Fumaric acid & fumarates: This is how dimethyl fumarate & Co.

Fumaric acid & fumarates This is how dimethyl fumarate & Co.

Fumaric acid occurs in all living organisms, but the substance is mainly contained in  fungi  and lichens. Chemical compounds that are formed from fumaric acid are the so-called fumarates, also known as fumaric acid esters. These have an immunosuppressive effect and are used in medicine to treat  psoriasis  and  multiple sclerosis  (MS). How exactly do fumarates work, how are they used and what side effects can occur when taking them?

Fumaric acid and fumarates – what is it?

Fumaric acid is a so-called dicarboxylic acid and belongs to the group of fruit acids. Another term for this is trans-butenedioic acid. It occurs naturally in all living things. However, the substance is increasingly contained in fungi, lichens and other plants.

Fumaric acid got its name from a plant called common fumitory (Fumaria officinalis), in which it occurs in particularly large quantities. Besides its use in medicine, fumaric acid is also used in the food industry. It is used there as an acidifier, for example in pudding powder,  chewing gum  or cake fillings. It can then be recognized in the list of ingredients by the label E 297.

Fumarates, in turn, are so-called esters, i.e. a chemical compound that is formed from fumaric acid – the esters are the salts of fumaric acid. In contrast to fumaric acid, its esters can be absorbed through the intestines.

Fumarate: Effect on psoriasis

Psoriasis, or psoriasis, is a common  skin condition characterized by scaly, inflamed patches of skin. One of the possible triggers of psoriasis is the overstimulation of certain cells in the immune system (TH1 and TH17 cells), which subsequently cause an inflammatory response in the body. Fumaric acid esters inhibit TH1 cells, which are overproduced in people with psoriasis. They act as so-called immunosuppressants.

For the treatment of moderate to severe psoriasis, two preparations containing fumarates are currently approved in Germany for the treatment of psoriasis for adult patients. One agent (Skilarence®) is based on the active ingredient  dimethyl fumarate  (DMF, also known as dimethyl fumarate). The other (Fumaderm®) on a  combination of DMF  with three salts of  ethyl hydrogen fumarates.

Strictly speaking, dimethyl fumarate is a so-called prodrug, i.e. a precursor of the actually active substance. DMF is easily absorbed into the blood and is then converted within the body into monomethyl fumarate, which then exerts its effects.

Fumaric acid esters in multiple sclerosis

Multiple sclerosis is a chronic inflammation of the central nervous system that causes permanent damage to the lining of the nerve cells in the spinal cord and brain.

Two types of fumarates are used in adults with relapsing remitting multiple sclerosis: the aforementioned  dimethyl fumarate and  diroximel  fumarate,  a further development of DMF.

In the case of multiple sclerosis, too, the esters, more precisely the monomethyl fumarate produced in the body, are said to inhibit the activity of the immune system and at the same time have an anti-inflammatory effect. The frequency of flare-ups can thus be reduced by taking the medication.

ingestion of fumarates

It is taken in tablet form and, in the case of psoriasis, only when local treatments have not worked.

The dosage should be taken as directed by a doctor and is usually increased to the final dose over the course of several weeks. If severe side effects occur, the dosage can be reduced again in consultation with the doctor. People with multiple sclerosis usually take two tablets a day and people with psoriasis take three tablets a day.

If there are gastrointestinal problems as a side effect, taking them with meals can counteract them.

possible side effects

The side effects of the drugs based on dimethyl fumarate (or diroximel fumarate) approved for the treatment of psoriasis or multiple sclerosis do not differ significantly. Diroximel fumarate only has a lower risk of developing gastrointestinal symptoms.

Drugs with DMF can cause the following side effects, among others:

  • Diarrhea , reddening of the skin and  hot flushes  on the face and neck and a mild form of leukopenia (low  white blood cell count ) or lymphopenia (insufficient  lymphocytes ) are very common  .
  • Abdominal cramps, transient  eosinophilia  (increase in eosinophilic granulocytes) and severe lymphopenia are common.
  • Occasionally sufferers report  nausea , dizziness, headaches or tiredness. Functional disorders of the kidneys, such as increased excretion of  protein  (proteinuria) and increased creatinine values ​​in the serum are occasionally registered.

In order to be able to identify changes as quickly as possible, such as low lymphocyte values ​​or increased excretion of protein, blood and urine tests are carried out regularly before the start of therapy and as part of treatment with fumaric acid esters.

In individual cases, serious side effects are possible

When using preparations with DMF or diroximel fumarate, a complete  blood count should be taken regularly (depending on the preparation every four weeks to every three months)  . The reason for this is the very rare occurrence of a serious disease in connection with the intake: progressive multifocal leukoencephalopathy (PML). This is a serious disease of the central nervous system.

This is triggered by the so-called JC virus (John Cunningham virus), which most people carry and which can trigger PML in the case of an immune deficiency. Symptoms include motor and sensory disorders.

If the blood count shows a strong weakening of the immune system due to very low lymphocyte values, the dose of the medication taken should be halved after consultation with a doctor to be on the safe side, or the therapy should be ended in order to avoid infection with the JC virus.

Contraindications – when use is not advisable

Drugs containing fumarates should not be taken if:

  • hypersensitivity to fumaric acid or fumarates
  • progressive multifocal leukoencephalopathy is suspected or present
  • have a severe gastrointestinal disease
  • known severe liver or kidney disease
  • you are pregnant or breastfeeding
  • the person concerned is under 18 years of age

The data on the use of fumaric acid esters during pregnancy and lactation are very limited. If possible, you should avoid using it during this time. In any case, when pregnancy becomes known, it should be discussed with the doctor treating you whether there is an alternative treatment, whether the therapy should be discontinued completely, or whether the individual health benefit outweighs the risk of the treatment.

Which interactions are possible?

If fumarates are taken at the same time as other medications, interactions can sometimes occur. The following should not be used at the same time as fumaric acid esters:

Since the esters of fumaric acid can have a negative effect on kidney function, it is generally not recommended to take drugs with similar effects at the same time. The simultaneous use of other agents based on fumaric acid should also be avoided in order to avoid an overdose.

Similar Posts

Leave a Reply

Your email address will not be published. Required fields are marked *