Composition, structure and packing
Capsules reddish-violet (light purple) color, opaque, oval, with an inscription on the surface of black ink "ROA 10", the contents of capsules - a homogeneous suspension from yellow to dark yellow.
1 capsule. Isotretinoin 10 mg
Other ingredients: soybean oil, yellow beeswax, hydrogenated soybean oil, soybean oil is partially hydrogenated.
The composition of the shell: gelatin, glycerol, Carion 83 (hydrolysed potato starch, mannitol, sorbitol), kantaksantin, titanium dioxide.
Composition of ink: shellac, iron oxide black pigment.
Capsule one half of a reddish-violet (purple) color, the other half white, opaque, oval, with an inscription on the surface of black ink "ROA 20", the contents of capsules - a homogeneous suspension from yellow to dark yellow.
1 capsule. Isotretinoin 20 mg
Other ingredients: soybean oil, yellow beeswax, hydrogenated soybean oil, soybeans oil partially hydrogenated.
The composition of the shell: gelatin, glycerol, Carion 83 (hydrolysed potato starch, mannitol, sorbitol), kantaksantin, titanium dioxide.
Composition of ink: shellac, iron oxide black pigment
Clinico-pharmacological group: Drug for the treatment of acne. Retinoids
Pharmacological action
Isotretinoin, the active ingredient Roakkutana - stereoisomer completely trans-retinoic acid (tretinoin).
The exact mechanism of action Roakkutana not yet been elucidated, but found that the improvement of the clinical picture of severe acne is associated with dose-dependent suppression of activity of sebaceous glands and histologically confirmed by a decrease in their size. Moreover, it is proved anti-inflammatory effects of isotretinoin on the skin.
Pharmacokinetics
The dynamics of drug concentration in blood can be predicted on the basis of the model of linear pharmacokinetics.
Absorption
In healthy volunteers and patients with cystic acne the maximum plasma concentrations (Cmax) after administration of 80-100 mg of isotretinoin was approximately 250 ng / ml were achieved within 1-4 hours.
Receiving isotretinoin with food increases the bioavailability of 2 times compared with the reception on an empty stomach, probably as a result of better absorption of this compound, which has high lipophilicity. Moreover, the reception of isotretinoin during the meal is accompanied, in general, a decrease in systemic bioavailability of oscillations.
Distribution
Isotretinoin is highly bound to plasma proteins (99.9%), so that a wide range of therapeutic concentrations of free (pharmacologically active) fraction of the drug is less than 0.1% of its total. The main binding protein is apparently albumin.
The volume of distribution of isotretinoin in humans is unknown, because the dosage form for intravenous use do not exist.
Isotretinoin crosses the placental barrier in quantities that cause congenital malformations of the fetus. Lipophilicity isotretinoin causes high probability that he gets into breast milk.
Metabolism
The main metabolite of isotretinoin is 4-oxo-isotretinoin, which is rapidly formed after oral administration. Furthermore, in vivo, and isotretinoin is metabolized by an alternative path to the formation of tretinoin (all-trans retinoic acid). No conclusive data on glyukuronizatsii metabolites in man is not, however, it is a high probability suggest animal studies. Studies in humans and in dogs indicate enterohepatic circulation of isotretinoin, which may play a role in individual differences in plasma concentrations of the drug.
Withdrawal
Apparently, isotretinoin is derived almost exclusively by hepatic metabolism and biliary excretion. In healthy volunteers and patients with cystic form of acne during the half-life of unmodified form of the drug after oral administration is, on average, 20 hours (7 - 39 hours).
The average half-life of 4-oksoizotretinoina in patients with cystic acne somewhat longer - an average of 25 hours (from 17 to 50 hours).
Pharmacokinetics in special clinical situations
Since isotretinoin is contraindicated in violation of the functions of the liver or kidneys, data on the pharmacokinetics of the drug in this group of patients is not available.
Statement
severe forms nodulocystica acne;
acne, which can not be done before therapy, in particular, cystic acne and konglobatnye, especially on the trunk.
Dosage regimen
Initial dose - 0.5 mg / kg per day. Often at the beginning of treatment is observed transient worsening of acne. Efficacy and side effects of isotretinoin are different for different patients, so after about 4 weeks of therapy necessary to adjust the individual maintenance dose ranging from 0.1 to 1.0 mg / kg per day. The highest daily dose (1 mg / kg) should be prescribed only for a limited time. The treatment usually lasts 16 weeks. In evaluating the results, it should be remembered that often the improvement continues even after the withdrawal of the drug. Therefore, before re-appointment of the course should be a break of at least 8 weeks. A second course of treatment is carried out in accordance with the above recommendations.
