DIMETHYL FUMARATE capsule, delayed release

Land: Verenigde Staten

Taal: Engels

Bron: NLM (National Library of Medicine)

Werkstoffen:

DIMETHYL FUMARATE (UNII: FO2303MNI2) (MONOMETHYL FUMARATE - UNII:45IUB1PX8R)

Beschikbaar vanaf:

Mylan Pharmaceuticals Inc.

Toedieningsweg:

ORAL

Prescription-type:

PRESCRIPTION DRUG

therapeutische indicaties:

Dimethyl fumarate delayed-release capsules are indicated for the treatment of relapsing forms of multiple sclerosis (MS), to include clinically isolated syndrome, relapsing-remitting disease, and active secondary progressive disease, in adults. Dimethyl fumarate delayed-release capsules are contraindicated in patients with known hypersensitivity to dimethyl fumarate or to any of the excipients of dimethyl fumarate delayed-release capsules. Reactions have included anaphylaxis and angioedema [see Warnings and Precautions (5.1)]. Available data from the TECFIDERA® Pregnancy Registry, observational studies, and pharmacovigilance with dimethyl fumarate use in pregnant women have not indicated an increased risk of major birth defects, miscarriage, or other adverse maternal or fetal outcomes. Most of the reported exposures to dimethyl fumarate occurred during the first trimester of pregnancy (see Data) . In animals, adverse effects on offspring survival, growth, sexual maturation, and neurobehavioral function were observed when dimethyl fumarate (DMF) was administered during pregnancy and lactation at clinically relevant doses (see Data) . The 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 2-4% and 15-20%, respectively. In a prospective observational TECFIDERA Pregnancy Registry (2013-2022), the rate of major birth defects among 362 live births and stillbirths from women who were exposed to dimethyl fumarate during pregnancy was 3.6% (95% CI: 1.9-6.1). No specific pattern of major birth defects was identified. Important potential study limitations include exposure misclassification, no adjustment for confounders, and lack of an internal comparator cohort. In rats administered DMF orally (25, 100, 250 mg/kg/day) throughout organogenesis, embryofetal toxicity (reduced fetal body weight and delayed ossification) was observed at the highest dose tested. This dose also produced evidence of maternal toxicity (reduced body weight). Plasma exposure (AUC) for monomethyl fumarate (MMF), the major circulating metabolite, at the no-effect dose is approximately three times that in humans at the recommended human dose (RHD) of 480 mg/day. In rabbits administered DMF orally (25, 75, and 150 mg/kg/day) throughout organogenesis, embryolethality and decreased maternal body weight were observed at the highest dose tested. The plasma AUC for MMF at the no-effect dose is approximately 5 times that in humans at the RHD. Oral administration of DMF (25, 100, and 250 mg/kg/day) to rats throughout organogenesis and lactation resulted in increased lethality, persistent reductions in body weight, delayed sexual maturation (male and female pups), and reduced testicular weight at the highest dose tested. Neurobehavioral impairment was observed at all doses. A no-effect dose for developmental toxicity was not identified. The lowest dose tested was associated with plasma AUC for MMF lower than that in humans at the RHD. There are no data on the presence of DMF or MMF in human milk. The effects on the breastfed infant and on milk production are unknown. The developmental and health benefits of breastfeeding should be considered along with the mother’s clinical need for dimethyl fumarate delayed-release capsules and any potential adverse effects on the breastfed infant from the drug or from the underlying maternal condition. Safety and effectiveness in pediatric patients have not been established. Clinical studies of dimethyl fumarate delayed-release capsules did not include sufficient numbers of patients aged 65 and over to determine whether they respond differently from younger patients.

Product samenvatting:

Dimethyl Fumarate Delayed-Release Capsules, USP are available containing 120 mg or 240 mg of dimethyl fumarate, USP. The 120 mg capsules are hard-shell gelatin capsules with a blue-green opaque cap and a white opaque body filled with white to off-white enteric coated pellets with no markings. The capsules are axially printed with MYLAN over DF 120 in black ink on both the cap and body. They are available as follows: NDC 0378-0396-14 bottles of 14 capsules The 240 mg capsules are hard-shell gelatin capsules with a blue-green opaque cap and a blue-green opaque body filled with white to off-white enteric coated pellets with no markings. The capsules are axially printed with MYLAN over DF 240 in black ink on both the cap and body. They are available as follows: NDC 0378-0399-91 bottles of 60 capsules Store at 20° to 25°C (68° to 77°F). [See USP Controlled Room Temperature.] Protect the capsules from light. Store in original container.

Autorisatie-status:

Abbreviated New Drug Application

Productkenmerken

DIMETHYL FUMARATE- DIMETHYL FUMARATE CAPSULE, DELAYED RELEASE
MYLAN PHARMACEUTICALS INC.
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HIGHLIGHTS OF PRESCRIBING INFORMATION
THESE HIGHLIGHTS DO NOT INCLUDE ALL THE INFORMATION NEEDED TO USE
DIMETHYL FUMARATE
DELAYED-RELEASE CAPSULES SAFELY AND EFFECTIVELY. SEE FULL PRESCRIBING
INFORMATION FOR
DIMETHYL FUMARATE DELAYED-RELEASE CAPSULES.
DIMETHYL FUMARATE DELAYED-RELEASE CAPSULES, FOR ORAL USE
INITIAL U.S. APPROVAL: 2013
RECENT MAJOR CHANGES
Warnings and Precautions, Serious Gastrointestinal Reactions (5.7)
12/2023
INDICATIONS AND USAGE
Dimethyl fumarate delayed-release capsules are indicated for the
treatment of relapsing forms of multiple
sclerosis (MS), to include clinically isolated syndrome,
relapsing-remitting disease, and active secondary
progressive disease, in adults. (1)
DOSAGE AND ADMINISTRATION
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•
•
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DOSAGE FORMS AND STRENGTHS
_Delayed-release capsules:_ 120 mg and 240 mg (3)
CONTRAINDICATIONS
Known hypersensitivity to dimethyl fumarate or any of the excipients
of dimethyl fumarate delayed-release
capsules. (4)
WARNINGS AND PRECAUTIONS
•
•
•
•
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ADVERSE REACTIONS
Most common adverse reactions (incidence ≥ 10% and ≥ 2% placebo)
were flushing, abdominal pain,
diarrhea, and nausea. (6.1)
TO REPORT SUSPECTED ADVERSE REACTIONS, CONTACT MYLAN AT 1-877-446-3679
(1-877-4-INFO-
RX) OR FDA AT 1-800-FDA-1088 OR WWW.FDA.GOV/MEDWATCH.
SEE 17 FOR PATIENT COUNSELING INFORMATION AND FDA-APPROVED PATIENT
LABELING.
REVISED: 3/2024
Starting dose: 120 mg twice a day, orally, for 7 days (2.1)
Maintenance dose after 7 days: 240 mg twice a day, orally (2.1)
Swallow dimethyl fumarate delayed-release capsules whole and intact.
Do not crush, chew, or sprinkle
capsule contents on food (2.1)
Take dimethyl fumarate delayed-release capsules with or without food
(2.1)
Anaphylaxis and Angioedema: Discontinue and do not restart dimethyl
fumarate delayed-release
capsules if these occur. (5.1)
Progressive Multifocal Leukoencephalopathy (PML): Withhold dimethyl
fumarate delayed-release
capsules at the