Wilzin

1 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

ANNEX I 

 

SUMMARY OF PRODUCT CHARACTERISTICS 

 



2 

1. NAME OF THE MEDICINAL PRODUCT 
 

Wilzin 25 mg hard capsules 

 

 

2. QUALITATIVE AND QUANTITATIVE COMPOSITION 
 

Each hard capsule contains 25 mg of zinc (corresponding to 83.92 mg of zinc acetate dihydrate). 

 

For a full list of excipients, see section 6.1. 

 

 

3. PHARMACEUTICAL FORM 
 

Hard capsule. 

Capsule with aqua blue opaque cap and body, imprinted "93-376”. 

 

 

4. CLINICAL PARTICULARS 
 

4.1 Therapeutic indications 
 

Treatment of Wilson’s disease. 

 

4.2 Posology and method of administration 
 

Wilzin treatment should be initiated under the supervision of a physician experienced in the treatment 

of Wilson’s disease (see section 4.4). Wilzin is a life-long therapy. 

 

There is no difference in dose between symptomatic and presymptomatic patients. 

Wilzin is available in hard capsules of 25 mg or 50 mg. 

 

 Adults: 
The usual dose is 50 mg 3 times daily with a maximum dose of 50 mg 5 times daily. 

 Children and adolescents: 
Data are very limited in children under 6 years but since the disease is fully penetrant, 

prophylactic treatment should be considered as early as possible. The recommended dose is as 

follows: 

- from 1 to 6 years: 25 mg twice daily 

- from 6 to 16 years if bodyweight under 57 kg: 25 mg three times daily 

- from 16 years or if bodyweight above 57 kg: 50 mg three times daily. 

 Pregnant women: 
A dose of 25 mg 3 times daily is usually effective but the dose should be adjusted to copper 

levels (see section 4.4 and section 4.6). 

 

In all cases, dose should be adjusted according to therapeutic monitoring (see section 4.4.). 

 

Wilzin must be taken on an empty stomach, at least 1 hour before or 2-3 hours after meals. In case of 

gastric intolerance, often occurring with the morning dose, this dose may be delayed to mid-morning, 

between breakfast and lunch. It is also possible to take Wilzin with a little protein, such as meat (see 

section 4.5). 

 

In children who are unable to swallow capsules, these should be opened and their content suspended in 

a little water (possibly sugar or syrup flavoured water). 

 

When switching a patient on chelating treatment to Wilzin for maintenance therapy, the chelating 

treatment should be maintained and co-administered for 2 to 3 weeks since this is the time it takes for 



3 

the zinc treatment to induce maximum metallothionein induction and full blockade of copper 

absorption. The administration of the chelating treatment and Wilzin should be separated by at least 

1 hour. 

 

4.3 Contraindications 
 

Hypersensitivity to the active substance or to any of the excipients. 

 

4.4 Special warnings and special precautions for use 
 

Zinc acetate dihydrate is not recommended for the initial therapy of symptomatic patients because of 

its slow onset of action. Symptomatic patients must be initially treated with a chelating agent; once 

copper levels are below toxic thresholds and patients are clinically stable, maintenance treatment with 

Wilzin can be considered. 

Nevertheless, while awaiting zinc induced duodenal metallothionein production and consequential 

effective inhibition of copper absorption, zinc acetate dehydrate could be administered initially in 

symptomatic patients in combination with a chelating agent. 

 

Although rare, clinical deterioration may occur at the beginning of the treatment, as has also been 

reported with chelating agents. Whether this is related to mobilisation of copper stores or to natural 

history of the disease remains unclear. A change of therapy is recommended in this situation. 

 

Caution should be exercised when switching patients with portal hypertension from a chelating agent 

to Wilzin, when such patients are doing well and the treatment is tolerated. Two patients of a series of 

16 died from hepatic decompensation and advanced portal hypertension after being changed from 

penicillamine to zinc therapy. 

 

Therapeutic monitoring 

The aim of the treatment is to maintain the plasma free copper (also known as non-ceruloplasmin 

plasma copper) below 250 microgram/l (normal: 100-150 microgram/l) and the urinary copper 

excretion below 125 microgram/24 h (normal: < 50 microgram/24 h). The non-ceruloplasmin plasma 

copper is calculated by subtracting the ceruloplasmin-bound copper from the total plasma copper, 

given that each milligram of ceruloplasmin contains 3 micrograms of copper. 

The urinary excretion of copper is an accurate reflection of body loading with excess copper only 

when patients are not on chelation therapy. Urinary copper levels are usually increased with chelation 

therapy such as penicillamine or trientine. 

The level of hepatic copper cannot be used to manage therapy since it does not differentiate between 

potentially toxic free copper and metallothionein bound copper. 

In treated patients, assays of urinary and/or plasma zinc may be a useful measure of treatment 

compliance. Values of urinary zinc above 2 mg/24 h and of plasma zinc above 1250 microgram/l 

generally indicate adequate compliance. 

 

Like with all anti-copper agents overtreatment carries the risk of copper deficiency, which is 

especially harmful for children and pregnant women since copper is required for proper growth and 

mental development. In these patient groups, urinary copper levels should be kept a little above the 

upper limit of normal or in the high normal range (i.e. 40 – 50 microgram/24 h). 

Laboratory follow-up including haematological surveillance and lipoproteins determination should 

also be performed in order to detect early manifestations of copper deficiency, such as anaemia and/or 

leukopenia resulting from bone marrow depression, and decrease in HDL cholesterol and HDL/total 

cholesterol ratio. 

As copper deficiency may also cause myeloneuropathy, physicians should be alert to sensory and 

motor symptoms and signs which may potentially indicate incipient neuropathy or myelopathy in 

patients treated with Wilzin. 

 



4 

4.5 Interaction with other medicinal products and other forms of interaction 
 

Other anti-copper agents 

Pharmacodynamic studies were conducted in Wilson’s disease patients on the combination of Wilzin 

(50 mg three times daily) with ascorbic acid (1 g once daily), penicillamine (250 mg four times daily), 

and trientine (250 mg four times daily). They showed no significant overall effect on copper balance 

although mild interaction of zinc with chelators (penicillamine and trientine) could be detected with 

decreased faecal but increased urinary copper excretion as compared with zinc alone. This is probably 

due to some extent of complexion of zinc by the chelator, thus reducing the effect of both active 

substances. 

When switching a patient on chelating treatment to Wilzin for maintenance therapy, the chelating 

treatment should be maintained and co-administered for 2 to 3 weeks since this is the time it takes for 

the zinc treatment to induce maximum metallothionein induction and full blockade of copper 

absorption. The administration of the chelating treatment and Wilzin should be separated by at least 

1 hour. 

