Penicillamine


Concise Prescribing Info
Indications/Uses
Listed in Dosage.
Dosage/Direction for Use
Adult : PO Severe active rheumatoid arthritis Initial: 125-250 mg/day for 1 mth then increase by same amount at 4-12 wk intervals. Maintenance: 500-750 mg/day. Discontinue if no response w/in 12 mth. Wilson’s disease 1,500-2,000 mg/day in divided doses. Maintenance: 750-1000 mg/day. Cystinuria Treatment: 1,000-4,000 mg/day in divided doses. Prophylaxis: 500-1,000 mg/day at bedtime. Lead poisoning 1,000-1,500 mg/day in divided doses. Chronic active hepatitis For maintenance after disease is controlled w/ corticosteroids: Initial: 500 mg/day in divided doses. Gradually increase dose over 3 mth to 1,250 mg daily w/ concurrent reduction of corticosteroid dose.
Dosage Details
Oral
Chronic active hepatitis
Adult: For maintenance after disease is controlled w/ corticosteroids: Initially, 500 mg daily in divided doses. Gradually increase dose over 3 mth to 1,250 mg daily w/ concurrent reduction of corticosteroid dose.
Elderly: Not recommended.

Oral
Lead poisoning
Adult: 1,000-1,500 mg daily in divided doses until urinary lead is stable at <0.5 mg daily.
Child: 15-20 mg/kg daily in 2-3 divided doses.
Elderly: 20 mg/kg daily in divided doses until urinary lead is stable at <0.5 mg daily.

Oral
Cystinuria
Adult: Treatment: 1,000-4,000 mg daily in divided doses, adjust to maintain urinary cystine levels not exceeding 200 mg/L. Prophylaxis: 500-1,000 mg daily at bedtime, adjust to maintain urinary cystine levels not exceeding 300 mg/L.
Child: 20-30 mg/kg daily in 2-3 divided doses, adjust to maintain urinary cystine levels not exceeding 200 mg/L.

Oral
Wilson's disease
Adult: 1,500-2,000 mg daily in divided doses, adjust to maintain -ve copper balance. Maintenance: 750-1,000 mg daily.
Child: ≤12 yr 20 mg/kg daily in 2-3 divided doses; >12 yr Maintenance: 750-1,000 mg daily.
Elderly: 20 mg/kg daily in divided doses.

