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Medically reviewed by Last updated on Feb 28, 2019.


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Index Terms

  • NTBC

Dosage Forms

Excipient information presented when available (limited, particularly for generics); consult specific product labeling.

Capsule, Oral:

Orfadin: 2 mg, 5 mg, 10 mg, 20 mg

Suspension, Oral:

Orfadin: 4 mg/mL (90 mL) [contains polysorbate 80, sodium benzoate]

Tablet, Oral:

Nityr: 2 mg, 5 mg, 10 mg

Brand Names: U.S.

  • Nityr
  • Orfadin

Pharmacologic Category

  • 4-Hydroxyphenylpyruvate Dioxygenase Inhibitor


In patients with HT-1, tyrosine metabolism is interrupted due to a lack of the enzyme (fumarylacetoacetate hydrolase) needed in the last step of tyrosine degradation. Toxic metabolites of tyrosine accumulate and cause liver and kidney toxicity. Nitisinone competitively inhibits 4-hydroxyphenyl-pyruvate dioxygenase, an enzyme present early in the tyrosine degradation pathway, thereby preventing the build-up of the toxic metabolites.


Vd: Healthy volunteers: 8.2 L


Minor metabolism possibly via CYP3A4


Healthy volunteers: Urine (Hall 2001)

Time to Peak

Healthy volunteers: Capsule: 3.5 hours (range: 0.8 to 8 hours); Suspension: 0.4 hours (range: 0.2 to 4 hours); Tablet: 3.5 hours (range: 1 to 4 hours)

Half-Life Elimination

Healthy volunteers: Terminal half-life: Capsule, suspension: 54 hours; Tablet: 59.3 hours

Protein Binding


Use: Labeled Indications

Hereditary tyrosinemia type 1: Treatment of hereditary tyrosinemia type 1 (HT-1) as an adjunct to dietary restriction of tyrosine and phenylalanine in adult and pediatric patients.


There are no contraindications listed in the manufacturer's labeling.

Canadian labeling: Additional contraindications (not in US labeling): Hypersensitivity to nitisinone or any component of the formulation; breastfeeding

Dosing: Adult

Note: Must be used in conjunction with a diet restricted in tyrosine and phenylalanine. Titrate dose as needed based on biochemical and/or clinical response. If the biochemical response is satisfactory, the dosage should be adjusted only according to body weight gain. Do not adjust dose according to plasma tyrosine concentration.

Hereditary tyrosinemia type 1 (HT-1): Oral: Initial: 0.5 mg/kg twice daily. Increase to 0.75 mg/kg twice daily if succinylacetone is detectable 4 weeks after initiation. Further increase may be needed based on the evaluation of all biochemical parameters (maximum dose: 2 mg/kg/day); dose may be administered once daily (eg, 1 to 2 mg/kg once daily) if serum and urine succinylacetone is undetectable after ≥4 weeks of therapy.

Dosing: Geriatric

Refer to adult dosing.

Dosing: Pediatric

Note: Must be used in conjunction with a diet restricted in tyrosine and phenylalanine. If using tablets, round calculated dose up to the nearest available tablet strength.

Hereditary tyrosinemia type 1 (HT-1): Infants, Children, and Adolescents: Oral: Initial: 0.5 mg/kg/dose twice daily; titrate dose individually based on biochemical markers (eg, plasma and/or urine succinylacetone concentrations, liver function parameters and alpha-fetoprotein concentrations) and clinical response. If succinylacetone concentrations are still detectable after 1 month of therapy, may increase dose to 0.75 mg/kg/dose twice daily; may further increase as needed up to a maximum of 1 mg/kg/dose twice daily; maximum daily dose: 2 mg/kg/day. Once the biochemical response is satisfactory, further dosage adjustments should be only according to body weight gain; in patients ≥5 years using capsules or oral suspension, daily dose may be transitioned to once daily (eg, 1 to 2 mg/kg/dose once daily) if serum and urine succinylacetone is undetectable after ≥4 weeks of stable therapy.


Suspension: Refer to manufacturer's product labeling for preparation instructions. Allow suspension to warm to room temperature (30 to 60 minutes). Shake vigorously for 5 seconds (bottles with adapter inserted) or 20 seconds (bottles without the adapter inserted); foam will form.


Capsules: Administer at least 1 hour prior to, or 2 hours after a meal. Capsules may be opened and contents suspended in a small quantity of water, formula, or apple sauce; administer immediately.

Suspension: Administer without regards to meals. Allow suspension to warm to room temperature (30 to 60 minutes) prior to preparation.

Tablets: Administer without regards to meals. Tablets may be disintegrated in water and administered using an oral syringe or crushed and mixed with applesauce (administration with other liquids or foods is not recommended [has not been studied]). Refer to manufacturer's labeling for detailed instructions.

Dietary Considerations

Nitisinone capsules should be taken at least 1 hour prior to, or 2 hours after a meal. Dietary restriction of tyrosine and phenylalanine is required.


Capsules: Store refrigerated at 2°C to 8°C (36°F to 46°F).

Suspension: Store refrigerated at 2°C to 8°C (36°F to 46°F) prior to first use. After opening, store at room temperature (up to 25°C [77°F]) for up to 60 days. Do not freeze.

