Dimethyl Fumarate Teva GmbH: Uses, Dosage & Side Effects

What Is Dimethyl Fumarate Teva GmbH and What Is It Used For?

Dimethyl Fumarate Teva GmbH contains the active substance dimethyl fumarate (DMF), a methyl ester of fumaric acid that belongs to the class of immunomodulatory agents. It is a generic version of the originator product Tecfidera, which was first approved by the European Medicines Agency (EMA) in 2014 and by the U.S. Food and Drug Administration (FDA) in 2013. As a generic medicine, Dimethyl Fumarate Teva GmbH has demonstrated bioequivalence to the originator, meaning it produces the same blood levels and therapeutic effects while meeting identical standards for pharmaceutical quality, safety, and efficacy.

Multiple sclerosis is a chronic, immune-mediated inflammatory and neurodegenerative disease of the central nervous system (CNS) that affects approximately 2.8 million people worldwide according to the Multiple Sclerosis International Federation. In MS, the immune system mistakenly attacks the protective myelin sheath surrounding nerve fibers in the brain and spinal cord, leading to inflammation, demyelination, axonal damage, and ultimately neuronal loss. Relapsing-remitting MS (RRMS) is the most common form, affecting approximately 85% of newly diagnosed patients. RRMS is characterized by clearly defined episodes of new or worsening neurological symptoms (relapses) followed by periods of partial or complete recovery (remissions).

Once ingested, dimethyl fumarate undergoes rapid presystemic hydrolysis by esterases in the gastrointestinal tract, blood, and tissues to form its primary active metabolite, monomethyl fumarate (MMF). The therapeutic mechanism of dimethyl fumarate in MS is multifaceted and not completely elucidated, but it is primarily attributed to activation of the nuclear factor (erythroid-derived 2)-like 2 (Nrf2) antioxidant response pathway. Under normal conditions, Nrf2 is sequestered in the cytoplasm by its inhibitor Keap1. Monomethyl fumarate modifies cysteine residues on Keap1, releasing Nrf2 to translocate to the nucleus where it binds to antioxidant response elements (AREs) and upregulates the expression of numerous cytoprotective and antioxidant genes, including heme oxygenase-1 (HO-1), NAD(P)H quinone dehydrogenase 1 (NQO1), and glutathione S-transferases. This enhanced antioxidant defense protects oligodendrocytes, neurons, and astrocytes from oxidative stress—a major contributor to neurodegeneration in MS.

Beyond neuroprotection, dimethyl fumarate exerts significant immunomodulatory effects. It promotes a shift in T-helper cell responses from pro-inflammatory Th1 and Th17 phenotypes toward anti-inflammatory Th2 profiles. This is mediated in part through activation of the hydroxycarboxylic acid receptor 2 (HCAR2, also known as GPR109A) on immune cells, leading to reduced production of pro-inflammatory cytokines including interferon-gamma (IFN-γ), interleukin-17 (IL-17), and tumor necrosis factor-alpha (TNF-α). Additionally, DMF promotes apoptosis of activated T cells, reduces dendritic cell maturation, and decreases the expression of adhesion molecules and chemokines that facilitate immune cell migration across the blood-brain barrier into the CNS. These combined effects result in reduced inflammatory infiltration and demyelination in the brain and spinal cord.

The clinical efficacy of dimethyl fumarate was established in two pivotal phase III, randomized, double-blind, placebo-controlled trials in patients with RRMS:

• DEFINE (Determination of the Efficacy and Safety of Oral Fumarate in Relapsing-Remitting MS): This trial enrolled 1,234 patients and demonstrated that dimethyl fumarate 240 mg twice daily reduced the annualized relapse rate by 53% compared to placebo over 2 years (p < 0.001). The proportion of patients who relapsed was reduced by 49%, and the risk of 12-week confirmed disability progression was reduced by 38% (p = 0.005). MRI outcomes showed an 85% reduction in the mean number of new or newly enlarging T2 hyperintense lesions and a 90% reduction in gadolinium-enhancing lesions.
• CONFIRM (Comparator and an Oral Fumarate in Relapsing-Remitting Multiple Sclerosis): This trial enrolled 1,430 patients and included an open-label glatiramer acetate comparator arm. Dimethyl fumarate 240 mg twice daily reduced the annualized relapse rate by 44% compared to placebo (p < 0.001). The drug also significantly reduced MRI-detected lesion activity, with a 71% reduction in new or newly enlarging T2 lesions and a 74% reduction in gadolinium-enhancing lesions compared to placebo.

