JADENU- deferasirox tablet, film coated JADENU- deferasirox granule

Страна: США

мова: англійська

Джерело: NLM (National Library of Medicine)

Активний інгредієнт:

DEFERASIROX (UNII: V8G4MOF2V9) (DEFERASIROX - UNII:V8G4MOF2V9)

Доступна з:

Novartis Pharmaceuticals Corporation

ІПН (Міжнародна Ім'я):

DEFERASIROX

Склад:

DEFERASIROX 90 mg

Адміністрація маршрут:

ORAL

Тип рецепту:

PRESCRIPTION DRUG

Терапевтичні свідчення:

JADENU is indicated for the treatment of chronic iron overload due to blood transfusions (transfusional hemosiderosis) in patients 2 years of age and older. JADENU is indicated for the treatment of chronic iron overload in patients 10 years of age and older with non-transfusion-dependent thalassemia (NTDT) syndromes and with a liver iron concentration (LIC) of at least 5 milligrams of iron per gram of liver dry weight (mg Fe/g dw) and a serum ferritin greater than 300 mcg/L. The safety and efficacy of JADENU when administered with other iron chelation therapy have not been established. JADENU is contraindicated in patients with: - Estimated GFR less than 40 mL/min/1.73 m2  [see Dosage and Administration (2.5), Warnings and Precautions (5.1)] ; - Poor performance status [see Warnings and Precautions (5.1, 5.3)] ; - High-risk myelodysplastic syndromes (this patient population was not studied and is not expected to benefit from chelation therapy) ; - Advanced malignancies [see Warnings and Precautions (5.1, 5.3)] ; - Platelet counts less than 50 x 109 /L [see Warnings and Precautions (5.3, 5.4)] ; - Known hypersensitivity to deferasirox or any component of JADENU [see Warnings and Precautions (5.7), Adverse Reactions (6.2)] . Risk Summary There are no studies with the use of JADENU in pregnant women to inform drug-associated risks. Administration of deferasirox to rats during pregnancy resulted in decreased offspring viability and an increase in renal anomalies in male offspring at doses that were about or less than the recommended human dose on a mg/m2 basis. No fetal effects were noted in pregnant rabbits at doses equivalent to the human recommended dose on an mg/m2 basis. JADENU should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus. The background risk of major birth defects and miscarriage for the indicated population is unknown. All pregnancies had a background risk of birth defect, loss, or other adverse outcomes. However, the background risk in the U.S. general population of major birth defects is 2% to 4% and of miscarriage is 15% to 20% of clinically recognized pregnancies. Data Animal Data In embryo-fetal developmental studies, pregnant rats and rabbits received oral deferasirox during the period of organogenesis at doses up to 100 mg/kg/day in rats and 50 mg/kg/day in rabbits (1.2 times the maximum recommended human dose (MRHD) on an mg/m2 basis). These doses resulted in maternal toxicity but no fetal harm was observed. In a prenatal and postnatal developmental study, pregnant rats received oral deferasirox daily from organogenesis through lactation day 20 at doses of 10, 30, and 90 mg/kg/day (0.1, 0.3, and 1.0 times the MRHD on a mg/m2 basis). Maternal toxicity, loss of litters, and decreased offspring viability occurred at 90 mg/kg/day (1.0 times the MRHD on a mg/m2 basis), and increases in renal anomalies in male offspring occurred at 30 mg/kg/day (0.3 times the MRHD on a mg/m2 basis). Risk Summary No data are available regarding the presence of JADENU or its metabolites in human milk, the effects of the drug on the breastfed child, or the effects of the drug on milk production. Deferasirox and its metabolites were excreted in rat milk. Because many drugs are excreted in human milk and because of the potential for serious adverse reactions in a breastfeeding child from deferasirox and its metabolites, a decision should be made whether to discontinue breastfeeding or to discontinue the drug, taking into account the importance of the drug to the mother. Contraception Counsel patients to use non-hormonal method(s) of contraception since JADENU can render hormonal contraceptives ineffective [see Drug Interactions (7.2)] . Transfusional Iron Overload The safety and effectiveness of JADENU have been established in pediatric patients 2 years of age and older for the treatment of transfusional iron overload [see Dosage and Administration (2.1)] . Safety and effectiveness have not been established in pediatric patients less than 2 years of age for the treatment of transfusional iron overload. Pediatric approval for treatment of transfusional iron overload was based on clinical studies of 292 pediatric patients 2 years to less than 16 years of age with various congenital and acquired anemias. Seventy percent of these patients had beta-thalassemia [see Indications and Usage (1), Dosage and Administration (2.1), Clinical Studies (14)] . In those clinical studies, 173 children (ages 2 to < 12 years) and 119 adolescents (ages 12 to < 17 years) were exposed to deferasirox. A trial conducted in treatment naïve pediatric patients, 2 to < 18 years of age with transfusional iron overload (NCT02435212) did not provide additional relevant information about the safety or effectiveness of the deferasirox granules dosage form (JADENU Sprinkle) compared to the deferasirox oral tablets for suspension dosage form (Exjade). Iron Overload in Non-Transfusion-Dependent Thalassemia Syndromes The safety and effectiveness of JADENU have been established in patients 10 years of age and older for the treatment of chronic iron overload with non-transfusion-dependent thalassemia (NTDT) syndromes [see Dosage and Administration (2.2)] . Safety and effectiveness have not been established in patients less than 10 years of age with chronic iron overload in NTDT syndromes. Pediatric approval for treatment of NTDT syndromes with liver iron (Fe) concentration (LIC) of at least 5 mg Fe per gram of dry weight and a serum ferritin