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Dimethyl Fumarate Mylan is a brand name for Dimethyl Fumarate. The medicine, its uses, side effects and dosage are the same regardless of brand.
Verbatim from this product's EMA label. Tap a section to expand.
Treatment should be initiated under supervision of a physician experienced in the treatment of multiple sclerosis. Posology The starting dose is 120 mg twice a day. 4). If a patient misses a dose, a double dose should not be taken. The patient may take the missed dose only if they leave 4 hours between doses.
Otherwise the patient should wait until the next scheduled dose. 3 Temporary dose reduction to 120 mg twice a day may reduce the occurrence of flushing and gastrointestinal adverse reactions. Within 1 month, the recommended maintenance dose of 240 mg twice a day should be resumed.
2). 8). 2). Based on the mode of action of the active substance there are no theoretical reasons for any requirement for dose adjustments in the elderly. Renal and hepatic impairment Dimethyl fumarate has not been studied in patients with renal or hepatic impairment.
2). 4). Paediatric population The posology is the same in adults and in paediatric patients aged 13 years and older. There are limited data available in children between 10 and 12 years old. 1 but no recommendation on a posology can be made.
The safety and efficacy of dimethyl fumarate in children aged less than 10 years have not been established. No data are available. Method of administration For oral use. The capsule should be swallowed whole. The capsule or its contents should not be crushed, divided, dissolved, sucked or chewed as the enteric-coating of the pellets prevents irritant effects on the gastrointestinal tract.
e. diarrhoea (14%), nausea (12%), abdominal pain (10%), abdominal pain upper (10%)). Flushing and gastrointestinal events tend to begin early in the course of treatment (primarily during the first month) and in patients who experience flushing and gastrointestinal events, these events may continue to occur intermittently throughout treatment with dimethyl fumarate.
The most commonly reported adverse reactions leading to treatment discontinuation are flushing (3%) and gastrointestinal events (4%). In phase 2 and 3 placebo-controlled and uncontrolled clinical studies, a total of 2 513 patients have received dimethyl fumarate for periods of up to 12 years with an overall exposure equivalent to 11 318 person-years.
A total of 1 169 patients have received at least 5 years of treatment with dimethyl fumarate, and 426 patients have received at least 10 years of treatment with dimethyl fumarate. The experience in uncontrolled clinical trials is consistent with the experience in the placebo-controlled clinical trials.
Tabulated list of adverse reactions Adverse reactions arising from clinical studies, post-authorisation safety studies and spontaneous reports, are presented in the table below. The adverse reactions are presented as MedDRA preferred terms under the MedDRA System Organ Class.
The incidence of the adverse reactions below is expressed according to the following categories: - Very common (≥1/10) - Common (≥1/100 to <1/10) - Uncommon (≥1/1 000 to <1/100) - Rare (≥1/10 000 to <1/1 000) - Very rare (<1/10 000) - Not known (frequency cannot be estimated from the available data) 10 MedDRA System Organ Class Adverse reaction Frequency category Infections and infestations Gastroenteritis Common Progressive multifocal leukoencephalopathy (PML) Not known Herpes zoster Not known Blood and lymphatic system disorders Lymphopenia Common Leucopenia Common Thrombocytopenia Uncommon Immune system disorders Hypersensitivity Uncommon Anaphylaxis Not known Dyspnoea Not known Hypoxia Not known Hypotension Not known Angioedema Not known Nervous system disorders Burning sensation Common Vascular disorders Flushing Very common Hot flush Common Respiratory, thoracic and mediastinal disorders Rhinorrhoea Not known Gastrointestinal disorders Diarrhoea Very common Nausea Very common Abdominal pain upper Very common Abdominal pain Very common Vomiting Common Dyspepsia Common Gastritis Common Gastrointestinal disorder Common Hepatobiliary disorders Aspartate aminotransferase increased Common Alanine aminotransferase increased Common Drug-induced liver injury Rare Skin and subcutaneous tissue disorders Pruritus Common Rash Common Erythema Common Alopecia Common Renal and urinary disorders Proteinuria Common General disorders and administration site conditions Feeling hot Common Investigations Ketones measured in urine Very common Albumin urine present Common White blood cell count decreased Common Description of selected adverse reactions Flushing In the placebo-controlled studies, the incidence of flushing (34% versus 4%) and hot flush (7% versus 2%) was increased in patients treated with dimethyl fumarate compared to placebo, respectively.
8). The clinical implications of these changes are unknown. g. creatinine, blood urea nitrogen and urinalysis) is recommended prior to treatment initiation, after 3 and 6 months of treatment, every 6 to 12 months thereafter and as clinically indicated.
4 Hepatic function Drug-induced liver injury, including liver enzyme increase (≥ 3 times upper limit of normal (ULN)) and elevation of total bilirubin levels (≥ 2xULN) can result from treatment with dimethyl fumarate. The time to onset can be days, several weeks or longer.
Resolution of the adverse reactions has been observed after treatment was discontinued. g. alanine aminotransferase (ALT), aspartate aminotransferase (AST)) and total bilirubin levels are recommended prior to treatment initiation and during treatment as clinically indicated.
8). Prior to initiating treatment with dimethyl fumarate, a current complete blood count, including lymphocytes, must be performed. If lymphocyte count is found to be below the normal range, thorough assessment of possible causes should be completed prior to initiation of treatment.
