Sotret, 10mg capsules, 30pcs

Composition

Each capsule contains isotretinoin 10 mg

Pharmacological action

Pharmaceutical group:

tissue regeneration stimulator.

Pharmaceutical effect:

Retinoid for systemic treatment of acne

Isotretinoin is a stereoisomer of all-trans-retinoic acid (tretinoin). The exact mechanism of action of Sotret has not yet been clarified, but 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. In addition, the anti-inflammatory effect of isotretinoin on the skin has been proven.

Hyperkeratosis of the epithelial cells of the hair bulb and sebaceous gland leads to exfoliation of corneocytes in the duct of the gland and to blockage of the latter with keratin and excess sebaceous secretions. This is followed by the formation of comedones and, in some cases, the addition of an inflammatory process. Sotret suppresses the proliferation of sebocytes and acts on acne, restoring the normal process of cell differentiation. Sebum is the main substrate for the growth of Propionibacterium acnes, so reducing the formation of sebum suppresses bacterial colonization of the duct.

Pharmacokinetics:

Since the kinetics of isotretinoin and its metabolites are 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 liver enzymes involved in drug metabolism.

Suction.

The absorption of isotretinoin from the gastrointestinal tract fluctuates. The absolute bioavailability of isotretinoin was not determined, since there is no form of release of the drug for intravenous use in humans. However, extrapolating the data obtained in the experiment on dogs suggests a rather low and variable systemic bioavailability. 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 reached in 2-4 hours. Plasma isotretinoin concentrations are approximately 1.7 times higher than blood concentrations, due to poor penetration of isotretinoin into red blood cells.

Taking isotretinoin with food increases bioavailability by 2 times compared to taking it on an empty stomach.

Distribution.

Isotretinoin binds strongly (99.9%) to plasma proteins, mainly albumins, so that in a wide range of therapeutic concentrations, the content of the free (pharmacologically active) fraction of the drug is less than 0.1% of its total amount.

The volume of distribution of isotretinoin in humans was not determined, since there is no dosage form for intravenous use. Steady-state concentrations of isotretinoin in the blood (C min ss) in 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. There is insufficient data on the penetration of isotretinoin into human tissues. The concentration of isotretinoin in the epidermis is two times lower than in the serum.

Metabolism.

After oral use, three main metabolites are detected in plasma: 4-oxo-isotretinoin, tretinoin (completely trans-retinoic acid) and 4-oxo-retinoin.

The main metabolite is 4-oxo-isotretinoin, whose plasma concentrations at steady state are 2.5 times higher than those of the initial drug. Less significant metabolites, including glucuronides, were also found, but the structure of not all metabolites was established.

Isotretinoin metabolites have biological activity that has been confirmed in several laboratory tests. Thus, the clinical effects of the drug in patients may be the result of the pharmacological activity of isotretinoin and its metabolites. Since isotretinoin and tretinoin (fully trans-retinoic acid) are reversibly converted to each other in vivo, tretinoin metabolism is related to isotretinoin metabolism. 20-30% of the isotretinoin dose is metabolized by isomerization. Enterohepatic circulation may play a significant role in the pharmacokinetics of isotretinoin in humans.

In vitro metabolic studies have shown that several CYP enzymes are involved in the conversion of isotretinoin to 4-oxo-isotretinoin and tretinoin. Apparently, none of the isoforms plays a dominant role in this process. Sotret and its metabolites do not significantly affect the activity of CYP enzymes.

Output.

After ingestion of radioactively labeled isotretinoin, approximately the same amount is detected in the urine and feces. The terminal half-life for an unchanged drug in patients with acne is, on average,19 hours. The terminal phase half-life of 4-oxo-isotretinoin appears to be longer, averaging 29 hours.

Isotretinoin belongs to natural (physiological) retinoids. Endogenous retinoid concentrations are restored approximately 2 weeks after the end of Sotret use.

Pharmacokinetics in special clinical cases.

Since isotretinoin is contraindicated in patients with impaired liver function, data on the pharmacokinetics of the drug in this group of patients are limited. Renal insufficiency does not affect the pharmacokinetics of isotretinoin.

