Package Insert: Information for the User

Nitisinona Dipharma 5 mg Hard Capsules

Nitisinona Dipharma 10 mg Hard Capsules

nitisinona

Read this package insert carefully before starting to take this medicine, as it contains important information for you.

• Keep this package insert, as you may need to read it again.
• If you have any questions, consult your doctor, pharmacist, or nurse.
• This medicine has been prescribed to you alone, and you should not give it to others even if they have the same symptoms as you, as it may harm them.
• If you experience any adverse effects, consult your doctor, pharmacist, or nurse, even if they are not listed in this package insert. See section 4.

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

2.What you need to know before starting to take Nitisinona Dipharma

3.How to take Nitisinona Dipharma

4.Possible adverse effects

5.Storage of Nitisinona Dipharma

6.Contents of the package and additional information

Nitisinona Dipharma contains the active ingredient nitisinona. Nitisinona is used to treat:

In these diseases, your body cannot completely break down the amino acid tyrosine (amino acids are the fundamental elements of proteins), forming toxic substances. These substances accumulate in your body. Nitisinona blocks the breakdown of tyrosine, and toxic substances are not formed.

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

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

Do not take Nitisinona Dipharma

• if you are allergic to nitisinona or any of the other ingredients of this medication (listed in section 6).

Do not breastfeed while taking this medication (see section “Pregnancy and breastfeeding”).

Warnings and precautions

Consult your doctor or pharmacist before starting to take Nitisinona Dipharma.

• Your ophthalmologist will examine your eyes before treatment and regularly during treatment with nitisinona. If you notice redness of the eyes or any other eye effect, contact your doctor immediately for an eye examination. Eye problems (see section 4) may be a sign of inadequate dietary control.

Blood samples will be taken during treatment to control whether the treatment is adequate and to ensure that there are no side effects causing blood abnormalities.

If you receive Nitisinona Dipharma for the treatment of hereditary tyrosinemia type I, you will have periodic liver checks because the disease affects the liver.

Your doctor should follow up every 6 months. If you experience any adverse effects, it is recommended to use shorter intervals.

Other medications and Nitisinona Dipharma

Inform your doctor or pharmacist if you are taking, have taken recently, or may have to take any other medication.

Nitisinona Dipharma may interfere with the effect of other medications, such as:

• Medications for epilepsy (such as phenytoin)
• Blood-thinning medications (such as warfarin)

Taking Nitisinona Dipharma with food

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

Pregnancy and breastfeeding

The safety of this medication has not been studied in pregnant women and breastfeeding women.

If you are pregnant or breastfeeding, or think you may be pregnant, or intend to become pregnant, consult your doctor or pharmacist before using this medication.Do not breastfeed while taking this medication (see section “Do not take Nitisinona Dipharma”).

Driving and operating machines

The influence of this medication on the ability to drive and operate machines is small. However, if you experience adverse effects that affect your vision, do not drive or operate machines until your vision has returned to normal (see section 4 “Possible adverse effects”).

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

For hereditary tyrosinemia type I, treatment with this medication should be initiated and supervised by a doctor experienced in treating the disease.

For hereditary tyrosinemia type I, the recommended daily dose is 1 mg/kg of body weight administered orally. Your doctor will adjust the dose individually.

It is recommended to administer the dose once a day.

However, due to limited data in patients with a body weight of less than 20 kg,

For AKU, the recommended dose is 10 mg once a day.

If you have trouble swallowing the capsules, you can open the capsules and mix the powder with a small amount of water or dietary supplement before taking it.

If you take more Nitisinona Dipharma than you should

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

In case of overdose or accidental ingestion, consult your doctor or pharmacist immediately or call the Toxicological Information Service, phone: 91 562 04 20, indicating the medication and the amount ingested.

If you forget to take Nitisinona Dipharma

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

If you interrupt treatment with Nitisinona Dipharma

If you think the medication's action is not adequate, inform your doctor. Do not change the dose or suspend treatment without first speaking with your doctor.

