EVRYSDI- risdiplam powder, for solution

País: Estados Unidos

Língua: inglês

Origem: NLM (National Library of Medicine)

Ingredientes ativos:

RISDIPLAM (UNII: 76RS4S2ET1) (RISDIPLAM - UNII:76RS4S2ET1)

Disponível em:

Genentech Inc.

Via de administração:

ORAL

Tipo de prescrição:

PRESCRIPTION DRUG

Indicações terapêuticas:

EVRYSDI is indicated for the treatment of spinal muscular atrophy (SMA) in pediatric and adult patients. None. There is a pregnancy exposure registry that monitors pregnancy and fetal/neonatal/infant outcomes in women exposed to EVRYSDI during pregnancy. Physicians are encouraged to register patients and pregnant women are encouraged to register themselves by calling 1-833-760-1098 or visiting https://www.evrysdipregnancyregistry.com. Risk Summary There are no adequate data on the developmental risk associated with the use of EVRYSDI in pregnant women. In animal studies, administration of risdiplam during pregnancy or throughout pregnancy and lactation resulted in adverse effects on development (embryofetal mortality, malformations, decreased fetal body weights, and reproductive impairment in offspring) at or above clinically relevant drug exposures [see Data]. The estimated background risk of major birth defects and miscarriage for the indicated populations is unknown. In the U.S. general population, the estimated background risk of major birth defect and miscarriage in clinically recognized pregnancies is 2% to 4% and 15% to 20%, respectively. Based on animal data, advise pregnant women of the potential risk to the fetus. Data Animal Data Oral administration of risdiplam (0, 1, 3, or 7.5 mg/kg/day) to pregnant rats throughout organogenesis resulted in decreased fetal body weights and increased incidences of fetal structural variations at the highest dose tested, which was not associated with maternal toxicity. The no-effect level for adverse effects on embryofetal development (3 mg/kg/day) was associated with maternal plasma exposure (AUC) approximately 2 times that in humans at the maximum recommended human dose (MRHD) of 5 mg. Oral administration of risdiplam (0, 1, 4, or 12 mg/kg/day) to pregnant rabbits throughout organogenesis resulted in embryofetal mortality, fetal malformations (hydrocephaly), and structural variations at the highest dose tested, which was associated with maternal toxicity. The no-effect dose for adverse effects on embryofetal development (4 mg/kg/day) was associated with maternal plasma exposure (AUC) approximately 4 times that in humans at the MRHD. When risdiplam (0, 0.75, 1.5, or 3 mg/kg/day) was orally administered to rats throughout pregnancy and lactation, gestation was prolonged in the dams, and delayed sexual maturation (vaginal opening) and impaired reproductive function (decreased numbers of corpora lutea, implantation sites, and live embryos) were observed in female offspring at the highest dose. The no-effect dose for adverse effects on pre- and postnatal development in rats (1.5 mg/kg/day) was associated with maternal plasma exposure (AUC) similar to that in humans at the MRHD. Risk Summary There are no data on the presence of risdiplam in human milk, the effects on the breastfed infant, or the effects on milk production. Risdiplam was excreted in the milk of lactating rats orally administered risdiplam. The developmental and health benefits of breastfeeding should be considered along with the mother's clinical need for EVRYSDI and any potential adverse effects on the breastfed infant from EVRYSDI or from the underlying maternal condition. Studies of risdiplam in juvenile and adult rats and in monkeys demonstrated adverse effects on the reproductive organs, including germ cells, in males at clinically-relevant plasma exposures [see Use in Specific Populations (8.4) and Nonclinical Toxicology (13.1)] . Pregnancy Testing Pregnancy testing is recommended for females of reproductive potential prior to initiating EVRYSDI [see Use in Specific Populations (8.1)] . Contraception EVRYSDI may cause embryofetal harm when administered to a pregnant woman [see Use in Specific Populations (8.1)]. Female Patients Advise female patients of reproductive potential to use effective contraception during treatment with EVRYSDI and for at least 1 month after her last dose. Infertility Male Patients Male fertility may be compromised by treatment with EVRYSDI [see Nonclinical Toxicology (13.1)] . Counsel male patients of reproductive potential receiving EVRYSDI about the potential effects on fertility. Male patients may consider sperm preservation prior to treatment. The safety and effectiveness of EVRYSDI in pediatric patients (neonates and older) have been established. Use of EVRYSDI for SMA is supported by evidence from adequate and well-controlled studies of EVRYSDI in patients 2 months of age and older with SMA. Use of EVRYSDI for SMA in patients 2 months of age and younger is supported by pharmacokinetic and safety data from pediatric patients 16 days and older, and pharmacokinetic modeling and simulation to identify the dosing regimen [see Clinical Pharmacology (12.3) and Clinical Studies (14)] . Juvenile Animal Toxicity Data Oral administration of risdiplam (0, 0.75, 1.5, 2.5 mg/kg/day) to young rats from postnatal day (PND) 4 through PND 31 resulted in decreased growth (body weight, tibia length) and delayed sexual maturation in males at the mid and high dose. The skeletal and body weight deficits persisted after cessation of dosing. Ophthalmic changes consisting of vacuoles in the anterior vitreous were seen at the high dose. Decreases in absolute B lymphocyte counts were observed at all doses after cessation of dosing. Decreases in testis and epididymis weights, which correlated with degeneration of the seminiferous epithelium in the testis, occurred at the mid and high doses; the histopathology findings were reversible, but organ weight