Translarna

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ANNEX I   
 

SUMMARY OF PRODUCT CHARACTERISTICS 



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This medicinal product is subject to additional monitoring. This will allow quick identification of 
new safety information. Healthcare professionals are asked to report any suspected adverse reactions. 
See section 4.8 for how to report adverse reactions. 
 
 
1. NAME OF THE MEDICINAL PRODUCT 
 
Translarna 125 mg granules for oral suspension 
Translarna 250 mg granules for oral suspension 
Translarna 1000 mg granules for oral suspension 
 
 
2. QUALITATIVE AND QUANTITATIVE COMPOSITION 
 
Translarna 125 mg granules for oral suspension 
Each sachet contains 125 mg ataluren. 
 
Translarna 250 mg granules for oral suspension 
Each sachet contains 250 mg ataluren. 
 
Translarna 1000 mg granules for oral suspension 
Each sachet contains 1000 mg ataluren. 
 
For the full list of excipients, see section 6.1. 
 
 
3. PHARMACEUTICAL FORM 
 
Granules for oral suspension. 
White to off-white granules. 
 
 
4. CLINICAL PARTICULARS 
 
4.1 Therapeutic indications  
 
Translarna is indicated for the treatment of Duchenne muscular dystrophy resulting from a nonsense 
mutation in the dystrophin gene, in ambulatory patients aged 2 years and older (see section 5.1). 
 
The presence of a nonsense mutation in the dystrophin gene should be determined by genetic testing 
(see section 4.4). 
 
4.2 Posology and method of administration 
 
Treatment with Translarna should only be initiated by specialist physicians with experience in the 
management of Duchenne/Becker muscular dystrophy. 
 
Posology 
 
Ataluren should be administered orally every day in 3 doses. 
 
The first dose should be taken in the morning, the second at midday, and the third in the evening. 
Recommended dosing intervals are 6 hours between morning and midday doses, 6 hours between 
midday and evening doses, and 12 hours between the evening dose and the first dose on the next day.  
 
The recommended dose is 10 mg/kg body weight in the morning, 10 mg/kg body weight at midday, 
and 20 mg/kg body weight in the evening (for a total daily dose of 40 mg/kg body weight). 

T 



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Translarna is available in sachets of 125 mg, 250 mg or 1000 mg. The table below provides 
information on which sachet strength(s) to use in the preparation of the recommended dose by body 
weight range.  
 

Weight 
Range 
(kg) 

Number of sachets 
Morning  Midday Evening 

125 mg 
sachets 

250 mg 
sachets 

1000 
mg 

sachets 

125 mg 
sachets 

250 mg 
sachets 

1000 
mg 

sachets 

125 mg 
sachets 

250 mg 
sachets 

1000 
mg 

sachets 
12 14 1 0 0 1 0 0 0 1 0 
15 16 1 0 0 1 0 0 1 1 0 
17 20 0 1 0 0 1 0 0 1 0 
21 23 0 1 0 0 1 0 1 1 0 
24 26 0 1 0 0 1 0 0 2 0 
27 31 0 1 0 0 1 0 1 2 0 
32 35 1 1 0 1 1 0 1 2 0 
36 39 1 1 0 1 1 0 0 3 0 
40 44 1 1 0 1 1 0 1 3 0 
45 46 0 2 0 0 2 0 1 3 0 
47 55 0 2 0 0 2 0 0 0 1 
56 62 0 2 0 0 2 0 0 1 1 
63 69 0 3 0 0 3 0 0 1 1 
70 78 0 3 0 0 3 0 0 2 1 
79 86 0 3 0 0 3 0 0 3 1 
87 93 0 0 1 0 0 1 0 3 1 
94 105 0 0 1 0 0 1 0 0 2 

106 111 0 0 1 0 0 1 0 1 2 
112 118 0 1 1 0 1 1 0 1 2 
119 125 0 1 1 0 1 1 0 2 2 
 
Delayed or missed dose 
If there is a delay in the administration of ataluren of less than 3 hours after the morning or midday 
doses or less than 6 hours after the evening dose, the dose should be taken with no changes to the 
subsequent dose schedules. If there is a delay of more than 3 hours after the morning or midday doses 
or more than 6 hours after the evening dose, the dose should not be taken, and patients should resume 
their usual dosing schedule. Patients should not take a double or extra dose if a dose is missed. It is 
important to administer the correct dose. Increasing the dose above the recommended dose may be 
associated with reduced effectiveness. 
 
Special populations 
 
Elderly 
The safety and efficacy of ataluren in patients aged 65 and older have not yet been established (see 
section 5.2). 
 
Renal impairment 
No dosage adjustment is required for patients with mild or moderate renal impairment. Treatment of 
patients with severe renal impairment (eGFR <30 ml/min) or end-stage renal disease is not 
recommended (see sections 4.4 and 5.2). 
 



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Hepatic impairment 
No dosage adjustment is required for patients with mild, moderate or severe hepatic impairment (see 
section 5.2).  
 
Paediatric population 
Paediatric patients with body weight ≥12 kg are treated as per the dosing recommendations by body 
weight range (see above dosing table). The recommended dose is the same for all age ranges, i.e. 
10 mg/kg body weight in the morning, 10 mg/kg body weight at midday, and 20 mg/kg body weight in 
the evening (for a total daily dose of 40 mg/kg body weight).  
 
The safety and efficacy of Translarna in children <12kg and aged 6 months to 2 years have not yet 
been established. No data are available. 
 
Method of administration 
 
Translarna should be administered orally after mixing it to a suspension in liquid or in semi-solid food. 
Sachets should only be opened at the time of dose preparation. The full contents of each sachet should 
be mixed with, at least 30 ml of liquid (water, milk, fruit juice) or 3 tablespoons of semi-solid food 
(yoghurt or apple sauce). The prepared dose should be mixed well before administration. The amount 
of the liquid or semi-solid food can be increased based on patient preference. Patients should take the 
entire dose. 
 
For instructions on reconstitution of the medicinal product before administration, see section 6.6. 
 
4.3 Contraindications 
 
Hypersensitivity to the active substance or to any of the excipients listed in section 6.1.  
 
Concomitant use of intravenous aminoglycosides (see sections 4.4 and 4.5). 
 
4.4 Special warnings and precautions for use 
 
Patients who do not have a nonsense mutation 
 
Patients must have a nonsense mutation in the dystrophin gene as part of their underlying disease state, 
as determined by genetic testing. Patients who do not have a nonsense mutation should not receive 
ataluren. 
 
Renal impairment 
 
An increase in ataluren exposure and in ataluren metabolite has been reported in patients with severe 
renal impairment (eGFR <30 ml/min). The toxicity of the metabolite is unknown. Higher ataluren 
exposure was associated with potential decrease in efficacy. Therefore, patients with severe renal 
impairment or end-stage renal disease should be treated with ataluren only if the anticipated clinical 
benefit outweighs the potential risk, and should be closely monitored for possible metabolite toxicity 
and decrease in efficacy. A lower ataluren dose should be considered. 
 
Treatment should not be initiated in previously untreated patients with eGFR <30 ml/min (see sections 
4.2 and 5.2). 
 
Changes in lipid profile 
 
Because changes in lipid profile (increased triglycerides and cholesterol) were reported for some 
patients in clinical trials, it is recommended that total cholesterol, LDL, HDL, and triglycerides be 
monitored on an annual basis in nonsense mutation Duchenne muscular dystrophy (nmDMD) 
patients receiving ataluren, or more frequently as needed based on the patient’s clinical status. 
 



