2010/09/17

Acnecutan

Composition, structure and packing

Hard gelatin capsules, № 3, brown; content capsules - waxy paste is yellow-orange color.

1 capsule. - 8 mg isotretinoin

Excipients: Gelyutsir 50/13 (a mixture of esters of stearic acid, polyethylene oxide and glycerine), refined soybean oil, Span 80 (sorbitan oleate - mixed esters of oleic acid and sorbitol).

The composition of the body and lid of the capsule: gelatin, dye, iron oxide red (E172), titanium dioxide (E171).

Hard gelatin capsules, № 1, block white cap - green; content capsules - waxy paste is yellow-orange color.

1 capsule. - Isotretinoin 16 mg

Excipients: Gelyutsir 50/13 (a mixture of esters of stearic acid, polyethylene oxide and glycerine), refined soybean oil, Span 80 (sorbitan oleate - mixed esters of oleic acid and sorbitol).

The composition of the capsule shell: gelatin, titanium dioxide (E171).

Composition caps capsule: gelatin, titanium dioxide (E171), color iron oxide yellow (E172), indigo (E132).

Clinico-pharmacological group

The drug for the treatment of acne. Retinoids

Pharmacological action

The drug for the treatment of acne. Isotretinoin - stereoisomer of all-trans retinoic acid (tretinoin).

The exact mechanism of action of isotretinoin has not yet been identified, but found that the improvement of the clinical picture of severe acne is associated with suppression of sebaceous glands and histologically confirmed by a decrease in their size.

Sebum - the main substrate for the growth of Propionibacterium acnes, thus reducing the production of sebum suppresses bacterial colonization of the duct. Aknekutan sebotsitov inhibits proliferation and acts on acne, restoring the normal process of cell differentiation, stimulates regeneration processes. Moreover, it is proved anti-inflammatory effects of isotretinoin on the skin.

Pharmacokinetics

Absorption

After oral absorption, variable, bioavailability and low variability (attributable fraction dissolved in the drug isotretinoin, and also may increase when taking the drug with food). In patients with acne Smah in an equilibrium state after taking isotretinoin at a dose of 80 mg on an empty stomach was 310 ng / ml (range 188-473 ng / ml) was achieved in 2-4 h. The concentration of isotretinoin in plasma is 1.7 times higher than in blood , due to poor penetration of isotretinoin into red blood cells.

Distribution

Binding to plasma proteins (mainly albumin) - 99.9%.

Css isotretinoin in patients with severe acne who received the drug at 40 mg 2, ranged from 120 ng / ml to 200 ng / ml. Concentrations of 4-oxo-isotretinoin (main metabolite) in these patients is 2.5 times higher than they are. The concentration of isotretinoin in the epidermis in 2 times lower than in serum.

Metabolism

Metabolized to form 3 major biologically active metabolite - 4-oxo-isotretinoin (main metabolite), tretinoin (all-trans-retinoic acid) and 4-oxo-retinoina, as well as less important metabolites, which also include glucuronide. Because in vivo isotretinoin and tretinoin reversibly transformed into each other, tretinoin metabolism is linked to the metabolism of isotretinoin. 20-30% of the dose of isotretinoin is metabolized by isomerization. In the pharmacokinetics of isotretinoin in humans may play a significant role enterohepatic circulation.

Studies in vitro have shown that in the transformation of isotretinoin to 4-oxo-isotretinoin and tretinoin involving several enzymes CYP. However, none of the isoforms, apparently does not play a dominant role. Isotretinoin and its metabolites have no significant effect on the enzyme activity of CYP.

Withdrawal

T1 / 2 of the terminal phase for isotretinoin on average - 19 hours T1 / 2 of the terminal phase for the 4-oxo-isotretinoin on average - 29 hours

Isotretinoin is derived from the kidneys and bile in approximately equal amounts. Refers to the natural (physiological) retinoids. The endogenous concentration of retinoids recovered in about 2 weeks after ingestion.

Pharmacokinetics in special clinical situations

Because the data on the pharmacokinetics of the drug in patients with hepatic impairment is limited, isotretinoin is contraindicated in this group of patients.

Renal insufficiency mild to moderate severity does not affect the pharmacokinetics of isotretinoin.

Indications for use of the drug
severe forms of acne (nodulocystica, konglobatnye, with the risk of acne scarring);
Acne is not amenable to other forms of therapy.

Dosage regimen

Inside, preferably during meals, 1-2

Therapeutic efficacy Aknekutana and its side effects are dose dependent and vary among different patients. This requires an individual dosage during treatment.

