Penicillamine GPO

Penicillamine GPO

penicillamine

Manufacturer:

GPO

Distributor:

GPO
Full Prescribing Info
Contents
Penicillamine.
Description
Each capsule contains Penicillamine 250 mg.
Exipients/Inactive Ingredients: Colloidal Silicon Dioxide and Magnesium Stearate.
Action
Pharmacology: Pharmacodynamics: Penicillamine chelates copper, iron, mercury, lead, and probably other heavy metals to form stable soluble complexes which are readily excreted by the kidneys. Copper is chelated by the combination of 2 molecules of penicillamine with one atom of the metal. In vitro, 1 g of penicillamine combines with about 200 mg of copper; however, in vivo administration of 1 g of penicillamine results in excretion of only about 2 mg of copper.
Pharmacokinetics: Absorption: Penicillamine is rapidly absorbed from the GI tract following oral administration. Bioavailability is about 40-70%. Absorption is not dose-dependent. Peak plasma concentrations occur at 1 to 4 hours after ingestion, regardless of dose. The presence of food, antacids, or iron in the GI tract will slow absorption by complexing with the drug. Co-administration of food with a single 500-mg dose reduced absorption to 52% of control. Co-administration of a single 500-mg dose with a magnesium-aluminum salt combination antacid reduced absorption to 66% of control; co-administered ferrous sulfate reduced absorption to 35% of control.
Distribution: The distribution of penicillamine is not well known, but it is believed to cross the placenta. The estimated distribution half-Life is 0.48 to 1.27 hours. Volume of Distribution is 57 to 93 L. Protein binding is about 80%, primarily to albumin. The drug also binds to erythrocytes and macrophages. Penicillamine appears in the plasma as free penicillamine, penicillamine disulfide, and cysteine-penicillamine disulfide.
Metabolism: Penicillamine undergoes hepatic metabolism. The metabolites are penicillamine disulfide, cystein-penicillamine disulfide and small amount of s-methyl-D-penicillamine.
Excretion: The drug is excreted in urine and feces, principally as inactive disulfides: penicillamine disulfide,penicillamine-cysteine disulfide, and small amounts of S-methyl-d-penicillamine. Drug excretion is primarily renal. One study determined that, of a total dose of penicillamine, approximately 50% was excreted in the urine and 20% in the feces. Approximately 30% of the drug remained unaccounted for. The percentage recovered in the urine as unchanged drug varies from 1.2% to 24.5%; the majority of penicillamine is excreted as disulfide metabolites. The elimination half-life has been estimated to be from 1 to 7.5 hours. In patients on long-term therapy, the half-life rises to 4 to 6 days, although traces of penicillamine can be detected in the serum weeks after discontinuation of therapy, possibly due to mobilization of a tissue-bound pool.
Toxicology: Preclinical safety data: Penicillamine has been shown to be teratogenic in rats when given in doses several times higher than those recommended for human use. There is no known LD50 value for penicillamine. In studies some rats died after oral administration of 10,000 mg/kg, but intra-peritoneal injections of a dose of 660 mg/kg caused no deaths.
Indications/Uses
Treatment of Wilson's disease (hepatolenticular degeneration).
Treatment of chronic lead poisoning.
Dosage/Direction for Use
Recommended dose: Physicians planning to use penicillamine should thoroughly familiarize themselves with its toxicity, special dosage considerations, and therapeutic benefits. Penicillamine should never be used casually. Each patient should remain constantly under the close supervision of the physician. Patients should be warned to report promptly any symptoms suggesting toxicity.
Penicillamine is a copper-chelating agent, and is most effectively used in conjunction with a low-copper diet (below 1 mg of copper per day). Patients must be maintained in negative copper balance and the minimum dose of penicillamine required to achieve this should be given. Doses more than 500 mg/day should be orally administered in divided doses.
Wilson's Disease: Optimal dosage can be determined by measurement of urinary copper excretion and the determination of free copper in the serum. The urine must be collected in copper-free glassware, and should be quantitatively analyzed for copper before, and soon after, initiation of therapy with penicillamine.
