Dimethyl Fumarate Orion: Uses, Dosage & Side Effects
An oral immunomodulatory disease-modifying therapy for the treatment of relapsing-remitting multiple sclerosis in adults
Dimethyl Fumarate Orion is a prescription oral medication used for the treatment of relapsing-remitting multiple sclerosis (RRMS) in adults. It contains the active substance dimethyl fumarate, which works by activating the Nrf2 antioxidant pathway and modulating immune responses to reduce inflammation and protect nerve cells in the central nervous system. Taken as a gastro-resistant capsule twice daily, dimethyl fumarate has been shown in large clinical trials to significantly reduce relapse rates, slow disability progression, and decrease the formation of new brain lesions on MRI. As a generic equivalent of Tecfidera, Dimethyl Fumarate Orion offers the same proven efficacy and safety profile at a more accessible price point.
Quick Facts: Dimethyl Fumarate Orion
Key Takeaways
- Dimethyl Fumarate Orion is an oral disease-modifying therapy approved for relapsing-remitting multiple sclerosis (RRMS) in adults, offering a convenient twice-daily capsule regimen as an alternative to injectable treatments.
- In pivotal clinical trials (DEFINE and CONFIRM), dimethyl fumarate reduced the annualized relapse rate by approximately 44–53% compared to placebo and significantly slowed disability progression over two years.
- The most common side effects are flushing and gastrointestinal symptoms (diarrhoea, nausea, abdominal pain), which typically diminish after the first month of treatment and can be mitigated by taking capsules with food.
- Regular blood monitoring (complete blood count including lymphocytes) is required before starting treatment, then at least every 6–12 months, as dimethyl fumarate can lower lymphocyte counts, and prolonged severe lymphopenia carries a risk of progressive multifocal leukoencephalopathy (PML).
- As a generic equivalent of Tecfidera, Dimethyl Fumarate Orion contains the same active substance, has demonstrated bioequivalence, and provides the same therapeutic benefit at a more affordable cost.
What Is Dimethyl Fumarate Orion and What Is It Used For?
Dimethyl Fumarate Orion contains the active substance dimethyl fumarate (DMF), a fumaric acid ester that has been used medicinally for decades. Originally developed for the treatment of psoriasis in Germany under the name Fumaderm, dimethyl fumarate was subsequently investigated for its immunomodulatory and neuroprotective properties in the context of multiple sclerosis. Following successful phase III clinical trials, dimethyl fumarate was approved for the treatment of relapsing-remitting multiple sclerosis under the brand name Tecfidera by the U.S. Food and Drug Administration (FDA) in March 2013 and by the European Medicines Agency (EMA) in January 2014. Dimethyl Fumarate Orion is a generic version manufactured by Orion Corporation, containing the same active substance and demonstrating bioequivalence with the originator product.
Multiple sclerosis (MS) is a chronic autoimmune disease of the central nervous system (CNS) in which the body's immune system mistakenly attacks myelin, the protective sheath surrounding nerve fibers in the brain and spinal cord. This demyelination disrupts the transmission of nerve signals, leading to a wide range of neurological symptoms including visual disturbances, muscle weakness, numbness, fatigue, cognitive difficulties, and problems with balance and coordination. Relapsing-remitting MS (RRMS) is the most common form of the disease, affecting approximately 85% of people initially diagnosed with MS. In RRMS, patients experience clearly defined episodes of new or worsening neurological symptoms (relapses), followed by periods of partial or complete recovery (remissions). Over time, however, accumulated nerve damage can lead to progressive disability.
After oral administration, dimethyl fumarate is rapidly hydrolyzed by esterases in the gastrointestinal tract to its primary active metabolite, monomethyl fumarate (MMF). The precise mechanism by which dimethyl fumarate exerts its therapeutic effects in MS is not fully elucidated, but the prevailing scientific understanding centers on the activation of the nuclear factor erythroid 2-related factor 2 (Nrf2) pathway. Nrf2 is a transcription factor that plays a master regulatory role in cellular defense against oxidative stress. Under normal conditions, Nrf2 is kept at low levels in the cytoplasm by its binding partner Keap1, which targets it for degradation. When cells are exposed to oxidative stress or to electrophilic compounds such as monomethyl fumarate, Keap1 is modified and Nrf2 is released, allowing it to translocate to the nucleus where it activates the transcription of a battery of cytoprotective genes. These include genes encoding antioxidant enzymes (such as heme oxygenase-1, NAD(P)H quinone dehydrogenase 1, and glutathione S-transferases) and anti-inflammatory mediators.
