TECFIDERA dimethyl fumarate 120 mg Capsule, 14-count
🆔 Identity & classification
Where does this data come from?
🏷️ RxNorm drug class
This medicine belongs to the Other immunosuppressants class.
Where does this data come from?
🏭 Manufacturer & labeler
Where does this data come from?
🩺 Clinical
Dimethyl fumarate is used to treat adults with relapsing forms of multiple sclerosis (MS; a disease in which the nerves do not function properly and people may experience weakness, numbness, loss of muscle coordination, and problems with vision, speech, and bladder control) including clinically isolated syndrome (CIS; nerve symptom episodes that last at least 24 hours), relapsing-remitting forms (course of disease where symptoms flare up from time to time), or secondary progressive forms (course of disease where relapses occur more often). Dimethyl fumarate is in a class of medications called...
Read the full MedlinePlus article ↗- Dimethyl fumarate (brand name Tecfidera, also available as a generic) is a prescription medicine for adults with relapsing forms of multiple sclerosis — meaning MS that comes and g...
- What exactly is dimethyl fumarate used for?
- The two most common things people notice early on are flushing — a sensation of warmth, redness, or tingling, usually in the face and chest — and stomach upset like belly pain, nau...
- What side effects should I expect, especially when I first start?
Patient education
Supplement & herbal interactions
Some supplements/herbs that may interact with Dimethyl Fumarate — tap one for details:
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Ask a licensed pharmacist directly — free, answered by our team.
💊 What it looks like
Where does this data come from?
🧪 Inactive Ingredients / Excipients
Inactive ingredients, also called excipients, are components of the drug product other than the active ingredient. They may include fillers, dyes, coatings, preservatives, flavors, or other formulation ingredients.
💡 Tap an ingredient (hover on desktop) to see what it is and why it’s used.
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UNII M28OL1HH48
Croscarmellose sodium is a plant-based substance derived from cellulose. It acts as a disintegrant, helping tablets and capsules break down quickly in the digestive system so the medicine can be absorbed.
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Dimethicone is a silicone-based oil that acts as an anti-foaming agent and lubricant in medicines. It reduces gas bubbles in liquid formulations and helps coat and protect the stomach lining when ingested.
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FD&C Blue No. 1 is a synthetic blue dye approved for use in foods and medicines. It serves as a colorant to give the medication its distinctive appearance and help with product identification.
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Ferric oxide yellow is a naturally occurring iron compound used as a colorant in medications. It gives tablets, capsules, and other forms a yellow or golden hue for identification and appearance.
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UNII XM0M87F357
A dark iron oxide compound that gives medicines their black or dark color. It's used as a colorant in tablets and capsules to help identify the product and make it visually distinctive.
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UNII 2G86QN327L
Gelatin is a protein derived from animal collagen, commonly used in medicines as a gelling agent and capsule material. It helps create soft or hard capsule shells that hold and release medication, and can also thicken liquid formulations.
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UNII 70097M6I30
Magnesium stearate is a salt made from magnesium and stearic acid, a fatty substance. It's used in tablets and capsules as a lubricant and glidant to help ingredients flow smoothly during manufacturing and prevent sticking.
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UNII NX76LV5T8J
A synthetic plastic polymer made from methacrylic acid and ethyl acrylate. It's used as a coating or binder to control how and where the medicine dissolves in your digestive system.
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UNII 74G4R6TH13
A synthetic polymer made by combining two plastic-like chemicals. It forms a coating on tablets or capsules that dissolves at a specific point in the digestive tract, controlling where and when the medicine releases.
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Microcrystalline cellulose is a purified form of cellulose, a natural fiber from plant sources. It acts as a binder and filler in tablets and capsules, helping hold ingredients together and give the medicine its shape and size.
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UNII 6OZP39ZG8H
Polysorbate 80 is a synthetic emulsifier derived from sorbitol and oleic acid. It helps mix oil and water-based ingredients together in medications and improves how the product disperses in the body.