Adult: Determination of 24-hour urinary copper excretion is a greatest value in the first week of therapy with penicillamine. In the absence of any drug reaction, a dose between 0.75 and 1.5 g that results in an initial 24-hour cupruresis of over 2 mg should be continued for about three months, by which time the most reliable method of monitoring maintenance treatment is the determination of free copper in the serum. This equals the difference between quantitatively determined total copper and ceruloplasmin-copper. Adequately treated patients will usually have less than 10 micrograms free copper/dL of serum. It is seldom necessary to exceed a dosage of 2 g/day.
If the patient is intolerant to therapy with penicillamine, alternative treatment is zinc compounds such as zinc sulfate.
In patients who cannot tolerate as much as 1 g/day initially, initiating dosage with 250 mg/day, and increasing gradually to the requisite amount, gives closer control of the effects of the drug and may help to reduce the incidence of adverse reactions.
Children: 1 month-12 years: 2.5 mg/kg twice daily, increased at 1–2 week intervals to 10 mg/kg twice daily.
12–18 years: 0.75 to 1 g twice daily, maximum dose 2 g daily for 1 year; usual maintenance dose 0.75 to 1 g daily.
Special populations: Elderly: Up to 20 mg per kg body weight daily in divided doses. The dosage should be adjusted to minimal level necessary achieve disease control.
Pregnancy: If pregnant, do not exceed a total dose of 500 to 750 mg daily. If a cesarean section is planned in advance, reduce dose to 250 mg daily for the last 6 weeks of pregnancy and postoperatively until wound healing is complete.
Chronic Lead Poisoning: Adult: The recommended dosage is 900 to 1500 mg a day, in three divided doses for one to two weeks, followed by 750 mg a day in divided doses until blood lead levels are reduced to 60 micrograms/dL, or until urinary lead excretion remains below 500 micrograms/L for two consecutive months.
Children: The recommended dosage is 30 to 40 mg/kg/day, or 600 to 750 mg/m2/day, not to exceed 750 mg a day. Penicillamine may be given to children as a single dose or in two divided doses. Treatment should be continued until blood lead levels remain below 40 micrograms/dL whole blood for two consecutive months and at least one of the following is achieved: erythrocyte protoporphyrin level decreases to less than three to five times the average normal level.
Excretion of δ-aminolevulinic acid decreases to upper limit of normal.
Excretion of coproporphyrin decreases to upper limit of normal.
Special populations: Elderly: 20 mg per kg body weight daily in divided doses until urinary lead is stabilised at less than 0.5 mg/day.
Renal Impairment: One study (Bennett et al, 1987) recommends that penicillamine be avoided in patients with moderate to severe renal failure (GFR less than 50 milliliters/minute). No dosage adjustment is necessary for patients with mild renal failure (GFR greater than 50 milliliters/minute).
Hepatic Impairment: Penicillamine is metabolized in the liver and may require a dosage adjustment; however, specific guidelines for dosage adjustments in hepatic impairment are not available.
Maximum Dosage Limits: Adults: 2 g/day for Wilson's disease; 1.5 g/day for lead toxicity; pregnancy see previously mentioned.
Elderly: 2 g/day for Wilson's disease; 1.5 g/day for lead toxicity.
Adolescents: 1 g/day for Wilson's disease; 1.5 g/day for lead toxicity.
Children: 1 g/day for Wilson's disease; 1.5 g/day for lead toxicity.
Mode of administration: Penicillamine must be orally administered on an empty stomach, at least one hour before meals or two hours after meals, and at least one hour apart from any other drug, food, or milk. This permits maximum absorption and reduces the likelihood of inactivation by metal binding. The last dose should be given at least 3 hours after the evening meal. For patients who cannot swallow capsules or tablets, the contents of a capsule may be administered in 15–30 mL of chilled pureed fruit or fruit juice.
The extemporaneous formulation of a penicillamine 50 milligrams/milliliter suspension, 300 milliliters, may be prepared using 60 penicillamine 250 milligram capsules, imitation cherry flavor powder (spray-dried) 3 grams, carboxymethylcellulose 3 grams, sucrose 150 grams, citric acid USP 300 milligrams, methylparaben, USP 360 milligrams, propylparaben, USP 60 milligrams, and a sufficient quantity of distilled water to bring the volume to 300 milliliters. This mixture should be labeled "shake well" and "refrigerate" and is stable for 30 days.
Overdosage
The treatment of penicillamine overdosage is nonspecific and essentially supportive. There is no known antidote.