greater than 300 mcg/L was based on 16 pediatric patients treated with deferasirox therapy (10 years to less than 16 years of age) with chronic iron overload and NTDT. Use of JADENU in these age groups is supported by evidence from adequate and well-controlled studies of deferasirox in adult and pediatric patients [see Indications and Usage (1.2), Dosage and Administration (2.2), Clinical Studies (14)] . In general, risk factors for deferasirox-associated kidney injury include preexisting renal disease, volume depletion, overchelation, and concomitant use of other nephrotoxic drugs. Acute kidney injury, and acute liver injury and failure has occurred in pediatric patients. In a pooled safety analysis, pediatric patients with higher deferasirox exposures had a greater probability of renal toxicity and decreased renal function, resulting in increased deferasirox exposure and progressive renal toxicity/kidney injury. Higher rates of renal AEs have been identified among pediatric patients receiving Exjade doses greater than 25 mg/kg/day equivalent to 17.5 mg/kg/day JADENU when their serum ferritin values were less than 1,000 mcg/L [see Dosage and Administration (2.5), Warnings and Precautions (5.1, 5.6), Adverse Reactions (6.1, 6.2)] . Monitoring recommendations for all pediatric patients with Transfusional Iron Overload and NTDT It is recommended that serum ferritin be monitored every month to assess the patient’s response to therapy and to minimize the risk of overchelation [see Warnings and Precautions (5.6)] . Monitor renal function by estimating GFR using an eGFR prediction equation appropriate for pediatric patients and evaluate renal tubular function. Monitor renal function more frequently in pediatric patients in the presence of renal toxicity risk factors, including episodes of dehydration, fever and acute illness that may result in volume depletion or decreased renal perfusion. Use the minimum effective dose [see Warnings and Precautions (5.1)] . Interrupt JADENU in pediatric patients with transfusional iron overload, and consider dose interruption in pediatric patients with non-transfusion-dependent iron overload, for acute illnesses, which can cause volume depletion, such as vomiting, diarrhea, or prolonged decreased oral intake, and monitor more frequently. Resume therapy as appropriate, based on assessments of renal function, when oral intake and volume status are normal. Evaluate the risk benefit profile of continued JADENU use in the setting of decreased renal function. Avoid use of other nephrotoxic drugs [see Dosage and Administration (2.5), Warnings and Precautions (5.1)] . Juvenile Animal Toxicity Data Renal toxicity was observed in adult mice, rats, and marmoset monkeys administered deferasirox at therapeutic doses. In a neonatal and juvenile toxicity study in rats, deferasirox was administered orally from postpartum Day 7 through 70, which equates to a human age range of term neonate through adolescence. Increased renal toxicity was identified in juvenile rats compared to adult rats at a dose based on mg/m2 approximately 0.4 times the recommended dose of 20 mg/kg/day. A higher frequency of renal abnormalities was noted when deferasirox was administered to non-iron overloaded animals compared to iron overloaded animals. Four hundred thirty-one (431) patients greater than or equal to 65 years of age were studied in clinical trials of deferasirox in the transfusional iron overload setting. Two hundred twenty-five (225) of these patients were between 65 and 75 years of age while 206 were greater than or equal to 75 years of age. The majority of these patients had myelodysplastic syndrome (MDS) (n = 393). In these trials, elderly patients experienced a higher frequency of adverse reactions than younger patients. Monitor elderly patients for early signs or symptoms of adverse reactions that may require a dose adjustment. Elderly patients are at increased risk for toxicity due to the greater frequency of decreased hepatic, renal, or cardiac function, and of concomitant disease or other drug therapy. Dose selection for an elderly patient should be cautious, usually starting at the low end of the dosing range. In elderly patients, including those with MDS, individualize the decision to remove accumulated iron based on clinical circumstances and the anticipated clinical benefit and risks of deferasirox tablets for oral suspension therapy. JADENU is contraindicated in patients with eGFR less than 40 mL/min/1.73 m2  [see Contraindications (4)] . For patients with renal impairment (eGFR 40 to 60 mL/min/1.73 m2 ), reduce the starting dose by 50% [see Dosage and Administration (2.4), Clinical Pharmacology (12.3)]. Exercise caution in pediatric patients with an eGFR between 40 and 60 mL/min/1.73 m2  [see Dosage and Administration (2.4)]. If treatment is needed, use the minimum effective dose with enhanced monitoring of glomerular and renal tubular function. Individualize dose titration based on improvement in renal injury [see Dosage and Administration (2.4, 2.5)] . JADENU can cause glomerular dysfunction, renal tubular toxicity, or both, and can result in acute renal failure. Monitor all patients closely for changes in eGFR and renal tubular dysfunction during JADENU treatment. If either develops, consider dose reduction, interruption or discontinuation of JADENU until glomerular or renal tubular function returns to baseline [see Dosage and Administration (2.4, 2.5), Warnings and Precautions (5.1)] . Avoid use in patients with severe (Child-Pugh C) hepatic impairment. For patients with moderate (Child-Pugh B) hepatic impairment, reduce the starting dose by 50%. Closely monitor patients with mild (Child-Pugh A) or moderate (Child-Pugh B) hepatic impairment for efficacy and adverse reactions that may require dose titration [see Dosage and Administration (2.4), Warnings and Precautions (5.2), Clinical Pharmacology (12.3)] .

