Rheumatoid arthritis: who and what is threatened by this chronic disease?

Why does rheumatoid arthritis develop?

The cause of rheumatoid arthritis is not only genetic predisposition. Sometimes infections and viruses - herpes, hepatitis B, measles, mumps - lead to inflammatory processes in the joint and connective tissue. If there is a pathological agent in the body, one or more unfavorable factors are enough to start the process of degradation in the mobile joints. The trigger for arthritis can be intoxication, hypothermia, excessive sunlight, stress and other negative circumstances.

In rheumatoid arthritis, the immune system produces antibodies that fight not foreign cells, but healthy cells and tissues. This is how inflammation occurs in the joint, the synovial membrane thickens and becomes dense. As it increases, it damages the cartilage, which leads to weakening of muscles, tendons and ligaments. An inflamed joint destroys bones. Outwardly, it may look like arthrosis, but the mechanism of thickening here is completely different from osteophytes.

The herpes virus in the body is one of the causes of rheumatoid arthritis

Methotrexate: the great and the terrible

No, no, today we will not talk about the Great and Terrible Goodwin from the Emerald City) Methotrexate... Whatever is attributed to this drug, as soon as it is not called (dangerous chemotherapy, terrible poison and poison, and these are only the most modest epithets). The fear of methotrexate is sometimes even greater than the fear of rheumatic disease itself. Patients secretly hate him and dream of “getting off” him as quickly as possible, drawing in their imagination terrible pictures of irreparable harm to the body. Meanwhile, methotrexate is one of the main drugs used in rheumatology. So who is he: friend or enemy? To be afraid or to accept without fear? We'll figure it out today...

Among modern medications used to treat rheumatoid arthritis and other rheumatic diseases, methotrexate occupies a special place. Back in the early 80s of the last century, several clinical trials were conducted on the effectiveness of the drug at a dose of 7.5–15 mg/week, and later – up to 25 mg/week in patients with rheumatoid arthritis. The clinical efficacy of the drug and its dose dependence were assessed. Until the early 90s, methotrexate was considered as a reserve drug, treatment with which was started when other basic anti-inflammatory drugs (DMARDs) were ineffective. Currently, methotrexate has received the status of the “gold standard” among DMARDs used to treat rheumatoid arthritis, I think you have heard this phrase more than once. According to preliminary estimates, more than half a million (!) patients use methotrexate for the treatment of rheumatoid arthritis alone. The unique place of methotrexate in the treatment of rheumatoid arthritis is determined by many circumstances.

First, the effectiveness of methotrexate has been confirmed in a large number of open-label, controlled studies and observational studies. It has been shown that when treating with methotrexate, the effectiveness lasts longer and the toxicity is less pronounced than when using other basic drugs. In Russia, methotrexate has been used for the treatment of patients with rheumatoid arthritis, including its early variants, since 1984, the maximum duration of continuous therapy is 28 years (on average 14.8 years) (according to the Research Institute of Rheumatology). According to Australian rheumatologists, 75.4% of patients have been using methotrexate for more than 6 years and 53% for more than 12 years. Preliminary results indicate the pharmacoeconomic advantages of methotrexate over other basic anti-inflammatory drugs. In addition, there are studies that confirm lower mortality with long-term therapy with methotrexate compared to other basic drugs.

The unique place of methotrexate in the treatment of rheumatoid arthritis is determined by the fact that it is currently one of the most effective standard DMARDs and can be prescribed at any stage of arthritis. It is characterized by the highest duration of continuous use and simple dosing. Methorexate therapy is characterized by well-known and controlled (!!!) toxic reactions, as well as a relatively low cost of treatment.

Mechanism of action

The mechanism of action of methotrexate is based on its antifolate properties. The anti-inflammatory activity of relatively low doses of the drug (10–20 mg/week), in contrast to ultra-high doses (100–1000 mg/m2), is realized due to the activity of its derivatives, which can induce the formation of a powerful anti-inflammatory mediator - adenosine. The adenosine-dependent effects of methotrexate include a decrease in the synthesis of pro-inflammatory cytokines interleukin-6, -8, -10, tumor necrosis factor (TNF), etc. These effects allow methotrexate prescribed for the treatment of rheumatic diseases to be considered not as immunosuppressive (suppressive immunity), but more as an anti-inflammatory drug, which is confirmed by clinical practice. Methotrexate has obvious immunomodulatory activity, inhibiting the synthesis of pro-inflammatory substances and stimulating the synthesis of anti-inflammatory substances.

