Adult Dosing
Hereditary tyrosinemia type I (HT-1)
- Start dose: 1 mg/kg/day PO divided bid
- If biochemical parameters (except plasma succinylacetone) are not normalized within 1 month of treatment, increase the dose to 1.5 mg/kg/day
- If biochemical parameters (except plasma succinylacetone) are not normalized after 3 months, increase the dose up to 2 mg/kg/day
- Max dose: 2 mg/kg/day
Notes: - Therapy should be taken at least 1 hr before or 2 hrs after a meal
- For those unable to swallow capsule, it can be taken by suspending the contents in a small amount of water just before use
- Patients and their parents/caregivers should be informed of the need to maintain dietary restriction of tyrosine and phenylalanine when taking nitisinone
Pediatric Dosing
Hereditary tyrosinemia type I (HT-1)
- Start dose: 1 mg/kg/day PO divided BID
- If biochemical parameters (except plasma succinylacetone) are not normalized within 1 month of treatment, increase the dose to 1.5 mg/kg/day
- If biochemical parameters (except plasma succinylacetone) are not normalized after 3 months, increase the dose up to 2 mg/kg/day
- Max dose: 2 mg/kg/day
Notes: - Therapy should be taken at least 1 hr before or 2 hrs after a meal
- For those unable to swallow capsule, it can be taken by suspending the contents in a small amount of water just before use
- Patients and their parents/caregivers should be informed of the need to maintain dietary restriction of tyrosine and phenylalanine when taking nitisinone
- A low-protein diet deficient in tyrosine and phenylalanine should be designed by a nutritionist experienced in managing children with inborn errors of metabolism
[Outline]
See Supplemental Patient Information
- Inadequate restriction of tyrosine and phenylalanine intake may result in increased plasma tyrosine levels. Maintain tyrosine levels <500 µmol/L to avoid toxicity. Blood tyrosine levels greater than 500 µmol/L may cause corneal ulcers/opacities, keratitis, conjunctivitis, eye pain, and photophobia. Slit-lamp examination of the eyes should be performed prior to initiation of therapy and during treatment on development of ocular adverse events. Variable degrees of mental retardation and delay in development have occurred during therapy. Perform laboratory assessment including plasma tyrosine levels in patients who exhibit an abrupt change in neurological status while receiving therapy. Therapy may cause painful hyperkeratotic plaques on the soles and palms
- Assess dietary tyrosine intake in patients treated with dietary restrictions and nitisinone who develop elevated plasma tyrosine levels
- Transient leucopenia, thrombocytopenia, or both have been reported during therapy. Monitor platelet and WBC counts regularly during therapy
- Monitor plasma nitisinone levels, plasma succinylacetone, urine 5-ALA, erythrocyte PBG-synthase activity, urine succinylacetone, LFTs, alpha-fetoprotein, platelet and WBC counts, and serum tyrosine and phenylalanine levels regularly during therapy
- Treatment should be administered by a physician well trained in the treatment of HT-1
Cautions: Use cautiously in
Supplemental Patient Information
- Inform patients and their caregivers of the need to maintain dietary restriction of tyrosine and phenylalanine when taking nitisinone to treat HT-1
- Advise patients and their caregivers to promptly report any unexplained eye symptoms, rash, jaundice, or excessive bleeding
Pregnancy Category:C
Breastfeeding: Safety unknown. As many drugs are excreted in human milk, manufacturer advises caution when administering to nursing women.