Огляд продуктів:

JADENU 90 mg tablets are light blue in color, film-coated, oval biconvex tablets with beveled edges, debossed with ‘NVR’ on one side and ‘90’ on a slight upward slope in between two debossed curved lines on the other side. They are available in bottles of 30 tablets……………………………………………(NDC 0078-0654-15) JADENU 180 mg tablets are medium blue in color, film-coated, oval biconvex tablet with beveled edges, debossed with ‘NVR’ on one side and ‘180’ on a slight upward slope in between two debossed curved lines on the other side. They are available in bottles of 30 tablets……………………………………………(NDC 0078-0655-15) JADENU 360 mg tablets are dark blue in color, film-coated, oval biconvex tablet with beveled edges, debossed with ‘NVR’ on one side and ‘360’ on a slight upward slope in between two debossed curved lines on the other side. They are available in bottles of 30 tablets……………………………………………(NDC 0078-0656-15) Store JADENU tablets at 20°C - 25°C (68°F - 77°F); excursions are permitted to 15°C to 30°C (59°F to 86°F) [see USP Controlled Room Temperature]. Protect from moisture. JADENU Sprinkle 90 mg granules are white to almost white granules in sachet. They are available in cartons of 30 sachets……………………………………………(NDC 0078-0727-15) JADENU Sprinkle 180 mg granules are white to almost white granules in sachet. They are available in cartons of 30 sachets……………………………………………(NDC 0078-0713-15) JADENU Sprinkle 360 mg granules are white to almost white granules in sachet. They are available in cartons of 30 sachets……………………………………………(NDC 0078-0720-15) Store JADENU Sprinkle granules at 20°C to 25°C (68°F to 77°F); excursions are permitted between 15°C to 30°C (59°F to 86°F) [see USP Controlled Room Temperature]. Protect from moisture.