Pharmacological properties

When taken orally, methotrexate, undergoing some changes, enters the liver through the portal vein. After taking methotrexate at a dose of 10–25 mg, drug absorption ranges from 25 to 100% (average 60–70%). The maximum concentration of the drug in the blood is achieved after 2–4 hours. Although taking methotrexate with food slows the achievement of peak concentrations, its absorption and bioavailability are not affected, so the drug can be taken with food. Methotrexate binds to albumin and is excreted primarily by the kidneys (80%) and to a lesser extent by the liver (10–30%). The development of renal failure leads to a slowdown in the release of the drug and increases its toxicity. Methotrexate metabolites (that is, substances formed during the transformation process in the body) are found inside cells for ≥7 days after a single dose, which determines the frequency of taking the drug once a week.

Side effects

Side effects that develop during treatment with methotrexate can be divided into three main groups:

1) effects associated with folate deficiency (stomatitis, inhibition of hematopoiesis) can usually be corrected by administering folic or folinic acids and/or discontinuing methotrexate (temporary or permanent). The use of methotrexate without the prescription of folic acid is unacceptable!!!

2) allergic reactions, which sometimes disappear when treatment is interrupted. Harbingers of such reactions can be considered the appearance of an unmotivated dry cough with a rapid change in ambient temperature, for example, when going outside, or, conversely, shortness of breath;

3) reactions associated with the accumulation of active metabolites of the drug (liver damage). According to a meta-analysis of placebo-controlled randomized clinical trials (RCTs), the incidence of adverse reactions during treatment with methotrexate is approximately 22%, and in patients receiving placebo it is 7%.

Gastrointestinal tract

Nausea and vomiting usually appear 1–8 days after taking methotrexate and last 1–3 days, but can occur at any time during treatment. In this case, it is necessary to temporarily discontinue the drug and switch to subcutaneous administration of the drug. For mild nausea on the day of taking the drug and/or the next day, Motilium can be used situationally. Methotrexate may slow the scarring of gastric and duodenal ulcers, especially during concomitant use of nonsteroidal anti-inflammatory drugs (NSAIDs). Ulcerative lesions of the mucous membrane of the upper gastrointestinal tract are a relative contraindication for the use of methotrexate. On the other hand, methotrexate is the most common and accessible drug for the treatment of arthritis, so the detection of ulcerative lesions of the mucous membrane only indicates the need for targeted and thorough antiulcer treatment, and not the exclusion of methotrexate from therapy. Patients are often successfully treated with methotrexate for many years without recurrence of acute gastric ulcers, especially since with the effectiveness of methotrexate, NSAIDs can be discontinued and the source of stress ulcers, such as pain, decreases or disappears.

Liver

The most common side effect during therapy is a temporary increase in the level of aminotransferases (ALAT, AST) and alkaline phosphatase (ALP). As a rule, the concentration of aminotransferases reaches a maximum 4–5 days after taking the drug and persists for 1–2 weeks. A two-fold increase in aminotransferase levels is NOT a reason to discontinue methotrexate, whereas a more significant increase indicates the need to reduce the dose or interrupt treatment. With a multiple increase, in addition to the abolition of methotrexate, hepatoprotectors are usually prescribed. After normalization of aminotransferase levels, therapy is resumed at a lower dose, and subsequently the dose can be increased or left unchanged. Data regarding the likelihood of developing liver cirrhosis during treatment are contradictory. There are reports that liver damage during treatment with methotrexate is more common in patients with psoriasis. Liver changes during morphological examination are detected in only 3–11% of patients receiving methotrexate for more than 2 years, but liver cirrhosis develops very rarely (approximately 1 in 1000 patients). Regular monitoring of aminotransferase levels is considered sufficient as an early and reliable marker of liver damage. In this regard, the complete abstinence of patients from alcohol is of fundamental importance!!! People with psoriasis and psoriatic arthritis are more likely to have more severe liver damage and a higher rate of progression of liver damage than people with rheumatoid arthritis. Risk factors for liver damage during treatment include:

• alcohol consumption,
• lack of folic acid intake,
• total dose of methotrexate and duration of therapy,
• presence of diabetes mellitus,
• obesity,
• elderly age.

