Methotrexate

Explanation / definition

Methotrexate is a long-term disease-modifying antirheumatic drug (DMARD) / basic therapeutic agent in the treatment of rheumatoid arthritis and psoriatic arthritis. It is used when there is high disease activity. If it is ineffective or less effective, methotrexate can also be combined with other DMARDs. During therapy with methotrexate, undesirable side effects can be countered with folic acid preparations without loss of effectiveness.

Methotrexate is also used in the treatment of various malignant tumor diseases. This indication will not be discussed in detail here.

Trade names

Lantarel ® from Wyeth Pharma GmbH
Metex ® from medac
MTX
and many more

Common typos

Metothrexate, metotrexate, methotrexate, methotrexad

Chemical name

Structural formula

Active ingredient

Methotrexate disodium

application areas

Methotrexate is used in severe forms / high disease activity rheumatoid arthritis and the Psoriatic arthritis.

Methotrexate (e.g. Lantarel ® / Metex ®) in the most severe forms of psoriasis (Psoriasis vulgaris), which cannot be adequately treated with other forms of therapy.

Methotrexate is also used in early forms Ectopic pregnancy used.

Dosage forms

• Tablets / film-coated tablets
• solution
• infusion

effect

Methotrexate is an antagonist of folic acid (folic acid antagonist) and, as an antimetabolite, inhibits the reproduction of rapidly dividing cells. Furthermore, as an immunosuppressant, methotrexate weakens undesirable defensive reactions and has an anti-inflammatory effect.

An improvement in the symptoms can usually be expected after 4-8 weeks. Symptoms may recur after stopping methotrexate (see: Discontinue cortisone). Therapy with methotrexate is generally long-term.

application

The tablets are swallowed whole with plenty of liquid (no dairy products), preferably in the evening (once a week), preferably not with meals.

Skin or mucous membrane contact should be avoided - otherwise rinse the affected areas immediately with plenty of water.

dosage

In rheumatoid arthritis and psoriatic arthritis, the starting dose is 7.5 mg once a week, always on the same day of the week. If the effect is insufficient and well tolerated, the dose can be increased gradually by 2.5 mg. A weekly dose of 20 mg methotrexate should not be exceeded.

For psoriasis vulgaris (dandruff), the starting dose is 7.5 - 22.5 mg methotrexate once a week, always on the same day of the week. If the effect is insufficient and well tolerated, the dose can be increased gradually. A weekly dose of 30 mg methotrexate should not be exceeded.

After achieving the desired success of the treatment, the dose should, if possible, be reduced gradually to the lowest effective maintenance dose.

Methotrexate (e.g. Lantarel ® / Metex ® / MTX ®) should be used in reduced doses and under close medical supervision for:

• Old age
• Bad general condition
• Fluid build-up in the abdomen or between the lung leaves (ascites, pleural effusion)
• Severely overweight
• Earlier, high-dose vitamin A therapy for psoriasis
• Reduced lung function

Side effects

The side effects depend on the dosage and the duration of use of methotrexate (e.g. Lantarel / Metex / MTX). They can appear during the entire duration of use, but are most common in the first six months.

Only the frequently and occasionally occurring side effects are listed here, rare, very rare or occasional side effects are not listed:

Frequent side effects:

• Loss of appetite,
• Nausea,
• Vomit,
• Stomach pain,
• Diarrhea,
• Inflammation and ulcers in the mouth and throat,
• Increase in liver values ​​(GOT, GPT, alkaline phosphatase

Uncommon side effects:

• Disorders of blood cell formation with a pathological reduction in red and white blood cells and platelets,
• allergic inflammation of the lungs and alveoli (pneumonitis, alveolitis),
• Skin redness,
• Skin rash,
• Itching,
• A headache,
• Fatigue,
• Drowsiness

While you are using methotrexate, you should see your doctor regularly (at least once a month for the first 6 months, then at least every three months) for a check-up.

Read all about this topic under: Methotrexate Side Effects

Interactions

While taking Methotrexate should no vaccinations with live vaccines be performed.

Alcohol consumption should avoided become. If you take other liver-damaging drugs (e.g. leflunomide, Azathioprine® , Sulfasalazine, retinoids) must be checked regularly by the doctor. This also applies to the simultaneous intake of sulfonamides, trimethoprim-sulfamethoxazole, Chloramphenicol, Pyrimethamine.