Статус Авторизація:

New Drug Application

інформаційний буклет

JADENU- DEFERASIROX GRANULE
Novartis Pharmaceuticals Corporation
----------
This Medication Guide has been approved by the
U.S. Food and Drug Administration.
Revised: July 2020
MEDICATION GUIDE
JADENU® (ja de neu)
(deferasirox)
tablets
JADENU® (ja de neu) Sprinkle
(deferasirox)
granules
What is the most important information I should know about JADENU and
JADENU Sprinkle?
JADENU and JADENU Sprinkle can cause serious side effects, including:
Kidney problems: JADENU AND JADENU Sprinkle can cause sudden (acute)
kidney problems,
including kidney failure that may require treatment with dialysis, and
may cause death. Deaths have
happened mostly in people who also have other health problems and had
a blood disorder that was in an
advanced stage. Adults and children who already have kidney problems
and are taking certain medicines
with JADENU or JADENU Sprinkle may also have an increased risk of
sudden kidney problems. Be
sure to tell your healthcare provider about all the medicines you take
during treatment with JADENU or
JADENU Sprinkle.
Your healthcare provider should do blood and urine tests to check your
or your child’s kidney function
before and during treatment with JADENU or JADENU Sprinkle. Call your
healthcare provider right
away if:
•
your child becomes sick with fever, vomiting, or diarrhea and cannot
drink fluids normally during
treatment with JADENU or JADENU Sprinkle. Your child may be
dehydrated. Your healthcare
provider may need to temporarily stop treatment with JADENU or JADENU
Sprinkle and treat
your child for dehydration to help prevent kidney problems. Your
healthcare provider may
monitor your child’s kidney function more closely.
•
you notice that you or your child are passing less urine than usual
during treatment with JADENU
or JADENU Sprinkle.
Liver problems. JADENU AND JADENU Sprinkle can cause liver problems,
including liver failure that
can sometimes cause death. Liver problems with JADENU or JADENU
Sprinkle may be more common
in people who are over 55 years of age but can also happ

Характеристики продукта

JADENU- DEFERASIROX TABLET, FILM COATED
JADENU- DEFERASIROX GRANULE
NOVARTIS PHARMACEUTICALS CORPORATION
----------
HIGHLIGHTS OF PRESCRIBING INFORMATION
THESE HIGHLIGHTS DO NOT INCLUDE ALL THE INFORMATION NEEDED TO USE
JADENU SAFELY AND
EFFECTIVELY. SEE FULL PRESCRIBING INFORMATION FOR JADENU.
JADENU (DEFERASIROX) TABLETS, FOR ORAL USE
JADENU SPRINKLE (DEFERASIROX) GRANULES, FOR ORAL USE
INITIAL U.S. APPROVAL: 2005
WARNING: RENAL FAILURE, HEPATIC FAILURE, AND GASTROINTESTINAL
HEMORRHAGE
_SEE FULL PRESCRIBING INFORMATION FOR COMPLETE BOXED WARNING._
JADENU MAY CAUSE SERIOUS AND FATAL:
ACUTE KIDNEY INJURY, INCLUDING ACUTE RENAL FAILURE REQUIRING DIALYSIS
AND RENAL TUBULAR
TOXICITY INCLUDING FANCONI SYNDROME (5.1)
HEPATIC TOXICITY, INCLUDING FAILURE (5.2)
GASTROINTESTINAL HEMORRHAGE (5.3)
JADENU THERAPY REQUIRES CLOSE PATIENT MONITORING, INCLUDING LABORATORY
TESTS OF RENAL
AND HEPATIC FUNCTION. (5)
RECENT MAJOR CHANGES
Indications and Usage, Limitations of Use (1.3)
7/2019
INDICATIONS AND USAGE
JADENU is an iron chelator indicated for the treatment of chronic iron
overload due to blood transfusions in
patients 2 years of age and older. (1.1)
JADENU is indicated for the treatment of chronic iron overload in
patients 10 years of age and older with
non-transfusion-dependent thalassemia (NTDT) syndromes, and with a
liver iron (Fe) concentration (LIC) of
at least 5 mg Fe per gram of dry weight (Fe/g dw) and a serum ferritin
greater than 300 mcg/L. (1.2)
Limitations of Use:
The safety and efficacy of JADENU when administered with other iron
chelation therapy have not been
established. (1.3)
DOSAGE AND ADMINISTRATION
Transfusional Iron Overload: Initial dose for patients with estimated
glomerular filtration rate (eGFR)
greater than 60 mL/min/1.73 m is 14 mg per kg (calculated to nearest
whole tablet or nearest whole
sachet content for granules) once daily. (2.1)
NTDT Syndromes: Initial dose for patients with eGFR greater than 60
mL/min/1.73 m is 7 mg per kg
(calculated to nearest whole tablet or nearest whole sachet conte