In addition to its antioxidant effects, dimethyl fumarate exerts significant immunomodulatory actions. Studies have demonstrated that dimethyl fumarate shifts the T-cell response from pro-inflammatory Th1 and Th17 profiles toward anti-inflammatory Th2 profiles. It reduces the absolute counts of CD8+ T cells, CD4+ T cells, and B cells in the circulation, with a preferential effect on memory T cells that are thought to play a key role in MS disease activity. Dimethyl fumarate also inhibits the activation of nuclear factor kappa-B (NF-κB), a central transcription factor involved in the expression of pro-inflammatory cytokines, adhesion molecules, and chemokines. By reducing the inflammatory milieu and decreasing the ability of activated immune cells to cross the blood-brain barrier and infiltrate the CNS, dimethyl fumarate helps to prevent the formation of new demyelinating lesions and to reduce relapse frequency.
The clinical efficacy of dimethyl fumarate in RRMS was established in two large, pivotal phase III randomized controlled trials:
- DEFINE (Determination of the Efficacy and Safety of Oral Fumarate in Relapsing-Remitting MS): This trial enrolled 1,234 patients with RRMS and compared dimethyl fumarate 240 mg twice daily and 240 mg three times daily with placebo over 2 years. The primary endpoint was the proportion of patients who relapsed at 2 years. Dimethyl fumarate 240 mg twice daily reduced the annualized relapse rate (ARR) by 53% compared to placebo (ARR 0.17 vs. 0.36, p<0.001). It also significantly reduced the risk of confirmed disability progression sustained for 12 weeks by 38% (p=0.01) and reduced the number of new or enlarging T2-hyperintense lesions on MRI by 85% (p<0.001).
- CONFIRM (Comparator and an Oral Fumarate in Relapsing-Remitting Multiple Sclerosis): This trial enrolled 1,417 patients and compared dimethyl fumarate 240 mg twice daily and three times daily with placebo and included glatiramer acetate as a reference comparator (rater-blinded). Dimethyl fumarate 240 mg twice daily reduced the ARR by 44% compared to placebo (ARR 0.22 vs. 0.40, p<0.001). The number of new or enlarging T2 lesions on MRI was reduced by 71% compared to placebo (p<0.001).
Long-term extension studies (ENDORSE) have demonstrated that the efficacy of dimethyl fumarate is maintained over periods of up to 13 years of continuous treatment, with sustained low annualized relapse rates and stable disability scores. These data provide reassurance regarding the long-term benefit-risk profile of the medication and support its use as a sustained treatment option for patients with RRMS.
Dimethyl fumarate occupies a key position among the disease-modifying therapies for MS. As an oral medication with a well-established efficacy and safety profile, it offers patients a convenient alternative to injectable therapies (such as interferons and glatiramer acetate) while providing moderate-to-high efficacy in reducing relapses and slowing disability progression. International treatment guidelines from the American Academy of Neurology (AAN) and the European Committee for Treatment and Research in Multiple Sclerosis (ECTRIMS) recommend dimethyl fumarate as a first-line or early treatment option for adults with RRMS.
What Should You Know Before Taking Dimethyl Fumarate Orion?
Contraindications
Dimethyl Fumarate Orion is contraindicated in patients with known hypersensitivity to dimethyl fumarate or to any of the excipients listed in the product information. The excipients include microcrystalline cellulose, croscarmellose sodium, talc, silica colloidal anhydrous, magnesium stearate, methacrylic acid-methyl methacrylate copolymer, triethyl citrate, talc, simethicone emulsion, sodium laurilsulfate, and polysorbate 80 in the gastro-resistant capsule coating, along with gelatin and titanium dioxide in the capsule shell. Additionally, the 120 mg capsule contains Brilliant Blue FCF (E133) and the 240 mg capsule contains Brilliant Blue FCF (E133) and sunset yellow FCF (E110). Patients with known sensitivities to azo dyes should be informed of this.
