Nitisinone Dipharma

Package leaflet: Information for the user

Nitisinone Dipharma 5 mg hard capsules, 10 mg hard capsules

Nitisinone
Generic Medicine
Please read this leaflet carefully before 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. Do not give it to other people, even if their symptoms are the same as yours, as it may be harmful.
• If you experience any side effect, including those not listed in this leaflet, talk to your doctor, pharmacist or nurse. See section 4.

Contents of this leaflet:

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

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

• The active substance in Nitisinone Dipharma is nitisinone. This medicine is used in adults, adolescents, and children (of any age group) for the treatment of a rare disease called hereditary tyrosinemia type 1. If you have this disorder, your body is unable to fully break down the amino acid tyrosine (amino acids are the building blocks of proteins), leading to the formation of harmful substances that accumulate in the body. Nitisinone Dipharma blocks the breakdown of tyrosine, thereby preventing the formation of these harmful substances.

Since tyrosine will remain in the body, you must follow a specific diet low in tyrosine and phenylalanine (another amino acid) during treatment with this medicine.

2. What you need to know before taking 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 breastfeed during treatment with this medicine; see section “Pregnancy and breastfeeding”.

Warnings and precautions
Talk to your doctor or pharmacist before taking Nitisinone Dipharma.

• If your eyes become red or you notice any other eye-related symptoms. Seek immediate medical advice for an ophthalmological examination. Eye disorders could be a sign of inadequate dietary control (see section 4).

During treatment, blood samples will be taken so that your doctor can monitor whether the treatment is appropriate and ensure that there are no unwanted effects that could cause changes in blood composition.
You will undergo regular liver check-ups, as the disease affects the liver.
Your doctor should carry out follow-up examinations every 6 months. If any adverse effects occur, shorter intervals between check-ups are recommended.
Other medicines and Nitisinone Dipharma
Inform your doctor or pharmacist if you are taking, have recently taken, or might take any other medicines.
Nitisinone Dipharma and food
If you start treatment with Nitisinone Dipharma taken together with food, it is recommended to continue taking it with food throughout the entire duration of treatment.
Pregnancy and breastfeeding
The safety of this medicine in pregnant and breastfeeding women has not been studied.
If you are planning a pregnancy, consult your doctor. If you become pregnant, you must contact your doctor immediately.
You must not breastfeed during treatment with this medicine; see section “Do not take Nitisinone Dipharma”.
Driving and using machines
This medicine has a minor influence on the ability to drive vehicles and use machinery. However, if you experience adverse reactions affecting your vision, do not drive or operate machinery until your normal vision has returned (see section 4 “Possible side effects”).

3. How to take Nitisinone Dipharma

Take this medicine exactly as directed by your doctor. If you have any doubts, consult your doctor or pharmacist.
Treatment with this medicine must be initiated and monitored by a doctor experienced in the management of 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 take the dose once daily. Data in patients with body weight <20 kg are limited; therefore, in this patient population, it is recommended to divide the total daily dose into two daily administrations.
If you have difficulty swallowing the capsules, you may open them and mix the powder with a small amount of water or a liquid meal replacement immediately before administration.

If you take more Nitisinone Dipharma than you should
If you take more medicine than prescribed, contact your doctor or pharmacist as soon as possible.

If you forget to take Nitisinone Dipharma
Do not take a double dose to make up for the missed dose. If you miss a dose, contact your doctor or pharmacist.

If you stop taking Nitisinone Dipharma
If you feel that the medicine is not working as expected, inform your doctor. Do not change the doses or stop treatment without consulting your doctor.

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

4. Possible side effects

Like all medicines, this medicine can cause side effects, although not everybody gets them.
If you notice any side effects affecting the eyes or vision, consult your doctor immediately for an ophthalmological examination. Treatment with nitisinone leads to increased levels of tyrosine in the blood, which may cause symptoms affecting the eyes. Common eye-related side effects (which may affect more than 1 in 10 people) due to elevated tyrosine levels include eye inflammation (conjunctivitis), corneal opacity and inflammation (keratitis), light sensitivity (photophobia), and eye pain. Inflammation of the eyelids (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), decrease in specific white blood cells (granulocytopenia).

Other uncommon side effects

• Increased number of white blood cells (leukocytosis).
• Itching, skin inflammation (exfoliative dermatitis), skin rashes.
• Reporting of side effects If you experience any side effect, including those not listed in this leaflet, tell your doctor or pharmacist. You can also report side effects directly via

segnalare-una-sospetta-reazione-avversa.
By reporting side effects, you can help provide more information on the safety of this medicine.