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UNII ETJ7Z6XBU4
Silicon dioxide is a naturally occurring mineral used as a glidant and anti-caking agent. It helps powder ingredients flow smoothly and prevents clumping during manufacturing and storage.
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UNII 368GB5141J
A detergent and foaming agent derived from coconut or palm oil. In medications, it helps break down and mix oil and water-based ingredients, aids in tablet disintegration, and improves how the drug dissolves and spreads in the mouth or digestive system.
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UNII 7SEV7J4R1U
A powder made from a naturally occurring mineral. In medicines, talc works as a glidant and anti-caking agent, helping tablets and capsules flow smoothly during manufacturing and preventing clumping.
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UNII 15FIX9V2JP
Titanium dioxide is a bright white mineral powder commonly used as a colorant and opacifying agent. It makes pills and tablets white or lighter in color and helps make coatings non-transparent.
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UNII 8Z96QXD6UM
Triethyl citrate is a clear liquid derived from citric acid. It acts as a plasticizer and solvent in tablet coatings and film formulations, helping the coating remain flexible and adhere properly to the medicine.
16 inactive ingredients listed in the exact product block matched to this NDC.
Where does this data come from?
ingredient classCode="IACT" elements from the exact product block matched by this NDC. Label-section narrative from DailyMed / the openFDA label index is shown separately when available.Inactive ingredient FAQ
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💲 Pricing
A drug doesn't have one price. Each row is a different public payment system, and none is what you'd pay at the counter — that depends on your insurance. The ⓘ on each row explains what it measures.
| Price system | Per each | Per package |
|---|---|---|
| Retail pharmacies payNADAC · weekly | Not in the retail survey — common for institutional, discontinued, or low-volume packs. | |
| Medicaid paysCMS SDUD · 12 mo | No recent Medicaid claims on file for this NDC — rare and low-volume NDCs are suppressed in the public data. | |
| Medicare drug plans payPart D · Q2 2026 | $174.33 | $2,440.67 / 14 capsules |
Where does this data come from?
🔁 Therapeutic equivalents
| Product | Labeler | Pack | NADAC/unit | TE | Status | Price vs. this |
|---|---|---|---|---|---|---|
| Dimethyl Fumarate 120 mg 31722-0657-31 | Camber | 14 capsules | $0.447 | AB | Availability likely | — |
| Dimethyl Fumarate 120 mg 43547-0024-14 | Solco | 14 capsules | $0.447 | AB | Availability likely | — |
| Dimethyl Fumarate 120 mg 43598-0429-52 | Dr. | 14 capsules | $0.447 | AB | Availability likely | — |
| Dimethyl Fumarate 120 mg 59651-0083-14 | Aurobindo | 14 capsules | $0.447 | AB | Availability likely | — |
| Dimethyl Fumarate 120 mg 69097-0322-89 | Cipla | 14 capsules | $0.447 | — | Availability likely | — |
| Dimethyl Fumarate 120 mg 69238-1318-04 | Amneal | 14 capsules | $0.447 | AB | Availability likely | — |
| Dimethyl Fumarate 120 mg 70512-0852-14 | SOLA | 14 capsules | $0.447 | AB | Availability likely | — |
| Dimethyl fumarate 120 mg 82249-0745-14 | CivicaScript | 14 capsules | $0.447 | AB | Availability likely | — |
| Dimethyl Fumarate 120 mg 16729-0416-04 | Accord | 14 capsules | $0.617 | AB | Availability likely | — |
| dimethyl fumarate 120 mg 24979-0127-02 | Upsher-Smith | 500 capsules | — | AB | FDA listed | — |
| Dimethyl Fumarate 120 mg 33342-0349-09 | Macleods | 60 capsules | — | AB | FDA listed | — |
| dimethyl fumarate 120 mg 51407-0442-14 | Golden | 14 capsules | — | AB | FDA listed | — |
| Tecfidera 120 mgthis 64406-0005-01 | Biogen | 14 capsules | — | AB | FDA listed | — |
| Dimethyl fumarate 120 mg 67877-0555-10 | Ascend | 1000 capsules | — | AB | FDA listed | — |
| Dimethyl Fumarate 120 mg 68462-0307-05 | Glenmark | 500 capsules | — | AB | FDA listed | — |
| Dimethyl Fumarate 120 mg 69539-0042-05 | MSN | 500 capsules | — | AB | FDA listed | — |
| dimethyl fumarate 120 mg 70710-1204-07 | Zydus | 14 capsules | — | — | FDA listed | — |
| dimethyl fumarate 120 mg 70771-1530-07 | Zydus | 14 capsules | — | — | FDA listed | — |
| Dimethyl Fumarate 120 mg 84677-0029-14 | Golden | 14 capsules | — | AB | FDA listed | — |
Where does this data come from?