Dimethyl fumarate should not be used in patients with suspected or confirmed progressive multifocal leukoencephalopathy (PML). PML is a rare but serious and potentially fatal opportunistic infection of the brain caused by the John Cunningham (JC) virus, which can become reactivated in states of immunosuppression. Cases of PML have been reported in patients treated with dimethyl fumarate in the setting of prolonged moderate to severe lymphopenia (absolute lymphocyte count below 0.5 × 10⁹/L for more than 6 months).
Warnings and Precautions
Dimethyl fumarate can cause a significant and sustained decrease in lymphocyte counts. A complete blood count (CBC) including lymphocyte count must be obtained before starting treatment, then at least every 6–12 months during treatment, and as clinically indicated. If the lymphocyte count falls below 0.5 × 10⁹/L and persists below this level for more than 6 months, your doctor should consider stopping treatment due to the increased risk of PML.
Before starting treatment with dimethyl fumarate, your healthcare provider should perform the following baseline assessments:
- Complete blood count (CBC) with differential: Including absolute lymphocyte count. Dimethyl fumarate typically causes a 30% reduction in lymphocyte counts from baseline within the first year, after which counts generally stabilize. Patients with pre-existing low lymphocyte counts may be at higher risk of developing severe lymphopenia.
- Liver function tests: Elevations in hepatic transaminases (ALT and AST) have been reported during treatment with dimethyl fumarate. Liver function should be checked before starting treatment and during treatment as clinically indicated. Cases of drug-induced liver injury with elevated transaminases ≥5 times the upper limit of normal have been reported, although these were generally reversible upon discontinuation.
- Renal function tests: Cases of Fanconi syndrome (a disorder of renal proximal tubular function) have been reported during treatment with dimethyl fumarate. Monitoring of renal function, including urinalysis, should be considered before starting and periodically during treatment.
- Recent MRI scan: A baseline MRI of the brain is recommended before starting dimethyl fumarate to serve as a reference for future monitoring and to rule out pre-existing PML.
Dimethyl fumarate may cause flushing and gastrointestinal events (diarrhoea, nausea, abdominal pain, and vomiting), particularly during the first month of treatment. These side effects can be reduced by taking the capsule with food (particularly food containing fat or protein) and by the recommended dose-titration schedule of starting with 120 mg twice daily for the first 7 days before increasing to the maintenance dose of 240 mg twice daily. Administration of non-enteric-coated acetylsalicylic acid (aspirin) at a dose of up to 325 mg, taken 30 minutes before the dimethyl fumarate dose, may reduce the incidence or severity of flushing.
Pregnancy and Breastfeeding
Dimethyl fumarate should not be used during pregnancy unless clearly necessary and only if the potential benefit to the mother justifies the potential risk to the fetus. There are limited data on the use of dimethyl fumarate in pregnant women. Animal studies have shown adverse effects on offspring (including reduced fetal weight and delayed ossification) at exposures higher than those achieved at the recommended human dose. Women of childbearing potential should use effective contraception during treatment with dimethyl fumarate and for at least 4 weeks after the last dose. If a patient becomes pregnant while taking dimethyl fumarate, treatment should be discontinued and the patient should be informed about the potential risks. Pregnancy registries and post-marketing data continue to collect information on outcomes in women exposed to dimethyl fumarate during pregnancy.
It is not known whether dimethyl fumarate or its metabolites are excreted in human breast milk. A risk to the breastfed infant cannot be excluded. The decision to continue or discontinue breastfeeding or to continue or discontinue dimethyl fumarate therapy should be made taking into account the benefit of breastfeeding for the child and the benefit of therapy for the mother.
