Nitisinone MDK

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ANNEX I 

 

SUMMARY OF PRODUCT CHARACTERISTICS 



 

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1. NAME OF THE MEDICINAL PRODUCT 

 

Nitisinone MDK 2 mg hard capsules 

Nitisinone MDK 5 mg hard capsules 

Nitisinone MDK 10 mg hard capsules 

 

 

2. QUALITATIVE AND QUANTITATIVE COMPOSITION 

 

Each capsule contains 2 mg nitisinone.  

Each capsule contains 5 mg nitisinone.  

Each capsule contains 10 mg nitisinone.  

For the full list of excipients, see section 6.1. 

 

 

3. PHARMACEUTICAL FORM 

 

Hard capsule. 

White, opaque capsules of 15.7 mm imprinted with black ink “2 mg” on the cap and “Nitisinone” on 

the body. 

White, opaque capsules of 15.7 mm imprinted with black ink “5 mg” on the cap and “Nitisinone” on 

the body. 

White, opaque capsules of 15.7 mm imprinted with black ink “10 mg” on the cap and “Nitisinone” on 

the body. 

The capsules contain a white to off white powder. 

 

 

4. CLINICAL PARTICULARS 

 

4.1 Therapeutic indications 

 

Treatment of adult and paediatric (in any age range) 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 daily 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 <20 kg, 

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 



 

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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.  

 

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 <20 kg, it is recommended to divide the 

total daily dose into two daily administrations in this patient population. 

 

Method of administration  

The capsule may be opened and the content suspended in a small amount of water or formula diet 

immediately before intake. 

 

Other pharmaceutical forms are available for paediatric patients who have difficulties swallowing 

capsules. 

 

It is recommended that if nitisinone treatment is initiated with food, this should be maintained on a 

routine basis, see section 4.5. 

 

4.3 Contraindications 

 

Hypersensitivity to the active substance or to any of the excipients listed in section 6.1. 

 

Mothers receiving nitisinone must not breast-feed (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 and thereafter regularly, at least once a year. 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.  



 

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Monitoring visits should be performed every 6 months; shorter intervals between visits are 

recommended in case of adverse events. 

 

Concomitant use with other medicinal products  

Nitisinone is a moderate CYP2C9 inhibitor. Nitisinone treatment may therefore result in increased 

plasma concentrations of co-administered medicinal products metabolized primarily via CYP2C9. 

Nitisinone treated patients who are concomitantly treated with medicinal products with a narrow 

therapeutic window metabolized through CYP2C9, such as warfarin and phenytoin, should be 

carefully monitored. Dose-adjustment of these co-administered medicinal products may be needed 

(see section 4.5). 

 

4.5 Interaction with other medicinal products and other forms of interaction 

 

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 data from a clinical interaction study with 80 mg nitisinone at steady-state, nitisinone is a 

moderate inhibitor of CYP2C9 (2.3-fold increase in tolbutamide AUC), therefore nitisinone treatment 

may result in increased plasma concentrations of co-administered medicinal products metabolized 

primarily via CYP2C9 (see section 4.4). 

 

Nitisinone is a weak inducer of CYP2E1 (30% decrease in chlorzoxazone AUC) and a weak inhibitor 

of OAT1 and OAT3 (1.7-fold increase in AUC of furosemide), whereas nitisinone did not inhibit 

CYP2D6 (see section 5.2). 

 

No formal food interactions studies have been performed with Nitisinone MDK hard capsules. 

However, nitisinone has been co-administered with food during the generation of efficacy and safety 

data. Therefore, it is recommended that if nitisinone treatment with Nitisinone MDK hard capsules is 

initiated with food, this should be maintained on a routine basis, see section 4.2. 

 

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. 

Nitisinone MDK 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 

 

Nitisinone 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  



 

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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. 

 

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 



 

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Pharmacotherapeutic group: Other alimentary tract and metabolism products, Various alimentary tract 

and metabolism products, ATC code: A16A X04. 

 

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 HT1, these intermediates are converted to the toxic 

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 normalized 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 summarized 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: 



 

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NTBC study (N=250) 

 Number 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. 

 

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 10 healthy male volunteers, after administration of a single dose of nitisinone capsules 

(1 mg/kg body weight) the terminal half-life (median) of nitisinone in plasma was 54 hours (ranging 

from 39 to 86 hours). 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. 

 

Based on data from a clinical interaction study with 80 mg nitisinone at steady-state, nitisinone caused 

a 2.3-fold increase in AUC of the CYP2C9 substrate tolbutamide, which is indicative of a moderate 

inhibition of CYP2C9. Nitisinone caused an approximate 30% decrease in chlorzoxazone AUC, 

indicative of a weak induction of CYP2E1. Nitisinone does not inhibit CYP2D6 since metoprolol 

AUC was not affected by the administration of nitisinone. Furosemide AUC was increased 1.7-fold, 

indicating a weak inhibition of OAT1/OAT3 (see sections 4.4 and 4.5). 

