Acnecutane capsules 16 mg 30 pcs
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Active ingredients
Isotretinoin
Release form
Capsules
Composition
1 tablet contains: Active ingredient: isotretinoin 16 mg. Adjuvants: Gelut; 50/13 (a mixture of esters of stearic acid polyethylene oxide and glycerol), purified soybean oil, Span 80; (sorbitan oleate - mixed esters of oleic acid and sorbitol). The composition of the capsule body: gelatin, titanium dioxide (E171). The composition of the capsule cap: gelatin, titanium dioxide (E171), iron dye yellow oxide (E172), indigo carmine (E132).
Pharmacological effect
The drug for the treatment of acne. Isotretinoin is a stereoisomer of fully trans retinoic acid (tretinoin). The exact mechanism of action of isotretinoin has not yet been identified, but it has been established that improving the clinical picture of severe forms of acne is associated with the suppression of sebaceous gland activity and a histologically confirmed decrease in their size. Propionibacterium acnes, therefore reducing the formation of sebum suppresses bacterial colonization of the duct. Acnecutane suppresses sebocyte proliferation and acts on acne, restoring the normal process of cell differentiation, stimulates regeneration processes. In addition, isotretinoin has an anti-inflammatory effect on the skin.
Pharmacokinetics
Absorption 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 a large proportion of dissolved isotretinoin in the drug, and may increase if it is taken with food. In patients with acne, Cmax in the equilibrium 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. DistributionPlasma protein binding (mainly albumin) - 99.9% .Css isotretinoin in the blood of patients with severe acne who took the drug 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 Metabolizes with the formation of 3 main biologically active metabolites - 4-oxo-isotretinoin (the main metabolite), tretinoin (all-trans retinoic acid) and 4-oxo-retinoin, and less significant metabolites, including glucuronides. Since in vivo isotretinoin and tretinoin are reversibly transformed 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, enterohepatic circulation may play a significant role. In vitro studies have shown that several cytochrome P450 enzymes are involved in the conversion of isotretinoin to 4-oxo-isotretinoin and tretinoin. Moreover, none of the isoforms, apparently, does not play a dominant role. Isotretinoin and its metabolites do not significantly affect the activity of cytochrome P450 enzymes. Output T1 / 2 of the terminal phase for isotretinoin is on average 19 hours. T1 / 2 of the terminal phase for 4-oxo-isotretinoin is on average 29 hours. about equal amounts. Refers to natural (physiological) retinoids. Endogenous concentrations of retinoids are restored approximately 2 weeks after the end of the drug.
Indications
- severe forms of acne (nodular-cystic, conglobate, acne with the risk of scarring); - acne that is not amenable to other therapies.
Contraindications
- pregnancy, established and planned (possibly teratogenic and embryotoxic action); - breastfeeding period; - liver failure; - hypervitaminosis A; - severe hyperlipidemia; - concomitant tetracycline therapy; - hypersensitivity to the drug or its components. children under 12 years old. With caution, you should prescribe the drug for diabetes, a history of depression, obesity, lipid metabolism disorders, alcoholism.
Precautionary measures
Application for abnormal liver function. It is recommended to monitor liver function and liver enzymes before treatment, 1 month after its onset, and then every 3 months or if indicated. A transient and reversible increase in hepatic transaminases is 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. Use for renal dysfunction In severe cases of chronic renal failure, the initial dose should be reduced to 8 mg / day. Use in children Acnecutane is not indicated in the treatment of acne during puberty and is not recommended for use in children up to 12 years.
