Nitisinone

eMC SPC 4.2 (Nitisinone 10mg hard capsules). HT-1: 'The recommended initial daily dose in the paediatric and adult population is 1 mg/kg body weight administered orally. The dose of nitisinone should be adjusted individually.' Treatment should be initiated and supervised by a physician experienced in the treatment of HT-1 and started as early as possible in all genotypes. A diet deficient in phenylalanine and tyrosine is required alongside nitisinone, with monitoring of plasma amino acids. Dose adjustment: if urine succinylacetone is still detectable one month after starting, increase to 1.5 mg/kg body weight/day; 2 mg/kg body weight/day may be needed based on evaluation of all biochemical parameters and is the maximum. If the biochemical response is satisfactory, adjust the dose only according to body weight gain. Monitor urine succinylacetone, liver function tests and alpha-fetoprotein; during initiation, when switching from twice daily to once daily dosing, or on deterioration, follow all available biochemical parameters more closely (plasma succinylacetone, urine 5-aminolevulinate, erythrocyte porphobilinogen-synthase activity). SEPARATE INDICATION - Alkaptonuria (AKU): 'The recommended dose in the adult AKU population is 10 mg once daily'; treatment initiated and supervised by a physician experienced in AKU; safety and efficacy in children aged 0 to 18 years with AKU have not been established (no data). Slit-lamp eye examination before initiation and at least annually thereafter; do not lower plasma tyrosine by reducing or stopping nitisinone in HT-1 - implement a more restricted tyrosine and phenylalanine diet if plasma tyrosine exceeds 500 micromol/l. If treatment is initiated with food, this should be maintained on a routine basis.

eMC SPC 4.2, HT-1: 'The dose recommendation in mg/kg body weight is the same in children and adults' - recommended initial daily dose 1 mg/kg body weight orally. If urine succinylacetone is still detectable one month after starting, increase to 1.5 mg/kg body weight/day; up to 2 mg/kg body weight/day may be needed based on all biochemical parameters, and that is the maximum for all patients. Once the biochemical response is satisfactory, adjust only for body weight gain. A phenylalanine- and tyrosine-deficient diet is required alongside treatment. Capsule contents may be suspended in a small amount of water, apple juice, soft food or formula diet (including amino-acid-modified infant formula with iron) immediately before intake; a 4 mg/ml oral suspension is available for paediatric patients who have difficulty swallowing capsules. Alkaptonuria: safety and efficacy in children aged 0 to 18 years have not been established. Verify against a children's formulary before use.