Formulary
Nitisinone: Indications, Dosing, Side Effects and Interactions
Nitisinone is a competitive inhibitor of 4-hydroxyphenylpyruvate dioxygenase which inhibits catabolism of tyrosine and thereby prevents accumulation of...
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Nitisinone: Indications, Dosing, Side Effects and Interactions
Nitisinone is a competitive inhibitor of 4-hydroxyphenylpyruvate dioxygenase which inhibits catabolism of tyrosine and thereby prevents accumulation of...
Drug action
Nitisinone is a competitive inhibitor of 4-hydroxyphenylpyruvate dioxygenase which inhibits catabolism of tyrosine and thereby prevents accumulation of harmful metabolites.
Indications and dose
**Hereditary tyrosinaemia type I (in combination with dietary restriction of tyrosine and phenylalanine) (specialist use only)**
- **Adult** (By Mouth Using Oral Suspension): Initially 1 mg/kg once daily, adjusted according to response; maximum 2 mg/kg per day.
**Alkaptonuria (specialist use only)**
- **Adult** (By Mouth Using Oral Suspension): 10 mg once daily.
**Hereditary tyrosinaemia type I (in combination with dietary restriction of tyrosine and phenylalanine) (specialist use only) for nitisinone**
- **Neonate** (By mouth): Initially 1 mg/kg daily in 1-2 divided doses, adjusted according to response; maximum 2 mg/kg per day.
- **Child** (By mouth): Initially 1 mg/kg daily in 1-2 divided doses, adjusted according to response; maximum 2 mg/kg per day.
**Hereditary tyrosinaemia type I (in combination with dietary restriction of tyrosine and phenylalanine) (specialist use only) for Orfadin capsules**
- **Neonate** (By mouth using capsules): Initially 1 mg/kg daily in 1-2 divided doses, adjusted according to response; maximum 2 mg/kg per day.
- **Child** (By mouth using capsules): Initially 1 mg/kg daily in 1-2 divided doses, adjusted according to response; maximum 2 mg/kg per day.
**Hereditary tyrosinaemia type I (in combination with dietary restriction of tyrosine and phenylalanine) (specialist use only) for Orfadin oral suspension**
- **Neonate** (By mouth using oral suspension): Initially 1 mg/kg daily in 1-2 divided doses, adjusted according to response; maximum 2 mg/kg per day.
- **Child** (By mouth using oral suspension): Initially 1 mg/kg daily in 1-2 divided doses, adjusted according to response; maximum 2 mg/kg per day.
Side effects
Common or very common Corneal opacity; eye inflammation; eye pain; granulocytopenia; increased risk of infection; leucopenia; photophobia; skin reactions; thrombocytopenia Uncommon Leucocytosis
Interactions
**Other interactions (6):**
- Nitisinone is metabolised in vitro by CYP 3A4 and dose-adjustment may therefore be needed when nitisinone is co-administered with inhibitors or inducers of this enzyme.
- Based data from a clinical interaction study with 80 mg nitisinone at steady-state, nitisinone is a moderate inhibitor of CYP2C9 (2.3-fold increase in tolbutamide AUC), therefore nitisinone...
- Nitisinone is a weak inducer of CYP2E1 (30% decrease in chlorzoxazone AUC) and a weak inhibitor of OAT1 and OAT3 (1.7-fold increase in AUC of furosemide), whereas nitisinone did not inhibit CYP2D6...
- No formal food interactions studies have been performed with Nitisinone hard capsules.
- However, nitisinone has been co-administered with food during the generation of efficacy and safety data.
- Therefore, it is recommended that if nitisinone treatment with Nitisinone hard capsules is initiated with food, this should be maintained on a routine basis, see section 4.2.
Pregnancy
Manufacturer advises avoid unless potential benefit outweighs risk-toxicity in animal studies.
Breast feeding
Manufacturer advises avoid-adverse effects in animal studies.
Medicinal forms
Capsule,Suspension
Clinical governance
**Author:** MedNext Clinical Team. **Clinical reviewer:** Dr Shameer Deen, MBBS, MS, MRCS. **Sources:** BNF, Indian Pharmacopoeia, CIMS India. **Correction:** Report errors at support@mednext.academy.
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