Orfadin Suspension

Generic name: nitisinone

Drug class: Hydroxyphenyl-pyruvate dioxygenase inhibitor

Dosage form: Oral suspension (4 mg/mL)

Route of administration: Oral

Dose:

• Adults and children: Initial dose of 0.5 mg/kg orally twice daily; may be titrated based on response, up to a maximum of 1 mg/kg twice daily. Maintenance dose may be adjusted to once daily for patients with undetectable succinylacetone levels after a minimum of 4 weeks on a stable dose.

Mechanism of action: Nitisinone is a competitive inhibitor of 4-hydroxyphenyl-pyruvate dioxygenase, an enzyme in the tyrosine catabolic pathway. By inhibiting this enzyme, nitisinone prevents the accumulation of toxic metabolites such as succinylacetone and succinylacetoacetate, which are responsible for liver and kidney toxicity in patients with hereditary tyrosinemia type 1 (HT-1).

Drug usage cases:

• Treatment of hereditary tyrosinemia type 1 (HT-1) in combination with dietary restriction of tyrosine and phenylalanine.
• Reduction of urine homogentisic acid (HGA) in patients with alkaptonuria (AKU).

Drug contraindications:

• None identified.

Side effects:

• Elevated plasma tyrosine levels
• Thrombocytopenia
• Leukopenia
• Conjunctivitis
• Corneal opacity
• Keratitis
• Photophobia
• Eye pain
• Blepharitis
• Cataracts
• Granulocytopenia
• Epistaxis
• Pruritus
• Exfoliative dermatitis
• Dry skin
• Maculopapular rash
• Alopecia
• Abdominal bloating
• Dark urine
• Abdominal pain
• Fatigue or weakness
• Headache
• Light-colored stools
• Loss of appetite
• Weight loss
• Vomiting
• Jaundice (yellowing of the skin or eyes)

Warnings:

• Maintain dietary restriction of tyrosine and phenylalanine during therapy to prevent elevated plasma tyrosine levels and associated complications.
• Monitor plasma and/or urine succinylacetone levels, liver function, and alpha-fetoprotein levels regularly during treatment.
• Patients receiving doses greater than 20 mL of oral suspension may experience headache, upset stomach, and diarrhea due to the glycerol component; report these symptoms to a healthcare provider.

Use during pregnancy or breastfeeding:

The safety of nitisinone during pregnancy and breastfeeding has not been established. Consult a healthcare provider to discuss potential risks and benefits before using this medication during pregnancy or while breastfeeding.