Will erase
Erase: instructions for use and reviews
- 1. Release form and composition
- 2. Pharmacological properties
- 3. Indications for use
- 4. Contraindications
- 5. Method of application and dosage
- 6. Side effects
- 7. Overdose
- 8. Special instructions
- 9. Application during pregnancy and lactation
- 10. Use in childhood
- 11. For violations of liver function
- 12. Drug interactions
- 13. Analogs
- 14. Terms and conditions of storage
- 15. Terms of dispensing from pharmacies
- 16. Reviews
- 17. Price in pharmacies
Latin name: Sotrat
ATX code: D10BA01
Active ingredient: isotretinoin (Isotretinoin)
Manufacturer: San Pharmaceutical Industries, Ltd. (Sun Pharmaceutical Industries, Ltd.) (India)
Description and photo update: 2019-05-07
Prices in pharmacies: from 1146 rubles.
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Erase is a drug used to treat acne.
Release form and composition
Dosage form - capsules: soft gelatinous, opaque, oval, with seams on the sides, with the inscription "RR" made with food black ink, at a dosage of 10 mg - light pink, at a dosage of 20 mg - burgundy; the capsules contain an orange-yellow oily suspension (in a cardboard box 1, 3 or 6 blisters of 10 capsules and instructions for use Erase).
Composition of 1 capsule:
- active substance: isotretinoin - 10 or 20 mg;
- auxiliary components (10/20 mg): refined soybean oil - 100.944 / 201.888 mg; hydrogenated vegetable oil - 32.13 / 64.26 mg; hydrogenated soybean oil - 7.65 / 15.3 mg; white beeswax - 9.18 / 18.36 mg; edetate butylhydroxyanisole - 0.016 / 0.032 mg; disodium - 0.08 / 0.16 mg;
- gelatin capsule (10/20 mg): glycerol - 29.277 mg; gelatin - 56 / 123.651 mg; dye iron oxide red - 0.0325 / 0 mg; dye red charming AC (Allura Red AC) - 0 / 0.198 mg; dye brilliant blue FCF - 0 / 0.011 mg; titanium dioxide - 0.19 / 0.495 mg; light liquid paraffin - in sufficient quantity; isopropanol - in sufficient quantity; purified water - in sufficient quantity;
- edible ink (10/20 mg): black S-1-17823 (isopropanol - 0.202 / 0.404 mg; shellac 45% in ethanol - 0.333 / 0.666 mg; propylene glycol - 0.015 / 0.03 mg; dye iron oxide black - 0, 17 / 0.355 mg; n-butanol - 0.017 / 0.034 mg; ammonium hydroxide - 0.008 / 0.016 mg) - 0.75 / 1.5 mg.
Pharmacological properties
Pharmacodynamics
The active substance is rubbed off - isotretinoin, is a stereoisomer of polytransretinoic acid (tretinoin). The mechanism of the effect of isotretinoin is not fully understood, however, it was found that the improvement of the clinical picture of severe forms of acne is affected by the suppression of the activity of the sebaceous glands and this is histologically confirmed by a decrease in their size. Isotretinoin has also been shown to have an anti-inflammatory effect on the skin.
As a result of hyperkeratosis of epithelial cells of the sebaceous gland and hair follicle, corneocytes slough off into the duct of the gland and the latter is blocked with excess sebaceous secretion and keratin. Then a comedone forms, in some cases further aggravated by the inflammatory process.
Thanks to the effect of isotretinoin, the proliferation of sebocytes is suppressed, which affects acne, the normal process of cell differentiation is restored. The main substrate for the growth of Propionibacterium acnes is sebum, a decrease in the production of which ensures the suppression of bacterial colonization of the duct.
Pharmacokinetics
The kinetics of isotretinoin and its metabolites is linear; therefore, the plasma concentration of a substance in the blood during therapy can be predicted based on data obtained after a single dose. This property of Sotret also proves that it does not affect the activity of liver enzymes involved in the metabolism of drugs.
Isotretinoin is absorbed in the gastrointestinal tract and has a direct dose-proportional relationship with the therapeutic range. The absolute bioavailability of isotretinoin was not determined, since there is no substance in a dosage form for intravenous administration in humans. However, based on extrapolated data obtained from preclinical studies, it can be assumed that systemic bioavailability is quite variable and low.
