nitisinone: prescribing and clinical use
Focused clinical detail for use alongside current product information, local policy and patient-specific assessment.
nitisinone: clinical details
Prescribing considerations
- Initiation and supervision should be by clinicians experienced in hereditary tyrosinaemia type 1 or alkaptonuria.
- For hereditary tyrosinaemia type 1, combine treatment with specialist restriction of tyrosine and phenylalanine and monitor dietary adherence.
- Counsel patients not to reduce or stop nitisinone independently in response to raised tyrosine.
- Review CYP2C9 substrates with a narrow therapeutic index and medicines that inhibit or induce CYP3A4.
- The oral suspension contains glycerol and sodium benzoate; bilirubin requires particular attention in jaundiced or premature neonates.
Contraindications and cautions
- Hypersensitivity to nitisinone or a formulation excipient.
- Breastfeeding during treatment, according to the selected product information.
Monitoring
- Plasma tyrosine and relevant amino acids, with dietary review.
- Baseline and regular slit-lamp eye examinations; urgent ophthalmology review for visual symptoms.
- Platelet and white-cell counts.
- For hereditary tyrosinaemia type 1: succinylacetone, liver function, liver imaging and alpha-fetoprotein, with investigation of rising alpha-fetoprotein or liver nodules.
- For alkaptonuria: assess keratopathy and monitor tyrosine where eye effects develop.
Clinical pharmacology
Nitisinone competitively inhibits 4-hydroxyphenylpyruvate dioxygenase. It prevents downstream toxic-metabolite formation in hereditary tyrosinaemia type 1 and reduces homogentisic acid formation in alkaptonuria, while predictably increasing tyrosine. It is a moderate CYP2C9 inhibitor and undergoes limited CYP3A4-mediated metabolism.
Formulation and product differences
- The suspension must be vigorously re-dispersed, measured with the supplied oral syringe and administered immediately without dilution.
- The suspension is taken with food and contains glycerol, sodium and sodium benzoate.
- Capsules may be swallowed or opened and mixed with a small amount of an appropriate liquid, soft food or formula immediately before use.
- Food practice with capsules should remain consistent once established.
nitisinone preparations and strengths
Capsule
Route: Oral
Strengths: 2 mg, 5 mg, 10 mg, 20 mg
Oral suspension
Route: Oral
Strengths: 4 mg/mL
nitisinone interactions
Tell the specialist team about all prescribed, over-the-counter and herbal products. Important product-specific interactions include:
Warfarin and other narrow-therapeutic-index CYP2C9 substrates
Nitisinone can increase exposure, so closer clinical or laboratory monitoring and adjustment by the prescriber may be required.
Phenytoin
Nitisinone can increase phenytoin exposure; monitoring and prescriber-led adjustment may be required.
Sources
These sources were used to prepare and review this medicine page.
Prepared and reviewed by the iatroX editorial team.