- Available:In stock825
- Availability date:2020-07-30
- Dosage form:tablets
- In stock:825 Items
active ingredient: penicillamine;
1 tablet contains penicillamine 250 mg;
excipients: lactose monohydrate, potato starch, povidone, talc, magnesium stearate, hypromellose, polyethylene glycol, titanium dioxide (e 171), azorubin (E 122).
Dosage form. Film-coated tablets.
Basic physical and chemical properties: purple-pink, round, biconvex film-coated tablets with a smooth surface, without stains and damage.
Pharmacotherapeutic group. Specific antirheumatic agents. ATX code M01S S01.
Pharmacodynamics. Penicillamine is a synthetic drug, a breakdown product of penicillin; it differs from cysteine in the presence of two methyl groups. It forms stable soluble complex compounds with heavy metal ions, which are excreted from the body in the urine. It has a high complexing activity against copper, mercury, lead, iron and calcium ions. The ability of the drug to form chelated compounds with copper makes it the means of choice for the treatment of hepatolenticular degeneration (Wilson's disease). The cause of the disease is a violation of copper metabolism, which leads to its accumulation in various organs: the brain, kidneys, liver, and eyeball. The drug Kuprenil® reduces the absorption of copper from food and helps to remove it from the body's tissues. In addition, the drug is an effective remedy for severe lead poisoning, poisoning with other heavy metals, in particular iron, Mercury.
The mechanism of action of penicillamine in rheumatoid joint inflammation has not been studied. Penicillamine reduces the concentration of rheumatoid factor (IgM) and immunoglobulin complexes in blood serum and synovial fluid with a slight decrease in the total concentration of immunoglobulins in blood serum.
In vitro, penicillamine inhibits the activity of T-lymphocytes without affecting B-lymphocytes.
Penicillamine has an antiurolytic effect. In patients with cystinuria, penicillamine forms complexes with cystine, resulting in the formation of penicillamine-Cysteine disulfide, which dissolves better than cystine, and is easily excreted by the kidneys. As a result, the concentration of cystine in the urine is significantly reduced, which is of great importance in the Prevention of cystine stones. With proper treatment, cystine stones gradually dissolve.
Pharmacokinetics. Penicillamine is easily absorbed from the gastrointestinal tract, reaching its maximum concentration in the blood after 2 hours. The drug Kuprenil® is metabolized in two phases: the Half − Life of the first phase is 1 hour, the second-5 hours. The drug penetrates almost all body tissues. Approximately 80% of Cuprenil® is excreted in the faeces and urine within 48 hours.
* Severe active rheumatoid arthritis.
* Wilson's disease (hepatolenticular degeneration).
* Lead poisoning.
* Hypersensitivity to any component of the drug.
* Systemic lupus erythematosus.
* Pregnancy (except in cases where the pregnant woman has Wilson's disease) and the period of breast-feeding.
* A history of aplastic anemia or agranulocytosis associated with penicillamine.
* Rheumatoid joint inflammation with concomitant or a history of kidney dysfunction — due to the possibility of negative effects of penicillamine on the kidneys.
* Chronic lead poisoning in the case of radiologically confirmed presence of lead in the gastrointestinal tract. The use of the drug can be started after removing lead from the gastrointestinal tract. Animal studies show that penicillamine can be ineffective and dangerous if excessive lead intake occurs during its use.
* Simultaneous use of gold preparations, antimalarials, cytostatics, oxyphenylbutazone, phenylbutazone, which, like penicillamine, cause adverse reactions from the hematopoietic system and kidneys.
* Moderate to severe renal failure.
* Severe penicillamine-related thrombocytopenia.
Interactions with other drugs and other types of interactions.
The drug Kuprenil® increases the body's need for vitamin B6.
Penicillamine is a pyridoxine antagonist, increases the excretion of pyridoxine in the urine, which can lead to anemia or peripheral neuritis.
The drug forms complex compounds with heavy metals, so when simultaneously treated with iron preparations, an interval of 2 hours should be maintained between taking these drugs and penicillamine.
