Cystagon

1 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

ANNEX I 

 

SUMMARY OF PRODUCT CHARACTERISTICS 



2 

1. NAME OF THE MEDICINAL PRODUCT 

 

CYSTAGON 50 mg hard capsules 

 

 

2. QUALITATIVE AND QUANTITATIVE COMPOSITION 

 

Each hard capsule contains 50 mg of cysteamine (as mercaptamine bitartrate) . 

 

For a full list of excipients, see section 6.1. 

 

 

3. PHARMACEUTICAL FORM 

 

Hard Capsule 

White, opaque hard capsules with CYSTA 50 on the body and MYLAN on the cap. 

 

 

4. CLINICAL PARTICULARS 

 

4.1 Therapeutic indication 

 

CYSTAGON is indicated for the treatment of proven nephropathic cystinosis. Cysteamine reduces 

cystine accumulation in some cells (e.g. leukocytes, muscle and liver cells) of nephropathic cystinosis 

patients and, when treatment is started early, it delays the development of renal failure. 

 

4.2 Posology and method of administration 

 

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

treatment of cystinosis. 

 

The goal of therapy is to keep leucocyte cystine levels below 1 nmol hemicystine/mg protein. White 

blood cell (WBC) cystine levels should therefore be monitored to adjust the dose. The WBC levels 

should be measured 5 to 6 hours after dosing and should be checked frequently when initiating therapy 

(e.g. monthly) and every 3-4 months when on a stable dose. 

 

• For children up to age 12 years, CYSTAGON dosing should be on the basis of body surface 

area (g/m2/day). The recommended dose is 1.30 g/m2/day of the free base divided four times 

daily.  

• For patients over age 12 and over 50 kg weight, the recommended CYSTAGON dose is 

2 g/day, divided four times daily. 

 

Starting doses should be 1/4 to 1/6 of the expected maintenance dose, increased gradually over 4-

6 weeks to avoid intolerance. The dose should be raised if there is adequate tolerance and the 

leucocyte cystine level remains >1 nmol hemicystine/mg protein. The maximum dose of CYSTAGON 

used in clinical trials was 1.95 g/m2/day. 

The use of doses higher than 1.95 g/m2/day is not recommended (see section 4.4). 

 

Digestive tolerance of cysteamine is improved when the medicinal product is taken just after or with 

food. 

 

In children who are at risk of aspiration, aged approximately 6 years and under, the hard capsules 

should be opened and the content sprinkled on food. Experience suggests that foods such as milk, 

potatoes and other starch based products seem to be appropriate for mixing with the powder. However, 

acidic drinks, e.g. orange juice, should generally be avoided as the powder tends not to mix well and 

may precipitate out. 

 



3 

Patients on dialysis or post-transplantation: 

Experience has occasionally shown that some forms of cysteamine are less well tolerated (i.e.leading 

to more adverse events) when patients are on dialysis. A closer monitoring of the leucocyte cystine 

levels is recommended in these patients. 

 

Patients with hepatic insufficiency: 

Dose adjustment is not normally required; however, leucocyte cystine levels should be monitored. 

 

4.3 Contraindications 

 

Hypersensitivity to the active substance or to any of the excipients 

The use of CYSTAGON is contra-indicated during breast-feeding. CYSTAGON should not be used 

during pregnancy, particularly during the first trimester, unless clearly necessary (see section 4.6 and 

section 5.3 as it is teratogenic in animals. 

 

CYSTAGON is contraindicated in patients who have developed hypersensitivity to penicillamine. 

 

4.4 Special warnings and precautions for use 

 

CYSTAGON therapy must be initiated promptly after confirmation of the diagnosis of nephropathic 

cystinosis to achieve maximum benefit. 

 

Nephropathic cystinosis must have been diagnosed by both clinical signs and biochemical 

investigations (leucocyte cystine measurements). 

 

Cases of Ehlers-Danlos like syndrome and vascular disorders on elbows have been reported in 

children treated with high doses of different cysteamine preparations (cysteamine chlorhydrate or 

cystamine or cysteamine bitartrate) mostly above the maximal dose 1.95 g/m2/day. These skin lesions 

were associated with vascular proliferation, skin striae and bone lesions. 

It is therefore recommended to monitor regularly skin and to consider X-ray examinations of the bone 

as necessary. Self-examination of the skin by the patient or the parents should also be advised. If any 

similar skin or bone abnormalities appear, it is recommended to decrease the dose of CYSTAGON. 

The use of doses higher than 1.95g/m2/day is not recommended (see sections 4.2 and 4.8). 

 

Monitoring of blood cell count is recommended on a regular basis. 

 

Oral cysteamine has not been shown to prevent eye deposition of cystine crystals. Therefore, where 

cysteamine ophthalmic solution is used for that purpose, its usage should continue. 

 

In contrast to phosphocysteamine, CYSTAGON does not contain phosphate. Most patients will 

already be receiving phosphate supplements and the dose of these may need to be altered when 

CYSTAGON is substituted for phosphocysteamine. 

 

Intact CYSTAGON hard capsules should not be administered to children under the age of 

approximately 6 years due to risk of aspiration (see section 4.2). 

 

4.5 Interaction with other medicinal products and other forms of interaction 

  

No interaction studies have been performed 

CYSTAGON can be administered with electrolyte and mineral replacements necessary for 

management of the Fanconi syndrome as well as vitamin D and thyroid hormones. Indomethacin and 

CYSTAGON have been used simultaneously in some patients. In cases of patients with kidney 

transplants, anti-rejection treatments have been used with cysteamine. 

 



4 

4.6 Pregnancy and lactation 

 

There are no adequate data from the use of cysteamine bitartrate in pregnant women. Studies in 

animals have shown reproductive toxicity, including teratogenesis (see section 5.3). The potential risk 

for humans is unknown. The effect on pregnancy of untreated cystinosis is also unknown. 

Therefore, CYSTAGON should not be used during pregnancy, particularly during the first trimester, 

unless clearly necessary. 

If a pregnancy is diagnosed or planned, the treatment should be carefully reconsidered and the patient 

must be advised of the possible teratogenic risk of cysteamine. 

 

CYSTAGON excretion in human's milk is unknown. However, due to the results of animal studies in 

breast-feeding mothers and neonates (see section 5.3), breast-feeding is contraindicated in women 

taking CYSTAGON.  

