Orfadin Generic Name & Formulations
Nitisinone 2mg, 5mg, 10mg, 20mg; caps.
4-hydroxyphenylpyruvate dioxygenase inhibitor.
Caps—60; Oral susp—90mL
Treatment of hereditary tyrosinemia type 1 (HT-1) in combination with dietary restriction of tyrosine and phenylalanine.
Orfadin Dosage and Administration
Adults and Children
Caps: take ≥1hr before or 2hrs after a meal. May open and mix contents in water, formula, or applesauce if difficulty swallowing caps or intolerant to oral susp. Initially 0.5mg/kg twice daily. Titrate individually as needed 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 1 month after treatment initiation; max 2mg/kg total daily dose may be needed. Maintenance: ≥5yrs with undetectable succinylacetone levels after a minimum of 4wks therapy on a stable dose: may give total daily dose once daily (eg, 1–2mg/kg once daily).
Orfadin Boxed Warnings
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 exams (including slit-lamp test) prior to starting therapy and regularly thereafter; reevaluate and measure plasma tyrosine levels if ocular symptoms develop. Perform lab tests (including plasma tyrosine levels) if abrupt change in neurologic status occurs. Monitor platelets, WBC counts during therapy. Oral susp: glycerol content (>20mL as a single-dose) may increase risk of adverse effects (eg, headache, upset stomach, diarrhea). Elderly. Pregnancy. Nursing mothers.
Potentiates sensitive CYP2C9 substrates (eg, celecoxib, tolbutamide) or CYP2C9 substrates with a narrow therapeutic index (eg, phenytoin, warfarin); reduce dose of these substrates by ½ or as needed. Potentiates OAT1/OAT3 substrates (eg, adefovir, ganciclovir, methotrexate); monitor.
Orfadin Adverse Reactions
Elevated tyrosine levels, thrombocytopenia, leukopenia, conjunctivitis, corneal opacity, keratitis, photophobia, eye pain, blepharitis, cataracts, granulocytopenia, epistaxis, pruritus, exfoliative dermatitis, dry skin, maculopapular rash, alopecia; hyperkeratotic plaques on the soles and palms.
Orfadin Clinical Trials
Orfadin Patient Counseling