If you have any doubts about the use of this medication, ask your doctor or pharmacist.

Like all medications, this medication may cause adverse effects, although not everyone will experience them.

If you notice any adverse effects related to the eyes, inform your doctor immediately so that they can perform an ophthalmological examination. Treatment with nitisinone increases blood tyrosine levels, which can cause eye-related symptoms. In patients with hereditary tyrosinemia type 1, frequently reported eye adverse effects (affecting more than 1 in 100 people) due to higher tyrosine levels are eye inflammation (conjunctivitis), corneal opacity and inflammation (keratitis), light sensitivity (photophobia), and eye pain. Blepharitis is a rare adverse effect (affecting up to 1 in 100 people).

In patients with AKU, eye irritation (keratopathy) and eye pain are frequently reported adverse effects (affecting more than 1 in 10 people).

Below are other adverse effects reported in patients with hereditary tyrosinemia type 1:

Other frequent adverse effects

Other rare adverse effects

• • Increased white blood cell count (leucocytosis),
  • itching (pruritus), skin inflammation (dermatitis exfoliativa), rash.
•  
• Below are other adverse effects reported in patients with AKU:
•  
• Other frequent adverse effects
• • bronchitis,
  • pneumonia,
  • itching (pruritus), rash.

Reporting 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 prospectus. You can also report them directly through the Spanish System of Pharmacovigilance of Medicines for Human Use ( www.notificaRAM.es ). By reporting adverse effects, you can contribute to providing more information on the safety of this medication.

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

Do not use this medication after the expiration date that appears onthe blister pack after “EXP” and onthe bottle and box after “CAD”. The expiration date is the last day of the month indicated.

Store at a temperature below 30°C.

Medicines should not be disposed of through drains or in the trash. Ask your pharmacist how to dispose of the packaging and medications that you no longer need. In this way, you will help protect the environment.

Nitisinona Dipharma Composition

• The active ingredient is nitisinona.

Nitisinona Dipharma 5 mg: each capsule contains 5 mg of nitisinona.

Nitisinona Dipharma 10 mg: each capsule contains 10 mg of nitisinona.

• The other components (excipients) are:

Capsule content:

Pregelatinized cornstarch

Stearic acid

Capsule coating:

Gelatin

Titanium dioxide (E171)

Printing ink:

Shellac

Propylene glycol

Aluminum lake Indigotina (E132)

Product appearance and packaging contents

The capsules are hard, white, opaque, made of gelatin, and have "company logo" and the dose "5" or "10" printed in dark blue. The capsule contains a powder that may be white or off-white.

Nitisinona Dipharma is available in plastic bottles with a tamper-evident closure of 60 capsules and OPA/Alu/PVC–Alu blister pack of 60 capsules.

Only some package sizes may be marketed.

Marketing Authorization Holder

Dipharma Arzneimittel GmbH

Offheimer Weg 33

65549 Limburg a.d. Lahn

Germany

Manufacturer

Doppel Farmaceutici srl

Viaa Volturno 48

20089 Quinti déStampi – Rozzano (MI), Italy

For more information about this medication, please contact the local representative of the marketing authorization holder:

Aurovitas Spain, S.A.U.

Avda. de Burgos, 16-D

28036 Madrid

Spain

Tel.: 91 630 86 45

This medication is authorized in the European Economic Area member states with the following names:

GermanyNitisinone Dipharma

AustriaNitisinon Dipharma

BelgiumNitisinone Dipharma

DenmarkNitisinone Dipharma

SpainNitisinona Dipharma

FranceNitisinone Dipharma

IrelandNitisinone Dipharma

ItalyNitisinone Dipharma

NorwayNitisinone Dipharma

NetherlandsNitisinone Dipharma

PortugalNitisinona Dipharma

United KingdomNitisinone Dipharma

SwedenNitisinone Dipharma

Last review date of this leaflet:February 2022

For detailed information about this medication, please visit the website of the Spanish Agency for Medicines and Medical Devices (AEMPS) (http://www.aemps.gob.es/).