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ALERT: U.S. Boxed Warning
The FDA-approved labeling includes a boxed warning. See Warnings/Precautions section for a concise summary of this information. For verbatim wording of the boxed warning, consult the product labeling or www.fda.gov.
Pronunciation
(pen i SIL a meen)
Generic Available (U.S.)
No
Index Terms
Brand Names: U.S.
Brand Names: Canada
Pharmacologic Category
Use: Labeled Indications
Treatment of Wilson's disease, cystinuria; adjunctive treatment of severe, active rheumatoid arthritis
Canadian labeling: Additional use (not in U.S. labeling): Treatment of chronic lead poisoning
Pregnancy Risk Factor
D
Pregnancy Considerations
Birth defects, including congenital cutix laxa and associated defects, have been reported in infants following penicillamine exposure during pregnancy. Use for the treatment of rheumatoid arthritis during pregnancy is contraindicated. Use for the treatment of cystinuria only if the possible benefits to the mother outweigh the potential risks to the fetus. Continued treatment of Wilson's disease during pregnancy protects the mother against relapse. Discontinuation has detrimental maternal and fetal effects. Daily dosage should be limited to 750 mg. For planned cesarean section, reduce dose to 250 mg/day for the last 6 weeks of pregnancy, and continue at this dosage until wound healing is complete.
Lactation
Excretion in breast milk unknown/contraindicated
Contraindications
Renal insufficiency (in patients with rheumatoid arthritis); patients with previous penicillamine-related aplastic anemia or agranulocytosis; breast-feeding; pregnancy (in patients with rheumatoid arthritis)
Canadian labeling: Additional contraindications (not in U.S. labeling): Hypersensitivity to penicillamine or any component of the formulation; use in patients with chronic lead poisoning who have radiographic evidence of lead-containing substances in the GI tract; pregnancy (in patients with chronic lead poisoning); concomitant use with gold therapy, antimalarial or cytotoxic drugs, oxyphenbutazone or phenylbutazone
Warnings/Precautions
Boxed warnings:
• Experienced physician: See “Other warnings/precautions” below.
• Toxicity symptoms: See “Concerns related to adverse effects” below.
Concerns related to adverse effects:
• Allergic reactions: Approximately 33% of patients will experience an allergic reaction. Rash may occur early (more commonly) or late in therapy; early-onset rash typically resolves within days of discontinuation of therapy and does not recur upon rechallenge with reduced dose; discontinue therapy for late-onset rash (eg, after >6 months) and do not rechallenge; rash typically recurs with rechallenge. Discontinue therapy for skin reactions accompanied by lymphadenopathy, fever, arthralgia, or other allergic reactions.
• Bronchiolitis obliterans: Has been reported rarely with use; instruct patients to report pulmonary symptoms (eg, unexplained wheezing or cough, exertional dyspnea) and consider pulmonary function testing in such patients.
• Dermatologic: Penicillamine increases the amount of soluble collagen; may increase skin friability, particularly at sites subject to pressure or trauma (eg, knees, elbows shoulders). Purpuric areas with localized bleeding (if skin is broken) or vesicles with dark blood may be observed. Effects are considered localized and do not necessitate discontinuation of therapy; may not recur with dose reduction. Macular cutaneous eruptions are sometimes observed in conjunction with drug fever, usually 2 -3 weeks after therapy initiation. Dose reduction may be considered prior to surgical procedures. May resume normal recommended dosing postoperatively once wound healing is complete.
• Drug fever: Drug fever may be observed, usually 2-3 weeks after therapy initiation. Discontinue use in patients with rheumatoid arthritis, Wilson's disease, or cystinuria who develop a marked febrile response. Consider alternative therapy for patients with rheumatoid arthritis due to high incidence of fever reoccurrence with penicillamine rechallenge. May resume therapy at a reduced dose in Wilson's disease or cystinuria upon resolution of fever; dose should then be gradually titrated to effective dose.