persisted after cessation of dosing. Impaired female reproductive performance (decreased mating index, fertility index, and conception rate) was observed at the high dose. A no-effect dose for adverse developmental effects on preweaning rats was not identified. The lowest dose tested (0.75 mg/kg/day) was associated with plasma exposures (AUC) lower than that in humans at the maximum recommended human dose (MRHD) of 5 mg/day. Oral administration of risdiplam (0, 1, 3, or 7.5 mg/kg/day) to young rats from PND 22 through PND 112 produced a marked increase in micronuclei in the bone marrow, male reproductive organ histopathology (degeneration/necrosis of the seminiferous tubule epithelium, oligo/aspermia in the epididymis, spermatic granulomas), and adverse effects on sperm parameters (decreased sperm concentration and motility, increased sperm morphology abnormalities) at the highest dose tested. Increases in T lymphocytes (total, helper, and cytotoxic) were observed at the mid and high doses. The reproductive and immune effects persisted after cessation of dosing. The no-effect dose (1 mg/kg/day) for adverse effects on postweaning juvenile rats was associated with plasma exposures (AUC) lower than that in humans at the MRHD. Clinical studies of EVRYSDI did not include patients aged 65 years and older to determine whether they respond differently from younger adult patients. INSTRUCTIONS FOR USE EVRYSDI® [ev-RIZ-dee] (risdiplam) for oral solution Please read and understand this Instructions for Use and the Patient Information leaflet before you start taking EVRYSDI for information about EVRYSDI and how to prepare and give EVRYSDI through an oral syringe, gastrostomy tube (G-tube), or nasogastric tube (NG-tube). If you have any questions about how to take EVRYSDI, contact your healthcare provider. EVRYSDI should come as a liquid in a bottle when you receive it from the pharmacy. Do not take EVRYSDI and contact your pharmacist if the medicine in the bottle is a powder. Each EVRYSDI carton contains (see Figure A): Important information about EVRYSDI - Ask your healthcare provider to show you the correct oral syringe you should use and how to measure your prescribed daily dose. - Always use the reusable oral syringes that come with EVRYSDI to measure your prescribed daily dose. If your carton does not contain two identical syringes, contact your pharmacist. - Always take EVRYSDI exactly as your healthcare provider tells you to take it. - Take EVRYSDI 1 time daily after a meal at approximately the same time each day. - Do not take EVRYSDI if the bottle adapter is not in the bottle. If the bottle adapter is not in the bottle, contact your pharmacist. - Do not mix EVRYSDI into food or liquids. Do not mix EVRYSDI with formula or milk. - Do not take EVRYSDI if the bottle or oral syringes are damaged. - Avoid getting EVRYSDI on your skin or in your eyes. If EVRYSDI gets on your skin, wash the area with soap and water. If EVRYSDI gets in your eyes, rinse your eyes with water. - If you spill EVRYSDI, dry the area with a dry paper towel and then clean with water. Throw away the paper towel in the trash and wash your hands well with soap and water. - If there is not enough EVRYSDI left in the bottle for your prescribed dose, throw away (discard) the bottle with remaining EVRYSDI and used oral syringes according to your local requirements. - Use a new bottle of EVRYSDI to get your prescribed dose. Do not mix EVRYSDI from the new bottle with the bottle you are currently using. How to store EVRYSDI - Store EVRYSDI in the refrigerator between 36°F to 46°F (2°C to 8°C). Do not freeze. - If necessary, EVRYSDI can be kept at room temperature up to 104°F (up to 40°C) for a combined total of 5 days. EVRYSDI can be removed from, and returned to, a refrigerator. The total combined time out of refrigeration should not be more than 5 days. Throw away EVRYSDI if it has been kept at room temperature for more than 5 days. - Store EVRYSDI in the original amber bottle in an upright position with the cap tightly closed. - Throw away (discard) any unused portion of EVRYSDI 64 days after mixed by the pharmacist (constitution) when stored in the refrigerator at 36°F to 46°F (2°C to 8°C). Please see the Discard After date written on the bottle label (see Figure C). - Ask your pharmacist for the Discard After date if it is not written on the bottle label. - Throw away any unused portion of EVRYSDI that has been kept above 104°F (40°C). - Keep EVRYSDI, all medicines and syringes out of the reach of children. A) Preparing and withdrawing your dose How to prepare your dose of EVRYSDI If you are taking your dose of EVRYSDI by mouth, follow the instructions in "B) How to take a dose of EVRYSDI by mouth ". If you are taking your dose of EVRYSDI through a gastrostomy tube, follow the instructions in "C) How to give a dose of EVRYSDI through a gastrostomy tube ". If you are taking your dose of EVRYSDI through a nasogastric tube, follow the instructions in "D) How to give a dose of EVRYSDI through a nasogastric tube ". B) How to take a dose of EVRYSDI by mouth Sit upright when taking a dose of EVRYSDI by mouth. C) How to give a dose of EVRYSDI through a gastrostomy tube If you are giving EVRYSDI through a gastrostomy tube, ask your healthcare provider to show you how to inspect the gastrostomy tube before giving EVRYSDI. D) How to give a dose of EVRYSDI through a nasogastric tube If you are giving EVRYSDI through a nasogastric tube, ask your healthcare provider to show you how to inspect the nasogastric tube before giving EVRYSDI. E) How to clean the oral syringe after use EVRYSDI is a registered trademark of Genentech, Inc. Distributed by: Genentech, Inc. 1 DNA Way South San Francisco, CA 94080-4990 Approved: 3/2023 This Instructions for Use has been Approved by the U.S. Food and Drug Administration. ©2023 Genentech, Inc. All Rights Reserved

