Nitisinone

329.22800

329.23

K5BN214699

DTXSID9042673

A16AX04|A - Alimentary tract and metabolism

2914700090

97.03000

3.25780

1.484g/cm3

140-142 °C @ Solvent: Water

486.2ºC at 760mmHg

247.9ºC

1.535

8.11e-03 g/L

1.32E-09mmHg at 25°C

Side effects include elevated plasma levels of this amino acid, hepatic and liver failure.

Type 1 tyrosinemia is a rare disease and clinical experience with use of nitisinone is limited. Therapy can be accompanied by mild elevations in serum aminotransferase levels, but these are generally mild (less than 3 times the upper limit of normal [ULN]) and often resolve even without dose modification. The aminotransferase elevations are not accompanied by symptoms or increases in serum alkaline phosphatase or bilirubin levels and rarely require dose modification. There have been no reports of clinically apparent liver injury attributed to nitisinone in the treatment of tyrosinemia or in experimental studies of its use in other disorders of tyrosine metabolism such as alkaptonuria.

Used as an adjunct to dietary restriction of tyrosine and phenylalanine in the treatment of hereditary tyrosinemia type 1.|FDA Label|Hereditary tyrosinemia type 1 (HT 1)Orfadin is indicated for the treatment of adult and paediatric (in any age range) patients with confirmed diagnosis of hereditary tyrosinemia type 1 (HT 1) in combination with dietary restriction of tyrosine and phenylalanine.Alkaptonuria (AKU)Orfadin is indicated for the treatment of adult patients with alkaptonuria (AKU).|Treatment of adult and paediatric patients with confirmed diagnosis of hereditary tyrosinemia type 1 (HT-1) in combination with dietary restriction of tyrosine and phenylalanine.|Treatment of adult and paediatric (in any age range) patients with confirmed diagnosis of hereditary tyrosinemia type 1 (HT 1) in combination with dietary restriction of tyrosine and phenylalanine.,|Treatment of tyrosinemia type 1

Nitisinone is an inhibitor of the tyrosine catabolism that is used to treat hereditary tyrosinemia, type 1, in which accumulation of intermediates of tyrosine metabolism causes severe and progressive hepatic and renal injury. Nitisinone has been associated with mild, transient serum aminotransferase elevations, but has not been linked to instances of clinically apparent acute liver injury or jaundice.

Genetic Disorder Agents

Hereditary tyrosinemia type 1 occurs due to a deficiency in fumarylacetoacetase (FAH), the final enzyme in the tyrosine catabolic pathway. Nitisinone inhibits catabolism of tyrosine by preventing the catabolic intermediates. In patients with HT-1, these catabolic intermediates are converted to the toxic metabolites succinylacetone and succinylacetoacetate, which are responsible for the observed liver and kidney toxicity. Succinylacetone can also inhibit the porphyrin synthesis pathway leading to the accumulation of 5-aminolevulinate, a neurotoxin responsible for the porphyric crises characteristic of HT-1.

Compounds or agents that combine with an enzyme in such a manner as to prevent the normal substrate-enzyme combination and the catalytic reaction. (See all compounds classified as Enzyme Inhibitors.)

The capsule and liquid formulations are bioequivalent in both the plasma concentration-time curve and maximum plasma concentration (Cmax).

~54 hours

Nitisinone is a competitive inhibitor of 4-hydroxyphenyl-pyruvate dioxygenase, an enzyme upstream of fumarylacetoacetate hydrolyase (FAH) in the tyrosine catabolic pathway. By inhibiting the normal catabolism of tyrosine in patients with hereditary tyrosinemia type 1 (HT-1), nitisinone prevents the accumulation of the catabolic intermediates maleylacetoacetate and fumarylacetoacetate.

2-(2-nitro-4-(trifluoromethyl)benzoyl)cyclohexane-1,3-dione

Human drugs -> Orfadin -> EMA Drug Category|Other alimentary tract and metabolism products -> Human pharmacotherapeutic group|Human drugs -> Nityr -> EMA Drug Category|Human drugs -> Nitisinone MDK (previously Nitisinone MendeliKABS) -> EMA Drug Category|Human drugs -> Rare disease (orphan)|Human Drugs -> EU pediatric investigation plans|Human Drugs -> FDA Approved Drug Products with Therapeutic Equivalence Evaluations (Orange Book) -> Active Ingredients