The initial dose Aknekutana - 400 mg / kg, in some cases up to 800 mg / kg / In severe forms of disease or body acne may require a dose up to 2 mg / kg /

Optimal exchange rate cumulative dose - 100-120 mg / kg. Complete remission is achieved, usually for 16-24 weeks. When poor tolerability of the recommended dose therapy can be continued in a smaller dose, but longer. The majority of patients of acne completely disappear after a single course of treatment.

When relapse is possible to carry out secondary treatment in the same daily and cumulative dose. A second course appointed not earlier than 8 weeks after the first, because improvement can be deferred nature.

In chronic renal failure, severe initial dose should be reduced to 8 mg.

Side effect

Most side effects are dose dependent. Usually side effects are reversible after dose adjustment or discontinuation of the drug, but some may persist after cessation of treatment.

Symptoms associated with hypervitaminosis A: dryness of the skin, mucous membranes, including lips (cheilitis), nasal cavity (bleeding), the larynx and pharynx (hoarseness), eyes (conjunctivitis, reversible corneal opacity and intolerance of contact lenses).

Dermatological reactions: skin peeling of palms and soles, rash, itching, erythema face / dermatitis, sweating, pyogenic granuloma, paronychia, onihodistrofii, increased proliferation of granulation tissue, persistent hair thinning, reversible alopecia, fulminant form of acne, hirsutism, hyperpigmentation, photosensitivity, Light travmiruemost skin. At the beginning of treatment may be exacerbation of acne that persists for several weeks.
On the part of the musculoskeletal system: pain in muscles with increased levels of CK in serum or without it, joint pain, hyperostosis, arthritis, calcification of ligaments and tendons, tendinitis.
From the side of the central nervous system: excessive fatigue, headache, increased intracranial pressure (pseudotumor of the brain: headache, nausea, vomiting, blurred vision, swelling of the optic nerve), seizures, rarely - depression, psychosis, suicidal thoughts.
From the senses: xerophthalmia, individual cases of violations of visual acuity, photophobia, violation of dark adaptation (mitigation twilight vision), rarely - breach of color vision (passing drug discontinuation), lenticular cataract, keratitis, blepharitis, conjunctivitis, eye irritation, optic neuritis nerve, edema of the optic nerve (as a manifestation of intracranial hypertension), hearing loss at certain frequencies of sound, difficulty wearing contact lenses.
On the part of the digestive system: dryness of the oral mucosa, bleeding gums, gingivitis, nausea, diarrhea, inflammatory bowel disease (colitis, ileitis), bleeding, pancreatitis (especially with concomitant hypertriglyceridemia above 800 mg / dL). Described rare cases of pancreatitis with a fatal outcome. It was transient and reversible elevation of hepatic 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 Aknekutan.
On the part of the respiratory system: rarely - bronchospasm (more frequently in patients with bronchial asthma in history).
On the part of the hemopoietic system: anemia, lower hematocrit, leukopenia, neutropenia, increase or decrease in the number of platelets, the acceleration of ESR.

Laboratory indicators: hypertriglyceridemia, hypercholesterolemia, hyperuricaemia, lower HDL, seldom - hyperglycemia. During the reception Aknekutana were reported for the first time identified diabetes. In some patients, especially those in intensive physical activity, described individual cases of increased activity of CK in serum.

Infections: 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.

Teratogenic and embryotoxic effects: congenital malformations - hydro and microcephaly, hypoplasia of the cranial nerves, microphthalmia, congenital malformations of the cardiovascular system, parathyroid glands, disruption of formation of the skeleton (hypoplasia of finger phalanges, skull, cervical vertebrae, femur, ankle, bone forearm, facial skull, cleft palate), low-lying, ears, hypoplasia of ears, hypoplasia or absence of external auditory canal, hernia of the brain and spinal cord, bone fusion, fusion of fingers and toes, developmental disorders thymus, fetal death in the perinatal period, premature birth, miscarriage, premature closure of epiphyseal growth zones, in experiments on animals - pheochromocytoma.

Contraindications to the use of the drug
pregnancy is established and planned (possibly teratogenic and embryotoxic action);
Lactation (breastfeeding);
hepatic impairment;
hypervitaminosis A;
marked hyperlipidemia;
concomitant therapy tetracyclines;
Hypersensitivity to the drug or its components.

Aknekutan not indicated for the treatment of acne during puberty and not recommended for children under 12 years.

Precautions should be prescribed medication for diabetes, a history of depression, obesity, lipid disorders, alcoholism.

Pregnancy and lactation

Pregnancy - an absolute contraindication for therapy Aknekutanom.

If pregnancy occurs despite the warnings, during treatment or within months after therapy, there is a very great danger of having a child with severe developmental disabilities.