Use during pregnancy and lactation
Pregnancy is an absolute contraindication for treatment 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 having a child with severe developmental defects. Isotretinoin is a drug with a strong teratogenic effect. If pregnancy occurs at a time when a woman orally takes isotretinoin (at any dose or even a short time), there is a very high risk of having a child with developmental disabilities. Annecutane is contraindicated for women of childbearing age, unless the condition of the woman meets all of the following criteria: - severe a form of acne that is resistant to the usual methods of treatment; the patient must understand and follow the instructions of the doctor; the patient must be informed by the doctor about the dangers of the onset of taking during the treatment with Acnecutane, for one month after it and urgent consultation in case of suspected pregnancy; - the patient should be warned about the possible ineffectiveness of contraceptives; - the patient must confirm that she understands the precautions; - the patient must understand the need for and continuously use effective methods of contraception during one month before treatment with Acnecutane, during treatment and within a month after its termination; it is desirable to use simultaneously 2 different methods of contraception,including the barrier; - the patient should receive a negative result of a reliable pregnancy test within 11 days before the start of the drug; a pregnancy test is strongly recommended to be carried out monthly during treatment and 5 weeks after the end of therapy; - the patient should begin treatment with Acnecutane only on the 2-3 day of the next normal menstrual cycle; - the patient should understand the need for a mandatory visit to the doctor every month; about the recurrence of the disease, the patient should always use the same effective methods of contraception for one month before the start of treatment with Acnecutane, during treatment and during after it is completed, as well as undergo the same reliable pregnancy test; - the patient should fully understand the need for precautions and confirm her understanding and desire to use reliable contraceptive methods that the doctor explained to her. Use of contraceptives according to the above instructions should be treated with isotretinoin recommend even to women who usually do not use contraceptive methods due to infertility (with the exception of patients undergoing hysterectomy), amenorrhea or who report that they are not sexually active. The doctor must be sure that: - The patient suffers from severe form of acne (nodular-cystic, conglobate acne or acne with the risk of scarring); acne that is not susceptible to other types of therapy; - a negative result was obtained from a reliable pregnancy test before starting the drug, during therapy and 5 weeks after the end of therapy; dates and results of the pregnancy test must 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 termination; - the patient is able understand and fulfill all of the above requirements for the prevention of pregnancy; - the patient meets all of the above conditions. Pregnancy test According to current practice, eating a pregnancy with a minimum sensitivity of 25 mME / ml should be held in the first 3 days of the menstrual cycle: Prior terapiiDlya exclude the possibility of pregnancy prior to the use of contraceptives and the result of the date of initial pregnancy test should be registered doctor.In patients with irregular menstruation, the time of the pregnancy test depends on sexual activity, it should be carried out 3 weeks after unprotected intercourse. The doctor must inform the patient about the methods of contraception. A pregnancy test is carried out on the day of Aknekutan's appointment or 3 days before the patient's visit to the doctor. The specialist should register the test results. The drug can only be prescribed to patients receiving effective contraception for at least 1 month before starting therapy with Acnecutane. During therapy, the patient should 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 violations of the menstrual cycle. If there is evidence, a pregnancy test is conducted on the day of the visit or 3 days before the visit to the doctor, test results must be recorded. End of therapy After 5 weeks of the end of therapy, a test is performed to rule out pregnancy. A prescription for Acnecutane to a woman capable of childbirth can be discharged only for 30 days of treatment, the continuation of therapy requires a new prescription of the drug by a doctor. A pregnancy test, prescription and receiving the drug should be carried out in one day. If, despite precautions taken, during treatment with Acnecutane or within a month after its termination, the pregnancy nevertheless occurred, there is a high risk of very severe fetal malformations. the occurrence of pregnancy therapy Aknekutanom stop. The feasibility of maintaining a pregnancy should be discussed with a physician specializing in teratology. Since isotretinoin has a high lipophilicity, it is very likely that it passes into breast milk. Because of the possible side effects of Acnecutane, it should not be prescribed to nursing mothers. Male patients Existing evidence suggests that in women, exposure to the drug coming from the semen and seminal fluid of men taking Acnecutane is not sufficient for the appearance of the teratogenic effects of Acnecutane. Men should exclude the possibility of taking the drug by other persons, especially women.
Dosage and administration
Inside, preferably with meals, 1-2 times / day. The therapeutic efficacy of Acnecutane and its side effects depend on the dose and vary in different patients. This necessitates individual selection of the dose during treatment. The initial dose of Acnecutane 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 cumulative course dose is 100-120 mg / kg. Complete remission is usually achieved in 16-24 weeks. If the recommended dose is poorly tolerated, 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. Repeated course prescribed not earlier than 8 weeks after the first, because improvement may be delayed. In severe chronic renal failure, the initial dose should be reduced to 8 mg / day.
