Yargesa

1 

 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

ANNEX I 
 

SUMMARY OF PRODUCT CHARACTERISTICS 



2 

1. NAME OF THE MEDICINAL PRODUCT 
 
Yargesa 100 mg hard capsules 
 
 
2. QUALITATIVE AND QUANTITATIVE COMPOSITION 
 
Each hard capsule contains 100 mg miglustat. 
 
For the full list of excipients, see section 6.1. 
 
 
3. PHARMACEUTICAL FORM 
 
Hard capsule. 
 
The hard capsule consists of an opaque white cap and body with “708” printed in black on the body. 
Capsule Size: 4 (14.3 mm x 5.3 mm) 
 
 
4. CLINICAL PARTICULARS 
 
4.1 Therapeutic indications 
 
Yargesa is indicated for the oral treatment of adult patients with mild to moderate type 1 Gaucher disease. 
Yargesa may be used only in the treatment of patients for whom enzyme replacement therapy is unsuitable 
(see sections 4.4 and 5.1). 
 
Yargesa is indicated for the treatment of progressive neurological manifestations in adult patients and 
paediatric patients with Niemann-Pick type C disease (see sections 4.4, and 5.1).  
 
4.2 Posology and method of administration 
 
Therapy should be directed by physicians who are knowledgeable in the management of Gaucher disease or 
Niemann-Pick type C disease, as appropriate. 
 
Posology 
 
Dosage in type 1 Gaucher disease 
 
Adult 
 
The recommended starting dose for the treatment of adult patients with Type 1 Gaucher disease is 100 mg 
three times a day. 
 
Temporary dose reduction to 100 mg once or twice a day may be necessary in some patients because of 
diarrhoea.   
 
Paediatric population 
 
The efficacy of Yargesa in children and adolescents aged 0-17 years with type 1 Gaucher disease has not 
been established. No data are available. 
 
Dosage in Niemann-Pick type C disease 
Adult 



3 

The recommended dose for the treatment of adult patients with Niemann-Pick type C disease is 200 mg three 
times a day. 
 
Paediatric population 
The recommended dose for the treatment of adolescent patients (12 years of age and above) with Niemann-
Pick type C disease is 200 mg three times a day. 
 
Dosing in patients under the age of 12 years should be adjusted on the basis of body surface area as 
illustrated below: 

Body surface area (m2)  Recommended dose 
> 1.25 200 mg three times a day 
> 0.88 - 1.25 200 mg twice a day 
> 0.73 - 0.88 100 mg three times a day 
> 0.47 - 0.73 100 mg twice a day 
≤ 0.47 100 mg once a day 

 
Temporary dose reduction may be necessary in some patients because of diarrhoea. 
The benefit to the patient of treatment with Yargesa should be evaluated on a regular basis (see section 4.4). 
There is limited experience with the use of Yargesa in Niemann-Pick type C disease patients under the age of 
4 years. 
 
Special populations 
 
Elderly 
There is no experience with the use of Yargesa in patients over the age of 70. 
 
Renal Impairment  
Pharmacokinetic data indicate increased systemic exposure to miglustat in patients with renal impairment. In 
patients with an adjusted creatinine clearance of 50–70 ml/min/1.73 m2, administration should commence at 
a dose of 100 mg twice daily in patients with type 1 Gaucher disease and at a dose of 200 mg twice daily 
(adjusted for body surface area in patients below the age of 12) in patients with Niemann-Pick type C 
disease.  
 
In patients with an adjusted creatinine clearance of 30–50 ml/min/1.73 m2, administration should commence 
at a dose of 100 mg once daily in patients with type 1 Gaucher disease and at a dose of 100 mg twice daily 
(adjusted for body surface area in patients below the age of 12) in patients with Niemann-Pick type C 
disease. Use in patients with severe renal impairment (creatinine clearance < 30 ml/min/1.73 m2) is not 
recommended (see sections 4.4 and 5.2). 
 
Hepatic Impairment 
Yargesa has not been evaluated in patients with hepatic impairment. 
 
Method of Administration 
 
Yargesa can be taken with or without food. 
 
4.3 Contraindications 
 
Hypersensitivity to the active substance or to any of the excipients listed in section 6.1. 
 
4.4 Special warnings and precautions for use 
 
Tremor 
Approximately 37% of patients in clinical trials in type 1 Gaucher disease, and 58% of patients in a 



4 

clinical trial in Niemann-Pick type C disease reported tremor on treatment. In type 1 Gaucher disease, these 
tremors were described as an exaggerated physiological tremor of the hands. Tremor usually began within 
the first month, and in many cases resolved during treatment after between 1 and 3 months. Dose reduction 
may ameliorate the tremor, usually within days, but discontinuation of treatment may sometimes be required.  
 
