Orfadin 2 mg, 5 mg, 10 mg

/ Megapharm

Posology: Nitisinone treatment should be initiated and supervised by a physician experienced in the treatment of HT-1 patients. Treatment of all genotypes of the disease should be initiated as early as possible to increase overall survival and avoid complications such as liver failure, liver cancer and renal disease. Adjunct to the nitisinone treatment, a diet deficient in phenylalanine and tyrosine is required and should be followed by monitoring of plasma amino acids. The dose of nitisinone should be adjusted individually. The recommended initial dose in the paediatric and adult population is 1 mg/kg body weight/day
divided in 2 doses administered orally.
Dose adjustment: During regular monitoring, it is appropriate to follow urine succinylacetone, liver function test values and alpha-fetoprotein levels. If urine succinylacetone is still detectable one month after the start of nitisinone treatment, the nitisinone dose should be increased to 1.5 mg/kg body weight/day divided in 2 doses. A dose of 2 mg/kg body weight/day may be needed based on the evaluation of all biochemical parameters. This dose should be considered as a maximal dose for all patients. If the biochemical response is satisfactory, the dose should be adjusted only according to body weight gain.
However, in addition to the tests above, during the 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 (PBG)-synthase activity).
Special populations: There are no specific dose recommendations for elderly or patients that have renal or hepatic impairment.
Paediatric population: The safety and effect of nitisinone have been studied in the paediatric population. The dose recommendation in mg/kg body weight is the same in children and adults.
Method of administration: The capsule may be opened and the content suspended in a small amount of water or formula diet immediately before intake.

Treatment of patients with confirmed diagnosis of hereditary tyrosinemia type 1 (HT-1) in combination with dietary restriction of tyrosine and phenylalanine.

Hypersensitivity to the active substance or to any of the excipients. Lactation.

Should not be used during pregnancy unless clearly necessary.
See prescribing information for full details.

Thrombocytopenia, leucopenia, granulocytopenia. Conjunctivitis, corneal opacity, keratitis, photophobia, eye pain. Treatment is associated with elevated tyrosine levels. Elevated levels of tyrosinine have been associated with corneal opacities and hyperkeratotic lesions. Restrictions of tyrosine and pheylalaline in the diet should limit the toxicity associated with this type of tyrosinemia.
See prescribing information for full details.

No formal interaction studies with other medicdbinal products have been conducted.
See prescribing information for full details.

Pregnancy: There are no adequate data from the use of nitisinone in pregnant women. Studies in animals have shown reproductive toxicity. The potential risk for humans is unknown. Nitisinone should not be used during pregnancy unless clearly necessary.
Lactation: It is not known whether nitisinone is excreted in human breast milk. Animal studies have shown adverse postnatal effects via exposure of nitisinone in milk. Therefore, mothers receiving nitisinone must not breast-feed, since a risk to the suckling child cannot be excluded.