 

4.7 Effects on ability to drive and use machines 
 

CYSTAGON has minor or moderate influence on the ability to drive and use machines 

CYSTAGON may cause drowsiness. When starting therapy, patients should not engage in potentially 

hazardous activities until the effects of the medicinal product on each individual are known. 

 

4.8 Undesirable effects 

 

Approximately 35% of patients can be expected to experience adverse reactions. These mainly involve 

the gastrointestinal and central nervous systems. When these effects appear at the initiation of 

cysteamine therapy, temporary suspension and gradual reintroduction of treatment may be effective in 

improving tolerance. 

 

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

defined as: very common (≥ 1/10), common (≥1/100 to 1/10) and uncommon (≥1/1,000 to 1/100). 

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

 

Investigations Common: Liver function tests abnormal 

Blood and lymphatic system disorders Uncommon: Leukopenia 

Nervous system disorders Common: Headache, encephalopathy 

Uncommon: Somnolence, convulsions 

Gastrointestinal disorders Very common: Vomiting, nausea, diarrhoea 

Common: Abdominal pain, breath odour, dyspepsia, 

gastroenteritis 

Uncommon: Gastrointestinal ulcer 

Renal and urinary disorders Uncommon: Nephrotic syndrome 

Skin and subcutaneous tissue disorders Common: Skin odour abnormal, rash 

Uncommon: Hair colour changes, skin striae, skin 

fragility (molluscoid pseudotumor on elbows) 

Musculoskeletal and connective tissue 

disorders 

Uncommon: Joint hyperextension, leg pain, genu 

valgum, osteopenia, compression fracture, scoliosis. 

Metabolism and nutrition disorders Very common: Anorexia 

  

General disorders and administration site 

conditions 

Very  common: Lethargy, pyrexia 

Common: Asthenia 

Immune system disorders Uncommon: Anaphylactic reaction 

Psychiatric disorders  Uncommon: Nervousness, hallucination 

 

 

 



5 

Cases of nephrotic syndrome have been reported within 6 months of starting therapy with progressive 

recovery after treatment discontinuation. In some cases, histology showed a membranous 

glomerulonephritis of the renal allograft and hypersensitivity interstitial nephritis. 

 

Cases of Ehlers-Danlos like syndrome and vascular disorders on elbows have been reported in 

children chronically treated with high doses of different cysteamine preparations (cysteamine 

chlorhydrate or cystamine or cysteamine bitartrate) mostly above the maximal dose 1.95 g/m2/day. 

In some cases, these skin lesions were associated with vascular proliferation, skin striae and bone 

lesions first seen during an X-ray examination. Bone disorders reported were genu valgum, leg pain 

and hyperextensive joints, osteopenia, compression fractures, and scoliosis. 

In cases where histopathological examination of the skin was performed, the results suggested 

angioendotheliomatosis. 

One patient subsequently died of acute cerebral ischemia with marked vasculopathy.  

In some patients, the skin lesions on elbows regressed after CYSTAGON dose reduction. 

Cysteamine mechanism of action by interfering with the cross-linking of collagen fibers has been 

postulated (see section 4.4). 

 

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 

 

An overdose of cysteamine may cause progressive lethargy. 

 

Should overdosage occur, the respiratory and cardiovascular systems should be supported 

appropriately. No specific antidote is known. It is not known if cysteamine is removed by 

haemodialysis. 

 

 

5. PHARMACOLOGICAL PROPERTIES 

 

5.1 Pharmacodynamic properties 

 

Pharmacotherapeutic group: Alimentary tract and metabolism product, ATC code: A16AA04.  

 

Normal individuals and heterozygous subjects for cystinosis have white cell cystine levels of < 0.2, 

and usually below 1 nmol hemicystine/mg protein, respectively. Individuals with nephropathic 

cystinosis have elevations of white cell cystine above 2 nmol hemicystine/mg protein 

 

Cysteamine reacts with cystine to form the mixed disulfide of cysteamine and cysteine.  

The mixed disulfide is then exported from the lysosomes by an intact lysine transport system. The 

decrease in leucocyte cystine levels is correlated to the cysteamine plasma concentration over the six 

hours following the administration of CYSTAGON.  

 

The leucocyte cystine level reaches its minimum (mean ( sd) value: 1.8  0.8 hours) slightly later 

than the peak plasma cysteamine concentration (mean ( sd) value: 1.4  0.4 hours) and returns to its 

baseline level as the plasma cysteamine concentration decreases at 6 hours post-dose. 

 

In one clinical study, baseline white cell cystine levels were 3.73 (range 0.13 to 19.8) nmol 

hemicystine/mg protein and were maintained close to 1 nmol hemicystine/mg protein with a 

cysteamine dose range of 1.3 to 1.95 g/m2/day.  

An earlier study treated 94 children with nephropathic cystinosis with increasing doses of cysteamine 

to attain white cell cystine levels of less than 2 nmol hemicystine/mg protein 5 to 6 hours post-dose, 

and compared their outcome with an historical control group of 17 children treated with placebo. The 



6 

principal efficacy measurements were serum creatinine and calculated creatinine clearance and growth 

(height). The mean white cell cystine level attained during treatment was 1.7 + 0.2 nmol 

hemicystine/mg protein. Among cysteamine patients, glomerular function was maintained over time. 

Placebo treated patients, in contrast, experienced a gradual rise in serum creatinine. Patients on 

treatment maintained growth as compared to untreated patients. However, growth velocity did not 

increase enough to allow patients to catch up the normal for their age. Renal tubular function was not 

affected by treatment. Two other studies have shown similar results. 

 

In all studies, patient response was better when treatment was started at an early age with good renal 

function. 

 

5.2 Pharmacokinetic properties 

 

Following a single oral dose of cysteamine bitartrate equivalent to 1.05 g of cysteamine free base in 

healthy volunteers, the mean ( sd) values for the time to peak and peak plasma concentration are 1.4 

( 0.5) hours and 4.0 ( 1.0) µg/ml, respectively. In patients at steady state, these values are 1.4 ( 0.4) 

hours and 2.6 ( 0.9) µg/ml, respectively, after a dose ranging from 225 to 550 mg. 

Cysteamine bitartrate (CYSTAGON) is bioequivalent to cysteamine hydrochloride and 

phosphocysteamine. 

 

The in vitro plasma protein binding of cysteamine, which is mostly to albumin, is independent of 

plasma drug concentration over the therapeutic range, with a mean ( sd) value of 54.1 % ( 1.5). The 

plasma protein binding in patients at steady state is similar: 53.1 % ( 3.6) and 51.1 % ( 4.5) at 1.5 

and 6 hours post-dose, respectively. 