Resumo do produto:

Each amber glass bottle of EVRYSDI is packaged with a bottle adapter, two 1 mL reusable oral syringes, two 6 mL reusable oral syringes, and one 12 mL reusable oral syringe. EVRYSDI for oral solution is a light yellow, pale yellow, yellow, greyish yellow, greenish yellow, or light green powder. Each bottle contains 60 mg of risdiplam (NDC 50242-175-07). Store the dry powder at 20°C to 25°C (68°F to 77°F), excursions permitted between 15°C to 30°C (59°F to 86°F) [see USP controlled room temperature] . Keep in the original carton. Keep the constituted oral solution of EVRYSDI in the original amber bottle to protect from light. Store in a refrigerator at 2°C to 8°C (36°F to 46°F) [see Dosage and Administration (2.4)]. If refrigeration is not available, EVRYSDI can be kept at room temperature up to 40°C (up to 104°F) for a combined total of 5 days. EVRYSDI can be removed from, and returned to, a refrigerator. The total combined time out of refrigeration should not exceed 5 days.

Status de autorização:

New Drug Application

Características técnicas

EVRYSDI- RISDIPLAM POWDER, FOR SOLUTION
GENENTECH INC.
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HIGHLIGHTS OF PRESCRIBING INFORMATION
THESE HIGHLIGHTS DO NOT INCLUDE ALL THE INFORMATION NEEDED TO USE
EVRYSDI SAFELY AND
EFFECTIVELY. SEE FULL PRESCRIBING INFORMATION FOR EVRYSDI.
EVRYSDI (RISDIPLAM) FOR ORAL SOLUTION
INITIAL U.S. APPROVAL: 2020
INDICATIONS AND USAGE
EVRYSDI is a survival of motor neuron 2 (SMN2) splicing modifier
indicated for the treatment of spinal
muscular atrophy (SMA) in pediatric and adult patients. (1)
DOSAGE AND ADMINISTRATION
EVRYSDI must be constituted by a healthcare provider prior to
dispensing.
Administer orally once daily after a meal using the provided oral
syringe. (2.1, 2.4)
AGE AND BODY WEIGHT
RECOMMENDED DAILY DOSAGE
Less than 2 months of age
0.15 mg/kg
2 months to less than
2 years of age
0.2 mg/kg
2 years of age and older weighing less
than 20 kg
0.25 mg/kg
2 years of age and older weighing 20 kg or
more
5 mg
See Full Prescribing Information for important preparation and
administration instructions. (2.1, 2.4)
DOSAGE FORMS AND STRENGTHS
For Oral Solution: 60 mg of risdiplam as a powder for constitution to
provide 0.75 mg/mL solution. (3)
CONTRAINDICATIONS
None. (4)
ADVERSE REACTIONS
The most common adverse reactions in later-onset SMA (incidence at
least 10% of patients treated with
EVRYSDI and more frequent than control) were fever, diarrhea, and
rash. (6.1)
The most common adverse reactions in infantile-onset SMA were similar
to those observed in later-onset
SMA patients. Additionally, adverse reactions with an incidence of at
least 10% were upper respiratory
tract infection, lower respiratory tract infection, constipation,
vomiting, and cough. (6.1)
TO REPORT SUSPECTED ADVERSE REACTIONS, CONTACT GENENTECH AT
1-888-835-2555 OR FDA AT
1-800-FDA-1088 OR WWW.FDA.GOV/MEDWATCH.
DRUG INTERACTIONS
Avoid coadministration with drugs that are substrates of multidrug and
toxin extrusion (MATE)
transporters. (7.1)
USE IN SPECIFIC POPULATIONS
Pregnancy: Based on animal data, may cause fetal harm. (8.1)
SEE 17 FOR PATIE