Nityr

1 

  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

ANNEX I 
 

SUMMARY OF PRODUCT CHARACTERISTICS 



2 

1. NAME OF THE MEDICINAL PRODUCT 
 
Nityr 10 mg tablets 
 
 
2. QUALITATIVE AND QUANTITATIVE COMPOSITION 
 
Each tablet contains 10 mg nitisinone. 
 
Excipient with known effect 
 
Each tablet contains less than 120 mg of lactose (as monohydrate). 
 
For the full list of excipients, see section 6.1. 
 
 
3. PHARMACEUTICAL FORM 
 
Tablet. 
 
White to beige, round (7 x 2.3 mm), flat tablets which may display light yellow to brown speckles, 
marked “10” on one side and “L” on the other side. 
 
 
4. CLINICAL PARTICULARS 
 
4.1 Therapeutic indications 
 
Treatment of adult and paediatric patients with confirmed diagnosis of hereditary tyrosinemia type 1 
(HT-1) in combination with dietary restriction of tyrosine and phenylalanine.  
 
4.2 Posology and method of administration 
 
Nitisinone treatment should be initiated and supervised by a physician experienced in the treatment of 
HT-1 patients. 
 
Posology 
Treatment of all genotypes of the disease should be initiated as early as possible to increase overall 
survival and avoid complications such as liver failure, liver cancer and renal disease. Adjunct to the 
nitisinone treatment, a diet deficient in phenylalanine and tyrosine is required and should be followed 
by monitoring of plasma amino acids (see sections 4.4 and 4.8). 
 
The recommended initial dose in the paediatric and adult population is 1 mg/kg body weight 
administered orally. The dose of nitisinone should be adjusted individually. It is recommended to 
administer the dose once daily. However, due to the limited data in patients with body weight <20kg, 
it is recommended to divide the total daily dose into two daily administrations in this patient 
population.  
 
Dose adjustment 
During regular monitoring, it is appropriate to follow urine succinylacetone, liver function test values 
and alpha-fetoprotein levels (see section 4.4). If urine succinylacetone is still detectable one month 
after the start of nitisinone treatment, the nitisinone dose should be increased to 1.5 mg/kg body 
weight/day. A dose of 2 mg/kg body weight/day may be needed based on the evaluation of all 
biochemical parameters. This dose should be considered as a maximal dose for all patients. If the 
biochemical response is satisfactory, the dose should be adjusted only according to body weight gain. 
 



3 

However, in addition to the tests above, during the initiation of therapy, switch from twice daily to 
once daily dosing or if there is a deterioration, it may be necessary to follow more closely all available 
biochemical parameters (i.e. plasma succinylacetone, urine 5-aminolevulinate (ALA) and erythrocyte 
porphobilinogen (PBG)-synthase activity). 
 
Special populations 
There are no specific dose recommendations for elderly or patients that have renal or hepatic 
impairment. 
 
Paediatric population 
The dose recommendation in mg/kg body weight is the same in children and adults. However, due to 
the limited data in patients with body weight <20kg, it is recommended to divide the total daily dose 
into two daily administrations in this patient population.  
 
Method of administration  
The tablets may be taken with or without food. Tablets are not suitable for breaking to make up 
additional strengths. 
 
For patients who require additional strengths (i.e. between multiples of 10 mg or lower than 10 mg) 
other medicinal products with lower strengths are available. 
 
For paediatric patients who have difficulties swallowing tablets, other pharmaceutical forms are 
available.  
 
4.3 Contraindications 
 
Hypersensitivity to the active substance or to any of the excipients listed in section 6.1. 
 
Breastfeeding (see sections 4.6 and 5.3). 
 
4.4 Special warnings and precautions for use 
 
Monitoring of plasma tyrosine levels 
It is recommended that a slit-lamp examination of the eyes is performed before initiation of nitisinone 
treatment. A patient displaying visual disorders during treatment with nitisinone should without delay 
be examined by an ophthalmologist. It should be established that the patient is adhering to his/her 
dietary regimen and the plasma tyrosine concentration should be measured. A more restricted tyrosine 
and phenylalanine diet should be implemented in case the plasma tyrosine level is above 500 
micromol/l. It is not recommended to lower the plasma tyrosine concentration by reduction or 
discontinuation of nitisinone, since the metabolic defect may result in deterioration of the patient’s 
clinical condition. 
 