In patients with rheumatoid arthritis receiving methotrexate, aminotransferase levels should be monitored at least once every 3 months!

Methotrexate and viral hepatitis

A serious problem is the prescription of methotrexate in the presence of carriage of hepatitis B and/or C viruses. Determination of markers of hepatitis B and C is included in the standards for examining patients before prescribing methotrexate. However, when HBsAg or anti-HCV is detected, further studies to determine viremia and its severity are usually not carried out. Apparently, incomplete examination, as well as the lack of long-term observations, are often the reasons for a calm attitude towards prescribing methotrexate to such patients.

Hematopoietic system

Changes in blood parameters during methotrexate therapy are observed relatively rarely (no more than 1–3% of cases). Cases of leukopenia, thrombocytopenia, megaloblastic anemia, and pancytopenia have been described. Pancytopenia (that is, a decrease in all blood counts) is a deadly complication of therapy. The severity of this condition correlates with the dose of the drug, the presence of renal failure, concomitant infection, folic acid deficiency, and the combination of methotrexate with other toxic drugs. Unfortunately, taking folic acid does not prevent the development of pancytopenia. Elderly patients are at greatest risk of developing severe cytopenia. Normalization of hematopoiesis after discontinuation of the drug in most patients occurs within 2 weeks, but in some cases it becomes necessary to prescribe high doses of folate and even a colony-stimulating factor. In addition to cytopenia, that is, a decrease in blood counts, methotrexate in some cases can cause leukocytosis (that is, an increase in the level of white blood cells) without developing an infection.

Infectious complications during methotrexate therapy develop relatively often. These may be recurrent respiratory diseases, purulent bronchitis, and less often - unusually severe fungal and viral infections - nocardiosis, pulmonary aspergillosis and toxoplasmosis, herpes, cryptococcosis, Pneumocystis pneumonia. The development of severe infections is grounds for urgent withdrawal of methotrexate. But fortunately, according to several studies, long-term use of methotrexate is NOT associated with an increased risk of infectious complications.

Teratogenicity

Methotrexate is embryotoxic and has a teratogenic effect. Low doses of methotrexate can lead to the development of defects in the fetus, for example, the so-called “methotrexate syndrome”. Developmental delays and mental impairment have been described in children born to mothers who took the drug during pregnancy. Since even a single dose of methotrexate can cause defects in the fetus, this drug is contraindicated for pregnant women or women planning pregnancy! Methotrexate remains in the cells for a long time, so a washout period of at least 3–6 months is recommended before conception.

The cardiovascular system

An important advantage of methotrexate, which distinguishes it from other basic drugs, is the reduction in the risk of cardiovascular complications, which are the main cause of premature death in patients with rheumatoid arthritis. According to the literature and numerous studies in recent years, in patients with rheumatoid arthritis during treatment with methotrexate, there is a decrease in mortality from cardiovascular complications (up to 70%!!!) compared to patients receiving other DMARDs. It is believed that the beneficial effect of methotrexate on the cardiovascular system may be associated with increased formation of adenosine. However, many patients develop hypercholesterolemia (increased cholesterol levels in the blood), which requires the prescription of statins. Patients with rheumatoid arthritis often experience increased homocysteine ​​concentrations and impaired homocysteine ​​metabolism, regardless of treatment. Hyperhomocysteinemia is considered a risk factor for thrombosis. This indicates the need for long-term studies assessing all possible factors determining the development and progression of cardiovascular system pathology in patients.

