Posology : מינונים

4.2   Posology and method of administration

Orfadin hard capsules treatment should be initiated and supervised by a physician experienced in the treatment of HT-1 patients.

Posology
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 Orfadin hard capsules treatment, a diet deficient in phenylalanine and tyrosine is required and should be followed by monitoring of plasma amino acids (see sections 4.4 and 4.8).


The recommended initial dose in the paediatric and adult population is 1 mg/kg body weight administered orally. The dose of Orfadin hard capsules should be adjusted individually. It is recommended to administer the dose once daily. However, due to the limited data in patients with body weight <20 kg, it is recommended to divide the total daily dose into two daily administrations in this patient population.

Dose adjustment
During regular monitoring, it is appropriate to follow urine succinylacetone, liver function test values and alpha-fetoprotein levels (see section 4.4). If urine succinylacetone is still detectable one month after the start of Orfadin hard capsules treatment, the Orfadin hard capsules 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, switch from twice daily to once daily dosing 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 impairmentPaediatric population
.
The dose recommendation in mg/kg body weight is the same in children and adults.
However, due to the limited data in patients with body weight <20 kg, it is recommended to divide the total daily dose into two daily administrations in this patient population.


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

It is recommended that if Orfadin hard capsules treatment is initiated with food, this should be maintained on a routine basis, see section 4.5.