Liver monitoring 
The liver function should be monitored regularly by liver function tests and liver imaging. It is 
recommended to also monitor serum alpha-fetoprotein concentrations. Increase in serum 
alpha-fetoprotein concentration may be a sign of inadequate treatment. Patients with increasing 
alpha-fetoprotein or signs of nodules in the liver should always be evaluated for hepatic malignancy. 
 
Platelet and white blood cell (WBC) monitoring 
It is recommended that platelet and WBC counts are monitored regularly, as a few cases of reversible 
thrombocytopenia and leucopenia were observed during clinical evaluation. 
 
Monitoring visits should be performed every 6 months; shorter intervals between visits are 
recommended in case of adverse events. 
 
Lactose 



4 

Patients with rare hereditary problems of galactose intolerance, total lactase deficiency or 
glucose-galactose malabsorption should not take this medicinal product. 
 
4.5 Interaction with other medicinal products and other forms of interaction 
 
No formal interaction studies with other medicinal products have been conducted. 
 
Nitisinone is metabolised in vitro by CYP 3A4 and dose-adjustment may therefore be needed when 
nitisinone is co-administered with inhibitors or inducers of this enzyme. 
 
Based on in vitro studies, nitisinone is not expected to inhibit CYP 1A2, 2C9, 2C19, 2D6, 2E1 or 3A4-
mediated metabolism. 
 
A food effect study has been conducted with Nityr. The study demonstrated that Nityr can be 
administered with or without food without affecting its bioavailability.  
 
4.6 Fertility, pregnancy and lactation 
 
Pregnancy 
There are no adequate data from the use of nitisinone in pregnant women. Studies in animals have 
shown reproductive toxicity (see section 5.3). The potential risk for humans is unknown. Nityr should 
not be used during pregnancy unless the clinical condition of the woman requires treatment with 
nitisinone. 
 
Breast-feeding 
It is unknown whether nitisinone is excreted in human breast milk. Animal studies have shown 
adverse postnatal effects via exposure of nitisinone in milk. Therefore, mothers receiving nitisinone 
must not breast-feed, since a risk to the suckling child cannot be excluded (see sections 4.3 and 5.3). 
 
Fertility 
There are no data on nitisinone affecting fertility. 
 
4.7 Effects on ability to drive and use machines 
 
Nityr has minor influence on the ability to drive and use machines. Adverse reactions involving the 
eyes (see section 4.8) can affect the vision. If the vision is affected the patient should not drive or use 
machines until the event has subsided. 
 
4.8 Undesirable effects 
 
Summary of the safety profile 
By its mode of action, nitisinone increases tyrosine levels in all nitisinone treated patients. Eye-related 
adverse reactions, such as conjunctivitis, corneal opacity, keratitis, photophobia, and eye pain, related 
to elevated tyrosine levels are therefore common. Other common adverse reactions include 
thrombocytopenia, leucopenia, and granulocytopenia. Exfoliative dermatitis may occur uncommonly. 
 
Tabulated list of adverse reactions 
The adverse reactions listed below by MedDRA system organ class and absolute frequency, are based 
on data from a clinical trial and post-marketing use. Frequency is defined as very common (≥1/10), 
common (≥1/100 to <1/10), uncommon (≥1/1,000 to <1/100), rare (≥1/10,000 to <1/1,000), very rare 
(<1/10,000), not known (cannot be estimated from the available data). Within each frequency 
grouping, adverse reactions are presented in order of decreasing seriousness. 
 



5 

MedDRA system organ 
class 

Frequency Adverse reaction 

Blood and lymphatic system 
disorders 

Common Thrombocytopenia, leucopenia, 
granulocytopenia 

Uncommon Leukocytosis 
Eye disorders Common Conjunctivitis, corneal opacity, 

keratitis, photophobia, eye pain 
Uncommon Blepharitis 

Skin and subcutaneous tissue 
disorders 

Uncommon Exfoliative dermatitis, 
erythematous rash, pruritus 

Investigations Very common Elevated tyrosine levels 
 
Description of selected adverse reactions 
Nitisinone treatment leads to elevated tyrosine levels. Elevated levels of tyrosine have been associated 
with eye-related adverse reactions, such as e.g. corneal opacities and hyperkeratotic lesions. 
Restriction of tyrosine and phenylalanine in the diet should limit the toxicity associated with this type 
of tyrosinemia by lowering tyrosine levels (see section 4.4). 
In clinical studies, granulocytopenia was only uncommonly severe (<0.5x109/L) and not associated 
with infections. Adverse reactions affecting the MedDRA system organ class ‘Blood and lymphatic 
system disorders’ subsided during continued nitisinone treatment. 
 