Cuprenil® should not be used together with drugs that inhibit bone marrow function, such as gold preparations, antimalarials, cytostatics, oxyphenylbutazone, phenylbutazone.
Antacids reduce the absorption of the drug.
Oral absorption of digoxin may decrease when co-administered with penicillamine.
Concomitant use of penicillamine and nonsteroidal anti-inflammatory drugs (NSAIDs) or other nephrotoxic agents increases the risk of impaired renal function.
Penicillamine may increase blood dyscrasia caused by clozapine.
Oral absorption of penicillamine may decrease when co-administered with zinc; zinc absorption may also decrease as a result of taking penicillamine.
Reactivation of phlebitis has been reported with concomitant use of penicillamine and diazepam.
Unexpected hypoglycemia has been reported in patients with Type I diabetes 6-8 weeks after penicillamine use for the treatment of rheumatoid arthritis. Patients needed to reduce their insulin dose. This phenomenon may be of an immunological nature.
Probenecid may reduce the therapeutic effects of penicillamine on cystinuria. It is assumed that the combined use of penicillamine and probenecid in patients with hyperuricemia is impractical.
When using Cuprenil®, constant monitoring by a doctor is required. During the use of the drug, it is necessary to conduct a general urinalysis, a morphological blood test with a smear, and determine the number of platelets every 2 weeks for the first 6 months of its use, and then every month. Patients should be informed about the possibility of symptoms of granulocytopenia and thrombocytopenia, such as fever, sore throat, chills, petechial hemorrhages, and bleeding. If these symptoms appear, the above studies should be repeated.
Usually, at the 2nd or 3rd week from the start of treatment, some patients may experience fever as a reaction to the drug. Fever may be accompanied by a rash. An allergic reaction of the third type in the form of a rash usually stops within a few days after discontinuation of the drug and rarely appears when its use is resumed in low doses.
If itching and rash occur, antihistamines can be used.
Much less often (6 months or later after the start of the drug) there is a late-type allergic reaction in the form of a rash, which requires discontinuation of the drug.
The appearance of a drug-induced rash with fever, joint pain, enlarged lymph nodes, and other allergic symptoms usually requires discontinuation of the drug.
Patients with penicillin allergy may be sensitized to penicillamine (cross-sensitization). The possibility of side effects caused by contamination of penicillamine with a trace amount of penicillin during the production process is excluded, since penicillamine is now produced synthetically, and not by splitting penicillin.
Due to the effect of penicillamine on collagen and elastin, the daily dose of the drug should be reduced to 250 mg before elective surgery. Treatment with large doses of the drug can be resumed only after complete healing of postoperative wounds.
Some patients taking penicillamine experience the following disorders: aplastic anemia, agranulocytosis, thrombocytopenia, Goodpascher syndrome, and myasthenia gravis.
During treatment with the drug, symptoms such as proteinuria and hematuria may occur, which may be a sign of the onset of glomerulonephritis, which can lead to nephrotic syndrome. Monitoring of such patients should be established. In some patients, the symptoms of proteinuria may disappear without discontinuation of the drug, while in other patients, treatment with penicillamine should be discontinued. If proteinuria and hematuria occur, the doctor should make sure that the symptoms of glomerular damage are associated with treatment.
If changes in urine are observed during penicillamine treatment in patients with Wilson's disease or cystinuria, the ratio of the risk of further use of the drug and the therapeutic benefit should be evaluated. When treating cystinuria with penicillamine, it is recommended to conduct an X-ray examination of the kidneys and urinary system once a year to quickly detect nephrolitis. Cystine stones form quickly, sometimes within 6 months.
Despite the small amount of data on cases of intrahepatic cholestasis and toxic hepatitis, it is recommended to conduct functional liver studies every 6 months during the entire period of use of the drug.
Although acute bronchitis is rare, patients should be warned to immediately inform the doctor about the appearance of symptoms such as shortness of breath during physical exertion, coughing of unclear etiology, wheezing. The need for a functional examination of the lungs should be considered.
