Nitisinone Dipharma 5 mg hard capsules EFG

Package leaflet: Information for the user

Introduction

Package leaflet: information for the user

Nitisinona Dipharma 2 mg hard capsules EFG

Nitisinona Dipharma 5 mg hard capsules EFG

Nitisinona Dipharma 10 mg hard capsules EFG

Nitisinona Dipharma 20 mg hard capsules EFG

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 questions, ask your doctor, pharmacist, or nurse.
• This medicine has been prescribed for you only, and you should not give it to others, even if they have the same symptoms as you, because it may harm them.
• If you experience any adverse effects, consult your doctor, pharmacist, or nurse, even if they are adverse effects not listed in this leaflet. See section 4.

Contents of this leaflet

1. What Nitisinona Dipharma is and what it is used for
2. What you need to know before taking Nitisinona Dipharma
3. How to take Nitisinona Dipharma
4. Possible side effects
5. How to store Nitisinona Dipharma
6. Contents of the pack and other information

1. What Nitisinona Dipharma is and what it is used for

Nitisinona Dipharma contains the active substance nitisinone. Nitisinone is used to treat:

• a rare disease called hereditary tyrosinemia type 1 in adults, adolescents, and children (of any age group).
• a rare disease called alkaptonuria (AKU) in adults.

In these diseases, your body cannot fully break down the amino acid tyrosine (amino acids are the building blocks of proteins), leading to the formation of toxic substances. These substances accumulate in your body. Nitisinone blocks the breakdown of tyrosine, thereby preventing the formation of toxic substances.

For the treatment of hereditary tyrosinemia type I, you must follow a special diet while taking this medicine, because tyrosine will still remain in your body. This diet is low in tyrosine and phenylalanine (another amino acid).

For the treatment of AKU, your doctor may advise you to follow a special diet.

2. What you need to know before starting Nitisinone Dipharma

Do not take Nitisinone Dipharma

• if you are allergic to nitisinone or to 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 starting Nitisinone Dipharma.

• An ophthalmologist will examine your eyes before starting treatment and regularly during treatment with nitisinone. If you notice redness of the eyes or any other eye-related symptoms, contact your doctor immediately for an ophthalmological examination. Eye problems (see section 4) may indicate inadequate dietary control.

During treatment, blood samples will be taken to monitor whether the treatment is appropriate and to ensure that there are no side effects causing blood abnormalities.

If you are receiving Nitisinone Dipharma for the treatment of hereditary tyrosinemia type I, periodic liver monitoring will be performed because the disease affects the liver.

Your doctor should monitor you every 6 months. If you experience any adverse reactions, shorter monitoring intervals are recommended.

Other medicines and Nitisinone Dipharma

Inform your doctor or pharmacist if you are taking, have recently taken, or might need to take any other medicines.

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

• Medicines for epilepsy (such as phenytoin)
• Medicines to prevent blood clots (such as warfarin)

Taking Nitisinone Dipharma with food

If you start treatment taking it with food, it is recommended to continue this regimen throughout the entire treatment.

Pregnancy and breast-feeding

The safety of this medicine in pregnant and breast-feeding women has not been studied.

If you are pregnant or breast-feeding, think you may be pregnant, or are planning to become pregnant, consult your doctor or pharmacist before using this medicine. Do not breast-feed while taking this medicine (see section “Do not take Nitisinone Dipharma”).

Driving and using machines

The effect of this medicine on the ability to drive and use machines is minor. However, if you experience adverse effects affecting vision, you should not drive or operate machinery until your vision returns to normal (see section 4 “Possible side effects”).

3. How to take Nitisinona Dipharma

Follow exactly the administration instructions for this medicine as indicated by your doctor. If in doubt, consult your doctor or pharmacist again.

For hereditary tyrosinemia type I, treatment with this medicine must be initiated and supervised by a physician experienced in managing this disease.

For hereditary tyrosinemia type I, the recommended 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, because data are limited in patients with body weight <20 kg, in this patient population it is recommended to divide the total daily dose into two doses per day.

For AKU, the recommended dose is 10 mg once daily.

If you have difficulty swallowing the capsules, you may open the capsules and mix the powder with a small amount of water, apple juice, soft food such as apple puree, or dietary supplement, including an amino acid infant formula, before taking it.

If you take more Nitisinona Dipharma than you should

If you have taken more of this medicine than you should have, inform your doctor or pharmacist immediately.

In case of overdose or accidental ingestion, contact your doctor or pharmacist immediately or call the Toxicology Information Service, telephone: 91 562 04 20, indicating the medicine and the amount ingested.

If you forget to take Nitisinona Dipharma

Do not take a double dose to make up for forgotten doses. If you have forgotten to take a dose, inform your doctor or pharmacist.

If you stop taking Nitisinona Dipharma

If you feel that the effect of the medicine is not adequate, inform your doctor. Do not change the dose or stop treatment without first speaking to your doctor.

