RAVICTI- glycerol phenylbutyrate liquid

Země: Spojené státy

Jazyk: angličtina

Zdroj: NLM (National Library of Medicine)

Aktivní složka:

GLYCEROL PHENYLBUTYRATE (UNII: ZH6F1VCV7B) (GLYCEROL PHENYLBUTYRATE - UNII:ZH6F1VCV7B)

Dostupné s:

Horizon Therapeutics USA, Inc.

INN (Mezinárodní Name):

GLYCEROL PHENYLBUTYRATE

Složení:

GLYCEROL PHENYLBUTYRATE 1.1 g in 1 mL

Podání:

ORAL

Druh předpisu:

PRESCRIPTION DRUG

Terapeutické indikace:

RAVICTI is indicated for use as a nitrogen-binding agent for chronic management of patients with urea cycle disorders (UCDs) who cannot be managed by dietary protein restriction and/or amino acid supplementation alone. RAVICTI must be used with dietary protein restriction and, in some cases, dietary supplements (e.g., essential amino acids, arginine, citrulline, protein-free calorie supplements). Limitations of Use: - RAVICTI is not indicated for the treatment of acute hyperammonemia in patients with UCDs because more rapidly acting interventions are essential to reduce plasma ammonia levels. - The safety and efficacy of RAVICTI for the treatment of N -acetylglutamate synthase (NAGS) deficiency has not been established. RAVICTI is contraindicated in patients with known hypersensitivity to phenylbutyrate. Signs of hypersensitivity include wheezing, dyspnea, coughing, hypotension, flushing, nausea, and rash. Risk Summary Limited available data with RAVICTI use in pregnant women are insufficient to inform a drug-associated risk of major birth defects and miscarriage. In an animal reproduction study, administration of oral glycerol phenylbutyrate to pregnant rabbits during organogenesis at doses up to 2.7–times the dose of 6.87 mL/m2 /day in adult patients resulted in maternal toxicity, but had no effects on embryo-fetal development. In addition, there were no adverse developmental effects with administration of oral glycerol phenylbutyrate to pregnant rats during organogenesis at 1.9 times the dose of 6.87 mL/m2 /day in adult patients; however, maternal toxicity, reduced fetal weights, and variations in skeletal development were observed in pregnant rats administered oral glycerol phenylbutyrate during organogenesis at doses greater than or equal to 5.7 times the dose of 6.87 mL/m2 /day in adult patients [ see Data] . Report pregnancies to Horizon at 1-866-479-6742. The estimated background risk of major birth defects and miscarriage for the indicated population is unknown. All pregnancies have a background risk of birth defect, loss or other adverse outcomes. 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 Oral administration of glycerol phenylbutyrate during the period of organogenesis up to 350 mg/kg/day in rabbits produced maternal toxicity, but no effects on embryo-fetal development. The dose of 350 mg/kg/day in rabbits is approximately 2.7 times the dose of 6.87 mL/m2 /day in adult patients, based on combined area under the plasma concentration-time curve [AUCs] for PBA and PAA. In rats, at an oral dose of 300 mg/kg/day of glycerol phenylbutyrate (1.9 times the dose of 6.87 mL/m2 /day in adult patients, based on combined AUCs for PBA and PAA) during the period of organogenesis, no effects on embryo-fetal development were observed. Doses of 650 mg/kg/day or greater produced maternal toxicity and adverse effects on embryo-fetal development including reduced fetal weights and cervical ribs at the 7th cervical vertebra. The dose of 650 mg/kg/day in rats is approximately 5.7 times the dose of 6.87 mL/m2 /day in adult patients, based on combined AUCs for PBA and PAA. No developmental abnormalities, effects on growth, or effects on learning and memory were observed through maturation of offspring following oral administration in pregnant rats with up to 900 mg/kg/day of glycerol phenylbutyrate (8.5 times the dose of 6.87 mL/m2 /day in adult patients, based on combined AUCs for PBA and PAA) during organogenesis and lactation. Risk Summary There are no data on the presence of RAVICTI in human milk, the effects on the breastfed infant, or the effects on milk production. Because of the potential for serious adverse reactions, including neurotoxicity and tumorigenicity in a breastfed infant, advise patients that breastfeeding is not recommended during treatment with RAVICTI. Patients 2 Years to 17 Years of Age The safety and effectiveness of RAVICTI in patients 2 years to less than 18 years of age have been established in 3 clinical studies: 2 open-label, fixed-sequence, switchover clinical studies from sodium phenylbutyrate to RAVICTI, and 1 long-term, open label safety study [see Adverse Reactions (6.1), Clinical Studies (14.2)] . Patients Less Than 2 Years of Age The safety and effectiveness of RAVICTI in patients with UCDs less than 2 years of age have been established in 3 open-label studies. Pharmacokinetics and pharmacodynamics (plasma ammonia), and safety were studied in 17 patients aged 2 months to less than 2 years of age and in 16 patients less than 2 months of age [see Adverse Reactions (6.1), Clinical Studies (14.3)] . Juvenile Animal Toxicity Data In a juvenile rat study with daily oral dosing performed on postpartum day 2 through mating and pregnancy after maturation, terminal body weight was dose-dependently reduced by up to 16% in males and 12% in females at 900 mg/kg/day or higher (3 times the dose of 6.87 mL/m2 /day in adult patients, based on combined AUCs for PBA and PAA). Learning, memory, and motor activity endpoints were not affected. However, fertility (number of pregnant rats) was decreased by up to 25% at 650 mg/kg/day or higher (2.6 times the dose of 6.87 mL/m2 /day in adult patients, based on combined AUCs for PBA and PAA). Clinical studies of RAVICTI did not include sufficient numbers of subjects 65 years of age and older to determine whether they respond differently than younger subjects. Other reported clinical experience has not identified differences in responses between the elderly and younger patients. 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. The efficacy and safety of RAVICTI in patients with renal impairment are unknown. Monitor ammonia levels closely when starting patients with impaired renal function on RAVICTI. No studies were conducted in patients with UCDs and hepatic impairment. Because conversion of PAA to PAGN occurs in the liver, patients with hepatic impairment may have reduced conversion capability and higher plasma PAA and PAA to PAGN ratio [see Clinical Pharmacology (12.3)] . Therefore, dosage for patients with moderate to severe hepatic impairment should be started at the lower end of the recommended dosing range and should be kept on the lowest dose necessary to control their ammonia levels [see Dosage and Administration (2.5)] .

