Orfadin 4mg/ml Oral Suspension

• 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. 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, pharmacist or nurse. This includes any possible side effects not listed in this leaflet. See section 4.

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

• 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”.

Talk to your doctor or pharmacist before taking Orfadin.

• 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).

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.

If you receive Orfadin for treatment of hereditary tyrosinemia type 1, 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.

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

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

• Medicines for epilepsy (such as phenytoin)
• Medicines against blood clotting (such as warfarin).

It is recommended that the oral suspension is taken with food.

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 Orfadin”.

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”).

This medicinal product contains 0.7 mg (0.03 mmol) sodium per ml.

A dose of 20 ml oral suspension (10 g glycerol) or more may cause headache, stomach upset and diarrhoea.

Sodium benzoate may increase jaundice (yellowing of the skin and eyes) in pre-term and full-term jaundiced neonates and develop into kernicterus (brain damage due to deposits of bilirubin in the brain). The newborn baby’s blood levels of bilirubin (a substance that causes the yellowing of the skin in high levels) will be closely monitored. If the levels are markedly higher than they should be, especially in premature babies with risk factors as acidosis (too low pH in the blood) and low albumin level (a protein in the blood) treatment with Orfadin capsules will be considered instead of the oral suspension until the bilirubin plasma levels are normalised.

The dose that your doctor prescribes you should be given in ml of suspension and not in mg. This is because the oral syringe which is used to withdraw the correct dose from the bottle is marked in ml. If your prescription is in mg, contact your pharmacist or doctor for advice.

The pack contains a bottle of medicine with a cap, a bottle adaptor and three oral syringes (1.5 ml, 3 ml and 6 ml). Always use one of the oral syringes provided to take the medicine.

• The 1.5-ml oral syringe (the smallest oral syringe) is marked from 0.1 ml to 1.5 ml with minor 0.05-ml graduations. It is used for measuring doses of less than or up to 1.5 ml.
• The 3 ml oral syringe (the middle sized oral syringe) is marked from 1 ml to 3 ml with minor 0.1-ml graduations. It is used for measuring doses of more than 1.5 ml and up to 3 ml.
• The 6 ml oral syringe (the largest oral syringe) is marked from 1 ml to 6 ml with minor 0.25-ml graduations. It is used for measuring doses of more than 3 ml.

It is important that you use the correct oral syringe when taking the medicine. Your doctor, pharmacist or nurse will advise which oral syringe to use depending on the dose that has been prescribed.

How to prepare a new bottle of medicine for first time use:

Before you take the first dose, shake the bottle vigorously since during long-term storage the particles will form a solid cake at the bottom of the bottle. Follow the instructions below:

1. Remove the bottle from the refrigerator. Note the date when the bottle is removed from the refrigerator on the bottle label.
2. Shake the bottle vigorously for at least 20 seconds until the solid cake at the bottom of the bottle is completely dispersed (Figure A).
3. Remove the child resistant screw cap by pushing it down firmly and turning it anti-clockwise (Figure B).
4. Place the open bottle upright on a table. Push the plastic adapter firmly into the neck of the bottle as far as you can (Figure C) and close the bottle with the child resistant screw cap.

For subsequent dosing see the instructions below ‘How to prepare a dose of medicine’.

How to prepare a dose of medicine

1. Shake the bottle vigorously for at least 5 seconds (Figure D).
2. Immediately thereafter, open the bottle by removing the child resistant screw cap.
3. Push the plunger inside the oral syringe fully down.
4. Keep the bottle in an upright position and insert the oral syringe firmly into the hole at the top of the bottle (Figure E).
5. Carefully turn the bottle upside down with the oral syringe in place (Figure F).
6. In order to withdraw the prescribed dose (ml), pull the plunger slowly down until the top edge of the plunger is exactly level with the line marking the dose (Figure F). If any air bubbles are observed inside the filled oral syringe, push the plunger back up until the air bubbles are expelled. Then pull the plunger down again until the top edge is exactly level with the line marking the dose.
7. Turn the bottle to an upright position again. Disconnect the oral syringe by gently twisting it out of the bottle.
8. The dose should be administered in the mouth immediately (without dilution) in order to avoid caking in the oral syringe. The oral syringe must be emptied slowly to allow swallowing; rapid squirting of the medicine may cause choking.
9. Replace the child resistant screw cap directly after use. The bottle adapter should not be removed.
10. The bottle may be stored at room temperature (not above 25°C).

Cleaning:

Clean the oral syringe immediately with cold tap water only, and if necessary, move the plunger in and out. Shake off excess water and leave the oral syringe to dry until the next dosing occasion. Do not disassemble the oral syringe.

If you have taken more of this medicine than you should, contact your doctor or pharmacist as soon as possible.

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 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.

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.

Other common side effects

• bronchitis
• pneumonia
• itching (pruritus), rash.

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:

or search for MHRA Yellow Card in the Google Play or Apple App Store

By reporting side effects you can help provide more information on the safety of this medicine.

• The active substance is nitisinone. Each ml contains 4 mg nitisinone.
• The other ingredients are hydroxypropylmethylcellulose, glycerol (see section 2), polysorbate 80, sodium benzoate (E211) (see section 2), citric acid monohydrate, sodium citrate (see section 2), strawberry aroma (artificial) and purified water.

The oral suspension is a white, slightly thicker opaque suspension. Before shaking the bottle, it may look like a solid cake in the bottom and a slightly opalescent liquid. It is provided in a 100 ml brown glass bottle with a white, child resistant screw cap. Each bottle contains 90 ml supension.

Each pack contains one bottle, one bottle adapter and three oral syringes.