Drugs Information Online
Drugs and diseases reference index

Drugs and diseases reference index

Drugs A-Z List

Diseases & Conditions A-Z List

Herbs & Supplements

Medical Dictionary

Full Article

Popular Drugs

Popular Diseases & Conditions

Drugs reference index «Nitisinone»


Pronunciation: (nit-IS-i-none)Class: Enzyme inhibitor

Trade Names:Orfadin- Capsules 2 mg- Capsules 5 mg- Capsules 10 mg


Competitive inhibitor of 4-hydroxyphenyl-pyruvate dioxygenase, an enzyme in the tyrosine catabolic pathway. Prevents accumulation of tyrosine catabolic intermediates maleylacetoacetate and fumarylacetoacetate. In patients with hereditary tyrosinemia type 1 (HT-1), these catabolic intermediates are converted into toxic metabolites (succinylacetone and succinylacetoacetate), responsible for the liver and kidney toxicity observed in these patients.



Mean time to reach C max is 3 h for the capsule and 15 min for the liquid.


Mean terminal t ½ is 54 h.

Indications and Usage

Adjunct to dietary restriction of tyrosine and phenylalanine in the treatment of hereditary tyrosinemia type 1.


Standard considerations.

Dosage and Administration

Adults and children

PO Initial dose: 1 mg/kg/day divided for morning and evening administration. Dose adjustment: Increase to 1.5 mg/kg/day after 1 mo if biochemical parameters (except plasma succinylacetone) are not normalized. Further increase to max dosage of 2 mg/kg/day may be needed in some patients.

General Advice

  • Administer each dose on an empty stomach at least 1 h before meals.
  • Total daily dose may be split unevenly in order to limit the total number of capsules given at each administration.
  • For patients who cannot swallow capsules, capsules may be opened and the contents suspended in a small amount of water, formula, or applesauce immediately before use. Do not prepare mixture ahead of time and store for future use.


Store capsules in refrigerator (36° to 46°F).

Drug Interactions

None well documented.

Laboratory Test Interactions

None well documented.

Adverse Reactions


Alopecia, dry skin, exfoliative dermatitis, maculopapular rash, pruritus (1%).


Conjunctivitis, corneal opacities, keratitis, photophobia (2%); blepharitis, cataracts, eye pain (1%).


Leukopenia, thrombocytopenia (3%); epistaxis, porphyria (1%).


Hepatic neoplasm (8%); liver failure (7%).



Regularly monitor urine succinylacetone, LFTs, alpha-fetoprotein, platelet and WBC counts, and serum tyrosine and phenylalanine levels. During initiation of therapy or acute exacerbations, more closely monitor all available biochemical parameters (eg, erythrocyte porphobilinogen synthase activity, plasma nitisinone concentration, plasma succinylacetone levels, urine 5aminolevulinic acid levels).


Regularly monitor liver by imaging (CT scan, MRI, ultrasound) and lab tests, including alpha-fetoprotein.


Perform slit-lamp examinations of the eyes before initiation of therapy and during any eye adverse reactions (eg, eye pain, photophobia, signs of inflammation).


Measure serum phosphate in patients with renal involvement at risk for secondary hyperphosphatemia and rickets.


Category C .




Nitisinone has been studied in patients ranging in age from birth to 21.7 yr of age.


Cautiously make dosage selection, usually starting at the lower end of the dosing range, reflecting the greater frequency of decreased hepatic and renal function and comorbidity.

High plasma tyrosine levels

A nutritionist skilled in managing children with inborn errors or metabolism should design a low-protein diet deficient in tyrosine and phenylalanine. Inadequate restriction of tyrosine and phenylalanine intake can result in elevations of plasma tyrosine. Keep tyrosine levels below 500 mcmol/L to avoid toxic effects to the eyes (conjunctivitis, corneal ulcers or opacities, eye pain, keratitis, photophobia), skin (painful hyperkeratotic plaques on the soles and palms), and nervous system (developmental delay, mental retardation). Implement a more restricted diet if plasma tyrosine level is above 500 mcmol/L. Do not adjust nitisinone dose to lower tyrosine level because the HT-1 metabolic defect may result in deterioration of the patient's clinical condition.

Porphyric crises/liver failure/hepatic neoplasms

Patients with HT-1 are at increased risk of developing porphyric crises, liver failure, or hepatic neoplasms requiring liver transplantation. Evaluate patients with increasing alpha-fetoprotein or signs of liver nodules for hepatic malignancy.


Transient thrombocytopenia, leukopenia, or both has been reported. In most patients, platelet and WBC counts normalized gradually without change in nitisinone dose.



Elevated tyrosine levels, 1 case of sunlight sensitivity.

Patient Information

  • Advise patient or caregiver to read patient information leaflet before using the first time and to reread and check for new information with each refill.
  • Advise patient or caregiver that medication is taken in the morning and evening and that the total dose may be split unevenly in order to limit number of capsules for each administration.
  • Advise patient or caregiver that each dose should be taken on an empty stomach, at least 1 h before meals.
  • Advise patient or caregiver that capsules may be opened and the contents suspended in a small amount of water, formula, or applesauce immediately before use. Caution patient or caregiver not to prepare mixture ahead of time and store for future use.
  • Caution patient or caregiver not to change the dose or stop taking unless advised by health care provider.
  • Emphasize to patient and/or caregiver the importance of maintaining dietary restriction of tyrosine and phenylalanine.
  • Instruct patient or caregiver to immediately report any of the following to health care provider: bleeding or unusual bruising, flu-like symptoms, itching, persistent nausea and/or vomiting, rash, unexplained eye symptoms, yellowing of skin or eyes.

Copyright © 2009 Wolters Kluwer Health.

  • Nitisinone MedFacts Consumer Leaflet (Wolters Kluwer)
  • nitisinone Concise Consumer Information (Cerner Multum)
  • nitisinone Advanced Consumer (Micromedex) - Includes Dosage Information
  • Orfadin Prescribing Information (FDA)

Comment «Nitisinone»