Side effects
Most side effects are dose dependent. Typically, side effects are reversible after dose adjustment or drug withdrawal, but some may persist after stopping treatment. Symptoms associated with hypervitaminosis A: dry skin, mucous membranes, including lips (cheilitis), nasal cavity (bleeding), larynx and pharynx (hoarseness), eyes (conjunctivitis, reversible corneal clouding and contact lens intolerance). Dermatological reactions: peeling of the skin of the palms and soles, rash, itching, erythema of the face / dermatitis, sweating, pyogenic granuloma, paronychia, onychodystrophy, increased proliferation of granulation tissue, persistent thinning of hair, reversible hair loss, fulminant forms of acne, hirsutism, hyperpigmentation, photosensitization, easy trauma to the skin. At the beginning of treatment, acne exacerbation can occur, which persists for several weeks. From the musculoskeletal system: muscle pain with increased levels of CPK in or without serum, joint pain, hyperostosis, arthritis, calcification of ligaments and tendons, tendinitis. From the CNS side : 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. For the sense organs: xerophthalmia, isolated cases of visual acuity, photophobia, violation of dark adaptation (reduction of the severity of twilight vision); rarely - color disturbance (passing after drug withdrawal), 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 in wearing contact lenses. On the digestive system: dryness of the oral mucosa, bleeding from the gums, gum inflammation, 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. A transient and reversible increase in the activity of hepatic transaminases, isolated cases of hepatitis was noted. In many of these cases, the changes did not go beyond the normal range and returned to baseline during treatment, but in some situations there was a need to reduce the dose or cancel Acnecutane. On the respiratory system: rarely - bronchospasm (often in patients with bronchial asthma in history). On the part of the hemopoietic system: anemia, decrease in hematocrit, leukopenia, neutropenia, increase or decrease in the number of platelets, accelerated ESR.Laboratory indicators: hypertriglyceridemia, hypercholesterolemia, hyperurice mission, lowering HDL; rarely - hyperglycemia. During the reception of Acnecutane, cases of newly diagnosed diabetes were reported. In some patients, especially those engaged in intense physical activity, isolated cases of increased serum CK activity are described. Infections: local or systemic infections caused by gram-positive pathogens (Staphylococcus aureus). Others: lymphadenopathy, hematuria, proteinuria, vasculitis (Wegener granulomatosis, allergic vasculitis) , systemic hypersensitivity reactions, glomerulonephritis. Teratogenic and embryotoxic effects: congenital deformities - hydro- and microcephaly, underdevelopment of the cranial nerves, microphthal tions,malformations of the cardiovascular system, parathyroid glands, impaired skeletal formation (underdevelopment of the digital phalanges, skull, cervical vertebrae, femur, ankles, forearm bones, facial skull, cleft palate), low location of the auricles, ear development, underdevelopment of the auricles, or wolf mouth), poor location of the auricles, ear development, underdevelopment of the auricles, or wolf mouth the absence of the external auditory canal, a hernia of the brain and spinal cord, bone fusion, the fusion of the fingers and toes, impaired development of the thymus gland; fetal death during the perinatal period, premature birth, miscarriages, premature closure of the epiphyseal growth zones; in the experiment on animals - pheochromocytoma.
Overdose
In the event of an overdose, signs of hypervitaminosis A may appear. In the first few hours after an overdose, gastric lavage may be necessary.
