Dimethyl Fumarate Hexal: Uses, Dosage & Side Effects
An oral immunomodulatory disease-modifying therapy for the treatment of relapsing forms of multiple sclerosis in adults
Dimethyl Fumarate Hexal is a prescription oral disease-modifying therapy used to treat relapsing forms of multiple sclerosis (MS) in adults. It contains the active substance dimethyl fumarate, which works by activating the Nrf2 antioxidant pathway to protect nerve cells from inflammatory damage and by modulating the immune system to reduce autoimmune attacks on the myelin sheath. Dimethyl Fumarate Hexal is taken as gastro-resistant capsules twice daily and has been shown in large-scale clinical trials to significantly reduce the rate of MS relapses, slow disability progression, and decrease the number of new brain lesions on MRI. As a generic medicine bioequivalent to Tecfidera, it offers the same clinical benefits at a more accessible cost.
Quick Facts: Dimethyl Fumarate Hexal
Key Takeaways
- Dimethyl Fumarate Hexal is an oral disease-modifying therapy for relapsing multiple sclerosis in adults, taken as gastro-resistant capsules twice daily with the maintenance dose of 240 mg twice daily.
- Clinical trials (DEFINE and CONFIRM) demonstrated that dimethyl fumarate reduces the annualized relapse rate by approximately 44–53%, slows disability progression, and significantly decreases new or enlarging brain lesions on MRI.
- The most common side effects are flushing and gastrointestinal symptoms (nausea, diarrhea, abdominal pain), which are most pronounced during the first month and typically diminish with continued treatment.
- Regular blood monitoring (complete blood count including lymphocyte counts) is required before and during treatment, as prolonged severe lymphopenia increases the risk of opportunistic infections including progressive multifocal leukoencephalopathy (PML).
- As a generic equivalent of Tecfidera, Dimethyl Fumarate Hexal has been demonstrated to be bioequivalent, providing the same efficacy and safety profile at a typically lower cost, making disease-modifying MS treatment more accessible.
What Is Dimethyl Fumarate Hexal and What Is It Used For?
Dimethyl Fumarate Hexal contains the active substance dimethyl fumarate (DMF), a fumaric acid ester that has been developed as a disease-modifying therapy for multiple sclerosis. Multiple sclerosis is a chronic autoimmune disease of the central nervous system (CNS) in which the body's immune system mistakenly attacks the myelin sheath, the protective insulation surrounding nerve fibers in the brain and spinal cord. This attack leads to inflammation, demyelination, and ultimately neuronal damage, resulting in a wide range of neurological symptoms including vision problems, muscle weakness, coordination difficulties, numbness, fatigue, and cognitive impairment.
Dimethyl fumarate was originally developed as a treatment for psoriasis (marketed as Fumaderm in Germany since 1994) before its potential in multiple sclerosis was recognized. The discovery that fumaric acid esters possess both anti-inflammatory and neuroprotective properties led to the development of dimethyl fumarate specifically for MS. The originator product, Tecfidera, was first approved by the U.S. Food and Drug Administration (FDA) in March 2013 and subsequently by the European Medicines Agency (EMA) in January 2014. Dimethyl Fumarate Hexal is a generic version that has been shown to be bioequivalent to Tecfidera, meaning it delivers the same amount of active substance in the body in the same way.
The mechanism of action of dimethyl fumarate is multifaceted and not fully elucidated, but several key pathways have been identified. After oral administration, dimethyl fumarate is rapidly hydrolyzed by esterases in the alkaline environment of the small intestine to its primary active metabolite, monomethyl fumarate (MMF). The principal pharmacodynamic effect of MMF is activation of the nuclear factor (erythroid-derived 2)-like 2 (Nrf2) transcriptional pathway. Nrf2 is a key regulator of cellular defense against oxidative stress. Under normal conditions, Nrf2 is kept at low levels in the cytoplasm by its inhibitor protein Keap1. MMF modifies specific cysteine residues on Keap1, leading to the release and nuclear translocation of Nrf2, where it binds to antioxidant response elements (AREs) in the promoter regions of various cytoprotective genes. This results in the upregulation of antioxidant enzymes such as heme oxygenase-1 (HO-1), NAD(P)H quinone dehydrogenase 1 (NQO1), and glutathione S-transferases, which protect cells against oxidative damage and inflammation.
