Index of drugs

Severe chronic hand eczema in adults who is not responding to treatment with strong topical corticosteroids. Response to treatment is more likely in patients with eczema mainly due to hyperkeratotic features than in those with eczema mostly in the form of a psorosis.

1 capsule contains 10 mg or 30 mg of alitretinoin. The preparation contains soybean oil and sorbitol.

Alitretinoin influences cell proliferation, cell differentiation, apoptosis, angiogenesis, keratinization, sebum production and immunomodulation. It binds to RAR and RXR receptors. The mechanism of action of alitretinoin in chronic hand eczema is unknown. Immunomodulatory and anti-inflammatory activity of alitretinoin has been demonstrated, which is important in skin inflammation. Alitretinoin limits the effect of CXCR3 ligands and CCL20 chemokines, which are expressed in eczematous skin lesions, in keratinocytes stimulated by cytokines and in skin endothelial cells. In addition, alitretinoin inhibits the proliferation of subsets of leukocytes activated by cytokines and antigen presenting cells. Alitretinine only minimally affects the secretion of sebum. Absorption of the drug from the gastrointestinal tract varies and is proportional to the dose in the therapeutic range of 10-30 mg. Total bioavailability has not been determined. When using the drug with a meal, the systemic exposure increases 4 times and the variability of the exposure decreases. The drug is strongly bound to plasma proteins. It is metabolised by oxidation in the liver via CYP3A4 to 4-oxo-allitinoin. Both compounds undergo isomerization to all-trans-retinoic acid and 4-oxo-all-trans-retinoic acid. The main metabolite, 4-oxo-allitinoin, undergoes glucuronidation and is excreted in the urine. Alitretinoin is an endogenous retinoid. It decomposes similarly to vitamin A, as a result of gradual disintegration of the side carbon chain. Alitretinoin concentrations return to normal range within 1-3 days after discontinuation of therapy. The drug is excreted mainly in the urine, and to a lesser extent (about 30%) with faeces. T_0,5 in the phase of elimination is 2-10 h. There is no accumulation of alitretinoin or its 4-oxo-metabolite.

Pregnancy is an absolute contraindication. The drug is contraindicated in women of childbearing age, unless all the conditions of the Pregnancy Prevention Program have been met. Breastfeeding period. Hypersensitivity to alitretinoin, to other retinoids or to any of the excipients, in particular to peanut or soy allergy. Hepatic dysfunction. Severe kidney problems. Hypercholesterolemia uncontrollable. Uncontrolled hypertriglyceridaemia. Uncontrolled hypothyroidism. Excess vitamin A. Simultaneous treatment with tetracyclines. The preparation contains soybean oil and sorbitol - should not be used in patients with allergy to peanut, soy or with rare congenital fructose intolerance.

The drug has teratogenic effects. It is contraindicated in women of childbearing age, unless all the conditions of the Pregnancy Prevention Program are met: the patient understands the risk of teratogenic effects, understands the need for close monthly observation, understands and accepts the need for effective contraception for 1 month before treatment, during the course of treatment and for 1 month after treatment. At least one, preferably two complementary methods of contraception should be used, including the mechanical method. Even if the patient does not have menstruation, she should follow all recommendations for effective contraception. The patient should be able to use effective contraception. The patient understands and accepts the need to undergo pregnancy tests before, during and 5 weeks after treatment. The patient certifies that she understood the risks and necessary precautions associated with the use of the drug. These provisions also apply to women who are not currently sexually active, unless the prescribing physician considers that there are clear reasons indicating that there is no risk of becoming pregnant.It is advisable to carry out pregnancy-tested pregnancy tests with a minimum sensitivity of 25 mlU / ml in the first 3 days of the menstrual cycle as described below. To make sure that the patient is not pregnant before using contraception, it is recommended to perform an initial pregnancy test supervised by medical personnel and to record its date and result. In patients who do not have regular menstruation, the date of such a pregnancy test should be determined taking into account the sexual activity of the patient. This test should be performed about 3 weeks after the last sexual intercourse, during which no contraception was used. The test supervised by the medical staff should also be carried out during consultations when the preparation is prescribed or within 3 days before the visit to the doctor issuing the prescription for the medicine; with the test, wait until the patient uses an effective method of contraception for at least 1 month. The test is to ensure that the patient is not pregnant when starting treatment with the preparation. Control visits should be carried out at 28-day intervals. The need for multiple monthly pregnancy tests supervised by medical personnel should be established, taking into account, inter alia, the sexual activity of the patient and the last cycles of menstruation (menstrual disorders, irregular menstruation or total absence of menstruation). When indicated, check-up pregnancy tests should be carried out on the day of the visit, in order to prescribe the preparation or within 3 days before the doctor's prescription. 5 weeks after the end of treatment, women should undergo a final pregnancy test to rule out pregnancy. Patients should not be blood donors during therapy and for 1 month after discontinuation because of the potential risk to the fetus in a pregnant woman receiving a blood transfusion. Particular care should be taken in the case of patients with a history of depression - they should be monitored for symptoms of depression and directed to appropriate treatment, if necessary. Discontinuation of alitretinoin may not be sufficient to alleviate these symptoms, therefore further psychiatric or psychological assessment may be necessary. UV radiation is compounded by retinoid therapy, so patients should avoid excessive exposure to sunlight and unattended use of the tanning bed. If necessary, a protective preparation with a high value of light protection factor of at least SPF 15 should be used. Patients who develop dry skin and mouth should be advised to use a moisturizing cream or milk for the skin and lip balm. Treatment with other systemic retinoids was associated with bone changes, including premature closure of the base of the bone, hyperostosis, tendon and ligament calcification. The dryness of the eyes associated with treatment with alitretinoin can be alleviated by using eye ointments or so-called artificial tears. Intolerance of contact lenses may occur, requiring the patient to wear glasses during treatment. Patients who have vision problems should be referred to an ophthalmologist. It may be necessary to discontinue treatment with alitretinoin. Patients who develop symptoms of benign intracranial hypertension should immediately stop taking alitretinoin. During treatment, serum cholesterol and triglyceride levels (fasting) should be monitored. Alitretinoin should be discontinued if hypertriglyceridemia can not be maintained at an acceptable level or if symptoms of pancreatitis occur. Triglyceride levels above 800 mg / dl (9 mmol / l) are sometimes associated with acute pancreatitis which may result in death. In the case of persistent clinically significant increases in transaminase levels, a dose reduction or discontinuation of treatment should be considered. If severe diarrhea occurs during treatment, consideration should be given to the diagnosis of intestinal inflammation and prompt discontinuation of the use of alitretinoin. In patients with diabetes mellitus, obesity, risk factors for cardiovascular disease or lipid metabolism disorders, more frequent monitoring of serum lipids may be necessary (it is recommended to start treatment with a dose of 10 mg once a day and increase it if necessary up to a maximum dose of 30 mg) .The preparation is not recommended for use in patients under 18 years of age.

