Last Updated on eMC 16-01-2014 View medicine  | Alliance Pharmaceuticals Contact details

When a pharmaceutical company changes an SPC or PIL, a new version is published on the eMC.  For each version, we show the dates it was published on the eMC and the reasons for change.

Reasons for adding or updating:

  • Change to section 4.8 - Undesirable effects
  • Change to section 4.8 - Undesirable effects - how to report a side effect

Date of revision of text on the SPC:08-01-2014

Legal Category:POM

Black Triangle (CHM): NO

Free-text change information supplied by the pharmaceutical company:



Changes are highlighted in red text below

Respiratory, thoracic and mediastinal disorders

         Not known:        Inflammatory conditions of the respiratory tract such as bronchiolitis, pneumonitis, yellow nail syndrome

 

Reporting of suspected adverse reactions

Reporting suspected adverse reactions after authorisation of the medicinal product is important.  It allows continued monitoring of the benefit/risk balance of the medicinal product.  Healthcare professionals are asked to report any suspected adverse reactions via the Yellow Card Scheme. Tel: Freephone 0808 100 3352. Website: www.mhra.gov.uk/yellowcard.

Reasons for adding or updating:

  • Change to section 4.1 - Therapeutic indications
  • Change to section 4.2 - Posology and method of administration

Date of revision of text on the SPC:01-11-2012

Legal Category:POM

Black Triangle (CHM): NO

Free-text change information supplied by the pharmaceutical company:

Changes highlighted in red below:

4.1 Therapeutic Indications

a)    Severe active rheumatoid arthritis, including juvenile forms

b)    Wilson’s disease (hepatolenticular degeneration) in adults and children (0 to 18 years)

c)    Cystinuria – dissolution and prevention of cystine stones in adults and children (0 to 18 years)

d)    Lead poisoning in adults and children (0 to 18 years)

e)    Chronic active hepatitis in adults

 

4.2 Posology and Method of Administration

For oral administration.

 

Distamine should be taken on an empty stomach at least half an hour before meals, or on retiring.

 

As the smallest available tablet is 125 mg, this might not be suitable for very young children.

 

a) Rheumatoid arthritis

 

Children: The usual maintenance dose is 15 to 20mg/kg/day. The initial dose should be lower (2.5 to 5mg/kg/day) and increased every four weeks over a period of three to six months. Please note that as the smallest available tablet is 125mg, this may not be suitable for children under eight years (or less than 26kg in weight).

 

b) Wilson’s disease

 

Children: Up to 20mg/kg/day in two or three divided doses, given 1 hour before meals.  For older children (>12 years) the usual maintenance dose is 0.75-1g daily. Minimum dose 500mg/day.

 

 

c) Cystinuria

 

Children: 20 to 30mg/kg/day in two or three divided doses, given 1h prior to meals, adjusted to maintain urinary cystine levels below 200mg/litre. No dose range established, but urinary cystine levels must be kept below 200mg/l. The minimum dose of Distamine required to achieve this should be given.

d) Lead poisoning

 

Children: Penicillamine should only be used in cases where blood lead levels <45mcg/dL.  A total of 15-20mg/kg/day in 2-3 doses should be used.20mg/kg/day.

 

e) Chronic active hepatitis


Children:
The safety and efficacy of penicillamine in children less than 18 years with chronic active hepatitis have not been established.  No data are available.

 

Reasons for adding or updating:

  • Change to section 4.3 - Contraindications
  • Change to section 4.4 - Special warnings and precautions for Use
  • Change to section 4.5 - Interaction with other medicinal products and other forms of interaction
  • Change to section 4.8 - Undesirable Effects

Date of revision of text on the SPC:09-06-2010

Legal Category:POM

Black Triangle (CHM): NO

Free-text change information supplied by the pharmaceutical company:



4.3 The following red text has been added:

Agranulocytosis, aplastic anaemia or severe thrombocytopenia due to penicillamine.


4.4 The following red text has been added:

Monitoring of blood and platelet counts should be carried out at appropriate intervals, together with urinalysis for detection of haematuria and proteinuria (see Section 4.8 “Undesirable effects”). Urinalysis should be carried out weekly at first, and following each increase in dose, then monthly, although longer intervals may be adequate for cystinuria and Wilson’s disease. Increasing or persistent proteinuria may necessitate withdrawal of therapy.

 

Concomitant use of NSAIDs and other nephrotoxic drugs may increase the risk of renal damage (see Section 4.5, “Interaction with other medicinal products and other forms of interaction”).

Penicillamine should be used with caution in patients who have had adverse reactions to gold.

Concomitant or previous treatment with gold may increase the risk of side effects with penicillamine treatment. Therefore penicillamine should be used with caution in patients who have previously had adverse reactions to gold and concomitant treatment with gold should be avoided (see Section 4.5, “Interaction with other medicinal products and other forms of interaction”).

