Dimethyl Fumarate- Tecfifdera- @- (Mar 2013) -Immunomodulator
Drug Name:Dimethyl Fumarate- Tecfifdera- @- (Mar 2013) -Immunomodulator
List Of Brands:
Indication Type Description:
Drug Interaction
Indication
Adverse Reaction
Contra-Indications
Dosages/ Overdosage Etc
Patient Information
Pharmacology/ Pharmacokinetics
Pregnancy and lactation
Drug Interaction:
No potential drug interactions with dimethyl fumarate or MMF were identified in
in vitro CYP inhibition and induction studies, or in P-glycoprotein studies.
Single doses of interferon beta-1a or glatiramer acetate did not alter the
pharmacokinetics of MMF. Aspirin, when administered approximately
30 minutes before TECFIDERA, did not alter the pharmacokinetics of MMF.
Indication:
TECFIDERA® (dimethyl fumarate) delayed-release capsules, for oral use
Initial U.S. Approval: 2013
RECENT MAJOR CHANGES
Warnings and Precautions, PML (5.2) 2/2016
Drug Name- Tecfidera
Active Ingredient - Dimethyl fumarate
To treat adults with relapsing forms of multiple sclerosis (MS)
Indication-
Multiple sclerosis (MS)
Approved by FDA on 27-3-2013 (Ref- FDA Approved List- 2013)
Dimethyl Furoate delayed release 120mg/240mg tablets
Indication
For relapsing remitting multiple sclerosis syndrome
Approved by FDA on 27-08-2014 ( Ref - FDA Approved List -2014)
Adverse Reaction:
Most common adverse reactions (incidence .10% and .2% placebo) were
flushing, abdominal pain, diarrhea, and nausea.
Contra-Indications:
CONTRAINDICATIONS
Known hypersensitivity to dimethyl fumarate or any of the excipients
of TECFIDERA.
WARNINGS AND PRECAUTIONS
.
Anaphylaxis and angioedema: Discontinue and do not restart
TECFIDERA if these occur.
.Progressive multifocal leukoencephalopathy (PML):
Withhold TECFIDERA at the first sign or symptom suggestive of PML.
Lymphopenia: Obtain a CBC including lymphocyte count before initiating
TECFIDERA, after 6 months, and every 6 to 12 months thereafter.
Consider interruption of TECFIDERA if lymphocyte
counts <0.5 x 109/L persist for more than six months.
Dosages/ Overdosage Etc:
Indication
For relapsing remitting multiple sclerosis syndrome
INDICATIONS AND USAGE
TECFIDERA is indicated for the treatment of patients with relapsing forms
of multiple sclerosis
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 TECFIDERA capsules whole and intact. Do not crush, chew,
or sprinkle capsule contents on food
Take TECFIDERA with or without food
DOSAGE FORMS AND STRENGTHS
Delayed-release capsules: 120 mg and 240 mg
Patient Information:
PATIENT COUNSELING INFORMATION
Advise the patient to read the FDA-approved patient labeling (Patient Information)
.Dosage
Inform patients that they will be provided two strengths of TECFIDERA when
starting treatment: 120 mg capsules for the 7 day starter dose and
240 mg capsules for the maintenance dose, both to be taken twice daily.
Inform patients to swallow TECFIDERA capsules whole and intact.
Inform patients to not crush, chew, or sprinkle capsule contents on food.
Inform patients that TECFIDERA can be taken with or without food
.Anaphylaxis and Angioedema
Advise patients to discontinue TECFIDERA and seek medical care if they
develop signs and symptoms of anaphylaxis or angioedema
Progressive Multifocal Leukoencephalopathy
Inform patients that progressive multifocal leukoencephalopathy (PML) has
occurred in patients who received TECFIDERA.
Inform the patient that PML is characterized by a progression of deficits
and usually leads to death or severe disability over weeks or months.
Instruct the patient of the importance of contacting their doctor if they develop
any symptoms suggestive of PML. Inform the patient that typical symptoms
associated with PML are diverse, progress over days to weeks, and include
progressive weakness on one side of the body or clumsiness of limbs,
disturbance of vision, and changes in thinking, memory, and orientation
leading to confusion and personality changes
Lymphocyte Counts
Tecfidera (dimethyl fumerate)
Approved Labeling Text Inform patients that TECFIDERA may decrease
lymphocyte counts. A blood test should be obtained before they start therapy.
Blood tests are also recommended after 6 months of treatment, every
6 to 12 months thereafter, and as clinically indicated .
Flushing and Gastrointestinal (GI) Reactions
Flushing and GI reactions (abdominal pain, diarrhea, and nausea) are the most
common reactions, especially at the initiation of therapy, and may decrease
over time.
Advise patients to contact their healthcare provider if they experience persistent
and/or severe flushing or GI reactions.
Advise patients experiencing flushing that taking TECFIDERA with food or taking
a non-enteric coated aspirin prior to taking TECFIDERA may help
Pregnancy and Pregnancy Registry
Instruct patients that if they are pregnant or plan to become pregnant while
taking TECFIDERA they should inform their physician.
Encourage patients to enroll in the TECFIDERA Pregnancy Registry if they
become pregnant while taking TECFIDERA. Advise patients to call
1-866-810-1462 or visit www.tecfiderapregnancyregistry.com for more
information
Pharmacology/ Pharmacokinetics:
CLINICAL PHARMACOLOGY
1. Mechanism of Action
The mechanism by which dimethyl fumarate (DMF) exerts its therapeutic effect
in multiple sclerosis is unknown. DMF and the metabolite, monomethyl fumarate
(MMF), have been shown to activate the Nuclear factor (erythroid-derived 2)-like
2 (Nrf2) pathway in vitro and in vivo in animals and humans.
The Nrf2 pathway is involved in the cellular response to oxidative stress.
MMF has been identified as a nicotinic acid receptor agonist in vitro.
2 Pharmacokinetics
After oral administration of TECFIDERA, dimethyl fumarate undergoes rapid
presystemic hydrolysis by esterases and is converted to its active metabolite,
monomethyl fumarate (MMF). Dimethyl fumarate is not quantifiable in plasma
following oral administration of TECFIDERA.
Therefore all pharmacokinetic analyses related to TECFIDERA were performed
with plasma MMF concentrations.
Pharmacokinetic data were obtained in subjects with multiple sclerosis and
healthy volunteers
Pregnancy and lactation:
USE IN SPECIFIC POPULATIONS
1. Pregnancy
Pregnancy Category C
There are no adequate and well-controlled studies 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.
TECFIDERA should be used during pregnancy only if the potential benefit justifies
the potential risk to the fetus
2. Nursing Mothers
It is not known whether this drug is excreted in human milk. Because many drugs are
excreted in human milk, caution should be exercised when TECFIDERA
is administered to a nursing woman.
3.Pediatric Use
Safety and effectiveness in pediatric patients have not been established.
4. Geriatric Use
Clinical studies of TECFIDERA did not include sufficient numbers of patients
aged 65 and over to determine whether they respond differently from younger patients.
