NITISINONE capsule

Land: USA

Språk: engelska

Källa: NLM (National Library of Medicine)

Aktiva substanser:

NITISINONE (UNII: K5BN214699) (NITISINONE - UNII:K5BN214699)

Tillgänglig från:

Bryant Ranch Prepack

Administreringssätt:

ORAL

Receptbelagda typ:

PRESCRIPTION DRUG

Terapeutiska indikationer:

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. None. Risk Summary Limited available data with nitisinone use in pregnant women are not sufficient to determine a drug-associated risk of adverse developmental outcomes. Animal reproduction studies have been conducted for nitisinone. In these studies, nitisinone was administered to mice and rabbits during organogenesis with oral doses of nitisinone up to 20 and 8 times respectively, the recommended initial dose of 1 mg/kg/day. In mice, nitisinone caused incomplete skeletal ossification of fetal bones and decreased pup survival at doses 0.4 times the recommended initial dose, and increased gestational length at doses 4 times the recommended initial dose. In rabbits, nitisinone caused maternal toxicity and incomplete skeletal ossification of fetal bones at doses 1.6 times the recommended initial dose [see Data]. The background risk of major birth defects and miscarriage for the indicated population are unknown. In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2 to 4% and 15 to 20%, respectively. Data Animal Data Reproduction studies have been performed in mice at oral doses of about 0.4, 4 and 20 times the recommended initial dose (1 mg/kg/day) and in rabbits at oral doses of about 1.6, 4 and 8 times the recommended initial dose based on the body surface area. In mice, nitisinone has been shown to cause incomplete skeletal ossification of fetal bones at 0.4, 4 and 20 times the recommended initial dose, increased gestational length at 4 and 20 times the recommended initial dose, and decreased pup survival at 0.4 times the recommended initial dose based on the body surface area. In rabbits, nitisinone caused incomplete skeletal ossification of fetal bones at 1.6, 4 and 8 times the recommended initial dose based on the body surface area. Risk Summary There are no data on the presence of nitisinone in human milk, the effects on the breastfed infant, or the effects on milk production. Data suggest that nitisinone is present in rat milk due to findings of ocular toxicity and lower body weight seen in drug naive nursing rat pups. The development and health benefits of breastfeeding should be considered along with the mother's clinical need for nitisinone and any potential adverse effects on the breastfed infant from nitisinone or from the underlying maternal condition. The safety and effectiveness of nitisinone have been established in pediatric patients for the treatment of HT-1 in combination with dietary restriction of tyrosine and phenylalanine. Use of nitisinone in pediatric patients is supported by evidence from one open-label, uncontrolled clinical study conducted in 207 patients with HT-1 ages 0 to 22 years (median age 9 months) [see Clinical Studies (14)]. Clinical studies of nitisinone did not include any subjects aged 65 and over. No pharmacokinetic studies of nitisinone have been performed in geriatric patients. In general, dose selection for an elderly patient should be cautious reflecting the greater frequency of decreased hepatic, renal, or cardiac function, and concomitant disease or other drug therapy in this patient population.

Produktsammanfattning:

Nitisinone Capsules 5 mg for oral administration containing 5 mg of nitisinone, are supplied as follows: White Opaque Hard gelatin capsule shell Size #3, imprinted with black ink as "009" on cap and "Novitium 5 mg" on body, filled with white to off white powder blend. NDC 63629-2235-1 Bottles of 60 capsules with child-resistant closure and tamper resistant induction sealing Store at room temperature between 20°C to 25°C (68°F to 77°F), excursions permitted to 15°C and 30°C (59°F and 86°F) [see USP Controlled Room Temperature].

Bemyndigande status:

Abbreviated New Drug Application

Produktens egenskaper

NITISINONE- NITISINONE CAPSULE
BRYANT RANCH PREPACK
----------
HIGHLIGHTS OF PRESCRIBING INFORMATION
THESE HIGHLIGHTS DO NOT INCLUDE ALL THE INFORMATION NEEDED TO USE
NITISINONE CAPSULES
SAFELY AND EFFECTIVELY. SEE FULL PRESCRIBING INFORMATION FOR
NITISINONE CAPSULES.
NITISINONE CAPSULES, FOR ORAL USE.
INITIAL U.S. APPROVAL: 2002
RECENT MAJOR CHANGES
Warnings and Precautions (5.1) 05/2019
INDICATIONS AND USAGE
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. (1)
DOSAGE AND ADMINISTRATION
Recommended Dosage (2.1):
The recommended starting dosage is 0.5 mg/kg orally twice daily.
Titrate the dosage based on biochemical and/or clinical response, as
described in the full prescribing
information.
The maximum total daily dosage is 2 mg/kg orally.
Administration (2.2):
Maintain dietary restriction of tyrosine and phenylalanine
Take Nitisinone capsules at least one hour before, or two hours after
a meal
For patients who have difficulties swallowing capsules, the capsules
may be opened and the contents
suspended in a small amount of water, formula or apple sauce
immediately before use.
DOSAGE FORMS AND STRENGTHS
Capsules: 2 mg, 5 mg, 10 mg. (3)
CONTRAINDICATIONS
None (4)
WARNINGS AND PRECAUTIONS
Elevated Plasma Tyrosine Levels, Ocular Symptoms, Developmental Delay
and Hyperkeratotic
Plaques: Inadequate restriction of tyrosine and phenylalanine intake
can lead to elevations in plasma
tyrosine, which at levels above 500 micromol/L can result in symptoms,
intellectual disability and
developmental delay or painful hyperkeratotic plaques on the soles and
palms; do not adjust nitisinone
dosage in order to lower the plasma tyrosine concentration. Obtain
slit-lamp examination prior to
treatment, regularly during treatment; Reexamine patients if symptoms
develop or tyrosine levels are
> 500 micromol/L. Assess plasma tyrosine levels in patients with a