An increased toxicity of Methotrexate has been observed with an existing folic acid deficiency or simultaneous use of medication that causes a folic acid deficiency (e.g. sulfonamides, trimethoprim-sulfamethoxazole).

A indirect dose increase cause penicillins, salicylates, Phenytoin, Barbiturates, tranquilizers, oral contraceptives, tetracyclines, amidopyrine derivatives, sulfonamides and p-aminobenzoic acid, p-aminohippuric acid, probenecid, NSAIDs.

Contraindications - When should methotrexate not be taken?

Methotrexate must not be taken if:

• Known hypersensitivity to methotrexate
• Kidney dysfunction
• Liver damage
• Diseases of the blood-forming system
• Increased alcohol consumption
• Infections
• Ulcers in the gastrointestinal area (gastric ulcer, duodenal ulcer / gastric ulcer)
• pregnancy and breast feeding period

Women of childbearing potential and men taking methotrexate should use effective contraception.
Even if the male partner is being treated, conception should be avoided during therapy with methotrexate and in the following three months after stopping methotrexate.

Prices

Since there is always talk of cost pressure in the healthcare system, we consider it important to find out prices for drugs (prices and drugs are exemplary and without recommendation):

Lantarel® 7.5 mg 10 tablets (N1) € 22.48

Lantarel® 7.5 mg 30 tablets (N2) € 49.13

Lantarel® 10 mg 10 tablets (N1) € 27.41

Lantarel® 10 mg 30 tablets (N2) € 62.20

Metex® 7.5 mg 10 tablets (N1) € 22.46

Metex® 7.5 mg 30 tablets (N2) € 49.13

Metex® 10 mg 10 tablets (N1) € 27.32

Metex® 10 mg 30 tablets (N2) € 62.20

Prescription requirement

There is a prescription requirement for all dosages!

Methotrexate for rheumatism

Methotrexate (MTX for short, trade name Lantarel®) is a drug that is very often called the so-called Anti-rheumatic drug for treatment rheumatic inflammation is used.

The terms "rheumatism"or diseases of the rheumatic type summarize hundreds of different diseases that are caused by inflammation.

Because methotrexate immunosuppressive acts, i.e. reactions of the body's defense system suppressed, it is used in diseases in which this body's own defense is disturbed.

Especially with rheumatic joint inflammation (e.g. rheumatoid arthritis or psoriatic arthritis) methotrexate is used.
But also with rheumatic diseases that lead to a Inflammation of vessels (Vasculitis) or internal organs (e.g. Lupus erythematosus), methotrexate can be used for treatment.

Rheumatic inflammation can vary depending on the type of illness permanent joint damage how Rheumatoid nodules on the elbows or permanent disorders of internal organs.

Methotrexate is mostly used in combination with pain therapy used to combat the underlying inflammatory process and counteract the permanent damage.

The course of the disease is usually positively influenced by drugs such as methotrexate, which is why these drugs are also used Basic drugs or disease modifying drugs (DMARD, Disease Modifying AntiRheumatoid Drugs) is called.

Since in most cases no exact cause of the rheumatic disease is known, the diseases can usually not be cured.
Therapy with methotrexate should always first after careful consideration possible risks and side effects of treatment with the risks of non-treatment (e.g. permanent joint and organ damage).

The way in which methotrexate has anti-inflammatory effects has not yet been conclusively clarified.
It probably engages in that Immune system activity one in which there is the proliferation of immune cells and the production of inflammatory mediators (endogenous substances that initiate or maintain an inflammatory reaction, e.g. Cytokines) inhibits.
This will make the joint-destroying inflammatory process slowed down.

The use of methotrexate has been shown to reduce inflammatory joint changes such as joint pain and swelling in most cases.
Morning stiffness and tiredness decrease and resilience increases.

The signs of inflammation in the blood often improve with methotrexate (e.g. the sedimentation rate).

Long-term studies also show that methotrexate can reduce the progression of inflammatory bone changes can stop.