 

In a pharmacokinetic study performed in 24 healthy volunteers for 24 hours, the mean estimate ( sd) 

for the terminal half-life of elimination was 4.8 ( 1.8) hours. 

 

The elimination of unchanged cysteamine in the urine has been shown to range between 0.3 % and 

1.7% of the total daily dose in four patients; the bulk of cysteamine is excreted as sulphate. 

 

Very limited data suggest that cysteamine pharmacokinetic parameters may not be significantly 

modified in patients with mild to moderate renal insufficiency. No information is available for patients 

with severe renal insufficiency. 

 

5.3 Preclinical safety data 

 

Genotoxicity studies have been performed: although in published studies using cysteamine, induction 

of chromosome aberrations in cultured eukaryotic cell lines has been reported, specific studies with 

cysteamine bitartrate did not show any mutagenic effects in the Ames test or any clastogenic effect in 

the mouse micronucleus test.  

 

Reproduction studies showed embryofoetotoxic effects (resorptions and post-implantation losses) in 

rats at the 100 mg/kg/day dose level and in rabbits receiving cysteamine 50 mg/kg/day. Teratogenic 

effects have been described in rats when cysteamine is administered over the period of organogenesis 

at a dose of 100 mg/kg/day.  

This is equivalent to 0.6 g/m2/day in the rat, which is less than half the recommended clinical 

maintenance dose of cysteamine, i.e. 1.30 g/ m2/day. A reduction of fertility was observed in rats at 

375 mg/kg/day, a dose at which body weight gain was retarded. At this dose, weight gain and survival 

of the offspring during lactation was also reduced. High doses of cysteamine impair the ability of 

lactating mothers to feed their pups. Single doses of the drug inhibit prolactin secretion in animals. 

Administration of cysteamine in neonate rats induced cataracts. 

High doses of cysteamine, either by oral or parenteral routes, produce duodenal ulcers in rats and mice 

but not in monkeys.  Experimental administration of the drug causes depletion of somatostatin in 

several animal species. The consequence of this for the clinical use of the drug is unknown.  

 

No carcinogenic studies have been conducted with CYSTAGON. 



7 

6. PHARMACEUTICAL PARTICULARS 

 

6.1 List of excipients 

 

Capsule content: 

microcrystalline cellulose,  

pregelatinized starch,  

magnesium stearate/sodium lauryl sulfate, 

colloidal silicon dioxide,  

croscarmellose sodium 

Capsule shell: 

gelatin,  

titanium dioxide,  

 

black ink on hard capsules containing E172 

 

6.2 Incompatibilities 

 

Not applicable. 

 

6.3 Shelf life 

 

2 years. 

 

6.4 Special precautions for storage 

 

Do not store above 25°C. 

Keep the container tightly closed in order to protect from light and moisture. 

 

6.5 Nature and contents of container 

 

HDPE bottles of 100 and 500 hard capsules. A desiccant unit containing black activated carbon and 

silica gel granules is included in the bottle. 

Not all pack sizes may be marketed. 

 

6.6 Special precautions for disposal and other handling 
 

Not applicable  

 

 

7. MARKETING AUTHORISATION HOLDER 
 

Recordati Rare Diseases 

Immeuble “Le Wilson” 

70, Avenue du Général de Gaulle 

F-92800 Puteaux 

France 

 

 

8. MARKETING AUTHORISATION NUMBERS 

 

EU/1/97/039/001 (100 hard capsules per bottle), EU/1/97/039/002 (500 hard capsules per bottle). 

 

 

9. DATE OF FIRST AUTHORISATION/RENEWAL OF THE AUTHORISATION 

 

Date of first authorisation: 23 June 1997. 



8 

Date of latest renewal: 23 June 2007. 

 

 

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 

 

CYSTAGON 150 mg hard capsules 

 

 

2. QUALITATIVE AND QUANTITATIVE COMPOSITION 

 

Each hard capsule contains 150 mg of cysteamine (as mercaptamine bitartrate)  

For a full list of excipients, see section 6.1. 

 

 

3. PHARMACEUTICAL FORM 

 

Hard Capsule 

White, opaque hard capsules with CYSTAGON 150 on the body and MYLAN on the cap. 

 

 

4. CLINICAL PARTICULARS 

 

4.1 Therapeutic indication 

 

CYSTAGON is indicated for the treatment of proven nephropathic cystinosis. Cysteamine reduces 

cystine accumulation in some cells (e.g. leukocytes, muscle and liver cells) of nephropathic cystinosis 

patients and, when treatment is started early, it delays the development of renal failure. 

 

4.2 Posology and method of administration 

 

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

treatment of cystinosis. 

 

The goal of therapy is to keep leucocyte cystine levels below 1 nmol hemicystine/mg protein. White 

blood cell (WBC) cystine levels should therefore be monitored to adjust the dose. The WBC levels 

should be measured 5 to 6 hours after dosing and should be checked frequently when initiating therapy 

(e.g. monthly) and every 3-4 months when on a stable dose. 

 

• For children up to age 12 years, CYSTAGON dosing should be on the basis of body surface 

area (g/m2/day). The recommended dose is 1.30 g/m2/day of the free base divided four times 

daily.  

• For patients over age 12 and over 50 kg weight, the recommended CYSTAGON dose is 

2 g/day, divided four times daily. 

 

Starting doses should be 1/4 to 1/6 of the expected maintenance dose, increased gradually over 4-

6 weeks to avoid intolerance. The dose should be raised if there is adequate tolerance and the 

leucocyte cystine level remains >1 nmol hemicystine/mg protein. The maximum dose of CYSTAGON 

used in clinical trials was 1.95 g/m2/day. 

The use of doses higher than 1.95 g/m2/day is not recommended (see section 4.4). 

 

Digestive tolerance of cysteamine is improved when the medicinal product is taken just after or with 

food. 

 

In children who are at risk of aspiration, aged approximately 6 years and under, the hard capsules 

should be opened and the content sprinkled on food. Experience suggests that foods such as milk, 

potatoes and other starch based products seem to be appropriate for mixing with the powder. However, 

acidic drinks, e.g. orange juice, should generally be avoided as the powder tends not to mix well and 

may precipitate out. 