Contraindications
Patients who are hypersensitive to this drug or to any ingredient in the formulation. (See Description.)
Pregnancy. Exceptions to this contraindication include the treatment of Wilson's disease or certain cases of cystinuria. (See Use in Pregnancy & Lactation.)
Breast-feeding. Although insufficient data are available on the administration of penicillamine while breast-feeding, alternative feeding methods be implemented if use of the drug is continued.
Patients with a history of penicillamine-related aplastic anemia, agranulocytosis or severe thrombocytopenia should not be restarted on penicillamine. (See Precautions and Adverse Reactions.)
Because penicilliamine use is associated with renal damage and the development of proteinuria and hematuria, use is contraindicated in rheumatoid arthritis patients with a history or other evidence of renal insufficiency, including renal disease, renal impairment, or renal failure.
Lupus erythematosus.
Warnings
The use of penicillamine has been associated with fatalities due to certain diseases such as aplastic anemia, agranulocytosis, thrombocytopenia, Goodpasture's syndrome, and myasthenia gravis.
Because of the potential for serious hematological and renal adverse reactions to occur at any time, routine urinalysis, white and differential blood cell count, hemoglobin determination, and direct platelet count must be done every two weeks for at least the first six months of penicillamine therapy and monthly thereafter. Patients should be instructed to report promptly the development of signs and symptoms of granulocytopenia and/or thrombocytopenia such as fever, sore throat, chills, bruising or bleeding. The above laboratory studies should then be promptly repeated.
Leukopenia and thrombocytopenia have been reported to occur in up to five percent of patients during penicillamine therapy. Leukopenia is of the granulocytic series and may or may not be associated with an increase in eosinophils. A confirmed reduction in WBC below 3,500 mandates discontinuance of penicillamine therapy.
Thrombocytopenia may be on an idiosyncratic basis, with decreased or absent megakaryocytes in the marrow, when it is part of an aplastic anemia. In other cases the thrombocytopenia is presumably on an immune basis since the number of megakaryocytes in the marrow has been reported to be normal or sometimes increased. The development of a platelet count below 100,000 even in the absence of clinical bleeding, requires at least temporary cessation of penicillamine therapy. A progressive fall in either platelet count or WBC in three successive determinations, even though values are still within the normal range, likewise requires at least temporary cessation.
Proteinuria and/or hematuria may develop during therapy and may be warning signs of membranous glomerulopathy which can progress to a nephrotic syndrome. Close observation of these patients is essential. In some patients the proteinuria disappears with continued therapy; in others, penicillamine must be discontinued. When a patient develops proteinuria or hematuria the physician must ascertain whether it is a sign of drug-induced glomerulopathy or is unrelated to penicillamine.
Rheumatoid arthritis patients who develop moderate degrees of proteinuria may be continued cautiously on penicillamine therapy, provided that quantitative 24-hour urinary protein determinations are obtained at intervals of one to two weeks. Penicillamine dosage should not be increased under these circumstances. Proteinuria which exceeds 1 g/24 hours, or proteinuria which is progressively increasing, requires either discontinuance of the drug or a reduction in the dosage. In some patients, proteinuria has been reported to clear following reduction in dosage.
In rheumatoid arthritis patients penicillamine should be discontinued if unexplained gross hematuria or persistent microscopic hematuria develops.
In patients with Wilson's disease or cystinuria the risks of continued penicillamine therapy in patients manifesting potentially serious urinary abnormalities must be weighed against the expected therapeutic benefits.
Because of rare reports of intrahepatic cholestasis and toxic hepatitis, liver function tests are recommended every six months for the duration of therapy. In Wilson’s disease, these are recommended every three months, at least during the first year of treatment.
Goodpasture's syndrome has occurred rarely. The development of abnormal urinary findings associated with hemoptysis and pulmonary infiltrates on x-ray requires immediate cessation of penicillamine.
Obliterative bronchiolitis has been reported rarely. The patient should be cautioned to report immediately pulmonary symptoms such as exertional dyspnea, unexplained cough or wheezing. Pulmonary function studies should be considered at that time.
Onset of new neurological symptoms has been reported with penicillamine.
