XADAGO- safinamide mesylate tablet, film coated

Kraj: Stany Zjednoczone

Język: angielski

Źródło: NLM (National Library of Medicine)

Składnik aktywny:

SAFINAMIDE MESYLATE (UNII: YS90V3DTX0) (SAFINAMIDE - UNII:90ENL74SIG)

Dostępny od:

MDD US Operations LLC, a subsidiary of Supernus Pharmaceuticals, Inc.

INN (International Nazwa):

safinamide mesylate

Skład:

safinamide 50 mg

Droga podania:

ORAL

Typ recepty:

PRESCRIPTION DRUG

Wskazania:

XADAGO is indicated as adjunctive treatment to levodopa/carbidopa in patients with Parkinson's disease (PD) experiencing "off" episodes. XADAGO is contraindicated in patients with: - Concomitant use of other drugs in the monoamine oxidase inhibitor (MAOI) class or other drugs that are potent inhibitors of monoamine oxidase, including linezolid. The combination may result in increased blood pressure, including hypertensive crisis [see Warnings and Precautions (5.1) and Drug Interactions (7.1)] . - Concomitant use of opioid drugs (e.g., meperidine and its derivatives, methadone, propoxyphene, or tramadol); serotonin-norepinephrine reuptake inhibitors (SNRIs), tricyclic, tetracyclic, or triazolopyridine antidepressants; cyclobenzaprine; methylphenidate, amphetamine, and their derivatives; or St John's wort. Concomitant use could result in life-threatening serotonin syndrome [see Warnings and Precautions (5.2) and Drug Interactions (7.2, 7.3, 7.5)] . - Concomitant use of dextromethorphan. The combination of MAOIs and dextromethorphan has been reported to cause episodes of psychosis or abnormal behavior [see Drug Interactions (7.4)] . - A history of a hypersensitivity to safinamide. Reactions have included swelling of the tongue and oral mucosa, and dyspnea. - Severe hepatic impairment (Child-Pugh C: 10-15) [see Use in Specific Populations (8.6)] . Risk Summary There are no adequate data on the developmental risk associated with the use of XADAGO in pregnant women. In animals, developmental toxicity, including teratogenic effects, was observed when safinamide was administered during pregnancy at clinically relevant doses. Developmental toxicity was observed at doses lower than those used clinically when safinamide was administered during pregnancy in combination with levodopa/carbidopa. The background risk of major birth defects and miscarriage for the indicated population is 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 In an embryofetal development study in rats, oral administration of safinamide (0, 50, 100, or 150 mg/kg/day) throughout organogenesis resulted in dose-related increases in fetal abnormalities (primarily urogenital malformations) at all doses. A no-effect dose for adverse effects on embryofetal development was not established. The lowest dose tested (50 mg/kg/day) is approximately 5 times the maximum recommended human dose (MRHD) of 100 mg on a body surface area (mg/m 2 ) basis. In a combination embryofetal development study of safinamide and levodopa (LD)/carbidopa (CD) in rats (80/20 mg/kg/day LD/CD in combination with 0, 25, 50, or 100 mg/kg/day safinamide or 100 mg/kg/day safinamide alone), increased incidences of fetal visceral and skeletal malformations and variations were observed at all doses of safinamide in combination with CD/LD and with safinamide alone. The lowest dose of safinamide tested (25 mg/kg/day) is approximately 2 times the MRHD on a mg/m 2 basis. In embryofetal development studies in rabbits, no developmental toxicity was observed at up to the highest oral dose of safinamide tested (100 mg/kg/day). However, when safinamide (0, 4, 12, or 40 mg/kg/day) was administered throughout organogenesis in a combination study of safinamide with LD/CD (80/20 mg/kg/day LD/CD), there was an increased incidence of embryofetal death and cardiac and skeletal malformations, compared to LD/CD alone. A no-effect dose for safinamide was not established; the lowest effect dose of safinamide tested (4 mg/kg/day) is less than the MRHD on a mg/m 2 basis. In a rat pre- and postnatal development study, oral administration of safinamide (0, 4, 12.5, or 37.5 mg/kg/day) throughout pregnancy and lactation resulted in skin discoloration of the offspring, presumed to be due to hepatobiliary toxicity, at the mid and high doses and decreased body weight and increased postnatal mortality in offspring at the highest dose tested. The no-effect dose (4 mg/kg/day) for adverse developmental effects is less than the MRHD on a mg/m 2 basis. Risk Summary There is no information regarding the presence of XADAGO or its metabolites in human milk, the effects on the breastfed infant, or the effects on milk production. The developmental and health benefits of breastfeeding should be considered along with the mothers' clinical need for XADAGO and any potential adverse effects on the breastfed infant from XADAGO or from the underlying maternal condition. Data Animal Data Skin discoloration, presumed to be caused by hyperbilirubinemia resulting from hepatobiliary toxicity, was observed in rat pups indirectly exposed to safinamide through the milk during the lactation period. Safety and effectiveness in pediatric patients have not been established. Of the 1516 subjects exposed to XADAGO in clinical studies, 38% were 65 and over, while 4% were 75 and over. No overall differences in safety or effectiveness were observed between these patients and younger patients, and other reported clinical experience has not identified differences in responses between the elderly and younger patients, but greater sensitivity of some older individuals cannot be ruled out. XADAGO plasma concentrations are increased in patients with hepatic impairment [see Clinical Pharmacology (12.3)] . In patients with moderate hepatic impairment (Child-Pugh B: 7-9), the maximum recommended dosage of XADAGO is 50 mg once daily [see Dosage and Administration (2.2)] . XADAGO has not been studied in patients with severe hepatic impairment (Child-Pugh C: 10-15), and is contraindicated in these patients. If patients progress from moderate to severe hepatic impairment, treatment with XADAGO should be stopped.