In approximately 10 to 20 percent In these cases, methotrexate therapy is not well tolerated, so that other basic drugs must be used.
The main side effects include nausea and Vomit, Inflammation of the oral mucosa, Cirrhosis of the liver and increased susceptibility to infection.

In some cases, a combination of methotrexate with other basic medications can also be useful.

How is methotrexate given for rheumatism?

Methotrexate is used in rheumatic diseases usually in small doses of 5-25 milligrams per week used and has mainly one in this dosage anti-inflammatory effect.

In much higher doses up to 10,000 milligrams daily For example, methotrexate is also used for treatment malignant cancers (Tumors) given.
At these high dosages there is a risk of unwanted side effects much greater than in the treatment of rheumatic diseases, the tolerance profile is even relatively good here.

Methotrexate is used once a week into the vein (intravenous, i.v.) or into the muscles (iintramuscular, i.m.) injected or taken in the form of tablets, although complete absorption of the drug is not always guaranteed (e.g. with diarrhea).

Besides, they are Methotrexate syringes better tolerated and the effect is stronger. It is imperative to ensure that methotrexate only once a week and is never taken in a shorter time interval.

Methotrexate usually works with a delay of 4-10 weeks, as well as other basic drugs used to treat rheumatism.
This delay time is often reduced by an additional intake of cortisone or cortisone-free anti-inflammatory drugs that work immediately.

The maximum effect is after three to four months reached.

Methotrexate therapy must be continued even if the rheumatic symptoms improve, as discontinuation can easily lead to a new flare-up.
So it is necessary that treatment with methotrexate long-term and regular he follows.

The use of methotrexate is not indicated if a allergy, pregnancy or Desire for children exists at Liver disease, Alcohol abuse, decreased blood formation or with severe Diabetes (Diabetes mellitus).

An intake of at least five milligrams is recommended Folic acid per week during methotrexate therapy to reduce side effects.

Methotrexate and folic acid

Methotrexate is an active ingredient that is called in the body Opponent of folic acid acts (a so-called folic acid antagonist).

Folic acid or vitamin B9 is important for that Cell division, in particular it plays a role in the production of building blocks of genetic material (DNA).

If the effect of folic acid is inhibited, the cell can no longer multiply.
Cancer cells or cells of the body's defense systemthat are too active and thus trigger a chronic inflammatory rheumatic disease can be prevented from cell growth and reproduction by the action of methotrexate.

Since methotrexate is an antagonist of folic acid, administration of folic acid can reverse the effect of methotrexate and act as a poisoning agent Antidote Act.

However, undesirable side effects of methotrexate can also be reduced or avoided entirely through a sensible administration of folic acid nausea, Inflammation of the oral mucosa, Liver enzyme increase, Hair loss and diarrhea.

How is folic acid given in combination with methotrexate?

The German Society for Rheumatology recommends a Folic acid supplementation (supplementary administration of folic acid in addition to food) with at least 5 milligrams of folic acid per week respectively.
For comparison: The daily dose recommended by the German Nutrition Society for folic acid is 400 micrograms.

However, you should start taking folic acid at the earliest 24-48 hours after taking or injecting methotrexate.
Most of the methotrexate is excreted on the first day after ingestion or injection of the syringe; a smaller amount of the methotrexate is first converted into a metabolic product that has a similar effect to methotrexate and is only excreted on the second day after methotrexate ingestion.

Folic acid supplementation is therefore essential after 48 hours recommended, since after this time there are no more significant amounts of methotrexate or its metabolic product in the body and the effect of the methotrexate is not significantly weakened.

Nevertheless, one achieves good protection against possible undesirable side effects.

The dosage of folic acid supplementation should, if necessary, be adjusted in the course of therapy; these are dosages up to 15 milligrams daily 5 days a week, starting 48 hours after administration of methotrexate is conceivable.
This increase in folic acid dose, for example, should if it occurs undesirable effects, especially one Increase in liver values be considered.

Alternatively, the Use of folinic acid in a dosage of 2.5 milligrams per week possible, there seem to be no relevant differences between folic acid or folinic acid supplementation.

The use of folic acid during treatment with methotrexate has been discussed controversially in the past.
There is concern that folic acid counteracts the effects of methotrexate rheumatic diseases could weaken or even cancel.