⏳ Availability & generic status
The FDA lists approved generic versions of this medicine, but that does not always mean a pharmacy can get one today. Patent rules, launch agreements, supply and pricing can affect when generics actually arrive.
Why the date isn’t exact: Generic timing can change because patents may be challenged, settled, licensed, added, removed, or worked around with a narrower label — and FDA approval does not always mean a pharmacy can get the generic today.
🛈 What do these terms mean?
- Patent
- Legal protection listed in the Orange Book that may delay generic approval or launch. Issued by the U.S. Patent & Trademark Office.
- Substance patent
- Covers the active drug molecule itself — the hardest to design around. A generic generally can’t launch until it expires.
- Formulation (product) patent
- Covers a specific formulation or dosage form. A generic can sometimes work around it with a different formulation.
- Method-of-use patent
- A patent covering one specific approved use of the drug — not necessarily the whole molecule. A generic can sometimes launch with a “skinny label” that carves out the protected use and keeps the others.
- Skinny label
- A generic label that omits a still-patented use when the FDA allows it — letting a generic reach the market for the unprotected uses.
- Exclusivity
- FDA-granted marketing protection, separate from patents — e.g. 5-yr new chemical entity, 7-yr orphan drug, or a +6-month pediatric extension.
- Paragraph IV
- A generic applicant’s formal challenge to a listed patent. It can potentially lead to earlier generic entry, but often involves litigation or a settlement.
- RLD / RS
- Reference Listed Drug — the brand product the FDA uses as the reference for generic applications. Reference Standard — the product the FDA expects generics to compare against in bioequivalence testing.
- TE / AB rating
- FDA therapeutic-equivalence rating. An AB rating generally means the FDA considers a generic therapeutically equivalent to — and substitutable for — the brand.
- LOE (loss of exclusivity)
- The latest patent or exclusivity currently listed — the loss-of-exclusivity / latest-listed-protection date shown on this page. Paragraph-IV challenges and settlements can move the real date earlier; FDA approval and a manufacturer’s decision to market can move it later.
Built from the FDA Orange Book. The bars above are scaled to each protection’s expiry; the red LOE marker is the last one to lapse.
| Patent | Type | Use code | Expires |
|---|---|---|---|
| US 8399514 ↗ | Method of use | U-1384 | Feb 7, 2028 |
| US 8399514 ↗ | Method of use | U-1384 | Feb 7, 2028 |
| US 10391160 ↗ | Method of use | U-3148 | Mar 13, 2035 |
| US 10959972 ↗ | Method of use | U-1384 | Nov 16, 2035 |
| US 10391160 ↗ | Method of use | U-3148 | Mar 13, 2035 |
| US 10959972 ↗ | Method of use | U-1384 | Nov 16, 2035 |
| US 10555993 ↗ | Method of use | U-3148 | Mar 13, 2035 |
| US 10555993 ↗ | Method of use | U-3148 | Mar 13, 2035 |
| US 11129806 ↗ | Method of use | U-1384 | Nov 16, 2035 |
| US 11129806 ↗ | Method of use | U-1384 | Nov 16, 2035 |
| US 10994003 ↗ | Method of use | U-3148 | Mar 13, 2035 |
| US 11007166 ↗ | Method of use | U-1384 | Nov 16, 2035 |
| US 11007167 ↗ | Method of use | U-1384 | Nov 16, 2035 |
| US 11007167 ↗ | Method of use | U-1384 | Nov 16, 2035 |
| US 10994003 ↗ | Method of use | U-3148 | Mar 13, 2035 |
| US 11007166 ↗ | Method of use | U-1384 | Nov 16, 2035 |
| US 11246850 ↗ | Method of use | U-1384 | Nov 16, 2035 |
| US 11246850 ↗ | Method of use | U-1384 | Nov 16, 2035 |
Is there a generic version of TECFIDERA DR 120 MG CAPSULE?