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Hypertension with use of concomitant systemic corticosteroids 
 
Because hypertension with use of concomitant systemic corticosteroids was reported for some 
patients in clinical trials, it is recommended that resting systolic and diastolic blood pressure be 
monitored every 6 months in nmDMD patients receiving ataluren concomitantly with 
corticosteroids, or more frequently as needed based on the patient’s clinical status.  
 
Renal function monitoring 
 
Because small increases in mean serum creatinine, blood urea nitrogen (BUN), and cystatin C were 
observed in the controlled studies of nmDMD, it is recommended that serum creatinine, BUN, and 
cystatin C be monitored every 6 to 12 months in nmDMD patients receiving ataluren, or more 
frequently as needed based on the patient’s clinical status. 
 
Potential interactions with other medicinal products 
 
Caution should be exercised when ataluren is co-administered with medicinal products that are 
inducers of UGT1A9, or substrates of OAT1 or OAT3 (see section 4.5). 
 
Aminoglycosides 
 
Aminoglycosides have been shown to reduce the readthrough activity of ataluren in vitro. In addition, 
ataluren was found to increase nephrotoxicity of intravenous aminoglycosides. The co-administration 
of these medicinal products with ataluren should be avoided (see section 4.3). Since the mechanism by 
which ataluren increases nephrotoxicity of intravenous aminoglycosides is not known, concomitant 
use of other nephrotoxic medicinal products with ataluren is not recommended. If this is unavoidable 
(e.g. vancomycin to treat MRSA) careful monitoring of renal function is advised (see section 4.5). 
 
4.5 Interaction with other medicinal products and other forms of interaction 
 
Aminoglycosides 
 
Ataluren should not be co-administered with intravenous aminoglycosides, based on cases of 
decreased renal function observed in a clinical trial in patients with nmCF (see section 4.3).  
 
Elevations of serum creatinine occurred in several nmCF patients treated with ataluren and 
intravenous aminoglycosides together with other antibiotics for cystic fibrosis exacerbations. The 
serum creatinine elevations resolved in all cases, with discontinuation of the intravenous 
aminoglycoside, and either continuation or interruption of Translarna. These findings suggested that 
co-administration of Translarna and intravenous aminoglycosides may potentiate the nephrotoxic 
effect of the aminoglycosides. Therefore, if treatment with intravenous aminoglycosides is necessary 
the treatment with Translarna should be stopped and can be resumed 2 days after administration of the 
aminoglycoside has ended. The effect of co-administration of ataluren with other nephrotoxic 
medicinal products is unknown. 
 
Dehydration may be a contributing factor in some of these cases. Patients should maintain adequate 
hydration while taking ataluren (see section 4.4). 
 
Effect of other medicinal products on ataluren pharmacokinetics 
Based on in vitro studies, ataluren is a substrate of UGT1A9. Co-administration of rifampicin, a strong 
inducer of metabolic enzymes including UGT1A9, decreased ataluren exposure by 29%. The 
significance of these findings for humans is unknown. Caution should be exercised when ataluren is 
co-administered with medicinal products that are inducers of UGT1A9 (e.g. rifampicin). 
 



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Effect of ataluren on pharmacokinetics of other medicinal products 
Based on in vitro studies, ataluren has the potential to inhibit UGT1A9, organic anion transporter 1 
(OAT1), organic anion transporter 3 (OAT3) and organic anion transporting polypeptide 1B3 
(OATP1B3). Co-administration of ataluren with mycophenolate mofetil in healthy subjects did not 
affect the exposure of its active metabolite, mycophenolic acid (a substrate of UGT1A9). No dose 
adjustment is required when ataluren is co-administered with medicinal products that are substrates of 
UGT1A9.  
 
In a clinical study to evaluate the potential for ataluren to inhibit the OATP1B3 transport system using 
a single-dose of 80 mg telmisartan, an in-vitro selective OATP1B3 substrate, ataluren increased the 
exposure to telmisartan by 28%. This effect is considered clinically not relevant. However, the 
magnitude of this effect could be larger for the 40 mg dose of telmisartan. Therefore, caution should 
be exercised when ataluren is co-administered with medicinal products that are substrates of OAT1 or 
OATP1B3 because of the risk of increased concentration of these medicinal products (e.g. oseltamivir, 
aciclovir, captopril, furosemide, bumetanide, valsartan, pravastatin, rosuvastatin, atorvastatin, 
pitavastatin).  
 
Caution should also be exercised when ataluren is co-administered with OAT3 substrates (e.g. 
ciprofloxacin), especially those OAT3 substrates with a narrow therapeutic window. In a clinical 
study, the extent of exposure for ciprofloxacin was 32% higher in the presence of ataluren. In a 
separate clinical study, the extent of exposure for adefovir was 60% higher in the presence of ataluren. 
Caution should be exercised when ataluren is co-administered with adefovir.  
 
Based on the in vitro studies, ataluren is not expected to be an inhibitor of neither p-gp mediated 
transport nor of cytochrome P450 mediated metabolism. Similarly, ataluren is not expected in vivo to 
be an inducer of cytochrome P450 isoenzymes.  
 
Coadministration of corticosteroids (deflazacort, prednisone, or prednisolone) with ataluren did not 
affect the plasma concentrations of ataluren. No clinically relevant change in the plasma 
concentrations of corticosteroids was seen with co-administration of ataluren. These data indicate no 
apparent drug-drug interaction between corticosteroids and ataluren, and no dose adjustments are 
required. 
 
Medicinal products that affect the p-glycoprotein transporter 
 
In vitro, ataluren is not a substrate for the p-glycoprotein transporter. The pharmacokinetics of ataluren 
are unlikely to be affected by medicinal products that inhibit the p-glycoprotein transporter. 
 
4.6 Fertility, pregnancy and lactation 
 
Pregnancy 
 
There are no adequate data from the use of ataluren in pregnant women. Studies in animals have 
shown reproductive toxicity only at doses that resulted in maternal toxicity (see section 5.3).  
As a precautionary measure, it is recommended to avoid the use of ataluren during pregnancy. 
 
Breastfeeding 
 
It is unknown whether ataluren/metabolites are excreted in human milk. Available 
pharmacodynamic/toxicological data in animals have shown excretion of ataluren/metabolites in milk 
(see section 5.3). A risk to the breastfed new-borns/infants cannot be excluded. 
 
Breast-feeding should be discontinued during treatment with ataluren. 
 



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Fertility 
 
Non-clinical data revealed no hazard for humans based on a standard male and female fertility study in 
rats (see section 5.3). 
 
4.7 Effects on ability to drive and use machines 
 
The effect of ataluren on driving, on cycling, or on using machines has not been tested. Patients who 
experience dizziness should use caution when driving, cycling or using machines.  
 
4.8 Undesirable effects 
 
Summary of the safety profile 
 
The safety profile of ataluren is based on pooled data from two randomised, double-blind, 48-week 
placebo-controlled studies conducted in a total of 232 male patients with Duchenne muscular 
dystrophy (nmDMD) caused by a nonsense mutation treated at the recommended dose of 
40 mg/kg/day (10, 10, 20 mg/kg; n=172) or at a dose of 80 mg/kg/day (20, 20, 40 mg/kg; n=60), as 
compared to placebo-treated patients (n=172). 
 
The most common adverse reactions in the 2 placebo-controlled studies were vomiting, diarrhoea, 
nausea, headache, upper abdominal pain, and flatulence, all occurring in ≥5% of all ataluren-treated 
patients. In both studies, 1/232 (0.43%) patients treated with ataluren discontinued due to an adverse 
reaction of constipation and 1/172 (0.58%) placebo patients discontinued treatment due to an adverse 
reaction of disease progression (loss of ambulation).  
 
