Summary for UKPID
PENICILLAMINE
Dr Alan Worsley Bsc(hons) PhD MRPharmS
National Poisons Information Service (Newcastle Centre)
Regional Drug & Therapeutics Centre
Wolfson Building
Claremont Place
Newcastle upon Tyne
NE1 4LP
UK
This monograph has been produced by staff of a National Poisons
Information Service Centre in the United Kingdom. The work was
commissioned and funded by the UK Departments of Health, and was
designed as a source of detailed information for use by poisons
information centres.
Peer review group: Directors of the UK National Poisons Information
Service.
PENICILLAMINE (Distamine)
Summary
Type of product
For the treatment of severe rheumatoid arthritis and cystinuria
Ingredients/tablet
Penicillamine 50, 125 and 250mg
Fatal Dose
Not Known- A 52 year old male presented at hospital 8 hours after
ingesting 3.1g. Symptoms included vomiting, dehydaration, abdominal
pain and tachycardia.
Features
Nausea and vomiting, abdominal pain, hyperpyrexia, thrombocytopaenia,
neutropaenia, proteinuria, haematuria and tachycardia
Management
Empty the stomach if >500mg ingested, maintain a good diuresis.
Monitor renal function and treat failure conventionally. Supportive
Antidotes
There are no specific antidotes
Elimination techniques
No data available
REFERENCES
ABPI Data Sheet Compendium. Datapharm publications Limited 1996-1997
British National Formulary. Number 32 (September 1996). British
Medical Associiation and Royal Pharmaceutical Society.
Dollery C, Therapeutic Drugs. (Pt 2), Churchill Livingstone. 1994
PENICILLAMINE
Brand Name
Distamine
Generic Name
Penicillamine
Chemical Group/family
Anti-rheumatic
BNF 10.13
Reference number
CAS-52-67-5 (penicillamine)
CAS-2219-30-9 (hydrochloride)
Manufacturer/supplier
Eli Lilly & Co Ltd,
Dextra Court,
Chapel Hill,
Basingstoke, Hants.
RG21 5SY
Tel: 01256 315000
Presentation
Penicillamine 50mg, 125 mg, 250 mg tablets.
Physicochemical properties:(Dollery)3
3,3-Dimethyl-D-cysteine
Molecular weight
149.2
pKa (COOH, NH, SH)
1.8, 7.9, 10.5
Solubility
in alcohol 1 in 530
in water 1 in 9
octanol/water partition coefficient -
USES
Indications
Penicillamine is indicated in Wilson's disease, cystinuria, rheumatoid
arthritis, juvenile chronic polyarthritis, palindromic rheumatism,
sero-negative polyarthritis, progressive systemic sclerosis, chronic
active hepatitis.
Therapeutic Dosage (BNF)2
Adults
Severe active rheumatoid arthritis, 500-750 mg daily maintenance (max
1.5g daily)
Wilson's disease, 1.5-2.0g daily in divided doses.
Cystinuria, 1-3g daily in divided doses (adjusted to maintain urinary
cysteine below 200mg/litre.
Chronic active hepatitis.
Child
Severe active rheumatoid arthritis15-20mg/kg maintenance.
Wilson's disease, up to 20mg/kg daily in divided doses.
Cystinuria, minimum dose to maintain urinary cysteine below
200mg/litre.
Contraindications
hypersensitivity (except in life threatening situations) systemic
lupus erythematosus.
Pharmacokinetics (Dollery)3
Oral absorption 40%
presystemic metabolism -
plasma half life
mean 1-6h
volume of distribution 0.8litre/kg
plasma protein binding up to 85%
Toxicokinetics
No specific data available
Adverse effects (Data Sheet)1
Nausea, anorexia, fever and rash may occur early in therapy.
Thrombocytopenia occurs commonly and neutropenia less often.
Proteinuria occurs in 30% of patients and is dose related. Haematuria
is rare.
Haemolytic anaemia, nephrotic syndrome.