 

Based on in vitro studies, nitisinone is not expected to inhibit CYP1A2, 2C19 or 3A4-mediated 

metabolism or to induce CYP1A2, 2B6 or 3A4/5. Nitisinone is not expected to inhibit P-gp, BCRP or 

OCT2-mediated transport. Nitisinone plasma concentration reached in clinical setting is not expected 

to inhibit OATP1B1, OATP1B3 mediated transport. 

 

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 significant reduced pup 

survival and pup growth during the weaning period at dose levels 125- and 25-fold higher, 



 

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respectively, 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 

 

Capsule content  

˗ Pregelatinised starch (maize)  
 

Capsule shell  

˗ Gelatin  
˗ Titanium dioxide (E171) 

 

Imprint  

˗ Black iron oxide (E172) 
˗ Shellac 

 
6.2 Incompatibilities 

 

Not applicable. 

 

6.3 Shelf life 

 

24 months. 

During the shelf life, the patient may store the capsules for a period of 2 months, after first opening the 

bottle, at a temperature not above 25°C, after which the medicinal product must be discarded. 

 

 

6.4 Special precautions for storage 

 

Store in a refrigerator (2°C - 8°C). Store in the original bottle in order to protect from light. 

 

6.5 Nature and contents of container 

 

HDPE plastic bottle with LDPE plastic cap containing 60 capsules.  

Each carton pack contains one 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 

 

MendeliKABS Europe Limited 

Unit 3D, North Point House 

North Point Business Park 

New Mallow Road 



 

9 

Cork, T23 AT2P, Ireland 

 

 

8. MARKETING AUTHORISATION NUMBER(S)  

 

EU/1/17/1217/001 

EU/1/17/1217/002 

EU/1/17/1217/003 

 

 

9. DATE OF FIRST AUTHORISATION/RENEWAL OF THE AUTHORISATION 

 

Date of first authorisation: 24 August 2017 

 

 

10. DATE OF REVISION OF THE TEXT 

 

 

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

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



 

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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 

 



 

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A. MANUFACTURER(S) RESPONSIBLE FOR BATCH RELEASE 

 

Name and address of the manufacturer(s) responsible for batch release 

 

Elara Pharmaservices Europe Limited 

239 Blanchardstown Corporate Park 

Ballycoolin, Dublin   

D15 KV21, Ireland 

 

 

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.  

 

 



 

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ANNEX III 

 

LABELLING AND PACKAGE LEAFLET 



 

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A. LABELLING 



 

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PARTICULARS TO APPEAR ON THE OUTER PACKAGING 

 

CARTON 

 

 

1. NAME OF THE MEDICINAL PRODUCT 

 

Nitisinone MDK 2 mg hard capsules 

Nitisinone MDK 5 mg hard capsules 

Nitisinone MDK 10 mg hard capsules 

nitisinone 

 

 

2. STATEMENT OF ACTIVE SUBSTANCE(S) 

 

Each capsule contains 2 mg nitisinone. 

Each capsule contains 5 mg nitisinone. 

Each capsule contains 10 mg nitisinone. 

 

 

3. LIST OF EXCIPIENTS 

 

 

4. PHARMACEUTICAL FORM AND CONTENTS 

 

60 hard capsules 

 

 

5. METHOD AND ROUTE(S) OF ADMINISTRATION 

 

Read the package leaflet before use. 

Oral use. 

 

 

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

OF THE SIGHT AND REACH OF CHILDREN 

 

Keep out of the sight and reach of children. 

 

 

7. OTHER SPECIAL WARNING(S), IF NECESSARY 

 

 

8. EXPIRY DATE 

 

EXP: 

 

 

9. SPECIAL STORAGE CONDITIONS 

 

Store in a refrigerator. 