Podsumowanie produktu:

50 mg (orange to copper colored with metallic gloss, round film-coated, biconcave shaped tablet embossed with "50" on one side; approximately 7 mm in diameter). 100 mg (orange to copper colored with metallic gloss, round film-coated, biconcave shaped tablet embossed with "100" on one side; approximately 9 mm in diameter). Store at 25°C (77°F); excursions permitted between 15°C to 30°C (59°F to 86°F) [see USP controlled room temperature].

Status autoryzacji:

New Drug Application

Charakterystyka produktu

XADAGO- SAFINAMIDE MESYLATE TABLET, FILM COATED
MDD US OPERATIONS LLC, A SUBSIDIARY OF SUPERNUS PHARMACEUTICALS, INC.
----------
HIGHLIGHTS OF PRESCRIBING INFORMATION
THESE HIGHLIGHTS DO NOT INCLUDE ALL THE INFORMATION NEEDED TO USE
XADAGO SAFELY AND
EFFECTIVELY. SEE FULL PRESCRIBING INFORMATION FOR XADAGO
.
XADAGO
(SAFINAMIDE) TABLETS, FOR ORAL USE.
INITIAL U.S. APPROVAL: 2017
INDICATIONS AND USAGE
XADAGO is a monoamine oxidase type B (MAO-B) inhibitor indicated as
adjunctive treatment to
levodopa/carbidopa in patients with Parkinson's disease (PD)
experiencing "off" episodes ( 1)
DOSAGE AND ADMINISTRATION
Start with 50 mg administered orally once daily at the same time of
day; after two weeks, the dose may
be increased to 100 mg once daily, based on individual need and
tolerability ( 2.1)
Hepatic Impairment: Do not exceed 50 mg once daily in patients with
moderate hepatic impairment;
contraindicated in patients with severe hepatic impairment ( 2.2, 4)
DOSAGE FORMS AND STRENGTHS
Tablets: 50 mg and 100 mg ( 3)
CONTRAINDICATIONS
XADAGO is contraindicated in patients with:
Concomitant use of the following drugs:
Other monoamine oxidase inhibitors or other drugs that are potent
inhibitors of monoamine oxidase
(e.g., linezolid) ( 4, 7.1)
Opioid drugs (e.g., tramadol, meperidine and related derivatives);
serotonin-norepinephrine
reuptake inhibitors; tri-or tetra-cyclic or triazolopyridine
antidepressants; cyclobenzaprine;
methylphenidate, amphetamine, and their derivatives; St. John's wort (
4, 7.2, 7.3, 7.5)
Dextromethorphan ( 4, 7.4)
A history of a hypersensitivity to safinamide ( 4)
Severe hepatic impairment (Child-Pugh C: 10-15) ( 4)
WARNINGS AND PRECAUTIONS
May cause or exacerbate hypertension ( 5.1)
May cause serotonin syndrome when used with MAO inhibitors,
antidepressants, or opioid drugs ( 5.2)
May cause falling asleep during activities of daily living ( 5.3)
May cause or exacerbate dyskinesia; consider levodopa dose reduction (
5.4)
May cause hallucinations and psychotic behavior ( 5.5)
May cause problems wi