 



10 

Patients on dialysis or post-transplantation: 

Experience has occasionally shown that some forms of cysteamine are less well tolerated (i.e. leading 

to more adverse events) when patients are on dialysis. A closer monitoring of the leucocyte cystine 

levels is recommended in these patients. 

 

Patients with hepatic insufficiency: 

Dose adjustment is not normally required; however, leucocyte cystine levels should be monitored. 

 

4.3 Contraindications 

 

Hypersensitivity to the active substance or to any of the excipients 

The use of CYSTAGON is contra-indicated during breast-feeding. CYSTAGON should not be used 

during pregnancy, particularly during the first trimester, unless clearly necessary (see section 4.6 and 

section 5.3), as it is teratogenic in animals. 

 

CYSTAGON is contraindicated in patients who have developed hypersensitivity to penicillamine. 

 

4.4 Special warnings and special precautions for use 

 

CYSTAGON therapy must be initiated promptly after confirmation of the diagnosis of nephropathic 

cystinosis to achieve maximum benefit. 

 

Nephropathic cystinosis must have been diagnosed by both clinical signs and biochemical 

investigations (leucocyte cystine measurements). 

 

Cases of Ehlers-Danlos like syndrome and vascular disorders on elbows have been reported in 

children treated with high doses of different cysteamine preparations (cysteamine chlorhydrate or 

cystamine or cysteamine bitartrate) mostly above the maximal dose 1.95 g/m2/day. These skin lesions 

were associated with vascular proliferation, skin striae and bone lesions. 

It is therefore recommended to monitor regularly skin and to consider X-ray examinations of the bone 

as necessary. Self-examination of the skin by the patient or the parents should also be advised. If any 

similar skin or bone abnormalities appear, it is recommended to decrease the dose of CYSTAGON. 

The use of doses higher than 1.95g/m2/day is not recommended (see sections 4.2 and 4.8). 

 

Monitoring of blood cell count is recommended on a regular basis. 

 

Oral cysteamine has not been shown to prevent eye deposition of cystine crystals. Therefore, where 

cysteamine ophthalmic solution is used for that purpose, its usage should continue. 

 

In contrast to phosphocysteamine, CYSTAGON does not contain phosphate. Most patients will 

already be receiving phosphate supplements and the dose of these may need to be altered when 

CYSTAGON is substituted for phosphocysteamine. 

 

Intact CYSTAGON hard capsules should not be administered to children under the age of 

approximately 6 years due to risk of aspiration (see section 4.2). 

 

4.5 Interaction with other medicinal products and other forms of interaction 

 

No interaction studies have been performed 

Interactions with other medicines have not been studied. CYSTAGON can be administered with 

electrolyte and mineral replacements necessary for management of the Fanconi syndrome as well as 

vitamin D and thyroid hormones. Indomethacin and CYSTAGON have been used simultaneously in 

some patients. In cases of patients with kidney transplants, anti-rejection treatments have been used 

with cysteamine. 

 



11 

4.6 Pregnancy and lactation 

 

There are no adequate data from the use of cysteamine bitartrate in pregnant women. Studies in 

animals have shown reproductive toxicity, including teratogenesis (see section 5.3). The potential risk 

for humans is unknown. The effect on pregnancy of untreated cystinosis is also unknown. 

Therefore, CYSTAGON should not be used during pregnancy, particularly during the first trimester, 

unless clearly necessary. 

If a pregnancy is diagnosed or planned, the treatment should be carefully reconsidered and the patient 

must be advised of the possible teratogenic risk of cysteamine. 

 

CYSTAGON excretion in human's milk is unknown. However, due to the results of animal studies in 

breast-feeding mothers and neonates (see section 5.3), breast-feeding is contra-indicated in women 

taking CYSTAGON.  

 

4.7 Effects on ability to drive and use machines 
 

CYSTAGON has minor or moderate influence on the ability to drive ans use machines 

CYSTAGON may cause drowsiness. When starting therapy, patients should not engage in potentially 

hazardous activities until the effects of the medicinal product on each individual are known. 

 

4.8 Undesirable effects 

 

Approximately 35% of patients can be expected to experience adverse reactions. These mainly involve 

the gastrointestinal and central nervous systems. When these effects appear at the initiation of 

cysteamine therapy, temporary suspension and gradual reintroduction of treatment may be effective in 

improving tolerance. 

 

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

defined as: very common (≥ 1/10), common (≥1/100 to 1/10) and uncommon (≥1/1,000 to 1/100). 

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

 

Investigations Common: Liver function tests abnormal 

Blood and lymphatic system disorders Uncommon: Leukopenia 

Nervous system disorders Common: Headache, encephalopathy 

Uncommon: Somnolence, convulsions 

Gastrointestinal disorders Very common: Vomiting, nausea, diarrhoea 

Common: Abdominal pain, breath odour, dyspepsia, 

gastroenteritis 

Uncommon: Gastrointestinal ulcer 

Renal and urinary disorders Uncommon: Nephrotic syndrome 

Skin and subcutaneous tissue disorders Common: Skin odour abnormal, rash 

Uncommon: Hair colour changes, skin striae, skin 

fragility (molluscoid pseudotumor on elbows) 

Musculoskeletal and connective tissue 

disorders 

Uncommon: Joint hyperextension, leg pain, genu 

valgum, osteopenia, compression fracture, scoliosis. 

Metabolism and nutrition disorders Very common: Anorexia 

  

General disorders and administration site 

conditions 

Very  common: Lethargy, pyrexia 

Common: Asthenia 

Immune system disorders Uncommon: Anaphylactic reaction 

Psychiatric disorders  Uncommon: Nervousness, hallucination 

 

 

 



12 

Cases of nephrotic syndrome have been reported within 6 months of starting therapy with progressive 

recovery after treatment discontinuation. In some cases, histology showed a membranous 

glomerulonephritis of the renal allograft and hypersensitivity interstitial nephritis. 

 

Cases of Ehlers-Danlos like syndrome and vascular disorders on elbows have been reported in 

children chronically treated with high doses of different cysteamine preparations (cysteamine 

chlorhydrate or cystamine or cysteamine bitartrate) mostly above the maximal dose 1.95 g/m2/day. 

In some cases, these skin lesions were associated with vascular proliferation, skin striae and bone 

lesions first seen during an X-ray examination. Bone disorders reported were genu valgum, leg pain 

and hyperextensive joints, osteopenia, compression fractures, and scoliosis. 

