Nitisinone
Generic Name: nitisinone
Brand Names:
Nityr
11 DESCRIPTION NITYR (nitisinone) is a hydroxyphenyl-pyruvate dioxygenase inhibitor. Nitisinone occurs as a white to yellowish-white, crystalline powder. It is practically insoluble in water, soluble in 2M sodium hydroxide and in methanol, and sparingly soluble in alcohol. The chemical name of nitisinone is 2-(2-nitro-4-trifluoromethylbenzoyl) cyclohexane-1,3-dione. The empirical formula is C 14 H 10 F 3 NO 5 and the molecular weight is 329.23.
Overview
11 DESCRIPTION NITYR (nitisinone) is a hydroxyphenyl-pyruvate dioxygenase inhibitor. Nitisinone occurs as a white to yellowish-white, crystalline powder. It is practically insoluble in water, soluble in 2M sodium hydroxide and in methanol, and sparingly soluble in alcohol. The chemical name of nitisinone is 2-(2-nitro-4-trifluoromethylbenzoyl) cyclohexane-1,3-dione. The empirical formula is C 14 H 10 F 3 NO 5 and the molecular weight is 329.23.
Uses
1 INDICATIONS AND USAGE NITYR ® is 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. NITYR is a hydroxyphenyl-pyruvate 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
2 DOSAGE AND ADMINISTRATION The recommended starting dosage is 0.5 mg/kg (actual body weight) administered orally twice daily. ( 2.1 ) Administer NITYR with or without food. ( 2.1 ) Maintain dietary restriction of tyrosine and phenylalanine when administering NITYR. ( 2.1 ) The recommended maintenance dosage of NITYR 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, is 1 to 2 mg/kg once daily. ( 2.1 ) See the full prescribing information for dosage titration and monitoring. ( 2.2 ) See the full prescribing information for preparation and administration instructions.
Side Effects
6 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 Cycle Pharmaceuticals Ltd. at 1-855-831-5413 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.
Interactions
7 DRUG INTERACTIONS CYP2C9 Substrates : Increased systemic exposure of these co-administered drugs; reduce the dosage. Additional dosage adjustments may be needed to maintain therapeutic drug concentrations for narrow therapeutic index drugs. ( 7 ) OAT1/OAT3 Substrates : Increased systemic exposure of these co-administered drugs; monitor for potential adverse reactions. ( 7 ) Nitisinone is a moderate CYP2C9 inhibitor, a weak CYP2E1 inducer and an inhibitor of OAT1/OAT3. TABLE 2 includes drugs with clinically significant drug interactions when administered concomitantly with NITYR and instructions for preventing or managing them. TABLE 2.
Warnings
5 WARNINGS AND PRECAUTIONS Ocular Symptoms, Developmental Delay and Hyperkeratotic Plaques Due To Elevated Plasma Tyrosine Levels: Inadequate restriction of tyrosine and phenylalanine intake can lead to elevations in plasma tyrosine and levels above 500 micromol/L may lead to ocular signs and symptoms, intellectual disability and developmental delay, or painful hyperkeratotic plaques on the soles and palms. ( 5.1 ) Do not adjust NITYR dosage in order to lower the plasma tyrosine concentration. ( 5.1 ) Obtain slit-lamp examination prior to treatment and regularly thereafter. Reexamine patients if symptoms develop or tyrosine levels are > 500 micromol/L. Assess plasma tyrosine levels in patients with an abrupt change in neurologic status. 4 CONTRAINDICATIONS None. None. ( 4 )
Pregnancy
8.1 Pregnancy Risk Summary Limited available data with nitisinone use in pregnant women are not sufficient to determine a drug-associated risk of adverse developmental outcomes. Animal reproduction studies have been conducted for nitisinone. In these studies, nitisinone was administered to mice and rabbits during organogenesis with oral doses of nitisinone up to 20 and 8-times respectively, the recommended initial dose of 1 mg/kg/day.
Storage
16 HOW SUPPLIED/STORAGE AND HANDLING How Supplied NITYR (nitisinone) tablet is white to beige, round, flat which may display light yellow to brown speckles, debossed with the “strength” in mg on one side and “L” on the other side. Each tablet contains 2, 5 or 10 mg nitisinone.
Frequently Asked Questions
What is Nitisinone used for?▼
1 INDICATIONS AND USAGE NITYR ® is 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. NITYR is a hydroxyphenyl-pyruvate 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 )
What are the side effects of Nitisinone?▼
6 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 Cycle Pharmaceuticals Ltd. at 1-855-831-5413 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.
Can I take Nitisinone during pregnancy?▼
8.1 Pregnancy Risk Summary Limited available data with nitisinone use in pregnant women are not sufficient to determine a drug-associated risk of adverse developmental outcomes. Animal reproduction studies have been conducted for nitisinone. In these studies, nitisinone was administered to mice and rabbits during organogenesis with oral doses of nitisinone up to 20 and 8-times respectively, the recommended initial dose of 1 mg/kg/day.
What are the important warnings for Nitisinone?▼
5 WARNINGS AND PRECAUTIONS Ocular Symptoms, Developmental Delay and Hyperkeratotic Plaques Due To Elevated Plasma Tyrosine Levels: Inadequate restriction of tyrosine and phenylalanine intake can lead to elevations in plasma tyrosine and levels above 500 micromol/L may lead to ocular signs and symptoms, intellectual disability and developmental delay, or painful hyperkeratotic plaques on the soles and palms. ( 5.1 ) Do not adjust NITYR dosage in order to lower the plasma tyrosine concentration. ( 5.1 ) Obtain slit-lamp examination prior to treatment and regularly thereafter. Reexamine patients if symptoms develop or tyrosine levels are > 500 micromol/L. Assess plasma tyrosine levels in patients with an abrupt change in neurologic status. 4 CONTRAINDICATIONS None. None. ( 4 )
Related Medications
Medical Disclaimer
This drug information is for educational purposes only and should not replace professional medical advice. Drug information is sourced from the FDA National Drug Code Directory and Structured Product Labeling. Always consult with a healthcare provider before starting, stopping, or changing any medication.