Land: USA
Språk: engelska
Källa: NLM (National Library of Medicine)
NITISINONE (UNII: K5BN214699) (NITISINONE - UNII:K5BN214699)
Bryant Ranch Prepack
ORAL
PRESCRIPTION DRUG
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.
Nitisinone Capsules 2 mg for oral administration containing 2 mg of nitisinone, are supplied as follows: White Opaque Hard gelatin capsule shell Size #3, imprinted with black ink as "008" on cap and "Novitium 2 mg" on body, filled with white to off white powder blend. NDC 63629-2234-1 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].
Abbreviated New Drug Application
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 Läs hela dokumentet