Paediatric population 
The safety profile is mainly based on the paediatric population since nitisinone treatment should be 
started as soon as the diagnosis of hereditary tyrosinemia type 1 (HT-1) has been established. From 
clinical study and post marketing data there are no indications that the safety profile is different in 
different subsets of the paediatric population or different from the safety profile in adult patients. 
 
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 
 
Accidental ingestion of nitisinone by individuals eating normal diets not restricted in tyrosine and 
phenylalanine will result in elevated tyrosine levels. Elevated tyrosine levels have been associated 
with toxicity to eyes, skin, and the nervous system. Restriction of tyrosine and phenylalanine in the 
diet should limit toxicity associated with this type of tyrosinemia. No information about specific 
treatment of overdose is available. 
 
 
5. PHARMACOLOGICAL PROPERTIES 
 
5.1  Pharmacodynamic properties 
 
Pharmacotherapeutic group: Other alimentary tract and metabolism products, Various alimentary tract 
and metabolism products, ATC code: A16AX04. 
 
Mechanism of action 
The biochemical defect in hereditary tyrosinemia type 1 (HT-1) is a deficiency of fumarylacetoacetate 
hydrolase, which is the final enzyme of the tyrosine catabolic pathway. Nitisinone is a competitive 
inhibitor of 4-hydroxyphenylpyruvate dioxygenase, an enzyme which precedes fumarylacetoacetate 
hydrolase in the tyrosine catabolic pathway. By inhibiting the normal catabolism of tyrosine in 
patients with HT-1, nitisinone prevents the accumulation of the toxic intermediates maleylacetoacetate 
and fumarylacetoacetate. In patients with HT-1, these intermediates are converted to the toxic 

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


6 

metabolites succinylacetone and succinylacetoacetate. Succinylacetone inhibits the porphyrin 
synthesis pathway leading to the accumulation of 5-aminolevulinate. 
 
Pharmacodynamic effects 
Nitisinone treatment leads to normalised porphyrin metabolism with normal erythrocyte 
porphobilinogen synthase activity and urine 5-aminolevulinate, decreased urinary excretion of 
succinylacetone, increased plasma tyrosine concentration and increased urinary excretion of phenolic 
acids. Available data from a clinical study indicates that in more than 90% of the patients urine 
succinylacetone was normalised during the first week of treatment. Succinylacetone should not be 
detectable in urine or plasma when the nitisinone dose is properly adjusted. 
 
Clinical efficacy and safety 
The clinical study was open-labelled and uncontrolled. The dosing frequency in the study was twice 
daily. Survival probabilities after 2, 4 and 6 years of treatment with nitisinone are summarised in the 
table below. 
 
NTBC study (N=250) 
Age at start of treatment 2 years 4 years 6 years 
≤ 2 months 93% 93% 93% 
≤ 6 months 93% 93% 93% 
> 6 months 96% 95% 95% 
Overall 94% 94% 94% 

 
Data from a study used as a historical control (van Spronsen et al., 1994) showed the following 
survival probability. 
 

Age at onset of 
symptoms 1 year 2 years 

< 2 months 38% 29% 
> 2-6 months 74% 74% 
> 6 months 96% 96% 

 
Treatment with nitisinone was also found to result in reduced risk for the development of 
hepatocellular carcinoma compared to historical data on treatment with dietary restriction alone. It was 
found that the early initiation of treatment resulted in a further reduced risk for the development of 
hepatocellular carcinoma. 
 
The 2-, 4-, and 6-year probability of no occurrence of HCC during nitisinone treatment for patients 
aged 24 months or younger at the start of treatment and for those older than 24 months at the start of 
treatment is shown in the following table: 
 
NTBC study (N=250) 
 Numbers of patients at Probability of no HCC (95% confidence interval) at 

Start 2 years 4 years 6 years 2 years 4 years 6 years 
All patients 250 155 86 15 98%   (95; 100) 

94%   
(90; 98) 

91%   
(81; 100) 

Start age ≤ 24 months 193 114 61 8 99%   (98; 100) 
99%   

(97; 100) 
99%   

(94; 100) 
Start age > 24 months 57 41 25 8 92%   (84; 100) 

82%   
(70; 95) 

75%   
(56; 95) 

 
In an international survey of patients with HT-1 on treatment with dietary restriction alone, it was 
found that HCC had been diagnosed in 18% of all patients aged 2 years and above. 
 