In addition to its neuroprotective effects via Nrf2 activation, dimethyl fumarate has significant immunomodulatory properties. It shifts the immune response from a predominantly pro-inflammatory Th1 and Th17 phenotype toward an anti-inflammatory Th2 phenotype. It also activates the hydroxycarboxylic acid receptor 2 (HCAR2, also known as GPR109A), which contributes to its anti-inflammatory effects. Treatment with dimethyl fumarate typically leads to a reduction in absolute lymphocyte counts, primarily affecting CD8+ T cells, followed by CD4+ T cells and, to a lesser extent, B cells and natural killer cells. This selective lymphocyte reduction is thought to be an important component of its therapeutic effect in MS, as it reduces the pool of autoreactive immune cells capable of attacking the myelin sheath.
Dimethyl Fumarate Hexal is indicated for the treatment of adult patients with relapsing-remitting multiple sclerosis (RRMS). This includes patients experiencing clinical relapses (acute episodes of new or worsening neurological symptoms) separated by periods of partial or complete recovery. The efficacy of dimethyl fumarate in relapsing MS has been established in two pivotal phase III clinical trials:
- DEFINE (Determination of the Efficacy and safety of oral Fumarate IN rElapsing-remitting MS): This randomized, double-blind, placebo-controlled trial enrolled 1,234 patients with RRMS. Patients treated with dimethyl fumarate 240 mg twice daily experienced a 53% reduction in the annualized relapse rate (ARR) compared with placebo over 2 years (ARR 0.17 vs. 0.36, p<0.001). The risk of 12-week confirmed disability progression was reduced by 38% (p=0.01). Additionally, dimethyl fumarate treatment reduced the number of new or newly enlarging T2 hyperintense lesions on MRI by 85% and gadolinium-enhancing lesions by 90%.
- CONFIRM (Comparator and an Oral Fumarate in Relapsing-Remitting Multiple Sclerosis): This trial enrolled 1,417 patients and included both a placebo arm and an active comparator arm (glatiramer acetate). Dimethyl fumarate 240 mg twice daily reduced the ARR by 44% compared with placebo (ARR 0.22 vs. 0.40, p<0.001). MRI outcomes also showed significant reductions in new T2 lesions (71% reduction) and gadolinium-enhancing lesions (74% reduction) compared with placebo.
Long-term extension studies (ENDORSE) have demonstrated sustained efficacy over up to 13 years of continuous treatment, with maintained low annualized relapse rates, stable disability levels, and a consistent safety profile. The proportion of patients remaining relapse-free at 5 years was approximately 63% among those who received dimethyl fumarate continuously from study entry. These long-term data provide important reassurance about the durability of treatment benefits.
Dimethyl fumarate represents an important advance in MS treatment as one of the first oral disease-modifying therapies with proven efficacy against both clinical relapses and MRI disease activity. Its oral administration, favorable efficacy profile, and well-characterized safety data have made it one of the most widely prescribed first-line treatments for relapsing MS worldwide. As a generic version, Dimethyl Fumarate Hexal makes this important treatment more accessible to patients.
What Should You Know Before Taking Dimethyl Fumarate Hexal?
Contraindications
Dimethyl Fumarate Hexal must not be used if you have a known hypersensitivity (allergy) to dimethyl fumarate or to any of the other ingredients in the capsule formulation. The excipients include microcrystalline cellulose, croscarmellose sodium, talc, silica colloidal anhydrous, magnesium stearate, triethyl citrate, methacrylic acid-methyl methacrylate copolymer, methacrylic acid-ethyl acrylate copolymer, simethicone, sodium laurilsulfate, polysorbate 80, gelatin, titanium dioxide, brilliant blue FCF, and iron oxide yellow. If you have a known allergy to any of these substances, inform your doctor before starting treatment.
Dimethyl Fumarate Hexal is also contraindicated in patients with suspected or confirmed progressive multifocal leukoencephalopathy (PML), a rare but serious brain infection caused by the JC virus. PML has been reported in patients treated with dimethyl fumarate, particularly in the context of prolonged severe lymphopenia (very low lymphocyte counts). Before initiating treatment, your doctor will assess your risk factors for PML and ensure that baseline blood tests are performed.