 

 

If concomitant oral iron, digoxin or antacid therapy is indicated, this should not be given within two hours of taking penicillamine (see Section 4.5, “Interaction with other medicinal products and other forms of interaction”).

 

Antihistamines, steroid cover, or temporary reduction of dose will control urticarial reactions (see Section 4.8 “Undesirable effects).

 

Reversible loss of taste may occur. Mineral supplements to overcome this are not recommended (see Section 4.8 “Undesirable effects).

 

Haematuria is rare, but if it occurs in the absence of renal stones or other known cause, treatment should be stopped immediately (see Section 4.8 “Undesirable effects).

 

A late rash, described as acquired epidermolysis bullosa and penicillamine dermopathy, may occur after several months or years of therapy. This may necessitate a reduction in dosage (see Section 4.8 “Undesirable effects).

 

Breast enlargement has been reported as a rare complication of penicillamine therapy in both women and men (see Section 4.8 “Undesirable effects). Danazol has been used successfully to treat breast enlargement which does not regress on drug discontinuation.

 

The use of DMARDs, including penicillamine, has been linked to the development of septic arthritis in patients with rheumatoid arthritis, although rheumatoid arthritis is a stronger predictor for the development of septic arthritis than the use of a DMARD (see Section 4.8 “Undesirable effects”).

 

Deterioration of the neurological symptoms of Wilson’s disease (dystonia, rigidity, tremor, dysarthria) have been reported following introduction of penicillamine in patients treated for this condition.  This may be a consequence of mobilisation and redistribution of copper from the liver to the brain (see Section 4.8 “Undesirable effects”).

 

Pyridoxine daily may be given to patients on long term therapy, especially if they are on a restricted diet, since penicillamine increases the requirement for this vitamin (see Section 4.5. Interactions with Other Medicinal Products and Other forms of Interaction).

4.5 The following red text has been added:

Pyridoxine daily may be given to patients on long term therapy, especially if they are on a restricted diet, since penicillamine increases the requirement for this vitamin (see Section 4.4 Special warnings and Precautions for Use).

4.8 The following red text has been added:

The most common of all side-effects are thrombocytopenia and proteinuria.

 

Thrombocytopenia occurs commonly. The reaction may occur at any time during treatment and is usually reversible (see Section 4.4 “Special Warnings and Precautions for Use”).

 

Proteinuria occurs in up to 30% of patients and is partially dose-related (see Section 4.4 “Special Warnings and Precautions for Use”).

 

Adverse reactions (Table 1) are ranked under heading of frequency, the most frequent first, using the following convention: very common (greater than or equal to 1 in 10); common (less than or equal to 1 in 100, less than 1 in 10); uncommon (greater than or equal to 1 in 1,000, less than 1 in 100); rare (greater than or less than 1 in 10,000, less than 1 in 1,000) very rare (less than 1 in 10,000), not known (where no valid estimate of the incidence has been derived).

 

NB: The incidence and severity of some of the adverse reactions, noted below, varies according to the dosage and nature of the disease under treatment.

 

Table 1

 

Blood and Lymphatic system disorders

          Common:           Thrombocytopenia

          Not known:         Neutropenia8., agranulocytosis1., aplastic anaemia1.,                                                haemolytic anaemia, leucopenia

 

Gastrointestinal disorders:

          Rare:                  Mouth ulceration, stomatitis

          Not known:         Pancreatitis, Nausea2., vomiting

 

General disorders and administration site conditions

          Not known:         Fever2.

Hepatobiliary disorders

          Not known:         Cholestatic jaundice

 

Immune system disorders

          Rare:                 Allergic reactions including hypersensitivity

 

Metabolism and nutrition disorders

          Not known:        Anorexia2.

 

Musculoskeletal and connective tissue disorders

          Not known:        Drug induced lupus erythamatosus, myasthenia gravis,                                           polymyositis, rheumatoid arthritis

 

Nervous system disorders

          Not known:        Loss of taste4.

 

Renal and urinary disorders

          Very common:  Proteinuria

          Rare:                 Haematuria5.

          Not known:        Nephrotic syndrome, glomerulonephritis, Goodpasture’s                                                      syndrome

 

Reproductive system and breast disorders

          Rare:                 Breast enlargement7.

 

Respiratory, thoracic and mediastinal disorders

         Not known:        Inflammatory conditions of the respiratory tract such as                                                        bronchiolitis, pneumonitis

 

Skin and subcutaneous tissue disorders

          Rare:                 Alopecia, pseudoxanthoma elasticum, elastosis perforans,                                     skin laxity

          Not known:        Rash2., urticarial reactions3., dermatomyositis, pemphigus,                                                 Stevens-Johnson syndrome, acquired epidermolysis bullosa6.,                                             penicillamine dermopathy6..

 

Vascular disorders    

         Not known:         Pulmonary haemorrhage

 

1. Deaths from agranulocytosis and aplastic anaemia have occurred.

 

2. Nausea, anorexia, fever and rash may occur early in therapy, especially when full doses are given from the start.

 

3. Antihistamines, steroid cover, or temporary reduction of dose will control urticarial reactions (see Section 4.4 “Special Warnings and Precautions for Use”).