• Gastrointestinal: Taste alteration may occur (rare in Wilson's disease); usually self-limited with continued therapy, however may last ≥2 months and result in total loss of taste. Oral ulceration (eg, stomatitis) may occur; typically recurs on rechallenge but often resolves with dose reduction. Other dose-related lesions (eg, glossitis, gingivostomatitis) have been observed with use and may require therapy discontinuation.
• Goodpasture's syndrome: Penicillamine has been associated with fatalities due to Goodpasture's syndrome. Discontinue therapy immediately in patients with abnormal urinary findings in association with hemoptysis and pulmonary infiltrates on chest x-ray.
• Hematologic toxicities: Penicillamine has been associated with fatalities due to agranulocytosis, aplastic anemia, and thrombocytopenia. Discontinue therapy for WBC <3500/mm3. Withhold therapy at least temporarily for platelet counts <100,000/mm3 or a progressive fall in WBC or platelets in 3 successive determinations, even though values may remain within the normal range. Monitor for signs/symptoms of leukopenia and thrombocytopenia.
• Hepatotoxicity: Monitor liver function tests periodically due to rare reports of intrahepatic cholestasis or toxic hepatitis. More frequent monitoring is required during the first year of therapy in patients with Wilson's disease.
• Lupus erythematosus-like syndrome: May be observed in some patients; positive antinuclear antibody (ANA) test does not necessitate therapy discontinuation but should alert clinicians of possible future development of lupus erythematosus-like syndrome.
• Pemphigus: May occur early or late in therapy; discontinue use with suspicion of pemphigus. May treat with high-dose corticosteroids alone, or in conjunction with an immunosuppressant; treatment duration can range from weeks to >1 year.
• Penicillin cross-sensitivity: Patients with a penicillin allergy may theoretically have cross-sensitivity to penicillamine; however, the possibility has been eliminated now that penicillamine is produced synthetically and no longer contains trace amounts of penicillin.
• Proteinuria/hematuria: Proteinuria or hematuria may develop; monitor for membranous glomerulopathy which can lead to nephrotic syndrome. In rheumatoid arthritis patients, discontinue if gross hematuria or persistent microscopic hematuria develop and discontinue therapy or reduce dose for proteinuria that is either >1 g/day or progressively increasing. Dose reduction may lead to resolution of proteinuria.
• Myasthenia gravis: Penicillamine has been associated with myasthenic syndrome, and in some cases, progression to myasthenia gravis. Resolution of symptoms has been observed in most cases following discontinuation of therapy.
• Toxicity symptoms: [U.S. Boxed Warning]: Patients should be warned to report promptly any symptoms suggesting toxicity (fever, sore throat, chills, bruising, or bleeding); toxicity may be dose related.
Disease-related concerns:
• Cystinuria: Continue treatment on a daily basis; interruptions of even a few days have been followed by hypersensitivity with reinstitution of therapy. Patients should receive pyridoxine supplementation (25 mg/day).
• Lead poisoning: Investigate, identify, and remove sources of lead exposure and confirm lead-containing substances are absent from the GI tract prior to initiating therapy. Do not permit patients to re-enter the contaminated environment until lead abatement has been completed. Penicillamine is considered to be a third-line agent for the treatment of lead poisoning in children due to the overall toxicity associated with its use (AAP, 2005; Chandran, 2010); penicillamine should only be used when unacceptable reactions have occurred with edetate CALCIUM disodium and succimer. Primary care providers should consult experts in the chemotherapy of lead toxicity before using chelation drug therapy.
• Rheumatoid arthritis: Patients with rheumatoid arthritis and impaired nutrition should receive pyridoxine supplementation (25 mg/day).
• Wilson's disease: Continue treatment on a daily basis; interruptions of even a few days have been followed by hypersensitivity with reinstitution of therapy. Worsening of neurologic symptoms may occur during initiation of therapy however discontinuation of therapy is not recommended; may consider concomitant use of short term dimercaprol in patients whose symptoms continue to worsen 1 month following therapy initiation. Patients should receive pyridoxine supplementation (25-50 mg/day; Roberts, 2008).