In cases where histopathological examination of the skin was performed, the results suggested 

angioendotheliomatosis. 

One patient subsequently died of acute cerebral ischemia with marked vasculopathy.  

In some the patients, the skin lesions on elbows regressed after CYSTAGON dose reduction. 

Cysteamine mechanism of action by interfering with the cross-linking of collagen fibers has been 

postulated (see section 4.4). 

 

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 

 

An overdose of cysteamine may cause progressive lethargy. 

 

Should overdosage occur, the respiratory and cardiovascular systems should be supported 

appropriately. No specific antidote is known. It is not known if cysteamine is removed by 

haemodialysis. 

 

 

5. PHARMACOLOGICAL PROPERTIES 

 

5.1 Pharmacodynamic properties 

 

Pharmacotherapeutic group: Alimentary tract and metabolism product, ATC code: A16AA04.  

 

Normal individuals and heterozygous subjects for cystinosis have white cell cystine levels of < 0.2, 

and usually below 1 nmol hemicystine/mg protein, respectively. Individuals with nephropathic 

cystinosis have elevations of white cell cystine above 2 nmol hemicystine/mg protein 

 

Cysteamine reacts with cystine to form the mixed disulfide of cysteamine and cysteine. 

 The mixed disulfide is then exported from the lysosomes by an intact lysine transport system. The 

decrease in leucocyte cystine levels is correlated to the cysteamine plasma concentration over the six 

hours following the administration of CYSTAGON.  

 

The leucocyte cystine level reaches its minimum (mean ( sd) value: 1.8  0.8 hours) slightly later 

than the peak plasma cysteamine concentration (mean ( sd) value: 1.4  0.4 hours) and returns to its 

baseline level as the plasma cysteamine concentration decreases at 6 hours post-dose. 

 

In one clinical study, baseline white cell cystine levels were 3.73 (range 0.13 to 19.8) nmol 

hemicystine/mg protein and were maintained close to 1 nmol hemicystine/mg protein with a 

cysteamine dose range of 1.3 to 1.95 g/m2/day.  

An earlier study treated 94 children with nephropathic cystinosis with increasing doses of cysteamine 

to attain white cell cystine levels of less than 2 nmol hemicystine/mg protein 5 to 6 hours post-dose, 

and compared their outcome with an historical control group of 17 children treated with placebo. The 



13 

principal efficacy measurements were serum creatinine and calculated creatinine clearance and growth 

(height). The mean white cell cystine level attained during treatment was 1.7 + 0.2 nmol 

hemicystine/mg protein. Among cysteamine patients, glomerular function was maintained over time. 

Placebo treated patients, in contrast, experienced a gradual rise in serum creatinine. Patients on 

treatment maintained growth as compared to untreated patients. However, growth velocity did not 

increase enough to allow patients to catch up the normal for their age. Renal tubular function was not 

affected by treatment. Two other studies have shown similar results. 

 

In all studies, patient response was better when treatment was started at an early age with good renal 

function. 

 

5.2 Pharmacokinetic properties 

 

Following a single oral dose of cysteamine bitartrate equivalent to 1.05 g of cysteamine free base in 

healthy volunteers, the mean ( sd) values for the time to peak and peak plasma concentration are 1.4 

( 0.5) hours and 4.0 ( 1.0) µg/ml, respectively. In patients at steady state, these values are 1.4 ( 0.4) 

hours and 2.6 ( 0.9) µg/ml, respectively, after a dose ranging from 225 to 550 mg. 

Cysteamine bitartrate (CYSTAGON) is bioequivalent to cysteamine hydrochloride and 

phosphocysteamine. 

 

The in vitro plasma protein binding of cysteamine, which is mostly to albumin, is independent of 

plasma drug concentration over the therapeutic range, with a mean ( sd) value of 54.1 % ( 1.5). The 

plasma protein binding in patients at steady state is similar: 53.1 % ( 3.6) and 51.1 % ( 4.5) at 1.5 

and 6 hours post-dose, respectively. 

 

In a pharmacokinetic study performed in 24 healthy volunteers for 24 hours, the mean estimate ( sd) 

for the terminal half-life of elimination was 4.8 ( 1.8) hours. 

 

The elimination of unchanged cysteamine in the urine has been shown to range between 0.3 % and 

1.7% of the total daily dose in four patients; the bulk of cysteamine is excreted as sulphate. 

 

Very limited data suggest that cysteamine pharmacokinetic parameters may not be significantly 

modified in patients with mild to moderate renal insufficiency. No information is available for patients 

with severe renal insufficiency. 

 

5.3 Preclinical safety data 

 

Genotoxicity studies have been performed: although in published studies using cysteamine, induction 

of chromosome aberrations in cultured eukaryotic cell lines has been reported, specific studies with 

cysteamine bitartrate did not show any mutagenic effects in the Ames test or any clastogenic effect in 

the mouse micronucleus test.  

 

Reproduction studies showed embryofoetotoxic effects (resorptions and post-implantation losses) in 

rats at the 100 mg/kg/day dose level and in rabbits receiving cysteamine 50 mg/kg/day. Teratogenic 

effects have been described in rats when cysteamine is administered over the period of organogenesis 

at a dose of 100 mg/kg/day.  

This is equivalent to 0.6 g/m2/day in the rat, which is less than half the recommended clinical 

maintenance dose of cysteamine, i.e. 1.30 g/ m2/day. A reduction of fertility was observed in rats at 

375 mg/kg/day, a dose at which body weight gain was retarded. At this dose, weight gain and survival 

of the offspring during lactation was also reduced. High doses of cysteamine impair the ability of 

lactating mothers to feed their pups. Single doses of the drug inhibit prolactin secretion in animals. 

Administration of cysteamine in neonate rats induced cataracts. 

High doses of cysteamine, either by oral or parenteral routes, produce duodenal ulcers in rats and mice 

but not in monkeys.  Experimental administration of the drug causes depletion of somatostatin in 

several animal species. The consequence of this for the clinical use of the drug is unknown.  

 

No carcinogenic studies have been conducted with CYSTAGON. 



14 

6. PHARMACEUTICAL PARTICULARS 

 

6.1 List of excipients 

 

Capsule content: 

microcrystalline cellulose,  

pregelatinized starch,  

magnesium stearate/sodium lauryl sulfate,  

colloidal silicon dioxide,  

croscarmellose sodium 

Capsule shell: 

gelatin,  

titanium dioxide,  

black ink on hard capsules containing E172 

 

6.2 Incompatibilities 

 

Not applicable. 