Occasionally, neurological symptoms become worse during initiation of therapy with penicillamine. Myasthenic syndrome sometimes progressing to myasthenia gravis has been reported. Ptosis and diplopia, with weakness of the extraocular muscles, are often early signs of myasthenia. In the majority of cases, symptoms of myasthenia have receded after withdrawal of penicillamine.
Most of the various forms of pemphigus have occurred during treatment with penicillamine. Pemphigus vulgaris and pemphigus foliaceus are reported most frequently, usually as a late complication of therapy. The seborrhea-like characteristics of pemphigus foliaceus may obscure an early diagnosis. When pemphigus is suspected, pencillamine should be discontinued.
Once instituted for Wilson's disease or cystinuria, treatment with penicillamine should, as a rule, be continued on a daily basis. Interruptions for even a few days have been followed by sensitivity reactions after reinstitution of therapy.
Special Precautions
Some patients may experience drug fever, a marked febrile response to penicillamine, usually in the second to third week following initiation of therapy. Drug fever may sometimes be accompanied by a macular cutaneous eruption. In the case of drug fever in patients with Wilson's disease or cystinuria, penicillamine should be temporarily discontinued until the reaction subsides. Then penicillamine should be reinstituted with a small dose that is gradually increased until the desired dosage is attained. Systemic steroid therapy may be necessary, and is usually helpful, in such patients in whom drug fever and rash develop several times.
The skin and mucous membranes should be observed for allergic reactions. Early and late rashes have occurred. Early rash occurs during the first few months of treatment and is more common. It is usually a generalized pruritic, erythematous, maculopapular or morbilliform rash and resembles the allergic rash seen with other drugs. Early rash usually disappears within days after stopping penicillamine and seldom recurs when the drug is restarted at a lower dosage. Pruritus and early rash may often be controlled by the concomitant administration of antihistamines. Less commonly, a late rash may be seen, usually after six months or more of treatment, and requires discontinuation of penicillamine. It is usually on the trunk, is accompanied by intense pruritus, and is usually unresponsive to topical corticosteroid therapy. Late rash may take weeks to disappear after penicillamine is stopped and usually recurs if the drug is restarted.
The appearance of a drug eruption accompanied by fever, arthralgia, lymphadenopathy or other allergic manifestations usually requires discontinuation of penicillamine.
Certain patients will develop a positive antinuclear antibody (ANA) test and some of these may show a lupus erythematosus-like syndrome similar to drug-induced lupus associated with other drugs. The lupus erythematosus-like syndrome is not associated with hypocomplementemia and may be present without nephropathy. The development of a positive ANA test does not mandate discontinuance of the drug; however, the physician should be alerted to the possibility that a lupus erythematosus-like syndrome may develop in the future.
Some patients may develop oral ulcerations which in some cases have the appearance of aphthous stomatitis. The stomatitis usually recurs on rechallenge but often clears on a lower dosage. Although rare, cheilosis, glossitis and gingivostomatitis have also been reported. These oral lesions are frequently dose-related and may preclude further increase in penicillamine dosage or require discontinuation of the drug.
Hypogeusia (a blunting or diminution in taste perception) has occurred in some patients. This may last two to three months or more and may develop into a total loss of taste; however, it is usually self-limited despite continued penicillamine treatment. Such taste impairment is rare in patients with Wilson's disease.
Penicillamine should not be used in patients who are receiving concurrently gold therapy, antimalarial or cytotoxic drugs, oxyphenbutazone or phenylbutazone because these drugs are also associated with similar serious hematologic and renal adverse reactions.
Patients who have had gold salt therapy discontinued due to a major toxic reaction may be at greater risk of serious adverse reactions with penicillamine but not necessarily of the same type.
Patients who are allergic to penicillin may theoretically have cross-sensitivity to penicillamine. The possibility of reactions from contamination of penicillamine by trace amounts of penicillin has been eliminated now that penicillamine is being produced synthetically rather than as a degradation product of penicillin.
Patients with Wilson's disease or cystinuria should be given 25 mg/day of pyridoxine during therapy, since penicillamine increases the requirement for this vitamin. Patients also may receive benefit from a multivitamin preparation, although there is no evidence that deficiency of any vitamin other than pyridoxine is associated with penicillamine. In Wilson's disease, multivitamin preparations must be copper-free.
