Drugs List

Therapeutic Indications

Uses

Cystinuria
Hepatitis - chronic active
Poisoning - lead
Severe active rheumatoid arthritis
Still's disease (juvenile arthritis)
Wilson's disease

Contraindications

Breastfeeding
Moderate renal impairment
Systemic lupus erythematosus

Precautions and Warnings

Elderly
History of adverse reaction to gold therapy
Mild renal impairment
Pregnancy

Blood counts should be performed before and periodically during treatment
Evaluate renal function before and during treatment
Advise patient to report unexplained fever, sore throat, bruising, bleeding
Monitor for haematuria and proteinuria
Treatment may adversely affect wound healing
Discontinue if platelet count <120,000 per cubic mm
Discontinue if white blood cell count < 2,500 per cubic mm
Discontinue immediately if haematuria occurs without known cause
Avoid giving oral dose at same time as food, antacids or mineral supplement

During the first 8 weeks of treatment, perform full blood counts weekly or fortnightly and in the week following any dose increase. Thereafter, perform full blood counts monthly and in the week following any dose increase. Longer periods between blood counts may be adequate in cystinuria or Wilson's disease.

Treatment may be restarted at a lower dose when blood counts return to the normal range, but should be permanently discontinued if leucopenia or thrombocytopenia recur.

Penicillamine may delay wound healing. It has been suggested that the dose should be reduced to 250mg daily, 6 weeks prior to surgery and during the postoperative period until healing has occurred.

Urticarial reactions may be controlled with antihistamines, steroids or temporary dose reduction.

A rash developing after several months or years of therapy (described as acquired epidermolysis bullosa and penicillamine dermopathy) may require a dose reduction.

The use of DMARDs, including penicillamine, has been linked to the development of septic arthritis in patients with rheumatoid arthritis.

Deterioration of the neurological symptoms of Wilson's disease (dystonia, rigidity, tremor and dysarthria) have been reported following introduction of penicillamine in patients treated for this condition.

Pregnancy and Lactation

Pregnancy

The safety of penicillamine during pregnancy has not been established.

Wilson's disease
Two retrospective studies reported successful delivery of 43 infants to 28 women taking 500mg to 2g of penicillamine daily. Several cases of reversible cutis laxa have been reported in infants where the mothers were taking penicillamine daily. There are reports both of congenital abnormalities and of successful outcomes in patients who have remained on penicillamine during pregnancy. If treatment is to be continued following a risk-benefit analysis, consideration should be given to reducing the dose to the lowest effective dose.
Schaefer (2007) suggests vitamin B6 (pyridoxine) supplementation should be considered.

Cystinuria
Normal infants have been delivered but there is one report of a severe connective tissue abnormality in an infant born to a mother taking 2g daily throughout pregnancy. Whenever possible treatment should be withheld during pregnancy, but assess benefit/risk if stones continue to form and treatment is considered necessary.

Rheumatoid arthritis or chronic active hepatitis
Treatment should be discontinued when pregnancy is diagnosed or suspected unless considered to be essential.

The use of all medication in pregnancy should be avoided whenever possible; particularly in the first trimester. Non-drug treatments should also be considered. When essential, a medication with the best safety record over time should be chosen, employing the lowest effective dose for the shortest possible time. Polypharmacy should be avoided. Teratogens taken in the pre-embryonic period, often quoted as lasting until 14-17 days post-conception, are believed to have an all-or-nothing effect. Where drugs have a short half-life, and when the date of conception is certain, this may allow women to be reassured where drug exposure has occurred within this time frame. Further advice may be available from the UK National Teratology Information Service (NTIS) and through ToxBase, available via password on the internet ( www.toxbase.org ) or if this is unavailable at the backup site ( www.toxbasebackup.org ).

Lactation

There is a lack of data on the use of penicillamine during lactation.

Treatment should either be discontinued or patient should cease breastfeeding infant.

Neonates, infants born prematurely, those with low birth weight, those with an unstable gastrointestinal function or who have serious illnesses may require special consideration. For any infant, if a drug is prescribed to the nursing mother, it should be at the lowest practical dose and for the shortest time. When drug administration is unavoidable and breastfeeding is to continue, minimisation of exposure of the infant to the drug may sometimes be achieved by timing the maternal doses to just after a feeding episode. Infants exposed to drugs via breast milk should be monitored for unusual signs or symptoms. Interactions between the drug received by the infant from the mother's milk and medication prescribed for the infant should also be considered, for example, when the drug given to the infant may prevent metabolism of the drug received via breast milk.
Specialist advice is available from the UK Drugs in Lactation Advisory Service at https://www.midlandsmedicines.nhs.uk/content.asp?section=6&subsection=17&pageIdx=1

