hese highlights do not include all the information needed to use ORFADIN safely and effectively. See full prescribing information for ORFADIN.
ORFADIN � (nitisinone) capsules, for oral use
ORFADIN � (nitisinone) oral suspension
Initial U.S. Approval: 2002
RECENT MAJOR CHANGES
Dosage and Administration, Dosage (2.1) 09/2017
INDICATIONS AND USAGE
ORFADIN is a hydroxy-phenylpyruvate dioxygenase inhibitor indicated for the treatment of adult and pediatric patients with hereditary tyrosinemia type 1 (HT-1) in combination with dietary restriction of tyrosine and phenylalanine. (1)
DOSAGE AND ADMINISTRATION
Recommended Dosage (2.1):
The recommended starting dosage is 0.5 mg/kg orally twice daily.
In patients 5 years of age and older who have undetectable serum and urine succinylacetone concentrations after a minimum of 4 weeks on a stable dosage of nitisinone, the total daily dose may be given once daily.
Titrate the dosage based on biochemical and/or clinical response, as described in the full prescribing information.
The maximum total daily dosage is 2 mg/kg orally .
Preparation and Administration Instructions (2.2):
For instructions on preparing, measuring and administering the oral suspension, see the full prescribing information.
Maintain dietary restriction of tyrosine and phenylalanine
Take ORFADIN capsules at least one hour before, or two hours after a meal
For patients who have difficulties swallowing capsules and who are intolerant to the oral suspension, the capsules may be opened and the contents suspended in a small amount of water, formula or apple sauce immediately before use.
Take ORFADIN oral suspension without regard to meals.
DOSAGE FORMS AND STRENGTHS
Capsules: 2 mg, 5 mg, 10 mg, 20 mg. (3)
Oral suspension: 4 mg/mL (3)
CONTRAINDICATIONS
None (4)
WARNINGS AND PRECAUTIONS
Elevated Plasma Tyrosine Levels, Ocular Symptoms, Developmental Delay and Hyperkeratotic Plaques: Inadequate restriction of tyrosine and phenylalanine intake can lead to elevations in plasma tyrosine, which at levels above 500 micromol/L can result in symptoms, intellectual disability and developmental delay or painful hyperkeratotic plaques on the soles and palms; do not adjust ORFADIN dosage in order to lower the plasma tyrosine concentration. Obtain slit-lamp examination prior to treatment and re-examination if symptoms develop. Assess plasma tyrosine levels in patients with an abrupt change in neurologic status. (5.1)
Leukopenia and Severe Thrombocytopenia: Monitor platelet and white blood cell counts. (5.2)
Risk of Adverse Reactions Due to Glycerol Content of ORFADIN Oral Suspension: Doses of 20 mL of ORFADIN oral suspension may cause headache, upset stomach and diarrhea due to the glycerol content. Consider switching patients to ORFADIN capsules. (5.3)
ADVERSE REACTIONS
Most common adverse reactions (>1%) are elevated tyrosine levels, thrombocytopenia, leukopenia, conjunctivitis, corneal opacity, keratitis, photophobia, eye pain, blepharitis, cataracts, granulocytopenia, epistaxis, pruritus, exfoliative dermatitis, dry skin, maculopapular rash and alopecia. (6.1)
To report SUSPECTED ADVERSE REACTIONS, contact Swedish Orphan Biovitrum at 1-866-773-5274 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.
DRUG INTERACTIONS
CYP2C9 Substrates: Potential for increased systemic exposure of these co-administered drugs, additional monitoring may be warranted. (7.1)
See 17 for PATIENT COUNSELING INFORMATION.
Revised: 9/2017