The FDA approved a generic — why can’t I get it at my pharmacy yet?
Why do different websites show different generic release dates?
What does “FDA listed” mean?
What does a patent or protection date mean here?
What does “current Orange Book estimate” mean?
Can a generic come out before the last patent expires?
Can a generic come out after the listed dates?
What is the difference between patents and exclusivity?
Why are there multiple patent dates?
Where does this data come from?
📊 Medicare Part D spend CMS · PART D · 2026 (Q1)
🔬 Reported adverse events (FAERS)
Top reported reactions
Age at onset
Reporter sex
Serious outcomes
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📦 Packaging — all sizes for this product
| Package NDC | Description | Marketing start | Status |
|---|---|---|---|
| 64406-0005-01 You're viewing this | 1 BOTTLE, PLASTIC in 1 CARTON (64406-005-01) / 14 CAPSULE in 1 BOTTLE, PLASTIC | 2013-03-27 | Active |
🧭 About this NDC listing & data coverage
What data is (and isn’t) available for this NDC — tap to expand
| NDC identity (package / product / labeler codes) | ✓ Available |
| Labeler | ✓ Available |
| Product & package description | ✓ Available |
| Marketing category & status | ✓ Available |
| Active ingredient / dosage form / route | ✓ Available |
| FDA label (SPL via DailyMed) | ✓ Available |
| Package photos | ✓ Available |
| Inactive ingredients (structured) | ✓ Available |
| NADAC pharmacy acquisition price (CMS) | — Not published for this NDC CMS publishes NADAC only for NDCs reported in its retail-pharmacy survey. |
| Orange Book / therapeutic-equivalence data | ✓ Available |
| HCPCS J-code billing crosswalk | — Not published for this NDC Most self-administered / retail products have no J-code — that is normal. |
| Medicaid utilization (CMS SDUD) | — Not published for this NDC CMS reports utilization only for NDCs with Medicaid claims above its privacy threshold. |
Questions about this listing
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📄 Full prescribing information FDA SPL
🎯 Indications and Usage ▾
1 INDICATIONS AND USAGE TECFIDERA is 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. TECFIDERA is 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 ▾
2 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 ( 2.1 ) Take TECFIDERA with or without food ( 2.1 )
2.1Dosing Information The starting dose for TECFIDERA is 120 mg twice a day orally. After 7 days, the dose should be increased to the maintenance dose of 240 mg twice a day orally. Temporary dose reductions to 120 mg twice a day may be considered for individuals who do not tolerate the maintenance dose.
Within 4 weeks, the recommended dose of 240 mg twice a day should be resumed. Discontinuation of TECFIDERA should be considered for patients unable to tolerate return to the maintenance dose. The incidence of flushing may be reduced by administration of TECFIDERA with food.
Alternatively, administration of non-enteric coated aspirin (up to a dose of 325 mg) 30 minutes prior to TECFIDERA dosing may reduce the incidence or severity of flushing [see Clinical Pharmacology ( 12.3 )] . TECFIDERA should be swallowed whole and intact. TECFIDERA should not be crushed or chewed, and the capsule contents should not be sprinkled on food.