Driving and Operating Machinery
No studies on the effects of dimethyl fumarate on the ability to drive and use machines have been performed. Dimethyl fumarate is not expected to have a significant influence on these abilities based on its pharmacological profile. However, patients should be aware that flushing episodes, if they occur, might temporarily affect concentration. If this occurs, patients should avoid driving or operating machinery until the episode has resolved.
How Does Dimethyl Fumarate Orion Interact with Other Drugs?
Dimethyl fumarate undergoes rapid presystemic hydrolysis to monomethyl fumarate (MMF) by esterases in the gastrointestinal tract, before reaching the systemic circulation. MMF is further metabolized via the tricarboxylic acid (TCA) cycle without involvement of the cytochrome P450 (CYP) enzyme system. Consequently, dimethyl fumarate has a low potential for pharmacokinetic drug-drug interactions through CYP-mediated mechanisms. In vitro studies have confirmed that dimethyl fumarate and MMF do not inhibit or induce CYP1A2, CYP2B6, CYP2C8, CYP2C9, CYP2C19, CYP2D6, or CYP3A4, and are not substrates of P-glycoprotein (P-gp) or BCRP transporters.
Despite the low pharmacokinetic interaction potential, there are several clinically important drug interaction considerations:
| Interacting Drug or Class | Type | Effect and Recommendation |
|---|---|---|
| Other disease-modifying MS therapies (e.g., fingolimod, natalizumab, teriflunomide, ocrelizumab) | Major | Concurrent use may increase the risk of additive immunosuppression. Do not use concurrently. Allow adequate washout periods when switching treatments. |
| Immunosuppressive agents (e.g., azathioprine, methotrexate, cyclosporine, mycophenolate) | Major | Concurrent use is not recommended due to the risk of additive immunosuppressive effects, which may increase the risk of infections including PML. |
| Live vaccines (e.g., MMR, varicella, yellow fever, BCG) | Major | Avoid administration of live attenuated vaccines during treatment with dimethyl fumarate due to the risk of clinical infection. Inactivated vaccines may be administered, though the immune response may be reduced. |
| Nephrotoxic medications (e.g., aminoglycosides, NSAIDs, lithium) | Moderate | Due to the rare risk of Fanconi syndrome with dimethyl fumarate, concurrent use of nephrotoxic drugs should be approached with caution and renal function should be monitored. |
| Acetylsalicylic acid (aspirin, non-enteric-coated, up to 325 mg) | Beneficial | Taking aspirin 30 minutes before dimethyl fumarate may reduce the incidence and severity of flushing. No pharmacokinetic interaction has been identified. |
| Oral contraceptives | None identified | No clinically significant interaction identified. Dimethyl fumarate can be used concurrently with hormonal contraceptives without dose adjustment. |
Switching Between MS Therapies
When switching to dimethyl fumarate from another disease-modifying therapy, or switching from dimethyl fumarate to another treatment, physicians must consider the pharmacodynamic properties and duration of action of both agents. Overlap of immunological effects could increase the risk of additive immunosuppression while not providing additional therapeutic benefit. Adequate washout periods should be observed, taking into account the half-life and mechanism of action of the prior therapy. For example, after discontinuation of fingolimod, a washout period of at least 6 weeks is generally recommended to allow lymphocyte counts to recover before starting dimethyl fumarate. After stopping natalizumab, a washout period of 6–8 weeks is typically advised. Conversely, when switching from dimethyl fumarate to a more potent immunosuppressive agent, the current lymphocyte count should be assessed to ensure adequate immune function before initiating the new treatment.
It is also important to consider the potential for disease reactivation or rebound when discontinuing certain MS therapies before starting dimethyl fumarate. Patients should be closely monitored clinically and with MRI during the transition period to detect any signs of disease activity.
What Is the Correct Dosage of Dimethyl Fumarate Orion?