C max (maximum concentration) of 310 ng / ml (in the range of 188-473 ng / ml) and reached 2-4 hours in plasma at steady state after receiving isotretinoin fasting at a dose of 80 mg in patients with acne. Plasma concentration of isotretinoin exceeds the concentration in blood by approximately 1.7 times, which is associated with its poor penetration into erythrocytes.
When isotretinoin is taken with food, its bioavailability is doubled in comparison with fasting.
Isotretinoin binds to a significant extent with blood plasma proteins, mainly albumin (99.9%). V d (volume of distribution) of a substance in humans was not determined.
In patients with severe acne, taking 40 mg of isotretinoin 2 times a day, the equilibrium concentration of the substance in the blood is in the range of 120-200 ng / ml. There is very little information on the penetration of isotretinoin into human tissues. The concentration of the substance in the epidermis is two times lower than the serum concentration.
Three main metabolites were found in the blood plasma after oral administration of the drug, these include tretinoin (polytransretinoic acid), 4-oxo-tretinoin and 4-oxo-isotretinoin. The latter is the main metabolite, its plasma concentrations in the equilibrium state exceed the concentration of the parent substance by 2.5 times. Other metabolites (including glucuronides), which are of lesser importance, have also been identified, but the structure has not been established for all metabolites.
The biological activity of isotretinoin metabolites has been confirmed by several studies. Thus, the clinical effect of Sotret may be due to the pharmacological activity of isotretinoin and its metabolites.
Isotretinoin and tretinoin are reversibly converted into each other, so the metabolism of the latter is associated with the metabolism of the parent substance. 20 to 30% of the dose is metabolized by isomerization. In the pharmacokinetic processes of isotretinoin in humans, an important role may be played by hepatic-intestinal recirculation. When carrying out studies of biotransformation processes, it was found that several cytochrome P 450 enzymes are involved in the conversion of the initial substance into 4-oxo-isotretinoin and tretinoin. Most likely, none of the isoforms plays a dominant role. Isotretinoin and its metabolites have no significant effect on the activity of cytochrome P 450 enzymes.
After oral administration of isotretinoin, which has been labeled with radioactive isotopes, approximately equal amounts are found in feces and urine. The T 1/2 (half-life) of the terminal phase for the unchanged parent substance in patients with acne averages 19 hours. The value of this indicator for 4-oxo-isotretinoin is possibly greater, and its average duration is 29 hours.
Isotretinoin is a natural (physiological) retinoid. Their endogenous concentrations are reached approximately 2 weeks after the end of the application.
Isotretinoin is contraindicated in patients with impaired hepatic function, therefore, information on the pharmacokinetic parameters of Erase in this group of patients is limited. Renal failure does not significantly reduce the plasma clearance of isotretinoin or 4-oxo-isotretinoin in the blood.
Indications for use
- acne in severe forms: nodular-cystic, acne with a risk of scarring or conglobata (multiple, piled up) acne;
- acne that does not respond to other treatments.
Contraindications
Absolute:
- liver failure;
- severe hyperlipidemia;
- hypervitaminosis A;
- combination therapy with tetracyclines;
- the presence of allergies to soy and peanuts (Erase contains hydrogenated soybean oil, hydrogenated vegetable oil, refined soybean oil);
- fertile age in women who do not comply with contraception during the period of taking Erase;
- pregnancy and lactation;
- age up to 12 years;
- individual intolerance to the components of the drug.
Relative (Erase capsules are used under medical supervision):
- violation of lipid metabolism;
- aggravated history of depressive disorders;
- obesity;
- diabetes;
- alcoholism.
Erase, instructions for use: method and dosage
Erase capsules are taken orally, simultaneously with food, 2 times a day.
The therapeutic effect and side reactions of Erase are determined by the dose and have variability in different categories of patients, so the dosage regimen should be determined individually.
At the beginning of treatment, it is recommended to take Erase in a daily dose of 0.5 mg / kg. In most cases, the dose is in the range of 0.5-1 mg / kg per day. With acne of the trunk or very severe forms of the disease, it is possible to prescribe higher daily doses - up to 2 mg / kg. No significant additional benefit is expected at a cumulative dose above 120–150 mg / kg.
The duration of the course is determined by the daily dose. Most often, to achieve remission, it is enough to take Erase for a duration of 16 to 24 weeks. In patients who are very difficult to tolerate the recommended dose, therapy may be longer, but the single dose should be reduced.