TECFIDERA can be taken with or without food.
2.2Blood Tests Prior to Initiation of Therapy Obtain a complete blood cell count (CBC) including lymphocyte count before initiation of therapy [see Warnings and Precautions ( 5.4 )] . Obtain serum aminotransferase, alkaline phosphatase, and total bilirubin levels prior to treatment with TECFIDERA [see Warnings and Precautions ( 5.5 )] .
💊 Dosage Forms and Strengths ▾
3 DOSAGE FORMS AND STRENGTHS TECFIDERA is available as hard gelatin delayed-release capsules containing 120 mg or 240 mg of dimethyl fumarate. The 120 mg capsules have a green cap and white body, printed with “BG-12 120 mg” in black ink on the body. The 240 mg capsules have a green cap and a green body, printed with “BG-12 240 mg” in black ink on the body. Delayed-release capsules : 120 mg and 240 mg ( 3 )
⛔ Contraindications ▾
4 CONTRAINDICATIONS TECFIDERA is contraindicated in patients with known hypersensitivity to dimethyl fumarate or to any of the excipients of TECFIDERA. Reactions have included anaphylaxis and angioedema [see Warnings and Precautions ( 5.1 )]. Known hypersensitivity to dimethyl fumarate or any of the excipients of TECFIDERA. ( 4 )
⚠️ Warnings and Cautions ▾
5 WARNINGS AND PRECAUTIONS Anaphylaxis and Angioedema: Discontinue and do not restart TECFIDERA if these occur. ( 5.1 ) Progressive Multifocal Leukoencephalopathy (PML): Withhold TECFIDERA at the first sign or symptom suggestive of PML. ( 5.2 ) Herpes Zoster and Other Serious Opportunistic Infections: Consider withholding TECFIDERA in cases of serious infection until the infection has resolved.
( 5.3 ) 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 10 9 /L persist for more than six months. ( 5.4 ) Liver Injury: Obtain serum aminotransferase, alkaline phosphatase, and total bilirubin levels before initiating TECFIDERA and during treatment, as clinically indicated.
Discontinue TECFIDERA if clinically significant liver injury induced by TECFIDERA is suspected. ( 5.5 )
5.1Anaphylaxis and Angioedema TECFIDERA can cause anaphylaxis and angioedema after the first dose or at any time during treatment. Signs and symptoms have included difficulty breathing, urticaria, and swelling of the throat and tongue. Patients should be instructed to discontinue TECFIDERA and seek immediate medical care should they experience signs and symptoms of anaphylaxis or angioedema.
5.2Progressive Multifocal Leukoencephalopathy Progressive multifocal leukoencephalopathy (PML) has occurred in patients with MS treated with TECFIDERA. PML is an opportunistic viral infection of the brain caused by the JC virus (JCV) that typically only occurs in patients who are immunocompromised, and that usually leads to death or severe disability. A fatal case of PML occurred in a patient who received TECFIDERA for 4 years while enrolled in a clinical trial.
During the clinical trial, the patient experienced prolonged lymphopenia (lymphocyte counts predominantly <0.5x10 9 /L for 3.5 years) while taking TECFIDERA [see Warnings and Precautions ( 5.4 )] . The patient had no other identified systemic medical conditions resulting in compromised immune system function and had not previously been treated with natalizumab, which has a known association with PML. The patient was also not taking any immunosuppressive or immunomodulatory medications concomitantly.
PML has also occurred in the postmarketing setting in the presence of lymphopenia (<0.9x10 9 /L). While the role of lymphopenia in these cases is uncertain, the PML cases have occurred predominantly in patients with lymphocyte counts <0.8x10 9 /L persisting for more than 6 months. At the first sign or symptom suggestive of PML, withhold TECFIDERA and perform an appropriate diagnostic evaluation.
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. MRI findings may be apparent before clinical signs or symptoms. Cases of PML, diagnosed based on MRI findings and the detection of JCV DNA in the cerebrospinal fluid in the absence of clinical signs or symptoms specific to PML, have been reported in patients treated with other MS medications associated with PML.