Přehled produktů:

RAVICTI® (glycerol phenylbutyrate) oral liquid 1.1 g/mL is supplied in multi-use, 25-mL glass bottles. The bottles are supplied in the following configurations: Store at 20°-25°C (68°-77°F) with excursions permitted to 15°-30°C (59°-86°F). Discard bottle 28 days after opening.

Stav Autorizace:

New Drug Application

Informace pro uživatele

Horizon Therapeutics, Inc.
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This Medication Guide has been approved by the U.S.
Food and Drug Administration.
Revised: September 2021
MEDICATION GUIDE
RAVICTI (rah-VIK- tee)
(glycerol phenylbutyrate)
oral liquid
What is the most important information I should know about RAVICTI?
RAVICTI may cause serious side effects, including:
Nervous system problems (Neurotoxicity). Phenylacetate (PAA), a
breakdown product of RAVICTI, may
cause nervous system side effects. Call your doctor or get medical
help right away if you get any of these
symptoms while taking RAVICTI:
•
sleepiness
•
lightheadedness
•
change in taste
•
problems with hearing
•
confusion
•
problems with memory
•
worsening of numbness, tingling, or
burning in your hands or feet
•
headache
•
feeling very tired (fatigue)
•
nausea
•
vomiting
Your doctor may do blood tests to measure the amount of PAA in your
blood during your treatment with
RAVICTI.
What is RAVICTI?
•
RAVICTI is a prescription medicine used for long-term management of
high blood levels of
ammonia (hyperammonemia) caused by a condition called a urea cycle
disorder (UCD). RAVICTI
should be used if the UCD cannot be managed with a low protein diet
and dietary supplements alone.
RAVICTI must be used along with a low protein diet and in some cases
dietary supplements.
•
RAVICTI is not used for the acute treatment of hyperammonemia in
people with UCD.
•
It is not known if RAVICTI is safe and effective for the treatment of
N-acetylglutamate synthase
(NAGS) deficiency.
Do not take RAVICTI if you are allergic to phenylbutyrate. Call your
doctor or go to the nearest hospital
emergency room if you have wheezing, shortness of breath, cough, low
blood pressure, flushing, nausea or a
rash while taking RAVICTI.
Before taking RAVICTI, tell your doctor about all of your medical
conditions, including if you:
•
have liver or kidney problems
•
have pancreas or bowel (intestine) problems
•
are pregnant or plan to become pregnant. It is not known if RAVICTI
will harm your

Charakteristika produktu

RAVICTI- GLYCEROL PHENYLBUTYRATE LIQUID
HORIZON THERAPEUTICS, INC.
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HIGHLIGHTS OF PRESCRIBING INFORMATION
THESE HIGHLIGHTS DO NOT INCLUDE ALL THE INFORMATION NEEDED TO USE
RAVICTI SAFELY AND
EFFECTIVELY. SEE FULL PRESCRIBING INFORMATION FOR RAVICTI.
RAVICTI (GLYCEROL PHENYLBUTYRATE) ORAL LIQUID
INITIAL U.S. APPROVAL: 1996
RECENT MAJOR CHANGES
Dosage and Administration (2.1, 2.6)
9/2021
INDICATIONS AND USAGE
RAVICTI is a nitrogen-binding agent indicated for chronic management
of patients with urea cycle disorders
(UCDs) who cannot be managed by dietary protein restriction and/or
amino acid supplementation alone.
RAVICTI must be used with dietary protein restriction and, in some
cases, dietary supplements. (1)
Limitations of Use:
RAVICTI is not indicated for treatment of acute hyperammonemia in
patients with UCDs. (1)
Safety and efficacy for treatment of N-acetylglutamate synthase (NAGS)
deficiency has not been
established. (1)
DOSAGE AND ADMINISTRATION
RAVICTI should be prescribed by a physician experienced in management
of UCDs. For administration
and preparation, see full prescribing information. (2.1, 2.6)
Switching From Sodium Phenylbutyrate Tablets or Powder to RAVICTI:
Patients should receive the dosage of RAVICTI that contains the same
amount of phenylbutyric acid,
see full prescribing information for conversion. (2.2)
Initial Dosage in Phenylbutyrate-Naïve Patients (2.3):
Recommended dosage range is 4.5 to 11.2 mL/m /day (5 to 12.4 g/m
/day).
For patients with some residual enzyme activity not adequately
controlled with dietary restriction, the
recommended starting dose is 4.5 mL/m /day.
Take into account patient's estimated urea synthetic capacity, dietary
protein intake, and diet
adherence.
Dosage Adjustment and Monitoring:
Follow plasma ammonia levels to determine the need for dosage
titration. (2.4)
Dosage Modifications in Patients with Hepatic Impairment:
Start dosage at lower end of range. (2.5, 8.7)
DOSAGE FORMS AND STRENGTHS
Oral liquid: 1.1 g/mL. (3)
CONTRAINDICATIONS
Known hypersensiti