Capsules are taken with food, small doses, once per day, higher doses - one or more devices per day.
Simultaneous external treatment
The simultaneous appointment of other drugs for the treatment of acne with keratolytic or exfoliative action, as well as UV-therapy, not shown. Patients should avoid insolation. You can assign external protivougrevye preparations mild.
Side effect
Most side effects are dose dependent Roakkutana. As a rule, the appointment of the recommended dose ratio of benefit and risk, given the severity of the disease, it is acceptable to the patient.
Symptoms associated with hypervitaminosis A: The most - dryness of the skin, mucous membranes of the lips, nasal cavity (bleeding), hypopharynx (hoarseness), eyes (conjunctivitis, reversible corneal opacity and intolerance to contact lenses).
The skin and its appendages: rash, itching, dermatitis face, sweating, pyogenic granuloma, paronychia, onihodistrofii, increased proliferation of granulation tissue, persistent hair thinning, reversible alopecia, fulminant form of acne, hirsutism, hyperpigmentation, photosensitivity.
Musculoskeletal system: muscle pain, joint pain, hyperostosis, and other changes in the bones, tendinitis. One patient described the development of hyperostosis of the spine and calcification of vertebral ligaments with subsequent compression of the spinal cord during prolonged (several years) treatment with another drug group retinoids - Tigasonom (etretinate). Roakkutan not designed for prolonged use, but keep in mind the likelihood of side effects if misused (too long) the application of the drug.
Central nervous system and mental sphere: behavioral disorders, depression, headache, increased intracranial pressure, seizures.
The senses: individual cases of violations of visual acuity, alleviate hearing in a certain range of sound waves, photophobia, violation of dark adaptation (decrease in severity twilight vision), cataracts, keratitis.
Gastrointestinal tract: nausea, inflammatory bowel disease (Colitis, ileitis), bleeding, transient and reversible elevation of transaminases, some cases of hepatitis. In many cases, these changes did not go beyond the limits of normal and returned to the original parameters in the treatment process, but in some situations it was necessary to reduce the dose or cancel Roakkutan.
Respiratory: bronchospasm.
The system of blood: reducing the number of leukocytes and erythrocytes, the increase or decrease in the number of platelets, the acceleration of ESR.
Laboratory changes: hypertriglyceridemia, hypercholesterolemia, hyperuricemia, isolated cases of reduction of HDL, especially in the appointment of the drug in large doses are predisposed patients (with family history, family history of disorders of fat metabolism, diabetes, obesity or alcoholism). These changes are also dose-dependent and normalized after dose reduction or discontinuation of the drug.
Immune system: Local or systemic infections caused by gram-positive pathogens (Staphylococcus aureus).
Other: lymphadenopathy, hematuria, proteinuria, pancreatitis (especially high risk in patients with hypertriglyceridemia> 800 mg), vasculitis (Wegener's granulomatosis).
Contraindications
pregnancy (see below),
hepatic and renal failure,
hypervitaminosis A
marked hyperlipidemia and increased sensitivity to the drug.
Pregnancy and lactation
Acceptance of the drug is contraindicated.
Cautions
Roakkutan should appoint only doctors, dermatologists, preferably with experience in the application of systemic retinoids and knowledgeable about the risk of teratogenicity using Roakkutana during pregnancy.
It is recommended to monitor liver function before treatment, after 1 month after it began, and then every 3 months. It should also determine the level of lipids in the serum of fasting (before treatment, after 1 month after the beginning and the end of the 3-4-month course of treatment).
In rare cases, patients receiving Roakkutan, described depression, psychotic symptoms and suicidal attempts. Although their causal connection with the use of the drug is not installed, you must be especially cautious in patients with a history of depression and monitor all patients for depression during treatment with medication, if necessary, directing them to the appropriate specialist.
Because of the possibility of bone changes need to appoint Roakkutan only in severe forms of the disease, carefully evaluating the ratio of potential benefits and risks, and limiting the use of the drug only severe cases.
Overdose
In case of overdose can appear signs of hypervitaminosis A. In the first few hours after the overdose may need a gastric lavage.
Drug Interactions
Because of the possible increase in symptoms of hypervitaminosis A should avoid the simultaneous appointment Roakkutana and vitamin A. Since tetracyclines can also cause increased intracranial pressure, their use in combination with Roakkutanom contraindicated.
Isotretinoin can weaken the effectiveness of micropyle with progesterone, so do not use contraceptives containing low doses of progesterone
Terms and Conditions of storage
Keep out of reach of children below 25 ° C. Shelf life - 5 years.