In most cases, acne disappears completely after a single course of treatment. With a pronounced relapse, the drug is prescribed again without changing the dosage regimen. A second course should be prescribed no earlier than 8 weeks after the end of the Erase, since during this period there may be an improvement.
In severe renal failure, the drug is started with a lower dose (for example, with a daily dose of 10 mg), then the dose is gradually increased to 1 mg / kg per day or the maximum tolerated.
For patients who are intolerant to the recommended dose, Erase can be prescribed at a lower dose for a longer course, taking into account the presence of an increased risk of relapse.
Side effects
Most of the disorders that occur during the use of Erase depend on the dose. Most often, the ratio of benefit and risk when prescribing recommended doses, given the severity of the disease, is acceptable for the patient.
Usually, adverse reactions after adjusting the dosage regimen or interrupting the course of therapy are reversible, but some of them may persist after the cancellation of Erase. In most cases, during the treatment period, the development of the following undesirable phenomena was observed: dryness of the skin and mucous membranes, for example, lips, nose and eyes (cheilitis, epistaxis and conjunctivitis).
Possible adverse reactions (> 10% - very common;> 1% and 0.1% and 0.01% and <0.1% - rarely; <0.01% - extremely rare):
- nervous system: often - headache; extremely rarely - dizziness, benign intracranial hypertension (pseudotumor of the brain, manifested in the form of headache, nausea, vomiting, visual disturbances, edema of the optic nerve), drowsiness, convulsions; with an unspecified frequency - excessive fatigue;
- central nervous system: rarely - aggressive behavior, frequent mood swings, excitability, exacerbation of depression, depression; extremely rarely - suicidal thoughts, psychotic disorder, inappropriate behavior, suicidal attempts, suicide;
- urinary system: often - proteinuria, hematuria; extremely rare - glomerulonephritis;
- respiratory system: often - nasopharyngitis, dryness of the mucous membrane of the larynx and nose, epistaxis; extremely rarely - hoarseness, bronchospasm (in most cases, against the background of a burdened history of bronchial asthma);
- digestive system: very often - a reversible and transient increase in the activity of hepatic transaminases; extremely rare - diarrhea, nausea, inflammatory bowel disease (including colitis, ileitis), pancreatitis (especially with concomitant hypertriglyceridemia> 800 mg / dL), hepatitis, dry throat, gastrointestinal bleeding; with an unspecified frequency - bleeding from the gums, dryness of the oral mucosa, inflammation of the gums; there is information about rare cases of pancreatitis with a fatal outcome;
- musculoskeletal system: very often - arthralgia, myalgia (with / without an increase in the serum activity of creatine phosphokinase in the blood); extremely rare - calcification of tendons and ligaments and other bone changes, hyperostosis, arthritis, tendinitis; with an unknown frequency - rhabdomyolysis, sometimes fatal;
- skin: very often - dermatitis, dryness of mucous membranes and skin, onychodystrophy, rash, itching, cheilitis, facial erythema, increased growth of granulation tissue, easy skin trauma; rarely - alopecia; extremely rare - photosensitivity, vasculitis (granulomatosis with polyangiitis, allergic vasculitis), fulminant forms of acne, nail dystrophy, hirsutism, hyperpigmentation, photodermatosis, pyogenic granuloma, increased sweating, persistent hair thinning, paronychia, reversible hair loss; at the beginning of therapy, there may be an exacerbation of acne lasting several weeks; with an unknown frequency - Stevens-Johnson syndrome, peeling of the skin of the soles and palms, toxic epidermal necrolysis;
- sense organs: very often - eye irritation, blepharitis, dry eye syndrome, conjunctivitis; extremely rarely - decreased night vision, isolated cases of visual acuity, contact lens intolerance, keratitis, cataracts, corneal opacity, color blindness and other color perception abnormalities, hearing impairment, visual impairment, papilledema (occurs as a manifestation of benign intracranial hypertension);
- hematopoietic organs: very often - thrombocytopenia, anemia, thrombocytosis, increased erythrocyte sedimentation rate; often neutropenia; extremely rare - lymphadenopathy; with an unknown frequency - leukopenia, decreased hematocrit;
- metabolism: extremely rare - hyperuricemia, diabetes mellitus;
- laboratory indicators: very often - a decrease in high-density lipoprotein indicators, hypertriglyceridemia; often - hyperglycemia, hypercholesterolemia; extremely rarely - an increase in the activity of creatine phosphokinase in the blood serum;
- allergic reactions: rarely - anaphylactic reactions, allergies, systemic hypersensitivity reactions, hypersensitivity;
- others: extremely rarely - systemic / local infections, the development of which is caused by gram-positive pathogens (Staphylococcus aureus).