If folic acid is added to methotrexate therapy, the rate of possible side effects can be reduced.

If you give too much folic acid too soon, it can lead to a Methotrexate less effective come.
However, the mechanism of action of methotrexate in rheumatic diseases is still largely unclear, so that this connection does not necessarily have to exist.
Nevertheless, many rheumatologists in Germany and Europe do not generally give folic acid.

In this country, methotrexate therapy is usually initially carried out without folic acid supplementation.
The additional administration of folic acid is only made if methotrexate is not well tolerated or if there is evidence of one in the blood count Folic acid deficiency (Macrocytosis = too large blood cells and hyperchromasia = too high a load on the red blood cells with the blood pigment hemoglobin) demonstrate.

In addition, the folic acid deficiency manifests itself through Inflammation of the mucous membranes, especially the oral mucosa.
If such symptoms occur, methotrexate therapy is discontinued briefly interrupted and folic acid given in high doses until the inflammation of the mucous membranes has subsided.

Continued treatment with methotrexate is carried out with an additional one Folic acid supplementation.

Effect of methotrexate

Methotrexate is an active ingredient used to treat chronic inflammatory diseases as well as treating various Cancers is used.

Methotrexate has three important effects: it works antineoplastic, immunosuppressive and anti-inflammatory.

Antineoplastic means that methotrexate is effective against malignant (malignant) Tumors (Neoplasms) works.

Substances that have an antineoplastic effect are classified as Cytostatics counted.
A cytostatic inhibits body cell growth or cell division.
A cytostatic is used in the chemotherapy used in cancer to inhibit tumor growth.

As a cytostatic, methotrexate is used against acute lymphatic and myeloid leukemia, against Non-Hodgkin lymphoma, against Osteosarcomas in children and adolescents and against solid tumors (Breast, lung, bladder cancer) used.

Methotrexate continues to work immunosuppressive, that means it has the functions of the body's defense system reduced.
This effect of methotrexate is mainly used in the treatment of diseases that are caused by a malfunction of the immune system or in which the immune system is directed against the body's own cells (Autoimmune disease).

Immunosuppressive active ingredients such as methotrexate are not without side effects and risks, as it comes to a fundamental restriction of the weight loss mechanisms Infection risk increases.

Likewise, the risk of cancer is increased, because that too Multiplication and spread of malignant cells in the organism is facilitated by the immunosuppression.

Methotrexate is used as an immunosuppressive drug in much lower doses than in cytostatic therapy and is used in Rheumatoid arthritis, severe forms of psoriasis (psoriasis) and less often with diseases Crohn's disease and Multiple sclerosis.

Methotrexate also works anti-inflammatory, so anti-inflammatory.
It intervenes in the inflammatory process in a biochemical way.

Methotrexate has a chemical structure very similar to that of Folic acid (Vitamin B9). Folic acid plays an important role in the production of building blocks for the genetic material (RNA and DNA), which a body cell needs in order to divide and function.

Due to its structure similar to folic acid, methotrexate acts as a Inhibitor of this endogenous production (biosynthesis) of the DNA building blocks, because as the "wrong" building block it prevents the "correct" incorporation of folic acid.
This means that a cell does not have enough DNA building blocks available that are needed for the cell to multiply.

Fast-growing tissue such as cancer cells, bone marrow, skin and mucous membrane cells are more sensitive to the effects of methotrexate than slow-growing tissue.

In the psoriasis (an area of ​​application of methotrexate) is opposite to cell growth normal skin greatly increased, which is why methotrexate can work well against cell growth here.

Methotrexate initially acts primarily on rapidly growing tissues such as tumor cells, but as a cell growth inhibitor it also acts on healthy cells, which is what the numerous side effects Explained by methotrexate.

Adverse effects of methotrexate

The most common side effects of methotrexate therapy are symptoms in the Gastrointestinal area how Inflammation of the oral mucosa, diarrhea, nausea and Abdominal discomfort.

The intestinal mucosa in particular is attacked by methotrexate, as it is a very strong and rapidly growing tissue, the cell division of which is inhibited by methotrexate.

Often a Bone marrow depression observed, i.e. a suspension of normal blood formation in the bone marrow.

