Rheumatoid arthritis with severe course. Wilson's disease (lento- and hepatic degeneration). Cystinuria. Lead poisoning. Chronic active hepatitis.
Composition:
1 tabl powl. contains 250 mg of penicillamine. Table. contain lactose and azorubine lake.
Action:
A drug that strongly binds metal molecules, mainly copper, mercury, lead, iron and others; the complexes formed are soluble in water and excreted in the urine through the kidneys. Penicillamine reduces the concentration of rheumatoid factor (IgM) and immunoglobulin complexes in serum and synovial fluid with a slight decrease in total serum immunoglobulin levels. In vitro, penicillamine inhibits T cell activity without affecting the activity of B-lymphocytes. The mechanism of action of penicillamine in rheumatoid arthritis is not known. In patients with cystinuria, penicillamine forms complexes with cystine to give penicillin-cysteine disulfide, which is more soluble than cystine and easily excreted through the kidneys. As a result, the concentration of cystine in the urine is significantly reduced, which is important in the prevention of cystine stones. In Wilson's disease, the medicine works by reducing the absorption of copper from food and removing it from the tissues. In addition, the drug is effective in severe forms of lead, as well as in poisoning with other heavy metals. It is easily absorbed from the gastrointestinal tract, the maximum effect is achieved after 2 hours. T0,5 it is two-phase: I phase is 1 hour, phase II is 5 hours. It permeates almost all tissues, about 80% excreted with faeces and urine within 48 hours.
Contraindications:
Hypersensitivity to the active substance or to any of the excipients. Lupus erythematosus. Patients who have experienced aplastic anemia or agranulocytosis in the past with penicillamine. Because of the potential for harmful effects on the kidneys, penicillamine should not be used in patients with rheumatoid arthritis with concurrent renal dysfunction now or in the past. Do not administer the medicinal product to patients with chronic lead poisoning who have been found to have lead-based X-ray detected in the gastrointestinal tract. Administration of the drug can be started after removing the above substance from the gastrointestinal tract. Animal studies suggest that penicillamine may be ineffective and dangerous if there is excessive consumption of lead during administration. Do not administer the medicinal product to patients using gold preparations, antimalarials, cytostatics, oxyphenylbutazone and phenylbutazone, because these medicines, like penicillamine, cause side effects from the hematopoietic system and kidneys.
Precautions:
Due to the possibility of disorders such as aplastic anemia, agranulocytosis, thrombocytopenia, Goodpasture syndrome and epidural myasthenia, every 2 weeks during the first 6 months of using the drug, and then monthly, perform: urinalysis, blood counts with smear and determine the number of platelets. In case of symptoms of granulocytopenia and / or thrombocytopenia such as: fever, sore throat, chills, bloody ecchymosis, bleeding, these tests should be repeated. During the therapy proteinuria and / or hematuria may occur, which may be a symptom of the beginning glomerulonephritis that may lead to nephrotic syndrome. Such patients should be observed. The symptoms of proteinuria may recede during treatment, if they persist, discontinue penicillin therapy. When proteinuria and hematuria occur, make sure that the symptoms of glomerular damage are related to the treatment. In patients with Wilson disease or cystinuria treated with penicillamine who have had changes in urine, the risk of continuing treatment with the therapeutic benefit should be assessed. In patients with cystinuria, it is recommended to perform X-ray of the urinary system once a year in order to detect kidney stones as soon as possible. Cystin stones form very quickly, sometimes within 6 months.It is recommended to perform liver function tests every six months during treatment (risk of cholestasis and hepatitis). In case of post-exercise dyspnoea, unexplained cough, wheezing, lung function tests should be considered. In the case of pemphigus disease, treatment with penicillamine should be stopped immediately and appropriate treatment should be given. Before the planned surgery, due to the effect of penicillamine on collagen and elastin, the daily dose of the drug should be reduced to 250 mg. Treatment with a higher dose may be resumed only after complete post-operative wound healing. Patients who discontinue the therapy with gold due to the occurrence of serious side effects may be at higher risk of side effects during treatment with penicillamine - re-treatment should be started at low doses, gradually increasing until an effective therapeutic dose is reached. Due to the lactose content, the drug should not be used in patients with rare hereditary galactose intolerance, lactase deficiency (Lapp type) or malabsorption of glucose-galactose. Due to the presence of azorubine lake, the preparation may cause allergic reactions.
Pregnancy and lactation:
It is not recommended for pregnant women with rheumatoid arthritis or cystinuria, due to reports of birth defects in children born to women treated with penicillamine due to rheumatoid arthritis or cystinuria during pregnancy. In Wilson's disease, it is recommended to reduce the daily doses to 1000 mg. If a caesarean section is to be performed, it is recommended to reduce the daily dose to 250 mg during the last 6 weeks of pregnancy and until the postoperative wounds have healed. There are no controlled studies in pregnant women. Animal studies have shown that when rats are given six times the maximum recommended human dose, penicillamine causes fetal malformations and cleft palate in the fetus. There are no data on the excretion of milk into breast milk, therefore penicillamine is not recommended for breastfeeding women.