7 

A study to evaluate the PK, efficacy and safety of once daily dosing compared to twice daily dosing 
was performed in 19 patients with HT-1. There were no clinically important differences in AEs or 
other safety assessments between once and twice daily dosing. No patient had detectable 
succinylacetone (SA) levels at the end of the once-daily treatment period. The study indicates that 
once daily administration is safe and efficacious across all ages of patients. Data is, however, limited 
in patients with body weight <20 kg. 
 
5.2 Pharmacokinetic properties 
 
Formal absorption, distribution, metabolism and elimination studies have not been performed with 
nitisinone. In 23 healthy volunteers, after administration of a single dose of Nityr tablets (10 mg) the 
terminal half-life (median) of nitisinone in plasma was 59 hours (ranging from 41 to 74 hours).   
 
A population pharmacokinetic analysis has been conducted on a group of 207 HT-1 patients. The 
clearance and half-life were determined to be 0.0956 l/kg body weight/day and 52.1 hours 
respectively. 
 
In vitro studies using human liver microsomes and cDNA-expressed P450 enzymes have shown 
limited CYP 3A4-mediated metabolism. 
 
5.3 Preclinical safety data 
 
Nitisinone has shown embryo-foetal toxicity in the mouse and rabbit at clinically relevant dose levels. 
In the rabbit, nitisinone induced a dose-related increase in malformations (umbilical hernia and 
gastroschisis) from a dose level 2.5-fold higher than the maximum recommended human dose 
(2 mg/kg/day). 
 
A pre- and postnatal development study in the mouse showed statistically significantly reduced pup 
survival and pup growth during the weaning period at dose levels 125- and 25-fold higher, 
respectively, then the maximum recommended human dose, with a trend toward a negative effect on 
pup survival starting from the dose of 5 mg/kg/day. In rats, exposure via milk resulted in reduced 
mean pup weight and corneal lesions. 
 
No mutagenic but a weak clastogenic activity was observed in in vitro studies. There was no evidence 
of in vivo genotoxicity (mouse micronucleus assay and mouse liver unscheduled DNA synthesis 
assay). Nitisinone did not show carcinogenic potential in a 26-week carcinogenicity study in 
transgenic mice (TgrasH2). 
 
 
6. PHARMACEUTICAL PARTICULARS 
 
6.1 List of excipients 
 
Glycerol dibehenate 
Lactose monohydrate  
 
6.2 Incompatibilities 
 
Not applicable. 
 
6.3 Shelf life 
 
3 years.   
 
During the shelf life, the patient may store the bottle after first opening for a period of 2 months, after 
which the medicinal product must be discarded. 
 



8 

6.4 Special precautions for storage 
 
This medicinal product does not require any special temperature storage conditions.  
Store in the original bottle to protect from light. 
 
For storage conditions after first opening of the medicinal product, see section 6.3. 
 
6.5 Nature and contents of container  
 
HDPE 75 mL square bottles with a tamper-evident child-resistant closure of polypropylene (PP). Each 
bottle contains 60 tablets. Each carton contains 1 bottle. 
 
6.6 Special precautions for disposal  
 
Any unused medicinal product or waste material should be disposed of in accordance with local 
requirements. 
 
7. MARKETING AUTHORISATION HOLDER 
 
Cycle Pharmaceuticals (Europe) Limited 
70 Sir John Rogerson’s Quay  
Dublin 2 
Ireland  
 
8. MARKETING AUTHORISATION NUMBER(S)  
 
EU/1/18/1290/001 
 
9. DATE OF FIRST AUTHORISATION/RENEWAL OF THE AUTHORISATION 
 
Date of first authorisation: 26 July 2018 
 
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


9 

 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

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 
 

 



10 

 
A. MANUFACTURER(S) RESPONSIBLE FOR BATCH RELEASE 

 
Name and address of the manufacturer(s) responsible for batch release 
Central Pharma (Contract Packing) Limited 
Caxton Road 
Elms Industrial Estate 
Bedford 
Bedfordshire 
MK41 0XZ 
UNITED KINGDOM 
 
 
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.  

 



11 

 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

ANNEX III 
 

LABELLING AND PACKAGE LEAFLET 



12 

 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

A. LABELLING 



13 

 
PARTICULARS TO APPEAR ON THE OUTER PACKAGING  
 
OUTER CARTON 
 
 
1. NAME OF THE MEDICINAL PRODUCT 
 
Nityr 10 mg tablets 
nitisinone 
 
 
2. STATEMENT OF ACTIVE SUBSTANCE(S) 
 
Each tablet contains 10 mg nitisinone 
 
 
3. LIST OF EXCIPIENTS 
 
Contains lactose, see leaflet for further information. 
 