Flu-like syndrome or post-dose reactions

Cases have been described of the appearance 24 hours after taking methotrexate of pain in the joints and muscles, general malaise, sometimes accompanied by fever and lasting from 1 to 4 days. These reactions indicate the need to discontinue treatment and are considered the second most common cause after gastrointestinal symptoms. Some patients experience headache, memory loss, and photophobia. Unfortunately, many patients complain of headaches of varying severity and memory loss. This is another area that requires study and identification of approaches to reduce the incidence of adverse reactions. The currently very limited number of available and effective DMARDs makes it impossible to discontinue methotrexate in many patients with headache and/or complaints of some memory loss. At the same time, the development of a post-dose reaction in all cases requires discontinuation of the drug.

Methotrexate nodulosis

In patients receiving methotrexate, the development of subcutaneous nodules has been described, differing from rheumatoid nodules in smaller size and atypical localization, this is called methotrexate nodulosis (nodulation). Typically, these atypical nodules are localized on the hands. Methotrexate nodulosis can develop in patients who are seronegative for rheumatoid factor (RF) and during the period of remission of arthritis. There is evidence that the administration of hydroxychloroquine in most cases leads to regression of nodulosis.

Methotrexate for psoriatic arthritis

Methotrexate has been used to treat psoriatic arthritis since 1964. Compared with other basic drugs, methotrexate is well tolerated in this disease, and the frequency of treatment interruptions is lower than with other drugs. However, 10–30% of patients experience side effects that require discontinuation of the drug. Liver damage develops 3 times more often than when treating patients with rheumatoid arthritis with methotrexate. Methotrexate has long been used to treat severe forms of psoriasis and psoriatic arthritis. Currently, the dose of methotrexate is usually 20–30 mg/week, with a maintenance dose of 10–15 mg/week. Typically, the indications for prescribing methotrexate for psoriasis and psoriatic arthritis are as follows:

• malignant form of psoriatic arthritis;
• rapidly progressing course of the disease;
• high laboratory activity;
• development of severe skin variants of psoriasis (exudative, pustular, erythrodermic);
• low effectiveness or poor tolerability of NSAIDs and glucocorticoids;
• ineffectiveness of other DMARDs.

Still's disease in adults

Positive results were obtained from the use of methotrexate at a dose of up to 20 mg/week: improvement and development of remission of the disease, a significant reduction in the dose of hormonal drugs, positive dynamics of laboratory parameters.

Dermatomyositis/polymyositis

The effectiveness of methotrexate in the treatment of these diseases does not depend on the route of administration (oral or intravenous) and is 50–75%. Methotrexate is often used in combination with glucocorticoids. Therapy begins with a small dose (7.5–10 mg/week), which is increased to 25–30 mg/week. If oral methotrexate is poorly tolerated, an intravenous route of administration is prescribed. Other methods (subcutaneous, intramuscular) are unacceptable in these cases. The dose of the drug is reduced gradually under careful monitoring of clinical manifestations and CPK levels.

Polymyalgia rheumatica and giant cell arteritis

In elderly patients suffering from these diseases, in the treatment of which glucocorticoids are used, the administration of methotrexate in doses of 10–12.5 mg/week has been considered in a number of studies as an opportunity to more quickly reduce the dose of hormones and maintain remission.

Subcutaneous use of methotrexate

In clinical practice, methotrexate is most often used orally, but recently there has been a trend toward more widespread subcutaneous administration of the drug, especially at doses ≥20 mg/week. The theoretical rationale for subcutaneous methotrexate is the wide variability in its oral availability (20–80%), whereas the availability of subcutaneous methotrexate is much higher and more consistent. According to a number of authors, switching patients from parenteral to oral methotrexate led to an increase in the clinical activity of the disease in 49–71% of cases and the development of undesirable side effects (nausea, increased aminotransferase levels). When parenteral administration of methotrexate was resumed, the majority of patients experienced normalization of such disorders. RK Moitra et al. analyzed the results of parenteral use of methotrexate in 102 patients who had previously taken it orally for 3–135 months, and noted an increase in clinical effect and a decrease in ESR in approximately half of the patients. In 2010, methotrexate appeared in Russia in prefilled syringes for subcutaneous administration (Metoject), which opened up new opportunities for optimizing the treatment of rheumatoid arthritis.

