Important Safety Information
Do not prescribe NITYR to patients allergic to nitisinone or any other ingredients.
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 ocular signs and symptoms including corneal ulcers, corneal opacities, keratitis, conjunctivitis, eye pain, and photophobia, intellectual disability and developmental delay or painful hyperkeratotic plaques on the soles and palms.
· Do not adjust the NITYR dosage in order to lower the plasma tyrosine concentration.
· Perform baseline ophthalmologic examination including slit-lamp examination prior to initiating treatment, and regularly during treatment. Reexamine patients if symptoms develop or tyrosine levels are > 500 micromol/L.
· Perform a clinical laboratory assessment, including plasma tyrosine levels, in patients with an abrupt change in neurologic status.
Leukopenia and Severe Thrombocytopenia Patients can develop leukopenia and severe thrombocytopenia: monitor platelet and white blood cell counts.
Most Common Adverse Reactions: The most common adverse reactions (≥1%) reported in patients with HT-1 taking nitisinone in the clinical trials 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.
Nitisinone is a moderate CYP2C9 inhibitor, a weak CYP2E1 inducer and an inhibitor of OAT1/OAT3.
Potential clinical impact of concomitant administration with CYP2C9 Substrates: Increased systemic exposure of co-administered drugs metabolized by CYP2C9. Intervention: reduce the dosage of the co-administered drugs metabolized by CYP2C9 by half. Additional dosage adjustments may be needed to maintain therapeutic drug concentrations for narrow therapeutic index drugs.
- Potential clinical impact of concomitant administration with OAT1/OAT3 Substrates: Increased exposure of these co-administered drugs; monitor for potential adverse reactions.
Use in Specific Populations:
Pregnancy: Limited available data with nitisinone use in pregnant women are not sufficient to determine a drug-associated risk of adverse developmental outcomes.
Lactation: The developmental and health benefits of breastfeeding should be considered along with the mother’s clinical need for NITYR and any potential adverse effects on the breastfed infant from NITYR or from the underlying maternal condition.
Pediatric Use: The safety and effectiveness of nitisinone have been established in pediatric patients for the treatment of HT-1 in combination with dietary restriction of tyrosine and phenylalanine. Use of NITYR in pediatric patients is supported by evidence from one open-label, uncontrolled clinical study conducted with another oral formulation of nitisinone in 207 patients with HT-1 ages 0 to 22 years (median age 9 months)
Geriatric Use: Clinical studies of nitisinone did not include any subjects aged 65 and over. No pharmacokinetic studies of nitisinone have been performed in geriatric patients. In general, dose selection for an elderly patient should be cautious reflecting the greater frequency of decreased hepatic, renal, or cardiac function, and concomitant disease or other drug therapy in this patient population.
For more detailed information, please refer to the full Prescribing Information.
To report SUSPECTED ADVERSE REACTIONS contact Cycle Pharmaceuticals at 1-855-831-5413, or the FDA at: 1-800-FDA-1088 or www.fda.gov/medwatch.
*NITYR® (nitisinone) Tablets is approved in the USA, Australia, New Zealand, the Kingdom of Saudi Arabia, the Kingdom of Morocco and Israel in 2, 5 and 10 mg strengths and in the EU, Egypt and Chile in 10 mg strength. Cycle Pharmaceuticals’ nitisinone products are also approved under a different name, NITISINONE TABLETS, in Canada in 2, 5, and 10 mg strengths. Registration conditions differ internationally.