Iron deficiency may develop, especially in pediatric patients and in menstruating women. In Wilson's disease, this may be a result of adding the effects of the low copper diet, which is probably also low in iron, and the penicillamine to the effects of blood loss or growth. If necessary, iron may be given in short courses, but a period of two hours should elapse between administration of penicillamine and iron, since orally administered iron has been shown to reduce the effects of penicillamine.
Penicillamine causes an increase in the amount of soluble collagen. In the rat this results in inhibition of normal healing and also a decrease in tensile strength of intact skin. In man this may be the cause of increased skin friability at sites especially subject to pressure or trauma, such as shoulders, elbows, knees, toes, and buttocks. Extravasations of blood may occur and may appear as purpuric areas, with external bleeding if the skin is broken, or as vesicles containing dark blood. Neither type is progressive. There is no apparent association with bleeding elsewhere in the body and no associated coagulation defect has been found. Therapy with penicillamine may be continued in the presence of these lesions. They may not recur if dosage is reduced. Other reported effects probably due to the action of penicillamine on collagen are excessive wrinkling of the skin and development of small, white papules at venipuncture and surgical sites.
The effects of penicillamine on collagen and elastin make it advisable to consider a reduction in dosage to 250 mg/day, when surgery is contemplated. Reinstitution of full therapy should be delayed until wound healing is complete.
Carcinogenesis, Mutagenesis, Impairment of Fertility: Long-term animal carcinogenicity studies have not been done with penicillamine. There is a report that five of ten autoimmune disease-prone NZB hybrid mice developed lymphocytic leukemia after 6 months' intraperitoneal treatment with a dose of 400 mg/kg penicillamine 5 days per week.
Penicillamine is directly mutagenic to S. typhimurium strain TA92 in the Ames test; mutagenicity is enhanced by kidney postmitochondrial subcellular fraction 9. Penicillamine does not induce gene mutations in Chinese hamster V79 cells.
Penicillamine induces sister-chromatid exchanges and chromosome aberrations in cultivated mammalian cells. No studies on the effect of penicillamine on fertility are available.
Effects on ability to drive and use machine: Not known. Dizziness has been reported with undefined frequency.
Use in Elderly: Clinical studies of penicillamine are limited in subjects aged 65 and over, they did not include sufficient numbers of elderly subjects aged 65 and over to adequately determine whether they respond differently from younger subjects. Review of reported clinical trials with penicillamine in the elderly suggest greater risk than in younger patients for overall skin rash and abnormality of taste. In general, dose selection for an elderly patient should be cautious, starting at the low end of the dosing range, reflecting the greater frequency of decreased hepatic, renal or cardiac function, and of concomitant disease or other drugs.
This drug is known to be substantially excreted by the kidney, and the risk of toxic reactions to this drug may be greater in patients with impaired renal function. Because elderly patients are more likely to have decreased renal function, care should be taken in dose selection, and careful monitoring of renal function is recommended.
Use In Pregnancy & Lactation
Pregnancy: Pregnancy Category D. Penicillamine can cause fetal harm when administered to a pregnant woman. Penicillamine has been shown to be teratogenic in rats when given in doses 6 times higher than the highest dose recommended for human use. Skeletal defects, cleft palates and fetal toxicity (resorptions) have been reported.
There are no controlled studies on the use of penicillamine in pregnant women. Although normal outcomes have been reported, characteristic congenital cutis laxa and associated birth defects have been reported in infants born of mothers who received therapy with penicillamine during pregnancy. Penicillamine should be used in women of childbearing potential only when the expected benefits outweigh the possible hazards. Women on therapy with penicillamine who are of childbearing potential should be apprised of this risk, advised to report promptly any missed menstrual periods or other indications of possible pregnancy, and followed closely for early recognition of pregnancy. If this drug is used during pregnancy, or if the patient becomes pregnant while taking this drug, the patient should be apprised of the potential hazard to the fetus.
Wilson's Disease: Reported experience shows that continued treatment with penicillamine throughout pregnancy protects the mother against relapse of the Wilson's disease, and that discontinuation of penicillamine has deleterious effects on the mother, which may be fatal.
Cystinuria: If possible, penicillamine should not be given during pregnancy to women with cystinuria. There are reports of women with cystinuria on therapy with penicillamine who gave birth to infants with generalized connective tissue defects who died following abdominal surgery. If stones continue to form in these patients, the benefits of therapy to the mother must be evaluated against the risk to the fetus.
