Fumaric acid ester

Author: Prof. Dr. med. Peter Altmeyer

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Last updated on: 16.05.2022

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Antipsoriatic with immunomodulating and proliferation-normalizing effect. The monopreparation dimethyl ester Skilarence® 30 mg and 120 mg, as well as Tecfidera® 120 mg and 240 mg and the mixture of monoethyl and dimethyl fumarate Fumaderm® initial (30 mg) and Fumaderm® (120 mg), which has long been known in dermatology, are used.

Pharmacodynamics (Effect)
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The pharmacological effects of fumaric acid esters have not yet been fully clarified. Probable is an antiproliferative effect on lymphocytes as well as a selective immunomodulatory antipsoriatic effect on activated T-lymphocytes. In co-cultures of keratinocytes and T-lymphocytes an inhibition of INF-gamma as well as an increased secretion of IL-10 could be detected. Thus FAE cause a reduction of lesional and global T-lymphocytes.

It is assumed that dimethylfumarate (DMF) interacts with the intracellular thiol system, which influences the cellular stability of the redox balance. Therefore, in the long run, an increase of reduced glutathione is observed. This increase inhibits redox-sensitive kinases, which consecutively inhibits phosphorylation and ubiquitination of the nuclear factor inhibitor kappa B ( NF-kappaB).

NF-kappaB itself has numerous target genes and mediates various effects. NF-kappaB is of great importance for the regulation of the immune response, cell proliferation and apoptosis. It inhibits the transcription of genes coding for pro-inflammatory mediators such as tumor necrosis factor, interleukin 8 and adhesion molecules. This results in a strong anti-inflammatory effect.

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Moderate and severe, therapy-resistant forms of psoriasis vulgaris, dimethyl fumarate also approved in multiple sclerosis.

Limited indication
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Hematological diseases. Renal failure

Dosage and method of use
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  • Oral application is done in increasing dosage, e.g. Fumaderm initial 1 tbl./day in week 1 up to a maximum of 6 tbl./day Fumaderm in week 6.
  • The weekly increase from 1 tablet/day Fumaderm initial to 4-5 tablets has proven to be effective. If well tolerated, it is then possible to switch to Fumaderm, keeping in mind that 1 tablet of Fumaderm is equivalent to 4 tablets of Fumaderm initial.
  • In many cases, however, administration of the max. TD of 6 tbl./day (= 1.29 g/day) Fumaderm p.o. is not necessary. After the skin symptoms have subsided (4-6 weeks after the start of therapy), it is recommended to reduce the daily intake to the individually required maintenance dose.
  • If necessary, discontinuation trials are indicated in order to check the acuity of the psoriasis and thus the need for further treatment.

The monopreparation with dimethyl fumarate (Skilarence®) is also slowly increased, starting with Skilarence® 30 mg 1 / day, increasing up to 3 tbl / day, depending on tolerability change to Skilarence® 120 mg or further up to 4 tbl Skilarence® 30 mg - note: 1 tablet Skilarence® 120 mg corresponds to 4 tbl Skilarence® 30 mg. If well tolerated, continue to increase individually depending on effect; the maximum dose of 6 tbl is rarely needed.

In multiple sclerosis, the dimethyl fumarate Tecfidera® is recommended at the beginning, in the first 7 days 2 x 1 Tbl a 120 mg / day, then daily 2 tablets Tecfidera® 240 mg / day.

Reminder. Before starting and during the course of therapy (initially every 2, later every 4 weeks) check the Diff.

Undesirable effects
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  • Gastrointestinal disorders, diarrhoea, flush, eosinophilia, leukopenia, in rare cases creatinine increase, proteinuria. The side effects such as flushed sensations and sensations of heat as well as gastrointestinal complaints usually decrease significantly with the duration of therapy.
  • Mild leukopenia, moderate to distinct lymphopenia are regular side effects of the therapy, rarely eosinophilia.
  • Although animal experiments have not shown any evidence of a teratogenic effect, fumarates must not be given during pregnancy.
  • A dose adjustment should be made in case of leukopenia, decrease in lymphocyte count < 500/μl, persistent eosinophilia > 25%, increase in creatinine > 30% or massive tubular proteinuria.
  • Malignoma induction: Based on clinical studies and spontaneous reports since the early 1990s, no evidence of an increased risk of malignancy was found in 110,000 patient-years. An antiproliferative and proaptotic effect was demonstrated in several studies. Recently, the development of Kaposi's sarcoma and malignant melanomahas been reported under therapy.

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Pregnancy, lactation, adolescents < 18 years, gastrointestinal ulcers, severe liver and kidney diseases.

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Psoriasis: Skilarence 30 mg®, Skilarence 120 mg®, Fumaderm®, Fumaderm initial®.

Multiple sclerosis: Tecfidera® 120mg/-240 mg enteric-coated hard capsules

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Remarkably, dimethyl fumarates have at times been used as antimicrobial (fungicidal) substances in the Chinese furniture industry (e.g. sofa cushions) and shoe industry. This can lead to contact allergic reactions among the production workers involved.

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  18. https://www.multiplesklerose.ch/PDF/de/Infoblaetter/02_MS-Medikamente/MS-Info_Tecfidera.pdf
  19. https://www.patienteninfo-service.de/a-z-liste/t/tecfideraR-120mg-240-mg-magensaftresistente-hartkapseln#3


Last updated on: 16.05.2022