Nitisinone
Pronunciation: Not specified in research notes..
- Generic name
- nitisinone
- Brand names
- ORFADIN
- Drug class
- 4-hydroxyphenylpyruvate dioxygenase (HPPD) inhibitor
- Form
- Capsules (2 mg, 5 mg, 10 mg, 20 mg)
- Route
- Oral
- Legal status
- Not specified in research notes.
Availability and supply rules vary by country
Trade names by country: United States · Canada
Australia: · Full directory
What nitisinone is and how it works
Nitisinone is a 4-hydroxyphenylpyruvate dioxygenase (HPPD) inhibitor used to treat hereditary tyrosinemia type 1 (HT-1) in adults and children. It must be used together with a strict diet low in tyrosine and phenylalanine. (1)
Treatment is managed by a specialist metabolic team. Dietary restrictions are essential and must not be changed without medical advice.
Mechanism of action: how nitisinone works
Nitisinone is a competitive inhibitor of 4-hydroxyphenylpyruvate dioxygenase (HPPD), an enzyme early in the tyrosine degradation pathway. By inhibiting HPPD, nitisinone prevents the formation of toxic metabolites fumarylacetoacetate and succinylacetone in patients with HT-1. (1)
What nitisinone is used for
Hereditary tyrosinemia type 1 (HT-1)
Nitisinone is indicated for the treatment of adult and pediatric patients with hereditary tyrosinemia type 1 in combination with dietary restriction of tyrosine and phenylalanine. (1)
Before taking nitisinone
Do not take / not appropriate for
- No contraindications are listed in the current US prescribing information. (all products) (1)
Tell your clinician about
- Any history of eye problems, vision changes, or sensitivity to light.
- Skin thickening or painful plaques on the palms or soles.
- All other medicines, especially blood thinners (e.g., warfarin) or those known to be metabolized by CYP2C9.
- Pregnancy, plans to become pregnant, or breastfeeding.
- Adherence to the prescribed tyrosine- and phenylalanine-restricted diet.
How to take nitisinone
- Take nitisinone capsules orally, usually twice daily (or once daily if directed by your specialist).
- Take each dose at least one hour before or two hours after a meal.
- If you cannot swallow capsules, they may be opened and the contents mixed with a small amount of water, formula, or apple sauce immediately before taking. Do not prepare in advance.
- The dose is based on body weight and must be prescribed and adjusted by your specialist metabolic team.
- Do not change the dose, frequency, or stop the restricted diet on your own.
Procedures and treatment changes
Tell the treating team before surgery, procedures, or any medicine change. Do not alter treatment without the responsible clinician. (1)
Missed dose
Guidance on missed doses is not provided in the research notes. Contact your prescriber for instructions.
Overdose
Information on overdose is not provided in the research notes. Seek immediate medical attention if an overdose is suspected.
Side effects
The following adverse effects have been reported in patients taking nitisinone. Elevated tyrosine levels are common and can cause eye and skin problems.
Elevated tyrosine levels
What to notice: Eye pain, redness, photophobia, blurred vision, or gritty sensation; painful skin thickening on palms or soles; developmental or intellectual changes.
What to do: Report any new or worsening eye or skin symptoms to your care team. Do not alter your diet without specialist advice. Regular blood monitoring is required. (1)
Eye disorders (conjunctivitis, corneal opacity, keratitis, photophobia, eye pain, blepharitis, cataracts)
What to notice: Redness, pain, sensitivity to light, blurred vision, or vision loss.
What to do: Report changes promptly. Attend scheduled slit-lamp eye examinations. (1)
Skin reactions (pruritus, exfoliative dermatitis, dry skin, maculopapular rash, alopecia)
What to notice: Itching, rash, hair loss, or peeling skin.
What to do: Discuss with your prescriber; do not stop treatment without advice. (1)
Blood cell disorders (thrombocytopenia, leukopenia, granulocytopenia)
What to notice: Unusual bruising, bleeding, or signs of infection (fever, sore throat).
What to do: Inform your care team promptly; blood counts are monitored regularly. (1)
Epistaxis (nosebleeds)
What to notice: Nosebleeds.
What to do: Inform your care team if frequent or severe. (1)
Severe eye or skin symptoms
What to notice: Rapid vision changes, severe eye pain, or extensive skin plaques.
What to do: Contact your prescriber immediately; diet adjustment may be needed. (1)
Signs of serious blood disorder
What to notice: Unexplained bleeding, bruising, or signs of infection.
What to do: Contact your care team promptly; blood counts need checking. (1)
Serious warnings
High plasma tyrosine with eye or skin complications — prompt medical attention
Symptoms: Eye pain, redness, light sensitivity, vision deterioration; painful or thickened skin on palms or soles.
Action: Inform your care team promptly; dietary adjustment and medical evaluation required. Do not self-adjust diet. (1)
Intellectual and developmental effects — prompt medical attention
Symptoms: Cognitive decline or developmental delay, especially in children.