If you have any further questions about the use of this medicine, ask your doctor or pharmacist.

4. Possible adverse effects

Like all medicines, this medicine can cause adverse effects, although not everyone will experience them.

If you notice any eye-related adverse effects, inform your doctor immediately so that an ophthalmological examination can be performed. Treatment with nitisinone increases blood levels of tyrosine, which can cause eye-related symptoms. In patients with hereditary tyrosinemia type 1, frequently reported ocular adverse effects (may affect more than 1 in 100 people) due to elevated tyrosine levels include ocular inflammation (conjunctivitis), corneal opacity and inflammation (keratitis), light sensitivity (photophobia), and eye pain. Inflammation of the eyelids (blepharitis) is an uncommon adverse effect (may affect up to 1 in 100 people).

In patients with AKU, eye irritation (keratopathy) and eye pain are very commonly reported adverse effects (may affect more than 1 in 10 people).

The following is a list of other adverse effects reported in patients with hereditary tyrosinemia type 1:

Other frequent adverse effects

• Decrease in platelet count (thrombocytopenia) and white blood cells (leukopenia), reduction in certain types of white blood cells (granulocytopenia).

Other uncommon adverse effects

• • increase in white blood cell count (leukocytosis),
  • itching (pruritus), skin inflammation (exfoliative dermatitis), rash.
• The following is a list of other adverse effects reported in patients with AKU:
• Other frequent adverse effects
  • bronchitis,
  • pneumonia,
  • itching (pruritus), rash.

Reporting of adverse effects

If you experience any type of adverse effect, consult your doctor, pharmacist, or nurse, even if it is a possible adverse effect not listed in this leaflet. You may also report them directly through the Spanish Pharmacovigilance System for Human Medicines (www.notificaRAM.es). By reporting adverse effects, you can help provide more information on the safety of this medicine.

5. Storage of Nitisinone Dipharma

Keep this medicine out of the sight and reach of children.

Do not use this medicine after the expiry date stated on the blister after "EXP" and on the bottle and carton after "CAD". The expiry date refers to the last day of the month indicated.

Store below 30 °C.

Medicines should not be disposed of via wastewater or household waste. Ask your pharmacist how to dispose of medicines and packaging once they are no longer needed. This will help protect the environment.

6. Contents of the pack and other information

Composition of Nitisinone Dipharma

• The active substance is nitisinone.

Nitisinone Dipharma 2 mg: each hard capsule contains 2 mg of nitisinone.

Nitisinone Dipharma 5 mg: each hard capsule contains 5 mg of nitisinone.

Nitisinone Dipharma 10 mg: each hard capsule contains 10 mg of nitisinone.

Nitisinone Dipharma 20 mg: each hard capsule contains 20 mg of nitisinone.

• The other components (excipients) are:

Contents of the hard capsule:

Pregelatinized starch (from maize)

Stearic acid

Capsule shell:

Gelatin

Titanium dioxide (E171)

Printing ink:

Shellac

Propylene glycol

Aluminium indigotine lake (E132)

Appearance of the product and contents of the pack

The capsules are hard, white, opaque, made of gelatin, and marked with the “company logo” and the dose “2”, “5”, “10”, or “20 mg” in dark blue. The capsule contains a powder which may be white or almost white.

Nitisinone Dipharma is available in plastic bottles with tamper-evident closure containing 60 capsules and in OPA/Alu/PVC-Alu unit-dose perforated blisters containing 60 capsules.

Only certain pack sizes may be marketed.

Marketing Authorisation Holder

Dipharma Arzneimittel GmbH

Offheimer Weg 33

65549 Limburg a.d. Lahn

Germany

Manufacturer

Doppel Farmaceutici S.r.l.

Via Volturno 48

20089 Quinto de Stampi – Rozzano (MI), Italy

For further information about this medicinal product, please contact the local representative of the Marketing Authorisation Holder:

Aurovitas Spain, S.A.U.

Avda. de Burgos, 16-D

28036 Madrid

Spain

Tel.: 91 630 86 45

This medicinal product is authorised in the European Economic Area member states under the following names:

Germany Nitisinone Dipharma

Austria Nitisinone Dipharma

Belgium Nitisinone Dipharma

Denmark Nitisinone Dipharma

Slovakia Nitisinone Dipharma

Spain Nitisinona Dipharma

Finland Nitisinone Dipharma

France Nitisinone Dipharma

Ireland Nitisinone Dipharma

Italy Nitisinone Dipharma

Norway Nitisinone Dipharma

Netherlands Nitisinone Dipharma

Portugal Nitisinona Dipharma

Sweden Nitisinone Dipharma

Date of the most recent revision of this leaflet: May 2025.

Detailed information on this medicinal product is available on the website of the Spanish Agency for Medicines and Health Products (AEMPS) (http://www.aemps.gob.es/).