Země: Spojené státy
Jazyk: angličtina
Zdroj: NLM (National Library of Medicine)
DIMETHYL FUMARATE (UNII: FO2303MNI2) (MONOMETHYL FUMARATE - UNII:45IUB1PX8R)
Camber Pharmaceuticals, Inc.
ORAL
PRESCRIPTION DRUG
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)]. Risk Summary There are no adequate data on the developmental risk associated with the use of dimethyl fumarate delayed-release capsules in pregnant women. 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] . 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. The background risk of major birth defects and miscarriage for the indicated population is unknown. Data Animal Data In rats administered DMF orally (25, 100, 250 mg/kg/day) throughout organogenesis, embryofetal toxicity (reduced fetal body weight and delayed ossification) were 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. Risk Summary 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.
Dimethyl fumarate is available as hard gelatin delayed-release capsules in two strengths containing either 120 mg or 240 mg of dimethyl fumarate. The 120 mg capsules are light blue opaque size '0' hard gelatin capsules imprinted with 'H' on cap and 'D12' on body filled with white to off white tablets. They are available as follows: 30-day Starter Pack NDC 31722-680-60 7-day bottle 120 mg capsules, quantity 14 23-day bottle 240 mg capsules, quantity 46 120 mg capsules: 7-day bottle of 14 capsules NDC 31722-657-31 Blister Pack of 100 (10x10) unit dose capsules NDC 31722-657-32 The 240 mg capsules are white opaque size '0el' hard gelatin capsules imprinted with 'H' on cap and 'D15' on body filled with white to off white tablets. They are available as follows: 240 mg capsules: 23-day bottle of 46 capsules NDC 31722-658-31 30-day bottle of 60 capsules NDC 31722-658-32 Blister Pack of 100 (10x10) unit dose capsules NDC 31722-658-33 Store at 20° to 25°C (68° to 77°F) [see USP Controlled Room Temperature]. Protect the capsules from light. Store in original container.
Abbreviated New Drug Application
DIMETHYL FUMARATE - DIMETHYL FUMARATE CAPSULE, DELAYED RELEASE DIMETHYL FUMARATE- DIMETHYL FUMARATE CAMBER PHARMACEUTICALS, INC. ---------- 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, Lymphopenia ( 5.4) 02/2023 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 • 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) 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 • 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 first sign or symptom suggestive of PML. ( 5.2) • Herpes Zoster and Other Serious Opportunistic Infections: Consider withholding dimethyl fumarate delayed-release capsules in cases of serious infection until the infection has resolved. ( 5.3) • Lymphopenia: Obtain a CBC including lymp Přečtěte si celý dokument