Indications

Severe forms of acne (nodular-cystic, conglobate acne, or acne with a risk of scarring).

Acne that does not respond to other types of therapy.

Use during pregnancy and lactation

Pregnancy is an absolute contraindication for Sotret 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 isotretinoin orally (in any dose and even for a short time), there is a very high risk of having a child with malformations. Sotret is contraindicated in women of childbearing age, unless the woman’s condition meets all of the following criteria: :

* she must have a severe form of acne that is resistant to conventional treatments;• she should be sure to understand and follow the doctor’s instructions;• she should be informed by the doctor about the danger of pregnancy during treatment with Sotret, within one month after it, and an urgent consultation if pregnancy is suspected. ;• she should be warned about the possible ineffectiveness of contraception;• she must confirm that she understands the nature of the precautions. ;• she should understand the need and continuously use effective methods of contraception for one month before treatment with Sotret, during treatment and for a month after it ends (see the section “Interaction with other drugs”); it is advisable to use 2 different methods of contraception at the same time, including barrier;•she should have a negative result of a reliable pregnancy test within 11 days before taking the drug; pregnancy test is strongly recommended to be performed monthly during treatment and 5 weeks after the end of therapy;• she should start treatment with Erasure only on day 2-3 of the next normal menstrual cycle;• she should understand the need for a mandatory visit to the doctor every month;• when treating for a relapse of the disease, she should constantly use the same effective methods of contraception for one month before starting treatment with Sotret, during treatment and for a month after its completion, as well as undergo the same reliable pregnancy test. ;• she must fully understand the need for precautionary measures and confirm her understanding and desire to use reliable methods of contraception that 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 contraception due to infertility (with the exception of patients who have undergone a hysterectomy), amenorrhea, or who report that they are not sexually active.

The doctor should be sure that: • the patient suffers from a severe form of acne (nodular cystic, conglobate acne or acne with a risk of scarring); acne that does not respond to other types of therapy;• a negative result of a reliable pregnancy test was obtained before taking 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 of contraception, including the barrier method, for one month before starting treatment with Sotret, during treatment and for one month after it ends;• the patient is able to understand and;• the patient meets all of the above conditions.

PA Pregnancy Test

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

Before starting therapy: • To rule out a possible pregnancy before starting contraception, the result and date of the initial pregnancy test must be recorded by the doctor. In patients with irregular menstruation, the time of the pregnancy test depends on sexual activity, it should be performed 3 weeks after unprotected sexual intercourse.The doctor should inform the patient about the methods of contraception. * The pregnancy test is performed on the day of the Erasure appointment or 3 days before the patient’s visit to the doctor. The specialist should record the test results. The drug can only be prescribed to patients who receive effective contraception for at least 1 month prior to the start of Sotret therapy.

During therapy:The patient should visit a 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 disorders. If there are indications, a pregnancy test is performed on the day of the visit or three days before the visit to the doctor, and 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 Erasing a woman capable of childbearing can be written out only for 30 days of treatment, the continuation of therapy requires a new prescription of the drug by the doctor. It is recommended that the pregnancy test, prescription, and medication should be performed on the same day. You should only issue an Eraser at the pharmacy within 7 days of the prescription being issued.

Full information about the teratogenic risk and strict adherence to measures to prevent pregnancy should be provided to both men and women.

Contraindications

-Pregnancy, lactation-liver failure, hypervitaminosis A, severe hyperlipidemia, concomitant therapy with tetracyclines. – Hypersensitivity to the drug or its components. – Children under 12 years of age. With caution:History of depression, diabetes mellitus, obesity, lipid metabolism disorders, alcoholism.

Side effects

Most of the side effects of Sotret are dose-dependent. As a rule, when prescribing the recommended doses, the benefit-risk ratio, taking into account the severity of the disease, is acceptable for the patient. Usually, side effects are reversible after dose adjustment or discontinuation of the drug, but some may persist after discontinuation of treatment.