Concurrent drug therapy issues:
• Hematopoietic-depressant drugs: Use with caution in patients on other hematopoietic-depressant drugs (eg, gold, immunosuppressants, antimalarials, phenylbutazone; Canadian labeling contraindicates concomitant use with these agents); hematologic and renal adverse reactions are similar.
Special populations:
• Elderly: Use with caution in the elderly; may be more susceptible to skin rash and/or taste alterations.
Other warnings/precautions:
• Experienced physician: [U.S. Boxed Warning]: Should be administered under the close supervision of a physician familiar with the toxicity and dosage considerations.
Adverse Reactions
Frequency not always defined and may vary by indication.
Cardiovascular: Vasculitis
Central nervous system: Anxiety, agitation, fever, Guillain-Barré syndrome, hyperpyrexia, psychiatric disturbances, worsening neurologic symptoms
Dermatologic: Alopecia, cheilosis, dermatomyositis, drug eruptions, exfoliative dermatitis, lichen planus, pemphigus, pruritus, rash (early and late: 5%), skin friability increased, toxic epidermal necrolysis, urticaria, wrinkling (excessive), yellow nail syndrome
Endocrine & metabolic: Hypoglycemia, thyroiditis
Gastrointestinal: Diarrhea (17%), taste alteration (12%), anorexia, epigastric pain, gingivostomatitis, glossitis, nausea, oral ulcerations, pancreatitis, peptic ulcer reactivation, vomiting
Hematologic: Thrombocytopenia (4%), leukopenia (2%), agranulocytosis, aplastic anemia, eosinophilia, hemolytic anemia, leukocytosis, monocytosis, red cell aplasia, sideroblastic anemia, thrombotic thrombocytopenia purpura, thrombocytosis
Hepatic: Alkaline phosphatase increased, hepatic failure, intrahepatic cholestasis, toxic hepatitis
Local: Thrombophlebitis, white papules at venipuncture and surgical sites
Neuromuscular & skeletal: Arthralgia, dystonia, myasthenia gravis, muscle weakness, neuropathies, polyarthralgia (migratory, often with objective synovitis), polymyositis
Ocular: Diplopia, extraocular muscle weakness, optic neuritis, ptosis, visual disturbances
Otic: Tinnitus
Renal: Proteinuria (6%), Goodpasture's syndrome, hematuria, nephrotic syndrome, renal failure, renal vasculitis
Respiratory: Asthma, interstitial pneumonitis, pulmonary fibrosis, obliterative bronchiolitis
Miscellaneous: Allergic alveolitis, anetoderma, elastosis perforans serpiginosa, lupus-like syndrome, lactic dehydrogenase increased, lymphadenopathy, mammary hyperplasia, positive ANA test
Metabolism/Transport Effects
None known.
Drug Interactions
Antacids: May decrease the serum concentration of PenicillAMINE. Risk D: Consider therapy modification
Digoxin: PenicillAMINE may decrease the serum concentration of Digoxin. Risk C: Monitor therapy
Iron Salts: May decrease the absorption of PenicillAMINE. Only oral iron salts are a concern. Exceptions: Ferric Gluconate; Ferumoxytol; Iron Dextran Complex; Iron Sucrose. Risk D: Consider therapy modification
Ethanol/Nutrition/Herb 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.
Storage
Store in tight, well-closed containers.
Mechanism of Action
Chelates with lead, copper, mercury and other heavy metals to form stable, soluble complexes that are excreted in urine; depresses circulating IgM rheumatoid factor, depresses T-cell but not B-cell activity; combines with cystine to form a compound which is more soluble, thus cystine calculi are prevented
Pharmacodynamics/Kinetics
Onset of action: Rheumatoid arthritis: 2-3 months; Wilson's disease: 1-3 months
Absorption: Rapid but incomplete
Protein binding: >80% to albumin and ceruloplasmin
Metabolism: Hepatic (small amounts metabolized to s-methyl-d-penicillamine)
Bioavailability: 40% to 70%; reduced by food, antacids, and iron
Half-life elimination: 1.7-7 hours (Roberts, 2008)
Time to peak, serum: 1-3 hours
Excretion: Urine (primarily as disulfides)
Dosage
Oral: Note: Dose reduction to 250 mg/day may be considered prior to surgical procedures. May resume normal recommended dosing postoperatively once wound healing is complete.