Dimethyl fumarate has not been studied in patients with pre-existing low lymphocyte counts and caution should be exercised when treating these patients. 5x109/L). After starting therapy, complete blood counts, including lymphocytes, must be performed every 3 months.
5x109/L) persisting for more than 6 months. 8x109/L for more than 6 months, the benefit/risk balance of treatment with dimethyl fumarate should be re-assessed. • In patients with lymphocyte counts below lower limit of normal (LLN) as defined by local laboratory reference range, regular monitoring of absolute lymphocyte counts is recommended.
Additional factors that might further augment the individual PML risk should be considered (see subsection on PML below). 1). Upon recovery and in the absence of alternative treatment options, decisions about whether or not to restart dimethyl fumarate after treatment discontinuation should be based on clinical judgement.
1. Suspected or confirmed progressive multifocal leukoencephalopathy (PML).
Not medical advice. Always read the patient information leaflet and follow your prescriber or pharmacist.
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g. warmth, redness, itching, and burning sensation). Flushing events tend to begin early in the course of treatment (primarily during the first month) and in patients who experience flushing, these events may continue to occur intermittently throughout treatment with dimethyl fumarate.
In patients with flushing, the majority had flushing events that were mild or moderate in severity. Overall, 3% of patients treated with dimethyl fumarate discontinued due to flushing. 5). g. diarrhoea [14% versus 10%], nausea [12% versus 9%], upper abdominal pain [10% versus 6%], abdominal pain [9% versus 4%], vomiting [8% versus 5%] and dyspepsia [5% versus 3%]) was increased in patients treated with dimethyl fumarate compared to placebo, respectively.
Gastrointestinal adverse reactions tend to begin early in the course of treatment (primarily during the first month) and in patients who experience gastrointestinal events, these events may continue to occur intermittently throughout treatment with dimethyl fumarate.
In the majority of patients who experienced gastrointestinal events, it was mild or moderate in severity. Four per cent (4%) of patients treated with dimethyl fumarate discontinued due to gastrointestinal adverse reactions. 2). Hepatic function Based on data from placebo-controlled studies, the majority of patients with elevations had hepatic transaminases that were < 3 times the ULN.
The increased incidence of elevations of hepatic transaminases in patients treated with dimethyl fumarate relative to placebo was primarily seen during the first 6 months of treatment. Elevations of alanine aminotransferase and aspartate aminotransferase ≥ 3 times ULN, respectively, were seen in 5% and 2% of patients treated with placebo and 6% and 2% of patients treated with dimethyl fumarate.
Discontinuations due to elevated hepatic transaminases were < 1% and similar in patients treated with dimethyl fumarate or placebo. Elevations in transaminases ≥ 3 times ULN with concomitant elevations in total bilirubin > 2 times ULN, were not observed in placebo-controlled studies.
Increase of liver enzymes and cases of drug-induced liver injury (elevations in […]
Magnetic resonance imaging (MRI) Before initiating treatment with dimethyl fumarate, a baseline MRI should be available (usually within 3 months) as a reference. The need for further MRI scanning should be considered in accordance with national and local recommendations.
MRI imaging may be considered as part of increased vigilance in patients considered at increased risk of PML. In case of clinical suspicion of PML, MRI should be performed immediately for diagnostic purposes. 8). PML is an opportunistic infection caused by John-Cunningham virus (JCV), which may be fatal or result in severe disability.
PML cases have occurred with dimethyl fumarate and other medicinal products containing fumarates in the setting of lymphopenia (lymphocyte counts below LLN). Prolonged moderate to severe 5 lymphopenia appears to increase the risk of PML with dimethyl fumarate, however, risk cannot be excluded in patients with mild lymphopenia.
Additional factors that might contribute to an increased risk of PML in the setting of lymphopenia are: - duration of dimethyl fumarate therapy. Cases of PML have occurred after approximately 1 to 5 years of treatment, although the exact relationship with duration of treatment is unknown.
8), and - prior immunosuppressive or immunomodulatory therapy (see below). Physicians should evaluate their patients to determine if the symptoms are indicative of neurological dysfunction and, if so, whether these symptoms are typical of MS or possibly suggestive of PML.
At the first sign or symptom suggestive of PML, dimethyl fumarate should be withheld and appropriate diagnostic evaluations, including determination of JCV DNA in cerebrospinal fluid (CSF) by quantitative polymerase chain reaction (PCR) methodology, need to be performed.
The symptoms of PML may be similar to an MS relapse. Typical symptoms associated with PML are diverse, progress over days to weeks, and include progressive weakness on one side of the body or clumsiness of limbs, disturbance of vision, and changes in thinking, memory, and orientation leading to confusion and personality changes.
Physicians should be particularly alert to symptoms suggestive of PML that the patient may not notice. Patients should also be advised to inform their partner or caregivers about their treatment, since they may notice symptoms that the patient is not aware of.
PML can only occur in the presence of a JCV infection. It should be considered that the influence of lymphopenia on the accuracy of serum anti-JCV antibody testing has not been studied in dimethyl fumarate treated patients. It should also be noted that a negative anti-JCV antibody test (in the presence of normal lymphocyte counts) does not preclude the possibility of subsequent JCV infection.
If a patient develops PML, dimethyl fumarate must be permanently discontinued. Prior treatment with immunosuppressive or immunomodulating therapies No studies […]