Long-term extension studies (ENDORSE) have demonstrated sustained efficacy and a consistent safety profile for up to 13 years of continuous treatment with dimethyl fumarate. The benefits observed in the original trials were maintained over the long term, with patients showing continued low relapse rates, stable disability scores, and reduced brain volume loss. These data have positioned dimethyl fumarate as one of the most widely prescribed first-line oral disease-modifying therapies for RRMS globally, recommended by both the American Academy of Neurology (AAN) and the European Committee for Treatment and Research in Multiple Sclerosis (ECTRIMS) in their treatment guidelines.

What Should You Know Before Taking Dimethyl Fumarate Teva GmbH?

Contraindications

Dimethyl Fumarate Teva GmbH must not be used in patients with known hypersensitivity to dimethyl fumarate or to any of the excipients in the formulation. There have been reports of serious allergic reactions including anaphylaxis and angioedema in patients treated with dimethyl fumarate. If a serious allergic reaction occurs, treatment must be discontinued immediately and not restarted. Patients with a history of hypersensitivity to other fumaric acid esters (such as those used in dermatological treatments for psoriasis) should exercise caution and discuss their history with their neurologist before initiating treatment.

Dimethyl fumarate should not be initiated in patients with severe active gastrointestinal disease, as the drug may exacerbate pre-existing gastrointestinal conditions. Patients with a history of severe gastrointestinal ulceration, perforation, or obstruction should undergo careful evaluation before treatment is considered. Additionally, treatment should generally not be started in patients with severe, pre-existing lymphopenia (lymphocyte counts below 0.5 × 10⁹/L), as further reductions could increase the risk of opportunistic infections.

Warnings and Precautions

Progressive Multifocal Leukoencephalopathy (PML): Cases of PML, a rare but serious and potentially fatal brain infection caused by the John Cunningham (JC) virus, have been reported in patients treated with dimethyl fumarate, primarily in those with prolonged moderate-to-severe lymphopenia (lymphocyte counts below 0.5 × 10⁹/L persisting for more than 6 months). A complete blood count (CBC) including lymphocyte count must be obtained before starting treatment, at 6 months, every 6–12 months thereafter, and as clinically indicated. If lymphocyte counts fall below 0.5 × 10⁹/L and persist at this level for more than 6 months, treatment discontinuation should be strongly considered. If PML is suspected, dimethyl fumarate must be withheld immediately and appropriate diagnostic evaluation (including MRI and cerebrospinal fluid analysis for JC virus DNA) must be performed.

Lymphocyte Counts: Dimethyl fumarate causes a mean decrease in lymphocyte counts of approximately 30% during the first year of treatment, after which levels typically stabilize. Approximately 2–6% of patients may develop severe, prolonged lymphopenia (Grade 3 or below 0.5 × 10⁹/L). The clinical significance of this reduction relates to the potential for increased susceptibility to infections, including opportunistic infections. Patients should be monitored for signs and symptoms of infection, and treatment should be interrupted in patients who develop a serious infection until the infection has resolved.

Flushing: Flushing is one of the most common adverse reactions to dimethyl fumarate and affects approximately 34–40% of patients. Flushing typically presents as warmth, redness, itching, or a burning sensation of the skin, predominantly of the face and upper body. It usually begins within 30 minutes of dosing and can last from minutes to hours. The mechanism appears to involve prostaglandin-mediated vasodilation through activation of HCAR2 receptors. Flushing tends to diminish significantly over the first month of treatment. Temporary administration of aspirin (up to 325 mg) taken 30 minutes before dosing may reduce the incidence and severity of flushing. Taking dimethyl fumarate with food also helps reduce flushing.