Cystinuria: Note: Adjust dose to limit cystine excretion to 100-200 mg/day (<100 mg/day with history of stone formation)
Children: 30 mg/kg/day in 4 divided doses
Adults: 1-4 g/day in 4 divided doses; usual dose: 2 g/day; initiation of therapy at 250 mg/day with gradual upward titration may reduce the risk of unwanted effects
Lead poisoning:
Canadian labeling:
Children: 30-40 mg/kg/day or 600-750 mg/m2/day in 1-2 divided doses (maximum dose: 750 mg/day); treat until blood lead concentrations <40 mcg/dL for 2 consecutive months and at least 1 of the following: Decrease in erythrocyte protoporphyrin level to <3-5 times the average normal level or the excretion of coproporphyrin or delta-aminolevulinic acid decreases to the upper limit of normal. Note: Manufacturer labeling recommends initiating therapy only in children who meet the following criteria: Asymptomatic, blood lead concentrations of 50-80 mcg/dL, erythrocyte protoporphyrin level >400-500 mcg/dL erythrocytes, excessive excretion of delta-aminolevulinic acid and/or coproporphyrin.
Adults: 900-1500 mg/day in 3 divided doses for 1-2 weeks, then 750 mg/day in divided doses until blood lead concentrations <60 mcg/dL or urinary lead excretion <500 mcg/L for 2 consecutive months
Alternate recommendations (unlabeled dosing): Note: The American Academy of Pediatrics (AAP) considers penicillamine a third-line agent for the management of lead poisoning (AAP, 2005; Chandran, 2010): Children: 10-15 mg/kg/day for 4-12 weeks (Chandran, 2010). Note: The CDC recommends chelation treatment when blood lead concentrations are >45 mcg/dL (CDC, 2002). Children with blood lead concentrations >70 mcg/dL or symptomatic lead poisoning should be treated with parenteral agents (AAP, 2005).
Rheumatoid arthritis:
Children (unlabeled use): Initial: 3 mg/kg/day (≤250 mg/day) for 3 months, then 6 mg/kg/day (≤500 mg/day) in divided doses twice daily for 3 months to a maximum of 10 mg/kg/day in 3-4 divided doses; maximum dose: 750 mg/day (Rosenberg, 1989)
Adults: Initial: 125-250 mg/day, may increase dose by 125-250 mg/day at 1- to 3-month intervals up to 1-1.5 g/day; discontinue in patients failing to improve after 3-4 months at these doses
Elderly: Therapy should be initiated at low end of dosing range and titrated upward cautiously.
Wilson's disease: Note: Dose that results in an initial 24-hour urinary copper excretion >2 mg/day should be continued for ~3 months; maintenance dose defined by amount resulting in <10 mcg serum free copper/dL.
Manufacturer labeling recommendations:
Adults: 750-1500 mg/day in divided doses; maximum dose: 2000 mg/day. Note: Limit daily dose to 750 mg/day (U.S. labeling) or 1000 mg/day (Canadian labeling) in pregnant women; if planned caesarian, limit dose to 250 mg/day during the last 6 weeks of pregnancy and postoperatively until wound healing is complete.
Elderly: Therapy should be initiated at low end of dosing range and titrated upward cautiously.
Alternate recommendations (unlabeled dosing): American Association for the Study of Liver Diseases (AASLD) guidelines (Roberts, 2008):
Children: 20 mg/kg/day in 2-3 divided doses, round off to the nearest 250 mg dose
Adults: To increase tolerability, therapy may be initiated at 250-500 mg/day then titrated upward in 250 mg increments every 4-7 days; usual maintenance dose: 750-1000 mg/day in 2 divided doses; maximum: 1000-1500 mg/day in 2-4 divided doses
Dosing adjustment in renal impairment:
Manufacturer labeling recommendations: No dosage adjustment provided in manufacturer's labeling; however, the manufacturer labeling does suggest a cautious approach to dosing as this drug undergoes mainly renal elimination.