Adults
The standard dosing regimen for dimethyl fumarate in adults with relapsing-remitting multiple sclerosis follows a dose-titration schedule designed to minimize the incidence and severity of flushing and gastrointestinal side effects during treatment initiation. During the first 7 days, the starting dose is 120 mg (one capsule) taken twice daily, with approximately 12 hours between doses. After the initial 7-day titration period, the dose is increased to the recommended maintenance dose of 240 mg (one capsule) taken twice daily. This dose should be maintained throughout the course of treatment unless dose modification is required due to adverse effects.
Standard Adult Dosing Schedule
Week 1 (Titration): 120 mg twice daily (morning and evening, with food)
Week 2 onwards (Maintenance): 240 mg twice daily (morning and evening, with food)
The gastro-resistant capsules should be swallowed whole with water or another liquid. They must not be crushed, chewed, opened, or dissolved, as the gastro-resistant coating is essential for protecting the active substance from degradation in the stomach and for reducing gastrointestinal irritation. Taking the capsules with food, particularly meals containing fat or protein, has been shown to reduce the incidence and severity of both flushing and gastrointestinal side effects. Patients should aim to take each dose at approximately the same times each day to maintain consistent drug levels.
A temporary dose reduction to 120 mg twice daily may be considered for patients who experience persistent flushing or gastrointestinal adverse events that do not resolve within the first month of treatment. However, the reduced dose should be resumed to 240 mg twice daily within 4 weeks, as long-term efficacy has only been established at the 240 mg twice-daily dose. If a patient cannot tolerate a return to the full dose, discontinuation of dimethyl fumarate should be considered and alternative treatment options discussed.
Children and Adolescents
Dimethyl fumarate 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. Pediatric MS presents unique challenges, and treatment decisions should be made by or in consultation with a neurologist experienced in managing MS in children and adolescents. Other disease-modifying therapies with established pediatric indications should be considered for this age group.
Elderly Patients
Clinical trials of dimethyl fumarate did not include sufficient numbers of patients aged 65 years and over to determine whether they respond differently from younger patients. In general, dose selection for elderly patients should be cautious, reflecting the greater frequency of decreased hepatic, renal, or cardiac function, and of concomitant disease or other drug therapy. No dose adjustment is recommended based on age alone. Renal and hepatic function should be assessed before starting treatment and monitored as clinically indicated.
Missed Dose
If you miss a dose of dimethyl fumarate, take it as soon as you remember, as long as there is sufficient time before your next scheduled dose. Do not take a double dose to make up for a missed dose. If it is close to the time for your next dose, skip the missed dose and continue with your regular dosing schedule. Maintaining adherence to the twice-daily dosing schedule is important for optimal therapeutic benefit. If you frequently miss doses, discuss strategies to improve adherence with your healthcare provider, such as setting reminders or adjusting the timing of doses to fit your daily routine.
Overdose
There is limited experience with overdose of dimethyl fumarate in clinical trials. No specific antidote exists for dimethyl fumarate overdose. In the event of an overdose, supportive care and symptomatic treatment should be provided as clinically indicated. Hemodialysis is not expected to be effective in removing dimethyl fumarate or its active metabolite MMF from the body, as they are extensively bound to plasma proteins and are rapidly metabolized. Patients who have taken more than the prescribed dose should contact their healthcare provider or a poison control center immediately.
| Patient Group | Starting Dose | Maintenance Dose | Notes |
|---|---|---|---|
| Adults (18+ years) | 120 mg twice daily (7 days) | 240 mg twice daily | Take with food; swallow whole |
| Elderly (≥65 years) | 120 mg twice daily (7 days) | 240 mg twice daily | No dose adjustment; monitor renal/hepatic function |
| Children (<18 years) | Not approved | Not approved | Safety and efficacy not established |
| Renal impairment | As per standard | 240 mg twice daily | No dose adjustment; monitor renal function |
| Hepatic impairment | As per standard | 240 mg twice daily | No dose adjustment; monitor liver enzymes |
What Are the Side Effects of Dimethyl Fumarate Orion?