 
4. PHARMACEUTICAL FORM AND CONTENTS 
 
60 tablets 
 
 
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 
 
Store in the original bottle in order to protect from light. 
Shelf life after first opening - 2 months 
Open date:            
 



14 

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 
 
Cycle Pharmaceuticals (Europe) Limited 
70 Sir John Rogerson’s Quay  
Dublin 2 
Ireland  
 
 
12. MARKETING AUTHORISATION NUMBER(S)  
 
EU/1/18/1290/001 
 
 
13. BATCH NUMBER 
 
Lot 
 
 
14. GENERAL CLASSIFICATION FOR SUPPLY 
 
 
15. INSTRUCTIONS ON USE 
 
 
16. INFORMATION IN BRAILLE 
 
Nityr 10 mg 
 
 
17. UNIQUE IDENTIFIER – 2D BARCODE 
 
2D barcode carrying the unique identifier included. 
 
 
18. UNIQUE IDENTIFIER - HUMAN READABLE DATA 
 
PC: 
SN:  
NN:  
 
 
 
 
 



15 

 
PARTICULARS TO APPEAR ON SMALL IMMEDIATE PACKAGING UNITS 
 
BOTTLE LABEL 
 
 
1. NAME OF THE MEDICINAL PRODUCT AND ROUTE(S) OF ADMINISTRATION 
 
Nityr 10 mg tablets 
nitisinone 
oral use 
 
 
2. METHOD OF ADMINISTRATION 
 
 
3. EXPIRY DATE 
 
EXP 
 
 
4. BATCH NUMBER 
 
Lot 
 
 
5. CONTENTS BY WEIGHT, BY VOLUME OR BY UNIT  
 
60 tablets 
 
 
6. OTHER 
 
Contains lactose 
 
Store in the original bottle to protect from light. 
 
Shelf life after first opening - 2 months 
Open date:            
Cycle Pharmaceuticals (Europe) Limited 
70 Sir John Rogerson’s Quay  
Dublin 2 
Ireland  
 
 
 
 
 
 
 
 
 
 
 
 



16 

 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

 
 
 
 
 
 

B. PACKAGE LEAFLET 



17 

Package leaflet: Information for the user 
 

Nityr 10 mg tablets 
nitisinone 

 
 
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, pharmacist or nurse. 
- This medicine has been prescribed for you. 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, pharmacist or nurse. This includes any possible 

side effects not listed in this leaflet. See section 4. 
 
What is in this leaflet 
 
1. What Nityr is and what it is used for  
2. What you need to know before you take Nityr  
3. How to take Nityr 
4. Possible side effects  
5. How to store Nityr 
6. Contents of the pack and other information  
 
 
1. What Nityr is and what it is used for 
 
The active ingredient of Nityr is nitisinone. This medicine is used for treatment of a rare disease called 
hereditary tyrosinemia type 1 in adults, adolescents and children.  
 
In this disease your body is unable to completely break down the amino acid tyrosine (amino acids are 
building blocks of our proteins), forming harmful substances. These substances are accumulated in 
your body. Nityr blocks the breakdown of tyrosine and the harmful substances are not formed.  
 
You must follow a special diet while you are taking this medicine, because tyrosine will remain in 
your body. This special diet is based on low tyrosine and phenylalanine (another amino acid) content.  
 
 
2. What you need to know before you take Nityr 
 
Do not take Nityr: 
- if you are allergic to nitisinone or any of the other ingredients of this medicine (listed in section 

6). 
-  Do not breast-feed while taking this medicine, see section “Pregnancy and breast-feeding”. 
 
Warnings and precautions  
Talk to your doctor or pharmacist before taking Nityr.  
 
- if you get red eyes or any other signs of effects on the eyes. Contact your doctor immediately for 

an eye examination. Eye problems could be a sign of inadequate dietary control (see section 4).  



18 

During the treatment, blood samples will be drawn in order for your doctor to check whether the 
treatment is adequate and to make sure that there are no possible side effects causing blood disorders. 
Your liver will be checked at regular intervals because the disease affects the liver.  
 
Follow-up by your doctor should be performed every 6 months. If you experience any side effects, 
shorter intervals are recommended.  
 