An open-label study was performed including patients aged 2-5 years (n=14) to evaluate the PK and 
safety of ataluren. A higher frequency of malaise (7.1%), pyrexia (42.9%), ear infection (28.6%), and 
rash (21.4%) were reported in patients aged 2-5 years compared with patients 5 years of age and older. 
However, these conditions are reported more frequently in the younger children in general. Safety data 
from 28 weeks of therapy showed a similar safety profile of ataluren in patients 2-5 years as compared 
with patients aged 5 years and older. 
 
Adverse reactions were generally mild or moderate in severity, and no treatment-related serious 
adverse events were reported among ataluren-treated patients in these 2 studies. 
 
Tabulated list of adverse reactions  
 
The adverse reactions reported in patients with nmDMD treated with the recommended daily dose of 
40 mg/kg/day ataluren in the 2 placebo-controlled studies are presented in Table 1. Adverse reactions 
reported in >1 patient in the 40 mg/kg/day group at a frequency greater than that of the placebo group 
are presented by MedDRA System Organ Class, Preferred Term, and frequency. Frequency groupings 
are defined to the following convention: very common (≥ 1/10) and common (≥ 1/100 to < 1/10).  
 



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Table 1. Adverse reactions reported in >1 ataluren-treated patients with nmDMD at a frequency 
greater than placebo in the 2 placebo-controlled studies (pooled analysis) 
 
System Organ Class Very common Common Frequency not 

known 
Metabolism and nutrition 
disorders 

 Decreased appetite, 
hypertriglyceridaemia 

Change in lipid 
profile 
(increased 
triglycerides and 
cholesterol) 

Nervous system disorders  Headache  

Vascular disorders  Hypertension   

Respiratory, thoracic, and 
mediastinal disorders  

 Cough, epistaxis  

Gastrointestinal disorders  Vomiting Nausea, upper abdominal 
pain, flatulence, abdominal 
discomfort, constipation  

 

Skin and subcutaneous tissue 
disorders 

 Rash erythematous  

Musculoskeletal and 
connective tissue disorders  

 Pain in extremity, 
musculoskeletal chest pain 

 

Renal and urinary disorders  Haematuria, enuresis Change in renal 
function tests 
(increased 
creatinine, blood 
urea nitrogen, 
cystatin C) 

General disorders and 
administration site conditions  

 Pyrexia, weight decreased  

 
In a 48-week open-label extension study in patients with nmDMD patients who were ambulant or non-
ambulant demonstrated a similar safety profile. Long term safety data is not available. 
 
Description of selected adverse reactions (laboratory abnormalities) 
 
Serum lipids 
An increase in serum lipids, i.e. cholesterol and triglycerides, was observed. There have been cases 
reported where this increase to abnormal high values was already observed after 4 weeks. 
 
Renal function tests 
During the randomised, placebo-controlled studies, small increases in mean serum creatinine, BUN, 
and cystatin C were observed. The values tended to stabilize early in the study and did not increase 
further with continued treatment. 
 
Reporting of suspected adverse reactions  
 
Reporting suspected adverse reactions after authorisation of the medicinal product is important. It 
allows continued monitoring of the benefit/risk balance of the medicinal product. Healthcare 
professionals are asked to report any suspected adverse reactions via the national reporting system 
listed in Appendix V. 
 



9 

4.9 Overdose 
 
Healthy volunteers receiving a single oral dose of 200 mg/kg of ataluren experienced transient, 
low-grade symptoms of headache, nausea, vomiting, and diarrhoea. No serious adverse reactions were 
observed in these subjects. In the event of a suspected overdose, supportive medical care should be 
provided including consulting with a healthcare professional and close observation of the clinical 
status of the patient. 
 
 
5. PHARMACOLOGICAL PROPERTIES 
 
5.1  Pharmacodynamic properties 
 
Pharmacotherapeutic group: Other drugs for disorders of the musculo-skeletal system, ATC code: 
M09AX03 
 
Mechanism of action 
 
A nonsense mutation in DNA results in a premature stop codon within an mRNA. This premature stop 
codon in the mRNA causes disease by terminating translation before a full-length protein is generated. 
Ataluren enables ribosomal readthrough of mRNA containing such a premature stop codon, resulting 
in production of a full-length protein. 
 
Pharmacodynamic effects 
 
Nonclinical in vitro experiments in nonsense mutation cellular assays and fish larvae cultured in an 
ataluren solution have shown that ataluren enabled ribosomal readthrough with a bell-shaped 
(inverted-U shaped) concentration-response relationship. It is hypothesised that the in vivo dose 
response relationship may also be bell-shaped, but in vivo data were too limited to confirm this 
hypothesis in a mouse model for nmDMD and in humans. 
 
Nonclinical in vitro studies suggest that continuous exposure to ataluren may be important for 
maximizing activity and that effects of the active substance on ribosomal read-through of premature 
stop codons reverse shortly after withdrawal of ataluren. 
 
Clinical efficacy and safety 
 
The efficacy and safety of Translarna were assessed in 2 randomised, double-blind, 
placebo-controlled, trials in nmDMD. The primary efficacy endpoint in both trials was change in 6 
Minute Walk Distance (6MWD) at Week 48. Other endpoints included in both trials were time to 
persistent 10% worsening in 6MWD, change in time to run/walk 10 meters at Week 48, change in 
time to climb 4 stairs at Week 48, and change in time to descend 4 stairs at Week 48. Patients were 
required to have documented confirmation of the presence of a nonsense mutation in the dystrophin 
gene as determined by gene sequencing.  
   
Study 1 evaluated 174 male patients, aged 5 to 20 years. All patients were required to be able to walk 
≥75 meters without the need for assistive devices during a screening 6-Minute Walk Test (6MWT). 
The majority of patients in all treatment groups were Caucasian (90%). Patients were randomised in a 
1:1:1 ratio and received ataluren or placebo 3 times per day (morning, midday, and evening), with 57 
receiving ataluren 40 mg/kg/day (10, 10, 20 mg/kg), 60 receiving ataluren 80 mg/kg/day (20, 20, 
40 mg/kg), and 57 receiving placebo.  
 



10 

In Study 1, a post hoc analysis of the primary endpoint showed that from baseline to Week 48, patients 
receiving ataluren 40 mg/kg/day had a 12.9 meters mean decline in 6MWD, and patients receiving 
placebo had a 44.1-meter mean decline in 6MWD (Figure 1). Thus, the mean change in observed 
6MWD from baseline to Week 48 was 31.3 meters better in the ataluren 40 mg/kg/day arm than in the 
placebo arm (p=0.056). In a statistical based model the estimated mean difference was 31.7 meters 
(adjusted p=0.0367). There was no difference between ataluren 80 mg/kg/day and placebo. 
 
These results indicate that ataluren 40 mg/kg/day slows the loss of walking ability in nmDMD 
patients. 
 
Figure 1. Mean Change in 6-Minute Walk Distance (Study 1) 

6 12 18 24 30 36 42 48
-60

-50

-40

-30

-20

-10

0

10

20

Placebo (N=57)

TRANSLARNA 10 mg/kg, 10 mg/kg, 20 mg/kg (N=57)

  Baseline

-12.9 m

-44.1 m

Weeks

M
et

er
s 

(±
SE

)

 
A post-hoc analysis of time to persistent 10% worsening in 6MWD showed that 26% of patients in the 
ataluren 40 mg/kg/day arm had progressed at Week 48 compared to 44% in the placebo group 
(p=0.0652) (Figure 2). There was no difference between ataluren 80 mg/kg/day and placebo. These 
results indicate that fewer patients receiving ataluren 40 mg/kg/day worsened in 6MWD over 48 
weeks. 
 