Warnings and Precautions
Dimethyl fumarate can cause a significant and sustained reduction in lymphocyte counts. Severe prolonged lymphopenia (lymphocyte counts below 0.5 x 109/L for more than 6 months) increases the risk of progressive multifocal leukoencephalopathy (PML), a rare and potentially fatal brain infection. Regular blood monitoring is mandatory. If lymphocyte counts remain below 0.5 x 109/L for more than 6 months, your doctor should consider discontinuing treatment.
Before starting and during treatment with Dimethyl Fumarate Hexal, the following precautions apply:
- Blood monitoring: A complete blood count (CBC) including differential white blood cell count and lymphocyte count must be obtained before starting treatment, at 6 months after initiation, and then every 6 to 12 months thereafter. More frequent monitoring may be necessary if clinically indicated. If lymphocyte counts fall below 0.5 x 109/L and remain at this level for more than 6 months, discontinuation of treatment should be strongly considered.
- Liver function: Elevations in hepatic transaminases (ALT and AST) have been reported in patients treated with dimethyl fumarate. Clinically significant liver injury, including cases of elevated liver enzymes greater than 5 times the upper limit of normal, has been reported. Liver function tests (including serum aminotransferases and total bilirubin levels) should be obtained before and during treatment as clinically indicated.
- Kidney function: Renal function (e.g., serum creatinine, blood urea nitrogen, and urinalysis) should be assessed before starting treatment and periodically during therapy, as cases of Fanconi syndrome (a disorder of renal tubular function) have been reported in patients taking fumaric acid esters.
- Infections: Because dimethyl fumarate lowers lymphocyte counts, it may increase susceptibility to infections, including opportunistic infections. Patients should be evaluated for signs and symptoms of infection before and during treatment. If a patient develops a serious infection, treatment interruption should be considered until the infection resolves.
- Previous immunosuppressive therapy: If you have been treated with other immunosuppressive or immunomodulatory medications, there may be an increased risk of additive immune system effects. Your doctor will carefully consider the timing of switching to dimethyl fumarate and may require a washout period.
- Vaccinations: Live vaccines should not be administered during treatment with Dimethyl Fumarate Hexal, as the reduced immune function may lead to an inadequate vaccine response or an increased risk of infection from live vaccine strains. Inactivated (killed) vaccines can generally be given, although the immune response may be diminished. If possible, complete any required vaccinations before starting treatment.
Pregnancy and Breastfeeding
Dimethyl Fumarate Hexal should not be used during pregnancy unless clearly necessary and the potential benefit to the mother justifies the potential risk to the fetus. Animal studies have shown adverse effects on reproduction and embryo-fetal development at high doses (associated with maternal toxicity). There are limited data on the use of dimethyl fumarate in pregnant women. Women of childbearing potential should use effective contraception during treatment and for at least 4 weeks after the last dose. If you become pregnant while taking Dimethyl Fumarate Hexal, discontinue treatment and consult your neurologist immediately to discuss alternative management strategies.
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 breastfeed during treatment should be made in consultation with your doctor, weighing the benefits of breastfeeding for the infant against the benefits of continued MS treatment for the mother. If breastfeeding is chosen, careful monitoring of the infant for any adverse effects is recommended.
Driving and Operating Machinery
No studies on the effects of dimethyl fumarate on the ability to drive and use machines have been performed. Based on the known pharmacological profile and adverse event data, dimethyl fumarate is not expected to significantly impair the ability to drive or operate machinery. However, the underlying disease (multiple sclerosis) itself can affect these abilities, and some patients may experience flushing or gastrointestinal symptoms that could temporarily affect concentration. Use caution if you experience any adverse effects that could impair your alertness.
Before starting Dimethyl Fumarate Hexal, your doctor should perform: (1) a complete blood count with differential and lymphocyte count, (2) liver function tests, (3) kidney function tests, and (4) a recent MRI scan as a baseline. Inform your doctor about any history of serious infections, low white blood cell counts, liver or kidney problems, or previous treatment with immunosuppressive medications.
