Inborn errors of metabolism:
Indications for NITYR:
Treatment of hereditary tyrosinemia type 1 (HT-1) in combination with dietary restriction of tyrosine and phenylalanine.
Adults and Children:
May crush tabs and mix with applesauce or disintegrate in water if difficulty swallowing tab; see full labeling. Initially 0.5mg/kg twice daily. Maintenance (in patients ≥5yrs with undetectable serum and urine succinylacetone levels after a minimum of 4 weeks on stable dose): may give 1–2mg/kg once daily. Titrate individually based on response. Monitor plasma and/or urine succinylacetone levels, liver function, and alpha-fetoprotein levels. Increase to 0.75mg/kg twice daily if succinylacetone is still detectable 4 weeks after initiation. Max: 2mg/kg/day.
Maintain dietary restriction of tyrosine and phenylalanine during therapy. Do not adjust dose to lower plasma tyrosine levels (maintain levels at <500μmol/L). Perform baseline eye exam (including slit-lamp test) prior to starting therapy and regularly thereafter; re-evaluate and assess plasma tyrosine levels if ocular symptoms develop or tyrosine >500μmol/L during therapy. Perform lab tests (including plasma tyrosine levels) if abrupt change in neurologic status occurs. Hyperkeratotic plaques (on the soles & palms). Monitor platelets, WBC counts during therapy. Pregnancy. Nursing mothers.
4-hydroxyphenylpyruvate dioxygenase inhibitor.
May potentiate CYP2C9 substrates (eg, celecoxib, tolbutamide, phenytoin, warfarin); reduce dose of substrates by ½; drugs with narrow therapeutic index may need additional dose adjustments. May potentiate OAT1/OAT3 substrates (adefovir, ganciclovir, methotrexate); monitor.
Elevated tyrosine levels, thrombocytopenia, leukopenia, conjunctivitis, corneal opacity, keratitis, photophobia, eye pain, blepharitis, cataracts, granulocytopenia, epistaxis, pruritus, exfoliative dermatitis, dry skin, maculopapular rash, alopecia.