Very often occurs as an undesirable effect Increase in liver enzymes (Transaminases) on what severe liver damage can arise.
In contrast to the complaints in the gastrointestinal area, this increase in liver enzymes can be caused by the additional administration of Folic acid can be prevented during methotrexate therapy.

Other side effects from treatment with methotrexate are Kidney dysfunction, Rashes, Hair loss, allergic reaction and inflammatory changes in the lungs (Pneumonitis).

Because of this, you are on methotrexate therapy regular laboratory controls essential for kidney and liver function.

For side effects like fever, shortness of breath or cough a doctor should be consulted immediately.

Methotrexate and alcohol

The active ingredient methotrexate is used against chronic rheumatic diseases used.

Since there is a highly dangerous drug improper handling of methotrexate can be harmful to your health and great care must be taken while using it.

As well as adverse effects of methotrexate like nausea and vomiting are also included Kidney and liver damage.

The likelihood of liver damage from methotrexate is increased by Alcohol consumption and the ingestion of others liver-damaging drugs (e.g. Azathioprine, leflunomide) elevated.
Therefore, alcohol consumption should be avoided entirely.

Methotrexate promotes the conversion of liver cells into functionless connective tissue. As alcohol intensifies this process, the risk of for example one increases Cirrhosis of the liver (connective tissue conversion of liver tissue).

Moderate alcohol consumption is also not recommended, as there is no reliable evidence of the amount of alcohol that can be consumed safely and without the risk of side effects during methotrexate therapy.

There are no long-term studies of alcohol consumption during treatment with methotrexate.
The findings so far only permit the recommendation to refrain from alcohol.

Basically, it is important as soon as side effects or symptoms occur during methotrexate therapy (be it related to alcohol consumption or not), it is essential to inform a doctor immediately.

Treatment with methotrexate should not be started if one Alcohol addiction exists in the person concerned. When using methotrexate, symptoms such as fatigue and dizziness occur, which in individual cases restricts the ability to operate machines or the ability to drive a motor vehicle.

This central nervous side effects are intensified in combination with alcohol, which is why alcohol consumption should be avoided during methotrexate therapy.

Read more about this at: Methotrexate and alcohol - are they compatible?

Do you have to give up alcohol entirely?

Methotrexate is an active ingredient that has liver can attack.
Additional alcohol consumption can also damage the liver.

In principle, the consumption of alcohol during methotrexate treatment is not prohibited, the general recommendation is Avoid alcohol.

To understand why methotrexate can damage the liver, one needs to know how the drug is metabolized.
Methotrexate is broken down in and through the liver kidney retired (which is why kidney damage can also occur as a side effect).

Most of the methotrexate is broken down and excreted in the liver on the first day after ingestion or injection of the syringe.
A smaller amount of methotrexate will initially work in the body in a manner similar to methotrexate Metabolic product rebuilt and only excreted on the second day after taking methotrexate.

In these 48 hours It is advisable to absolutely abstain from alcohol, since after this time there are no longer any significant quantities of methotrexate or its metabolic product in the body. So the risk becomes one increased liver damage largely avoided by the methotrexate.

Some doctrines hold that (more moderate) Consumption of alcohol after these 48 hours after administration of methotrexate may be justifiable in exceptional cases, but it should always be discussed with the attending physician.

Please also read: Methotrexate and alcohol - are they compatible?

Methotrexate and alcohol liver disease

The risk of a Liver and gallbladder disease can occur during therapy with methotrexate.
Especially with long-term use of methotrexate over more than two years and a total dose of about 1.5 grams Methotrexate.

The risk of this is all the greater when in addition to methotrexate treatment Alcohol consumed becomes.

But also in patients with previously damaged liver, Diabetes (Diabetes mellitus), Obesity and increased alcohol consumption the risk of liver damage from methotrexate is increased.

The Liver values should be checked very regularly. Very often there is an increase in liver function tests in the blood (GPT, GOT, alkaline phosphatase, bilirubin).

Occasionally, adverse effects are like Fatty liver, chronic liver fibrosis (Increase in connective tissue) and Cirrhosis of the liver to observe.

It happens less often acute inflammation of the liver (hepatitis) or Liver damage (Hepatotoxicity).

In very rare cases a acute liver breakdown occur.