July 30, 2016
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Side Effects


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.

ORFADIN was studied in one open-label, uncontrolled study of 207 patients with HT-1, ages 0 to 21.7 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 ORFADIN 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 dose is 0.5 mg/kg to 1 mg/kg twice daily [see DOSAGE AND ADMINISTRATION]. Median duration of treatment was 22.2 months (range 0.1 to 80 months).

The most serious adverse reactions reported during ORFADIN treatment were thrombocytopenia, leukopenia, porphyria, and ocular/visual complaints associated with elevated tyrosine levels [see WARNINGS AND PRECAUTIONS]. 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 ORFADIN 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 HT1 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*

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.

Read the Orfadin (nitisinone) Side Effects Center for a complete guide to possible side effects


Interaction With CYP2C9 Substrates

If ORFADIN is co-administered with drugs that are metabolized by CYP2C9, additional monitoring may be warranted because of a potential for increased systemic exposure of these drugs [see CLINICAL PHARMACOLOGY]. The risk is dependent upon the particular 2C9 substrate and its adverse reaction profile.

This monograph has been modified to include the generic and brand name in many instances.

Last reviewed on RxList: 6/21/2016

Side Effects

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