 

6.3 Shelf life 

 

2 years. 

 

6.4 Special precautions for storage 

 

Do not store above 25°C. 

Keep the container tightly closed in order to protect from light and moisture. 

 

6.5 Nature and contents of container 

 

HDPE bottles of 100 and 500 hard capsules. A desiccant unit containing black activated carbon and 

silica gel granules is included in the bottle. 

Not all pack sizes may be marketed. 

 

6.6 Special precautions for disposal and other handling 
 

Not applicable. 

 

7. MARKETING AUTHORISATION HOLDER 
 

Recordati Rare Diseases 

Immeuble “Le Wilson” 

70 avenue du Général de Gaulle 

F-92800 Puteaux 

France 

 

 

8. MARKETING AUTHORISATION NUMBERS 

 

EU/1/97/039/003 (100 hard capsules per bottle), EU/1/97/039/004 (500 hard capsules per bottle). 

 

 

9. DATE OF FIRST AUTHORISATION/RENEWAL OF THE AUTHORISATION 

 

Date of first authorisation: 23 June 1997. 

Date of latest renewal: 23 June 2007 



15 

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 



16 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

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 

 

 



17 

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 

 

 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. 

 

 



18 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

ANNEX III 

 

LABELLING AND PACKAGE LEAFLET 



19 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

A. LABELLING



20 

 

PARTICULARS TO APPEAR ON THE OUTER PACKAGING 

 

OUTER CARTON CYSTAGON 50 mg x 100 hard capsules 

OUTER CARTON CYSTAGON 50 mg x 500 hard capsules 

 

 

1. NAME OF THE MEDICINAL PRODUCT 

 

CYSTAGON 50 mg hard capsules  

Cysteamine  

 

 

2. STATEMENT OF ACTIVE SUBSTANCE(S) 

 

Each hard capsule contains 50 mg of cysteamine (as mercaptamine bitartrate) . 

 

 

3. LIST OF EXCIPIENTS 

 

 

4. PHARMACEUTICAL FORM AND CONTENTS 

 

100 hard capsules (with a desiccant unit in the bottle) 

500 hard capsules (with a desiccant unit in the bottle) 

 

 

5. METHOD AND ROUTE(S) OF ADMINISTRATION 

 

Oral use 

 

Read the package leaflet before 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 {month/year} 

 

 

9. SPECIAL STORAGE CONDITIONS 

 

Do not store above 25°C. 

Keep the container tightly closed in order to protect from light and moisture 



21 

 

10. SPECIAL PRECAUTIONS FOR DISPOSAL OF UNUSED MEDICINAL PRODUCTS 

OR WASTE MATERIALS DERIVED FROM SUCH MEDICINAL PRODUCTS, IF 

APPROPRIATE 

 

 

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/1/97/039/001 – 100 hard capsules 

EU/1/97/039/002 – 500 hard capsules 

 

 

13. MANUFACTURER’S BATCH NUMBER 

 

Batch {number} 

 

 

14. GENERAL CLASSIFICATION FOR SUPPLY 

 

Medicinal product subject to medical prescription. 

 

 

15. INSTRUCTIONS ON USE 

 

 

16. INFORMATION IN BRAILLE 

 

Cystagon 50 mg 

 

 

17. UNIQUE IDENTIFIER – 2D BARCODE 

 

2D barcode carrying the unique identifier included. 

 

 

18. UNIQUE IDENTIFIER - HUMAN READABLE DATA 

 

PC:  

SN:  

NN: 



22 

 

PARTICULARS TO APPEAR ON THE OUTER PACKAGING 

 

OUTER CARTON CYSTAGON 150 mg x 100 hard capsules 

OUTER CARTON CYSTAGON 150 mg x 500 hard capsules 

 

 

1. NAME OF THE MEDICINAL PRODUCT 

 

CYSTAGON 150 mg hard capsules  

Cysteamine  

 

 

2. STATEMENT OF ACTIVE SUBSTANCE(S) 

 

Each hard capsule contains 150 mg of cysteamine (as mercaptamine bitartrate) . 

 

 

3. LIST OF EXCIPIENTS 

 

 

4. PHARMACEUTICAL FORM AND CONTENTS 

 

100 hard capsules (with a desiccant unit in the bottle) 

500 hard capsules (with a desiccant unit in the bottle) 

 

 

5. METHOD AND ROUTE(S) OF ADMINISTRATION 

 

Oral use 

 

Read the package leaflet before 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 {month/year} 

 

 

9. SPECIAL STORAGE CONDITIONS 

 

Do not store above 25°C. 

Keep the container tightly closed in order to protect from light and moisture 



23 

 

10. SPECIAL PRECAUTIONS FOR DISPOSAL OF UNUSED MEDICINAL PRODUCTS 

OR WASTE MATERIALS DERIVED FROM SUCH MEDICINAL PRODUCTS, IF 

APPROPRIATE 

 

 

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/1/97/039/003 – 100 hard capsules 

EU/1/97/039/004 – 500 hard capsules 

 

 

13. MANUFACTURER’S BATCH NUMBER 

 

Batch {number} 

 

 

14. GENERAL CLASSIFICATION FOR SUPPLY 

 

Medicinal product subject to medical prescription. 

 

 

15. INSTRUCTIONS ON USE 

 

 

16. INFORMATION IN BRAILLE 

 

Cystagon 150 mg 

 

 

17. UNIQUE IDENTIFIER – 2D BARCODE 

 

2D barcode carrying the unique identifier included. 

 

 

18. UNIQUE IDENTIFIER - HUMAN READABLE DATA 

 

PC:  

SN: 

NN: 



24 

 

PARTICULARS TO APPEAR ON THE IMMEDIATE PACKAGING 

 

BOTTLE LABEL CYSTAGON 50 mg x 100 hard capsules 

BOTTLE LABEL CYSTAGON 50 mg x 500 hard capsules 

 

 

1. NAME OF THE MEDICINAL PRODUCT 

 

CYSTAGON 50 mg hard capsules  

Cysteamine  

 

 

2. STATEMENT OF ACTIVE SUBSTANCE(S) 

 

Each hard capsule contains 50 mg of cysteamine (as mercaptamine bitartrate) . 