 

Other medicinal products 

The absorption of zinc may be reduced by iron and calcium supplements, tetracyclines and 

phosphorus-containing compounds, while zinc may reduce the absorption of iron, tetracyclines, 

fluoroquinolones. 

 

Food 

Studies of the co-administration of zinc with food performed in healthy volunteers showed that the 

absorption of zinc was significantly delayed by many foods (including bread, hard boiled eggs, coffee 

and milk). Substances in food, especially phytates and fibres, bind zinc and prevent it from entering 

the intestinal cells. However, protein appears to interfere the least. 

 

4.6 Pregnancy and lactation 
 

Pregnancy 

Data on a limited number of exposed pregnancies in patients with Wilson’s disease give no indication 

of harmful effects of zinc on embryo/foetus and mother. Five miscarriages and 2 birth defects 

(microcephaly and correctable heart defect) were reported in 42 pregnancies. 

 

Animal studies conducted with different zinc salts do not indicate direct or indirect harmful effects 

with respect to pregnancy, embryonal/foetal development, parturition or postnatal development 

(see section 5.3).  

 

It is extremely important that pregnant Wilson’s disease patients continue their therapy during 

pregnancy. Which treatment should be used, zinc or chelating agent should be decided by the 

physician. Dose adjustments to guarantee that the foetus will not become copper deficient must be 

done and close monitoring of the patient is mandatory (see section 4.4). 

 

Lactation 
Zinc is excreted in human breast milk and zinc-induced copper deficiency in the breast-fed baby may 

occur. Therefore, breast-feeding should be avoided during Wilzin therapy. 

 

4.7 Effects on ability to drive and use machines 
 

No studies on the effects on the ability to drive and use machines have been performed. 

 

4.8 Undesirable effects 

 

Reported adverse reactions are listed below, by system organ class and by frequency. 



5 

Frequencies are defined as: very common (≥ 1/10), common (≥ 1/100 to < 1/10),  uncommon 

(≥ 1/1,000 to < 1/100), rare (≥ 1/10,000 to < 1/1,000), very rare (< 1/10,000), not known (cannot be 

estimated from the available data). 

Within each frequency grouping, undesirable effects are presented in order of decreasing seriousness. 
 

 

System organ class 

 

Adverse drug reactions 

Blood and lymphatic system disorders 

 

uncommon: sideroblastic anaemia, leukopenia 

Gastrointestinal disorders 

 

common: gastric irritation 

Investigations common: blood amylase, lipase and alkaline 

phosphatase increased 

 

 

Anaemia may be micro-, normo- or macrocytic and is often associated with leukopenia. Bone marrow 

examination usually reveals characteristic "ringed sideroblasts" (i.e. developing red blood cells 

containing iron-engorged paranuclear mitochondria). They may be early manifestations of copper 

deficiency and may recover rapidly following reduction of zinc dosage. However, they must be 

distinguished from haemolytic anaemia which commonly occurs where there is elevated serum free 

copper in uncontrolled Wilson’s disease. 

 

The most common undesirable effect is gastric irritation. This is usually worst with the first morning 

dose and disappears after the first days of treatment. Delaying the first dose to mid-morning or taking 

the dose with a little protein may usually relieve the symptoms. 

 

Elevations of serum alkaline phosphatase, amylase and lipase may occur after a few weeks of 

treatment, with levels usually returning to high normal within the first one or two years of treatment. 

 

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 national reporting system 

listed in Appendix V. 

 

 

4.9 Overdose 
 

Three cases of acute oral overdose with zinc salts (sulphate or gluconate) have been reported in the 

literature. Death occurred in a 35 year-old woman on the fifth day after ingestion of 6 g of zinc 

(40 times the proposed therapeutic dose) and was attributed to renal failure and haemorrhagic 

pancreatitis with hyperglycaemic coma. The same dose did not produce any symptoms except for 

vomiting in an adolescent who was treated by whole-bowel irrigation. Another adolescent who 

ingested 4 g of zinc had serum zinc level of about 50 mg/l 5 hours later and only experienced severe 

nausea, vomiting and dizziness. 

 

Treatment of overdose should be with gastric lavage or induced emesis as quickly as possible to 

remove unabsorbed zinc. Heavy metal chelation therapy should be considered if plasma zinc levels are 

markedly elevated (> 10 mg/l). 

 

 

5. PHARMACOLOGICAL PROPERTIES 

 

5.1  Pharmacodynamic properties 

 
Pharmacotherapeutic group: various alimentary tract and metabolism products, ATC code: A16AX05. 



6 

 

Wilson's disease (hepatolenticular degeneration) is an autosomal recessive metabolic defect in hepatic 

excretion of copper in the bile. Copper accumulation in the liver leads to hepatocellular injury and 

eventual cirrhosis. When the liver capacity of storing copper is exceeded copper is released into the 

blood and is taken up in extra hepatic sites, such as the brain, resulting in motor disorders and 

psychiatric manifestations. Patients may present clinically with predominantly hepatic, neurologic, or 

psychiatric symptoms. 

 

The active moiety in zinc acetate dihydrate is zinc cation, which blocks the intestinal absorption of 

copper from the diet and the reabsorption of endogenously secreted copper. Zinc induces the 

production of metallothionein in the enterocyte, a protein that binds copper thereby preventing its 

transfer into the blood. The bound copper is then eliminated in the stool following desquamation of the 

intestinal cells. 

 

Pharmacodynamic investigations of copper metabolism in patients with Wilson’s disease included 

determinations of net copper balance and radiolabelled copper uptake. A daily regimen of 150 mg of 

Wilzin in three administrations was shown to be effective in significantly reducing copper absorption 

and inducing a negative copper balance. 

 

5.2 Pharmacokinetic properties 
 

Since the mechanism of action of zinc is an effect on copper uptake at the level of the intestinal cell, 

pharmacokinetic evaluations based on blood levels of zinc do not provide useful information on zinc 

bioavailability at the site of action.  

 

Zinc is absorbed in the small intestine and its absorption kinetics suggest a tendency to saturation at 

increasing doses. Fractional zinc absorption is negatively correlated with zinc intake. It ranges from 30 

to 60% with usual dietary intake (7-15 mg/d) and decreases to 7% with pharmacological doses of 

100 mg/d. 

 

In the blood, about 80% of absorbed zinc is distributed to erythrocytes, with most of the remainder 

being bound to albumin and other plasma proteins. The liver is the main storage for zinc and hepatic 

zinc levels are increased during maintenance therapy with zinc. 