Symptoms associated with hypervitaminosis A: dry skin, mucous membranes, including lips (cheilitis), nasal cavity (bleeding), laryngopharynx (hoarseness of voice), eyes (conjunctivitis, reversible corneal opacity and contact lens intolerance). Skin and its appendages; rash, pruritus, facial erythema / dermatitis, sweating, pyogenic granuloma, paronychia, onychodystrophy, increased growth of granulation tissue, persistent thinning of hair, reversible hair loss, fulminant forms of acne, hirsutism, hyperpigmentation, photo-sensitization, photo-allergy, light skin injury. At the beginning of treatment, acne may worsen and persist for several weeks. Musculoskeletal system: muscle pain with or without elevated serum CPK, joint pain, hyperostosis, arthritis, calcification of ligaments and tendons, other bone changes, tendonitis.

Central nervous system and mental sphere: behavioral disorders, depression, headache, increased intracranial pressure (“psev to brain tumor”: headache, nausea, vomiting, visual impairment, edema of the optic nerve), convulsive seizures.

Sensory organs: some cases of visual acuity disorders, photophobia, dark adaptation disorders (decreased twilight vision acuity), rarely-color perception disorders (passing after discontinuation of the drug), lenticular cataracts, keratitis, blepharitis, conjunctivitis, eye irritation, optic nerve edema (as a manifestation of intracranial hypertension); hearing impairment at certain sound frequencies. Gastrointestinal tract; nausea, diarrhea, inflammatory bowel diseases (colitis, ileitis), bleeding; pancreatitis (especially with concomitant hypertriglyceridemia above 800 mg / dl). Rare cases of pancreatitis with fatal 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 normal limits and returned to the initial values during treatment, but in some situations it was necessary to reduce the dose or cancel the Erase.

 Respiratory organs: rarely-bronchospasm (more often in patients with a history of bronchial asthma).

Blood system: anemia, decreased hematocrit, leukopenia, neutropenia, increased or decreased platelet count, accelerated ESR.

Laboratory parameters: hypertriglyceridemia, hypercholesterolemia, hyperuricemia, decreased high-density lipoprotein levels, rarely hyperglycemia. While taking Sotret, cases of newly diagnosed diabetes mellitus were reported. In some patients, especially those engaged in intense physical activity, individual cases of increased serum creatinine kinase activity have been 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.

Interaction

Due to the possible increase in symptoms of hypervitaminosis A, concomitant use of Sotret and vitamin A should be avoided.

Since tetracyclines can also cause an increase in intracranial pressure, their use in combination with Sotret is contraindicated.

Isotretinoin can weaken the effectiveness of progesterone preparations, so you should not use contraceptives containing small doses of progesterone Combined use with local keratolytic or exfoliative preparations for the treatment of acne is contraindicated due to the possible increase in local irritation.

How to take, course of use and dosage

Standard dosage regimen Inside, with a meal once or twice a day.

The therapeutic efficacy of Sotret and its side effects depend on the dose and vary from patient to patient. This dictates the need for individual dose selection during treatment.

Treatment with Sotret should begin with a dose of 0.5 mg / kg per day. In most patients, the dose ranges from 0.5 to 1.0 mg / kg of body weight per day. Patients with very severe forms of the disease or with torso acne may require higher daily doses – up to 2.0 mg / kg. It is proved that the frequency of remission and prevention of relapses are optimal when using a course dose of 120-150 mg / kg (per course of treatment), so the duration of therapy in specific patients varies depending on the daily dose. Complete remission of acne can often be achieved in 16-24 weeks of treatment. In patients who do not tolerate the recommended dose very well, treatment can be continued at a lower dose, but it can be carried out longer.

In most patients, acne completely disappears after a single course of treatment. In case of an obvious relapse, a second course of treatment with Sotret is indicated in the same daily and course dose as the first one. Since the improvement can last up to 8 weeks after discontinuation of the drug, a second course should be prescribed no earlier than the end of this period.

