A1,
A2,
B,
C1,
C2,
D,
E,
F,
G-H,
I-K,
L,
M,
N,
O,
P1,
P2,
Q-R,
S,
T,
U-V,
W-Z
Orfadin Side Effects, and Drug Interactions - Nitisinone
Orfadin Side Effects, and Drug Interactions - Nitisinone
SIDE EFFECTS
In a clinical trial of 207 patients treated with Nitisinone
for HT-1, the most frequent adverse effects, regardless of causality assessment,
occurred in the following organ systems:
Liver and Biliary System: hepatic neoplasm 8%, liver
failure 7%.
Visual System: conjunctivitis 2%, corneal opacity 2%,
keratitis 2%, photophobia 2%, blepharitis 1%, eye pain 1%, cataracts 1%.
Hemic and Lymphatic: thrombocytopenia 3%, leucopenia
3%, porphyria 1%, epistaxis 1%.
Skin and Appendages: pruritis 1%, exfoliative dermatitis
1%, dry skin 1%, maculopapular rash 1%, alopecia 1%.
Adverse reactions that occurred in less than 1% of the patients,
regardless of causality assessment, are:
Body as a Whole: death.
Nervous System: seizures, brain tumor, encephalopathy,
headache, hyperkinesia.
Cardiovascular: cyanosis.
Digestive System: abdominal pain, diarrhea, enanthema,
gastritis, gastroenteritis, gastrointestinal hemorrhage, melena, tooth discoloration.
Liver and Biliary System: elevated hepatic enzymes,
hepatic function disorder, liver enlargement.
Metabolic and Nutritional Disorders: dehydration, hypoglycemia,
thirst.
Resistance Mechanism Disorder: infection, septicemia,
otitis.
Respiratory: bronchitis, respiratory insufficiency.
Musculoskeletal System: pathologic fracture.
Female Reproductive: amenorrhea.
Psychiatric: nervousness, somnolence.
Drug Interactions
No drug-drug interaction studies have been conducted with Nitisinone.
Drug/Laboratory Test Interactions
None known.
Carcinogenesis, Mutagenesis, Impairment of Fertility
Studies in animals have not been performed to evaluate the
carcinogenic potential of Nitisinone. Nitisinone was not mutagenic in the Ames
test. In a single dose-group study in rats given 100 mg/kg/day (12 times the
recommended clinical dose based on relative body surface area), reduced litter
size, decreased pup weight at birth and decreased survival of pups after birth
was demonstrated.
Pregnancy Category C:
Adequate reproductive toxicity studies have not been conducted
with Nitisinone. It is not known if Nitisinone can produce harm to the fetus
if administered to pregnant women. Nitisinone should be given to a pregnant
woman only if clearly needed.
Nursing Mothers
Although the exposure was not quantified, naive pups that were
exposed to Orfadin via breast milk showed signs of ocular toxicity and
lower body weight. This suggests that OrfadinÔ
is excreted via breast milk in rats. It is not known whether Nitisinone is excreted
in human milk. Because many drugs are excreted in human milk, caution should
be exercised when Nitisinone is administered to a nursing woman.
Pediatric Use
Nitisinone has been studied in patients ranging in age from
birth to 21.7 years. The median age of enrolment in a study of 207 patients
with HT-1 was 9 months.
Geriatric Use
Clinical studies of Nitisinone did not include any subjects
aged 65 and over to determine whether they respond differently from younger
subjects. HT-1 is presently a disease of the pediatric population. In general,
dose selection for an elderly patient should be cautious, usually starting at
the low end of the dosing range, reflecting the greater frequency of decreased
hepatic, renal, or cardiac function, and of concomitant disease or other drug
therapy in this patient population.
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