Cases of myasthenic syndrome, which sometimes led to the development of myasthenia gravis, are described. Drooping eyelids, diplopia with weakening of the eyeball muscles are often early symptoms of myasthenia gravis. Symptoms of myasthenia gravis in most cases disappear after the withdrawal of penicillamine.
If pemphigus occurs, penicillamine treatment should be discontinued. Treatment of pemphigus: high doses of corticosteroids in monotherapy or sometimes in combination with immunosuppressants. Treatment usually lasts for several weeks or months, and in some cases for more than 1 year.
Patients who have stopped treatment with gold preparations due to the presence of severe adverse reactions are at an increased risk of adverse reactions during treatment with penicillamine.
If penicillamine treatment has been suspended for any reason, it should be resumed with low doses and gradually increased until an effective therapeutic dose is reached.
Especially careful monitoring is necessary for elderly patients. Increased toxicity was observed in this category of patients regardless of renal function.
Possible reversible loss of taste. Mineral supplements are not recommended to overcome this phenomenon.
Deterioration of neurological symptoms of Wilson's disease (dystonia, rigidity, tremor, dysarthria) was recorded after the use of penicillamine. This may be due to the redistribution of copper from the liver to the brain.
Breast augmentation is possible in both women and men, as a rare complication of penicillamine treatment. Danazol is successfully used to treat this phenomenon, if it does not disappear after discontinuation of treatment.
Concomitant use of NSAIDs and other nephrotoxic medications increases the risk of kidney damage.
If the patient is recommended to be treated with oral iron preparations, digoxin, antacids, it is necessary to maintain a 2-hour interval after taking penicillamine.
Antihistamines, prescribing steroids, or temporarily reducing the dose controls the risk of allergic reactions.
In case of withdrawal of gold preparations, due to lack of effectiveness, the use of Cuprenil® can be started after 6 months.
Caution should be exercised when concomitant use of Cuprenil® and anti-inflammatory drugs or other agents that may cause impaired bone marrow function.
In patients with rheumatoid arthritis, penicillamine therapy should be discontinued if macrohematuria or persistent microhematuria of unclear etiology develops.
Some patients may test positive for antinuclear antibodies (Ana), and some may be diagnosed with lupus erythematosus. Lupus as a syndrome similar to drug-induced lupus may be associated with other medications. Lupus erythematosus as a syndrome is not associated with hypocomplementemia, it can be without nephropathy. A positive ANA test is not a prerequisite for stopping treatment. However, you should keep in mind the possibility of developing lupus erythematosus as a syndrome in the future.
Some patients may develop oral ulcers, which sometimes have the appearance of aphthous stomatitis. Cheilitis, glossitis, and gingivostomatitis have also been reported. These oral ulcers are often dose-related and may require dosage restrictions, but do not require discontinuation of the drug.
It should be used with caution in patients with mild renal failure.
After any dosage change, a complete blood count (including platelet count) and urine test should be performed.
Treatment should be discontinued if there is a decrease in the number of white blood cells or platelets, or progressive or severe proteinuria or hematuria occurs.
Due to the fact that penicillamine increases the body's need for vitamin B6, patients can be prescribed pyridoxine daily at a dose of 25 mg for a long time, especially if they are on a restrictive diet.
This medicine contains lactose monohydrate. Patients with rare hereditary galactose intolerance, Lappa lactase deficiency, or glucose-galactose malabsorption should not be prescribed this medication. Cuprenil® contains azorubin (E 122), which can cause allergic reactions.
Use during pregnancy or lactation.
No controlled trials involving pregnant women have been conducted. Penicillamine causes skeletal damage and cleft palate in rats when used at doses six times higher than the maximum dose recommended for humans.
Use during pregnancy depending on the indications
Rheumatoid arthritis in the active phase. This medication is not recommended for pregnant women with rheumatoid arthritis, as birth defects have been reported in children whose mothers were treated for rheumatoid arthritis with penicillamine during pregnancy.
Cystinuria. This medication is not recommended for pregnant women with cystinuria, as birth defects have been reported in children whose mothers were treated for cystinuria with penicillamine during pregnancy.