 

The plasma elimination half-life of zinc in healthy subjects is around 1 hour after a dose of 45 mg. The 

elimination of zinc results primarily from faecal excretion with relatively little from urine and sweat. 

The faecal excretion is in the greatest part due to the passage of unabsorbed zinc but it is also due to 

endogenous intestinal secretion. 

 

5.3 Preclinical safety data 
 

Preclinical studies have been conducted with zinc acetate and with other zinc salts. Pharmacological 

and toxicological data available showed large similarities between zinc salts and among animal 

species. 

The oral LD50 is approximately 300 mg zinc/kg body weight (about 100 to 150 times the human 

therapeutic dose). Repeat-dose toxicity studies have established that the NOEL (No Observed Effect 

Level) is about 95 mg zinc/kg body weight (about 48 times the human therapeutic dose). 

The weight of evidence, from in vitro and in vivo tests, suggests that zinc has no clinically relevant 

genotoxic activity. 

Reproduction toxicology studies performed with different zinc salts showed no clinically relevant 

evidence of embryotoxicity, foetotoxicity or teratogenicity. 

No conventional carcinogenicity study has been conducted with zinc acetate dihydrate. 

 



7 

 

6. PHARMACEUTICAL PARTICULARS 

 

6.1 List of excipients 
 

Capsule content 

maize starch 

magnesium stearate 

 

Capsule shell 

gelatin 

titanium dioxide (E171) 

brilliant blue FCF (E133) 

 

Printing ink 

black iron oxide (E172) 

shellac 

 

6.2 Incompatibilities 
 

Not applicable. 

 

6.3 Shelf life 
 

3 years. 

 

6.4 Special precautions for storage 
 

Do not store above 25°C. 

 

6.5 Nature and contents of container 
 

White HDPE bottle with a polypropylene and HDPE closure and contains a filler (cotton coil). Each 

bottle contains 250 capsules. 

 

6.6 Special precautions for disposal 

 

No special requirements 

 

 

7. MARKETING AUTHORISATION HOLDER 
 

Recordati Rare Diseases 

Immeuble “Le Wilson” 

70, avenue du Général de Gaulle 

F-92800 Puteaux 

France 

 

 

8. MARKETING AUTHORISATION NUMBER(S)  

 

EU/1/04/286/001 
 

 

9. DATE OF FIRST AUTHORISATION/RENEWAL OF THE AUTHORISATION 
 

Date of first authorisation: 13 October 2004 



8 

Date of latest renewal: 13 October 2009 

 

 

10. DATE OF REVISION OF THE TEXT 
 

 

 

Detailed information on this product is available on the website of the European Medicines Agency 

(EMA) http://www.ema.europa.eu 



9 

1. NAME OF THE MEDICINAL PRODUCT 
 

Wilzin 50 mg hard capsules 

 

 

2. QUALITATIVE AND QUANTITATIVE COMPOSITION 
 

Each hard capsule contains 50 mg of zinc (corresponding to 167.84 mg of zinc acetate dihydrate). 

 

Excipients: 

Each capsule contains 1.75 mg of sunset yellow FCF (E110) 

 

For a full list of excipients, see section 6.1. 

 

 

3. PHARMACEUTICAL FORM 
 

Hard capsule. 

Capsule with orange opaque cap and body, imprinted "93-377”. 

 

 

4. CLINICAL PARTICULARS 
 

4.1 Therapeutic indications 
 

Treatment of Wilson’s disease. 

 

4.2 Posology and method of administration 
 

Wilzin treatment should be initiated under the supervision of a physician experienced in the treatment 

of Wilson’s disease (see section 4.4). Wilzin is a life-long therapy. 
 

There is no difference in dose between symptomatic and presymptomatic patients. 

Wilzin is available in hard capsules of 25 mg or 50 mg. 

 

 Adults: 
The usual dose is 50 mg 3 times daily with a maximum dose of 50 mg 5 times daily. 

 Children and adolescents: 
Data are very limited in children under 6 years but since the disease is fully penetrant, 

prophylactic treatment should be considered as early as possible. The recommended dosage is 

as follows: 

- from 1 to 6 years: 25 mg twice daily 

- from 6 to 16 years if bodyweight under 57 kg: 25 mg three times daily 

- from 16 years or if bodyweight above 57 kg: 50 mg three times daily. 

 Pregnant women: 
A dose of 25 mg 3 times daily is usually effective but the dose should be adjusted to copper 

levels (see section 4.4 and section 4.6). 

 

In all cases, dose should be adjusted according to therapeutic monitoring (see section 4.4.). 

 

Wilzin must be taken on an empty stomach, at least 1 hour before or 2-3 hours after meals. In case of 

gastric intolerance, often occurring with the morning dose, this dose may be delayed to mid-morning, 

between breakfast and lunch. It is also possible to take Wilzin with a little protein, such as meat (see 

section 4.5). 

 

In children who are unable to swallow capsules, these should be opened and their content suspended in 

a little water (possibly sugar or syrup flavoured water). 



10 

 

When switching a patient on chelating treatment to Wilzin for maintenance therapy, the chelating 

treatment should be maintained and co-administered for 2 to 3 weeks since this is the time it takes for 

the zinc treatment to induce maximum metallothionein induction and full blockade of copper 

absorption. The administration of the chelating treatment and Wilzin should be separated by at least 

1 hour. 

 

4.3 Contraindications 
 

Hypersensitivity to the active substance or to any of the excipients. 

 

4.4 Special warnings and special precautions for use 
 

Zinc acetate dihydrate is not recommended for the initial therapy of symptomatic patients because of 

its slow onset of action. Symptomatic patients must be initially treated with a chelating agent; once 

copper levels are below toxic thresholds and patients are clinically stable, maintenance treatment with 

Wilzin can be considered. 

Nevertheless, while awaiting zinc induced duodenal metallothionein production and consequential 

effective inhibition of copper absorption, zinc acetate dehydrate could be administered initially in 

symptomatic patients in combination with a chelating agent. 

 

Although rare, clinical deterioration may occur at the beginning of the treatment, as has also been 

reported with chelating agents. Whether this is related to mobilisation of copper stores or to natural 

history of the disease remains unclear. A change of therapy is recommended in this situation. 

 

Caution should be exercised when switching patients with portal hypertension from a chelating agent 

to Wilzin, when such patients are doing well and the treatment is tolerated. Two patients of a series of 

16 died from hepatic decompensation and advanced portal hypertension after being changed from 

penicillamine to zinc therapy. 

