Penicillamine

Complexing compound. Forms chelate complexes with ions of copper, mercury, lead, iron, arsenic, calcium, zinc, cobalt , gold. When interacting with an amino acid, cysteine forms a disulfide with much greater solubility than cysteine. It is believed that penicillamine has an effect on various parts of the immune system (suppression of the T-helper function of lymphocytes , inhibition of neutrophil chemotaxis and the release of enzymes from the lysosomes of these cells, increased macrophage function). It has the ability to disrupt collagen synthesis by cleaving cross-links between newly synthesized tropocollagen molecules . In addition, penicillamine is an antagonist of pyridoxine (vitamin B6).

After oral administration, absorption from the gastrointestinal tract is about 50%. The maximum absorption is observed when taking penicillamine 1.5 hours after a meal. Unchanged penicillamine and its metabolites are excreted by the kidneys and through the intestines. About 60% is excreted within 24 hours. Currently, there is no satisfactory method for determining the level of penicillamine in blood plasma.

Konovalov-Wilson's disease ( hepatocerebral dystrophy ), cystinuria , rheumatoid arthritis .

Set individually, taking into account the indications and patient response to treatment. A single dose is not more than 500 mg.

In Konovalov-Wilson's disease, the daily dose for adults is 0.75-1.5 g. The dose is considered effective if the daily excretion of copper in urine (after the first week of treatment) exceeds 2 mg. In the future, the adequacy of the dose is determined on the basis of measuring the level of free copper in the blood serum (it should be less than 10 μg / ml). In some cases, the dose may be 2 g / day or more. For children - 20 mg / kg / day in divided doses, the minimum dose is 500 mg / day. With cystinuria, the daily dose for adults is 1-4 g (on average 2 g), for children - 30 mg / kg. The daily dose is divided into 4 doses, a large single dose is taken at night. The dose is selected individually based on the determination of urinary cysteine ​​excretion (the optimal level is considered not to exceed 100-200 mg / day in patients with no signs of urolithiasis and not exceeding 100 mg / day in patients with urolithiasis). During treatment, it is necessary to drink plenty of water, it is especially important to take an additional amount of fluid (at least 0.5 l) immediately before bedtime and at night.

With rheumatoid arthritis, the initial dose is 125-250 mg / day. Then, in case of good tolerance, the dose is increased by 125 mg every 1-2 months. The first signs of a therapeutic effect are usually observed no earlier than the 3rd month of constant use. If by this time there is no curative effect, provided that it is well tolerated, the dose is continued to be gradually increased (by 125 mg every 1-2 months). In the absence of a therapeutic effect, penicillamine is canceled by 6 months of therapy. When a satisfactory effect is achieved, continued use of penicillamine in the same dose is continued for a long time. It is believed that with rheumatoid arthritis, the effectiveness of penicillamine in low (250-500 mg / day) and high (750 mg / day or more) doses is the same, but in some patients only high doses are effective.

For children with rheumatoid arthritis, the initial dose is 2.5-5 mg / kg / day, the maintenance dose is 15-20 mg / kg / day.

Take on an empty stomach, at least 1 hour before or 2 hours after eating, and also no earlier than 1 hour after taking any other medicines.

• From the digestive system: anorexia , nausea , vomiting , diarrhea , aphthous stomatitis , glossitis ; rarely - hepatitis , intrahepatic cholestasis , pancreatitis .
• From the side of the central nervous system and peripheral nervous system: complete loss or distortion of taste sensations; rarely, reversible polyneuritis (associated with vitamin B6 deficiency ).
• From the urinary system: rarely - nephritis .
• From the hemopoietic system: rarely - eosinophilia , thrombocytopenia , leukopenia ; anemia (aplastic or hemolytic ), agranulocytosis .
• From the endocrine system: rarely - an increase in the mammary glands, sometimes with the development of galactorrhea (in women).
• From the respiratory system: rarely - interstitial pneumonitis, diffuse fibrosing alveolitis, Goodpasture syndrome .
• From the musculoskeletal system: rarely - myasthenia gravis , polymyositis , dermatomyositis .
• Skin and its appendages: allergic reactions: skin rash, rarely - epidermal necrolysis, allergic alveolitis, fever; rarely - alopecia .
• Lupus-like reactions (arthralgia, myalgia, erythematous rash, the appearance of antinuclear antibodies and antibodies to DNA in the blood).

Lactation (breastfeeding); hypersensitivity to penicillamine.

During pregnancy, patients with Konovalov-Wilson's disease or cystinuria continue with penicillamine treatment at a dose of not more than 1 g / day, in patients with rheumatoid arthritis, penicillamine is canceled. If necessary, use of penicillamine during lactation should stop breastfeeding.

Given the possibility of developing serious, sometimes life-threatening, adverse reactions (especially frequent in patients with rheumatoid arthritis), penicillamine is used only under constant medical supervision. During treatment, a urinalysis and a clinical blood test should be monitored once every 2 weeks during the first 6 months of treatment, then monthly; Once every 6 months, liver function is monitored. In Konovalov-Wilson’s disease or cystinuria, simultaneously with penicillamine, vitamin B6 is prescribed for continuous use (due to dietary restrictions used to treat these diseases); with prolonged treatment, these patients should undergo regular x-ray or ultrasound examinations of the kidneys and urinary tract. In case of the development of signs of vitamin B6 deficiency in patients with rheumatoid arthritis, as well as if the symptoms of this deficiency do not resolve on their own, vitamin B6 is additionally prescribed at a dose of 25 mg / day. A slow, gradual increase in the dose of penicillamine can reduce the frequency of some adverse reactions. In the event of the development of high temperature during treatment, damage to the lungs, liver, severe hematological or neurological disorders, myasthenia gravis, hematuria, lupus-like reactions or other serious adverse reactions, penicillamine is canceled and, if necessary, GCS is prescribed. In the case of the development of isolated proteinuria, if it does not increase and does not exceed 1 g / day, treatment with penicillamine is continued, in other cases it is canceled.

Iron preparations reduce the absorption of penicillamine and weaken its therapeutic effect. Penicillamine enhances the neurotoxic effect of isoniazid. With simultaneous use with penicillamine, a decrease in the level of digoxin in blood plasma is possible.

• S- nitroso- N- acetylpenicillamine