Side Effects

Agranulocytosis
Alopecia
Anorexia
Aplastic anaemia
Breast enlargement
Cholestatic jaundice
Dermatomyositis
Elastosis perforans
Epidermolysis bullosa
Fever
Glomerulonephritis
Goodpasture's syndrome
Haematuria
Haemolytic anaemia
Hypersensitivity reactions
Increases in hepatic enzymes
Inflammatory respiratory conditions
Leucopenia
Lupus erythematosus-like syndrome
Mouth ulcers
Myasthenia gravis-like syndrome
Nausea
Nephrotic syndrome
Neutropenia
Pancreatitis
Pemphigus
Pneumonitis
Polymyositis
Proteinuria
Pseudoxanthoma elasticum
Pulmonary haemorrhage
Rash
Rheumatoid arthritis-like syndrome (in non-rheumatoid conditions)
Skin laxity
Stevens-Johnson syndrome
Stomatitis
Taste loss (transient)
Thrombocytopenia
Urticaria
Vomiting

Presentation

All formulations of penicillamine.

Drugs List

Therapeutic Indications

Uses

Cystinuria
Hepatitis - chronic active
Poisoning - lead
Severe active rheumatoid arthritis
Still's disease (juvenile arthritis)
Wilson's disease

Dosage

Adults

Elderly

Children

Patients with Renal Impairment

Contraindications

Breastfeeding
Moderate renal impairment
Systemic lupus erythematosus

Precautions and Warnings

Elderly
History of adverse reaction to gold therapy
Mild renal impairment
Pregnancy

Blood counts should be performed before and periodically during treatment
Evaluate renal function before and during treatment
Advise patient to report unexplained fever, sore throat, bruising, bleeding
Monitor for haematuria and proteinuria
Treatment may adversely affect wound healing
Discontinue if platelet count <120,000 per cubic mm
Discontinue if white blood cell count < 2,500 per cubic mm
Discontinue immediately if haematuria occurs without known cause
Avoid giving oral dose at same time as food, antacids or mineral supplement

During the first 8 weeks of treatment, perform full blood counts weekly or fortnightly and in the week following any dose increase. Thereafter, perform full blood counts monthly and in the week following any dose increase. Longer periods between blood counts may be adequate in cystinuria or Wilson's disease.

Treatment may be restarted at a lower dose when blood counts return to the normal range, but should be permanently discontinued if leucopenia or thrombocytopenia recur.

Penicillamine may delay wound healing. It has been suggested that the dose should be reduced to 250mg daily, 6 weeks prior to surgery and during the postoperative period until healing has occurred.

Urticarial reactions may be controlled with antihistamines, steroids or temporary dose reduction.

A rash developing after several months or years of therapy (described as acquired epidermolysis bullosa and penicillamine dermopathy) may require a dose reduction.

The use of DMARDs, including penicillamine, has been linked to the development of septic arthritis in patients with rheumatoid arthritis.

Deterioration of the neurological symptoms of Wilson's disease (dystonia, rigidity, tremor and dysarthria) have been reported following introduction of penicillamine in patients treated for this condition.

Pregnancy and Lactation

Pregnancy

The safety of penicillamine during pregnancy has not been established.

Wilson's disease
Two retrospective studies reported successful delivery of 43 infants to 28 women taking 500mg to 2g of penicillamine daily. Several cases of reversible cutis laxa have been reported in infants where the mothers were taking penicillamine daily. There are reports both of congenital abnormalities and of successful outcomes in patients who have remained on penicillamine during pregnancy. If treatment is to be continued following a risk-benefit analysis, consideration should be given to reducing the dose to the lowest effective dose.
Schaefer (2007) suggests vitamin B6 (pyridoxine) supplementation should be considered.

Cystinuria
Normal infants have been delivered but there is one report of a severe connective tissue abnormality in an infant born to a mother taking 2g daily throughout pregnancy. Whenever possible treatment should be withheld during pregnancy, but assess benefit/risk if stones continue to form and treatment is considered necessary.

Rheumatoid arthritis or chronic active hepatitis
Treatment should be discontinued when pregnancy is diagnosed or suspected unless considered to be essential.