-e-... 



11 

Figure 2. Kaplan-Meier Curve of Time to Persistent 10% 6MWD Worsening (Study 1) 

0 6 12 18 24 30 36 42 48 54 60

Placebo (N=57)

TRANSLARNA 10 mg/kg, 10 mg/kg, 20 mg/kg (N=57)

10

20

30

40

50

60

70

80

90

100

26% worsening

44% worsening

Weeks

Pe
rc

en
t N

ot
 1

0%
 W

or
se

ne
d

 
In timed function tests (TFTs), tests of time to run/walk 10 meters, time to climb 4 stairs, and time to 
descend 4 stairs, ataluren-treated patients demonstrated smaller increases in the time it takes to 
run/walk 10 meters, climb 4 stairs, and descend 4 steps, indicating slowing of nmDMD progression 
relative to placebo. 
 
The mean change in timed function tests from baseline to Week 48 was better in the ataluren 40 
mg/kg/day arm than placebo in time to run/walk 10 meters (better by 1.5 seconds), time to climb 
4 stairs (better by 2.4 seconds), and time to descend 4 stairs (better by 1.6 seconds), Figure 3. 
 

I L ____ _ 
I 
"---- .. --. 

·-----"?... 
L----1-----:._, 

--•--•-.. ____ , 
L---



12 

Figure 3. Mean Change in Timed Function Tests (Study 1)  

 
6MWD Results in Patients with a Baseline 6MWD < 350 meters.  
 
In patients with a baseline 6MWD <350 meters, the mean change in observed 6MWD from baseline to 
Week 48 was 68 meters better in the ataluren 40 mg/kg/day arm than in the placebo arm (p=0.0053).   
 
In these patients, the mean change in timed function tests from baseline to Week 48 was better in the 
ataluren 40 mg/kg/day arm than placebo in time to run/walk 10 meters (better by 3.5 seconds), time to 
climb 4 stairs (better by 6.4 seconds), and time to descend 4 stairs (better by 5.0 seconds). 
 
Study 2 evaluated 230 male patients, ages 7 to 14 years. All patients were required to be able to walk 
≥150 meters and less than 80% predicted without the need for assistive devices during a screening 
6MWT. The majority of patients in both treatment groups were Caucasian (76%). Patients were 
randomised in a 1:1 ratio and received ataluren 40 mg/kg/day (n=115) or placebo (n=115) 3 times per 
day (morning, midday, and evening). 
 
Ataluren-treated patients experienced clinical benefit as measured by numerically favorable 
differences versus placebo across the primary and secondary efficacy endpoints. As the primary 
endpoint (change in 6MWD from baseline to Week 48) did not reach statistical significance (p≤0.05), 
all other p-values should be considered nominal. 
 
In the ITT population, the difference between the ataluren and placebo arms in mean change in 
observed 6MWD from baseline to Week 48 was 15.4 meters better in the ataluren 40 mg/kg/day arm 
than in the placebo arm. In a statistical based model the estimated mean difference was 13.0 meters 
(p=0.213), Figure 4. Separation between ataluren and placebo was maintained from Week 16 through 
the end of the study.   
 

~ 0 
10m Run/Walk 4-Stair Climb 4-Stair Descend 

"C 
C: 
0 
0 
Cl) 
rJ) 

w· 
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+I 
C: -1.5 s ca 
Cl) 

-2.4 s 
t7) E -1.6 s 
C: 4 
C: 

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3: ca ID 

E 6 e ..... 
Cl) ■ Translarna 10, 10, 20 mg/kg (N=57) Cl 

□ Placebo (N=57) C: ca 
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13 

Figure 4. Mean Change in 6-Minute Walk Distance (Study 2) 
 

8 1 6 2 4 3 2 4 0 4 8
-8 0

-7 0

-6 0

-5 0

-4 0

-3 0

-2 0

-1 0

0

P la c e b o  (N = 1 1 4 )

T R A N S L A R N A  1 0  m g /k g / 1 0  m g /k g , 2 0  m g /k g  (N = 1 1 4 )

  B a s e lin e

W e e k s

M
e

te
rs

 (
±

S
E

)

-4 2 .2

-5 7 .6

 
 
Over 48 weeks, ataluren-treated patients showed less decline in muscle function, as evidenced by 
smaller increases in the time to run/walk 10 meters, climb 4 steps, and descend 4 steps in the ataluren-
treated group relative to placebo. The differences favoring ataluren versus placebo in mean changes in 
timed function tests at Week 48 in the ITT population reached the threshold for a clinically meaningful 
difference (changes ~1 to 1.5 seconds). 
 
The mean change in timed function tests from baseline to Week 48 was better in the ataluren 
40 mg/kg/day arm than placebo in observed time to run/walk 10 meters (better by 1.2 seconds, 
p=0.117), time to climb 4 stairs (better by 1.8 seconds, p=0.058), and time to descend 4 stairs (better 
by 1.8 seconds, p=0.012), Figure 5. 
 

-B--

.... 



14 

Figure 5. Mean Change in Timed Function Tests (Study 2) 
 

 
 
Time to 10% worsening in 6MWD was defined as the last time that 6MWD was not 10% worse than 
baseline. In the ITT population, the hazard ratio for ataluren versus placebo was 0.75 (p=0.160), 
representing a 25% reduction in the risk of 10% 6MWD worsening.  
 
Paediatric population 
 
The safety, pharmacokinetics and exploratory effectiveness of Translarna were assessed in an open-
label study in children between 2 and 5 years of age with nmDMD. The efficacy of Translarna in 
children aged 2 - 5 years has been established on extrapolation from patients aged >5years. 
 
In the clinical program investigating the efficacy and safety of monotherapy ataluren in patients with 
nonsense mutation cystic fibrosis, no statistically significant effect was observed in the primary and 
key secondary clinical outcome measures (ppFEV1 and pulmonary exacerbation rate) in adults and 
children aged 6 years and older. 
 
The European Medicines Agency has waived the obligation to submit the results of studies with 
ataluren in two subsets of the paediatric population from birth to less than 28 days and infants from 
28 days to less than 6 months in nmDMD, as per Paediatric Investigation Plan (PIP) decision in the 
granted indication (see section 4.2 for information on paediatric use).  
 
The European Medicines Agency has deferred the obligation to submit the results of studies with 
ataluren in one subset of the paediatric population aged 6 months to less than 2 years old in nmDMD, 
as per Paediatric Investigation Plan (PIP) decision in the granted indication (see section 4.2 for 
information on paediatric use). 
 
This medicinal product has been authorised under a so-called ‘conditional approval’ scheme. This 
means that further evidence on this medicinal product is awaited.European Medicines Agency will 
review new information on this medicinal product at least every year and this SmPC will be updated as 
necessary. 
 

- 10m Run/Walk 4-Stair Climb 4-Stair Descend ti) 0 
"'C 
C 
0 
(,) 
(1) 
ti) 

u.i 2 (/) 
+I 
C 

-1.8 s ns -1 .2 s (1) 
C) E -1.8 s 
C -
C (1) 4 
(1) C 

l!? (1) 
0 
3: 

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E 6 
0 
'- • TRANSLARNA 10, 10, 20 mg/kg (N=114) -a, 

□ Placebo (N=114) C) 
C 
ns 
~ 
(.) 8 



15 

5.2 Pharmacokinetic properties 
 
Administration of ataluren on a body weight-adjusted basis (mg/kg) resulted in similar steady-state 
exposures (AUC) among children and adolescents with nmDMD over a broad range of body weights. 
Although ataluren is practically insoluble in water, ataluren is readily absorbed after oral 
administration as a suspension.  
 
