Package Leaflet: Information for the User

Orfadin 2 mg Hard Capsules

Orfadin 5 mg Hard Capsules

Orfadin 10 mg Hard Capsules

Orfadin 20 mg Hard Capsules

nitisinona

Read this leaflet carefully before you start taking this medicine because it contains important information for you.

- Keep this leaflet, as 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 pass it on to others even if they have the same symptoms as you, as it may harm them.

- If you experience any side effects, talk to your doctor, pharmacist or nurse. See section 4.

1. What Orfadin is and what it is used for

2. What you need to know before you start taking Orfadin

3. How to take Orfadin

4. Possible side effects

5. Storage of Orfadin

6. Contents of the pack and additional information

Orfadin contains the active ingredient nitisinona. Orfadin is used to treat:

• an uncommon disease called hereditary tyrosinemia type 1 in adults, adolescents, and children (of any age group).
• an uncommon disease called alcaptonuria (AKU) in adults

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

For the treatment of hereditary tyrosinemia type 1, 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 Orfadin

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

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

Warnings and precautions

Consult your doctor or pharmacist before starting to take Orfadin.

-A specialist will examine your eyes before treatment and regularly during treatment with nitisinone. 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 check if the treatment is adequate and to ensure that there are no blood-related side effects.

If you are taking Orfadin for the treatment of hereditary tyrosinemia type 1, you will have regular liver checks because the disease affects the liver.

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

Other medicines and Orfadin

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

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

- epilepsy medicines (such as phenytoin)

- blood clotting medicines (such as warfarin)

Use of Orfadin with food

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

Pregnancy and breastfeeding

The safety of this medicine has not been studied in pregnant women and in women who are breastfeeding.

Consult your doctor if you plan to become pregnant. If you become pregnant, you must consult your doctor immediately.

Do not breastfeed while taking this medicine (see section “Do not take Orfadin”).

Driving and operating machines

The influence of this medicine on the ability to drive and use machines is small.

However, if you experience side effects that affect your vision, do not drive or use machines until your vision has returned to normal (see section 4 “Possible side effects”).

Follow exactly the medication administration instructions provided by your doctor. If in doubt, ask your doctor or pharmacist.

For hereditary tyrosinemia type1,the treatment with this medication should be initiated and supervised by a doctor experienced in treating the disease.

For hereditary tyrosinemia type1,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 <20

For AKU, the recommended dose is 10mg 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 Orfadin than you should

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

If you forget to take Orfadin

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 Orfadin

If you believe the medication's action is not adequate, inform your doctor. Do not change the dose or discontinue 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, the frequently reported adverse ocular effects (which can affect 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, an infrequent adverse effect (which can affect up to 1 in 100 people), is inflammation of the eyelids.

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

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

Other frequent adverse effects

• Decreased platelet count (thrombocytopenia) and white blood cell count (leucopenia), reduction of certain types of white blood cells (granulocytopenia).

Other infrequent adverse effects

-Increased white blood cell count (leucocytosis),

-itching (pruritus), skin inflammation (dermatitis exfoliativa), rash.

The following 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 national notification system included in theAppendix V.By reporting adverse effects, you can contribute to providing more information about 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 on the bottle and box after “EXP”. The expiration date is the last day of the month indicated.

Store in the refrigerator (between 2 °C and 8 °C).

The medication can be stored for a single period of 2 months (for 2 mg capsules) or 3 months (for 5 mg, 10 mg, and 20 mg capsules) at a temperature not exceeding 25 °C, after which it must be discarded.

Do not forget to note on the bottle the date when you removed it from the refrigerator.

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

Composition of Orfadin

• The active ingredient is nitisinone.

Orfadin 2 mg:Each capsule contains 2 mg of nitisinone.

Orfadin 5 mg:Each capsule contains 5 mg of nitisinone.

Orfadin 10 mg:Each capsule contains 10 mg of nitisinone.

Orfadin 20 mg:Each capsule contains 20 mg of nitisinone.

• The other components (excipients) are:

Contents of the capsule: pregelatinized cornstarch.

Capsule coating: gelatin, titanium dioxide (E 171).

Printing: iron oxide (E 172), shellac, propylene glycol, ammonium hydroxide.

Appearance of the product and contents of the packaging

The capsules are hard, white, opaque, made of gelatin, and have "NTBC" and the dose "2 mg", "5 mg", "10 mg" or "20 mg" printed in black. The capsule contains a powder that may be white or grayish.

The capsules are packaged in plastic bottles with tamper-evident closures. Each bottle contains 60 capsules.

Marketing Authorization Holder

Swedish Orphan Biovitrum International AB

SE-112 76 Stockholm

Sweden

Manufacturer

Apotek Produktion & Laboratorier AB

Prismavägen 2

SE-141 75 Kungens Kurva

Sweden

Last review date of this leaflet: 04/2024.

The detailed information on this medicine is available on the website of the European Medicines Agency:http://www.ema.europa.eu/.There are also links to other websites on rare diseases and orphan medicines.