Nitisinone
Mechanism :
Nitisinone competitively inhibits 4-hydroxyphenyl-pyruvate dioxygenase, an enzyme present early in the tyrosine degradation pathway, thereby preventing the build-up of the toxic metabolites.
Indication :
- Hereditary tyrosinemia type 1
Contraindications :
Hypersensitivity to nitisinone or any component of the formulation; breastfeeding.
Dosing :
Initial:
0.5 mg/kg twice daily. Increase to 0.75 mg/kg twice daily if succinylacetone is detectable 4 weeks after initiation.
Adverse Effect :
Increased plasma tyrosine, alopecia, exfoliative dermatitis, porphyria, leukopenia, thrombocytopenia, granulocytopenia, hepatic failure, hepatic neoplasm, conjunctivitis, corneal opacity, keratitis. Photophobia, epistaxis.
Interaction :
No known significant interactions.
Tyrosine toxicity can occur without proper dietary restriction of tyrosine and phenylalanine.
Hepatic Dose :
No dose adjustments are recommended.