NITYR Tablet Ref.[115378] Active ingredients: Nitisinone

Posology

HT-1

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 (see sections 4.4 and 4.8).

Starting dose 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. 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 HT-1

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 nitisinone treatment, the nitisinone dose should be increased to 1.5 mg/kg body weight/day. 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).

AKU

Nitisinone treatment should be initiated and supervised by a physician experienced in the treatment of AKU patients.

The recommended dose in the adult AKU population is 10 mg once daily.

Special populations

There are no specific dose recommendations for elderly or patients that have renal or hepatic impairment.

Paediatric population

HT-1: 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.

AKU: The safety and efficacy of Nityr in children aged 0 to 18 years with AKU have not been established. No data are available.

Method of administration

The tablets may be taken with or without food. Tablets are not suitable for breaking to make up additional strengths.

For patients who require additional strengths (i.e. between multiples of 10 mg or lower than 10 mg) other medicinal products with lower strengths are available.

For paediatric patients who have difficulties swallowing tablets, other pharmaceutical forms are available.

Accidental ingestion of nitisinone by individuals eating normal diets not restricted in tyrosine and phenylalanine will result in elevated tyrosine levels. Elevated tyrosine levels have been associated with toxicity to eyes, skin, and the nervous system. Restriction of tyrosine and phenylalanine in the diet should limit toxicity associated with this type of tyrosinemia. No information about specific treatment of overdose is available.

3 years.

During the shelf life, the patient may store the bottle after first opening for a period of 2 months, after which the medicinal product must be discarded.

This medicinal product does not require any special temperature storage conditions. Store in the original bottle in order to protect from light.

HDPE 75 mL square bottle with a tamper-evident child-resistant closure of polypropylene (PP). Each bottle contains 60 tablets. Each carton contains 1 bottle.

Any unused medicinal product or waste material should be disposed of in accordance with local requirements.