Dosage in special cases

In patients with severe renal insufficiency, treatment should begin with a lower dose (for example,10 mg/day) and then increase to 1 mg/kg/day or the maximum tolerated dose.

Overdose

In case of overdose, signs of hypervitaminosis may appear.

Gastric lavage may be necessary in the first few hours after an overdose.

Special instructions

Sotret should only be prescribed by physicians, preferably dermatologists, who have experience with the use of systemic retinoids and are aware of the risk of teratogenicity of the drug. In order to avoid accidental exposure of the drug to the body of other people, patients who receive or shortly before (1 month) received Erasure should not take donor blood.

It is recommended to monitor liver function and liver enzymes before treatment,1 month after its start, and then every 3 months or as indicated. 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 cancel it.

Fasting serum lipids 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 when following a diet. A clinically significant increase in triglyceride levels should be monitored, since their rise above 800 mg / dl or 9 mmol / L may be accompanied by the development of acute pancreatitis, possibly with a fatal outcome.

If there is persistent hypertriglyceridemia or symptoms of pancreatitis, Erasure should be discontinued. Depression, psychotic symptoms, and very rarely suicide attempts have been reported in patients treated with Sotret. 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 monitored for depression during treatment with the drug, if necessary referring them to the appropriate specialist. However, cancellation of the Erasure may not lead to the disappearance of symptoms and may require further monitoring and treatment by a specialist. In rare cases, at the beginning of therapy, there is an exacerbation of acne, which passes within 7-10 days without dose adjustment.

Several years after using Sotret for the treatment of dyskeratosis, bone changes, including premature closure of epiphyseal growth zones, hyperostosis, calcification of ligaments and tendons, developed at a total course dose and duration of therapy that was higher than recommended for acne treatment.Therefore, when prescribing the drug to any patient, the ratio of possible benefit and risk should be carefully evaluated beforehand.

Patients receiving Erasure are recommended to use a moisturizing ointment or body cream, lip balm to reduce dryness of the skin and mucous membranes at the beginning of therapy. While taking Sotret, there may be pain in the muscles and joints, an increase in serum creatinine phosphokinase, which may be accompanied by a decrease in tolerance to intense physical activity.

Deep chemical dermoabrasion and laser treatment should be avoided in patients receiving Erasure, as well as for 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 Erasure and for 6 months after it, do not perform epilation with wax applications due to the risk of epidermal detachment, scarring and dermatitis.

Since some patients may experience a decrease in night vision acuity, which sometimes persists even after the end of therapy, patients should be informed about the possibility of this condition, advising them to exercise caution when driving at night. The state of visual acuity should be carefully monitored. Dryness of the conjunctiva of the eyes, corneal opacities, deterioration of night vision and keratitis usually disappear after discontinuation of the drug. If the eye mucosa is dry, you can use applications of a moisturizing eye ointment or an artificial tear preparation. Patients with conjunctival dryness should be monitored for possible development of keratitis. Patients presenting with vision complaints should be referred to an ophthalmologist and consider whether to cancel the Erasure. If you are intolerant to contact lenses, glasses should be used during therapy. You should limit your exposure to sunlight and UV rays. If necessary, use a sunscreen with a high protective factor value of at least 15 SPF.

Rare cases of benign intracranial hypertension (“pseudo brain tumor”) are described, including when combined with tetracyclines. In such patients, Erasure should be discontinued immediately. Inflammatory bowel disease may occur during Erasure therapy. In patients with severe hemorrhagic diarrhea, Erasure should be discontinued immediately.

Rare cases of anaphylactic reactions that occurred only after previous external use 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 mellitus, obesity, chronic alcoholism, or impaired fat metabolism) may need more frequent laboratory monitoring of glucose and lipid levels during treatment with Sotret. If diabetes is present or suspected, a more frequent blood glucose test is recommended.

Form of production

Capsules.

Storage conditions

In a place protected from light and moisture, at a temperature not exceeding 25 °C

Shelf life

2 years

Active ingredient

Isotretinoin

Conditions of release from pharmacies

By prescription

Dosage form

Capsules

Indications

Severe Acne