 

Therapeutic monitoring 

The aim of the treatment is to maintain the plasma free copper (also known as non-ceruloplasmin 

plasma copper) below 250 microgram/l (normal: 100-150 microgram/l) and the urinary copper 

excretion below 125 microgram/24 h (normal: < 50 microgram/24 h). The non-ceruloplasmin plasma 

copper is calculated by subtracting the ceruloplasmin-bound copper from the total plasma copper, 

given that each milligram of ceruloplasmin contains 3 micrograms of copper. 

The urinary excretion of copper is an accurate reflection of body loading with excess copper only 

when patients are not on chelation therapy. Urinary copper levels are usually increased with chelation 

therapy such as penicillamine or trientine. 

The level of hepatic copper cannot be used to manage therapy since it does not differentiate between 

potentially toxic free copper and metallothionein bound copper. 

In treated patients, assays of urinary and/or plasma zinc may be a useful measure of treatment 

compliance. Values of urinary zinc above 2 mg/24 h and of plasma zinc above 1250 microgram/l 

generally indicate adequate compliance. 

 

Like with all anti-copper agents overtreatment carries the risk of copper deficiency, which is 

especially harmful for children and pregnant women since copper is required for proper growth and 

mental development. In these patient groups, urinary copper levels should be kept a little above the 

upper limit of normal or in the high normal range (i.e. 40 – 50 microgram/24 h). 

Laboratory follow-up including haematological surveillance and lipoproteins determination should 

also be performed in order to detect early manifestations of copper deficiency, such as anaemia and/or 

leukopenia resulting from bone marrow depression, and decrease in HDL cholesterol and HDL/total 

cholesterol ratio. 

As copper deficiency may also cause myeloneuropathy, physicians should be alert to sensory and 

motor symptoms and signs which may potentially indicate incipient neuropathy or myelopathy in 

patients treated with Wilzin. 

 



11 

The capsule shell contains sunset yellow FCF (E110), which may cause allergic reactions. 

 

4.5 Interaction with other medicinal products and other forms of interaction 
 

Other anti-copper agents 

Pharmacodynamic studies were conducted in Wilson’s disease patients on the combination of Wilzin 

(50 mg three times daily) with ascorbic acid (1 g once daily), penicillamine (250 mg four times daily), 

and trientine (250 mg four times daily). They showed no significant overall effect on copper balance 

although mild interaction of zinc with chelators (penicillamine and trientine) could be detected with 

decreased faecal but increased urinary copper excretion as compared with zinc alone. This is probably 

due to some extent of complexion of zinc by the chelator, thus reducing the effect of both active 

substances. 

When switching a patient on chelating treatment to Wilzin for maintenance therapy, the chelating 

treatment should be maintained and co-administered for 2 to 3 weeks since this is the time it takes for 

the zinc treatment to induce maximum metallothionein induction and full blockade of copper 

absorption. The administration of the chelating treatment and Wilzin should be separated by at least 

1 hour. 

 

Other medicinal products 

The absorption of zinc may be reduced by iron and calcium supplements, tetracyclines and 

phosphorus-containing compounds, while zinc may reduce the absorption of iron, tetracyclines, 

fluoroquinolones. 

 

Food 

Studies of the co-administration of zinc with food performed in healthy volunteers showed that the 

absorption of zinc was significantly delayed by many foods (including bread, hard boiled eggs, coffee 

and milk). Substances in food, especially phytates and fibres, bind zinc and prevent it from entering 

the intestinal cells. However, protein appears to interfere the least. 

 

4.6 Pregnancy and lactation 
 

Pregnancy 

Data on a limited number of exposed pregnancies in patients with Wilson’s disease give no indication 

of harmful effects of zinc on embryo/foetus and mother. Five miscarriages and 2 birth defects 

(microcephaly and correctable heart defect) were reported in 42 pregnancies. 

 

Animal studies conducted with different zinc salts do not indicate direct or indirect harmful effects 

with respect to pregnancy, embryonal/foetal development, parturition or postnatal development 

(see section 5.3).  

 

It is extremely important that pregnant Wilson’s disease patients continue their therapy during 

pregnancy. Which treatment should be used, zinc or chelating agent should be decided by the 

physician. Dose adjustments to guarantee that the foetus will not become copper deficient must be 

done and close monitoring of the patient is mandatory (see section 4.4). 

 

Lactation 

Zinc is excreted in human breast milk and zinc-induced copper deficiency in the breast-fed baby may 

occur. Therefore, breast-feeding should be avoided during Wilzin therapy. 

 

4.7 Effects on ability to drive and use machines 
 

No studies on the effects on the ability to drive and use machines have been performed. 

 

4.8 Undesirable effects 

 

Reported adverse reactions are listed below, by system organ class and by frequency.  



12 

Frequencies are defined as: very common (≥ 1/10), common (≥ 1/100 to < 1/10),  uncommon 

(≥ 1/1,000 to < 1/100), rare (≥ 1/10,000 to < 1/1,000), very rare (< 1/10,000), not known (cannot be 

estimated from the available data). 

Within each frequency grouping, undesirable effects are presented in order of decreasing seriousness. 
 

System organ class 

 

Adverse drug reactions 

Blood and lymphatic system disorders 

 

uncommon: sideroblastic anaemia, leukopenia 

Gastrointestinal disorders 

 

common: gastric irritation 

Investigations common: blood amylase, lipase and alkaline 

phosphatase increased 

 

 

Anaemia may be micro-, normo- or macrocytic and is often associated with leukopenia. Bone marrow 

examination usually reveals characteristic "ringed sideroblasts" (i.e. developing red blood cells 

containing iron-engorged paranuclear mitochondria). They may be early manifestations of copper 

deficiency and may recover rapidly following reduction of zinc dosage. However, they must be 

distinguished from haemolytic anaemia which commonly occurs where there is elevated serum free 

copper in uncontrolled Wilson’s disease. 
 

The most common undesirable effect is gastric irritation. This is usually worst with the first morning 

dose and disappears after the first days of treatment. Delaying the first dose to mid-morning or taking 

the dose with a little protein may usually relieve the symptoms. 

 

Elevations of serum alkaline phosphatase, amylase and lipase may occur after a few weeks of 

treatment, with levels usually returning to high normal within the first one or two years of treatment. 

 

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 national reporting system 

listed in Appendix V. 