 

4. Reversible loss of taste may occur Mineral supplements to overcome this are not recommended (see Section 4.4 “Special Warnings and Precautions for Use”).

 

5. Haematuria is rare, but if it occurs in the absence of renal stones or other known cause, treatment should be stopped immediately (see Section 4.4 “Special Warnings and Precautions for Use”).

 

6. A late rash, described as acquired epidermolysis bullosa and penicillamine dermopathy, may occur after several months or years of therapy (see Section 4.4 “Special Warnings and Precautions for Use”).

 

7. Breast enlargement has been reported as a rare complication of penicillamine therapy in both women and men (see Section 4.4 “Special Warnings and Precautions for Use”).

 

8. The reaction may occur at any time during treatment and are usually reversible (see Section 4.4 “Special Warnings and Precautions for Use”).

 

The development of septic arthritis in patients with rheumatoid arthritis has been linked to the use of DMARDs, including penicillamine (see Section 4.4 “Special Warnings and Precautions for Use”).

 

Deterioration of the neurological symptoms of Wilson’s disease (dystonia, rigidity, tremor, dysarthria) have been reported following introduction of penicillamine in patients treated for this condition (see Section 4.4 “Special Warnings and Precautions for Use”).

Reasons for adding or updating:

  • Change to section 4.4 - Special warnings and precautions for Use
  • Change to section 4.5 - Interaction with other medicinal products and other forms of interaction

Date of revision of text on the SPC:23-04-2010

Legal Category:POM

Black Triangle (CHM): NO

Free-text change information supplied by the pharmaceutical company:



Section 4.4 - Now includes the following red text
Withdrawal of treatment should be considered if platelets fall below 120,000/mm3 or white blood cells below 2,500/mm3, or if three successive falls are noted within the normal range. Treatment may be restarted at a reduced dose when counts return to normal, but should be permanently withdrawn on recurrence of leucopenia or thrombocytopenia. Penicillamine may potentiate the bone marrow suppression caused by clozapine

If concomitant oral iron, digoxin or antacid therapy is indicated, this should not be given within two hours of taking penicillamine.

Section 4.5 - now includes the following red text

Concomitant use of iron or antacids : oral absorption of penicillamine may be reduced by concomitant administration of iron or antacids (see Section 4.4 “Special Warnings and Precautions for Use”).

 

Concomitant use of digoxin: oral absorption of digoxin may be reduced by concomitant administration of penicillamine (see Section 4.4 “Special Warnings and Precautions for Use”).

 

Concomitant use of NSAIDs and other nephrotoxic drugs may increase the risk of renal damage (see Section 4.4 “Special Warnings and Precautions for Use”).

 

Concomitant use of gold: concomitant use not recommended (see Section 4.4 “Special Warnings and Precautions for Use”).

 

Concomitant use of clozapine: penicillamine may potentiate the blood dyscrasias seen with clozapine (see Section 4.4 “Special Warnings and Precautions for Use”).

 

Concomitant use of zinc: oral absorption of penicillamine may be reduced by concomitant administration of zinc; absorption of zinc may also reduced by penicillamine.

Reasons for adding or updating:

  • Change to section 4.8 - Undesirable Effects

Date of revision of text on the SPC:27-03-2009

Legal Category:POM

Black Triangle (CHM): NO

Free-text change information supplied by the pharmaceutical company:

Section 4.8 - The following red text has been included

Pseudoxanthoma elasticum, elastosis perforans and skin laxity have been reported rarely.

 

The use of DMARDs, including penicillamine, has been linked to the development of septic arthritis in patients with rheumatoid arthritis, although rheumatoid arthritis is a stronger predictor for the development of septic arthritis than the use of a DMARD.

Reasons for adding or updating:

  • Change to section 10 date of revision of the text
  • Change to section 1 -Name of the Medicinal product

Date of revision of text on the SPC:26-01-2009

Legal Category:POM

Black Triangle (CHM): NO

Free-text change information supplied by the pharmaceutical company:

Section 1. The following text has been added

Penicillamine 250mg Film-coated tablets

Reasons for adding or updating:

  • Change to section 1 - trade name
  • Change to section 2 - qualitative and quantitative composition
  • Change to section 3 - pharmaceutical form
  • Change to section 4.6 - Pregnancy and Lactation
  • Change to section 4.8 - Undesirable Effects
  • Change to section 6.1 - List of Excipients
  • Change to section 6.2 - Incompatibilities
  • Change to section 6. 4 - Special Precautions for Storage
  • Change to section 6. 6 - Instruction for Use/Handling
  • Change to section 10 (date of (partial) revision of the text

Reasons for adding or updating:

  • New SPC for eMC ie an SPC for an existing product, but one that is new for the eMC