How Does Dimethyl Fumarate Hexal Interact with Other Drugs?
Dimethyl fumarate has a favorable pharmacokinetic profile with regard to drug interactions. After oral ingestion, it is rapidly and extensively hydrolyzed by esterases in the gut to its active metabolite monomethyl fumarate (MMF) before reaching the systemic circulation. DMF itself is not detectable in plasma. MMF is subsequently metabolized via the tricarboxylic acid (TCA) cycle, ultimately being eliminated as carbon dioxide (CO2) through exhalation. Crucially, this metabolic pathway does not involve the cytochrome P450 (CYP) enzyme system, which is the primary source of pharmacokinetic drug-drug interactions for most oral medications.
In vitro studies have confirmed that dimethyl fumarate and its metabolite MMF do not inhibit or induce any of the major CYP enzymes (CYP1A2, CYP2B6, CYP2C8, CYP2C9, CYP2C19, CYP2D6, and CYP3A4). Similarly, MMF is not a substrate for P-glycoprotein (P-gp) or breast cancer resistance protein (BCRP) transporters at clinically relevant concentrations. These findings indicate that dimethyl fumarate is unlikely to affect the pharmacokinetics of co-administered drugs, and that its own pharmacokinetics are unlikely to be affected by CYP inhibitors or inducers.
Despite the favorable pharmacokinetic profile, several important pharmacodynamic interactions should be considered:
| Drug Category | Examples | Interaction Risk | Clinical Recommendation |
|---|---|---|---|
| Other MS disease-modifying therapies | Fingolimod, natalizumab, teriflunomide, ocrelizumab | Additive immunosuppression | Avoid concurrent use; allow appropriate washout periods when switching |
| Systemic immunosuppressants | Azathioprine, methotrexate, ciclosporin, mycophenolate | Increased infection risk due to combined immunosuppression | Concurrent use not recommended |
| Live vaccines | MMR, varicella, BCG, yellow fever, live influenza | Risk of vaccine-strain infection or inadequate immune response | Contraindicated during treatment; vaccinate before starting therapy |
| Nephrotoxic drugs | Aminoglycosides, NSAIDs (high-dose chronic), cisplatin | Potential additive effects on renal tubular function | Monitor renal function closely if co-administration is necessary |
| Inactivated vaccines | Influenza (inactivated), COVID-19 (mRNA/protein), hepatitis B | Potentially reduced immune response | Can be given; check antibody titers if clinically important |
| Symptomatic MS medications | Baclofen, gabapentin, amantadine, modafinil | No significant interaction identified | Safe to use concurrently |
| Interferon beta | Interferon beta-1a (Avonex, Rebif), interferon beta-1b (Betaferon) | Potential additive effects on lymphocyte counts | Concurrent use not recommended; allow washout period when switching |
A specific clinical consideration involves the timing of switching from one MS disease-modifying therapy to another. When switching from therapies that have long-lasting effects on the immune system (such as fingolimod, which sequesters lymphocytes in lymph nodes, or natalizumab, which blocks lymphocyte migration into the CNS, or alemtuzumab, which depletes lymphocytes), an appropriate washout period is essential before starting dimethyl fumarate. This is to avoid excessive or prolonged immunosuppression from overlapping drug effects. Your neurologist will determine the appropriate timing based on your specific treatment history and current blood count results.
Concomitant use of dimethyl fumarate with short courses of corticosteroids (such as methylprednisolone for acute MS relapses) has not been associated with clinically meaningful interactions in clinical trials and is considered acceptable. However, prolonged systemic corticosteroid use should be avoided due to the combined immunosuppressive effect.
Although dimethyl fumarate does not have traditional pharmacokinetic drug interactions, its immunomodulatory effects require careful consideration when combining with other medications that affect the immune system. Always inform your neurologist and pharmacist about all medications, supplements, and over-the-counter products you are taking. When switching between MS therapies, your doctor will plan the transition carefully to minimize the risk of both disease reactivation and excessive immunosuppression.
What Is the Correct Dosage of Dimethyl Fumarate Hexal?