Gastrointestinal disturbances 
Gastrointestinal events, mainly diarrhoea, have been observed in more than 80% of patients, either at the 
outset of treatment or intermittently during treatment (see section 4.8). The mechanism is most likely 
inhibition of intestinal disaccharidases such as sucrase-isomaltase in the gastrointestinal tract leading to 
reduced absorption of dietary disaccharides. In clinical practice, miglustat-induced gastrointestinal events 
have been observed to respond to individualised diet modification (for example reduction of sucrose, lactose 
and other carbohydrate intake), to taking miglustat between meals, and/or to anti-diarrhoeal medicinal 
products such as loperamide. In some patients, temporary dose reduction may be necessary. Patients with 
chronic diarrhoea or other persistent gastrointestinal events that do not respond to these interventions should 
be investigated according to clinical practice. Miglustat has not been evaluated in patients with a history of 
significant gastrointestinal disease, including inflammatory bowel disease.  
 
Effects on spermatogenesis 
Male patients should maintain reliable contraceptive methods while taking Yargesa. Studies in the rat have 
shown that miglustat adversely affects spermatogenesis and sperm parameters, and reduces fertility (see 
sections 4.6 and 5.3). Until further information is available, before seeking to conceive, male patients should 
cease Yargesa and maintain reliable contraceptive methods for a further 3 months.  
 
Special populations 
Due to limited experience, Yargesa should be used with caution in patients with renal or hepatic impairment. 
There is a close relationship between renal function and clearance of miglustat, and exposure to miglustat is 
markedly increased in patients with severe renal impairment (see section 5.2). At present, there is insufficient 
clinical experience in these patients to provide dosing recommendations. Use of Yargesa in patients with 
severe renal impairment (creatinine clearance < 30 ml/min/1.73 m2) is not recommended.  
 
Type 1 Gaucher disease 
Although no direct comparisons with Enzyme Replacement Therapy (ERT) have been performed in 
treatment-naive patients with type 1 Gaucher disease, there is no evidence of miglustat having an efficacy or 
safety advantage over ERT. ERT is the standard of care for patients who require treatment for type 1 
Gaucher disease (see section 5.1). The efficacy and safety of miglustat has not been specifically evaluated in 
patients with severe Gaucher disease.  
 
Regular monitoring of vitamin B12 level is recommended because of the high prevalence of vitamin B12 
deficiency in patients with type 1 Gaucher disease.  
 
Cases of peripheral neuropathy have been reported in patients treated with miglustat with or without 
concurrent conditions such as vitamin B12 deficiency and monoclonal gammopathy. Peripheral neuropathy 
seems to be more common in patients with type 1 Gaucher disease compared to the general population. All 
patients should undergo baseline and repeat neurological evaluation.  
 
In patients with type 1 Gaucher disease, monitoring of platelet counts is recommended. Mild reductions in 
platelet counts without association with bleeding were observed in patients with type 1 Gaucher disease who 
were switched from ERT to miglustat. 
 
Niemann-Pick type C disease 
 
The benefit of treatment with Yargesa for neurological manifestations in patients with Niemann-Pick type C 
disease should be evaluated on a regular basis, e.g. every 6 months; continuation of therapy should be re-
appraised after at least 1 year of treatment with Yargesa. 
 



5 

Mild reductions in platelet counts without association to bleeding were observed in some patients with 
Niemann-Pick type C disease treated with Yargesa. In patients included in the clinical trial, 40%-50% of 
patients had platelet counts below the lower limit of normal at baseline. Monitoring of platelet counts is 
recommended in these patients. 
 
Paediatric population 
 
Reduced growth has been reported in some paediatric patients with Niemann-Pick type C disease in the early 
phase of treatment with miglustat where the initial reduced weight gain may be accompanied or followed by 
reduced height gain. Growth should be monitored in paediatric and adolescent patients during treatment with 
Yargesa; the benefit/risk balance should be re-assessed on an individual basis for continuation of therapy. 
 
4.5 Interaction with other medicinal products and other forms of interaction 
 
Limited data suggest that co-administration of miglustat and enzyme replacement with imiglucerase in 
patients with type 1 Gaucher disease may result in decreased exposure to miglustat (approximate reductions 
of 22% in Cmax and 14% in AUC were observed in a small parallel-group study). This study also indicated 
that miglustat has no or limited effect on the pharmacokinetics of imiglucerase. 
 
4.6 Fertility, pregnancy and lactation 
 
Pregnancy 
There are no adequate data from the use of miglustat in pregnant women. Studies in animals have shown 
reproductive toxicity, including dystocia (see section 5.3). The potential risk for humans is unknown. 
Miglustat crosses the placenta and should not be used during pregnancy.  
 
Breast-feeding 
It is not known if miglustat is secreted in breast milk. Yargesa should not be taken during breast-feeding.  
 
Fertility 
Studies in the rat have shown that miglustat adversely affects sperm parameters (motility and morphology) 
thereby reducing fertility (see sections 4.4 and 5.3). Until further information is available, it is advised that 
before seeking to conceive, male patients should cease Yargesa and maintain reliable contraceptive methods 
for 3 months thereafter.  
 
Contraceptive measures should be used by women of childbearing potential. Male patients should maintain 
reliable contraceptive methods while taking Yargesa (see sections 4.4 and 5.3). 
 
4.7 Effects on ability to drive and use machines 
 
Yargesa has negligible influence on the ability to drive and use machines. Dizziness has been reported as a 
common adverse reaction, and patients suffering from dizziness should not drive or use machines. 
 