 

 

4.9 Overdose 
 

Three cases of acute oral overdose with zinc salts (sulphate or gluconate) have been reported in the 

literature. Death occurred in a 35 year-old woman on the fifth day after ingestion of 6 g of zinc 

(40 times the proposed therapeutic dose) and was attributed to renal failure and haemorrhagic 

pancreatitis with hyperglycaemic coma. The same dose did not produce any symptoms except for 

vomiting in an adolescent who was treated by whole-bowel irrigation. Another adolescent who 

ingested 4 g of zinc had serum zinc level of about 50 mg/l 5 hours later and only experienced severe 

nausea, vomiting and dizziness. 

 

Treatment of overdose should be with gastric lavage or induced emesis as quickly as possible to 

remove unabsorbed zinc. Heavy metal chelation therapy should be considered if plasma zinc levels are 

markedly elevated (> 10 mg/l). 

 

 

5. PHARMACOLOGICAL PROPERTIES 

 

5.1  Pharmacodynamic properties 

 
Pharmacotherapeutic group: various alimentary tract and metabolism products, ATC code: A16AX05. 

 



13 

Wilson's disease (hepatolenticular degeneration) is an autosomal recessive metabolic defect in hepatic 

excretion of copper in the bile. Copper accumulation in the liver leads to hepatocellular injury and 

eventual cirrhosis. When the liver capacity of storing copper is exceeded copper is released into the 

blood and is taken up in extra hepatic sites, such as the brain, resulting in motor disorders and 

psychiatric manifestations. Patients may present clinically with predominantly hepatic, neurologic, or 

psychiatric symptoms. 

 

The active moiety in zinc acetate dihydrate is zinc cation, which blocks the intestinal absorption of 

copper from the diet and the reabsorption of endogenously secreted copper. Zinc induces the 

production of metallothionein in the enterocyte, a protein that binds copper thereby preventing its 

transfer into the blood. The bound copper is then eliminated in the stool following desquamation of the 

intestinal cells. 

 

Pharmacodynamic investigations of copper metabolism in patients with Wilson’s disease included 

determinations of net copper balance and radiolabelled copper uptake. A daily regimen of 150 mg of 

Wilzin in three administrations was shown to be effective in significantly reducing copper absorption 

and inducing a negative copper balance. 

 

5.2 Pharmacokinetic properties 
 

Since the mechanism of action of zinc is an effect on copper uptake at the level of the intestinal cell, 

pharmacokinetic evaluations based on blood levels of zinc do not provide useful information on zinc 

bioavailability at the site of action.  

 

Zinc is absorbed in the small intestine and its absorption kinetics suggest a tendency to saturation at 

increasing doses. Fractional zinc absorption is negatively correlated with zinc intake. It ranges from 30 

to 60% with usual dietary intake (7-15 mg/d) and decreases to 7% with pharmacological doses of 

100 mg/d. 

 

In the blood, about 80% of absorbed zinc is distributed to erythrocytes, with most of the remainder 

being bound to albumin and other plasma proteins. The liver is the main storage for zinc and hepatic 

zinc levels are increased during maintenance therapy with zinc. 

 

The plasma elimination half-life of zinc in healthy subjects is around 1 hour after a dose of 45 mg. The 

elimination of zinc results primarily from faecal excretion with relatively little from urine and sweat. 

The faecal excretion is in the greatest part due to the passage of unabsorbed zinc but it is also due to 

endogenous intestinal secretion. 

 

5.3 Preclinical safety data 
 

Preclinical studies have been conducted with zinc acetate and with other zinc salts. Pharmacological 

and toxicological data available showed large similarities between zinc salts and among animal 

species. 

The oral LD50 is approximately 300 mg zinc/kg body weight (about 100 to 150 times the human 

therapeutic dose). Repeat-dose toxicity studies have established that the NOEL (No Observed Effect 

Level) is about 95 mg zinc/kg body weight (about 48 times the human therapeutic dose). 

The weight of evidence, from in vitro and in vivo tests, suggests that zinc has no clinically relevant 

genotoxic activity. 

Reproduction toxicology studies performed with different zinc salts showed no clinically relevant 

evidence of embryotoxicity, foetotoxicity or teratogenicity. 

No conventional carcinogenicity study has been conducted with zinc acetate dihydrate. 

 

6. PHARMACEUTICAL PARTICULARS 

 

6.1 List of excipients 
 

Capsule content 



14 

maize starch 

magnesium stearate 

 

Capsule shell 

gelatin 

titanium dioxide (E171) 

sunset yellow FCF (E110) 

 

Printing ink 

black iron oxide (E172) 

shellac 

 

6.2 Incompatibilities 
 

Not applicable. 

 

6.3 Shelf life 
 

3 years. 

 

6.4 Special precautions for storage 
 

Do not store above 25°C. 

 

6.5 Nature and contents of container 
 

White HDPE bottle with a polypropylene and HDPE closure and contains a filler (cotton coil). Each 

bottle contains 250 capsules. 

 

6.6 Special precautions for disposal 
 

No special requirements 

 

7. MARKETING AUTHORISATION HOLDER 
 

Recordati Rare Diseases 

Immeuble “Le Wilson” 

70, avenue du Général de Gaulle 

F-92800 Puteaux 

France 

 

8. MARKETING AUTHORISATION NUMBER(S)  

 

EU/1/04/286/002 
 

9. DATE OF FIRST AUTHORISATION/RENEWAL OF THE AUTHORISATION 
 

Date of first authorisation: 13 October 2004 

Date of latest renewal: 13 October 2009 

 

10. DATE OF REVISION OF THE TEXT 

 

 

 

Detailed information on this product is available on the website of the European Medicines Agency 

(EMA) http://www.ema.europa.eu 



15 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

ANNEX II 

 

A. MANUFACTURER RESPONSIBLE FOR BATCH RELEASE 
 

B. CONDITIONS OR RESTRICTIONS REGARDING SUPPLY 
AND USE 

 

C. OTHER CONDITIONS AND REQUIREMENTS OF THE 
MARKETING AUTHORISATION 

 

D. CONDITIONS OR RESTRICTIONS WITH REGARD TO 
THE SAFE AND EFFECTIVE USE OF THE MEDICINAL 

PRODUCT 



16 

A. MANUFACTURER RESPONSIBLE FOR BATCH RELEASE 

 

Name and address of the manufacturer responsible for batch release 

 

Recordati Rare Diseases 

Immeuble "Le Wilson" 

70, avenue du Général de Gaulle 

F-92800 Puteaux 

France 

 

or 

 

Recordati Rare Diseases 

Eco River Parc 

30, rue des Peupliers 

F-92000 Nanterre 

France 

 

The printed package leaflet of the medicinal product must state the name and address of the 

manufacturer responsible for the release of the concerned batch. 