Dimethyl Fumarate Hexal should always be used exactly as your doctor has instructed. The medication is available as gastro-resistant (enteric-coated) hard capsules in two strengths: 120 mg (for the initial titration phase) and 240 mg (for maintenance therapy). The gastro-resistant coating is essential as it prevents the active substance from being released in the stomach, where it could cause increased gastrointestinal irritation, and instead allows release in the small intestine where absorption occurs.
Adults
The recommended dosing regimen for Dimethyl Fumarate Hexal in adult patients involves a titration period followed by maintenance dosing:
| Phase | Dose | Frequency | Duration |
|---|---|---|---|
| Titration (Week 1) | 120 mg | Twice daily (morning and evening) | 7 days |
| Maintenance (Week 2 onwards) | 240 mg | Twice daily (morning and evening) | Long-term / as directed |
The initial titration period of 120 mg twice daily for the first week is designed to minimize the incidence and severity of flushing and gastrointestinal side effects, which are most common during the early weeks of treatment. Some doctors may extend the titration period to 2 or even 4 weeks (for example, 120 mg once daily for 1 week, then 120 mg twice daily for 1 week, then 240 mg once daily for 1 week, before reaching the full dose) if patients have difficulty tolerating the standard titration schedule.
Important administration instructions:
- Take with food: Administration with food, particularly a meal containing some fat, has been shown to significantly reduce the incidence and severity of flushing and gastrointestinal side effects. A meal or substantial snack before taking each dose is strongly recommended, especially during the first few months of treatment.
- Swallow whole: The capsules must be swallowed whole with water or another non-alcoholic beverage. Do not crush, chew, dissolve, or open the capsules, as this would destroy the gastro-resistant coating and lead to increased gastrointestinal side effects and potentially altered drug absorption.
- Consistent timing: Try to take the capsules at approximately the same times each day (for example, with breakfast and with dinner) to maintain consistent blood levels and to help establish a routine.
- Temporary dose reduction: If patients experience persistent flushing or gastrointestinal symptoms despite taking the capsules with food, a temporary reduction to 120 mg twice daily for up to 4 weeks may be considered. The full maintenance dose of 240 mg twice daily should be resumed after this period, as the lower dose may not provide optimal therapeutic benefit.
Children and Adolescents
The safety and efficacy of dimethyl fumarate in children and adolescents below 18 years of age have not been fully established in large-scale controlled trials. Use in this population is generally not recommended unless under the specific guidance of a specialist neurologist who determines that the potential benefits outweigh the risks. Pediatric clinical trials are ongoing, and updated dosing recommendations for younger patients may become available in the future.
Elderly Patients
Clinical trials of dimethyl fumarate included a limited number of patients aged 55 and older, and did not include sufficient numbers of patients aged 65 and over to determine whether they respond differently from younger patients. No specific dose adjustment is recommended for elderly patients based on age alone. However, as elderly patients may have decreased renal and hepatic function and may be taking multiple medications, careful monitoring is advisable. The known decrease in immune function associated with aging should also be considered when evaluating the benefits and risks of treatment.
Missed Dose
If you miss a dose of Dimethyl Fumarate Hexal, take it as soon as you remember, provided there are at least several hours before the next scheduled dose. Do not take a double dose to compensate for the missed one. If it is almost time for your next dose, skip the missed dose and continue with your regular dosing schedule. If you frequently forget doses, consider using a pill organizer, alarm, or smartphone reminder application to help maintain adherence. Consistent dosing is important for maintaining the therapeutic effect of the medication.
Overdose
If you have taken more Dimethyl Fumarate Hexal than you should, contact your doctor or local poison control center immediately. There is limited experience with overdose of dimethyl fumarate in clinical settings. Based on the known pharmacological profile, symptoms of overdose may include more intense flushing, gastrointestinal symptoms (nausea, vomiting, diarrhea, abdominal pain), and potentially an increase in the known adverse effects of the drug. There is no specific antidote for dimethyl fumarate overdose. Treatment should be supportive, with management of symptoms as they arise. Given the short half-life of MMF (approximately 1 hour), the acute effects of an overdose would be expected to resolve relatively quickly, although gastrointestinal symptoms may persist for longer.