General characteristics of ataluren after administration 
 
Absorption 
Peak plasma levels of ataluren are attained approximately 1.5 hours after dosing in subjects who 
received medicinal product within 30 minutes of a meal. Based on the urinary recovery of 
radioactivity in a single-dose study of radiolabelled ataluren, the oral bioavailability of ataluren is 
estimated to be ≥ 55%. Ataluren plasma concentrations at steady state increase proportionally with 
increasing dose. Steady-state plasma concentrations are dose-proportional for ataluren doses between 
10 and 50 mg/kg, and no accumulation is observed after repeated dosing.  
 
Distribution 
In vitro, ataluren is 99.6% bound to human plasma proteins and the binding is independent of plasma 
concentration. Ataluren does not distribute into red blood cells. 
 
Biotransformation 
Ataluren is metabolized by conjugation via uridine diphosphate glucuronosyltransferase (UGT) 
enzymes, predominantly UGT1A9 in liver, intestine and kidney.  
 
In vivo, the only metabolite detected in plasma after oral administration of radio-labelled ataluren was 
the ataluren-O-1β-acyl glucuronide; exposure to this metabolite in humans was approximately 8% of 
the plasma AUC of ataluren. 
 
Elimination 
Ataluren plasma half-life ranges from 2-6 hours and is unaffected either by dose or repeated 
administration. The elimination of ataluren is likely dependent on hepatic and renal glucuronidation of 
ataluren followed by renal and hepatic excretion of the resulting glucuronide metabolite. 
 
After a single oral dose of radiolabelled ataluren, approximately half of the administered radioactive 
dose is recovered in the faeces and the remainder was recovered in the urine. In the urine, unchanged 
ataluren and the acyl glucuronide metabolite account for <1% and 49%, respectively, of the 
administered dose. 
 
Linearity/non-linearity 
Steady-state plasma concentrations are dose-proportional for ataluren doses between 10 and 50 mg/kg, 
and no accumulation is observed after repeated dosing. Based on data in healthy volunteers, the 
relative bioavailability of ataluren is approximately 40% lower at steady-state than after the initial 
dose. The onset of reduction in relative bioavailability is estimated to occur approximately 60 hours 
after the first dose. The steady-state is established after approximately two weeks of thrice daily 
dosing. 
 
Characteristic in specific groups of subjects or patients 
 
Age 
Based on data from subjects ranging in age from 2 years to 57 years, there is no apparent effect of age 
on ataluren plasma exposure. Age-adjusted dosing is not required. 
 
The pharmacokinetics of ataluren has been evaluated in study PTC124-GD-030 over a duration of 4 
weeks. Ataluren plasma concentrations in patients from 2 to less than 5 years old were consistent with 
those seen in patients above the age of 5 years receiving the 10/10/20 mg/kg dose regimen. 
 



16 

Gender 
Females were not studied in nmDMD clinical trials. However there were no apparent effects of gender 
on ataluren plasma exposure in other populations. 
 
Race 
It is unlikely that the pharmacokinetics of ataluren are significantly affected by UGT1A9 
polymorphisms in a Caucasian population. Due to the low number of other races included in the 
clinical studies, no conclusions can be drawn on the effect of UGT1A9 in other ethnic groups. 
 
Renal impairment 
No dosage adjustment is required for patients with mild or moderate renal impairment. 
In a pharmacokinetic study in subjects with varying degrees of renal impairment, following a single 
dose administration, ataluren plasma exposure changed by -13%, 27%, and 61% for the mild, 
moderate and severe groups, respectively, and 46% for the end-stage renal disease group compared 
with the normal renal function group. In addition, a 3 to 8 fold increase in ataluren metabolite has been 
reported in patients with severe renal impairment (eGFR <30 ml/min). Following multiple dosing, the 
increase in ataluren and ataluren metabolite is anticipated to be higher in patients with severe renal 
impairment and end-stage renal disease when compared with patients with normal renal function at 
steady state. Patients with severe renal impairment (eGFR <30 ml/min) or end-stage renal disease 
should be treated with ataluren only if the anticipated clinical benefit outweighs the potential risk (see 
sections 4.2 and 4.4). 
 
Hepatic impairment 
Based on a pharmacokinetic assessment conducted in groups with either mild, moderate or severe 
hepatic impairment versus a control group of healthy subjects, no dose adjustment is required for 
patients with any degree of hepatic impairment. No apparent differences of the total ataluren exposure 
in the control, mild, and severe hepatic impairment groups were observed. An approximately 40% 
decrease of mean total ataluren exposure in the moderate hepatic impairment group versus the control 
group was noted probably due to the small sample size and variability. 
 
Non-ambulatory 
There were no apparent differences in either steady-state relative bioavailability or apparent clearance 
due to loss of ambulation. No dosing adjustment is needed for patients who are becoming non-
ambulatory. 
 
5.3 Preclinical safety data 
 
Non-clinical data reveal no special hazard for humans based on conventional studies of safety 
pharmacology and genotoxicity.  
 
A standard package of reproduction toxicity studies was available. No effects on male and female 
fertility were observed, but effects of early juvenile treatment on fertility during adulthood were not 
investigated. In rats and rabbits embryo-foetal toxicity (e.g. increased early resorptions, post-
implantation loss, decreased viable foetuses) and signs of delayed development (increased skeletal 
variations) were found in the presence of maternal toxicity. Exposure at the no observed adverse effect 
level (NOAEL) was similar to (rabbit) or 4 times (rat) the systemic exposure in humans (40 
mg/kg/day). Placental transfer was shown of radiolabelled ataluren in rats. At a single tested, relatively 
low, maternal dose of 30 mg/kg, the concentration of foetal radioactivity was ≤ 27% of the maternal 
concentration. In the rat pre/postnatal developmental toxicity study, at exposure about 5 times human 
exposure, significant maternal toxicity as well as effects on offspring body weight and development of 
ambulatory activity were observed. The maternal systemic exposure at the no observed effect level 
(NOEL) for neonatal toxicity was about 3 times human exposure. At a single, relatively low, maternal 
dose of 30 mg/kg radiolabelled ataluren, the highest measured concentration of radioactivity in rat 
milk was 37% of the maternal plasma concentration. Presence of radioactivity in pup plasma 
confirmed absorption from the milk by the pups. 
 



17 

Renal toxicity (nephrosis in the distal nephron) occurred in repeat oral dose studies in mice at systemic 
exposure equivalent to 0.3 times the steady state AUC in patients administered Translarna at 
respective morning, midday, and evening doses of 10-, 10-, 20-mg/kg and higher. 
 
In a 26-week transgenic mouse model for carcinogenicity, no evidence of carcinogenicity was found. 
In a 2-year rat carcinogenicity study, one case of hibernoma was found. In addition, at exposure much 
higher than in patients an increase of (rare) urinary bladder tumours was found. Significance of the 
urinary bladder tumours for humans is considered unlikely. 
 
One out of two 26-week rat repeat dose studies, initiated in 4-5 weeks old rats, showed a dose related 
increase of the incidence of malignant hibernoma, a rare tumour in rats. In addition, one case of 
malignant hibernoma was found at the highest dose in a 2-year rat carcinogenicity study. Background 
incidence of this tumour type in rats as well as humans is very low and the mechanism causing these 
tumours in the rat studies (including its relation to ataluren treatment) is unknown. The significance 
for humans is not known. 
 