5. How to store 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 carton and vial (after EXP.). The expiry date refers to the last day of that month.
Store below 30°C.
Do not dispose of any medicine via wastewater or household waste. Ask your pharmacist how to dispose of medicines you no longer use. This will help protect the environment.

6. Package contents and other information

What Nitisinone Dipharma contains

• The active substance is nitisinone. Nitisinone Dipharma 5 mg: each capsule contains 5 mg of nitisinone. Nitisinone Dipharma 10 mg: each capsule contains 10 mg of nitisinone.

• The other components are:
  Capsule contents:
  Pregelatinized corn starch
  Stearic acid

  Capsule shell:
  Gelatin
  Titanium dioxide (E171)

  Printed ink:
  Lacquer
  Propylene glycol
  Indigo carmine aluminium lake (E132)

Description of the appearance of Nitisinone Dipharma and package contents
The hard capsules are white, opaque, printed with the number “5” or “10” and the “company logo” in dark blue. The capsules contain a white or almost white powder.
Nitisinone Dipharma is available in plastic bottles with child-resistant closure containing 60 capsules, and in unit-dose OPA/Alu/PVC-Alu blisters containing 60 capsules.
Not all pack sizes may be marketed.

Marketing Authorization 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

This medicinal product is authorized in the European Economic Area countries under the following names:
Austria Nitisinon Dipharma
Belgium Nitisinone Dipharma
Denmark Nitisinone Dipharma
France Nitisinone Dipharma
Germany Nitisinone Dipharma
Ireland Nitisinone Dipharma
Italy Nitisinone Dipharma
Norway Nitisinone Dipharma
Netherlands Nitisinone Dipharma
Portugal Nitisinona Dipharma
Spain Nitisinona Dipharma
Sweden Nitisinone Dipharma

Further information
More detailed information on this medicinal product is available on the website of the Italian Medicines Agency (Agenzia Italiana del Farmaco) at: http://www.agenziafarmaco.gov.it

Package leaflet: Information for the user

Nitisinone Dipharma 2 mg hard capsule, 20 mg hard capsule

Nitisinone
Generic Medicine
Please read this leaflet carefully before 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. Do not give it to other people, even if their symptoms are the same as yours, because it could be harmful.
• If you experience any side effects, including those not listed in this leaflet, contact your doctor, pharmacist, or nurse. See section 4.

Contents of this leaflet:

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

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

• The active substance in Nitisinone Dipharma is nitisinone. This medicine is used in adults, adolescents, and children (of any age) for the treatment of a rare disease called hereditary tyrosinemia type 1. If you have this disorder, your body is unable to fully break down the amino acid tyrosine (amino acids are the building blocks of proteins), leading to the formation of harmful substances that accumulate in the body. Nitisinone Dipharma blocks the breakdown of tyrosine, thereby preventing the formation of these harmful substances.

Since tyrosine will remain in the body, during treatment with this medicine you must follow a specific diet low in tyrosine and phenylalanine (another amino acid).

2. What you need to know before taking 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 breastfeed during treatment with this medicine; see section “Pregnancy and breastfeeding”.

Warnings and precautions
Talk to your doctor or pharmacist before taking Nitisinone Dipharma.

• Your eyes will be examined by an ophthalmologist before starting treatment with nitisinone and regularly during treatment. If your eyes become red or you notice any other eye-related symptoms, contact your doctor immediately for an eye examination. Eye disorders could be a sign of inadequate dietary control (see section 4).

During treatment, blood samples will be taken so that your doctor can monitor whether the treatment is appropriate and ensure that there are no adverse effects that could cause changes in blood composition.
You will undergo regular liver check-ups, as the disease affects the liver.
Your doctor should perform follow-up examinations every 6 months. If any adverse reactions occur, shorter intervals between check-ups are recommended.
Other medicines and Nitisinone Dipharma
Inform your doctor or pharmacist if you are taking, have recently taken, or might take any other medicines.
Nitisinone Dipharma may interfere with the effect of other medicines, such as:

• Medicines for epilepsy (such as phenytoin)
• Anticoagulant medicines (such as warfarin)

Nitisinone Dipharma with food
If you start treatment taking the medicine with food, it is recommended to continue taking it with food throughout the entire treatment period.
Pregnancy and breastfeeding
The safety of this medicine in pregnant and breastfeeding women has not been studied.
If you are planning a pregnancy, consult your doctor. If you become pregnant, you must contact your doctor immediately.
You must not breastfeed during treatment with this medicine; see section “Do not take Nitisinone Dipharma”.
Driving and using machines
This medicine impairs slightly the ability to drive and use machines. However, if you experience adverse reactions affecting your vision, do not drive or operate machinery until you have recovered normal visual function (see section 4 “Possible side effects”).

