Penicillamine has FDA approval as a treatment for Wilson disease and cystinuria. It also is used as an off-label treatment option for lead poisoning in children.
Penicillamine can chelate heavy metals such as lead, copper, and mercury and form a soluble complex that is renally excreted in the urine. It also can combine and form disulfide bonds with cysteine and facilitates the excretion in urine. This helps to prevent the formation of cystine calculi.
In rheumatoid arthritis, it can depress T cell activity.
It has a plasma peak time of 1 to 3 hours and a peak plasma concentration of 1 to 2 mg/L for the 250 mg dose. More than 80% is protein-bound, and it is excreted in the urine.
It usually exists as 250 mg tablets and 125 mg or 250 mg capsules.
Penicillamine should be taken at least 1 hour before meals or 2 hours after meals. Some protocols recommend taking the drug at least 2 hours before meals in cases of lead poisoning. It is also advisable to take the medication at least 1 hour apart from other drugs or zinc-containing products and if the patient is consuming milk or antacids. It is a strong recommendation to supplement the patient with pyridoxine. In patients with Wilson disease, 25 to 50 mg/day of pyridoxine is advised. A multivitamin regimen without copper can also be an option. In patients with rheumatoid arthritis or cystinuria, the recommendation is to take 25 mg of pyridoxine per day. The last dose of the day should be taken at least 3 hours after dinner.
Most Common Adverse Effects
Less Common Adverse Effects
Rare Adverse Effects
Penicillamine is contraindicated in the following conditions:
Breastfeeding: The presence of the drug in breast milk is unknown and not documented. There is a manufacturer's advice against breastfeeding.
Given the adverse effects, recommendations are to monitor and watch out for the following:
The drug should be used with caution in the elderly as they are more at risk of developing a skin rash and gastrointestinal side effects.
Penicillamine also interacts with the following drugs:
The following drugs decrease the levels of penicillamine:
The following drugs increase levels of penicillamine:
During the first month of therapy, it is advisable to check the blood cell levels with a complete blood count, platelet count, and urinalysis as well as to properly monitor for any changes in the skin, lymph nodes, and body temperature twice weekly. From the second month until the fifth month, the laboratory and physical findings should be checked every two weeks, and from the sixth month onwards, it should receive testing every month.
Patients should understand to report any symptoms suggesting toxicity such as fever, bleeding, bruising, and chills. Gold sodium thiomalate can cause toxicity of penicillamine and should be avoided.
Healthcare workers, including the nurse practitioner, who prescribe penicillamine, should be familiar with its pharmacology. Because the agent can bind many drugs and minerals, regular monitoring of the patient is necessary. The pharmacist should educate the patient not to take the other medications at the same time as penicillamine. Finally, before prescribing this agent, always ask if the patient has any allergies. Nearly 30% of patients do develop some type of allergic reaction to penicillamine.
|||Treatment guidelines for lead exposure in children. American Academy of Pediatrics Committee on Drugs.,, Pediatrics, 1995 Jul [PubMed PMID: 7596706]|
|||Perrett D, The metabolism and pharmacology of D-penicillamine in man. The Journal of rheumatology. Supplement. 1981 Jan-Feb [PubMed PMID: 7014876]|
|||Levy RS,Fisher M,Alter JN, Penicillamine: review and cutaneous manifestations. Journal of the American Academy of Dermatology. 1983 Apr [PubMed PMID: 6222087]|
|||Hsu HL,Huang FC,Ni YH,Chang MH, Steroids used to desensitize penicillamine allergy in Wilson disease. Acta paediatrica Taiwanica = Taiwan er ke yi xue hui za zhi. 1999 Nov-Dec [PubMed PMID: 10927964]|
|||Bruguera-Àvila N,Sánchez-Martínez E,Garcia-Olivé I,Pérez-Ochoa JF,Martínez-Barenys C,Ruiz-Manzano J, Obliterating bronchiolitis in a patient treated with (D)-penicillamine. Archivos de bronconeumologia. 2013 Sep [PubMed PMID: 23582262]|
|||Khashoggi M,Machet L,Perrinaud A,Brive D,Machet MC,Maruani A,Vaillant L, [D-penicillamine-induced pemphigus: changes in anti-32-2B immunostaining patterns]. Annales de dermatologie et de venereologie. 2013 Aug-Sep [PubMed PMID: 24034638]|
|||D-Penicillamine-induced ANCA-associated crescentic glomerulonephritis in Wilson disease., Bienaimé F,Clerbaux G,Plaisier E,Mougenot B,Ronco P,Rougier JP,, American journal of kidney diseases : the official journal of the National Kidney Foundation, 2007 Nov [PubMed PMID: 17954295]|
|||Rapidly progressive glomerulonephritis with D-penicillamine., Nanke Y,Akama H,Terai C,Kamatani N,, The American journal of the medical sciences, 2000 Dec [PubMed PMID: 11149553]|
|||D-penicillamine-induced crescentic glomerulonephritis and antimyeloperoxidase antibodies in a patient with scleroderma. Case report and review of the literature., Karpinski J,Jothy S,Radoux V,Levy M,Baran D,, American journal of nephrology, 1997 [PubMed PMID: 9426850]|
|||Vajdi T,Lee WW,Paravar T, Penicillamine-associated cutis laxa and milia en plaque - case report and review of cutaneous changes associated with penicillamine. Dermatology online journal. 2016 May 15; [PubMed PMID: 27617526]|
|||Xu SQ,Li XF,Zhu HY,Liu Y,Fang F,Chen L, Clinical efficacy and safety of chelation treatment with typical penicillamine in cross combination with DMPS repeatedly for Wilson's disease. Journal of Huazhong University of Science and Technology. Medical sciences = Hua zhong ke ji da xue xue bao. Yi xue Ying De wen ban = Huazhong keji daxue xuebao. Yixue Yingdewen ban. 2013 Oct; [PubMed PMID: 24142730]|