Many of these patients subsequently became symptomatic with PML. Therefore, monitoring with MRI for signs that may be consistent with PML may be useful, and any suspicious findings should lead to further investigation to allow for an early diagnosis of PML, if present. Lower PML-related mortality and morbidity have been reported following discontinuation of another MS medication associated with PML in patients with PML who were initially asymptomatic compared to patients with PML who had characteristic clinical signs and symptoms at diagnosis.
It is not known whether these differences are due to early detection and discontinuation of MS treatment or due to differences in disease in these patients.
5.3 He…
🤒 Adverse Reactions ▾
6 ADVERSE REACTIONS The following important adverse reactions are described elsewhere in labeling: Anaphylaxis and Angioedema [see Warnings and Precautions ( 5.1 )]. Progressive multifocal leukoencephalopathy [see Warnings and Precautions ( 5.2 ) ]. Herpes Zoster and Other Serious Opportunistic Infections [see Warnings and Precautions ( 5.3 )].
Lymphopenia [see Warnings and Precautions ( 5.4 )]. Liver Injury [see Warnings and Precautions ( 5.5 )]. Flushing [see Warnings and Precautions ( 5.6 )].
Serious Gastrointestinal Reactions [see Warnings and Precautions ( 5.7 )] Most common adverse reactions (incidence ≥10% and ≥2% placebo) were flushing, abdominal pain, diarrhea, and nausea. ( 6.1 ) To report SUSPECTED ADVERSE REACTIONS, contact Biogen at 1-800-456-2255 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.
6.1Clinical Trials Experience Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in clinical practice. In placebo-controlled and uncontrolled clinical studies, a total of 2513 patients have received TECFIDERA and been followed for periods up to 13 years with an overall exposure of 11,318 person-years. Approximately 1169 patients have received more than 5 years of treatment with TECFIDERA, and 426 patients have received at least 10 years of treatment with TECFIDERA.
Adverse Reactions in Placebo-Controlled Trials In the two well-controlled studies demonstrating effectiveness, 1529 patients received TECFIDERA with an overall exposure of 2244 person-years [see Clinical Studies ( 14 )]. The adverse reactions presented in the table below are based on safety information from 769 patients treated with TECFIDERA 240 mg twice a day and 771 placebo-treated patients. The most common adverse reactions (incidence ≥10% and ≥2% more than placebo) for TECFIDERA were flushing, abdominal pain, diarrhea, and nausea.
Table 1: Adverse Reactions in Study 1 and 2 reported for TECFIDERA 240 mg BID at ≥ 2% higher incidence than placebo TECFIDERA N=769 % Placebo N=771 % Flushing 40 6 Abdominal pain 18 10 Diarrhea 14 11 Nausea 12 9 Vomiting 9 5 Pruritus 8 4 Rash 8 3 Albumin urine present 6 4 Erythema 5 1 Dyspepsia 5 3 Aspartate aminotransferase increased 4 2 Lymphopenia 2 <1 Gastrointestinal TECFIDERA caused GI events (e.g., nausea, vomiting, diarrhea, abdominal pain, and dyspepsia). The incidence of GI events was higher early in the course of treatment (primarily in month 1) and usually decreased over time in patients treated with TECFIDERA compared with placebo.
Four percent (4%) of patients treated with TECFIDERA and less than 1% of placebo patients discontinued due to gastrointestinal events. The incidence of serious GI events was 1% in clinical trial patients treated with TECFIDERA; these events, none of which were fatal, included vomiting (0.3%) and abdominal pain (0.3%). Hepatic Transaminases An increased incidence of elevations of hepatic transaminases in patients treated with TECFIDERA was seen primarily during the first six months of treatment, and most patients with elevations had levels < 3 times the upper limit of normal (ULN) during controlled trials.