A 1-year study in 10-12 weeks old dogs demonstrated findings in the adrenal gland (focal 
inflammation and degeneration in the glucocorticoid-producing regions of the cortex) and a mild 
compromise of cortisol production after exogenous stimulation with adrenocorticotropic hormone. 
These findings were seen in dogs at systemic exposure equivalent to 0.8 times the steady state AUC in 
patients administered Translarna at respective morning, midday, and evening doses of 40 mg/kg/day 
and higher. In a rat distribution study a high adrenal concentration of ataluren was observed. 
 
In addition to the above mentioned effects, several other less adverse effects were found in the repeat 
dose studies; in particular decreased body weight gain, food intake and increased liver weight without 
a histological correlate and of unclear clinical significance. Also rat and dog studies showed changes 
in plasma lipid (cholesterol and triglycerides) suggestive of changes in fat metabolism. 
 
No adverse findings, including in the adrenal gland, were observed in a 3-month study in neonatal 
dogs (1-week old) followed by a 3-month recovery period up to steady state systemic exposures 
equivalent to the steady state AUC in patients. In preliminary studies in neonatal dogs (1-week old), 
initial systemic exposures equivalent to 5-10 times the steady state AUC in patients were not tolerated 
in some animals. 
 
 
6. PHARMACEUTICAL PARTICULARS 
 
6.1 List of excipients  
 
Polydextrose (E1200) 
Macrogol 
Poloxamer 
Mannitol (E421) 
Crospovidone 
Hydroxyethyl cellulose 
Artificial vanilla flavour: maltodextrin, artificial flavours and propylene glycol. 
Silica, colloidal anhydrous (E551) 
Magnesium stearate 
 
6.2 Incompatibilities 
 
Not applicable 
 



18 

6.3 Shelf life 
 
4 years 
 
Each prepared dose is best administered immediately after preparation. The prepared dose should be 
discarded if not consumed within 24 hours of preparation if kept refrigerated (2 – 8 °C), or within 
3 hours at room temperature (15 – 30 °C). 
 
6.4 Special precautions for storage 
 
This medicinal product does not require any special storage conditions. 
For storage conditions after dilution of the medicinal product, see section 6.3. 
 
6.5 Nature and contents of container  
 
Heat-sealed laminated aluminium foil sachet: polyethylene terephthalate (child resistance), 
polyethylene (colouring and polyester/foil bond), aluminium foil (moisture barrier), adhesive 
(polyurethane class), copolymer of ethylene and methacrylic acid (sealant resin for packaging 
integrity). 
 
Pack of 30 sachets.  
 
6.6 Special precautions for disposal and other handling 
 
Sachets should only be opened at the time of dose preparation. The full contents of each sachet should 
be mixed with at least 30 ml of liquid (water, milk, fruit juice), or 3 tablespoons of semi-solid food 
(yoghurt or apple sauce). The prepared dose should be mixed well before administration. The amount 
of the liquid or semi-solid food can be increased based on patient preference.  
 
Any unused medicinal product or waste material should be disposed of in accordance with local 
requirements. 
 
 
7. MARKETING AUTHORISATION HOLDER 
 
PTC Therapeutics International Limited 
5th Floor 
3 Grand Canal Plaza 
Grand Canal Street Upper 
Dublin 4 
D04 EE70 
Ireland 
 
 
8. MARKETING AUTHORISATION NUMBERS 
 

Translarna 125 mg granules for oral suspension 
EU/1/13/902/001 
 
Translarna 250 mg granules for oral suspension 
EU/1/13/902/002 
 
Translarna 1000 mg granules for oral suspension 
EU/1/13/902/003 

 
 



19 

9. DATE OF FIRST AUTHORISATION/RENEWAL OF THE AUTHORISATION 
 

Date of first authorisation: 31 July 2014 
Date of latest renewal: 25 July 2019 

 
 
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. 
 



20 

 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

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 
 
E. SPECIFIC OBLIGATION TO COMPLETE POST-AUTHORISATION MEASURES 

FOR THE CONDITIONAL MARKETING AUTHORISATION 
 

 



21 

A. MANUFACTURER RESPONSIBLE FOR BATCH RELEASE 
 
Name and address of the manufacturer responsible for batch release 
Almac Pharma Services Ltd. 
Seagoe Industrial Estate 
Craigavon 
Co. Armagh BT63 5UA 
United Kingdom 
 
PTC Therapeutics International Limited 
5th Floor 
3 Grand Canal Plaza 
Grand Canal Street Upper 
Dublin 4 
D04 EE70 
Ireland 
 
Almac Pharma Services (Ireland) Limited 
Finnabair Industrial Estate 
Dundalk, Co. Louth, A91 P9KD 
Ireland 
 
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. 
The marketing authorisation holder shall submit the first periodic safety update report for this 
product within 6 months following authorisation.  
 
 
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. 
 



22 

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.  
 
If the submission of a PSUR and the update of a RMP coincide, they can be submitted at the same 
time. 
 
 
E. SPECIFIC OBLIGATION TO COMPLETE POST-AUTHORISATION MEASURES 
FOR THE CONDITIONAL MARKETING AUTHORISATION  
 
This being a conditional marketing authorisation and pursuant to Article 14(7) of Regulation (EC) 
No 726/2004, the MAH shall complete, within the stated timeframe, the following measures: 
 
Description Due date 
In order to confirm the efficacy and safety of ataluren in the treatment of ambulant 
patients with nmDMD aged 5  years or older, the MAH should conduct and submit 
the results of a multicentre, randomised, double-blind, 18-month, placebo-
controlled study, followed by a 18-month open label extension, according to an 
agreed protocol. 
 

Final study 
report to be 
submitted 
Due date:  
September 
2022 
 



23 

 
 
 

 
 

 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

ANNEX III 
 

LABELLING AND PACKAGE LEAFLET



24 

 
 
 
 
 
 
 
 

 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

A. LABELLING 



25 

PARTICULARS TO APPEAR ON THE OUTER PACKAGING 
 
Carton Box 
 
 
1. NAME OF THE MEDICINAL PRODUCT 
 
Translarna 125 mg granules for oral suspension 
ataluren 
 
 
2. STATEMENT OF ACTIVE SUBSTANCE(S) 
 
Each sachet contains 125 mg of ataluren 
 
 
3. LIST OF EXCIPIENTS 
 
 
 
4. PHARMACEUTICAL FORM AND CONTENTS 
 
Granules for oral suspension 
30 sachets 
 
 
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 
 
 
 



26 

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 
 
PTC Therapeutics International Limited 
5th Floor 
3 Grand Canal Plaza 
Grand Canal Street Upper 
Dublin 4 
D04 EE70 
Ireland 
 
 
12. MARKETING AUTHORISATION NUMBER(S)  
 
EU/1/13/902/001 
 
 
13. BATCH NUMBER 
 
Lot 
 
 
14. GENERAL CLASSIFICATION FOR SUPPLY 
 
Medicinal product subject to medical prescription 
 
 
15. INSTRUCTIONS ON USE 
 
 
 
16. INFORMATION IN BRAILLE 
 
Translarna 125 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}  
 
 



27 

MINIMUM PARTICULARS TO APPEAR ON SMALL IMMEDIATE PACKAGING UNITS 
 
Aluminium sachet 
 
 
1. NAME OF THE MEDICINAL PRODUCT AND ROUTE(S) OF ADMINISTRATION 
 
Translarna 125 mg granules for oral suspension 
ataluren 
 
Oral use 
 
 
2. METHOD OF ADMINISTRATION 
 
Read the package leaflet before use 
 
 
3. EXPIRY DATE 
 
EXP 
 
 
4. BATCH NUMBER 
 
Lot 
 
 
5. CONTENTS BY WEIGHT, BY VOLUME OR BY UNIT 
 
125 mg  
 
 
6. OTHER 
 
 
 