Alternate recommendations:
Clcr <50 mL/minute: Avoid use (Aronoff, 2007)
Hemodialysis: Dialyzable; Administer 33% of usual dose (Aronoff, 2007); a dosing decrease from 250 mg/day to 250 mg 3 times/week after dialysis has been suggested in the treatment of rheumatoid arthritis (Swarup, 2004).
Dosage adjustment in hepatic impairment: No dosage adjustment provided in manufacturer's labeling; however, only a small fraction is metabolized hepatically.
Administration: Oral
Doses ≤ 500 mg may be administered as single dose; doses >500 mg should be administered in divided doses. For patients who cannot swallow, contents of capsules may be administered in 15-30 mL of chilled puréed fruit or fruit juice within 5 minutes of administration. 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. Canadian labeling recommends administering at least 2 hours before meals in patients with lead poisoning.
Cystinuria: If administering 4 equal doses is not feasible, administer the larger dose at bedtime.
Monitoring Parameters
Urinalysis, CBC with differential, platelet count, skin, lymph nodes, and body temperature twice weekly during the first month of therapy, then every 2 weeks for 5 months, then monthly; LFTs every 6 months; signs/symptoms of hypersensitivity
Cystinuria: Urinary cystine, annual X-ray for renal stones
Lead poisoning: Serum lead concentration (baseline and 7-21 days after completing chelation therapy); hemoglobin or hematocrit, iron status, free erythrocyte protoporphyrin or zinc protoporphyrin; neurodevelopmental changes
Wilson's disease: Serum non-ceruloplasmin bound copper, 24-hour urinary copper excretion, LFTs every 3 months (at least) during the first year of treatment; periodic ophthalmic exam
Urinalysis: Monitor for proteinuria and hematuria. A quantitative 24-hour urine protein at 1- to 2-week intervals initially (first 2-3 months) is recommended if proteinuria develops.
Reference Range
Wilson's disease: 24-hour urinary copper excretion: 200-500 mcg (3-8 micromoles)/day
Dietary Considerations
Should be taken at least 1 hour before or 2 hours after meals on an empty stomach (Note: Canadian labeling recommends administration at least 2 hours before meals in patients with lead poisoning). Pyridoxine supplementation is recommended. Patients with Wilson's disease should receive 25-50 mg/day of pyridoxine (Roberts, 2008); a multivitamin (without copper) may also be considered. Patients with cystinuria or patients with rheumatoid arthritis and impaired nutritional intake should receive 25 mg/day of pyridoxine. For Wilson's disease, decrease copper in diet to <1-2 mg/day and omit chocolate, nuts, shellfish, mushrooms, liver, raisins, broccoli, copper-enriched cereal, multivitamins with copper, and molasses. May consider short courses of iron supplementation if dietary modifications (eg, low copper diet in Wilson's disease, low methionine diet in cystinuria) results in iron deficiency; pediatric patients and menstruating women may be particularly susceptible to iron deficiency. Allow 2 hours between administration of iron supplementation and penicillamine as iron may decrease drug absorption. For cystinuria, increase daily fluid intake including 1 pint (~500 mL) of fluid prior to bedtime and 1 additional pint during the night. For lead poisoning, decrease calcium in diet.
Patient Education
Capsules may be opened and contents mixed in 15-30 mL of chilled fruit juice or puree; do not take with milk or milk products. Avoid or limit alcohol and excess intake of vitamin A. It is preferable to take penicillamine on empty stomach, 1 hour before or 2 hours after meals. Maintain adequate hydration, unless instructed to restrict fluid intake. For Wilson's disease, avoid chocolate, shellfish, nuts, mushrooms, liver, broccoli, and molasses. For lead poisoning, decrease dietary calcium. For cystinuria, take with large amounts of water. You may experience anorexia, taste alteration, nausea, vomiting, or diarrhea. Report persistent fever or chills; unhealed sores; white spots or sores in mouth or vaginal area; extreme fatigue; signs of infection; breathlessness, respiratory difficulty, or unusual cough; unusual bruising/bleeding; blood in urine, stool, mouth, or vomitus; swollen face or extremities; skin rash or itching; muscle pain or cramping; or pain on urination.