Overdose
Isotretinoin is a derivative of vitamin A. The likelihood of acute toxicity of vitamin A is very low, however, with an accidental overdose, signs of hypervitaminosis may appear in the form of hoarseness, conjunctivitis, contact lens intolerance, dry mucous membranes and skin, cheilitis, reversible corneal opacity. Acute vitamin A toxicity manifests itself as severe headache, vomiting or nausea, drowsiness, itching, and irritability.
Symptoms and signs of an erase overdose should be similar. Most likely they are reversible and transient and do not require special treatment.
special instructions
Erase should be prescribed only by doctors, preferably dermatologists, who have the necessary experience in therapy with systemic retinoids and are aware of the existing risk of teratogenicity of the drug.
To avoid accidental exposure to Rubbed on the body of other people, patients during the treatment period and for a month after the end of the drug intake should not donate blood.
Monitoring of liver function and liver enzymes is recommended before starting therapy and 30 days after. Subsequently, unless the doctor prescribes otherwise, monitoring is carried out once every 3 months. There is evidence of an unstable and reversible increase in hepatic transaminases, most often within the normal range. In cases where the activity of hepatic transaminases exceeds the norm, the dose of the drug should be reduced, or it will be canceled.
Serum lipid control is checked before starting treatment (on an empty stomach), 30 days after and thereafter - once every 3 months (unless otherwise instructed by the doctor).
As a rule, the elevated serum lipid level decreases to normal values with dose reduction, abolition of Erase and adherence to a diet. Isotretinoin leads to an increase in the level of triglycerides in the blood plasma. In cases where hypertriglyceridemia cannot be controlled at an acceptable level, or if symptoms of pancreatitis are present, the drug is discontinued. An increase in triglyceride levels above 800 mg / dL (9.01 mmol / L) can sometimes be associated with acute pancreatitis, which can be fatal.
The patients who took Erase had the following mental disorders: depression, aggressiveness, excitability, depression, psychotic symptoms, mood swings, in very rare cases - suicidal thoughts, suicidal attempts and suicide. Patients with a history of depression need special attention. However, all patients should be monitored for signs of depression and receive appropriate treatment when needed.
It should be borne in mind that to relieve symptoms, only withdrawal is not enough; in the future, the patient may need a psychological or psychiatric assessment of the condition.
Sometimes at the initial stage of treatment, an acute attack of acne is observed, but with continued therapy for 7-10 days, it fades away, as a rule, without changing the treatment regimen.
Avoid exposure to ultraviolet radiation and intense sunlight. If necessary, sunscreens with a high protection factor (at least SPF 15) should be used.
For 5-6 months after the end of the reception of Erase, it is contraindicated to carry out intensive chemical dermabrasion and laser treatment of the skin. This is associated with the risk of hypertrophic scar formation in atypical areas, in more rare cases - with the development of post-inflammatory hypo- or hyperpigmentation in the treated skin areas. Due to the likelihood of epidermal detachment, patients who have been using Erase are contraindicated to carry out the epilation procedure using wax.
Combination therapy with topical keratolytic or exfoliating agents should be avoided, as this can lead to increased local irritation. From the beginning of taking Erase, patients are recommended to use moisturizing ointments or creams and lip balm, which will reduce the likelihood of dry lips and skin at the beginning of therapy.
There are reports of the development of serious skin reactions against the background of the use of Erase, including polymorphic erythema, Stevens-Johnson syndrome and toxic epidermal necrolysis. These disorders are difficult to distinguish from other possible skin reactions, therefore patients should be instructed about the potential risk of their occurrence. If these symptoms appear, therapy is canceled.
Rare reports of anaphylactic reactions have indicated that they sometimes appear after topical retinoid therapy. Also rarely reported on the development of allergic reactions from the skin. There are reports of severe cases of allergic vasculitis of the extremities, often with accessory skin patches and purpuric involvement. In such cases, it is necessary to cancel the therapy with Erase and establish careful monitoring of the patient's condition.