Elevations of alanine aminotransferase and aspartate aminotransferase to ≥ 3 times the ULN occurred in a small number of patients treated with both TECFIDERA and placebo and were balanced between groups. There were no elevations in transaminases ≥ 3 times the ULN with concomitant elevations in total bilirubin > 2 times the ULN. Discontinuations due to elevated hepatic transaminases were < 1% and were similar in patients treated with TECFIDERA or placebo.
Eosinophilia A transient increase in mean eosinophil counts was seen during the first 2 months of therapy.
6.2Postmarketing Experience The following adverse reactions have been identified during post-approval use of TECFIDERA. Because these rea…
👥 Use in Specific Populations ▾
8 USE IN SPECIFIC POPULATIONS
8.1Pregnancy Risk Summary 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.
Data Human Data 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.
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.
8.2Lactation 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 TECFIDERA and any potential adverse effects on the breastfed infant from the drug or from the underlying maternal condition.
8.4Pediatric Use Safety and effectiveness in pediatric patients have not been established.
8.5Geriatric 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.
🤰 Pregnancy ▾
8.1Pregnancy Risk Summary 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.
Data Human Data 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.
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.
🧒 Pediatric Use ▾
8.4Pediatric Use Safety and effectiveness in pediatric patients have not been established.
🧓 Geriatric Use ▾
8.5Geriatric 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.
🧬 Clinical Pharmacology ▾
12 CLINICAL PHARMACOLOGY
12.1Mechanism 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 .
12.2Pharmacodynamics Potential to prolong the QT interval In a placebo controlled thorough QT study performed in healthy subjects, there was no evidence that dimethyl fumarate caused QT interval prolongation of clinical significance (i.e., the upper bound of the 90% confidence interval for the largest placebo-adjusted, baseline-corrected QTc was below 10 ms).
12.3Pharmacokinetics 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. Absorption The median T max of MMF is 2-2.5 hours. The peak plasma concentration (C max ) and overall exposure (AUC) increased approximately dose proportionally in the dose range studied (120 mg to 360 mg).
Following administration of TECFIDERA 240 mg twice a day with food, the mean C max of MMF was 1.87 mg/L and AUC was 8.21 mg.hr/L in MS patients. A high-fat, high-calorie meal did not affect the AUC of MMF but decreased its C max by 40%. The T max was delayed from 2.0 hours to 5.5 hours.
In this study, the incidence of flushing was reduced by approximately 25% in the fed state. Distribution The apparent volume of distribution of MMF varies between 53 and 73 L in healthy subjects. Human plasma protein binding of MMF is 27-45% and independent of concentration.
Metabolism In humans, dimethyl fumarate is extensively metabolized by esterases, which are ubiquitous in the gastrointestinal tract, blood, and tissues, before it reaches the systemic circulation. Further metabolism of MMF occurs through the tricarboxylic acid (TCA) cycle, with no involvement of the cytochrome P450 (CYP) system. MMF, fumaric and citric acid, and glucose are the major metabolites in plasma.
Elimination Exhalation of CO 2 is the primary route of elimination, accounting for approximately 60% of the TECFIDERA dose. Renal and fecal elimination are minor routes of elimination, accounting for 16% and 1% of the dose respectively. Trace amounts of unchanged MMF were present in urine.
The terminal half-life of MMF is approximately 1 hour and no circulating MMF is present at 24 hours in the majority of individuals. Accumulation of MMF does not occur with multiple doses of TECFIDERA. Specific Populations Body weight, gender, and age do not require dosage adjustment.
No studies have been conducted in subjects with hepatic or renal impairment. However, neither condition would be expected to affect exposure to MMF and therefore no dosage adjustment is necessary. Drug Interaction Studies 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. Oral Contraceptives The coadministration of dimethyl fumarate with a combined oral contraceptive (norelgestromin and ethinyl estradiol) did not elicit any relevant effects in oral contraceptives exposure.
No interaction studies have been performed with oral contraceptives containing other progesto…
🧬 Mechanism of Action ▾
12.1Mechanism 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 .