Oral
Rheumatoid arthritis
Adult: For severe active cases: Initially, 125-250 mg daily for 1 mth, increase by same amount at 4-12 wk intervals until remission. Maintenance: 500-750 mg (up to 1,500 mg if required) daily in divided doses. If remission is sustained for 6 mth, dose may be reduced by 125-250 mg at 12 wk intervals. Discontinue if no response w/in 12 mth.
Child: For severe active cases: Initially, 2.5-5 mg/kg daily, increase by same amount at 4 wk intervals for 3-6 mth. Maintenance: 15-20 mg/kg daily.
Elderly: For severe active cases: Initially, ≤125 mg for 1 mth, increase by same amount at 4-12 wk intervals. Max: 1,000 mg daily.
Special Patient Group
Patients to undergo surgery (including pregnant patients w/ Wilson’s disease who are undergoing caesarean section): 250 mg daily 6 wk prior to surgery and post-op until complete wound healing.
Pregnant patients w/ Wilson’s disease: 1 g daily.
Renal Impairment
Moderate to severe: Contraindicated.
Administration
Should be taken on an empty stomach. Take 1 hr before or 2 hr after meals, & at least 1 hr apart from any other drug, food, milk, antacid, Zn- or Fe-containing prep.
Contraindications
Hypersensitivity to penicillamine. History of agranulocytosis, aplastic anaemia or severe thrombocytopenia w/ penicillamine; SLE. Moderate to severe renal impairment. Pregnancy (except in the treatment of Wilson’s disease) and lactation. Concomitant use w/ antimalarials, immunosuppressants, clozapine, gold.
Special Precautions
Patient w/ hypersensitivity to penicillin. Patients undergoing surgery. Mild renal impairment. Elderly, childn. Pregnancy (patients treated w/ Wilson’s disease).
Adverse Reactions
Significant: Oral ulcerations, hypogeusia, worsening of neurological symptoms (e.g. dystonia, rigidity, tremor, dysarthria), breast enlargement, leucopenia, rash w/ or w/o fever, arthralgia and lymphadenopathy (e.g. epidermolysis bullosa); pemphigus foliaceus, pemphigus vulgaris, increased soluble collagen levels (leading to increased skin friability, extravasation, increased wrinkling of the skin and development of small, white papules at venipuncture and surgical sites), Fe deficiency, drug fever w/ or w/o macular cutaneous eruption, lupus erythematosus, intrahepatic cholestasis or toxic hepatitis, allergic reactions. Rarely, cheilosis, glossitis, gingivostomatitis, obliterative bronchiolitis, proteinuria and haematuria may or may not lead to glomerulonephritis, renal failure.
GI: Anorexia, epigastric pain, nausea, vomiting, diarrhoea.
Potentially Fatal: Agranulocytosis, aplastic anaemia, thrombocytopenia, myasthenia syndrome leading to myasthenia gravis (manifested by ptosis, diplopia, weakness of extraocular muscles). Rarely, Goodpasture’s syndrome, renal vasculitis.
MonitoringParameters
Monitor urinalysis, CBC w/ differential, platelet count, skin and lymph nodes reactions and body temp twice wkly for 1 mth, then every 2 wk for 5 mth; LFT every 6 mth; signs and symptoms of hypersensitivity. Monitor urinary cystine and perform annual X-ray for renal stones in patients w/ cystinuria; serum lead conc, Hb or haematocrit, Fe status, free erythrocyte protoporphyrin or zinc protoporphyrin and neurodevelopmental changes in patients w/ lead poisoning; serum non-ceruloplasmin bound copper, 24-hr urinary copper excretion, ophth status in patients w/ Wilson’s disease.
Drug Interactions
Increased risk of renal adverse effects w/ NSAIDs and other nephrotoxic drugs. May decrease the absorption of digoxin. Decreased absorption w/ Fe and other heavy metals. Increases requirement for pyridoxine.
Potentially Fatal: Increased risk of serious renal or haematological adverse effects w/ antimalarials, immunosuppressants, clozapine, gold.
Food Interaction
Decreased absorption w/ food intake.
Action
Description: Penicillamine in rheumatoid arthritis has an unknown mechanism but, it suppresses the disease activity. It also decreases circulating IgM rheumatoid factor and T-cell activity. It interacts w/ cystine to form a more soluble complex thereby reducing urinary concentration of cystine and preventing renal calculi development. It is a chelating agent which aids the removal of heavy-metal ions including copper, lead, arsenic and mercury from the body by forming complexes that are readily excreted by the kidney.
Onset: Rheumatoid arthritis: 2-3 mth; Wilson’s disease: 1-3 mth.
Pharmacokinetics:
Absorption: Rapidly but incompletely absorbed from the GI tract. Decreased absorption w/ food. Time to peak plasma concentration: W/in 1-3 hr.
Distribution: Plasma protein binding: >80% mainly to albumin; binds also to α-globulins, ceruloplasmin, erythrocytes, macrophages.
Metabolism: Metabolised in the liver to S-methyl-D-penicillamine.
Excretion: Via urine (approx 80%, mainly as mixed disulfides; some as penicillamine copper complex and S-methyl-D-penicillamine). Elimination half-life: 1.7-7 hr.
Chemical Structure

Chemical Structure Image
Penicillamine

Source: National Center for Biotechnology Information. PubChem Database. Penicillamine, CID=5852, https://pubchem.ncbi.nlm.nih.gov/compound/Penicillamine (accessed on Jan. 22, 2020)

Storage
Store between 20-25°C.
ATC Classification
M01CC01 - penicillamine ; Belongs to the class of penicillamine and similar antirheumatic agents.
References
Anon. Penicillamine. Lexicomp Online. Hudson, Ohio. Wolters Kluwer Clinical Drug Information, Inc. https://online.lexi.com. Accessed 02/10/2017.

Buckingham R (ed). Penicillamine. Martindale: The Complete Drug Reference [online]. London. Pharmaceutical Press. https://www.medicinescomplete.com. Accessed 02/10/2017.

Cuprimine Capsule (Aton Pharma, Inc.). DailyMed. Source: U.S. National Library of Medicine. https://dailymed.nlm.nih.gov/dailymed/. Accessed 02/10/2017.

Depen Tablet (Meda Pharmaceuticals Inc.). DailyMed. Source: U.S. National Library of Medicine. https://dailymed.nlm.nih.gov/dailymed/. Accessed 02/10/2017.

Joint Formulary Committee. Penicillamine. British National Formulary [online]. London. BMJ Group and Pharmaceutical Press. https://www.medicinescomplete.com. Accessed 02/10/2017.

McEvoy GK, Snow EK, Miller J et al (eds). Penicillamine. AHFS Drug Information (AHFS DI) [online]. American Society of Health-System Pharmacists (ASHP). https://www.medicinescomplete.com. Accessed 02/10/2017.

Disclaimer: This information is independently developed by MIMS based on Penicillamine from various references and is provided for your reference only. Therapeutic uses, prescribing information and product availability may vary between countries. Please refer to MIMS Product Monographs for specific and locally approved prescribing information. Although great effort has been made to ensure content accuracy, MIMS shall not be held responsible or liable for any claims or damages arising from the use or misuse of the information contained herein, its contents or omissions, or otherwise. Copyright © 2020 MIMS. All rights reserved. Powered by MIMS.com
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