Wilson's Disease. Despite the fact that developmental defects were not observed in newborns whose mothers were treated with penicillamine during pregnancy, it is recommended to reduce the daily dose to 1000 mg. If a caesarean section is planned, the daily dose of the drug should be reduced to 250 mg during the last six weeks of pregnancy and after surgery until the postoperative wound is completely healed.
There are no data on the release of the drug into breast milk. The drug is not recommended for use during breast-feeding.
Ability to influence the reaction rate when driving vehicles or other mechanisms.
The drug is considered safe and does not affect the reaction rate when driving vehicles or other mechanisms.
Dosage and administration.
The dosage regimen depends on the indications. The drug Kuprenil® is taken at least 30 minutes before meals.
Rheumatoid arthritis and juvenile rheumatoid arthritis
Adults-125-250 mg per day for the 1st month of use of the drug. Then the dose is increased for 4-12 weeks by 125-250 mg until remission is achieved, after which the minimum effective dose is used. If the therapeutic effect is not achieved within 12 months of using the drug, the use of the drug should be discontinued.
The maintenance dose is usually 500-750 mg per day. The dose should not exceed 1.5 g of the drug per day. After achieving remission lasting 6 months, the dose of the drug is recommended to be gradually reduced by 125-250 mg every 12 weeks.
In elderly patients, the initial dose should not exceed 125 mg per day during the 1st month of use of the drug. The dose can then be increased every 4-12 weeks by 125 mg until remission is achieved. The dose should not exceed 1 g of the drug per day.
Children-usually the maintenance dose is 15-20 mg/kg of body weight per day. The initial dose is 2.5–5 mg/kg of body weight per day, it can be increased gradually every 4 weeks for 3-6 months until the minimum effective dose is reached.
Adults - 1.5-2 g of the drug per day in several doses. After achieving remission of the disease, the dose can be reduced to 0.75 g or 1.0 g per day. Patients with a negative copper balance should use the minimum effective dose of the drug.
A dose of 2 g per day should not be used for more than 1 year.
Elderly patients - 20 mg/kg of body weight per day in several doses. The dose should be chosen in such a way as to achieve remission of the disease and maintain a negative copper balance.
Children-usually 20 mg/kg of body weight per day in 2-3 doses 1 hour before meals. For children over 12 years of age, the dose of the drug is usually 0.75–1 g per day. The minimum dose is 500 mg per day.
It is advisable to establish the minimum effective dose after quantitative determination of the concentration of amino acids in the urine by chromatographic method.
Dissolution of cystine stones
Adults-1-3 g per day in several doses. Keep the concentration of cystine in the urine below 200 mg/l.
Prevention of cystine stones
Adults - 0.5-1 g per day until the concentration of cystine in the urine reaches below 300 mg/l.
Elderly patients are prescribed a minimum dose until the concentration of cystine in the urine reaches below 200 mg/l.
Children-from 20 to 30 mg/kg/day in 2-3 doses, 1 hour before meals. The dose should be adjusted until the concentration of cystine in the urine reaches below 200 mg/l.
Note. During treatment, it is recommended to consume a large amount of liquid, at least 3 liters per day. The patient needs to drink 0.5 liters of water before going to bed, then 0.5 liters at night, when the urine is concentrated and more acidic than during the day. Usually, the more fluids a patient drinks, the lower their need for penicillamine.
A low-methionine diet is also recommended so that cystine formation is as low as possible, but due to the low protein content, such a diet is not recommended for children during the growth period and pregnant women.
Adults - 1-1.5 g per day in several doses before reducing the level of lead in the urine to 0.5 mg/day.
Elderly patients - 20 mg/kg of body weight in several doses before reducing the level of lead in the urine to 0.5 mg/day.
In children, this medicine should be used if the concentration of lead in the blood is less than 45 mg/dL. The total daily dose should be from 15 to 20 mg/kg in 2-3 doses.
Children. The drug in this dosage is used for children over 12 years of age according to the section "dosage and administration".
No cases of acute penicillamine poisoning have been observed. But in therapeutic doses, the drug can cause various undesirable side effects.
