Uses of medication:
Nitisinone is a hydroxy-phenylpyruvate dioxygenase used in the treatment of adult and pediatric patients (in any age range) with a confirmed diagnosis of HT-1 (Hereditary tyrosinemia type 1) in conjunction with dietary restriction of tyrosine and phenylalanine.
Dosage: The recommended starting dosage of Nitisinone capsules is 0.5 mg/kg administered orally twice daily at least 1 hour before, or 2 hours after a meal.
Maintenance Regimen: In individuals aged five years and more who have not detectable serum as well as urine succinylacetone concentrations following at least 4 weeks on a stable treatment with nitisinone, the total daily nitisinone dose may be given once daily (e.g., 1 mg/kg to 2 mg/kg once daily).
Dosage Titration: The dosage can be titrated in each patient on behalf of biochemical response and/or clinical response. Monitor plasma or urine succinylacetone concentrations, alpha-fetoprotein levels, and liver function parameters. If succinylacetone is still detectable in urine or blood 4 weeks after the beginning of nitisinone therapy, increase the dosage of nitisinone to 0.75 mg/kg twice daily. A maximum total daily dosage of 2 mg/kg may be required on behalf of the evaluation of all biochemical parameters.
Treatment Reactions: The most commonly reported side effects of Nitisinone 2mg/5mg/10mg capsules are:
- elevated tyrosine levels
- corneal opacity
- eye pain
- exfoliative dermatitis
- dry skin
- maculopapular rash
Warnings and Precautions:
- The slit-lamp examination needs to be performed prior to Nitisinone 10mg capsule therapy and thereafter regularly, at least yearly. A patient with visual disorders during treatment without delay be examined by an ophthalmologist.
- Monitor should liver function regularly by liver function tests and liver imaging. It is prescribed to also assess serum alpha-fetoprotein concentrations. An elevation in serum alpha-fetoprotein concentration may indicate inadequate therapy. Those with elevated alpha-fetoprotein or signs of nodules in the liver need to be assessed for hepatic malignancy.
- There are reports that patients treated with Nitisinone capsules and dietary restrictions developed transient leucopenia, thrombocytopenia, or both. One patient who developed Leucopenia and thrombocytopenia improved after the dose of Nitisinone decreased from 2-1 mg/kg. No patients developed infections or bleeding due to the episodes of Leucopenia and thrombocytopenia. One should regularly monitor platelet and white blood cell counts (WBCs) during nitisinone therapy.
- There are no satisfactory data on the use of nitisinone in the pregnant population. Studies in animals have demonstrated reproductive toxicity. The probable risk for humans is not known. Do not use Nitisinone during pregnancy unless the clinical condition of the respective patient needs this treatment.
- It is not known whether this drug is excreted in breast milk (human). Animal findings have demonstrated adverse postnatal effects via exposure to nitisinone in milk. So Therefore, those on Treatment of Tyrosinemia type 1 with nitisinone capsules must avoid breastfeeding, since the risk to the suckling child cannot be excluded.
- Nitisinone has minimal influence on the potential to drive and use machinery. Certain side effects involving the eyes may affect the vision. In case of affected vision, the respective patient must avoid driving or using any machinery until the complication has subsided.