Several years after treatment with isotretinoin for dyskeratosis, which lasted longer and at higher doses than in the case of acne therapy, the development of bone changes, including hyperostosis, premature closure of the epiphyseal growth zones, calcification of tendons and ligaments, was noted. Against the background of taking Erase, the following are possible: arthralgia, myalgia, an increase in serum creatine phosphokinase (can occur with intense physical activity).
Patients should take into account the likelihood of reduced night vision. This violation can sometimes persist even after the end of the reception Erase. Careful monitoring of visual acuity is necessary.
Usually, dryness of the conjunctiva of the eyes, corneal opacity, keratitis and deterioration in night vision after the abolition of Erase disappear. If the mucous membrane of the eyes is dry, it is possible to use applications of a moisturizing eye ointment or artificial tear preparations. The condition of patients with dry conjunctiva should be monitored for possible keratitis. If patients complain of vision, they should be referred for a consultation with an ophthalmologist and to assess the feasibility of further administration of Erase. During therapy, if you are intolerant to contact lenses, you need to use glasses. Exposure to sunlight and ultraviolet rays must be limited.
There are rare cases of benign intracranial hypertension (pseudotumor of the brain), including against the background of the combined use of Erase with tetracyclines. The main signs and symptoms of the disease: edema of the optic nerve head, headache, indigestion (in the form of vomiting and nausea), visual impairment. In such cases, immediate cancellation is required.
Patients with impaired renal function and renal insufficiency should start treatment with low doses, then gradually increase the dose to the maximum tolerated.
In the presence of a burdened history of disorders of the digestive system, it will erase can lead to inflammatory bowel diseases. With severe hemorrhagic diarrhea, the drug is immediately canceled.
Patients belonging to a high-risk group (with obesity, diabetes mellitus, lipid metabolism disorders, alcoholism) during therapy may need more frequent laboratory monitoring of blood lipids and glucose levels. There are reports of elevated blood sugar and new cases of diabetes during isotretinoin therapy.
Influence on the ability to drive vehicles and complex mechanisms
A decrease in the acuity of twilight vision during therapy with Erase may be sudden, which must be taken into account when driving. It is also necessary to take into account the likelihood of the occurrence of such adverse reactions as drowsiness, visual disturbances and dizziness. In the event of the occurrence of these violations, one should refrain from driving.
Application during pregnancy and lactation
Erase during pregnancy / lactation is not prescribed.
Pregnancy is an absolute contraindication for Erase therapy. Isotretinoin has a strong teratogenic effect. In case of pregnancy during the period of therapy (when taking any dose of the drug) or within one month after completion of treatment, there is a high risk of having a child with severe malformations.
Isotretinoin is highly lipophilic, so there is a significant chance that the substance passes into breast milk. To avoid the development of possible adverse reactions, nursing women should not take Erase.
It will be contraindicated to use in women of childbearing age, unless the patient's condition meets all of the criteria listed below:
- Presence of severe acne that is resistant to conventional treatments.
- The ability to undergo a thorough monthly medical supervision and follow medical instructions.
- Understanding of the existing risk of pregnancy and the need for urgent consultation if there is a risk of its occurrence.
- Understanding the likely ineffectiveness of contraceptives.
A woman should continuously use effective methods of contraception for one month before starting to take Erase, their use should be continued during the entire period of therapy and for another month after the end of treatment. It is recommended to use two different methods of contraception at the same time, including barrier.
Therapy should only begin on days 2–3 of the next normal menstrual cycle. The patient must be aware and accept that a pregnancy test during treatment should be carried out every month and 5 weeks after the end of therapy.
The physician should make sure that the patient understands and understands the risks involved and the need to take precautions.
If the use of Erase is prescribed for a relapse of the disease, a woman should constantly use the same effective methods of contraception for one month before starting the drug, during treatment and for a month after its completion, and also undergo a reliable pregnancy test.
All women are obliged to follow all the recommendations on effective contraception. This applies to patients who usually do not use contraceptive methods due to amenorrhea, infertility (except for women who have undergone a hysterectomy), or who report that they are not sexually active.
Based on current practice, a pregnancy test with a minimum sensitivity of 25 mIU / ml should be performed in the first three days of the menstrual cycle.
