Orfadin 4 mg/ml oral suspension
Spain
Table of Contents
Patient Information Leaflet
Introduction
Patient Information Leaflet
Orfadin 4 mg/ml oral suspension
nitisinone
Read the entire leaflet carefully before you start taking this medicine, as it contains important information for you.
- Keep this leaflet, as you may need to read it again.
- If you have any questions, consult your doctor, pharmacist or nurse.
- This medicine has been prescribed for you personally and must not be given to others, even if they have the same symptoms as you, because it could harm them.
- If you experience any adverse effects, consult your doctor, pharmacist or nurse, even if these are effects not listed in this leaflet. See section 4.
Leaflet Contents
- What Orfadin is and what it is used for
- What you need to know before taking Orfadin
- How to take Orfadin
- Possible side effects
- How to store Orfadin
- Contents of the pack and other information
1. What Orfadin is and what it is used for
Orfadin contains the active substance nitisinone. Orfadin is used to treat:
- a rare condition called hereditary tyrosinemia type 1 in adults, adolescents, and children (of any age)
- a rare condition 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. Orfadin blocks the breakdown of tyrosine, thereby preventing the formation of toxic substances.
For the treatment of hereditary tyrosinemia type 1, you must follow a special diet while taking this medicine, because tyrosine will still be present 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 Orfadin
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 breast-feed while taking this medicine (see section “Pregnancy and breast-feeding”).
Warnings and precautions
Talk to your doctor or pharmacist before starting to take Orfadin.
- An ophthalmologist will examine your eyes before 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 affecting the blood.
If you are receiving Orfadin for the treatment of hereditary tyrosinemia type 1, you will have periodic liver monitoring 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 Orfadin
Inform your doctor or pharmacist if you are taking, have recently taken, or might need to take any other medicines.
Orfadin may interfere with the effect of other medicines, such as:
- medicines for epilepsy (such as phenytoin)
- medicines to prevent blood clotting (such as warfarin)
Use of Orfadin with food
It is recommended to take the oral suspension with food.
Pregnancy and breast-feeding
The safety of this medicine has not been studied in pregnant or breast-feeding women.
Consult your doctor if you are planning to become pregnant. If you become pregnant, you must consult your doctor immediately.
Do not breast-feed while taking this medicine (see section “Do not take Orfadin”).
Driving and using machines
The effect of this medicine on the ability to drive and use machines is minor. However, if you experience any adverse effects affecting vision, you should not drive or use machines until your vision returns to normal (see section 4 “Possible side effects”).
Orfadin contains sodium, glycerol and sodium benzoate
This medicine contains 0.7 mg (0.03 mmol) of sodium per ml.
A dose of 20 ml or more of the oral suspension (10 g of glycerol) may cause headache, stomach discomfort, and diarrhoea.
Sodium benzoate may increase jaundice (yellowing of the skin and eyes) in jaundiced premature or full-term neonates and may lead to kernicterus (brain damage caused by deposition of bilirubin in the brain). In newborns, blood levels of bilirubin (a substance that at high concentrations causes yellowing of the skin) must be strictly monitored. If levels are significantly higher than normal, especially in premature infants with risk factors such as acidosis (blood pH too low) or low albumin concentration (a blood protein), treatment with Orfadin capsules should be considered instead of the oral suspension until plasma bilirubin concentrations have normalized.
3. How to take Orfadin
Follow exactly the instructions for taking this medicine given by your doctor. If you are unsure, ask your doctor or pharmacist.
Carefully follow the instructions provided below on preparation and administration of the dose to ensure that you receive the correct dose.
For hereditary tyrosinemia type 1, treatment with this medicine should be initiated and supervised by a physician experienced in managing this disease.
For hereditary tyrosinemia type 1, 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, due to limited data 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.
The oral suspension must be administered directly into the mouth undiluted, using the oral dosing syringe.
Orfadin must not be injected. Do not attach a needle to the syringe.
How to prepare the prescribed dose
The dose prescribed by your doctor should be administered in ml of suspension, not in mg. This is because the oral dosing syringe used to withdraw the correct dose from the bottle is marked in ml. If your prescription is in mg, contact your doctor or pharmacist for advice.
The package contains a medicine bottle with a closure cap, a bottle adapter, and three oral dosing syringes (1.5 ml, 3 ml, and 6 ml). Always use these oral dosing syringes to take the medicine.
- The 1.5 ml oral syringe (the smallest) is graduated from 0.1 ml to 1.5 ml in increments of 0.05 ml. It is used to measure doses up to 1.5 ml.
- The 3 ml oral syringe (medium) is graduated from 1 ml to 3 ml in increments of 0.1 ml. It is used to measure doses greater than 1.5 ml and up to 3 ml.
- The 6 ml oral syringe (the largest) is graduated from 1 ml to 6 ml in increments of 0.25 ml. It is used to measure doses greater than 3 ml.