 

 



 

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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 

 

MendeliKABS Europe Limited 

Unit 3D, North Point House 

North Point Business Park 

New Mallow Road 

Cork, T23 AT2P, Ireland 

 

 

12. MARKETING AUTHORISATION NUMBER(S)  

 

EU/1/17/1217/001 

EU/1/17/1217/002  

EU/1/17/1217/003 

 

 

13. BATCH NUMBER 

 

Lot: 

 

 

14. GENERAL CLASSIFICATION FOR SUPPLY 

 

 

15. INSTRUCTIONS ON USE 

 

 

16. INFORMATION IN BRAILLE 

 

Nitisinone MDK 2 mg 

Nitisinone MDK 5 mg 

Nitisinone MDK 10 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}  



 

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MINIMUM PARTICULARS TO APPEAR ON SMALL IMMEDIATE PACKAGING UNITS 

 

BOTTLE LABEL 

 

 

1. NAME OF THE MEDICINAL PRODUCT AND ROUTE(S) OF ADMINISTRATION 

 

Nitisinone MDK 2 mg hard capsules 

Nitisinone MDK 5 mg hard capsules 

Nitisinone MDK 10 mg hard capsules 

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 capsules 

 

 

6. OTHER 

 

Store in a refrigerator. 

Store in the original bottle in order to protect from light. 

Can be stored for a single period of 2 months at a temperature not above 25°C, after which it must be 

discarded.  

Date when removed from refrigerator: 

 

MendeliKABS Europe Limited 



 

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B. PACKAGE LEAFLET 



 

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Package leaflet: Information for the user 

 

Nitisinone MDK 2 mg hard capsules 

Nitisinone MDK 5 mg hard capsules 

Nitisinone MDK 10 mg hard capsules 

 

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 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 Nitisinone MDK is and what it is used for  

2. What you need to know before you take Nitisinone MDK  

3. How to take Nitisinone MDK 

4. Possible side effects  

5. How to store Nitisinone MDK 

6. Contents of the pack and other information 

 

 

1. What Nitisinone MDK is and what it is used for 

 

The active ingredient of Nitisinone MDK is nitisinone. This medicine is used for treatment of a rare 

disease called hereditary tyrosinemia type 1 in adults, adolescents and children (in any age range).  

 

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. Nitisinone MDK 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 Nitisinone MDK  

 

Do not take Nitisinone MDK: 

- 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 Nitisinone MDK. 

 

- Your eyes will be checked by an ophthalmologist before and regularly during nitisinone 

treatment. 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).  

 



 

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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 Nitisinone MDK 

Tell your doctor or pharmacist if you are taking, have recently taken or might take any other 

medicines. 

 

Nitisinone MDK may interfere with the effect of other medicines, such as: 

- Medicines for epilepsy (such as phenytoin) 

- Medicines against blood clotting (such as warfarin) 

 

Nitisinone MDK with food and drink 

If you start Nitisinone MDK treatment by taking it with food, it is recommended that you carry on 

taking it with 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 Nitisinone MDK”. 

 

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”). 

 

 

3. How to take Nitisinone MDK 

 

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 weight administered orally. 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. 

 

If you have problems with swallowing the capsules, you may open the capsule and mix the powder 

with a small amount of water or formula diet just before you take it. 

 

If you take more Nitisinone MDK 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 Nitisinone MDK 

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 Nitisinone MDK 



 

20 

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) caused 

by higher tyrosine levels 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 Nitisinone MDK 

 

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 the bottle after “EXP”. 

The expiry date refers to the last day of that month. 

 

Store in a refrigerator (2°C - 8°C). Store in the original bottle in order to protect from light. 

The medicine can be stored for a period of 2 months, after first opening the bottle, at a temperature not 

above 25°C, after which it must be discarded. 

 

Do not forget to mark the date on the bottle, when removed from the refrigerator. 

 

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 Nitisinone MDK contains  

- The active substance is nitisinone.  

Nitisinone MDK 2 mg: Each capsule contains 2 mg nitisinone.  

Nitisinone MDK 5 mg: Each capsule contains 5 mg nitisinone.  

Nitisinone MDK 10 mg: Each capsule contains 10 mg nitisinone. 



 

21 

 

- The other ingredients are: 

 Capsule content: pregelatinised maize starch 

 Capsule shell: gelatin, titanium dioxide (E171) 

 Printing ink: black iron oxide (E172), shellac glaze 

 

What Nitisinone MDK looks like and contents of the pack 

Nitisinone MDK capsules are 15.7 mm long, white, opaque, hard gelatin capsules, imprinted with 

“Nitisinone” and the strength “2 mg”, “5 mg” or “10 mg”, in black. The capsule contains a white to 

off-white powder.  

 

The capsules are packaged in plastic bottles. Each bottle contains 60 capsules. Each carton pack 

contains one bottle. 

 

Marketing Authorisation Holder 

MendeliKABS Europe Limited 

Unit 3D, North Point House 

North Point Business Park 

New Mallow Road 

Cork, T23 AT2P, Ireland 

 

Manufacturer 

Elara Pharmaservices Europe Limited 

239 Blanchardstown Corporate Park 

Ballycoolin, Dublin   

D15 KV21, Ireland 

 

This leaflet was last revised in 

 

Other sources of information 

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

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


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