Geriatric Considerations
Close monitoring of elderly is necessary; since steady-state serum/tissue concentrations rise slowly, “go slow” with dose increase intervals; steady-state concentrations decline slowly after discontinuation suggesting extensive tissue distribution. Skin rashes and taste abnormalities occur more frequently in the elderly than in young adults; leukopenia, thrombocytopenia, and proteinuria occur with equal frequency in both younger adults and elderly. Since toxicity may be dose related, it is recommended not to exceed 750 mg/day in the elderly.
Dental Health: Effects on Dental Treatment
Key adverse event(s) related to dental treatment: Oral ulcerations, glossitis, gingivostomatitis, and taste alteration.
Dental Health: Vasoconstrictor/Local Anesthetic Precautions
No information available to require special precautions
Mental Health: Effects on Mental Status
May cause anxiety, agitation, visual and psychic disturbances
Mental Health: Effects on Psychiatric Treatment
May cause aplastic anemia; use caution with clozapine and carbamazepine. May cause dystonia. May cause thrombocytopenia; monitor in patients receiving valproate.
Nursing: Physical Assessment/Monitoring
Monitor for an allergic reaction. Teach patient actions to take if an allergic reaction should occur.
Dosage Forms
Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Capsule, oral:
Cuprimine®: 250 mg
Tablet, oral:
Depen®: 250 mg [scored]
Pricing: U.S. (www.drugstore.com)
Capsules (Cuprimine)
250 mg (30): $209.08
Tablets (Depen Titratabs)
250 mg (30): $146.99
Extemporaneously Prepared
A 50 mg/mL oral suspension may be made with capsules. Mix the contents of sixty 250 mg capsules with 3 g carboxymethylcellulose, 150 g sucrose, 300 mg citric acid, and parabens (methylparaben 120 mg, propylparaben 12 mg). Add quantity of propylene glycol sufficient to make 100 mL, then add quantity of purified water sufficient to make 300 mL. Cherry flavor may be added. Label "shake well" and "refrigerate". Stable for 30 days refrigerated.
DeCastro FJ, Jaeger RQ, and Rolfe UT, "An Extemporaneously Prepared Penicillamine Suspension Used to Treat Lead Intoxication," Hosp Pharm, 1977, 2:446-8.
References
Adelman HM, Winters PR, Mahan CS, et al, “D-Penicillamine-Induced Myasthenia Gravis; Diagnosis Obscured by Coexisting Chronic Obstructive Pulmonary Disease,” Am J Med Sci, 1995, 309(4):191-3.
Albert C, Aynard B, Terbe V, et al, “D-Penicillamine Induced Rapidly Progressive Glomerulonephritis With Membranous Nephropathy in a Patient With Rheumatoid Arthritis,” Clin Exp Rheumatol, 1994, 12(Suppl 11):108.
American Academy of Pediatrics Committee on Environmental Health, “Lead Exposure in Children: Prevention, Detection, and Management,” Pediatrics, 2005, 116(4):1036-46.
Andonopoulos AP, Terzis E, and Tsibri E, “D-Penicillamine Induced Myasthenia Gravis in Rheumatoid Arthritis: An Unpredictable Common Occurrence?” Clin Rheumatol, 1994, 13(4):586-8.
Aronoff GR, Bennett WM, Berns JS, et al, Drug Prescribing in Renal Failure: Dosing Guidelines for Adults and Children, 5th ed. Philadelphia, PA: American College of Physicians; 2007, p 104.
Aronow R and Fleschmann LE, “Mercury Poisoning in Children,” Clin Pediatr (Phila), 1976, 15(10):936-45.
Centers for Disease Control and Prevention (CDC), Guidelines for the Identification and Management of Lead Exposure in Pregnant and Lactating Women, Atlanta: CDC; 2010.
Centers for Disease Control and Prevention (CDC), “Interpreting and Managing Blood Lead Levels <10 microg/dL in Children and Reducing Childhood Exposures to Lead: Recommendations of CDC's Advisory Committee on Childhood Lead Poisoning Prevention,” MMWR Recomm Rep, 2007, 56(RR-8):1-16.