It is important to use the correct oral dosing syringe to take the medicine. Your doctor, pharmacist, or nurse will advise you on how to use the oral dosing syringe based on the prescribed dose.
How to prepare a new bottle of medicine for first use:
Before taking the first dose, the bottle must be shaken vigorously, as particles may form a solid precipitate at the bottom during prolonged storage. Follow the instructions below:
- Remove the bottle from the refrigerator and record the date on the bottle label.
- Shake the bottle vigorously for at least 20 seconds until the solid sediment at the bottom is completely dispersed (Figure A).
- Remove the child-resistant screw cap by pressing down firmly and turning counterclockwise (Figure B).
- Place the open bottle upright on the table. Firmly push the plastic adapter into the neck of the bottle as far as possible (Figure C), then close the bottle with the child-resistant screw cap.
For subsequent doses, refer to the instructions below under “How to prepare a dose of the medicine.”
How to prepare a dose of the medicine
- Shake the bottle vigorously for at least 5 seconds (Figure D).
- Immediately remove the child-resistant screw cap and open the bottle.
- Push the plunger of the oral dosing syringe fully down.
- Keep the bottle upright and firmly insert the oral dosing syringe into the opening of the adapter at the top of the bottle (Figure E).
- Carefully invert the bottle without removing the oral dosing syringe (Figure F).
- To withdraw the prescribed dose (in ml), slowly pull the plunger down until the top edge of the plunger aligns exactly with the mark indicating the dose (Figure F). If you see any air bubbles in the oral syringe, push the plunger back up to expel the bubbles. Then pull the plunger down again until the top edge aligns exactly with the dose mark.
- Place the bottle upright again. Gently twist and pull the oral dosing syringe to remove it from the bottle.
- The dose must be administered immediately into the mouth (undiluted) to prevent precipitation in the oral syringe. The oral syringe should be emptied slowly to allow the patient to swallow the medicine; if the medicine is dispensed too quickly, choking may occur.
- Immediately replace the child-resistant screw cap. The bottle adapter must not be removed.
- The bottle may be kept at room temperature (not exceeding 25°C).
Cleaning:
Clean the oral dosing syringe immediately with cold tap water only, and if necessary, move the plunger in and out. Shake off excess water and allow the oral syringe to dry before the next use. Do not disassemble the oral syringe.
If you take more Orfadin than you should
If you have taken more of this medicine than you should have, inform your doctor or pharmacist immediately.
If you forget to take Orfadin
Do not take a double dose to make up for a missed dose. If you forget to take a dose, inform your doctor or pharmacist.
If you stop taking Orfadin
If you feel that the medicine is not working properly, inform your doctor. Do not change the dose or stop treatment without first talking to your doctor.
If you have any questions about the use of this medicine, ask your doctor or pharmacist.
4. Possible adverse effects
Like all medicines, this medicine may cause adverse effects, although not everyone experiences 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 may 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 frequently 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 national reporting system included in Appendix V. By reporting adverse effects, you can help provide more information on the safety of this medicine.
5. Storage of Orfadin
Keep this medicine out of the sight and reach of children.
Do not use this medicine after the expiry date stated on the vial and carton after "EXP". The expiry date refers to the last day of the month indicated.
Store in a refrigerator (between 2 °C and 8 °C).
Do not freeze.
Keep the vial in an upright position.
After first opening, the medicine may be stored for a single period of 2 months at a temperature not exceeding 25 °C, after which it must be discarded.
Remember to write on the vial the date it was removed from the refrigerator.
Medicines should not be disposed of via wastewater or household waste. Ask your pharmacist how to dispose of medicines and packaging that you no longer need. This will help protect the environment.
6. Contents of the pack and other information
Composition of Orfadin
- The active substance is nitisinone. Each ml contains 4 mg of nitisinone.
- The other components are hypromellose, glycerol (see section 2), polysorbate 80, sodium benzoate (E211) (see section 2), monohydrate citric acid, sodium citrate (see section 2), artificial strawberry flavour, and purified water.
Appearance of the product and contents of the container
The oral suspension is a white, opaque, slightly viscous suspension. Before shaking, the bottle may show a solid cake at the bottom with a slightly opalescent supernatant.
It is supplied in a 100 ml amber glass bottle with a white child-resistant screw cap. Each bottle contains 90 ml of oral suspension.
Each pack contains one bottle, a bottle adapter, and 3 oral syringes.
Marketing Authorisation Holder
Swedish Orphan Biovitrum International AB
SE-112 76 Stockholm
Sweden
Manufacturer
Apotek Produktion & Laboratorier AB
Celsiusgatan 43
SE-212 14 Malmö
Sweden
Apotek Produktion & Laboratorier AB
Prismavägen 2
SE-141 75 Kungens Kurva
Sweden
Date of the most recent revision of this leaflet:
Detailed information on this medicine is available on the European Medicines Agency website: http://www.ema.europa.eu/. There are also links to other websites on rare diseases and orphan medicines.