Orfadin Patient, Information, Instructions - Nitisinone

Orfadin Patient, Information, Instructions - Nitisinone

PATIENT INFORMATION

Patients and their parents or caregivers should be advised of the need to maintain dietary restriction of tyrosine and phenylalanine when taking Nitisinone to treat hereditary tyrosinemia type 1.

Patients and their parents or caregivers should be advised to report promptly unexplained eye symptoms, rash, jaundice, or excessive bleeding (see WARNINGS and ADVERSE REACTIONS).

Laboratory Tests

• Plasma Nitisinone concentration, urine and plasma succinylacetone levels, urine 5-ALA levels, and erythrocyte PBG-synthase activity were used during clinical trials to guide drug dosage. The probability of recurrence of abnormal values of urine succinylacetone was 1% at a Nitisinone concentration of 37 µmol/L (95% confidence interval: 23-51 µmol/L). Assays for plasma Nitisinone concentration, plasma succinyl acetone, urine 5-ALA, and erythrocyte PBG-synthase activity are not routinely available in the U.S. However, urine succinylacetone levels can be used to guide drug dose adjustment (see DOSAGE and ADMINISTRATION).

• Serum alpha-fetoprotein concentrations are generally markedly elevated at the time of diagnosis, and gradually decrease during the course of Nitisinone treatment. Increases during therapy may be a sign of inadequate treatment. An exponential increase in serum alpha-fetoprotein concentration should be promptly evaluated for potential liver neoplasia. • Platelet and white blood cell counts should be monitored regularly because of the risk of transient thrombocytopenia and leukopenia (see WARNINGS).

• Serum phosphate should be measured as a screening test for patients with renal involvement at risk of secondary hypophosphatemia and rickets. • Plasma tyrosine levels should be kept below 500 µmol/L in order to avoid toxic effects (see WARNINGS).