In conclusion, I would like to highlight the following points:

1. From the standpoint of evidence-based medicine, methotrexate is a DMARD that can be used in various types and durations of rheumatoid arthritis, in patients with undifferentiated arthritis, in early rheumatoid arthritis to achieve (induce) remission, in various rheumatic diseases.
2. The sufficiently high effectiveness of the drug, the possibility of dose adjustment and the low frequency of intolerance reactions allow therapy to be carried out continuously for many years.
3. The dose of methotrexate should be individualized, and therapy should be aimed at suppressing the activity and progression of the disease. Treatment should begin with a dose of 10-15 mg/week and increase by 5 mg every 2-4 weeks up to 25-30 mg/week depending on effectiveness and tolerability.
4. Before prescribing methotrexate, risk factors for severe adverse reactions, including alcohol consumption, should be assessed.
5. Treatment with methotrexate should be interrupted at least 3-6 months before the planned pregnancy.
6. And, perhaps, the most important thing: the success and safety of methotrexate therapy, as with the use of other drugs, depend on the partnership between the doctor and the patient. If you have any doubts or questions, you can always contact your doctor, I won’t get tired of repeating this!!! If you believe in the success of treatment, you will definitely achieve it!

How does it manifest itself?

The inflammatory process first affects small joints - hands and feet, and over time affects large ones. The joints are damaged symmetrically. Unlike arthrosis of the knee, shoulder or elbow, pain after exercise does not intensify, but rather subsides. Symptoms appear in waves: acute pain attacks are followed by a lull. The disease begins with morning stiffness, and without treatment ends with joint deformation.

Characteristic symptoms of the disease are redness and swelling in the joint area, local fever. A person experiences general weakness and malaise, internal organs are affected, and other complications develop.

Is the joint swelling? Contact a rheumatologist

How are medications used?

The dosage of the drug is selected by the attending physician on an individual basis. Of course, if there are no contraindications. Use no more than once a week.

The patient must undergo a test before use. About a week in advance, a test injection is given with a small amount of medicine; if the body reacts normally, then treatment can be carried out.

If side effects occur, the drug is not used. First, the minimum dose of the drug is administered, which is 7.5 mg. Then it is gradually increased if well tolerated and for existing indications.

After a couple of months from the first use, you can notice the effect. The course can last quite a long time, up to several years.

What are the risks of rheumatoid arthritis?

The disease is very insidious because it can cause serious complications on the body systems:

• Lungs - 25-30% of people with this diagnosis develop pleurisy, nodules appear in the lungs, and the pleura becomes inflamed.
• Eyes – about a third of people complain of dry eyes and dry mouth.
• Heart – the risk of developing heart failure is twice as high as in others, pericarditis is common.
• Skin – A quarter of patients have characteristic nodules under the surface of the skin.
• Blood – a third of people develop anemia.
• Bones – rheumatoid arthritis is often combined with osteoporosis, arthrosis, and systemic atherosclerosis.
• Infections – the risk of cancer and other infections increases significantly.

Rheumatoid arthritis complicates the course of concomitant pathologies

Can vaccines cause autoimmune disorders?

It is likely that vaccines can cause autoimmune diseases (AIDs) through the same mechanism as infections [2]. There is no direct evidence of such a dependence. It is almost impossible to find out whether vaccination was the trigger for the onset of AIDS. Researchers disagree: the first report isolated cases and try to link them with vaccination, the second experimentally reject such a connection [2–4].

Another important question: how will autoimmune diseases behave after vaccinations, is the risk justified?

There is a possibility that [2.11]:

• the virus from the vaccine will develop into a real infection;
• the effect of the vaccine will not appear at all or will be insufficient;
• autoimmune disease will become more complicated after vaccination.

First things first.

How to make a diagnosis

Rheumatoid arthritis has similar symptoms to a number of other joint diseases. Even with arthrosis with synovitis, swelling is also present, but the disease has a completely different nature. Therefore, to make an accurate diagnosis, patient complaints and visual examination are not enough. One of the characteristic signs of rheumatoid arthritis is the presence of morning stiffness for an hour or more, as well as swelling for a period of more than six weeks.