Capsules reddish-violet (light purple) color, opaque, oval, with an inscription on the surface of black ink "ROA 10", the contents of capsules - a homogeneous suspension from yellow to dark yellow.
1 capsule. Isotretinoin 10 mg
Other ingredients: soybean oil, yellow beeswax, hydrogenated soybean oil, soybean oil is partially hydrogenated.
The composition of the shell: gelatin, glycerol, Carion 83 (hydrolysed potato starch, mannitol, sorbitol), kantaksantin, titanium dioxide.
Composition of ink: shellac, iron oxide black pigment.
Capsule one half of a reddish-violet (purple) color, the other half white, opaque, oval, with an inscription on the surface of black ink "ROA 20", the contents of capsules - a homogeneous suspension from yellow to dark yellow.
1 capsule. Isotretinoin 20 mg
Other ingredients: soybean oil, yellow beeswax, hydrogenated soybean oil, soybeans oil partially hydrogenated.
The composition of the shell: gelatin, glycerol, Carion 83 (hydrolysed potato starch, mannitol, sorbitol), kantaksantin, titanium dioxide.
Composition of ink: shellac, iron oxide black pigment
Clinico-pharmacological group: Drug for the treatment of acne. Retinoids
Pharmacological action
Isotretinoin, the active ingredient Roakkutana - stereoisomer completely trans-retinoic acid (tretinoin).
The exact mechanism of action Roakkutana not yet been elucidated, but found that the improvement of the clinical picture of severe acne is associated with dose-dependent suppression of activity of sebaceous glands and histologically confirmed by a decrease in their size. Moreover, it is proved anti-inflammatory effects of isotretinoin on the skin.
Pharmacokinetics
The dynamics of drug concentration in blood can be predicted on the basis of the model of linear pharmacokinetics.
Absorption
In healthy volunteers and patients with cystic acne the maximum plasma concentrations (Cmax) after administration of 80-100 mg of isotretinoin was approximately 250 ng / ml were achieved within 1-4 hours.
Receiving isotretinoin with food increases the bioavailability of 2 times compared with the reception on an empty stomach, probably as a result of better absorption of this compound, which has high lipophilicity. Moreover, the reception of isotretinoin during the meal is accompanied, in general, a decrease in systemic bioavailability of oscillations.
Distribution
Isotretinoin is highly bound to plasma proteins (99.9%), so that a wide range of therapeutic concentrations of free (pharmacologically active) fraction of the drug is less than 0.1% of its total. The main binding protein is apparently albumin.
The volume of distribution of isotretinoin in humans is unknown, because the dosage form for intravenous use do not exist.
Isotretinoin crosses the placental barrier in quantities that cause congenital malformations of the fetus. Lipophilicity isotretinoin causes high probability that he gets into breast milk.
Metabolism
The main metabolite of isotretinoin is 4-oxo-isotretinoin, which is rapidly formed after oral administration. Furthermore, in vivo, and isotretinoin is metabolized by an alternative path to the formation of tretinoin (all-trans retinoic acid). No conclusive data on glyukuronizatsii metabolites in man is not, however, it is a high probability suggest animal studies. Studies in humans and in dogs indicate enterohepatic circulation of isotretinoin, which may play a role in individual differences in plasma concentrations of the drug.
Withdrawal
Apparently, isotretinoin is derived almost exclusively by hepatic metabolism and biliary excretion. In healthy volunteers and patients with cystic form of acne during the half-life of unmodified form of the drug after oral administration is, on average, 20 hours (7 - 39 hours).
The average half-life of 4-oksoizotretinoina in patients with cystic acne somewhat longer - an average of 25 hours (from 17 to 50 hours).
Pharmacokinetics in special clinical situations
Since isotretinoin is contraindicated in violation of the functions of the liver or kidneys, data on the pharmacokinetics of the drug in this group of patients is not available.
Statement
severe forms nodulocystica acne;
acne, which can not be done before therapy, in particular, cystic acne and konglobatnye, especially on the trunk.
Dosage regimen
Initial dose - 0.5 mg / kg per day. Often at the beginning of treatment is observed transient worsening of acne. Efficacy and side effects of isotretinoin are different for different patients, so after about 4 weeks of therapy necessary to adjust the individual maintenance dose ranging from 0.1 to 1.0 mg / kg per day. The highest daily dose (1 mg / kg) should be prescribed only for a limited time. The treatment usually lasts 16 weeks. In evaluating the results, it should be remembered that often the improvement continues even after the withdrawal of the drug. Therefore, before re-appointment of the course should be a break of at least 8 weeks. A second course of treatment is carried out in accordance with the above recommendations.