 

 

3. LIST OF EXCIPIENTS 

 

 

4. PHARMACEUTICAL FORM AND CONTENTS 

 

100 hard capsules (with a desiccant unit in the bottle) 

500 hard capsules (with a desiccant unit in the bottle) 

 

 

5. METHOD AND ROUTE(S) OF ADMINISTRATION 

 

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 {month/year} 

 

 

9. SPECIAL STORAGE CONDITIONS 

 

Do not store above 25°C. 

Keep the container tightly closed in order to protect from light and moisture 

 



25 

 

10. SPECIAL PRECAUTIONS FOR DISPOSAL OF UNUSED MEDICINAL PRODUCTS 

OR WASTE MATERIALS DERIVED FROM SUCH MEDICINAL PRODUCTS, IF 

APPROPRIATE 

 

 

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/1/97/039/001 – 100 hard capsules 

EU/1/97/039/002 – 500 hard capsules 

 

 

13. MANUFACTURER’S BATCH NUMBER 

 

Batch {number} 

 

 

14. GENERAL CLASSIFICATION FOR SUPPLY 

 

Medicinal product subject to medical prescription. 

 

 

15. INSTRUCTIONS ON USE 

 

 

16. INFORMATION IN BRAILLE 

 

 

17. UNIQUE IDENTIFIER – 2D BARCODE 

 

2D barcode carrying the unique identifier included. 

 

 

18. UNIQUE IDENTIFIER - HUMAN READABLE DATA 

 

PC: 

SN:  

NN: 



26 

 

PARTICULARS TO APPEAR ON THE IMMEDIATE PACKAGING 

 

BOTTLE LABEL CYSTAGON 150 mg x 100 hard capsules 

BOTTLE LABEL CYSTAGON 150 mg x 500 hard capsules 

 

 

1. NAME OF THE MEDICINAL PRODUCT 

 

CYSTAGON 150 mg hard capsules  

Cysteamine 

 

 

2. STATEMENT OF ACTIVE SUBSTANCE(S) 

 

Each hard capsule contains 150 mg of cysteamine (as mercaptamine bitartrate) . 

 

 

3. LIST OF EXCIPIENTS 

 

 

4. PHARMACEUTICAL FORM AND CONTENTS 

 

100 hard capsules (with a desiccant unit in the bottle) 

500 hard capsules (with a desiccant unit in the bottle) 

 

 

5. METHOD AND ROUTE(S) OF ADMINISTRATION 

 

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 {month/year} 

 

 

9. SPECIAL STORAGE CONDITIONS 

 

Do not store above 25°C. 

Keep the container tightly closed in order to protect from light and moisture 

 



27 

 

10. SPECIAL PRECAUTIONS FOR DISPOSAL OF UNUSED MEDICINAL PRODUCTS 

OR WASTE MATERIALS DERIVED FROM SUCH MEDICINAL PRODUCTS, IF 

APPROPRIATE 

 

 

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/1/97/039/003 – 100 hard capsules 

EU/1/97/039/004 – 500 hard capsules 

 

 

13. MANUFACTURER’S BATCH NUMBER 

 

Batch {number} 

 

 

14. GENERAL CLASSIFICATION FOR SUPPLY 

 

Medicinal product subject to medical prescription. 

 

 

15. INSTRUCTIONS ON USE 

 

 

16. INFORMATION IN BRAILLE 

 

 

17. UNIQUE IDENTIFIER – 2D BARCODE 

 

2D barcode carrying the unique identifier included. 

 

 

18. UNIQUE IDENTIFIER - HUMAN READABLE DATA 

 

PC:  

SN: 

NN: 

 



28 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

B. PACKAGE LEAFLET 
 



29 

PACKAGE LEAFLET: INFORMATION FOR THE USER 

 

CYSTAGON 50 mg Hard Capsules 

CYSTAGON 150 mg Hard Capsules 

Cysteamine bitartrate (mercaptamine bitartrate) 

 

 

Read all of this leaflet carefully before you start using this medicine. 
- Keep this leaflet. You may need to read it again. 
- If you have further questions, please ask your doctor or your pharmacist. 
- This medicine has been prescribed for you. 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 CYSTAGON is and what it is used for 

2. Before you use CYSTAGON 

3. How to use CYSTAGON 

4. Possible side effects 

5. How to store CYSTAGON 
6. Further information 

 

 

1. WHAT CYSTAGON IS AND WHAT IT IS USED FOR 
 

Cystinosis is a metabolic disease called ‘nephropathic cystinosis’ which is characterized by an 

abnormal accumulation of the amino acid cystine in various organs of the body such as the kidney, 

eye, muscle, pancreas, and brain. Cystine build up causes kidney damage and excretion of excess 

amounts of glucose, proteins and electrolytes. Different organs are affected at different ages. 

 

CYSTAGON is prescribed to manage this rare inherited disorder. CYSTAGON is a medicine that 

reacts with cystine to decrease its level within the cells.  

 

 

2. BEFORE YOU USE CYSTAGON 
 

Do not use CYSTAGON 
- if you -or your child- are allergic (hypersensitive) to cysteamine bitartrate or penicillamine or 

any of the other ingredients of Cystagon. 

- If you are pregnant, this is particularly relevant during the first trimester 
- if you are breast-feeding. 
 

Take special care with CYSTAGON 
- When your or your child’s disorder has been confirmed by leucocyte cystine measurements, the 

therapy with CYSTAGON must be started as soon as possible. 

- A few cases of skin lesions on elbows like little hard lumps have been reported in children 
treated with high doses of different cysteamine preparations. These lesions were associated with 

skin striae and bone lesions such as fracture and bone deformities, and with laxity of joints. 

Your doctor could require a regular physical and X-ray examination for the skin and the bones 

to control the effects of the medicinal product. Self examination of your or your child’s skin is 

recommended. If any skin or bone abnormalities appear, please inform your doctor 

immediately. 

- Your doctor could require controlling the blood cell count on a regular basis. 
- CYSTAGON has not been shown to prevent cystine crystals accumulating in the eye. Where 

cysteamine ophthalmic solution has been used for that purpose, its usage should continue. 



30 

- In contrast to phosphocysteamine, another active substance close to cysteamine bitartrate, 
CYSTAGON does not contain phosphate. You may already be receiving phosphate supplements 

and the dose of these may need to be changed when CYSTAGON is substituted for 

phosphocysteamine. 

- To avoid any risk of aspiration in the lungs, the capsules should not be given to children under 
the age of approximately 6 years. 

 

Using other medicines 

Please inform your doctor or pharmacist if you are taking or have recently taken any other medicines, 

even those not prescribed. 