3. How to take Nitisinone Dipharma

Take this medicine exactly as directed by your doctor. If you have any doubts, consult your doctor or pharmacist.
Treatment with this medicine should be initiated and monitored by a physician experienced in the management 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 take the dose once daily. Data in patients with body weight <20 kg are limited; therefore, in this patient population, it is recommended to divide the total daily dose into two daily administrations.
If you have difficulty swallowing the capsules, you may open them and mix the powder with a small amount of water or a liquid meal replacement just before taking it.

If you take more Nitisinone Dipharma than you should
If you take more medicine than you should, contact your doctor or pharmacist as soon as possible.

If you forget to take Nitisinone Dipharma
Do not take a double dose to make up for the missed dose. If you miss a dose, contact your doctor or pharmacist.

If you stop taking Nitisinone Dipharma
If you feel that the medicine is not working as expected, inform your doctor. Do not change the dose or stop treatment without informing your doctor.

If you have any questions about the use of this medicine, consult 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 affecting the eyes or vision, consult your doctor immediately for an eye examination. Treatment with nitisinone leads to increased levels of tyrosine in the blood, which may cause symptoms affecting the eyes. Common eye-related side effects (which may affect more than 1 in 10 people) due to elevated tyrosine levels include eye inflammation (conjunctivitis), corneal opacity and inflammation (keratitis), sensitivity to light (photophobia), and eye pain. Inflammation of the eyelids (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), decreased levels of specific white blood cells (granulocytopenia). Other uncommon side effects
• Increased number of white blood cells (leukocytosis).
• Itching, skin inflammation (exfoliative dermatitis), skin rashes.

Reporting of side effects
If you get any side effects, including those not listed in this leaflet, talk to your doctor or pharmacist. You can also report side effects directly via the national reporting system.
By reporting side effects, you can help provide more information on the safety of this medicine.

5. How to store 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 carton and vial (after EXP.). The expiry date refers to the last day of that month.
Store below 30°C.
Do not dispose of any medicine via wastewater or household waste. Ask your pharmacist how to dispose of medicines you no longer use. This will help protect the environment.

6. Package contents and other information

What Nitisinone Dipharma contains

• The active substance is nitisinone. Nitisinone Dipharma 2 mg: each hard capsule contains 2 mg of nitisinone. Nitisinone Dipharma 20 mg: each hard capsule contains 20 mg of nitisinone.

• The other components are:
  Contents of the hard capsule:
  Pregelatinized starch
  Stearic acid

  Capsule shell:
  Gelatin
  Titanium dioxide (E171)

  Printing ink:
  Lacquer
  Propylene glycol
  Indigo carmine aluminium lake (E132)

Description of the appearance of Nitisinone Dipharma and package contents
The hard capsules are white, opaque, printed with the number “2” or “20” and the “company logo” in dark blue. The capsules contain a white or almost white powder.
Nitisinone Dipharma is available in plastic bottles with child-resistant closure containing 60 capsules, and in unit-dose divisible blisters made of OPA / Alu / PVC – Alu containing 60 capsules.
Not all pack sizes may be marketed.

Marketing Authorization 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

This medicinal product is authorized in the European Economic Area countries under the following names:
Austria Nitisinon Dipharma
Belgium Nitisinone Dipharma
Denmark Nitisinone Dipharma
France Nitisinone Dipharma
Germany Nitisinone Dipharma
Ireland Nitisinone Dipharma
Italy Nitisinone Dipharma
Norway Nitisinone Dipharma
Netherlands Nitisinone Dipharma
Portugal Nitisinona Dipharma
Spain Nitisinona Dipharma
Sweden Nitisinone Dipharma

Further information
More detailed information on this medicinal product is available on the website of the Italian Medicines Agency (Agenzia Italiana del Farmaco) at: http://www.aifa.gov.it