Flushing and gastrointestinal symptoms are most common during the first month of treatment and typically diminish over time. Strategies to minimize these effects include: (1) always taking capsules with a meal, especially one containing fat; (2) following the recommended titration schedule; (3) taking non-enteric-coated aspirin (325 mg) approximately 30 minutes before each dose if flushing is bothersome (discuss with your doctor first); and (4) being patient, as these symptoms typically improve significantly within the first 2–3 months of treatment.
What Are the Side Effects of Dimethyl Fumarate Hexal?
Like all medicines, Dimethyl Fumarate Hexal can cause side effects, although not everyone who takes it will experience them. The side effect profile of dimethyl fumarate has been extensively characterized through the pivotal clinical trials (DEFINE, CONFIRM), long-term extension studies (ENDORSE), and more than a decade of post-marketing surveillance worldwide. The majority of side effects are mild to moderate in severity and tend to decrease in frequency and intensity with continued treatment.
Understanding the side effects and their typical time course is important for managing expectations and maintaining treatment adherence. Many patients who initially experience flushing or gastrointestinal symptoms find that these effects diminish substantially after the first 1–3 months of treatment. Working closely with your healthcare team during this early period is essential.
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, chest, and upper back)
- Diarrhea
- Nausea
- Abdominal (stomach) pain or cramping
Common
May affect up to 1 in 10 people
- Vomiting
- Dyspepsia (indigestion)
- Gastritis (inflammation of the stomach lining)
- Gastrointestinal disorder
- Burning sensation
- Hot flush
- Itching (pruritus)
- Rash
- Proteinuria (protein in the urine)
- Feeling of warmth
- Elevated liver enzymes (ALT, AST)
- Lymphopenia (decreased lymphocyte count)
- Leukopenia (decreased white blood cell count)
- Albumin in urine
- Ketones in urine
Uncommon
May affect up to 1 in 100 people
- Hypersensitivity (allergic) reactions
- Anaphylaxis
- Herpes zoster (shingles)
- Severe lymphopenia (lymphocyte count < 0.5 x 109/L)
Rare
May affect up to 1 in 1,000 people
- Progressive multifocal leukoencephalopathy (PML) — in the context of prolonged severe lymphopenia
- Fanconi syndrome (renal tubular disorder)
- Angioedema (swelling of the face, lips, tongue, or throat)
Not Known
Frequency cannot be estimated from available data
- Hepatic injury (liver damage) with elevated transaminases
- Herpes simplex infections (including encephalitis and meningitis in the setting of severe lymphopenia)
Flushing is the most characteristic side effect of dimethyl fumarate. It typically presents as a warm, red, itchy, or burning sensation of the skin, predominantly affecting the face, neck, chest, and upper back. Flushing episodes usually begin within 30 minutes of taking a dose and can last from a few minutes to several hours. In clinical trials, flushing occurred in approximately 40% of patients during the first month of treatment but decreased to approximately 5% by month 12. Flushing is thought to be mediated through activation of the HCAR2 (GPR109A) receptor on Langerhans cells in the skin, leading to the release of prostaglandin D2. Taking dimethyl fumarate with food and, if necessary, pre-treatment with non-enteric-coated aspirin (325 mg, taken 30 minutes before the dose) have been shown to reduce the severity and frequency of flushing episodes.
Gastrointestinal side effects (diarrhea, nausea, abdominal pain, vomiting) are the other major category of common adverse events. These effects are also most prominent during the first month of treatment, with approximately 14–18% of patients experiencing abdominal pain and 12–14% experiencing diarrhea in the early weeks. By month 3, the incidence of gastrointestinal events typically decreases to levels comparable to placebo. Administration with food is the most effective strategy for reducing gastrointestinal symptoms.
Lymphopenia deserves special attention. In clinical trials, dimethyl fumarate treatment led to a mean decrease in lymphocyte counts of approximately 30% from baseline during the first year of treatment, with a plateau thereafter. The majority of patients maintain lymphocyte counts within the normal range, but approximately 2–6% of patients may develop grade 3 lymphopenia (lymphocyte count < 0.5 x 109/L). Prolonged severe lymphopenia (lasting more than 6 months) is the primary risk factor for PML. For this reason, regular blood count monitoring is mandatory, and treatment discontinuation should be considered if severe lymphopenia persists.