Hepatotoxicity: Clinically significant cases of liver injury have been reported with dimethyl fumarate, including elevated serum aminotransferase levels exceeding 5 times the upper limit of normal (ULN). These events typically occurred within the first 6 months of treatment and resolved after discontinuation. Liver function tests (serum aminotransferases and total bilirubin) should be obtained before treatment initiation and during treatment as clinically indicated.

Pregnancy and Breastfeeding

There are limited data on the use of dimethyl fumarate in pregnant women. Animal reproduction studies at high doses have shown adverse effects on embryo-fetal development, including reduced fetal weight and skeletal variations in rats and rabbits. Based on the available preclinical data, dimethyl fumarate should not be used during pregnancy unless clearly necessary and only if the potential benefit justifies the potential risk to the fetus. Women of childbearing potential should use effective contraception during treatment and should discuss family planning with their neurologist before starting therapy.

It is not known whether dimethyl fumarate or its metabolites are excreted in human breast milk. Animal studies have shown that monomethyl fumarate is present in the milk of lactating rats. A decision must be made whether to discontinue breastfeeding or to discontinue dimethyl fumarate therapy, taking into account the benefit of breastfeeding for the child and the benefit of therapy for the woman. Current guidelines from most neurological societies recommend against breastfeeding while on dimethyl fumarate treatment, although evolving data are being reviewed.

Fertility: No data from human studies on the effects of dimethyl fumarate on fertility are available. In animal studies, no adverse effects on fertility were observed at clinically relevant doses. However, patients who are planning to conceive should discuss the timing of treatment discontinuation with their neurologist, as the drug has a relatively short half-life and washout period compared to other MS therapies.

How Does Dimethyl Fumarate Teva GmbH Interact with Other Drugs?

The pharmacokinetic profile of dimethyl fumarate is favorable in terms of drug interactions. After oral administration, DMF is rapidly hydrolyzed to its active metabolite monomethyl fumarate (MMF), which is then further metabolized via the tricarboxylic acid (TCA) cycle to carbon dioxide and water. Crucially, this metabolic pathway does not involve the cytochrome P450 (CYP) enzyme system, and MMF does not inhibit or induce CYP enzymes at therapeutically relevant concentrations. As a result, dimethyl fumarate is not expected to affect the pharmacokinetics of medications metabolized by CYP enzymes. In vitro studies have also confirmed that MMF is not a significant substrate for, or inhibitor of, the major drug transporters (P-glycoprotein, BCRP, OAT1, OAT3, OCT1, OCT2, OATP1B1, OATP1B3).

Despite the low potential for pharmacokinetic interactions, several clinically important pharmacodynamic interactions should be considered when prescribing dimethyl fumarate. The most significant of these involves concurrent use with other immunosuppressive or immunomodulatory agents. Because dimethyl fumarate reduces lymphocyte counts and modulates immune function, combining it with other treatments that affect the immune system could lead to additive immunosuppression and an increased risk of infections, including opportunistic infections.

Major Interactions

Minor Interactions

When switching from another disease-modifying therapy to dimethyl fumarate, an adequate washout period must be observed to allow for immune system recovery before initiating the new treatment. The duration of the washout period depends on the previous therapy: for natalizumab, a washout of at least 2–3 months is recommended; for fingolimod, at least 1–2 months to allow lymphocyte recovery; and for anti-CD20 antibodies, at least 6 months or until B-cell repopulation is confirmed. During the transition period, a current CBC should be obtained to confirm that lymphocyte counts are within an acceptable range before starting dimethyl fumarate.

Patients should inform their healthcare provider about all medications they are taking, including over-the-counter drugs and herbal supplements. While dimethyl fumarate has a low pharmacokinetic interaction potential, the immunomodulatory effects of the drug require careful consideration when co-prescribing any agent that may affect immune function. Vaccination status should be reviewed before starting treatment, and all necessary vaccinations—particularly live vaccines—should be completed before therapy initiation whenever possible.

What Is the Correct Dosage of Dimethyl Fumarate Teva GmbH?

Adults

Food has a significant impact on tolerability. Taking dimethyl fumarate with a meal or substantial snack reduces the peak plasma concentration (C_max) of monomethyl fumarate by approximately 40%, which correlates with a meaningful reduction in flushing severity and gastrointestinal symptoms. The overall extent of absorption (AUC) is not significantly affected by food, so there is no reduction in therapeutic efficacy when taken with meals. Patients should be counseled to take each dose with food consistently throughout their treatment.