28 

PARTICULARS TO APPEAR ON THE OUTER PACKAGING 
 
Carton Box 
 
 
1. NAME OF THE MEDICINAL PRODUCT 
 
Translarna 250 mg granules for oral suspension 
ataluren 
 
 
2. STATEMENT OF ACTIVE SUBSTANCE(S) 
 
Each sachet contains 250 mg of ataluren 
 
 
3. LIST OF EXCIPIENTS 
 
 
 
4. PHARMACEUTICAL FORM AND CONTENTS 
 
Granules for oral suspension 
30 sachets 
 
 
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 
 
 
 



29 

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 
 
PTC Therapeutics International Limited 
5th Floor 
3 Grand Canal Plaza 
Grand Canal Street Upper 
Dublin 4 
D04 EE70 
Ireland 
 
 
12. MARKETING AUTHORISATION NUMBER(S)  
 
EU/1/13/902/002 
 
 
13. BATCH NUMBER 
 
Lot 
 
 
14. GENERAL CLASSIFICATION FOR SUPPLY 
 
Medicinal product subject to medical prescription 
 
 
15. INSTRUCTIONS ON USE 
 
 
 
16. INFORMATION IN BRAILLE 
 
Translarna 250 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}  
 
 
 



30 

MINIMUM PARTICULARS TO APPEAR ON SMALL IMMEDIATE PACKAGING UNITS 
 
Aluminium sachet 
 
 
1. NAME OF THE MEDICINAL PRODUCT AND ROUTE(S) OF ADMINISTRATION 
 
Translarna 250 mg granules for oral suspension 
ataluren 
 
Oral use 
 
 
2. METHOD OF ADMINISTRATION 
 
Read the package leaflet before use 
 
 
3. EXPIRY DATE 
 
EXP 
 
 
4. BATCH NUMBER 
 
Lot 
 
 
5. CONTENTS BY WEIGHT, BY VOLUME OR BY UNIT 
 
250 mg  
 
 
6. OTHER 
 
 
 



31 

PARTICULARS TO APPEAR ON THE OUTER PACKAGING 
 
Carton Box 
 
 
1. NAME OF THE MEDICINAL PRODUCT 
 
Translarna 1000 mg granules for oral suspension 
ataluren 
 
 
2. STATEMENT OF ACTIVE SUBSTANCE(S) 
 
Each sachet contains 1000 mg of ataluren 
 
 
3. LIST OF EXCIPIENTS 
 
 
 
4. PHARMACEUTICAL FORM AND CONTENTS 
 
Granules for oral suspension 
30 sachets 
 
 
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 
 
 
 



32 

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 
 
PTC Therapeutics International Limited 
5th Floor 
3 Grand Canal Plaza 
Grand Canal Street Upper 
Dublin 4 
D04 EE70 
Ireland 
 
 
12. MARKETING AUTHORISATION NUMBER(S)  
 
EU/1/13/902/003  
 
 
13. BATCH NUMBER 
 
Lot 
 
 
14. GENERAL CLASSIFICATION FOR SUPPLY 
 
Medicinal product subject to medical prescription 
 
 
15. INSTRUCTIONS ON USE 
 
 
 
16. INFORMATION IN BRAILLE 
 
Translarna 1000 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} 
 
 
 



33 

MINIMUM PARTICULARS TO APPEAR ON SMALL IMMEDIATE PACKAGING UNITS 
 
Aluminium sachet 
 
 
1. NAME OF THE MEDICINAL PRODUCT AND ROUTE(S) OF ADMINISTRATION 
 
Translarna 1000 mg granules for oral suspension 
ataluren 
 
Oral use 
 
 
2. METHOD OF ADMINISTRATION 
 
Read the package leaflet before use 
 
 
3. EXPIRY DATE 
 
EXP 
 
 
4. BATCH NUMBER 
 
Lot 
 
 
5. CONTENTS BY WEIGHT, BY VOLUME OR BY UNIT 
 
1000 mg  
 
 
6. OTHER 
 
 
 



34 

 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

B. PACKAGE LEAFLET 



35 

Package leaflet: Information for the patient 
 

Translarna 125 mg granules for oral suspension 
Translarna 250 mg granules for oral suspension 

Translarna 1000 mg granules for oral suspension 
ataluren 

 
This medicine is subject to additional monitoring. This will allow quick identification of new 

safety information. You can help by reporting any side effects you may get. See the end of section 4 
for how to report side effects. 
 
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 Translarna is and what it is used for 
2. What you need to know before you take Translarna 
3. How to take Translarna 
4. Possible side effects  
5. How to store Translarna 
6. Contents of the pack and other information 
 
 
1. What Translarna is and what it is used for 
 
Translarna is a medicine that contains the active substance ataluren. 
 
Translarna is used to treat Duchenne muscular dystrophy resulting from a specific genetic defect that 
affects normal muscle function. 
 
Translarna is used to treat patients aged 2 years and older, who are able to walk. 
 
You or your child will have been tested by your doctor before starting treatment with Translarna, in 
order to confirm that your disease is suitable for treatment with this medicine. 
 
How does Translarna work? 
 
Duchenne muscular dystrophy is caused by genetic changes that result in an abnormality in a muscle 
protein called dystrophin which is needed for muscles to work properly. Translarna enables the 
production of working dystrophin and helps muscles work properly. 
 
 
2. What you need to know before you take Translarna 
 
Do not take Translarna 
- If you are allergic to ataluren or any of the other ingredients of this medicine (listed in section 6). 
- If you are receiving treatment with certain antibiotics, such as gentamicin, tobramycin, or 

streptomycin by injection into a vein. 
 



36 

Warnings and precautions  
Your doctor must have done a blood test to confirm that your disease is suitable for treatment with 
Translarna. If you have any kidney problem, your doctor should check your kidney function regularly.  
 
If you have severe kidney problems (eGFR <30 ml/min) or if you are receiving dialysis because your 
kidneys do not work (end-stage renal disease) your doctor will establish if treatment with Translarna is 
suitable for you. 
 
Your doctor will test the levels of lipids (fats such as cholesterol and triglycerides) in your blood and 
your kidney function every 6 to 12 months. Your doctor will monitor your blood pressure every 
6 months, if you are taking a corticosteroid medicine. 
 
Children and adolescents 
Do not give this medicine to children under the age of 2 years or weighing less than 12 kg as it has not 
been tested in this group of patients. 
 
Other medicines and Translarna 
Tell your doctor if you are taking, have recently taken, or might take any other medicines. In particular 
do not take Translarna with the antibiotics gentamicin, tobramycin, or streptomycin given by injection. 
These may affect your kidney function.  
 
Tell your doctor if you are taking any of the following medicines:  
 
Medicine Usually prescribed for 
acyclovir treatment of chickenpox [varicella] 
adefovir treatment of chronic hepatitis B and/or HIV 
atorvastatin lipid-lowering 
benzylpenicillin severe infections 
bumetanide treatment or prevention of congestive heart failure 
captopril treatment or prevention of congestive heart failure 
ciprofloxacin treatment of infections 
famotidine treatment of active duodenal ulcer, gastroesophageal reflux disease 
furosemide treatment or prevention of congestive heart failure 
methotrexate rheumatoid arthritis, psoriasis 
olmesartan essential hypertension in adults 
oseltamivir prevention of influenza 
phenobarbital sleep-inducing, prevention of seizures 
pitavastatin lipid-lowering 
pravastatin lipid-lowering 
rifampicin treatment for tuberculosis 
rosuvastatin lipid-lowering 
sitagliptin type 2 diabetes 
valsartan treatment or prevention of congestive heart failure 
 
Some of these medicines were not tested together with Translarna and your doctor may decide to 
monitor you closely. 
 