Centers for Disease Control and Prevention (CDC), Managing Elevated Blood Lead Levels Among Young Children: Recommendations from the Advisory Committee on Childhood Lead Poisoning Prevention, Atlanta: CDC; 2002.
Chandran L and Cataldo R, “Lead Poisoning: Basics and New Developments,” Pediatr Rev, 2010, 31(10):399-406.
Cullen NM, Wolf LR, and St Clair D, “Pediatric Arsenic Ingestion,” Am J Emerg Med, 1995, 13(4):432-5.
Gracia RC and Snodgrass WR, “Lead Toxicity and Chelation Therapy," Am J Health Syst Pharm, 2007, 64(1):45-53.
Hryhorczuk DO, Meyers L, and Chen G, “Treatment of Mercury Intoxication in a Dentist With N-Acetyl-D,L-Penicillamine,” J Toxicol Clin Toxicol, 1982, 19(4):401-8.
Kandola L, Swannell AJ, and Hunter A, “Acquired Sideroblastic Anaemia Associated With Penicillamine Therapy for Rheumatoid Arthritis,” Ann Rheum Dis, 1995, 54(6):529-30.
Kosnett MJ, Wedeen RP, Rothenberg SJ, et al, “Recommendations for Medical Management of Adult Lead Exposure,” Environ Health Perspect, 2007, 115(3):463-71.
Lifshitz M and Levy J, “Efficacy of D-Penicillamine in Reducing Lead Concentrations in Children: A Prospective, Uncontrolled Study,” J Pharm Technol, 2000, 16(3):98-101.
Lyle WH, “Penicillamine in Metal Poisoning,” J Rheumatol Suppl, 1981, 7:96-9.
Multz CV, “Cholestatic Hepatitis Caused by Penicillamine,” JAMA, 1981, 246(6):674-5.
Negishi M, Matsuda A, Kaga S, et al, “A Case of Agranulocytosis Which Occurred Several Hours After the Readministration of D-Penicillamine Accompanied by Shivering-Chillness,” Arerugi, 1995, 44(2):96-9.
Oga M, Matsui N, Anai T, et al, “Copper Disposition of the Fetus and Placenta in a Patient With Untreated Wilson's Disease,” Am J Obstet Gynecol, 1993, 169(1):196-8.
Piomelli S, “Childhood Lead Poisoning,” Pediatr Clin North Am, 2002, 49(6):1285-304.
Roberts EA and Schilsky ML, “Diagnosis and Treatment of Wilson Disease: An Update. American Association for Study of Liver Diseases (AASLD),” Hepatology, 2008, 47(6):2089-111.
Rosa FW, “Teratogen Update. Penicillamine,” Teratology, 1986, 33(1):127-31.
Rosenberg AM. “Advanced Drug Therapy for Juvenile Rheumatoid Arthritis,” J Pediatr, 1989, 114(2):171-8.
Shannon M and Townsend MK, “Adverse Effects of Reduced-Dose d-Penicillamine in Children With Mild to Moderate Lead Poisoning,” J Toxicol Clin Toxicol, 1999, 37(5):625.
Smith DB and Gallagher BB, “The Effect of Penicillamine on Seizure Threshold. The Role of Pyridoxine,” Arch Neurol, 1970, 23(1):59-62.
Stein HB, Patterson AC, Offer RC, et al, “Adverse Effects of D-Penicillamine in Rheumatoid Arthritis,” Ann Intern Med, 1980, 92:24-9.
Swarup A, Sachdeva N, and Schumacher Jr HP, “Dosing of Antirheumatic Drugs in Renal Disease and Dialysis,” J Clin Rheumatol, 2004, 10(4):190-204.
“Treatment Guidelines for Lead Exposure in Children. American Academy of Pediatrics Committee on Drugs,” Pediatrics, 1995, 96(1 Pt 1):155-60.
International Brand Names
Lexi-Comp.com
Last full review/revision March 2012
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