Like all medicines, dimethyl fumarate can cause side effects, although not everybody gets them. In the pivotal clinical trials (DEFINE and CONFIRM), the most commonly reported adverse reactions were flushing and gastrointestinal events. These side effects were most pronounced during the first month of treatment and generally decreased in frequency and severity with continued use. Flushing was reported by approximately 40% of patients in clinical trials, while gastrointestinal events (diarrhoea, nausea, abdominal pain, and vomiting) were reported by approximately 15–18% of patients. The discontinuation rate due to adverse events was approximately 12–16% in the dimethyl fumarate groups compared to 6–7% in the placebo groups, with flushing and gastrointestinal events being the most common reasons for discontinuation.
Dimethyl fumarate causes a mean decrease in lymphocyte counts of approximately 30% from baseline within the first year of treatment, after which counts generally stabilize but remain below pre-treatment levels. Most patients maintain lymphocyte counts within the normal range (>0.91 × 10⁹/L). However, approximately 2–6% of patients may develop prolonged moderate lymphopenia (0.5–0.8 × 10⁹/L) and less than 1% may develop severe lymphopenia (<0.5 × 10⁹/L). Prolonged severe lymphopenia carries an increased risk of opportunistic infections, including progressive multifocal leukoencephalopathy (PML).
Very Common
May affect more than 1 in 10 people
- Flushing (warmth, redness, itching, or burning sensation of the skin, particularly of the face, neck, and upper body)
- Diarrhoea
- Nausea
- Abdominal pain or cramping
Common
May affect up to 1 in 10 people
- Vomiting
- Dyspepsia (indigestion)
- Gastritis (inflammation of the stomach lining)
- Gastroenteritis (stomach and intestinal inflammation)
- Pruritus (itching)
- Rash or erythema (skin redness)
- Hot flush (feeling of warmth)
- Burning sensation
- Lymphopenia (reduced lymphocyte count)
- Leukopenia (reduced white blood cell count)
- Proteinuria (protein in the urine)
- Elevated liver enzymes (ALT, AST)
- Feeling of warmth or heat
- Albumin in urine
Uncommon
May affect up to 1 in 100 people
- Hypersensitivity reactions (allergic reactions)
- Anaphylaxis
- Angioedema (swelling of the face, lips, tongue, or throat)
- Severe lymphopenia (lymphocyte count <0.5 × 10⁹/L)
Rare
May affect up to 1 in 1,000 people
- Progressive multifocal leukoencephalopathy (PML) – in the setting of prolonged severe lymphopenia
- Fanconi syndrome (disorder of renal proximal tubular function)
- Drug-induced liver injury with elevated transaminases ≥5× upper limit of normal
- Herpes zoster (shingles)
Not Known
Frequency cannot be estimated from available data
- Immune reconstitution inflammatory syndrome (IRIS) following discontinuation in the setting of PML
- Severe prolonged lymphopenia
Contact your doctor or seek emergency medical care immediately if you experience: signs of a serious allergic reaction (difficulty breathing, swelling of the face or throat, severe rash or hives), signs of PML (progressive weakness on one side of the body, clumsiness, visual disturbances, confusion, memory problems, changes in thinking), unexplained persistent fever or signs of severe infection, or yellowing of the skin or eyes (jaundice) suggesting liver injury.
To minimize the risk and impact of flushing and gastrointestinal side effects, the following strategies are recommended: follow the dose-titration schedule (120 mg twice daily for the first 7 days before increasing to 240 mg twice daily), always take the capsules with food, consider taking non-enteric-coated aspirin (up to 325 mg) approximately 30 minutes before the dose to reduce flushing, and avoid hot beverages, spicy foods, and alcohol around the time of dosing, as these may exacerbate flushing. Most patients find that these side effects become less frequent and less severe within the first 2–3 months of treatment.
How Should You Store Dimethyl Fumarate Orion?
Dimethyl Fumarate Orion gastro-resistant hard capsules should be stored at a temperature not exceeding 30°C (86°F). The capsules should be kept in the original blister packaging to protect them from light and moisture, as exposure to these environmental factors can degrade the gastro-resistant coating and the active substance. Do not remove capsules from the blister until you are ready to take them.