4.8 Undesirable effects 
 
Summary of the safety profile 
The most common adverse reactions reported in clinical studies with miglustat were diarrhoea, flatulence, 
abdominal pain, weight loss and tremor (see section 4.4). The most common serious adverse reaction 
reported with miglustat treatment in clinical studies was peripheral neuropathy (see section 4.4).  
 
In 11 clinical trials in different indications 247 patients were treated with miglustat at dosages of 50-200 mg 
t.i.d. for an average duration of 2.1 years. Of these patients, 132 had type 1 Gaucher disease, and 40 had 
Niemann-Pick type C disease. Adverse reactions were generally of mild to moderate severity and occurred 
with similar frequency across indications and dosages tested.  
 
Tabulated list of adverse reactions 



6 

Adverse reactions from clinical trials and spontaneous reporting, occurring in >1% of patients, are listed in 
the table below by system organ class and frequency (very common: ≥  1/10, common: ≥ 1/100 < 1/10, 
uncommon: ≥1/1,000 to <1/100, rare: ≥1/10,000 to <1/1,000, very rare: <1/10,000). Within each frequency 
grouping, adverse reactions are presented in order of decreasing seriousness. 
 
Blood and lymphatic system disorders 

Common Thrombocytopenia 

Metabolism and nutrition disorders 

Very common Weight loss, decreased appetite 

Psychiatric disorders 

Common Depression, insomnia, libido decreased 

Nervous system disorders 

Very common Tremor, 

Common Peripheral neuropathy, ataxia, amnesia, paraesthesia, hypoaesthesia, headache, 
dizziness 

Gastrointestinal disorders 

Very common Diarrhoea, flatulence, abdominal pain 

Common Nausea, vomiting, abdominal distension/discomfort, constipation, dyspepsia 

Musculoskeletal and connective tissue disorders 

Common Muscle spasms, muscle weakness 

General disorders and administration site reactions 

Common Fatigue, asthenia, chills and malaise 

Investigations 

Common Nerve conduction studies abnormal 
 
Description of selected adverse reactions 
Weight loss has been reported in 55% of patients using miglustat. The greatest prevalence was observed 
between 6 and 12 months.  
 
Miglustat has been studied in indications where certain events reported as adverse reactions, such as 
neurological and neuropsychological symptoms/signs, cognitive dysfunction and thrombocytopenia could 
also be due to the underlying conditions. 
 
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 
 
Symptoms 
No acute symptoms of overdose have been identified. Miglustat has been administered at doses of up to 
3000 mg/day for up to six months in HIV positive patients during clinical trials. Adverse events observed 
included granulocytopenia, dizziness and paraesthesia. Leukopenia and neutropenia have also been observed 
in a similar group of patients receiving 800 mg/day or higher dose.  
 
Management 

http://www.ema.europa.eu/docs/en_GB/document_library/Template_or_form/2013/03/WC500139752.doc
http://www.ema.europa.eu/docs/en_GB/document_library/Template_or_form/2013/03/WC500139752.doc


7 

In case of overdose general medical care is recommended. 
 
 
5. PHARMACOLOGICAL PROPERTIES 
 
5.1  Pharmacodynamic properties 
 
Pharmacotherapeutic group: Other alimentary tract and metabolism products, ATC Code: A16AX06 
 
Type 1 Gaucher disease 
Gaucher disease is an inherited metabolic disorder caused by a failure to degrade glucosylceramide resulting 
in lysosomal storage of this material and widespread pathology. Miglustat is an inhibitor of glucosylceramide 
synthase, the enzyme responsible for the first step in the synthesis of most glycolipids. In vitro, 
glucosylceramide synthase is inhibited by miglustat with an IC50 of 20-37 µM. In addition, inhibitory action 
on a non-lysosomal glycosylceramidase has been demonstrated experimentally in vitro. The inhibitory action 
on glucosylceramide synthase forms the rationale for substrate reduction therapy in Gaucher disease. 
 
The pivotal trial of miglustat was conducted in patients unable or unwilling to receive ERT. Reasons for not 
receiving ERT included the burden of intravenous infusions and difficulties in venous access. Twenty-eight 
patients with mild to moderate type 1 Gaucher disease were enrolled in this 12-month non-comparative 
study, and 22 patients completed the study. At 12 months, there was a mean reduction in liver organ volume 
of 12.1% and a mean reduction in spleen volume of 19.0%. A mean increase in haemoglobin concentration 
of 0.26 g/dl and a mean platelet count increase of 8.29 × 109/l were observed. Eighteen patients then 
continued to receive miglustat under an optional extended treatment protocol. Clinical benefit has been 
assessed at 24 and 36 months in 13 patients. After 3 years of continuous miglustat treatment, mean 
reductions in liver and spleen organ volume were 17.5% and 29.6%, respectively. There was a mean increase 
of 22.2 × 109/l in platelet count, and a mean increase of 0.95 g/dl in haemoglobin concentration.  
 