The use of all medication in pregnancy should be avoided whenever possible; particularly in the first trimester. Non-drug treatments should also be considered. When essential, a medication with the best safety record over time should be chosen, employing the lowest effective dose for the shortest possible time. Polypharmacy should be avoided. Teratogens taken in the pre-embryonic period, often quoted as lasting until 14-17 days post-conception, are believed to have an all-or-nothing effect. Where drugs have a short half-life, and when the date of conception is certain, this may allow women to be reassured where drug exposure has occurred within this time frame. Further advice may be available from the UK National Teratology Information Service (NTIS) and through ToxBase, available via password on the internet ( www.toxbase.org ) or if this is unavailable at the backup site ( www.toxbasebackup.org ).

Lactation

There is a lack of data on the use of penicillamine during lactation.

Treatment should either be discontinued or patient should cease breastfeeding infant.

Neonates, infants born prematurely, those with low birth weight, those with an unstable gastrointestinal function or who have serious illnesses may require special consideration. For any infant, if a drug is prescribed to the nursing mother, it should be at the lowest practical dose and for the shortest time. When drug administration is unavoidable and breastfeeding is to continue, minimisation of exposure of the infant to the drug may sometimes be achieved by timing the maternal doses to just after a feeding episode. Infants exposed to drugs via breast milk should be monitored for unusual signs or symptoms. Interactions between the drug received by the infant from the mother's milk and medication prescribed for the infant should also be considered, for example, when the drug given to the infant may prevent metabolism of the drug received via breast milk.
Specialist advice is available from the UK Drugs in Lactation Advisory Service at https://www.midlandsmedicines.nhs.uk/content.asp?section=6&subsection=17&pageIdx=1

Side Effects

Agranulocytosis
Alopecia
Anorexia
Aplastic anaemia
Breast enlargement
Cholestatic jaundice
Dermatomyositis
Elastosis perforans
Epidermolysis bullosa
Fever
Glomerulonephritis
Goodpasture's syndrome
Haematuria
Haemolytic anaemia
Hypersensitivity reactions
Increases in hepatic enzymes
Inflammatory respiratory conditions
Leucopenia
Lupus erythematosus-like syndrome
Mouth ulcers
Myasthenia gravis-like syndrome
Nausea
Nephrotic syndrome
Neutropenia
Pancreatitis
Pemphigus
Pneumonitis
Polymyositis
Proteinuria
Pseudoxanthoma elasticum
Pulmonary haemorrhage
Rash
Rheumatoid arthritis-like syndrome (in non-rheumatoid conditions)
Skin laxity
Stevens-Johnson syndrome
Stomatitis
Taste loss (transient)
Thrombocytopenia
Urticaria
Vomiting

Overdosage

It is strongly recommended that the UK National Poisons Information Service be consulted on cases of suspected or actual overdose where there is doubt over the degree of risk or about appropriate management.

The following number will direct the caller to the relevant local centre (0844) 892 0111

Information may be obtained if you have access to ToxBase the primary clinical toxicology database of the National Poisons Information Service. This is available via password on the internet ( www.toxbase.org ) or if this is unavailable at the backup site ( www.toxbasebackup.org ).

Further Information

Last Full Review Date: June 2013

Reference Sources

Drugs During Pregnancy and Lactation: Treatment Options and Risk Assessment, 2nd edition (2007) ed. Schaefer, C., Peters, P. and Miller, R. Elsevier, London.

Drugs in Pregnancy and Lactation: A Reference Guide to Fetal and Neonatal Risk, 9th edition (2011) ed. Briggs, G., Freeman, R. and Yaffe, S. Lippincott Williams & Wilkins, Philadelphia.

Martindale: The Complete Drug Reference, 37th edition (2011) ed. Sweetman, S. Pharmaceutical Press, London.

Medications and Mothers' Milk, 14th Edition (2010) Hale, T. Hale Publishing, Amarillo, Texas.

Summary of Product Characteristics: Distamine 125mg film-coated tablets. Alliance Pharmaceuticals. Revised November 2012.
Summary of Product Characteristics: Distamine 250mg film-coated tablets. Alliance Pharmaceuticals. Revised November 2012.

Summary of Product Characteristics: Penicillamine 125mg tablets. Kent Pharmaceuticals. Revised February 2013.
Summary of Product Characteristics: Penicillamine 250mg tablets. Kent Pharmaceuticals. Revised February 2013.

The Renal Drug Handbook. 3rd edition. (2009) ed. Ashley, C and Currie, Radcliffe Publishing Ltd, Abingdon.

NICE Evidence Services Available at: www.nice.org.uk Last accessed: 26 September 2017

US National Library of Medicine. Toxicology Data Network. Drugs and Lactation Database (LactMed).
Available at: https://toxnet.nlm.nih.gov/cgi-bin/sis/htmlgen?LACT
Penicillamine Last revised: April 3, 2013
Last accessed: June 11, 2013