Pregnancy is an absolute contraindication for treatment with the preparation. If, despite taking precautions to prevent pregnancy during treatment with the product or one month after discontinuing such treatment, the patient becomes pregnant, there is a significant risk of very severe and serious malformation of the fetus. Alitretinoin belongs to the retinoids, which means that it has a strong teratogenic effect. Fetal developmental defects associated with retinoid exposure include abnormalities o.u.n. (hydrocephalus, developmental defects / cerebellar abnormalities, microcephaly), facial dysmorphia, cleft palate, external ear abnormalities (no external ear, small external auditory tubules or lack thereof), eye abnormalities (minor), cardiovascular abnormalities (defects of the cone and stem arterial, such as the tetralogy of Fallot, the translation of large vessels, defects of the septum), thymic anomalies and parathyroid abnormalities. An increased incidence of spontaneous abortions was also found. If the woman being treated with the product becomes pregnant, the treatment should be discontinued and the patient should be referred to a doctor with a specialization or experience in the field of teratology in order to evaluate and seek advice. Alitretinoin is a highly lipophilic substance; therefore, it is very likely to be excreted in human milk - the use of alitretinoin is contraindicated in breast-feeding mothers. Small amounts of alitretinoin were measured in healthy volunteers sperm receiving 40 mg of alitretinoin; however, nothing indicates cumulation of the drug in semen. Assuming that the drug is completely absorbed through the vagina, such amounts of the drug would have a negligible effect on endogenous plasma concentrations of the patients' partners. Therefore, they do not appear to pose a risk to the fetus if the partner is pregnant. On the basis of non-clinical observations, it was found that male fertility may be impaired due to treatment with the preparation.

Very common: headache, hypertriglyceridemia, reduced high density lipoprotein, hypercholesterolemia. Common: anemia, increased iron binding capacity, decreased number of monocytes, increased number of thrombocytes, decreased TSH concentration, decreased concentration of free T4, conjunctivitis, dry eyes, eye irritation, hot flushes, increased transaminases, dry skin, dry mouth, inflammation of the lips , eczema, dermatitis, erythema, alopecia, joint pain, myalgia, increased phosphocreatine kinase activity in the blood. Uncommon: blurred vision, cataracts, nosebleeds, pruritus, rash, flaking of the skin, eczema with cracks in the skin, exostosis (hyperstosis), ankylosing spondylitis. Rare: mild intracranial hypertension, vasculitis. Frequency unknown: depression, mood changes, suicidal thoughts. In clinical studies with alitretinoin, the following adverse events were not observed, but they were observed with other retinoids: inflammatory bowel disease, diabetes, color blindness (color vision deficiencies) and contact lens intolerance. Treatment of retinoids with general effects was accompanied by changes in bone mineralization and out-of-body calcification. In clinical trials with alitretinoin, degenerative changes of the spine and calcification of the ligaments in patients with chronic hand eczema before treatment (baseline) with low progression in a small number of patients during treatment were frequently observed. These observations corresponded to age-related degenerative changes. Bone density measurements (DXA) did not indicate a dose-related effect on bone mineralization.

Orally. Adults. The preparation should only be prescribed by a dermatologist or physician experienced in the use of retinoids with general effects. Women of childbearing potential should be discharged in an amount limited to 30 days of treatment; continuation of treatment requires a new prescription. It is best to have a pregnancy test, write a prescription and make a prescription the same day. The prescription should be completed within a maximum of 7 days from the date of the prescription. The recommended dose ranges from 10 mg to 30 mg once a day. The recommended starting dose is 30 mg once a day.In patients with unacceptable adverse reactions to higher doses, a dose reduction to 10 mg once a day may be considered. A treatment cycle lasting 12-24 weeks depending on the response to treatment may be used. Discontinuation of therapy should be considered in patients who continue to have severe disease after the first 12 weeks of treatment. If relapse occurs, patients may benefit from further treatment cycles. The preparation should not be prescribed if the patient's eczema can be adequately controlled by standard care, including skin protection, avoidance of allergens and irritants, and treatment with strong topical corticosteroids.
Kaps. should be taken once daily with food.