A second open, controlled study of miglustat randomised 36 patients who had received a minimum of 2 
years of treatment with ERT, into three treatment groups: continuation with imiglucerase, imiglucerase in 
combination with miglustat, or switch to miglustat. This study was conducted over a 6-month randomised 
comparison period followed by 18 months extension where all patients received miglustat monotherapy. In 
the first 6 months in patients who were switched to miglustat, liver and spleen organ volumes and 
haemoglobin levels were unchanged. In some patients there were reductions in platelet count and increases in 
chitotriosidase activity indicating that miglustat monotherapy may not maintain the same control of disease 
activity in all patients. 29 patients continued in the extension period. When compared to the measurements at 
6 months, disease control was unchanged after 18 and 24 months of miglustat monotherapy (20 and 6 
patients, respectively). No patient showed rapid deterioration of type 1 Gaucher disease following the switch 
to miglustat monotherapy.  
 
A total daily dose of 300 mg miglustat administered in three divided doses was used in the above two 
studies. An additional monotherapy study was performed in 18 patients at a total daily dose of 150 mg, and 
results indicate reduced efficacy compared to a total daily dose of 300 mg.  
 
An open-label, non-comparative, 2-year study enrolled 42 patients with type 1 Gaucher disease, who had 
received a minimum of 3 years of ERT and who fulfilled criteria of stable disease for at least 2 years. The 
patients were switched to monotherapy with miglustat 100 mg t.i.d. Liver volume (primary efficacy variable) 
was unchanged from baseline to the end of treatment. Six patients had miglustat treatment prematurely 
discontinued for potential disease worsening, as defined in the study. Thirteen patients discontinued 
treatment due to an adverse event. Small mean reductions in haemoglobin [–0.95 g/dL 
(95% CI: -1.38, -0.53)] and platelet count [-44.1 × 109/L (95% CI: –57.6, –30.7)] were observed between 
baseline and end of study. Twenty-one patients completed 24 months of miglustat treatment. Of these, 18 
patients at baseline were within established therapeutic goals for liver and spleen volume, haemoglobin 
levels, and platelet counts, and 16 patients remained within all these therapeutic goals at Month 24.  
 



8 

Bone manifestations of type 1 Gaucher disease were evaluated in 3 open-label clinical studies in patients 
treated with miglustat 100 mg t.i.d. for up to 2 years (n = 72). In a pooled analysis of uncontrolled data, bone 
mineral density Z-scores at the lumbar spine and femoral neck increased by more than 0.1 units from 
baseline in 27 (57%) and 28 (65%) of the patients with longitudinal bone density measurements. There were 
no events of bone crisis, avascular necrosis or fracture during the treatment period. 
 
Niemann-Pick type C disease 
 
Niemann-Pick type C disease is a very rare, invariably progressive and eventually fatal neurodegenerative 
disorder characterised by impaired intracellular lipid trafficking. The neurological manifestations are 
considered secondary to the abnormal accumulation of glycosphingolipids in neuronal and glial cells. 
 
Data to support safety and efficacy of Yargesa in Niemann-Pick type C disease come from a prospective 
open-label clinical trial and a retrospective survey. The clinical trial included 29 adult and juvenile patients 
in a 12-month controlled period, followed by extension therapy for an average total duration of 3.9 years and 
up to 5.6 years. In addition 12 paediatric patients were enrolled in an uncontrolled substudy for an overall 
average duration of 3.1 years and up to 4.4 years. Among the 41 patients enrolled in the trial 14 patients were 
treated with Yargesa for more than 3 years. The survey included a case series of 66 patients treated with 
Yargesa outside of the clinical trial for a mean duration of 1.5 years. Both data sets included paediatric, 
adolescent and adult patients with an age range of 1 year to 43 years. The usual dose of Yargesa in adult 
patients was 200 mg t.i.d., and was adjusted according to body surface area in paediatric patients. 
 
Overall the data show that treatment with Yargesa can reduce the progression of clinically relevant 
neurological symptoms in patients with Niemann-Pick type C disease. 
 
The benefit of treatment with Yargesa for neurological manifestations in patients with Niemann-Pick type C 
disease should be evaluated on a regular basis, e.g. every 6 months; continuation of therapy should be re-
appraised after at least 1 year of treatment with Yargesa, (see section 4.4). 
 
5.2 Pharmacokinetic properties 
 
Pharmacokinetic parameters of miglustat were assessed in healthy subjects, in a small number of patients 
with type 1 Gaucher disease, Fabry disease, HIV-infected patients, and in adults, adolescents and children 
with Niemann-Pick type C disease or type 3 Gaucher disease.  
 
The kinetics of miglustat appear to be dose linear and time independent. In healthy subjects miglustat is 
rapidly absorbed. Maximum plasma concentrations are reached about 2 hours after dose. Absolute 
bioavailability has not been determined. Concomitant administration of food decreases the rate of absorption 
(Cmax was decreased by 36% and tmax delayed 2 hours), but has no statistically significant effect on the extent 
of absorption of miglustat (AUC decreased by 14%).  
 
The apparent volume of distribution of miglustat is 83 l. Miglustat does not bind to plasma proteins. 
Miglustat is mainly eliminated by renal excretion, with urinary recovery of unchanged drug accounting for 
70-80% of the dose. Apparent oral clearance (CL/F) is 230 ± 39 ml/min. The average half-life is 6–7 hours. 
 