Temporary dose reductions back to 120 mg twice daily may be considered to manage gastrointestinal adverse effects or flushing during the early weeks of treatment. However, the full maintenance dose of 240 mg twice daily should be resumed within 4 weeks, as the long-term efficacy data are based on the 240 mg twice-daily regimen. If a patient cannot tolerate the maintenance dose after several attempts at dose titration, an alternative disease-modifying therapy should be considered.

Children

Dimethyl Fumarate Teva GmbH is not approved for use in children and adolescents under 18 years of age. The safety and efficacy of dimethyl fumarate in the pediatric population have not been established in controlled clinical trials. While there is some emerging observational data suggesting that dimethyl fumarate may be used off-label in adolescents with RRMS, dosing recommendations for this age group have not been formally established by regulatory authorities. Any use in pediatric patients should only be considered under the supervision of a specialist experienced in pediatric MS treatment.

Elderly

Clinical trials of dimethyl fumarate included a limited number of patients aged 55 years and older, and very few patients over 65 years. No dosage adjustment is recommended based on age alone. However, age-related changes in renal and hepatic function should be taken into account, and more frequent monitoring of complete blood counts and renal and liver function may be appropriate in older patients. Elderly patients may also be more susceptible to infections due to age-related immune senescence, which could be compounded by the lymphocyte-lowering effects of dimethyl fumarate.

Missed Dose

If a dose of dimethyl fumarate is missed, the patient should take the next dose as scheduled. A double dose should not be taken to make up for the missed dose. Since dimethyl fumarate has a short half-life (approximately 1 hour for the active metabolite MMF), missing a single dose is unlikely to have a significant impact on the overall therapeutic effect, provided that adherence is maintained over time. However, consistent adherence to the twice-daily dosing schedule is important for maintaining optimal therapeutic benefit and steady-state drug levels.

Overdose

There is limited experience with overdose of dimethyl fumarate. In clinical studies, doses up to 720 mg three times daily (approximately 4.5 times the recommended daily dose) have been administered without serious acute adverse events. The most likely symptoms of overdose would be an exaggeration of the known adverse effects, particularly severe flushing, gastrointestinal disturbance (nausea, vomiting, diarrhea, abdominal pain), and potentially more pronounced lymphopenia. There is no specific antidote for dimethyl fumarate overdose. Treatment should be symptomatic and supportive. Given the rapid metabolism and short half-life of the drug, symptoms of overdose would be expected to resolve relatively quickly. Hemodialysis is unlikely to be effective in removing dimethyl fumarate or MMF from the circulation due to their rapid metabolism.

What Are the Side Effects of Dimethyl Fumarate Teva GmbH?

Dimethyl fumarate has been extensively studied in clinical trials involving more than 2,600 patients and in post-marketing surveillance over more than a decade of clinical use. The safety profile is well characterized, with the most frequent adverse reactions being flushing and gastrointestinal events. These are generally mild to moderate in severity and tend to decrease substantially during the first month of treatment. Approximately 3% of patients in clinical trials discontinued treatment due to flushing and approximately 4% due to gastrointestinal adverse events.

The side effects of dimethyl fumarate are categorized below by frequency according to the internationally recognized MedDRA convention. Understanding these frequencies helps patients and clinicians put the likelihood of each adverse event into proper perspective:

The flushing associated with dimethyl fumarate deserves special attention, as it is the most distinctive side effect and the leading reason patients seek management strategies. Flushing typically begins within 30 minutes of taking the capsule and may last from a few minutes to several hours. It presents as warmth, redness, itching, or a burning sensation, predominantly affecting the face, neck, chest, and upper extremities. The mechanism involves activation of HCAR2 (also known as the niacin receptor or GPR109A) on Langerhans cells and keratinocytes in the skin, leading to prostaglandin D2 release and subsequent vasodilation. Several strategies can help manage flushing: taking the medication with food (particularly a meal containing fat and protein), pre-treatment with non-enteric-coated aspirin 325 mg taken 30 minutes before dosing, gradual dose escalation, and timing the dose during periods of lower physical activity.