 

B. CONDITIONS OR RESTRICTIONS REGARDING SUPPLY AND USE  

 

Medicinal product subject to restricted medical prescription (See Annex I: Summary of Product 

Characteristics, section 4.2) 

 

 

C.  OTHER CONDITIONS AND REQUIREMENTS OF THE MARKETING 

AUTHORISATION 

 

The holder of this marketing authorisation must inform the European Commission about the marketing 

plans for the medicinal product authorised by this decision. 

 

 Periodic Safety Update Reports 
 

The requirements for submission of periodic safety update reports for this medicinal product are 

set out in the list of Union reference dates (EURD list) provided for under Article 107c(7) of 

Directive 2001/83/EC and any subsequent updates published on the European medicines web-

portal. 

 

 

D. CONDITIONS OR RESTRICTIONS WITH REGARD TO THE SAFE AND 

EFFECTIVE USE OF THE MEDICINAL PRODUCT   

 

 Risk Management Plan (RMP) 
 

Not applicable. 

 



17 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

ANNEX III 

 

LABELLING AND PACKAGE LEAFLET 



18 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

A. LABELLING 



19 

 

PARTICULARS TO APPEAR ON THE OUTER PACKAGING AND ON THE IMMEDIATE 

PACKAGING 

 

OUTER CARTON BOX AND BOTTLE LABEL (Wilzin 25 mg hard capsules) 

 

 

1. NAME OF THE MEDICINAL PRODUCT 

 

Wilzin 25 mg hard capsules 

Zinc 

 

 

2. STATEMENT OF ACTIVE SUBSTANCE(S) 

 

Each hard capsule contains 25 mg of zinc (corresponding to 83.92 mg of zinc acetate dihydrate). 

 

 

3. LIST OF EXCIPIENTS 

 

 

 

4. PHARMACEUTICAL FORM AND CONTENTS 

 

250 hard capsules. 

 

 

5. METHOD AND ROUTE(S) OF ADMINISTRATION 

 

Read the package leaflet before use. 

Oral use. 

 

 

6. SPECIAL WARNING THAT THE MEDICINAL PRODUCT MUST BE STORED OUT 

OF THE REACH AND SIGHT OF CHILDREN 

 

Keep out of the reach and sight of children. 

 

 

7. OTHER SPECIAL WARNING(S), IF NECESSARY 

 

 

8. EXPIRY DATE 

 

EXP 

 

 

9. SPECIAL STORAGE CONDITIONS 

 

Do not store above 25°C. 

 

 

10. SPECIAL PRECAUTIONS FOR DISPOSAL OF UNUSED MEDICINAL PRODUCTS 

OR WASTE MATERIALS DERIVED FROM SUCH MEDICINAL PRODUCTS, IF 

APPROPRIATE 

 



20 

 

11. NAME AND ADDRESS OF THE MARKETING AUTHORISATION HOLDER 

 

Recordati Rare Diseases 

Immeuble “Le Wilson” 

70, avenue du Général de Gaulle 

F-92800 Puteaux 

France 

 

 

12. MARKETING AUTHORISATION NUMBER(S) 

 

EU/1/04/286/001 
 

 

13. MANUFACTURER’S BATCH NUMBER 

 

Batch 

 

 

14. GENERAL CLASSIFICATION FOR SUPPLY 

 

Medicinal product subject to medical prescription. 

 

 

15. INSTRUCTIONS ON USE 

 

 

16. INFORMATION ON BRAILLE 

 

Wilzin 25 mg 

 

 

17. UNIQUE IDENTIFIER – 2D BARCODE 

 

2D barcode carrying the unique identifier included. 

 

 

18. UNIQUE IDENTIFIER - HUMAN READABLE DATA 

 

PC:  

SN:  

NN: 



21 

 

PARTICULARS TO APPEAR ON THE OUTER PACKAGING AND ON THE IMMEDIATE 

PACKAGING 

 

OUTER CARTON BOX AND BOTTLE LABEL (Wilzin 50 mg hard capsules) 

 

 

1. NAME OF THE MEDICINAL PRODUCT 

 

Wilzin 50 mg hard capsules 

Zinc 

 

2. STATEMENT OF ACTIVE SUBSTANCE(S) 

 

Each hard capsule contains 50 mg of zinc (corresponding to 167.84 mg of zinc acetate dihydrate) . 

 

 

3. LIST OF EXCIPIENTS 

 

Contains E110. See the package leaflet for further information. 

 

 

4. PHARMACEUTICAL FORM AND CONTENTS 

 

250 hard capsules. 

 

 

5. METHOD AND ROUTE(S) OF ADMINISTRATION 

 

Read the package leaflet before use. 

Oral use. 

 

 

6. SPECIAL WARNING THAT THE MEDICINAL PRODUCT MUST BE STORED OUT 

OF THE REACH AND SIGHT OF CHILDREN 

 

Keep out of the reach and sight of children. 

 

 

7. OTHER SPECIAL WARNING(S), IF NECESSARY 

 

 

8. EXPIRY DATE 

 

EXP 

 

 

9. SPECIAL STORAGE CONDITIONS 

 

Do not store above 25°C. 

 

 

10. SPECIAL PRECAUTIONS FOR DISPOSAL OF UNUSED MEDICINAL PRODUCTS 

OR WASTE MATERIALS DERIVED FROM SUCH MEDICINAL PRODUCTS, IF 

APPROPRIATE 

 



22 

 

11. NAME AND ADDRESS OF THE MARKETING AUTHORISATION HOLDER 

 

Recordati Rare Diseases 

Immeuble “Le Wilson” 

70, avenue du Général de Gaulle 

F-92800 Puteaux 

France 

 

 

12. MARKETING AUTHORISATION NUMBER(S) 

 

EU/1/04/286/002 
 

 

13. MANUFACTURER’S BATCH NUMBER 

 

Batch 

 

 

14. GENERAL CLASSIFICATION FOR SUPPLY 

 

Medicinal product subject to medical prescription. 

 

 

15. INSTRUCTIONS ON USE 

 

 

16. INFORMATION ON BRAILLE 

 

Wilzin 50 mg 

 

 

17. UNIQUE IDENTIFIER – 2D BARCODE 

 

2D barcode carrying the unique identifier included. 

 

 

18. UNIQUE IDENTIFIER - HUMAN READABLE DATA 

 

PC:  

SN:  
NN: 

 



23 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

B. PACKAGE LEAFLET 



24 

PACKAGE LEAFLET: INFORMATION FOR THE USER 
 

Wilzin 25 mg hard capsules 

Wilzin 50 mg hard capsules 
zinc 

 

Read all of this leaflet carefully before you start taking this medicine. 
- Keep this leaflet. You may need to read it again. 
- If you have any further questions, please ask your doctor or pharmacist. 
- This medicine has been prescribed for you personally. Do not pass it on to others. It may harm 

them, even if their symptoms are the same as yours. 