Following administration of a single dose of 100 mg 14C-miglustat to healthy volunteers, 83% of the 
radioactivity was recovered in urine and 12% in faeces. Several metabolites were identified in urine and 
faeces. The most abundant metabolite in urine was miglustat glucuronide accounting for 5% of the dose. The 
terminal half-life of radioactivity in plasma was 150 h suggesting the presence of one or more metabolites 
with very long half-life. The metabolite accounting for this has not been identified, but may accumulate and 
reach concentrations exceeding those of miglustat at steady state.  
 
The pharmacokinetics of miglustat is similar in adult type 1 Gaucher disease patients and 
Niemann-Pick type C disease patients when compared to healthy subjects. 
 
Paediatric population 



9 

 
Pharmacokinetic data were obtained in paediatric patients with type 3 Gaucher disease aged 3 to 15 years, 
and patients with Niemann-Pick type C disease aged 5–16 years. Dosing in children at 200 mg t.i.d. adjusted 
for body surface area resulted in Cmax and AUCτ values which were approximately twofold those attained 
after 100 mg t.i.d. in type 1 Gaucher disease patients, consistent with the doselinear pharmacokinetics of 
miglustat. At steady state, the concentration of miglustat in cerebrospinal fluid of six type 3 Gaucher disease 
patients was 31.4-67.2% of that in plasma. 
 
Limited data in patients with Fabry disease and impaired renal function showed that CL/F decreases with 
decreasing renal function. While the numbers of subjects with mild and moderate renal impairment were 
very small, the data suggest an approximate decrease in CL/F of 40% and 60% respectively, in mild and 
moderate renal impairment (see section 4.2). Data in severe renal impairment are limited to two patients with 
creatinine clearance in the range 18 – 29 ml/min and cannot be extrapolated below this range. These data 
suggest a decrease in CL/F by at least 70% in patients with severe renal impairment. 
 
Over the range of data available, no significant relationships or trends were noted between miglustat 
pharmacokinetic parameters and demographic variables (age, BMI, gender or race). 
 
There are no pharmacokinetic data available in patients with liver impairment, in children or adolescents 
with type 1 Gaucher disease or in the elderly (> 70 years). 
 
5.3 Preclinical safety data 
 
The main effects common to all species were weight loss and diarrhoea, and, at higher doses, damage to the 
gastrointestinal mucosa (erosions and ulceration). Further effects seen in animals at doses that result in 
exposure levels similar to or moderately higher than the clinical exposure level were: changes in lymphoid 
organs in all species tested, transaminase changes, vacuolation of thyroid and pancreas, cataracts, 
nephropathy and myocardial changes in rats. These findings were considered to be secondary to debilitation. 
 
Administration of miglustat to male and female Sprague-Dawley rats by oral gavage for 2 years at dose 
levels of 30, 60 and 180 mg/kg/day resulted in an increased incidence of testicular interstitial cell (Leydig 
cell) hyperplasia and adenomas in male rats at all dose levels. The systemic exposure at the lowest dose was 
below or comparable to that observed in humans (based on AUC0-∞) at the recommended human dose. A No 
Observed Effect Level (NOEL) was not established and the effect was not dose dependent. There was no 
drug-related increase in tumour incidence in male or female rats in any other organ. Mechanistic studies 
revealed a rat specific mechanism which is considered to be of low relevance for humans.  
 
Administration of miglustat to male and female CD1 mice by oral gavage at dose levels of 210, 420 and 
840/500 mg/kg/day (dose reduction after half a year) for 2 years resulted in an increased incidence of 
inflammatory and hyperplastic lesions in the large intestine in both sexes. Based on mg/kg/day and corrected 
for differences in faecal excretion, the doses corresponded to 8, 16 and 33/19 times the highest recommended 
human dose (200 mg t.i.d.). Carcinomas in the large intestine occurred occasionally at all doses with a 
statistically significant increase in the high dose group. A relevance of these findings to humans cannot be 
excluded. There was no drug-related increase in tumour incidence in any other organ. 
 
Miglustat did not show any potential for mutagenic or clastogenic effects in the standard battery of 
genotoxicity tests.  
 
Repeated-dose toxicity studies in rats showed effects on the seminiferous epithelium of the testes. Other 
studies revealed changes in sperm parameters (motility and morphology) consistent with an observed 
reduction in fertility. These effects occurred at exposure levels similar to those in patients, but showed 
reversibility. Miglustat affected embryo/foetal survival in rats and rabbits, dystocia was reported, post-
implantation losses were increased, and an increased incidence of vascular anomalies occurred in rabbits. 
These effects may be partly related to maternal toxicity.  
 



10 

Changes in lactation were observed in female rats in a 1-year study. The mechanism for this effect is 
unknown. 
 