Interaction with other drugs
Tetracycline antibiotics, corticosteroids 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, tertinoid, tertinoidom, tertinoidom, tertinoidomine retinol, tazaroten, adapalen) increases the risk of hypervitaminosis A.Izotretinoin may weaken the effectiveness of progesterone drugs, so do not use contraceptives with small doses of progesterone. Combined use with local keratolytic drugs for the treatment of acne is not recommended due to possible increased 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 liver enzymes before treatment, 1 month after its onset, and then every 3 months or according to indications. A transient and reversible increase in hepatic transaminases is noted, in most cases within normal limits. If the level of liver transaminases exceeds the norm, it is necessary to reduce the dose of the drug or cancel it. You should also determine the level of fasting serum lipids before treatment, 1 month after the start, and then every 3 months or according to indications.Usually, lipid concentrations are normalized after dose reduction or discontinuation of the drug, as well as dietary compliance. A clinically significant increase in triglyceride levels must be monitored, since their elevation above 800 mg / dL or 9 mmol / L may be accompanied by the development of acute pancreatitis, possibly fatal. If persistent hypertriglyceridemia or symptoms of pancreatitis Acnecutane should be canceled. In rare cases, patients treated with Acnecutane described depression, psychotic symptoms, and very rarely - suicide attempts. Although their causal relationship with the use of the drug has not been established, special care must be taken in patients with depression in history and all patients should be monitored for depression during treatment with the drug, if necessary, referring them to the appropriate specialist. However, the cancellation of Acnecutane may not lead to the disappearance of symptoms and may require further observation and treatment by a specialist. In rare cases, at the beginning of therapy acne exacerbation is noted, which passes for 7-10 days without adjusting the dose of the drug. evaluate the ratio of possible benefits and risks. For patients receiving Acnecutane, it is recommended to use moisturizing ointment or body cream, lip balm to reduce dry skin and mucous membranes in starting therapy. Acnekutan can cause pain in muscles and joints, increased serum CK, which may be accompanied by a decrease in tolerance to intense physical exertion. Avoid deep chemical dermo-abrasion and laser treatment in patients receiving Acnecutane, as well as for 5-6 months after the end of treatment due to the possibility of enhanced scarring at atypical sites and the occurrence of hyper- and hypopigmentation. During the treatment with Acnecutane and for 6 months after it, epilation cannot be performed using wax because of the risk of epidermis detachment, development of scars and dermatitis. Some patients may experience a reduction in visual acuity sometimes should be informed about the possibility of this state, recommending them to be careful when driving a car at night. The state of visual acuity must be carefully monitored. Dry conjunctival eyes, corneal opacities, blurred night vision and keratitis usually disappear after discontinuation of the drug.For dryness of the mucous membrane of the eyes, you can use applications of moisturizing eye ointment or preparation of artificial tears. It is necessary to observe patients with dry conjunctiva for possible development of keratitis. Patients complaining of vision should be referred to an ophthalmologist and consider the advisability of canceling Acnecutane. If contact lenses are intolerant, glasses should be used at the time of therapy. The effects of solar insolation and UV therapy should be limited. If necessary, a sunscreen with a high protective factor of at least 15 SPF should be used. Rare cases of the development of benign intracranial hypertension (brain pseudo-tumor) are described, including when combined with tetracyclines. In such patients, Acnecutane should be abolished immediately. When treating with Acnecutane, inflammatory bowel disease may occur. In patients with severe hemorrhagic diarrhea, Acnecutane should be immediately discontinued. Rare cases of anaphylactic reactions that occurred only after previous external use of retinoids have been described. Severe allergic reactions dictate the need for drug withdrawal and careful monitoring of the patient. Patients in the high-risk group (with diabetes, obesity, chronic alcoholism or impaired metabolism) may need more frequent laboratory monitoring of glucose and lipids in the treatment of Acnecutane. If diabetes is present or suspected, a more frequent determination of glycemia is recommended. Patients with diabetes mellitus are recommended to conduct more frequent monitoring of glucose in the blood. During the period of treatment and within 30 days after its termination, it is necessary to completely exclude blood sampling from potential donors in order to completely exclude the possibility of pregnant women getting this blood (high risk of teratogenic and embryotoxic effects) Influence on the ability to drive motor vehicles and control mechanisms. During the treatment period, care must be taken when driving motor vehicles and occupying others. they are potentially hazardous activities that require increased concentration of attention and quickness of psychomotor reactions (when taking the first dose).