📦 How Supplied / Storage and Handling ▾
16 HOW SUPPLIED/STORAGE AND HANDLING TECFIDERA is available as hard gelatin delayed-release capsules in two strengths containing either 120 mg or 240 mg of dimethyl fumarate. The green and white 120 mg capsules are printed with “BG-12 120 mg” in black ink. The green 240 mg capsules are printed with “BG-12 240 mg” in black ink.
TECFIDERA is available as follows: 30-day Starter Pack, (NDC 64406-007-03): 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 64406-005-01) 240 mg capsules: 30-day bottle of 60 capsules (NDC 64406-006-02) Store at 15°C to 30°C (59 to 86°F). Protect the capsules from light. Store in original container.
📋 Description ▾
11 DESCRIPTION TECFIDERA contains dimethyl fumarate which is also known by its chemical name, dimethyl (E) butenedioate, (C 6 H 8 O 4 ). It has the following structure: Dimethyl fumarate is a white to off-white powder that is highly soluble in water with a molecular mass of 144.13. TECFIDERA is provided as hard gelatin delayed-release capsules for oral administration, containing 120 mg or 240 mg of dimethyl fumarate consisting of the following inactive ingredients: microcrystalline cellulose, silicified microcrystalline cellulose, croscarmellose sodium, talc, silica colloidal silicon dioxide, magnesium stearate, triethyl citrate, methacrylic acid copolymer - Type A, methacrylic acid copolymer dispersion, simethicone (30% emulsion), sodium lauryl sulphate, and polysorbate 80.
The capsule shell, printed with black ink, contains the following inactive ingredients: gelatin, titanium dioxide, FD&C blue 1; brilliant blue FCF, yellow iron oxide and black iron oxide. Structural Formula
💬 Information for Patients ▾
17 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 [see Dosage and Administration ( 2.1 )]. Anaphylaxis and Angioedema Advise patients to discontinue TECFIDERA and seek medical care if they develop signs and symptoms of anaphylaxis or angioedema [see Warnings and Precautions ( 5.1 )].
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 [see Warnings and Precautions ( 5.2 )] . Herpes Zoster and Other Serious Opportunistic Infections Inform patients that herpes zoster and other serious opportunistic infections have occurred in patients who received TECFIDERA.
Instruct the patient of the importance of contacting their doctor if they develop any signs or symptoms associated with herpes zoster or other serious opportunistic infections [see Warnings and Precautions ( 5.3 )]. Lymphocyte Counts 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 [see Warnings and Precautions ( 5.3 ), Adverse Reactions ( 6.1 )] . Liver Injury Inform patients that TECFIDERA may cause liver injury. Instruct patients treated with TECFIDERA to report promptly any symptoms that may indicate liver injury, including fatigue, anorexia, right upper abdominal discomfort, dark urine, or jaundice.
A blood test should be obtained before patients start therapy and during treatment, as clinically indicated [see Warnings and Precautions ( 5.4 )] . Flushing Inform patients that flushing is one of 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.
Advise patients experiencing flushing that taking TECFIDERA with food or taking a non-enteric coated aspirin prior to taking TECFIDERA may help [see Adverse Reactions ( 6.1 )]. Gastrointestinal (GI) Events Inform patients that GI events (abdominal pain, diarrhea, and nausea) are some of the most common adverse reactions, especially at the initiation of therapy, and may decrease over time. Some patients may experience more severe GI events.
Advise patients to immediately contact their healthcare provider and discontinue TECFIDERA if they experience gastrointestinal bleeding (e.g., rectal bleeding, bloody diarrhea, hematemesis) or other serious gastrointestinal adverse events (e.g., severe abdominal pain, severe vomiting and/or diarrhea) [see Warnings and Precautions ( 5.7 )] . PPI-41347-18 Manufactured for: Biogen Inc. Cambridge, MA 02142 TECFIDERA is a registered trademark of Biogen. © Biogen 2013 - 2024