, skin and mucosa infections with Gram-positive bacteria, increased creatine kinase in the blood, excessive granulation, malaise. Not known: erythema multiforme, Stevens-Johnson syndrome and toxic epidermal necrolysis.

Orally. Isotretinoin may only be prescribed by a physician experienced in the treatment of severe forms of acne with general retinoids and full knowledge of the risk of isotretinoine treatment and the requirements for monitoring the patient, or under the supervision of a physician meeting these conditions. Adults, including adolescents and elderly patients: treatment should start at a dose of 0.5 mg / kg. per day. It is necessary to adjust the dosage individually. For most patients, the dose is 0.5 mg / kg. up to 1 mg / kg per day. Long-term remission and the incidence of relapse are more dependent on the total dose given than the duration of treatment or the daily dose.It has been demonstrated that no significant additional therapeutic benefit should be expected after using the cumulative dose of 120-150 mg / kg. The duration of treatment depends on the individual daily dose. Treatment lasting from 16 to 24 weeks is usually sufficient to achieve remission. In the majority of patients, the complete resolution of acne symptoms is achieved after a single treatment cycle. In the event of a clear relapse, a repetition of the treatment cycle may be considered using the same daily and cumulative dose. Due to the fact that the further disappearance of acne symptoms may occur up to 8 weeks after the end of treatment, you should not take another treatment cycle before this time. In patients with severe renal impairment, treatment should be started with a lower dose (eg 10 mg / day). The dose should then be increased to not more than 1 mg / kg / day or up to the maximum dose tolerated by the patient. In patients with severe intolerance of the product after the recommended dose, treatment with a lower dose may be continued. This results in prolonged therapy and is associated with a higher risk of relapse. To achieve the maximum possible treatment efficacy in these patients, the highest dose tolerated by the patient should be continued.
The capsules should be taken with food once or twice a day.