The first test should be done before using contraception. The results must be recorded by a doctor. This will eliminate pregnancy before contraception begins. The timing of the test in women with irregular periods depends on sexual activity and should be done three weeks after unprotected intercourse.
The next test is scheduled on the day you start taking Erase or 3 days before the visit to the doctor. Test results must be recorded by a specialist. The drug can only be used by women who receive effective contraception for at least one month before starting treatment.
During the period of taking Sotret, you need to visit a doctor every 28 days. The need for a monthly pregnancy test is determined according to local practice and should take into account the woman's sexual activity and previous menstrual irregularities. If there is evidence, a pregnancy test is carried out on the day of the visit or three days before the visit to the doctor, its results must be registered.
After the end of therapy, after 5 weeks, another test should be performed. Fertile women can only be prescribed a prescription for 30 days of Erase; a new prescription is required to continue therapy. It is recommended to have a pregnancy test, prescription and medication on the same day.
At the pharmacy, the drug must be dispensed only within 7 days from the date of the prescription.
Both women and men should be informed about the teratogenic risk of taking Erase and the need for strict adherence to measures to prevent pregnancy.
According to existing data, the exposure of isotretinoin, which came from the semen and seminal fluid of men who take erase, in women is insufficient for the appearance of teratogenic effects of the substance. Male patients should be warned against sharing their medicine with anyone, especially women.
In cases where, despite the observance of all precautions, pregnancy did occur during treatment and within 30 days after its termination, the existing high risk of very severe fetal malformations (mainly from the heart, central nervous system and large blood vessels) should be taken into account. vessels) and an increase in the likelihood of spontaneous miscarriage.
When pregnancy occurs, Sotret's reception is canceled. The feasibility of preserving it should be discussed with a doctor who specializes in teratology. There is documentary evidence of severe congenital malformations of the fetus associated with the use of isotretinoin, including the following diseases / conditions:
- cerebellar malformations;
- hydrocephalus;
- cardiovascular anomalies, including septal defects, transposition of great vessels, tetrad of Fallot;
- pathology of the parathyroid glands;
- malformations of the thymus gland, face, including the cleft palate;
- microphthalmia;
- microcephaly;
- anomaly of the external ear, including the absence of the external ear, microtia, absence / narrowing of the external auditory canal.
Pediatric use
It will not be prescribed for patients under 12 years of age.
For violations of liver function
Application is contraindicated in liver failure.
Drug interactions
- vitamin A and other retinoids (including acitretin, tretinoin, retinol, tazarotene, adapalene): with combined use, the symptoms of hypervitaminosis A may increase, so this combination should be avoided;
- tetracyclines: simultaneous use is contraindicated, since it can lead to an increase in intracranial pressure;
- keratolytic or exfoliative topical preparations for the treatment of acne: the combination is contraindicated due to the likelihood of increased local irritation;
- progesterone drugs: when used during treatment with Erase, their effectiveness may be weakened, in this regard, contraceptives containing small doses of progesterone should not be used.
Analogs
The counterparts of Sotret are Verocutane, Acnecutane, Roaccutane.
Terms and conditions of storage
Store in a place protected from light at temperatures up to 25 ° C. Keep out of the reach of children.
Shelf life is 2 years.
Terms of dispensing from pharmacies
Dispensed by prescription.
Reviews about Erase
Reviews about Erase regarding its effectiveness are mostly positive. Many people note that the drug has a long-term therapeutic effect, as a result of which acne disappears and the oily sheen of the skin disappears. At the same time, almost everyone points to the development of side effects, most often in the form of dry lips, less often - nausea and depression. Also, the disadvantages include the high cost and lack of funds in many pharmacies.
Price for wipes in pharmacies
Approximate price for Erase, 10 mg capsules, 30 pcs. in the package is 1382 rubles.
Will erase: prices in online pharmacies
Drug name Price Pharmacy |
Will erase 10 mg capsules 30 pcs. 1146 RUB Buy |
Will erase 20 mg capsules 30 pcs. 1757 RUB Buy |
Maria Kulkes Medical journalist About the author
Education: First Moscow State Medical University named after I. M. Sechenov, specialty "General Medicine".
Information about the drug is generalized, provided for informational purposes only and does not replace the official instructions. Self-medication is hazardous to health!