Nitisinone Capsules The FDA-approved generic medication to treat adult and pediatric patients with hereditary tyrosinemia type 1 (HT-1) in combination with dietary restrictions of tyrosine and phenylalanine

Important Safety Information

INDICATION
Nitisinone capsules are 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.

IMPORTANT SAFETY INFORMATION
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 levels and levels greater than 500 micromol/L may lead to the following:

• Ocular signs and symptoms including corneal ulcers, corneal opacities, keratitis, conjunctivitis, eye pain, and photophobia
  • Obtain slit-lamp examination prior to treatment and re-examination if symptoms develop.
• Variable degrees of intellectual disability and developmental delay
  • Assess plasma tyrosine levels in patients with an abrupt change in neurological status.
• Painful hyperkeratotic plaques on the soles and palms.

Maintain concomitant reduction in dietary tyrosine and phenylalanine while on nitisinone.
Maintain plasma tyrosine levels below 500 micromol/L.
Do not adjust the dosage of nitisinone in order to lower the plasma tyrosine concentration.

Leukopenia and Severe Thrombocytopenia
In clinical trials, patients treated with nitisinone and dietary restriction developed transient leukopenia (3%), thrombocytopenia (3%), or both (1.5%) without any resulting infections or bleeding. Monitor platelet and white blood cell count during treatment with nitisinone.

ADVERSE REACTIONS
The most common adverse reactions (>1%) are elevated tyrosine levels, thrombocytopenia, leukopenia, conjunctivitis, corneal opacity, keratitis, photophobia, eye pain, blepharitis, cataracts, granulocytopenia, epistaxis, pruritis, exfoliative dermatitis, dry skin, maculopapular rash and alopecia.

DRUG INTERACTIONS
If nitisinone is co-administered with drugs that are metabolized by CYP2C9, additional monitoring and dosage adjustments may be necessary because of a potential for increased systemic exposure. The risk is dependent upon the particular 2C9 substrate and its adverse reaction profile:

• CYP2C9 Substrates: Dosage adjustments may be needed to maintain therapeutic drug concentrations for narrow therapeutic index drugs.
• OAT1/OAT3 Substrates: 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 development outcomes.
• Lactation: There are no data on the presence of nitisinone in human milk, the effects on the breastfed infant, or the effects on milk production.
• 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.
• Geriatric Use: Clinical studies of nitisinone did not include any subjects aged 65 and over.

Please read the Full Prescribing Information here

To report suspected adverse reactions, contact Analog Pharma at 1-844-884-5505 or [email protected].