Capsules are taken with food, small doses, once per day, higher doses - one or more devices per day.
Simultaneous external treatment
The simultaneous appointment of other drugs for the treatment of acne with keratolytic or exfoliative action, as well as UV-therapy, not shown. Patients should avoid insolation. You can assign external protivougrevye preparations mild.
Side effect
Most side effects are dose dependent Roakkutana. As a rule, the appointment of the recommended dose ratio of benefit and risk, given the severity of the disease, it is acceptable to the patient.
Symptoms associated with hypervitaminosis A: The most - dryness of the skin, mucous membranes of the lips, nasal cavity (bleeding), hypopharynx (hoarseness), eyes (conjunctivitis, reversible corneal opacity and intolerance to contact lenses).
The skin and its appendages: rash, itching, dermatitis face, sweating, pyogenic granuloma, paronychia, onihodistrofii, increased proliferation of granulation tissue, persistent hair thinning, reversible alopecia, fulminant form of acne, hirsutism, hyperpigmentation, photosensitivity.
Musculoskeletal system: muscle pain, joint pain, hyperostosis, and other changes in the bones, tendinitis. One patient described the development of hyperostosis of the spine and calcification of vertebral ligaments with subsequent compression of the spinal cord during prolonged (several years) treatment with another drug group retinoids - Tigasonom (etretinate). Roakkutan not designed for prolonged use, but keep in mind the likelihood of side effects if misused (too long) the application of the drug.
Central nervous system and mental sphere: behavioral disorders, depression, headache, increased intracranial pressure, seizures.
The senses: individual cases of violations of visual acuity, alleviate hearing in a certain range of sound waves, photophobia, violation of dark adaptation (decrease in severity twilight vision), cataracts, keratitis.
Gastrointestinal tract: nausea, inflammatory bowel disease (Colitis, ileitis), bleeding, transient and reversible elevation of transaminases, some cases of hepatitis. In many cases, these changes did not go beyond the limits of normal and returned to the original parameters in the treatment process, but in some situations it was necessary to reduce the dose or cancel Roakkutan.
Respiratory: bronchospasm.
The system of blood: reducing the number of leukocytes and erythrocytes, the increase or decrease in the number of platelets, the acceleration of ESR.
Laboratory changes: hypertriglyceridemia, hypercholesterolemia, hyperuricemia, isolated cases of reduction of HDL, especially in the appointment of the drug in large doses are predisposed patients (with family history, family history of disorders of fat metabolism, diabetes, obesity or alcoholism). These changes are also dose-dependent and normalized after dose reduction or discontinuation of the drug.
Immune system: Local or systemic infections caused by gram-positive pathogens (Staphylococcus aureus).
Other: lymphadenopathy, hematuria, proteinuria, pancreatitis (especially high risk in patients with hypertriglyceridemia> 800 mg), vasculitis (Wegener's granulomatosis).
Contraindications
pregnancy (see below),
hepatic and renal failure,
hypervitaminosis A
marked hyperlipidemia and increased sensitivity to the drug.
Pregnancy and lactation
Acceptance of the drug is contraindicated.
Cautions
Roakkutan should appoint only doctors, dermatologists, preferably with experience in the application of systemic retinoids and knowledgeable about the risk of teratogenicity using Roakkutana during pregnancy.
It is recommended to monitor liver function before treatment, after 1 month after it began, and then every 3 months. It should also determine the level of lipids in the serum of fasting (before treatment, after 1 month after the beginning and the end of the 3-4-month course of treatment).
In rare cases, patients receiving Roakkutan, described depression, psychotic symptoms and suicidal attempts. Although their causal connection with the use of the drug is not installed, you must be especially cautious in patients with a history of depression and monitor all patients for depression during treatment with medication, if necessary, directing them to the appropriate specialist.
Because of the possibility of bone changes need to appoint Roakkutan only in severe forms of the disease, carefully evaluating the ratio of potential benefits and risks, and limiting the use of the drug only severe cases.
Overdose
In case of overdose can appear signs of hypervitaminosis A. In the first few hours after the overdose may need a gastric lavage.
Drug Interactions
Because of the possible increase in symptoms of hypervitaminosis A should avoid the simultaneous appointment Roakkutana and vitamin A. Since tetracyclines can also cause increased intracranial pressure, their use in combination with Roakkutanom contraindicated.
Isotretinoin can weaken the effectiveness of micropyle with progesterone, so do not use contraceptives containing low doses of progesterone
Terms and Conditions of storage
Keep out of reach of children below 25 ° C. Shelf life - 5 years.
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