- If any of the side effects gets serious, or if you notice any side effects not listed in this leaflet, 
please tell your doctor or pharmacist. 

 

 

In this leaflet:  

1. What Wilzin is and what it is used for 

2. Before you take Wilzin 

3. How to take Wilzin 

4. Possible side effects 

5 How to store Wilzin 

6. Further information 

 

 

1. WHAT WILZIN IS AND WHAT IT IS USED FOR 
 

Wilzin belongs to a group of medicines called Various Alimentary Tract and metabolism products.  

 

Wilzin is indicated in the treatment of Wilson’s disease, which is a rare inherited defect in copper 

excretion. Dietary copper, which cannot be properly eliminated, accumulates first in the liver, then in 

other organs such as the eyes and the brain. This potentially leads to liver damage and neurological 

disorders. 

Wilzin blocks the absorption of copper from the intestine thereby preventing its transfer into the blood 

and its further accumulation in the body. Unabsorbed copper is then eliminated in the stool. 

 

Wilson’s disease will persist during the entire lifetime of the patient and therefore the need for this 

treatment is life-long. 

 

 

2. BEFORE YOU TAKE WILZIN 

 

Do not take Wilzin 
If you are allergic (hypersensitive) to zinc or any of the other ingredients of Wilzin. 

 

Take special care with Wilzin 

Wilzin is usually not recommended for initial therapy of patients with signs and symptoms of 

Wilson’s disease because of its slow onset of action. 

 

If you are currently treated with another anti-copper agent, for example, penicillamine, your doctor 

may add Wilzin before stopping the initial treatment. 

 

As with other anti-copper agents such as penicillamine, your symptoms may get worse after starting 

the treatment. In this case, you must inform your doctor. 

 

In order to follow up your condition and treatment your doctor will check your blood and urine on a 

regular basis. This is to ensure that you receive sufficient treatment. Monitoring may detect evidence 



25 

of insufficient treatment (copper excess) or excessive treatment (copper deficiency), both of which can 

be harmful, particularly to growing children and pregnant women. 

You should tell your doctor if you experience unusual muscle weakness or abnormal feeling in your 

limbs as this may indicate excessive treatment. 
 

Taking other medicines 
Please tell your doctor or your pharmacist if you are taking or have recently taken any other 

medicines, including medicines obtained without a prescription. 

Please consult your doctor before taking any other medicines which may reduce the effectiveness of 

Wilzin, such as iron, calcium supplements, tetracyclines (antibiotics) or phosphorus. Conversely, the 

effectiveness of some medicines, such as iron, tetracyclines or fluoroquinolones (antibiotics), may be 

reduced by Wilzin. 

 

Taking Wilzin with food and drink 

Wilzin should be taken on an empty stomach, separated from mealtimes. Dietary fibres and some dairy 

products, in particular, delay the absorption of zinc salts. Some patients experience stomach upset after 

the morning dose. Please discuss the matter with your Wilson’s disease doctor if this affects you. 

This side effect may be reduced by postponing the first dose of the day until mid-morning (between 

breakfast and the midday meal). It may also be minimised by taking the first dose of Wilzin with a 

small amount of protein-containing food, such as meat (but not milk). 

 

Pregnancy 

Please consult your doctor if you plan to become pregnant. It is very important to continue anti-copper 

therapy during pregnancy. 

If you become pregnant during therapy with Wilzin, your doctor will decide which treatment and 

which dose is best in your situation.  

 

Breast-feeding 

Breast-feeding should be avoided if you are on Wilzin therapy. Please discuss with your doctor. 

 

Driving and using machines 
No studies of the effects on the ability to drive and use machines have been performed. 

 

Important information about some of the ingredients of Wilzin 

Wilzin 50 mg hard capsules contains sunset yellow FCF (E110) which may cause allergic reactions. 

 

 

3. HOW TO TAKE WILZIN 

 

Always take Wilzin exactly as your doctor has told you. You should check with your doctor or 

pharmacist if you are not sure. For the different dose regimens Wilzin is available in hard capsules of 

25 mg or 50 mg. 

 

 For adults: 
The usual dose is 1 hard capsule of Wilzin 50 mg (or 2 hard capsules of Wilzin 25 mg) three times 

daily with a maximum dose of 1 hard capsule of Wilzin 50 mg (or 2 hard capsules of 

Wilzin 25 mg) five times daily. 

 For children and adolescents: 
The usual dose is: 

 - from 1 to 6 years: 1 hard capsule of Wilzin 25 mg twice daily 

 - from 6 to 16 years if bodyweight under 57 kg: 1 hard capsule of Wilzin 25 mg three times 

daily 

 - from 16 years or if bodyweight above 57 kg: 2 hard capsules of Wilzin 25 mg or 1 hard 

capsule of Wilzin 50 mg three times daily. 

 

Always take Wilzin on an empty stomach, at least one hour before or 2-3 hours after meals. 



26 

If the morning dose is not well tolerated (see section 4) it is possible to delay it to mid-morning, 

between breakfast and lunch. It is also possible to take Wilzin with a little protein, such as meat. 

 

If you have been prescribed Wilzin with another anti-copper agent, such as penicillamine, keep an 

interval of at least 1 hour between the two medicines. 

 

To administer Wilzin to children who are unable to swallow capsules, open the capsule and mix the 

powder with a little water (possibly flavoured with sugar or syrup). 
 

If you take more Wilzin than you should: 
If you take more Wilzin than prescribed, you may experience nausea, vomiting and dizziness. In this 

case you must ask your doctor for advice. 

 

If you forget to take Wilzin: 
Do not take a double dose to make up for a forgotten individual dose. 

 

If you have any further questions on the use of this medicine, ask your doctor. 

 

 

4. POSSIBLE SIDE EFFECTS 
 

Like all medicines, Wilzin can cause side effects, although not everybody gets them..  

 

These side effects may occur with certain frequencies, which are defined as follows:  

 very common: affects more than 1 user in 10 

 common:  affects 1 to 10 users in 100 

 uncommon:  affects 1 to 10 users in 1,000 

 rare:   affects 1 to 10 users in 10,000 

 very rare:  affects less than 1 user in 10,000 

 not known:  frequency cannot be estimated from the available data. 
 

Common:  

 After Wilzin intake, gastric irritation may occur, especially at the beginning of treatment. 