Isotretinoin - a drug with a strong teratogenic effect. If pregnancy occurs in a period when a woman takes oral isotretinoin (in any dose, and even a short time), there is a very great danger of having a child with developmental disabilities.

Aknekutan contraindicated in women of childbearing age, unless the condition of women does not satisfy all of the following criteria:
severe form of acne resistant to conventional treatments;
patient must understand and comply with the doctor's;
the patient should be informed by a doctor about the dangers of becoming pregnant during treatment Aknekutanom, within one month after it and urgent consultations with suspected pregnancy;
the patient should be advised of the possible failure of contraception;
the patient should confirm that he understood precautions;
patient should understand the need for continuous and use effective methods of contraception for one month before treatment Aknekutanom, during treatment and within a month after graduation, it is desirable to use simultaneously two different methods of contraception, including barrier;
the patient must be received a negative result reliable pregnancy test within 11 days prior to the medication; pregnancy test is highly recommended monthly during treatment and after 5 weeks after therapy;
the patient should begin treatment Aknekutanom only 2-3 days following a normal menstrual cycle;
patient should understand the need for mandatory medical visits each month;
in the treatment of the recurrence of the disease the patient should always use the same effective methods of contraception for one month prior to treatment Aknekutanom, during treatment and within a month after its completion, as well as go through the same reliable pregnancy test;
the patient should fully understand the need for precautionary measures and to confirm their understanding and desire to use reliable methods of contraception, which she explained to the doctor.

The use of contraceptives by the above instructions during isotretinoin treatment should be recommended even to those women who do not normally use contraceptive methods because of infertility (except for patients who had undergone hysterectomy), amenorrhea, or who reported that not sexually active.

The physician must be sure that:
the patient is suffering from severe acne (nodulocystica, konglobatnye acne or acne scarring risk); acne is not amenable to other forms of therapy;
negative results of reliable pregnancy test before taking the drug during therapy and after 5 weeks after therapy; dates and results of pregnancy test must be documented;
the patient uses at least one, preferably two effective methods of contraception, including barrier methods, within one month prior to treatment Aknekutanom, during treatment and within a month after its completion;
the patient is able to understand and comply with all the above requirements for prevention of pregnancy;
patient meets all the above conditions.

Pregnancy test

In line with existing practice, a pregnancy test with a minimum sensitivity of 25 mME / ml should be in the first 3 days of the menstrual cycle:

Prior therapy

To exclude the possibility of pregnancy before the contraceptive use results and the date of the initial pregnancy test must be registered with a doctor. In patients with irregular menses during pregnancy tests depends on sexual activity, it should be performed 3 weeks after unprotected intercourse. The physician should inform the patient about methods of contraception.

A pregnancy test carried out on the day of the appointment Aknekutana or 3 days before the visit of the patient to the doctor. Professionals should record the test results. The drug can be assigned only to patients who receive effective contraception for at least 1 month before therapy Aknekutanom.

During therapy

The patient should visit a doctor every 28 days. The need monthly pregnancy testing is determined in accordance with local practice and subject to sexual activity prior to menstrual disorders. Where indicated, a pregnancy test conducted on the day of the visit or 3 days before the visit to the doctor, test results should be recorded.

End therapy

After 5 weeks after the treatment is carried out a test to exclude pregnancy.

Recipe for Aknekutan woman capable of procreation, may be issued only on 30 days of treatment, continuation of therapy requires a new prescription of a physician. Recommended pregnancy tests, prescription and receive drugs to carry out in one day.

Delivery of Aknekutana the pharmacy should be undertaken only within 7 days from the date of prescription.

Male patients

Existing evidence suggests that women exhibit drug originating in semen and semen of men taking Aknekutan not sufficient for the appearance of teratogenic effects Aknekutana. Men should exclude the possibility of taking the drug by other persons, especially women.

If, notwithstanding the precautionary measures during treatment Aknekutanom or within one month after graduation, pregnancy still occurred, there is a high risk of very severe malformations of the fetus. In the event of pregnancy therapy Aknekutanom stop. It should discuss the advisability of maintaining it with a doctor specializing in teratology.

Lactation

Since isotretinoin has a high lipophilicity, it is likely that he gets into breast milk. Because of possible side effects Aknekutan not appoint nursing mothers.

Application for violations of liver function

It is recommended to monitor liver function and liver enzymes at baseline, 1 month after it began, and then every 3 months or when indicated. Noted a transient and reversible increase in hepatic transaminases, in most cases within the normal range. If the level of hepatic transaminases above the norm, it is necessary to reduce the dose or cancel it.