Side effects:
Common: thrombocytopenia, lymphadenopathy, fever, joint pain, kidney glomerular damage, urinary tract infection, hypersensitivity reactions, urticaria, erythema, pruritus, stomatitis. Uncommon: agranulocytosis, aplastic anemia, hemolytic anemia, leukopenia. Rare: chronic bronchitis, optic neuritis, tinnitus, pancreatitis, peptic ulcer recurrence, cholestatic jaundice, exfoliative dermatitis, toxic epidermal necrolysis, pemphigus, epidural myelitis, lupus-like syndrome, Goodpasteure syndrome. In most cases, the symptoms of myasthenia gravis disappear after discontinuation of penicillamine. Usually, in the second or third week of the start of treatment, some patients may develop a fever as a response to the medicine. Fever can often be accompanied by a rash. An early-type allergic reaction in the form of a rash usually disappears within a few days of discontinuation of the drug and rarely occurs after restarting the administration of small doses of the drug. In the case of pruritus and rash, antihistamines can be given. Much less often, usually after 6 months or later, the so-called an allergic reaction of the late type in the form of a rash, which results in the need to discontinue the drug. The occurrence of a drug eruption with fever, joint pain, lymphadenopathy and other allergic symptoms usually results in the need to discontinue the drug.
Dosage:
Orally.Rheumatoid arthritis, including juvenile rheumatoid arthritis. Adults: 125 to 250 mg / day in the first month of use; then the dose should be increased every 2 to 12 weeks by 125 to 250 mg until the disease is remitted. Then use the minimum effective dose that allows you to stop the symptoms of the disease. The drug should be discontinued if efficacy is not achieved after 12 months of use. The usual maintenance dose is 500 to 750 mg / day. Do not use a dose higher than 1500 mg / day. After remission for 6 months, it is recommended to gradually reduce the dose of 125-250 mg every 12 weeks.Elderly patients: Do not use an initial dose of more than 125 mg / day in the first month of use. The dose can then be increased by 125 mg every 4 to 12 weeks until the disease is remitted. Do not use a dose higher than 1000 mg / day. Children: The usual maintenance dose is 15 to 20 mg / kg / day. The starting dose should be lower (2.5 to 5.0 mg / kg / day), it can be increased gradually every 4 weeks for 3 to 6 months. The drug should be used at least 30 minutes before a meal.Wilson's disease. Adults: 1500-2000 mg / day in divided doses. After remission, the dose may be reduced to 750 mg or 1000 mg / day. In patients with negative copper balance, the lowest effective dose of penicillamine should be used. Doses of 2000 mg / day should not be used for more than 1 year. Elderly patients: 20 mg / kg / day in divided doses. The dose should be chosen in such a way as to obtain remission of the disease symptoms and maintain a negative copper balance. The drug should be used at least 30 minutes before a meal. Children: Usually 20 mg / kg / day in 2 or 3 divided doses, given 1 hour before a meal. For children> 12 years, the usual dose is 750 mg to 1000 mg / day.Cystinuria. It is best to set the lowest effective dose after quantifying the concentration of amino acids in the urine by means of chromatography.Dissolution of cystine stones. Adults: 1000 to 3000 mg / day in divided doses. The cystine concentration in the urine should be kept below 200 mg / l.Prevention of cystine stones Adults: 500 to 1000 mg / day until a urinary cystine concentration of less than 300 mg / l is achieved. Elderly patients: use the minimum dose to achieve cystine concentration <200 mg / l. The drug should be used at least 30 minutes before a meal. Children: 20 to 30 mg / kg / day in 2 or 3 divided doses, given 1 hour before a meal, so as to obtain a concentration of cystine in urine <200 mg / l. During treatment, it is recommended to drink a lot of liquids in an amount not less than 3 l / day. The patient should drink 500 ml of water before bedtime and then 500 ml at night, when the urine is more concentrated and more acidic than during the day. Usually, the more a patient drinks fluids, the less his penicillin need. A methionine-poor diet is also recommended so that cystine production is as low as possible. Such a diet is not recommended in children during growth or in women during pregnancy due to low protein content.Lead poisoning. Adults: 1000 to 1500 mg / day in divided doses until excretion of lead in urine reaches 0.5 mg / day. Elderly patients: 20 mg / kg / day in divided doses until excretion of lead in the urine of 0.5 mg / day is achieved. Children: The total dose should be 15 to 20 mg / kg / day in 2-3 divided doses. The drug should be used only in cases where the concentration of lead in the blood is <45 μg / dL. The drug should be used at least 30 minutes before a meal.Chronic active hepatitis. Adults: The starting dose is 500 mg / day in divided doses. The dose can then be gradually increased every 3 months until the dose reaches 1250 mg / day. You should not be given corticosteroids during treatment. Liver function tests should be performed periodically to assess liver function. The drug should be used at least 30 minutes before a meal. Children: the safety and efficacy of penicillamine in children under 18 with this diagnosis has not been established. Due to the availability of the tabl. only at a dose of 250 mg, the drug is not suitable for use in children <12 years.