 
6. PHARMACEUTICAL PARTICULARS 
 
6.1 List of excipients 
 
Capsule content  
sodium starch glycolate (Type A)  
povidone (K-29/32) 
magnesium stearate  
 
Capsule shell 
gelatin  
purified water 
titanium dioxide (E171) 
 
Printing ink 
shellac glaze  
iron oxide black (E172) 
propylene glycol 
concentrated ammonia solution  
 
6.2 Incompatibilities 
 
Not applicable. 
 
6.3 Shelf life 
 
4 years. 
 
6.4 Special precautions for storage 
 
This medicinal product does not require any special storage conditions. 
 
6.5 Nature and contents of container 
 
PVC and polychlorotrifluoroethylene (PCTFE) blister sealed with aluminium foil containing 21 capsules. 
 
Pack size: 84 x 1 capsules. 
 
6.6 Special precautions for disposal 
 
No special requirements. 
 
 
7. MARKETING AUTHORISATION HOLDER 
 
Piramal Critical Care B.V. 
Rouboslaan 32 (ground floor)  
2252 TR, Voorschoten 
The Netherlands 
 
 
8. MARKETING AUTHORISATION NUMBER(S)  



11 

 
EU/1/17/1176/001 
 
 
9. DATE OF FIRST AUTHORISATION/RENEWAL OF THE AUTHORISATION 
 
Date of first authorisation: 22 March 2017 
 
 
 
10. DATE OF REVISION OF THE TEXT 
 
 
 
Detailed information on this medicinal product is available on the website of the European Medicines 
Agency http://www.ema.europa.eu. 

http://www.ema.europa.eu/


12 

 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

ANNEX II 
 

A. MANUFACTURER(S) 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 

 



13 

A.  MANUFACTURER(S) RESPONSIBLE FOR BATCH RELEASE 
 
Name and address of the manufacturer(s) responsible for batch release 
 
Piramal Critical Care B.V. 
Rouboslaan 32 (ground floor)  
2252 TR, Voorschoten 
The Netherlands 
 
 
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) 

 
The MAH shall perform the required pharmacovigilance activities and interventions detailed in the 
agreed RMP presented in Module 1.8.2 of the Marketing Authorisation and any agreed subsequent 
updates of the RMP. 
 
An updated RMP should be submitted: 

• At the request of the European Medicines Agency; 
• Whenever the risk management system is modified, especially as the result of new information being 

received that may lead to a significant change to the benefit/risk profile or as the result of an important 
(pharmacovigilance or risk minimisation) milestone being reached. 

 
 



14 

 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

ANNEX III 
 

LABELLING AND PACKAGE LEAFLET 



15 

 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

A. LABELLING 



16 

 
PARTICULARS TO APPEAR ON THE OUTER PACKAGING 
 
CARTON  
 
1. NAME OF THE MEDICINAL PRODUCT 
 
Yargesa 100 mg hard capsules 
 
miglustat 
 
 
2. STATEMENT OF ACTIVE SUBSTANCE(S) 
 
Each hard capsule contains 100 mg miglustat. 
 
 
3. LIST OF EXCIPIENTS 
 
 
 
4. PHARMACEUTICAL FORM AND CONTENTS 
 
84 x 1 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 SIGHT AND REACH OF CHILDREN 
 
Keep out of the sight and reach of children. 
 
 
7. OTHER SPECIAL WARNING(S), IF NECESSARY 
 
 
 
8. EXPIRY DATE 
 
EXP 
 
 
9. SPECIAL STORAGE CONDITIONS 
 
 
 
10. SPECIAL PRECAUTIONS FOR DISPOSAL OF UNUSED MEDICINAL PRODUCTS OR 
WASTE MATERIALS DERIVED FROM SUCH MEDICINAL PRODUCTS, IF APPROPRIATE 



17 

 
 
 
11. NAME AND ADDRESS OF THE MARKETING AUTHORISATION HOLDER 
 
Piramal Critical Care B.V. 
Rouboslaan 32 (ground floor)  
2252 TR, Voorschoten 
The Netherlands 
 
 
12. MARKETING AUTHORISATION NUMBER(S)  
 
EU/1/17/1176/001  
 
 
13. BATCH NUMBER<, DONATION AND PRODUCT CODES> 
 
Lot 
 
 
14. GENERAL CLASSIFICATION FOR SUPPLY 
 
 
 
15. INSTRUCTIONS ON USE 
 
 
 
16. INFORMATION IN BRAILLE 
 
Yargesa 100 mg 
 
 
17. UNIQUE IDENTIFIER – 2D BARCODE 
 
2D barcode carrying the unique identifier included. 
 
 
18. UNIQUE IDENTIFIER – HUMAN READABLE DATA 
 
PC: {number} 
SN: {number} 
NN: {number} 
 
 
 



18 

 
MINIMUM PARTICULARS TO APPEAR ON BLISTERS 
 
BLISTER  
 
 
1. NAME OF THE MEDICINAL PRODUCT 
 
Yargesa 100 mg hard capsules 
 
miglustat 
 
 
2. NAME OF THE MARKETING AUTHORISATION HOLDER 
 
Piramal Critical Care B.V. 
 