Symptoms. Acute allergic reactions may occur, especially at the beginning of treatment.
Cross-sensitization with penicillin may occur.
Treatment. Treatment is symptomatic.
Allergic reactions: stop using the drug and use corticosteroids, then resume using penicillamine, starting with minimal doses, gradually reaching effective therapeutic doses.
Iron and vitamin B6 deficiency: compensate for iron and vitamin B6 deficiency.
Taste disorders: prescribe 5-10 mg of copper per day in the form of 5-10 drops of a 4% Solution of CuSO4·5h2o in fruit juice, divided into two doses.
Copper should not be used in patients with Wilson's disease.
The frequency of adverse reactions is determined as follows: very often (≥ 1/10); often (≥ 1/100 to
From the respiratory, thoracic and mediastinal organs. Rare: chronic bronchitis.
From the side of the hepatobiliary system. Rare: cholestatic jaundice.
From the side of the hearing organs. Rare: tinnitus.
From the immune system. Common hypersensitivity reactions.
From the musculoskeletal system and connective tissue. Common: arthralgia. Rare: myasthenia gravis, lupus-like syndrome.
From the blood and lymphatic system. Common: thrombocytopenia, enlarged lymph nodes. Infrequently: agranulocytosis, aplastic anemia, hemolytic anemia, leukopenia.
From the side of the kidneys and urinary system. Common: glomerulonephritis, urinary tract infection. Rare: Goodpascher syndrome.
From the skin and subcutaneous tissue. Common: rash, urticaria, erythema, pruritus. Rare: exfoliative dermatitis, toxic epidermal necrolysis (Lyell's syndrome), pemphigus, edema.
From the side of the visual organs. Rare: optic neuritis.
From the gastrointestinal tract. Often stomatitis. Rare: pancreatitis, relapse of gastric ulcer.
General disorders. Often: fever.
Also, when using penicillamine, the following adverse reactions may occur.
From the gastrointestinal tract: oral ulcers, anorexia, nausea, vomiting, diarrhea, aphthous stomatitis, glossitis, complete loss or distortion of taste sensations, acute colitis, ileal ulcers, stenosis, elastosis.
From the skin and subcutaneous tissue: elastic pseudoxanthoma, skin weakness, penicillin — induced lupus erythematosus, impaired collagen and elastin metabolism (pemphigoid, dermatomyositis, negative effects on hair, increased skin fragility, hemorrhagic lesions, wrinkles and sagging skin), oral lichen planus, alopecia, Stevens-Johnson syndrome, bullous epidermolysis, lupus-like reactions (erythematous rash, the appearance of antinuclear antibodies to DNA).
Musculoskeletal and connective tissue disorders: rheumatoid arthritis, septic arthritis, lower back and back pain, polymyositis (rarely involving the heart), dermatomyositis.
From the blood and lymphatic system: agranulocytosis and aplastic anemia with a fatal outcome, myelotoxicity and myelosuppression, thrombocytopenic purpura, eosinophilia.
Nervous system disorders: worsening neurological symptoms of Wilson's disease (dystonia, rigidity, dysarthria), reversible polyneuritis (associated with pyridoxine deficiency), polyneuritis, sensory and motor neuropathies, myasthenia gravis (including ptosis, diplopia, general weakness, respiratory muscle weakness).
From the hepatobiliary system: intrahepatic cholestasis, hepatotoxicity.
From the kidneys and urinary system: nephritis, hematuria, proteinuria, glomerulonephritis, nephrotic syndrome.
Respiratory, thoracic and mediastinal disorders: allergic alveolitis, interstitial pneumonitis, diffuse fibrotic alveolitis, pulmonary bleeding, rhinitis, sinusitis.
From the cardiovascular system: heart block, Adams — Stokes syndrome, fatal myocarditis.
From the reproductive system: breast enlargement with the development of galactorrhea (in women).
From the side of the visual organs: blepharitis.
Expiration date. 3 years.
Storage conditions. Store at a temperature not exceeding 25 ° C OUT of the reach of children.