Pregnancy
Penicillamine crosses the placenta to the fetus and has been
administered during pregnancy for the treatment of rheumatoid
arthritis, cystinuria and Wilson's disease4. Conflicting reports
suggest that penicillamine should either be stopped during
pregnancy5, or be continued during pregnancy with the treatment of
Wilson's disease, but discontinued in the treatment of rheumatoid
arthritis6.
The use of penicillamine has been observed in approximately 100
pregnancies. Eight anomalies were observed, of which 5 cases were
cutis laxa. The later three cases were not thought to be related to
penicillamine, because they did not conclude connective tissue
anomalies7.
Breast Milk
There are no reports that describe the use of penicillamine during
lactation or if the drug is excreted in milk have been located.
Authors of one review recomend avoiding penicillamine during
lactation5.
Interactions (BNF)2
Antacids: reduced absorption of penicillamine
Iron: reduced absorption of penicillamine
Zinc:reduced absorption of penicillamine
EPIDEMIOLOGY OF POISONING
Limited specific data of penicillamine poisoning are available.
A 52 year old male presented at hospital 8 hours after ingesting 3.1 g
penicillamine. Symptoms included, vomiting, dehydration, abdominal
pain and tachycardia.
Side effects reported at therapeutic dosage include:
Initially nausea, anorexia, fever and skin reactions; taste loss
(mineral supplements not recommended); blood disorders including
thrombocytopaenia, agranulocytosis and aplastic anaemia; proteinuria,
rarely haematuria (withdraw immediately); haemolytic anaemia,
nephrotic syndrome, lupus erythematosus-like syndrome, myasthenia
Gravis-like syndrome, pemphigus, Goodpasture's syndrome, and
Stevens-Johnson syndrome also reported; in non-rheumatoid conditions
rheumatoid arthritis-like syndrome also reported; late rashes (reduce
dose or withdraw treatment).
MANAGEMENT
No specific details available
Decontamination
If ingestion is within 2 hours, 50-100grams (adults) or 25-50 grams
(children) of oral activated charcoal may be administered. Lactulose
(20ml) should be given to prevent constipation. There is no data to
indicate whether or not this is effective in penicillamine poisoning.
Supportive care
General supportive care should be given
Monitoring
As no data are available on penicillamine poisoning vital signs should
be monitored-pulse, blood pressure, respiration.
Antidotes
There are no specific antidotes
Elimination techniques
No data available
Investigations
No data is available on penicilllamine poisoning, but routine
investigations including renal function tests, urinalysis and
electrolytes could be carried out.
Case Data
Other Toxicological Data
No data available
Ecotoxicological Data
No data available
Hazard Warnngs
No data available
Waste disposal data
No data available
Author
Dr Alan Worsley Bsc(hons) PhD MRPharmS
National Poisons Information Service (Newcastle Centre)
Regional Drug & Therapeutics Centre
Wolfson Building
Claremont Place
Newcastle upon Tyne
NE1 4LP
UK
This monograph was produced by the staff of the Newcastle Centre of
the National Poisons Information Service in the United Kingdom. The
work was commissioned and funded by the UK Departments of Health, and
was designed as a source of detailed information for use by poisons
information centres.
Peer review was undertaken by the Directors of the UK National Poisons
Information Service.
Last updated January 1997
REFERENCES
1. ABPI Data Sheet Compendium. Datapharm Publications Limited. 1996-
1997
2. British National Formulary. Number 32 (september 1996). British
Medical Association and Royal Pharmaceutical Society.
3. Dollery C. Therapeutic Drugs. (Suppl 2), Churchill Livingstone.
1994
4. Crawhall JC et al . BMJ (1967);2:216-8
5. Ostensen M et Husby G. Scand J Rheumatol. (1985);14:1-7
6. Miehle W. Z Rhematol (1988);47(suppl 1):20-3
7. Gal P et Ravenel SD. J Clin Dysmorphol (1984);2:9-12