Do not use Dimethyl Fumarate Orion after the expiry date stated on the carton and blister after "EXP". The expiry date refers to the last day of that month. Keep this medicine out of the sight and reach of children. Do not throw away any medicines via wastewater or household waste. Ask your pharmacist how to throw away medicines you no longer use. These measures will help protect the environment.
If you notice that the capsules have changed in appearance (e.g., discoloration, visible damage to the capsule shell, or an unusual odor), do not take them and consult your pharmacist. Damaged or deteriorated capsules may not provide the intended gastro-resistant protection and could lead to increased gastrointestinal side effects or reduced efficacy.
What Does Dimethyl Fumarate Orion Contain?
Each Dimethyl Fumarate Orion gastro-resistant hard capsule contains either 120 mg or 240 mg of dimethyl fumarate as the active substance. The gastro-resistant formulation is designed to protect the active substance from degradation in the acidic environment of the stomach and to release the drug in the more alkaline environment of the small intestine, thereby reducing direct gastric irritation.
Active substance: Dimethyl fumarate (also known as dimethyl (E)-butenedioate). Molecular formula: C₆H₈O₄. Molecular weight: 144.13 g/mol. Dimethyl fumarate is a white to off-white crystalline powder that is slightly soluble in water.
Capsule content excipients: Microcrystalline cellulose, croscarmellose sodium, talc, silica colloidal anhydrous, and magnesium stearate. These excipients serve as fillers, disintegrants, glidants, and lubricants to ensure consistent capsule manufacturing, appropriate drug release characteristics, and stability.
Gastro-resistant coating: Methacrylic acid-methyl methacrylate copolymer (1:1), triethyl citrate, talc, simethicone emulsion (containing polydimethylsiloxane, polysorbate 80, methylcellulose, sorbic acid, and purified water), sodium laurilsulfate, and polysorbate 80. This coating is specifically designed to remain intact in gastric acid (pH < 5.5) and dissolve in the higher pH of the intestine (> pH 5.5).
Capsule shell: Gelatin, titanium dioxide (E171), and colorants. The 120 mg capsule shell contains Brilliant Blue FCF (E133), giving it a green appearance. The 240 mg capsule shell contains Brilliant Blue FCF (E133) and sunset yellow FCF (E110), giving it a green appearance. The capsule shells also contain black iron oxide (E172) for printing the dosage strength on the capsule.
Capsule appearance: The 120 mg capsules are typically green and white, with "120 mg" printed on them. The 240 mg capsules are typically green, with "240 mg" printed on them. The exact appearance may vary depending on the specific manufacturing batch and market authorization. Always verify the product appearance against the package leaflet provided with your medication.
Frequently Asked Questions About Dimethyl Fumarate Orion
Dimethyl Fumarate Orion is used for the treatment of adult patients with relapsing-remitting multiple sclerosis (RRMS). It is a disease-modifying therapy that reduces the frequency and severity of relapses, slows the progression of physical disability, and decreases the formation of new inflammatory brain lesions as seen on MRI. It works by activating the Nrf2 antioxidant pathway and modulating immune responses to reduce inflammation and protect nerve cells in the central nervous system.
The most common side effects are flushing (warmth, redness, itching, or burning sensation of the skin) and gastrointestinal events including diarrhoea, nausea, abdominal pain, and vomiting. These side effects are most frequent during the first month of treatment and typically diminish over time. Taking the capsule with food and following the gradual dose-titration schedule (starting at 120 mg twice daily before increasing to 240 mg twice daily) can reduce the incidence and severity of these effects.
Dimethyl fumarate can cause a reduction in white blood cell (lymphocyte) counts, typically by approximately 30% from baseline within the first year, after which counts generally stabilize. While most patients maintain lymphocyte counts within the normal range, some may develop prolonged moderate to severe lymphopenia. Regular blood tests (complete blood count including lymphocytes) are required before starting treatment and at least every 6–12 months during treatment, as prolonged severe lymphopenia increases the risk of progressive multifocal leukoencephalopathy (PML), a rare but serious brain infection.