Progressive multifocal leukoencephalopathy (PML) is the most serious potential adverse effect of dimethyl fumarate. PML is a rare, progressive, and often fatal brain infection caused by the John Cunningham (JC) virus, which is latent in approximately 50–60% of the general population. In the context of immunosuppression, the JC virus can reactivate and infect oligodendrocytes in the brain, leading to progressive demyelination. As of post-marketing surveillance data, all confirmed cases of PML in patients taking dimethyl fumarate have occurred in the setting of prolonged lymphopenia, typically with lymphocyte counts below 0.5 x 109/L for 6 months or more. Early symptoms of PML can mimic an MS relapse and include progressive weakness, vision changes, confusion, personality changes, and speech difficulties. If PML is suspected, treatment should be stopped immediately and urgent neurological evaluation, including brain MRI and cerebrospinal fluid testing for JC virus DNA, should be performed.
Contact your doctor or seek emergency medical care immediately if you experience: signs of a severe allergic reaction (difficulty breathing, facial or throat swelling, severe rash, feeling faint); new or worsening neurological symptoms that could suggest PML (progressive weakness on one side, vision changes, confusion, personality changes); signs of serious infection (high fever, severe fatigue, unexplained weight loss); or symptoms of liver problems (yellowing of skin or eyes, dark urine, persistent nausea, upper right abdominal pain).
How Should You Store Dimethyl Fumarate Hexal?
Proper storage of Dimethyl Fumarate Hexal is important to maintain the quality, safety, and therapeutic effectiveness of the medication. The gastro-resistant capsules are designed to withstand the acidic environment of the stomach, and their integrity can be compromised by exposure to excessive heat, moisture, or light.
Follow these storage guidelines:
- Temperature: Store at temperatures below 30 °C (86 °F). Do not freeze the capsules. Avoid storing them in locations that may become excessively warm, such as in a car on a hot day, near a radiator, or in direct sunlight.
- Protect from light and moisture: Keep the capsules in the original blister packaging until you are ready to take them. The blister pack provides protection from moisture and light, which can degrade the gastro-resistant coating and the active substance.
- Do not transfer to other containers: Do not place the capsules in a daily pill organizer for extended periods, as this removes them from their protective packaging and may expose them to moisture and light.
- Keep out of reach of children: Store the medication in a secure location where children cannot access it. The capsules should not be used by anyone other than the patient for whom they were prescribed.
- Expiry date: Do not use Dimethyl Fumarate Hexal after the expiry date printed on the blister and carton. The expiry date refers to the last day of that month.
- Disposal: Do not dispose of unused capsules via household waste or wastewater. Ask your pharmacist about local medication take-back programs or approved disposal methods to protect the environment.
If you notice any visible changes in the appearance of the capsules, such as discoloration, softening, cracking, or a strong unusual odor, do not take them. Return the affected capsules to your pharmacist for safe disposal and obtain a replacement supply.
What Does Dimethyl Fumarate Hexal Contain?
Each gastro-resistant hard capsule of Dimethyl Fumarate Hexal contains the following components:
Active substance:
- 120 mg capsule: Each capsule contains 120 mg of dimethyl fumarate.
- 240 mg capsule: Each capsule contains 240 mg of dimethyl fumarate.
Other ingredients (excipients):
The capsule core contains:
- Microcrystalline cellulose (a commonly used pharmaceutical filler)
- Croscarmellose sodium (helps the capsule contents disintegrate properly)
- Talc (used as a glidant to improve powder flow during manufacturing)
- Silica colloidal anhydrous (anti-caking agent)
- Magnesium stearate (lubricant used in capsule manufacturing)
- Triethyl citrate (plasticizer for the enteric coating)
- Methacrylic acid-methyl methacrylate copolymer (1:1) — the primary component of the gastro-resistant (enteric) coating that protects the active substance from stomach acid
- Methacrylic acid-ethyl acrylate copolymer (1:1) — additional enteric coating component
- Simethicone (anti-foaming agent)
- Sodium laurilsulfate (surfactant)
- Polysorbate 80 (emulsifier)
The capsule shell is made of gelatin and contains colorants including titanium dioxide (E171), brilliant blue FCF (E133), and iron oxide yellow (E172). The capsule size and color may differ between the 120 mg and 240 mg strengths to help differentiate the two doses.