 Changes in blood tests have been reported, including an increase in some liver and pancreatic 
enzymes. 

 

Uncommon:  

 A decrease in blood red and white cells may occur. 
 

Reporting of side effects 

If you get any side effects, talk to your doctor or pharmacist. This includes any possible side effects 

not listed in this leaflet. You can also report side effects directly via the national reporting system 

listed in Appendix V. By reporting side effects you can help provide more information on the safety of 

this medicine. 

 

 

5. HOW TO STORE WILZIN 
 

 Keep out of the reach and sight of children. 
 

 Do not use Wilzin after the expiry date stated on the bottle and the carton, after EXP. The expiry 
date refers to the last day of that month. 

 

 Do not store above 25°C. 
 



27 

Medicines should not be disposed of via wastewater or household waste. Ask your pharmacist how to 

dispose of medicines no longer required. These measures will help to protect the environment. 

 

 

6. FURTHER INFORMATION 

 

What Wilzin contains 

 

The active substance is zinc. Each hard capsule contains 25 mg of zinc (corresponding to 83.92 mg of 

zinc acetate dihydrate) or 50 mg of zinc (corresponding to 167.84 mg of zinc acetate dihydrate).  

The other ingredients are maize starch and magnesium stearate. The capsule shell contains gelatin, 

titanium dioxide (E171) and either brilliant blue FCF (E133) for Wilzin 25 mg, or sunset yellow FCF 

(E110) for Wilzin 50 mg. The printing ink contains black iron oxide (E172) and shellac. 

 

 

What Wilzin looks like and contents of the pack 

 

Wilzin 25 mg is an aqua blue hard capsule imprinted "93-376”.  

Wilzin 50 mg is an orange opaque hard capsule imprinted “93-377”. 

It is available in packs of 250 hard capsules in a polyethylene bottle closed by a polypropylene and 

polyethylene closure. The bottle also contains a cotton filler. 

 

Marketing Authorisation Holder  

Recordati Rare Diseases 

Immeuble “Le Wilson” 

70, avenue du Général de Gaulle 

F-92800 Puteaux 

France 

 

Manufacturer 

Recordati Rare Diseases 

Immeuble “Le Wilson” 

70, avenue du Général de Gaulle 

F-92800 Puteaux 

France 

 

or 

 

Recordati Rare Diseases 

Eco River Parc 

30, rue des Peupliers 

F-92000 Nanterre 

France 

 

For any information about this medicine, please contact the local representative of the Marketing 

Authorisation Holder. 

 

Belgique/België/Belgien 

Recordati 
Tél/Tel: +32 2 46101 36 

Lietuva 

Recordati AB. 

Tel: + 46 8 545 80 230 

Švedija 

 

България 

Recordati Rare Diseases 

Teл.: +33 (0)1 47 73 64 58 

Франция  

Luxembourg/Luxemburg 

Recordati 

Tél/Tel: +32 2 46101 36 

Belgique/Belgien 



28 

Česká republika 

Recordati Rare Diseases 

Tel: +33 (0)1 47 73 64 58 

Francie 

 

Magyarország 

Recordati Rare Diseases 

Tel: +33 (0)1 47 73 64 58 

Franciaország  

Danmark 

Recordati AB. 

Tlf : +46 8 545 80 230 

Sverige 

 

Malta 

Recordati Rare Diseases 

Tel: +33 1 47 73 64 58 

Franza 

 

Deutschland 

Recordati Rare Diseases Germany GmbH 

Tel: +49 731 140 554 0 

Nederland 

Recordati 

Tel: +32 2 46101 36 

België 

 

Eesti 

Recordati AB. 

Tel: + 46 8 545 80 230  

Rootsi 

 

Norge 

Recordati AB. 

Tlf : +46 8 545 80 230 

Sverige  

 

Ελλάδα 

Recordati Rare Diseases  

Τηλ: +33 1 47 73 64 58 
Γαλλία 

 

Österreich 

Recordati Rare Diseases Germany GmbH 

Tel: +49 731 140 554 0 

Deutschland 

 

España 

Recordati Rare Diseases Spain S.L.U. 

Tel: + 34 91 659 28 90 

Polska 

Recordati Rare Diseases 

Tel: +33 (0)1 47 73 64 58 

Francja  

 

France 

Recordati Rare Diseases 

Tél: +33 (0)1 47 73 64 58 

 

Portugal 

Jaba Recordati S.A. 

Tel: +351 21 432 95 00 

 

Hrvatska 

Recordati Rare Diseases 

Tél: +33 (0)1 47 73 64 58 

Francuska 

 

România 

Recordati Rare Diseases 

Tel: +33 (0)1 47 73 64 58 

Franţa 

Ireland 

Recordati Rare Diseases 

Tel: +33 (0)1 47 73 64 58 

France 

Slovenija 

Recordati Rare Diseases 

Tel: +33 (0)1 47 73 64 58 

Francija  

 

Ísland 

Recordati AB. 

Simi:+46 8 545 80 230 

Svíþjóð 

 

Slovenská republika 

Recordati Rare Diseases 

Tel: +33 (0)1 47 73 64 58 

Francúzsko  

 

Italia 

Recordati Rare Diseases Italy Srl 

Tel: +39 02 487 87 173 

 

Suomi/Finland 

Recordati AB. 

Puh/Tel : +46 8 545 80 230 

Sverige 

 

 

 



29 

Κύπρος 

Recordati Rare Diseases 

Τηλ : +33 1 47 73 64 58 
Γαλλία 

 

Sverige 

Recordati AB. 

Tel : +46 8 545 80 230 

 

Latvija 

Recordati AB. 

Tel: + 46 8 545 80 230  

Zviedrija 

 

United Kingdom 

Recordati Rare Diseases UK Ltd. 

Tel: +44 (0)1491 414333 

 

 

This leaflet was last approved in  

 

Detailed information on this medicine is available on the European Medicines Agency (EMA) web 

site: http://www.ema.europa.eu. There are also links to other websites about rare diseases and 

treatments. 


	SUMMARY OF PRODUCT CHARACTERISTICS
	A. MANUFACTURER RESPONSIBLE FOR BATCH RELEASE
	B. CONDITIONS OR RESTRICTIONS REGARDING SUPPLY AND USE
	C. OTHER CONDITIONS AND REQUIREMENTS OF THE MARKETING AUTHORISATION
	D. CONDITIONS OR RESTRICTIONS WITH REGARD TO THE SAFE AND EFFECTIVE USE OF THE MEDICINAL PRODUCT
	A. LABELLING
	B. PACKAGE LEAFLET