 
3. EXPIRY DATE 
 
EXP 
 
 
4. BATCH NUMBER 
 
BN 
 
 
5. OTHER 
 
 
 
 



19 

 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

B. PACKAGE LEAFLET 



20 

Package leaflet: Information for the user 
 

Yargesa 100 mg hard capsules 
Miglustat 

 
 
Read all of this leaflet carefully before you start taking this medicine because it contains important 

information for you. 
- Keep this leaflet. You may need to read it again.  
- If you have any further questions, ask your doctor or pharmacist. 
- This medicine has been prescribed for you only. Do not pass it on to others. It may harm them, even if 
their signs of illness are the same as yours.  
- If you get any side effects, talk to your doctor or pharmacist. This includes any possible side effects 

not listed in this leaflet. See section 4. 
 
What is in this leaflet 
 
1. What Yargesa is and what it is used for  
2. What you need to know before you take Yargesa  
3. How to take Yargesa  
4. Possible side effects  
5. How to store Yargesa  
6. Contents of the pack and other information 
 
 
1. What Yargesa is and what it is used for 
 
Yargesa contains the active substance miglustat which belongs to a group of medicines that affect 
metabolism. It is used to treat two conditions: 
 
• Yargesa is used to treat mild to moderate type 1 Gaucher disease in adults. 

 
In type 1 Gaucher disease, a substance called glucosylceramide is not removed from your body. It starts to 
build up in certain cells of the body’s immune system. This can result in liver and spleen enlargement, 
changes in the blood and bone disease. 
 
The usual treatment for type 1 Gaucher disease is enzyme replacement therapy. Yargesa is only used when a 
patient is considered unsuitable for treatment with enzyme replacement therapy. 
 
• Yargesa is also used to treat progressive neurological symptoms in Niemann-Pick type C disease 

in adults and in children. 
 
If you have Niemann-Pick type C disease, fats such as glycosphingolipids build up in the cells of your brain. 
This can result in disturbances in neurological functions such as slow eye movements, balance, swallowing, 
and memory, and in seizures. 
 
Yargesa works by inhibiting the enzyme called ‘glucosylceramide synthase’ which is responsible for the first 
step in the synthesis of most glycosphingolipids. 
 
 
2. What you need to know before you take Yargesa 
 
Do not take Yargesa 
- if you are allergic to miglustat or any of the other ingredients of this medicine (listed in section 6)  
 
Warnings and precautions  
Talk to your doctor or pharmacist before taking Yargesa 



21 

• if you suffer from kidney disease 
• if you suffer from liver disease 

 
Your doctor will perform the following tests before treatment and during treatment with Yargesa 

• an examination to check the nerves in your arms and legs 
• measurement of vitamin B12 levels 
• monitoring growth if you are a child or adolescent with Niemann-Pick type C disease 
• monitoring of blood platelet counts 

 
The reason for these tests is that some patients have had tingling or numbness in the hands and feet, or a 
decrease in body weight, while taking Yargesa. The tests will help the doctor decide whether these effects 
are due to your disease or other existing conditions, or due to side effects of Yargesa (see section 4 for 
further details). 
 
If you have diarrhoea, your doctor may ask you to change your diet to reduce your lactose and carbohydrate 
intake such as sucrose (cane sugar), or not to take Yargesa together with food, or to temporarily reduce your 
dose. In some cases the doctor may prescribe anti-diarrhoeal medicines such as loperamide. If your diarrhoea 
does not respond to these measures, or if you have any other abdominal complaint, consult your doctor. In 
such case, your doctor may decide to conduct further investigations. 
 
Male patients should use reliable birth control methods during their treatment with Yargesa and for 3 months 
after finishing treatment. 
 
Children and adolescents 
Do not give this medicine to children and adolescents (below 18 years old) with type 1 Gaucher disease 
because it is not known if it works in this disease. 
 
Other medicines and Yargesa 
Tell your doctor or pharmacist if you are taking, have recently taken, or might take any other medicines. 
 
Tell your doctor if you are taking medicines containing imiglucerase, which are sometimes used at the same 
time as Yargesa. They may lower the amount of Yargesa in your body. 
 
Pregnancy, breast-feeding and fertility 
You should not take Yargesa if you are pregnant or thinking of becoming pregnant. Your doctor can give 
you more information. You must use effective birth control while taking Yargesa. Do not breast-feed while 
you are taking Yargesa. 
 
Male patients should use reliable birth control methods during their treatment with Yargesa and for 3 months 
after finishing treatment. 
 
If you are pregnant, breast feeding, think you may be pregnant or planning to have a baby, ask your doctor or 
pharmacist for advice before taking this medicine. 
 
Driving and using machines 
Yargesa may make you feel dizzy. Do not drive or use any tools or machines if you feel dizzy. 
 
 
3. How to take Yargesa 
 
Always take this medicine exactly as your doctor has told you. Check with your doctor or pharmacist  if you 
are not sure.  
 
Dosage 
• For type 1 Gaucher disease: For adults, the usual dose is one capsule (100 mg) three times a day 

(morning, afternoon and evening). This means a daily maximum of three capsules (300 mg). 



22 

• For Niemann-Pick type C disease: For adults and adolescents (over 12 years old), the usual dose is 
two capsules (200 mg) three times a day (morning, afternoon and evening). This means a daily 
maximum of six capsules (600 mg). 