Rheumatoid Arthritis: Penicillamine should not be administered to rheumatoid arthritis patients who are pregnant and should be discontinued promptly in patients in whom pregnancy is suspected or diagnosed.
There is a report that a woman with rheumatoid arthritis treated with less than one gram a day of penicillamine during pregnancy gave birth (cesarean delivery) to an infant with growth retardation, flattened face with broad nasal bridge, low set ears, short neck with loose skin folds, and unusually lax body skin.
Labor and delivery: No data available.
Nursing mothers: see Contraindication.
Adverse Reactions
Penicillamine is a drug with a high incidence of untoward reactions, some of which are potentially fatal. Therefore, it is mandatory that patients receiving penicillamine therapy remain under close medical supervision throughout the period of drug administration. (See Precautions.)
The most common side-effects are thrombocytopenia and proteinuria.
Thrombocytopenia occurs commonly. It may occur any time during treatment and is usually reversible. Proteinuria occurs in up to 30% of patients and is partially dose-related (see Precautions).
Adverse reactions are ranked under heading of frequency, the most frequent first, using the following convention: Very common (>1/10), Common (1/100, <1/10), Uncommon (1/1000, <1/100), Rare (1/10,000, < 1/1000), Very rare (<1/10,000), including isolated reports. Not known (where no valid estimate of the incidence has been derived).
Blood and lymphatic system disorders: Common: Thrombocytopenia.
Not known: Neutropenia, agranulocytosis, aplastic anaemia, haemolytic anaemia, leucopoenia, sideroblastic anemia, thrombotic thrombocytopenic purpura, red cell aplasia, monocytosis, leukocytosis, eosinophilia, thrombocytosis.
Immune system disorders: Rare: Allergic reactions including hypersensitivity.
Not known: Drug eruptions which may be accompanied by fever, arthralgia, or lymphadenopathy have occurred.
Metabolism and nutrition disorders: Not known: Anorexia.
Psychiatric disorders: Not known: Confusion.
Nervous system disorders: Not known: Loss of taste, headache, dizziness, tinnitus, optic neuritis and peripheral sensory and motor neuropathies (including polyradiculoneuropathy, i.e. Guillain-Barré syndrome), muscular weakness (with or without peripheral neuropathies), visual and psychic disturbances; mental disorders; agitation, anxiety.
Eye disorders: Not known: Abnormal vision.
Ear and labyrinth disorders: Rare: Deafness.
Vascular disorders: Not known: Pulmonary haemorrhage.
Respiratory, thoracic and mediastinal disorders: Not known: Dyspnoea, pleural effusion, alveolitis, pulmonary fibrosis, bronchiolitis, pneumonitis.
Gastrointestinal disorders: Rare: Mouth ulceration, stomatitis, glossitis.
Not known: Pancreatitis, nausea, vomiting, diarrhoea, epigastric pain, blunting, diminution cheilosis, gingivostomatitis.
Hepatobiliary disorders: Not known: Cholestatic jaundice.
Skin and subcutaneous tissue disorders: Rare: Alopecia, pseudoxanthoma elasticum, elastosis perforans, skin laxity.
Not known: Rash, urticarial reactions, epidermolysis bullosa, penicillamine dermopathy, dermatomyositis, pemphigus, Stevens-Johnson syndrome, pruritus, exfoliative dermatitis.
Musculoskeletal, connective tissue and bone disorders: Not known: Drug induced lupus erythamatosus, myasthenia gravis, polymyositis, rheumatoid arthritis, dystonia.
Renal and urinary disorders: Very common: Proteinuria.
Rare: Haematuria.
Not known: Nephrotic syndrome, glomerulonephritis, Goodpasture's syndrome.
Reproductive system and breast disorders: Rare: Breast enlargement.
General disorders and administration site conditions: Not known: Fever.
Note: Deaths from agranulocytosis and aplastic anaemia have occurred Nausea, anorexia, fever, rash, vomiting, diarrhoea, headaches, dizziness, abnormal vision and confusion may occur early in therapy especially when full doses are given from the start.