Application for violations of renal function

In chronic renal failure, severe initial dose should be reduced to 8 mg /

Cautions

It is recommended to monitor liver function and liver enzymes at baseline, 1 month after it began, and then every 3 months or when indicated. Noted a transient and reversible increase in hepatic transaminases, in most cases within the normal range. If the level of hepatic transaminases above the norm, it is necessary to reduce the dose or cancel it.

It should also determine the level of lipids in the serum of fasting before treatment, after 1 month after the start, and then every 3 months or when indicated. Typically, the concentration of lipid normalized after dose reduction or discontinuation of the drug, as well as a diet.

Should be monitored clinically significant increase in the level of triglycerides, as they rise above 800 mg / dL or 9 mmol / l may be associated with the development of acute pancreatitis, possibly with fatal consequences. With persistent hypertriglyceridemia or symptoms of pancreatitis Aknekutan should be abolished.

In rare cases, patients receiving Aknekutan, described depression, psychotic symptoms and very rarely - 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. However, the abolition Aknekutana may not lead to the disappearance of symptoms and may require further observation and treatment by a specialist.

In rare cases, early treatment of acne growing worse, which passes within 7-10 days without a correction dose.

In the appointment of the drug to any patient must first carefully assess the ratio of potential benefits and risks.

Patients receiving Aknekutan recommended to use moisturizing cream or body lotion, lip balm to reduce dry skin and mucous membranes in the beginning of therapy.

During the course of Aknekutana possible pains in muscles and joints, increase of serum CK, which may be accompanied by a decrease in tolerance of intense physical exertion.

Should be avoided deep chemical dermoabrazii and laser treatment in patients receiving Aknekutan, as well as within 5-6 months after treatment because of the possibility of enhanced scarring in atypical areas and the emergence of hyper-and hypopigmentation. In the course of treatment Aknekutanom and within 6 months after it could not hold epilation with applications of wax because of the risk of detachment of the epidermis, the development of scars and dermatitis.

Because some patients can reduce the severity of night vision, which sometimes persists after therapy, patients should be informed about this condition, encouraging them to exercise caution when driving at night. Condition of visual acuity should be carefully monitored. The dryness of the conjunctiva of the eye, corneal opacity, the deterioration of night vision and keratitis usually resolve after discontinuation of the drug. When dry eye mucosa can use applications moisturizing eye ointment or preparation of artificial tears. Need to observe patients with dryness of the conjunctiva for possible development of keratitis. Patients complained of vision, should be sent to an ophthalmologist and to consider whether the abolition of Aknekutana. If intolerance of contact lenses during therapy should be used glasses.

It should limit the effects of solar insolation and UV therapy. If necessary, use a sunscreen with a high protective factor of at least 15 SPF.

Described rare cases of benign intracranial hypertension (pseudotumor of the brain), including in combined therapy with tetracyclines. In these patients should be lifted immediately Aknekutan.

In therapy Aknekutanom may cause inflammatory bowel disease. In patients with severe hemorrhagic diarrhea should immediately cancel Aknekutan.

Described rare cases of anaphylactic reactions, which occurred only after previous topical use of retinoids. Severe allergic reactions necessitate discontinuation of the drug and careful monitoring of patients.

Patients at high risk (with diabetes, obesity, chronic alcoholism or problems with fat metabolism) in the treatment Aknekutanom may require more frequent laboratory control of blood glucose and lipids. If you have diabetes or suspected, it is recommended more frequent determination of blood glucose. Diabetics should conduct more frequent monitoring of blood glucose.

During the period of treatment and within 30 days after it should be totally excluded blood samples from potential donors for the complete elimination of the possibility of getting blood in pregnant patients (high risk of teratogenic and embryotoxic action).

Effects on ability to drive vehicles and management mechanisms

During the period of treatment must be careful when driving and other lesson potentially dangerous activities which require high concentration and speed of psychomotor reactions (when receiving the first dose).

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

Tetracycline antibiotics, reducing the effectiveness of SCS Aknekutana.

The simultaneous use with drugs that increase photosensitivity (including sulfonamides, tetracyclines, thiazides) increase the risk of sunburn.

The simultaneous use of other retinoids (including atsitretinom, tretinoin, retinol, tazarotenom, adapalenom) increases the risk of hypervitaminosis A.

Isotretinoin can weaken the efficacy of progesterone, so you should not use contraceptives containing low doses of progesterone.

Combined application of local keratolytic preparations for the treatment of acne is not recommended because of the possible increase in local irritation.

Because tetracyclines increase the risk of increasing intracranial pressure, the simultaneous use of isotretinoin is contraindicated.

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Drug prescription.

Terms and Conditions of storage

The drug should be stored in a dry place protected from light, away from children at or above 25 ° C. Shelf life - 2 years. Do not use after the expiry date.

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