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Nitisinone oral


Oral formulations containing nitisinone.

Drugs List

  • nitisinone 10mg capsules
  • nitisinone 20mg capsules
  • nitisinone 2mg capsules
  • nitisinone 4mg/ml oral suspension sugar-free
  • nitisinone 5mg capsules
  • ORFADIN 10mg capsules
  • ORFADIN 20mg capsules
  • ORFADIN 2mg capsules
  • ORFADIN 4mg/ml oral suspension
  • ORFADIN 5mg capsules
  • Therapeutic Indications


    Hereditary tyrosinaemia type 1


    Initiate treatment as early as possible to increase overall survival and to avoid complications such as liver failure, liver cancer and renal disease. When initiated prior to the age of 12 months a 13.5 fold reduced risk for the development of hepatocellular carcinoma has been seen.

    Adjust the dose of nitisinone according to the individual and based on the evaluation of all available parameters.

    It is important that adjunct to the treatment with nitisinone, that the patient also has a diet deficient in phenylalanine and tyrosine. Plasma amino acids should be monitored.


    Hereditary tyrosinemia type 1 (HT-1)
    The initial recommended dose is 1mg/kg body weight once daily.

    In patients with a body weight of less than 20kg, the recommended total daily dose should be given in two divided doses.

    Alkaptonuria (AKU)
    10mg once daily.


    The initial recommended dose is 1mg/kg body weight once daily.

    In patients with a body weight of less than 20kg, the recommended total daily dose should be given in two divided doses.

    Additional Dosage Information

    Succinylacetone should not be detectable in urine when the nitisinone dose is properly adjusted. The nitisinone dose should be increased to 1.5mg/kg body weight once daily, if urine succinylacetone is still detectable one month after treatment is initiated. The maximal dose for all patients is 2mg/kg body weight/day and should only be given based on the evaluation of all biochemical parameters. If the biochemical response is satisfactory, the dose should be adjusted only according to body weight gain.


    The capsule may be opened immediately before intake and the contents suspended in a small amount of water or formula diet.

    If nitisinone treatment using capsules is initiated with food, it is recommended that this should be maintained on a routine basis.

    Oral suspension
    Oral suspension should be taken with food.



    Precautions and Warnings

    Children under 18 years
    Children weighing less than 20kg

    Advise visual disturbances may affect ability to drive or operate machinery
    Treatment to be initiated and supervised by a specialist
    Perform slit-lamp eye examination before initiation and at least annually
    Monitor hepatic function regularly
    Monitor serum alpha-fetoprotein concentrations regularly in HT-1
    Monitor urine succinylacetone regularly in hereditary tyrosinemia type 1
    Perform regular white blood cell and platelet counts
    Advise patient to report new visual problems and symptoms
    Refer immediately visual disturbances to a specialist
    Not licensed for all indications in all age groups
    Advise patient not to take St John's wort concurrently
    Advise patient grapefruit products may increase plasma level
    Dietary restrictions should be maintained

    Before initiating treatment it is generally recommended that a slit-lamp examination of the eyes is performed and thereafter regularly, at least once a year. If the patient is displaying visual disorders during treatment with nitisinone then the patient should be examined by an ophthalmologist without delay.

    In HT-1, plasma tyrosine concentration should be monitored in order to ensure that the patient is adhering to their dietary regimen. If the plasma tyrosine concentration is above 500 micromol per litre then a more restricted tyrosine and phenylalanine diet should be implemented. It is not advisable to lower the plasma tyrosine concentration by reduction or discontinuation of nitisinone, since the metabolic defect may result in deterioration of the patient's clinical condition.

    In AKU patients who develop keratopathies, plasma tyrosine levels should be monitored. A restricted diet in tyrosine and phenylalanine should be implemented to keep the plasma tyrosine level below 500 micromol per litre. Nitisinone should be temporarily discontinued and can be reintroduced once the symptoms have been resolved.

    In HT-1 treatment, it is important to regularly monitor urine succinylacetone, the liver function by liver function tests and liver imaging. Serum alpha-fetoprotein concentration should also be monitored and if an increase is detected it may be a sign of inadequate treatment. If increases are detected or there are signs of nodules in the liver then hepatic malignancy should be excluded.

    During initiation of therapy or if there is a deterioration, it may be necessary to follow more closely all available biochemical parameters (i.e. plasma succinylacetone, urine 5-aminolevulinate (ALA) and erythrocyte porphobilinogen (PGB)-synthase activity) in addition to the tests above.

    Monitoring visits should be performed every 6 months or sooner in the case of adverse events.

    Pregnancy and Lactation


    Use nitisinone with caution during pregnancy.

    Animal studies performed have shown adverse postnatal effects via exposure of nitisinone in milk. The potential risk for humans is unknown as there is no adequate data from the use of nitisinone in pregnant women. Nitisinone should not therefore be used during pregnancy unless clearly necessary.


    Nitisinone is contraindicated during breastfeeding.

    It is recommended that women receiving nitisinone should not breastfeed as it has not been established whether nitisinone is excreted in human breast milk. Animal studies have shown adverse postnatal effects via exposure of nitisinone in milk.


    The importance of adhering to a diet deficient in phenylalanine and tyrosine should be explained.

    Patient should be advised to inform their physician immediately if they experience visual disturbances during treatment.

    Advise patient that adverse reactions of nitisinone involving the eyes can affect vision. If vision is affected the patient should be advised not to drive or use machines until the event has subsided.

    Advise the patient not to take St John's wort concurrently.

    Advise the patient that grapefruit products may increase the plasma level of nitisinone.

    Side Effects

    Corneal opacities
    Erythematous rash
    Exfoliative dermatitis
    Eye pain


    It is strongly recommended that the UK National Poisons Information Service be consulted on cases of suspected or actual overdose where there is doubt over the degree of risk or about appropriate management.

    The following number will direct the caller to the relevant local centre (0844) 892 0111

    Information may be obtained if you have access to ToxBase the primary clinical toxicology database of the National Poisons Information Service. This is available via password on the internet ( ) or if this is unavailable at the backup site ( ).

    Further Information

    Last Full Review Date: October 2015

    Reference Sources

    Martindale: The Complete Drug Reference, 37th edition (2011) ed. Sweetman, S. Pharmaceutical Press, London.

    Summary of Product Characteristics: Orfadin 2 mg, 5 mg, 10 mg and 20 mg hard capsules. Swedish Orphan Biovitrum Ltd. Revised October 2020.

    Summary of Product Characteristics: Orfadin 4 mg/ml oral suspension. Swedish Orphan Biovitrum Ltd. Revised October 2020.

    NICE Evidence Services Available at: Last accessed: 14 January 2019

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    Medscape UK | Univadis prescription drug monographs & interactions are based on FDB Multilex Content

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    FDB Disclaimer : FDB Multilex is intended for the use of healthcare professionals and is provided on the basis that the healthcare professionals will retain FULL and SOLE responsibility for deciding what treatment to prescribe or dispense for any particular patient or circumstance.