Action: Report to your specialist; tight tyrosine control is essential. (1)
Interactions
| Medicine or test | Effect | Action |
|---|---|---|
| Drugs metabolized by CYP2C9 (e.g., warfarin) | Nitisinone inhibits CYP2C9, potentially increasing the effects of these drugs. | Your prescriber may need to reduce the dose of the affected medication. Monitor for signs of bleeding if taking warfarin. (1) |
| Substrates of OAT1/OAT3 transporters | Nitisinone may affect their excretion. | Discuss with your specialist; monitoring may be needed. (1) |
Pregnancy, breastfeeding, kidney/liver function, age
Children and adolescents
Nitisinone is used in children of all ages with HT-1. Dosing is weight-based; specialist management is required. (1)
Pregnancy
Limited human data available; animal studies showed skeletal ossification effects. Use only if the potential benefit justifies the potential risk, as determined by your care team. (1)
Breastfeeding
No data on presence in human milk; a decision should be made together with your care team whether to breastfeed while on nitisinone. (1)
Monitoring
Before starting
- Baseline slit-lamp eye examination, plasma tyrosine, liver function tests, alpha-fetoprotein, and complete blood count.
During treatment
- Regular monitoring of plasma succinylacetone, liver function, alpha-fetoprotein, plasma tyrosine (target below 500 µmol/L), platelet and white blood cell counts, and periodic slit-lamp eye exams.
Storage
Store capsules in the refrigerator at 2–8°C (36–46°F). May be kept at room temperature up to 25°C (77°F) for a maximum of 45 days; do not return to the refrigerator after room-temperature storage if not used within that period.
Professional information
Clinician-facing context only. Refer to the full prescribing information for complete dosing, monitoring, and safety details.
United States
Indication: Hereditary tyrosinemia type 1 (HT-1)
Dose summary: Starting dose 0.5 mg/kg orally twice daily; titrate based on biochemical response. Maximum 2 mg/kg daily. Once daily dosing may be considered in patients 5 years and older with undetectable succinylacetone after at least 4 weeks on a stable dose.
Renal context: Not specified in research notes. (1)
Hepatic guidance
Not specified in research notes; specialist guidance required.
Overdose note
No specific information available. In case of overdose, manage symptomatically and monitor tyrosine levels. (1)
Frequently asked questions
What diet must I follow while taking nitisinone?
You must follow a strict diet low in tyrosine and phenylalanine, as prescribed by your metabolic specialist. This diet is essential to prevent complications from high tyrosine levels. (1)
Why are regular eye exams necessary?
High tyrosine levels can cause eye problems like corneal opacity or keratitis. Regular slit-lamp exams detect these changes early so that dietary adjustments can be made. (1)
Can I take nitisinone once daily?
In some children aged 5 years and older who have had a stable response for at least 4 weeks, the total daily dose may be taken once daily. This decision must be made by your specialist. (1)
What is the mechanism of action of nitisinone?
Nitisinone is a competitive inhibitor of 4-hydroxyphenylpyruvate dioxygenase (HPPD), an enzyme early in the tyrosine degradation pathway. By inhibiting HPPD, nitisinone prevents the formation of toxic metabolites fumarylacetoacetate and succinylacetone in patients with HT-1. (1)
What is the generic name of Nitisinone?
The generic name is nitisinone. It is sold under brand names including ORFADIN. (1)
What class of drug is nitisinone?
Nitisinone is classed as: 4-hydroxyphenylpyruvate dioxygenase (HPPD) inhibitor. (1)
References
- ORFADIN (nitisinone) capsules — prescribing informationU.S. Food and Drug Administration (DailyMed) · United States · dated 2021-11 · accessed 2026-08-08 · source 1
- NITISINONE CAPSULE [PAR HEALTH USA, LLC] — US prescribing information (DailyMed SPL)U.S. National Library of Medicine (DailyMed) · US · accessed 2026-08-14 · source 2
- Nitisinone — patient drug information (MedlinePlus)U.S. National Library of Medicine (MedlinePlus) · US · accessed 2026-08-14 · source 3
- ORFADIN — FDA approval record (Drugs@FDA NDA206356)U.S. Food and Drug Administration · US · accessed 2026-08-14 · source 4
- nitisinone — RxNorm normalized drug concept (RXCUI 61805)U.S. National Library of Medicine (RxNorm) · US · accessed 2026-08-14 · source 5
Brand names by country
Single-ingredient nitisinone names are shown separately by country. Product availability, strengths, and supply rules can change; combination products are not included here.
Priority countries
United States
- Orfadin10 mg, 2 mg, 5 mg, 4 mg/mL, 20 mg · swedish orphan biovitrum ab (publ)
- NITYR2 mg, 5 mg, 10 mg · cycle pharmaceuticals ltd.
- HARLIKU2 mg · cycle pharmaceuticals ltd.
Canada
- ORFADIN
- MDK-NITISINONE