Penicillamine may cause allergic reactions such as urticaria and erythema accompanied by hyperpyrexia. Transient rashes and fever may occur early in therapy; if persistent, antihistamines or temporary withdrawal of treatment with or without a short course of steroids may be necessary. Penicillamine may be re-introduced at a lower dosage. If steroids are given, penicillamine should be reintroduced before steroid withdrawal. Urticarial reactions have been reported (see Precautions).
Reversible loss of taste may occur (See Precautions).
Haematuria may occur rarely, (see Precautions).
A late rash, described as "epidermolysis bullosa" and "penicillamine dermopathy" may occur, after several months or years of therapy and may necessitate discontinuation of treatment.
Breast enlargement has been reported as a rare complication of penicillamine therapy in both women and men (see Precautions).
Neutropenia may occur at any time during treatment and is usually reversible.
Others: Adverse reactions that have been reported rarely include thrombophlebitis; lichen planus; polymyositis; mammary hyperplasia; toxic epidermal necrolysis; anetoderma (cutaneous macular atrophy), thyroiditis. Vasculitis, including fatal renal vasculitis, has also been reported.
Increased skin friability, excessive wrinkling of skin, and development of small white papules at venipuncture and surgical sites have been reported; yellow nail syndrome. Iron deficiency may occur in menstruating women.
The development of septic arthritis in patients with rheumatoid arthritis has been linked to the use of DMARDS, including penicillamine.
Some patients may develop a migratory polyarthralgia, often with objective synovitis.
Deterioration of the neurological symptoms of Wilson's disease (dystonia, rigidity, tremor, dysarthria) have been reported following introduction of penicillamine in patients treated for this condition. This may be a consequence of mobilisation and redistribution of copper from the liver to the brain.
Drug Interactions
Drug-Drug Interactions: Antacids: Concomitant oral antacids should not be given within 2 hours of taking penicillamine as oral absorption of penicillamine may be reduced.
Digoxin: Concomitant digoxin should not be given within 2 hours of taking penicillamine as oral absorption of digoxin may be reduced.
Gold therapy, antimalarials, immunosuppressive (except glucocorticoids) or cytotoxic drugs, clozapine, oxyphenbutazone or phenylbutazone: Pencillamine should not be used in patients who are receiving concurrent gold therapy, antimalarials, immunosuppressive or cytotoxic drugs, clozapine, oxyphenbutazone or phenylbutazone since these drugs have a propensity to cause similar serious haematologic and/or renal adverse reactions.
Iron Salts: Concomitant oral iron should not be given within 2 hours of taking penicillamine as oral absorption of penicillamine may be reduced. Only oral iron salts are a concern. Exceptions: Ferric Gluconate; Ferumoxytol; Iron Dextran Complex; Iron Sucrose.
NSAIDs and Nephrotoxic drugs: Concomitant use of NSAIDs (except topical) and other nephrotoxic drugs may increase the risk of renal damage.
Levodopa: Coadministration with levodopa may result in elevated levodopa levels.
Pyridoxine: vitamin B6 excretion can be increased during the administration of penicillamine, possibly causing anemia or peripheral neuritis. Pyridoxine dosages may need to be increased during concomitant administration of penicillamine.
Zinc: penicillamine reduces absorption of zinc , also absorption of penicillamine reduced by zinc.
Drug-Food/Ethanol Interactions: Ethanol: Management: Avoid or limit ethanol.
Food: Penicillamine serum levels may be decreased if taken with food. Management: Administer on an empty stomach 1 hour before or 2 hours after meals and at least 1 hour apart from other drugs, milk, antacids, and zinc- or iron-containing products. Certain disease states require further diet adjustment. Limit intake of vitamin A.
Drug-Laboratory Interactions: Penicillamine may cause alteration of the biodistribution of technetium Tc-99m gluceptate.
Caution For Usage
Incompatibilities: Not applicable.
Storage
Shelf-Life: 2 years.
Store at a temperature not exceeding 30°C. Protect from light & moisture.
ATC Classification
M01CC01 - penicillamine ; Belongs to the class of penicillamine and similar antirheumatic agents.
Presentation/Packing
Cap 250 mg (white to off-white powder in white hard gelatin capsule no.1 printed in black ink with "GPO" on cap and "OP01" on body) x 10 x 10's.
Register or sign in to continue
Asia's one-stop resource for medical news, clinical reference and education
Sign up for free
Already a member? Sign in