 

Using CYSTAGON with food and drink 
For children under approximately six years of age, the hard capsule may be opened and the contents 

sprinkled on food (e.g. milk, potatoes or starch based foods) or mixed in formula. Do not add to acidic 

drinks e.g. orange juice. Consult the doctor for complete directions. 

 

Pregnancy  
You should not use CYSTAGON if you are pregnant. Please consult your doctor if you plan to 

become pregnant. 

 

Breast-feeding 

CYSTAGON must not be used during breast-feeding. 

 

Driving and using machines  

CYSTAGON may cause some drowsiness. When starting therapy, you or your child should not 

engage in potentially hazardous activities until the effects of the drug are well known. 

 

 

3. HOW TO USE CYSTAGON 
 

Always use CYSTAGON exactly as your doctor or your  child’s doctor  has told you. You should 

check with your doctor if you are not sure. 

The dose of CYSTAGON prescribed for you or your child will depend on your or your child's age and 

weight.  

For children up to age 12 years, the dose will be based on the body size (surface area), the usual dose 

being 1.30 g/m2 of body surface area per day.  

For patients over age 12 and over 50 kg weight, the usual dose is 2g/day. 

In any case the usual dose should not exceed 1.95 g/m2/day. 

CYSTAGON should be taken or given only by mouth and exactly as your or your child's doctor 

directs. In order for CYSTAGON to work correctly, you must do the following: 

- Follow your doctor's directions exactly. Do not increase or decrease the amount of medicine 
without your doctor's approval. 

- Hard capsules should not be given to children under approximately six years of age because 
they may not be able to swallow them and they may choke. For children under approximately 

six years of age, the hard capsule may be opened and the contents sprinkled on food (e.g. milk, 

potatoes or starch based foods) or mixed in formula. Do not add to acidic drinks e.g. orange 

juice. Consult the doctor for complete directions. 

- Your or your child's medical treatment may include, in addition to CYSTAGON, one or more 
supplements to replace important electrolytes lost through the kidneys. It is important to take or 

give these supplements exactly as instructed. If several doses of the supplements are missed or 

weakness or drowsiness develops, call the doctor for instructions. 

- Regular blood tests to measure the amount of cystine inside white blood cells are necessary to 
help determine the correct dose of CYSTAGON. Your or your child's doctor will arrange for the 

blood tests to be done. Regular blood and urine tests to measure the levels of the body's 

important electrolytes are also necessary to help your or your child's doctor correctly adjust the 

doses of these supplements. 

 



31 

CYSTAGON should be taken 4 times a day, every 6 hours, preferably just after or with food. It is 

important to take the dose as close to every 6 hours as possible. 

 

Treatment with CYSTAGON should continue indefinitely, as instructed by your doctor. 

 

If you use more CYSTAGON than you should: 

You should contact your or your child's doctor or the hospital emergency department immediately if 

more medicine has been taken than has been prescribed, drowsiness develops . 

 

If you forget to take CYSTAGON: 

If a dose of medicine is missed, it should be taken as soon as possible. However if it is within two 

hours of the next dose, skip the missed dose and go back to the regular dosing schedule. Do not take a 

double dose to make up for a forgotten dose. 

 

 

4. POSSIBLE SIDE EFFECTS 
 

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

 

CYSTAGON may cause some people to become drowsy or less vigilant than they are normally. Make 

sure you know how you or your child reacts to this medicine before doing anything that could be 

dangerous if not alert. 

 

The following side effects were reported as follows: very common (occurring in at least one in 10 

patients), common (occurring in at least one in 100 patients), uncommon (occurring in at least one 

in1,000 patients), rare (occurring in at least one in 10,000 patients), very rare (occurring in at least one 

in 100,000 patients). 

 

- Very common: vomiting, nausea, diarrhoea, loss of appetite, fever and sensation of sleep 

 

- Common: abdominal pain or discomfort, unpleasant breath and body odour, skin eruption, 

gastroenteritis, fatigue, headache, encephalopathy (brain disorder) and liver function test 

abnormalities. 

 

-  Uncommon: skin striae, skin lesion (little-hard lumps on elbows), joint laxity, leg pain, bone 

fracture, scoliosis (deviation of the vertebral column), bone deformity and fragility, hair 

discoloration, severe allergic reaction, somnolence, fits, nervousness, hallucination, decrease in 

white blood cells, gastrointestinal ulcer manifested by bleeding in the digestive tract and effect 

on the kidney manifested by swelling of the extremities and weight gain. 

Since some of these side effects are serious, ask your or your child’s doctor to explain their warning 

signs. 

 

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 CYSTAGON 
 

Keep out of the reach and sight of children. 

 

Do not use after the expiry date which is stated on the label. The expiry date refers to the last day of 

that month. 

 



32 

Do not store above 25°C and keep the container tightly closed in order to protect from light and 

moisture. 

6. FURTHER INFORMATION 

 

What CYSTAGON contains 

- The active substance is cysteamine bitartrate (mercaptamine bitartrate). Each hard capsule of 
CYSTAGON 50 mg contains 50 mg of cysteamine (as mercaptamine bitartrate) Each hard 

capsule of CYSTAGON 150 mg contains 150 mg of cysteamine (as mercaptamine bitartrate)  

- The other ingredients are microcrystalline cellulose, starch, pregelatinized, magnesium 
stearate/sodium lauryl sulphate, colloidal silicon dioxide, croscarmellose sodium, capsule shells: 

gelatin, titanium dioxide, black ink on hard capsules (E172). 

 

What CYSTAGON looks like and contents of the pack 

Hard Capsules 

- Cystagon 50 mg: white, opaque hard capsules with CYSTA 50 on the body and MYLAN on the cap. 

Bottles of 100 or 500 hard capsules. All pack sizes may be not marketed. 

 

- Cystagon 150 mg: white, opaque hard capsules with CYSTAGON 150 on the body and MYLAN on 

the cap. 

Bottles of 100 or 500 hard capsules. All pack sizes may be not marketed. 

 

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 

 



33 

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 

 

Κύπρος 

Recordati Rare Diseases 

Τηλ : +33 1 47 73 64 58 

Sverige 

Recordati AB. 

Tel : +46 8 545 80 230 



34 

Γαλλία  

 

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 on  

 

Detailed information on this medicine is available on the European Medicines Agency web site: 

http://www.ema.europa.eu 


	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