Pregnancy and breast-feeding 
If you are pregnant or breast-feeding, think you may be pregnant or are planning to have a baby, ask 
your doctor for advice before taking this medicine. If you become pregnant while taking Translarna, 
consult your doctor immediately as it is recommended not to take Translarna while you are pregnant 
or breast-feeding.  
 
Driving and using machines 
If you feel dizzy, do not drive, cycle or use machines. 
 



37 

 
3. How to take Translarna 
 
Always take this medicine exactly as your doctor or pharmacist has told you. Check with them if you 
are not sure. 
 
Translarna is available in the following sachet strengths: 125 mg, 250 mg and 1000 mg of ataluren per 
sachet. Your doctor or pharmacist will tell you the exact number of sachets and what strength to take 
at each time. 
 
Your dose of Translarna depends on your body weight. The recommended dose is 10 mg/kg body 
weight in the morning, 10 mg/kg body weight at midday, and 20 mg/kg body weight in the evening 
(adding up to a total daily dose of 40 mg/kg body weight). 
 
The medicine is taken by mouth mixed in liquid or semi-solid food.  
 
Open the sachet only at the time you are taking the medicine and use the entire amount from the 
sachet. The full contents of each sachet should be mixed with at least 30 ml of liquid (water, milk, fruit 
juice) or 3 tablespoons of semi-solid food (yoghurt or apple sauce). Mix the prepared dose well before 
taking it. The amount of the liquid or semi-solid food can be increased based on your preference. 
 
Posology table 
 

Weight 
Range 
(kg) 

Number of Sachets 
Morning  Midday Evening 

125 
mg 

sachets 

250 
mg 

sachets 

1000 
mg 

sachets 

125 mg 
sachets 

250 mg 
sachets 

1000 
mg 

sachets 

125 mg 
sachets 

250 mg 
sachets 

1000 
mg 

sachets 
12 14 1 0 0 1 0 0 0 1 0 
15 16 1 0 0 1 0 0 1 1 0 
17 20 0 1 0 0 1 0 0 1 0 
21 23 0 1 0 0 1 0 1 1 0 
24 26 0 1 0 0 1 0 0 2 0 
27 31 0 1 0 0 1 0 1 2 0 
32 35 1 1 0 1 1 0 1 2 0 
36 39 1 1 0 1 1 0 0 3 0 
40 44 1 1 0 1 1 0 1 3 0 
45 46 0 2 0 0 2 0 1 3 0 
47 55 0 2 0 0 2 0 0 0 1 
56 62 0 2 0 0 2 0 0 1 1 
63 69 0 3 0 0 3 0 0 1 1 
70 78 0 3 0 0 3 0 0 2 1 
79 86 0 3 0 0 3 0 0 3 1 
87 93 0 0 1 0 0 1 0 3 1 
94 105 0 0 1 0 0 1 0 0 2 
106 111 0 0 1 0 0 1 0 1 2 
112 118 0 1 1 0 1 1 0 1 2 
119 125 0 1 1 0 1 1 0 2 2 
 
 



38 

Take Translarna by mouth 3 times per day; in the morning, midday and evening. There should be 
6 hours between morning and midday doses, 6 hours between midday and evening doses, and 12 hours 
between the evening dose and the first dose on the next day. For example, you might take Translarna 
at 7:00 AM in the morning with breakfast, at 1:00 PM in the afternoon with lunch, and again at around 
7:00 PM in the evening with dinner.  
 
Drink water or other liquids regularly to avoid dehydration while taking Translarna. 
 
If you take more Translarna than you should 
Contact your doctor if you take more than the recommended dose of Translarna.  
You may experience mild headache, nausea, vomiting or diarrhoea.  
 
If you forget to take Translarna 
If you are late in taking Translarna by less than 3 hours after the morning or midday doses, or by less 
than 6 hours after the evening dose, take the dose. Remember to take the next dose on time.  
If you are late by more than 3 hours after the morning or midday doses, or by more than 6 hours after 
the evening dose, do not take the dose. But, take the next doses on time.  
 
Do not take a double dose to make up for a forgotten dose. It is important to take the correct dose. 
Translarna may not be as effective in treating your symptoms if you take more than the recommended 
dose. 
 
If you stop taking Translarna 
Do not stop taking Translarna without talking to your doctor. 
 
If you have any further questions on the use of this medicine, ask your doctor. 
 
 
4. Possible side effects 
 
Like all medicines, this medicine can cause side effects, although not everybody gets them. You may 
have one or more of the following side effects after taking Translarna: 
 
Very common side effects (may affect more than 1 in 10 people): 
- Vomiting 
 
Common side effects (may affect up to 1 in 10 people): 
- Decreased appetite 
- High blood triglyceride levels 
- Headache 
- Feeling sick 
- Weight loss 
- High blood pressure 
- Cough 
- Nosebleed 
- Constipation 
- Wind 
- Stomach discomfort 
- Stomach pain 
- Rash 
- Arm or leg pain 
- Chest pain 
- Involuntary urination 
- Blood in urine  
- Fever 

 



39 

Frequency not known (frequency cannot be estimated from the available data): 
- Increases in blood lipids 
- Increases in test for kidney function 
 
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 Translarna 
 
Keep this medicine out of the sight and reach of children. 
 
Do not use this medicine after the expiry date, which is stated on the carton and sachet after ‘EXP’. 
The expiry date refers to the last day of that month. 
 
This medicine does not require any special storage conditions.  
 
Take each prepared dose immediately after preparation. Discard the prepared dose if not taken within 
24 hours of preparation if kept refrigerated (2 – 8 °C), or within 3 hours at room temperature 
(15 - 30 °C). 
 
Do not throw away any medicines via wastewater or household waste. Ask your pharmacist how to 
throw away medicines you no longer use. These measures will help protect the environment. 
 
 
6. Contents of the pack and other information 
 
What Translarna contains 
Translarna is available in 3 strengths, each containing 125 mg, 250 mg and 1000 mg of the active 
substance, called ataluren. The other ingredients are: polydextrose (E1200), macrogol, poloxamer, 
mannitol (E421), crospovidone, hydroxyethyl cellulose, artificial vanilla flavour (maltodextrin, 
artificial flavours and propylene glycol), silica, colloidal anhydrous (E551), magnesium stearate. 
 
What Translarna looks like and contents of the pack 
Translarna is white to off-white granules for oral suspension in sachets. 
Translarna is available in packs containing 30 sachets. 
 
Marketing Authorisation Holder 
PTC Therapeutics International Limited 
5th Floor 
3 Grand Canal Plaza 
Grand Canal Street Upper 
Dublin 4 
D04 EE70 
Ireland 
 
Manufacturer 
Almac Pharma Services 
22 Seagoe Industrial Estate 
Craigavon BT63 5QD 
United Kingdom  
 



40 

PTC Therapeutics International Limited 
5th Floor 
3 Grand Canal Plaza 
Grand Canal Street Upper 
Dublin 4 
D04 EE70 
Ireland 
 
Almac Pharma Services (Ireland) Limited 
Finnabair Industrial Estate 
Dundalk, Co. Louth, A91P9KD 
Ireland 
 
This leaflet was last revised in 
 
This medicine has been given ‘conditional approval’. This means that there is more evidence to come 
about this medicine. 
The European Medicines Agency will review new information on this medicine at least every year and 
this leaflet will be updated as necessary. 
 
Detailed information on this medicine is available on the European Medicines Agency web site: 
http://www.ema.europa.eu. There are also links to other websites about rare diseases and treatments. 

 


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