Patients with known allergies to any of the listed excipients should inform their doctor or pharmacist before starting treatment. The formulation does not contain lactose or gluten.
Frequently Asked Questions About Dimethyl Fumarate Hexal
Dimethyl Fumarate Hexal is a generic version of Tecfidera. Both contain the same active ingredient (dimethyl fumarate) at the same doses (120 mg and 240 mg gastro-resistant capsules). As a generic medicine approved by the European Medicines Agency, Dimethyl Fumarate Hexal has demonstrated bioequivalence to Tecfidera, meaning it delivers the same amount of active substance to the bloodstream in the same way. The efficacy, safety profile, and quality standards are equivalent. The primary difference is typically the cost, with generic versions generally being more affordable, which can improve access to this important MS treatment.
Dimethyl fumarate begins to exert its immunomodulatory effects within weeks of starting treatment, but the full clinical benefit in terms of reducing MS relapses and MRI activity develops over several months. In clinical trials, significant reductions in MRI lesion activity were observed within the first 6 months of treatment, and the reduction in annualized relapse rate was measured over a 2-year period. It is important to continue taking the medication as prescribed even if you do not notice immediate improvements, as the protective effects are cumulative. Your neurologist will typically evaluate treatment effectiveness using a combination of clinical assessments (relapse frequency, disability progression) and MRI scans at regular intervals, usually after 6 to 12 months of treatment.
Flushing is the most common side effect during the first few weeks of treatment and typically decreases significantly over time. To manage flushing: (1) always take the capsules with a substantial meal, especially one containing some fat; (2) discuss with your doctor whether taking non-enteric-coated aspirin (325 mg) approximately 30 minutes before each dose may help (this has been shown in studies to reduce flushing severity); (3) your doctor may temporarily reduce the dose to 120 mg twice daily for up to 4 weeks if symptoms are severe; (4) avoid alcohol, hot beverages, and spicy foods around the time of dosing, as these can worsen flushing. Most patients find that flushing resolves or becomes very mild within the first 1–3 months of treatment.
There is no specific contraindication to moderate alcohol consumption during treatment with dimethyl fumarate. However, alcohol can worsen flushing episodes (as it causes vasodilation), and it may exacerbate gastrointestinal side effects such as nausea and stomach irritation. Additionally, both alcohol and dimethyl fumarate can affect liver function, so excessive alcohol consumption should be avoided. Discuss your alcohol intake with your doctor, who can advise you based on your individual circumstances and liver function test results.
Blood tests (complete blood count including lymphocyte count, and liver function tests) are required before starting treatment, then at approximately 6 months, and then at least every 6 to 12 months during treatment. If your lymphocyte count shows a declining trend or falls below normal levels, your doctor may request more frequent monitoring (e.g., every 3 months). If your lymphocyte count falls below 0.5 x 109/L, more frequent monitoring is essential, and if it remains at this level for more than 6 months, your doctor will likely discuss discontinuing treatment due to the increased risk of PML. Your doctor may also request kidney function tests periodically.
You should not stop taking Dimethyl Fumarate Hexal without consulting your neurologist, as stopping a disease-modifying therapy can lead to a return of MS disease activity (relapses and new MRI lesions). Unlike some other MS therapies (notably fingolimod), dimethyl fumarate has not been strongly associated with severe disease rebound upon discontinuation. However, the protective effect against relapses and disease progression will cease once the medication is stopped. If discontinuation is necessary (for example, due to persistent severe lymphopenia or planning a pregnancy), your neurologist will discuss the timing and whether switching to an alternative disease-modifying therapy is appropriate for your situation.
References
- European Medicines Agency (EMA). Tecfidera (dimethyl fumarate) – Summary of Product Characteristics. Last updated 2024. Available from: EMA – Tecfidera.
- U.S. Food and Drug Administration (FDA). Tecfidera (dimethyl fumarate) – Prescribing Information. Revised 2024. Available from: FDA – Tecfidera Label.
- 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.
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