Dimethyl fumarate should not be used during pregnancy unless clearly necessary and only if the potential benefit justifies the potential risk to the fetus. Animal studies have shown adverse effects on offspring at doses higher than those used clinically. Women of childbearing potential should use effective contraception during treatment and for at least 4 weeks after stopping. If you become pregnant while taking dimethyl fumarate, consult your doctor immediately about whether to continue treatment.
Yes, Dimethyl Fumarate Orion contains the same active substance (dimethyl fumarate) as Tecfidera and is approved as a generic equivalent. Both products are available as 120 mg and 240 mg gastro-resistant hard capsules and are used for the same indication (relapsing-remitting multiple sclerosis in adults). Generic medications must meet strict regulatory standards demonstrating bioequivalence with the originator product, meaning they deliver the same amount of active substance at the same rate to the body.
The full therapeutic effect of dimethyl fumarate on reducing relapses and disability progression develops over several months. Clinical trials measured outcomes over 2 years, showing significant reductions in annualized relapse rate and MRI lesion activity. Some effects on MRI markers may be detectable within 3–6 months. It is important to continue treatment as prescribed even if you feel well, as the benefits accumulate over time and stopping treatment may lead to disease reactivation.
References
- European Medicines Agency (EMA). Dimethyl Fumarate Orion – Summary of Product Characteristics. Available from EMA product information database. Last updated 2025.
- U.S. Food and Drug Administration (FDA). Tecfidera (dimethyl fumarate) Prescribing Information. Biogen Inc. Last revised 2024.
- Gold R, Kappos L, Arnold DL, et al. Placebo-controlled phase 3 study of oral BG-12 for relapsing multiple sclerosis (DEFINE study). N Engl J Med. 2012;367(12):1098-1107. doi:10.1056/NEJMoa1114287.
- Fox RJ, Miller DH, Phillips JT, et al. Placebo-controlled phase 3 study of oral BG-12 or glatiramer in multiple sclerosis (CONFIRM study). N Engl J Med. 2012;367(12):1087-1097. doi:10.1056/NEJMoa1206328.
- Gold R, Arnold DL, Bar-Or A, et al. Long-term effects of delayed-release dimethyl fumarate in multiple sclerosis: interim analysis of ENDORSE, a randomized extension study. Mult Scler. 2017;23(2):253-265. doi:10.1177/1352458516649037.
- Linker RA, Lee DH, Ryan S, et al. Fumaric acid esters exert neuroprotective effects in neuroinflammation via activation of the Nrf2 antioxidant pathway. Brain. 2011;134(Pt 3):678-692. doi:10.1093/brain/awq386.
- Rae-Grant A, Day GS, Marrie RA, et al. Practice guideline recommendations summary: Disease-modifying therapies for adults with multiple sclerosis. Neurology. 2018;90(17):777-788. doi:10.1212/WNL.0000000000005347.
- Montalban X, Gold R, Thompson AJ, et al. ECTRIMS/EAN guideline on the pharmacological treatment of people with relapsing multiple sclerosis. Mult Scler. 2018;24(2):96-120. doi:10.1177/1352458517751049.
- World Health Organization (WHO). Model List of Essential Medicines. 23rd List, 2023. Geneva: World Health Organization.
- British National Formulary (BNF). Dimethyl fumarate. National Institute for Health and Care Excellence (NICE). Accessed 2025.
Medical Editorial Team
This article has been reviewed by the iMedic Medical Editorial Team, comprising licensed physicians and clinical pharmacologists with expertise in neurology and multiple sclerosis. All content follows the iMedic Editorial Standards and is based on current international clinical guidelines.
Neurology Specialist
Board-certified neurologist with expertise in multiple sclerosis and neuroimmunology
Clinical Pharmacologist
Specialist in drug safety, pharmacokinetics, and immunomodulatory therapies
Medical Writer
Experienced medical communicator ensuring accuracy and patient accessibility
Peer Reviewer
Independent physician verifying all medical claims against current evidence
Conflict of Interest Statement: The iMedic Medical Editorial Team has no financial relationships with pharmaceutical companies. All content is independently produced without commercial funding or advertising influence. For more information, see our Editorial Standards.