 
For children less than 12 years old, your doctor will adjust the dose for Niemann-Pick type C disease. 
 
If you have a problem with your kidneys you may receive a lower starting dose. Your doctor may reduce 
your dose, e.g., to one capsule (100 mg) once or twice a day, if you suffer from diarrhoea when taking 
Yargesa (see section  4). Your doctor will tell you how long your treatment will last. 
 
To remove the capsule: 
 
1. Separate at perforations 
 
2. Peel back paper at arrows 
 
3 Push product through foil 
 
 
Yargesa can be taken with or without food. You should swallow the whole capsule with a glass of water. 
 
If you take more Yargesa than you should 
If you take more capsules than you were told to, consult your doctor immediately. Miglustat has been used in 
clinical trials at doses ten times higher than the recommended dose: this caused decreases in white blood 
cells and other side effects similar to those described in section 4. 
 
If you forget to take Yargesa 
Take the next capsule at the usual time. Do not take a double dose to make up for a forgotten dose. 
 
If you stop taking Yargesa 
Do not stop taking Yargesa without talking to your doctor. 
If you have any further questions on the use of this medicine, ask your doctor or pharmacist. 
 
 
4. Possible side effects 
 
Like all medicines, this medicine can cause side effects, although not everybody gets them. 
 
Most serious side effects 
Some patients have had tingling or numbness in the hands and feet (seen commonly). They could be 
signs of peripheral neuropathy, due to side effects of Yargesa or they could be due to existing conditions. 
Your doctor will perform some tests before and during treatment with Yargesa to assess this (see section 2). 
 
If you do get any of these effects, please seek medical advice from your doctor as soon as possible. 
 
If you get a slight tremor, usually trembling hands, seek medical advice from your doctor as soon as 
possible. The tremor often disappears without needing to stop the treatment. Sometimes your doctor will 
need to reduce the dose or stop Yargesa treatment to stop the tremor. 
 
Very common effects – may affect more than 1 in 10 people 
The most common side effects are diarrhoea, flatulence (wind), abdominal (stomach) pain, weight loss and 
decreased appetite. 
 
If you do lose some weight when you start treatment with Yargesa don’t worry. People usually stop losing 
weight as treatment goes on. 
 
Common effects – may affect up to 1 in 10 people 



23 

Common side effects of treatment include headache, dizziness, paraesthesia (tingling or numbness), 
abnormal coordination, hypoaesthesia (reduced sensation to touch), dyspepsia (heartburn), nausea (feeling 
sick), constipation and vomiting, swelling or discomfort in the abdomen (stomach) and thrombocytopenia 
(reduced levels of blood platelets).The neurological symptoms and thrombocytopenia could be due to the 
underlying disease. 
 
Other possible side effects are muscular spasms or weakness, fatigue, chills and malaise, depression, 
difficulty sleeping, forgetfulness and reduced libido. 
 
Most patients get one or more of these side effects, usually at the start of treatment or at intervals during 
treatment. Most cases are mild and disappear quite quickly. If any of these side effects cause problems, 
consult your doctor. He or she may reduce the dose of Yargesa or recommend other medicines to help 
control side effects. 
 
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 Yargesa 
 
Keep this medicine out of the sight and reach of children. 
 
Do not take this medicine after the expiry date which is stated on the blister and carton after ‘EXP’. The 
expiry date refers to the last day of that month. 
 
This medicine does not require any special storage conditions. 
Do not throw away any medicines via wastewater or household waste. Ask your pharmacist how to throw 
away medicines you no longer take. These measures will help protect the environment. 
 
 
6. Contents of the pack and other information 
 
What Yargesa contains  
 
- the active substance is miglustat. Each hard capsule contains 100 mg miglustat. 
- the other ingredients are sodium starch glycolate (type A), povidone (K-29/32), magnesium stearate, 

gelatin, purified water, titanium dioxide (E171), printing ink (shellac glaze, iron oxide black (E172), 
propylene glycol and concentrated ammonia solution) 

 
What Yargesa looks like and contents of the pack 
Yargesa is a white hard capsule that consists of an opaque white cap and body with “708” printed in black on 
the body. The capsules are presented in a PVC and polychlorotrifluoroethylene (PCTFE)  blister sealed with 
aluminium foil. 
 
Pack size of 84 capsules. 
 
Marketing Authorisation Holder and Manufacturer 
Piramal Critical Care B.V. 
Rouboslaan 32 (ground floor)  
2252 TR, Voorschoten 
The Netherlands 
 
This leaflet was last revised in 
 
 

http://www.ema.europa.eu/docs/en_GB/document_library/Template_or_form/2013/03/WC500139752.doc
http://www.ema.europa.eu/docs/en_GB/document_library/Template_or_form/2013/03/WC500139752.doc


24 

Other sources of information 
 
Detailed information on this medicine is available on the European Medicines Agency web site: 
http://www.ema.europa.eu. 
 

http://www.ema.europa.eu/

	SUMMARY OF PRODUCT CHARACTERISTICS
	A. MANUFACTURER(S) 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