Gastrointestinal side effects (nausea, diarrhea, abdominal pain, vomiting) are the second most common category of adverse reactions. Like flushing, these symptoms are most prominent during the first month of treatment and typically diminish significantly over time. The gastro-resistant capsule formulation is designed to delay dissolution and reduce direct gastric irritation, but some patients may still experience significant GI symptoms. Strategies to manage gastrointestinal side effects include always taking the capsule with food, starting with the lower 120 mg dose for the first week, and, if needed, temporary dose reduction back to 120 mg twice daily for an additional period before re-escalating to the maintenance dose.

If you experience any side effects that concern you, or if symptoms persist or worsen, contact your healthcare provider. Report any signs of infection (fever, persistent cough, night sweats), unexplained neurological symptoms (changes in vision, confusion, speech difficulties, weakness), or signs of liver problems (yellowing of the skin or eyes, dark urine, right upper abdominal pain) immediately.

How Should You Store Dimethyl Fumarate Teva GmbH?

Proper storage of Dimethyl Fumarate Teva GmbH is essential to maintain the drug’s stability, potency, and safety throughout its shelf life. The gastro-resistant hard capsules should be stored at temperatures not exceeding 30°C (86°F). The medication should be kept in its original blister packaging until the time of use to protect the capsules from moisture and light, both of which can degrade the active ingredient and compromise the integrity of the gastro-resistant coating.

Do not transfer the capsules to pill organizers, weekly dosette boxes, or other containers unless they are used within a short period, as prolonged exposure to ambient humidity and light may affect capsule quality. Do not store the medication in the bathroom or near sources of heat or moisture. The capsules should not be refrigerated or frozen, as extreme temperatures may damage the gastro-resistant coating.

Check the expiry date on the blister pack and outer carton before each use. Do not use Dimethyl Fumarate Teva GmbH after the expiry date, which refers to the last day of the stated month. Medicines should not be disposed of via wastewater or household waste. Ask your pharmacist how to dispose of medicines you no longer use, in accordance with local regulations for pharmaceutical waste. This helps protect the environment.

Keep Dimethyl Fumarate Teva GmbH out of the sight and reach of children. If a child accidentally ingests the medication, seek immediate medical attention and bring the medication packaging for identification.

What Does Dimethyl Fumarate Teva GmbH Contain?

Active substance: Dimethyl fumarate. Each gastro-resistant hard capsule contains either 120 mg or 240 mg of dimethyl fumarate. Dimethyl fumarate is a dimethyl ester of fumaric acid with the molecular formula C₆H₈O₄ and a molecular weight of 144.13 g/mol. It appears as a white to off-white crystalline powder.

Excipients: The inactive ingredients in Dimethyl Fumarate Teva GmbH capsules serve important functions in maintaining drug stability, controlling release, and ensuring the gastro-resistant properties of the formulation. The gastro-resistant coating is critical for protecting the active ingredient through the acidic environment of the stomach and allowing release in the more alkaline environment of the small intestine, which reduces direct gastric irritation and improves tolerability.

Typical excipients in dimethyl fumarate gastro-resistant capsules include:

• Capsule fill: Microcrystalline cellulose, croscarmellose sodium, talc, silica colloidal anhydrous, magnesium stearate, and methacrylic acid-ethyl acrylate copolymer (as the enteric coating of the microtablets or pellets within the capsule).
• Capsule shell: Hypromellose, titanium dioxide (E171), and various iron oxide colorants. The 120 mg capsule is typically green and white, while the 240 mg capsule is typically green.
• Enteric coating: Methacrylic acid-methyl methacrylate copolymer, triethyl citrate (plasticizer), and simethicone to prevent the coating from dissolving in the stomach.

Patients with known hypersensitivity to any of the excipients should not take this medication and should consult their physician about alternative formulations. The capsules do not contain lactose, gluten, or animal-derived gelatin (as they use hypromellose capsule shells), which may be relevant for patients with specific dietary restrictions or sensitivities. Always refer to the patient information leaflet included with the medication for the most up-to-date and complete list of excipients.