Tablets: Store at 20°C to 25°C (68°F to 77°F); excursions permitted to 15°C and 30°C (59°F and 86°F).

Drug Interactions

There are no known significant interactions.

Adverse Reactions


Endocrine & metabolic: Increased plasma tyrosine

1% to 10%:

Dermatologic: Alopecia (1%), exfoliative dermatitis (1%), maculopapular rash (1%), pruritus (1%), xeroderma (1%)

Endocrine & metabolic: Porphyria (1%)

Hematologic & oncologic: Leukopenia (3%), thrombocytopenia (3%), granulocytopenia (1%)

Hepatic: Hepatic failure (7%), hepatic neoplasm (malignant: 5%; benign: 3%)

Ophthalmic: Conjunctivitis (2%), corneal opacity (2%), keratitis (2%), photophobia (2%), blepharitis (1%), cataract (1%), eye pain (1%)

Respiratory: Epistaxis (1%)

<1%, postmarketing, and/or case reports: Abdominal pain, brain disease, brain neoplasm, bronchitis, corneal ulcer, cyanosis, diarrhea, enanthema, gastric distress, gastrointestinal hemorrhage, headache, hepatomegaly, hyperkinesia, hypoglycemia, increased liver enzymes, melena, seizure, septicemia


Concerns related to adverse effects:

• Dermatologic effects: Failure to adequately restrict dietary tyrosine and phenylalanine may lead to hyperkeratotic plaques on the soles and palms.

• Hematologic effects: Leukopenia and/or thrombocytopenia have been reported; may improve with dose reduction. May be due to underlying liver disease rather than drug-related (McKiernan 2006). Monitor platelets and WBC regularly during therapy.

• Neurological effects: Failure to adequately restrict dietary tyrosine and phenylalanine may lead to variable degrees of intellectual disability and developmental delay; clinical laboratory assessment including tyrosine levels is recommended for any patient exhibiting abrupt changes in neurological status while on therapy.

• Ocular effects: Failure to adequately restrict dietary tyrosine and phenylalanine may lead to ocular toxicities (eg, conjunctivitis, corneal ulcers, corneal opacities, eye pain, keratitis, photophobia). Slit-lamp examination of the eyes is recommended prior to initiation of therapy and in patients who develop photophobia, eye pain, or signs of inflammation (eg, redness, swelling, burning of the eyes). Immediate measurement of plasma tyrosine concentration is also recommended in patients who develop ocular symptoms.

Dosage form specific issues:

• Glycerol: Oral suspension contains 500 mg/mL of glycerol; oral doses of glycerol ≥10 g may cause headache, upset stomach, and diarrhea. Patients receiving single doses >20 mL are at increased risk for these adverse reactions; consider switching patients unable to tolerate the oral suspension to nitisinone capsules.

Other warnings/precautions:

• Dietary restrictions: Must be used with dietary restriction of tyrosine and phenylalanine; inadequate restriction can result in toxic effects to the eyes, skin, and nervous system. Evaluate plasma tyrosine concentrations in patients who develop signs and symptoms of toxicity. Nutritional consultation is recommended.

Monitoring Parameters

Dietary tyrosine and phenylalanine (assess dietary intake with tyrosine concentrations >500 micromole/L); urine and/or plasma succinylacetone, liver function parameters, and alpha-fetoprotein levels (in addition, at initiation or if there is a deterioration of the patient's clinical condition, may also monitor urine 5-aminolevulinate and erythrocyte porphobilinogen-synthase activity); body weight; slit-lamp examination (prior to initiation of therapy and in patients who develop symptoms of ocular toxicity); plasma tyrosine (as clinically indicated with side effects; concentrations should be kept <500 micromole/L to avoid toxicity); platelet and white blood cell counts (regularly during therapy).

Note: Plasma succinylacetone may take up to 3 months to normalize after start of therapy.

Pregnancy Considerations

Adverse events have been observed in animal reproduction studies.

Patient Education

• Discuss specific use of drug and side effects with patient as it relates to treatment. (HCAHPS: During this hospital stay, were you given any medicine that you had not taken before? Before giving you any new medicine, how often did hospital staff tell you what the medicine was for? How often did hospital staff describe possible side effects in a way you could understand?)

• Have patient report immediately to prescriber signs of liver problems (dark urine, feeling tired, lack of appetite, nausea, abdominal pain, light-colored stools, vomiting, or yellow skin or eyes), skin changes on extremities, vision changes, eye pain, severe eye irritation, confusion, chills, pharyngitis, bleeding, or bruising (HCAHPS).

• Educate patient about signs of a significant reaction (eg, wheezing; chest tightness; fever; itching; bad cough; blue skin color; seizures; or swelling of face, lips, tongue, or throat). Note: This is not a comprehensive list of all side effects. Patient should consult prescriber for additional questions.

Intended Use and Disclaimer: Should not be printed and given to patients. This information is intended to serve as a concise initial reference for healthcare professionals to use when discussing medications with a patient. You must ultimately rely on your own discretion, experience and judgment in diagnosing, treating and advising patients.

Further information

Always consult your healthcare provider to ensure the information displayed on this page applies to your personal circumstances.