Nitisinone
Generic: NITISINONE
Basic Information
Manufacturer
Bryant Ranch Prepack
Product Type
HUMAN PRESCRIPTION DRUG
Route of Administration
ORAL
FDA Set ID
b7c38003-6899-4508-a69a-aef1231de22c
Indications & Usage
1 INDICATIONS & USAGE Nitisinone capsules are indicated for the treatment of adult and pediatric patients with hereditary tyrosinemia type 1 (HT-1) in combination with dietary restriction of tyrosine and phenylalanine.
Nitisinone is a hydroxy-phenylpyruvate dioxygenase inhibitor indicated for the treatment of adult and pediatric patients with hereditary tyrosinemia type 1 (HT-1) in combination with dietary restriction of tyrosine and phenylalanine.
Nitisinone is a hydroxy-phenylpyruvate dioxygenase inhibitor indicated for the treatment of adult and pediatric patients with hereditary tyrosinemia type 1 (HT-1) in combination with dietary restriction of tyrosine and phenylalanine.
Adverse Reactions
6 ADVERSE REACTIONS Most common adverse reactions (>1%) are elevated tyrosine levels, thrombocytopenia, leukopenia, conjunctivitis, corneal opacity, keratitis, photophobia, eye pain, blepharitis, cataracts, granulocytopenia, epistaxis, pruritus, exfoliative dermatitis, dry skin, maculopapular rash and alopecia.
( 6.1 ) To report SUSPECTED ADVERSE REACTIONS, contact Novitium Pharma at 1-855-204-1431 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.
6.1 Clinical trials experience Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in clinical practice.
Nitisinone was studied in one open-label, uncontrolled study of 207 patients with HT-1, ages 0 to 22 years at enrollment (median age 9 months), who were diagnosed with HT-1 by the presence of succinylacetone in the urine or plasma.
The starting dose of nitisinone was 0.3 to 0.5 mg/kg twice daily, and the dose was increased in some patients to 1 mg/kg twice daily based on weight, biochemical, and enzyme markers.
The recommended starting dosage of nitisinone is 0.5 mg/kg twice daily [see Dosage and Administration ( 2.1 )].
Median duration of treatment was 22 months (range 0.1 to 80 months).
The most serious adverse reactions reported during nitisinone treatment were thrombocytopenia, leukopenia, porphyria, and ocular/visual complaints associated with elevated tyrosine levels [see Warnings and Precautions ( 5.1 , 5.2 )] .
Fourteen patients experienced ocular/visual events.
The duration of the symptoms varied from 5 days to 2 years.
Six patients had thrombocytopenia, three of which had platelet counts 30,000/microL or lower.
In 4 patients with thrombocytopenia, platelet counts gradually returned to normal (duration up to 47 days) without change in nitisinone dose.
No patients developed infections or bleeding as a result of the episodes of leukopenia and thrombocytopenia.
Patients with HT- 1 are at increased risk of developing porphyric crises, hepatic neoplasms, and liver failure requiring liver transplantation.
These complications of HT-1 were observed in patients treated with nitisinone for a median of 22 months during the clinical trial (liver transplantation 13%, liver failure 7%, malignant hepatic neoplasms 5%, benign hepatic neoplasms 3%, porphyria 1%).
The most common adverse reactions reported in the clinical trial are summarized in Table 1.
TABLE 1 Most Common Adverse Reactions in Patients with HT-1 Treated with Nitisinone* Elevated tyrosine levels >10% Leukopenia 3% Thrombocytopenia 3% Conjunctivitis 2% Corneal opacity 2% Keratitis 2% Photophobia 2% Eye pain 1% Blepharitis 1% Cataracts 1% Granulocytopenia 1% Epistaxis 1% Pruritus 1% Exfoliative dermatitis 1% Dry skin 1% Maculopapular rash 1% Alopecia 1% *reported in at least 1% of patients Adverse reactions reported in less than 1% of the patients, included death, seizure, brain tumor, encephalopathy, hyperkinesia, cyanosis, abdominal pain, diarrhea, enanthema, gastrointestinal hemorrhage, melena, elevated hepatic enzymes, liver enlargement, hypoglycemia, septicemia, and bronchitis.
( 6.1 ) To report SUSPECTED ADVERSE REACTIONS, contact Novitium Pharma at 1-855-204-1431 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.
6.1 Clinical trials experience Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in clinical practice.
Nitisinone was studied in one open-label, uncontrolled study of 207 patients with HT-1, ages 0 to 22 years at enrollment (median age 9 months), who were diagnosed with HT-1 by the presence of succinylacetone in the urine or plasma.
The starting dose of nitisinone was 0.3 to 0.5 mg/kg twice daily, and the dose was increased in some patients to 1 mg/kg twice daily based on weight, biochemical, and enzyme markers.
The recommended starting dosage of nitisinone is 0.5 mg/kg twice daily [see Dosage and Administration ( 2.1 )].
Median duration of treatment was 22 months (range 0.1 to 80 months).
The most serious adverse reactions reported during nitisinone treatment were thrombocytopenia, leukopenia, porphyria, and ocular/visual complaints associated with elevated tyrosine levels [see Warnings and Precautions ( 5.1 , 5.2 )] .
Fourteen patients experienced ocular/visual events.
The duration of the symptoms varied from 5 days to 2 years.
Six patients had thrombocytopenia, three of which had platelet counts 30,000/microL or lower.
In 4 patients with thrombocytopenia, platelet counts gradually returned to normal (duration up to 47 days) without change in nitisinone dose.
No patients developed infections or bleeding as a result of the episodes of leukopenia and thrombocytopenia.
Patients with HT- 1 are at increased risk of developing porphyric crises, hepatic neoplasms, and liver failure requiring liver transplantation.
These complications of HT-1 were observed in patients treated with nitisinone for a median of 22 months during the clinical trial (liver transplantation 13%, liver failure 7%, malignant hepatic neoplasms 5%, benign hepatic neoplasms 3%, porphyria 1%).
The most common adverse reactions reported in the clinical trial are summarized in Table 1.
TABLE 1 Most Common Adverse Reactions in Patients with HT-1 Treated with Nitisinone* Elevated tyrosine levels >10% Leukopenia 3% Thrombocytopenia 3% Conjunctivitis 2% Corneal opacity 2% Keratitis 2% Photophobia 2% Eye pain 1% Blepharitis 1% Cataracts 1% Granulocytopenia 1% Epistaxis 1% Pruritus 1% Exfoliative dermatitis 1% Dry skin 1% Maculopapular rash 1% Alopecia 1% *reported in at least 1% of patients Adverse reactions reported in less than 1% of the patients, included death, seizure, brain tumor, encephalopathy, hyperkinesia, cyanosis, abdominal pain, diarrhea, enanthema, gastrointestinal hemorrhage, melena, elevated hepatic enzymes, liver enlargement, hypoglycemia, septicemia, and bronchitis.