Other medicines and Nityr  
Tell your doctor or pharmacist if you are taking, have recently taken or might take any other 
medicines.  
 
Nityr with food  
Nityr can be taken with or without food throughout your course of treatment.  
 
Pregnancy and breast-feeding  
The safety of this medicine has not been studied in pregnant and breast-feeding women.  
Please contact your doctor if you plan to become pregnant. If you become pregnant you should contact 
your doctor immediately.  
Do not breast-feed while taking this medicine, see section “Do not take Nityr”.  
 
Driving and using machines  
This medicine has minor influence on the ability to drive and use machines. However, if you 
experience side effects affecting your vision you should not drive or use machines until your vision is 
back to normal (see section 4 “Possible side effects”).  
 
Nityr contains lactose  
If you have been told by your doctor that you have an intolerance to some sugars, contact your doctor 
before taking this medicine. 
 
 
3. How to take Nityr 
 
Always take this medicine exactly as your doctor has told you. Check with your doctor or pharmacist 
if you are not sure.  
 
Treatment with this medicine should be started and supervised by a doctor experienced in the 
treatment of the disease (hereditary tyrosinemia type 1).  
 
The recommended total daily dose is 1 mg/kg body administered orally weight. Your doctor will 
adjust the dose individually.  
It is recommended to administer the dose once daily. However, due to the limited data in patients with 
body weight <20 kg, it is recommended to divide the total daily dose into two daily administrations in 
this patient population. 
 
Patients who have problems swallowing Nityr tablets whole, are recommended to take alternative 
nitisinone formulations.   

 
If you take more Nityr than you should  
If you have taken more of this medicine than you should, contact your doctor or pharmacist as soon as 
possible.  
 
If you forget to take Nityr 
Do not take a double dose to make up for a forgotten dose. If you forget to take a dose, contact your 
doctor or pharmacist.  
 
If you stop taking Nityr  



19 

If you have the impression that the medicine is not working properly, talk to your doctor. Do not 
change the dose or stop the treatment without talking to your doctor.  
 
If you have any further questions on the use of this medicine, ask your doctor, pharmacist or nurse. 
 
 
4. Possible side effects 
 
Like all medicines, this medicine can cause side effects, although not everybody gets them. 
 
If you notice any side effects relating to the eyes, talk to your doctor immediately to have an eye 
examination. Treatment with nitisinone leads to higher levels of tyrosine in the blood which can cause 
eye related symptoms. Common eye related side effects (may affect more than 1 in 10 people) are 
inflammation in the eye (conjunctivitis), opacity and inflammation in the cornea (keratitis), sensitivity 
to light (photophobia) and eye pain. Inflammation of the eyelid (blepharitis) is an uncommon side 
effect (may affect up to 1 in 100 people). 
 
Other common side effects  
- Reduced number of platelets (thrombocytopenia) and white blood cells (leukopenia), shortage of 

certain white blood cells (granulocytopenia).  
 
Other uncommon side effects  
- increased number of white blood cells (leucocytosis),  
- itching (pruritus), skin inflammation (exfoliative dermatitis), rash.  
 
Reporting of side effects 
If you get any side effects, talk to your doctor, pharmacist or nurse. 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 Nityr 
 
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 bottle and the carton after “EXP”.  
The expiry date refers to the last day of that month.  
 
This medicine does not require any special temperature storage conditions.  
Store in the original bottle to protect from light.  
Once the bottle is opened, the medicine can be stored for a period of 2 months, after which it must be 
discarded. 
 
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 to protect the environment.  
 
 
6. Contents of the pack and other information 
 
What Nityr contains  
- The active substance is nitisinone.  
- Each tablet contains 10 mg nitisinone.  
- The other ingredients are glycerol dibehenate, and lactose monohydrate (see section 2 under 

‘Nityr contains lactose’). 
 

 

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


20 

What Nityr looks like and contents of the pack  
The tablets are white to beige, round, flat which may display light yellow to brown speckles marked 
with “L” on one side and “10” on the other side.  
The tablets are packaged in plastic square bottles with a tamper-evident child-resistant closure. Each 
bottle contains 60 tablets. Each carton contains 1 bottle. 
 
Marketing Authorisation Holder  
Cycle Pharmaceuticals (Europe) Limited 
70 Sir John Rogerson’s Quay  
Dublin 2 
Ireland  
 
Manufacturer 
Central Pharma Contract Packaging Limited 
MK41 0XZ, Bedford 
UK 
  
This leaflet was last revised in  
 
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
	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