At the diagnostic stage, the following examinations are prescribed:

• Ultrasound or MRI of joints;
• X-ray;
• clinical blood test and ESR;
• C-reactive protein;
• analysis for rheumatoid factor;
• antibodies to cyclic citrullinated peptide, etc.

X-ray of the joint will help distinguish rheumatoid arthritis from arthrosis

Is it possible to get vaccinated?

The vaccine is given only outside periods of exacerbation. The response to the vaccine depends on the type and severity of AIDS, the type of vaccine, the patient’s age, and treatment regimen [2–4].

Types of vaccines [2–4]:

1. Live attenuated vaccines are highly effective. However, with reduced immunity, for example, while taking immunosuppressants, a weakened pathogen from a live vaccine can “take root” in the human body. In general, live vaccines are contraindicated in patients undergoing immunotherapy.

BE CAREFUL

A patient with reduced immunity can become infected from a household member who has received a live vaccine against rotavirus, polio and some other infections.

2. Inactivated vaccines (with a “killed” pathogen) or inert (subunit, split vaccines - with a non-virulent fragment) are weaker than live ones. Adjuvants and revaccination are required. However, they are safer and less demanding on storage conditions than live vaccines.
3. Recombinant (vector) vaccines consist of a non-pathogenic viral carrier and a DNA or RNA fragment of the pathogen. Some scientists suggest that the vector may behave like a virus from a live vaccine [11]. This has not been shown in practice. Their effectiveness and safety are comparable to inactivated ones.
4. Prior to COVID-19 vaccines, messenger RNA vaccines There is not enough information to talk about the safety of this type of coronavirus vaccine for autoimmune diseases. At the same time, there are no theoretical grounds to assume the opposite.

Special instructions for the use of Methotrexate "Ebewe"

Treatment with methotrexate should be carried out under the supervision of a qualified oncologist with experience in the use of anticancer chemotherapeutic agents. Methotrexate should be used with extreme caution in cases of bone marrow suppression, renal failure, peptic ulcers, ulcerative colitis, ulcerative stomatitis, diarrhea, severe general condition, as well as in the treatment of children and the elderly. In the presence of pleural exudate or ascites, the cavities should be drained before treatment with methotrexate. If this is not possible, methotrexate therapy should not be prescribed. If symptoms of gastrointestinal toxicity (usually initially manifesting as stomatitis) occur, methotrexate treatment should be discontinued. If therapy is continued, hemorrhagic enteritis and intestinal perforation are possible, which pose a threat to the patient's life. Methotrexate may reduce fertility and cause oligospermia, menstrual irregularities and amenorrhea. These effects are usually reversible and disappear after discontinuation of therapy. In addition, methotrexate is embryotoxic, teratogenic and abortogenic. If one of the sexual partners is taking methotrexate, the couple should use contraception throughout the entire treatment period and for at least 3 months after the end of therapy. Before starting treatment with methotrexate or before repeated courses of therapy, it is necessary to examine the patient, assess kidney and liver function, determine the number of blood cells and compare them with previous values. Patients being treated with methotrexate should be closely monitored so that if signs of toxic effects or adverse reactions occur, the necessary measures can be taken immediately. During treatment with methotrexate, it is necessary to regularly carry out the following laboratory tests: complete blood count, urinalysis, renal function tests and liver function tests. When treating with the drug in high doses, it is also necessary to determine the concentration of methotrexate in the blood plasma. Particular attention should be paid to signs of hepatotoxicity, which may occur in the absence of significant changes in liver test results. Treatment with methotrexate should be stopped (or not started if this is the case initially) if there are any abnormal liver function tests or liver biopsies. The corresponding indicators usually normalize within 2 weeks, after which, according to the doctor’s decision, methotrexate therapy can be continued. Methotrexate can cause bone marrow suppression, even when used in relatively safe doses. If there is a significant decrease in the number of leukocytes or platelets, methotrexate therapy should be immediately suspended and appropriate supportive treatment should be prescribed. When treated with the drug in high doses, a precipitate of methotrexate or its metabolites may form in the renal tubules. To prevent this phenomenon, it is recommended to prescribe sodium bicarbonate (5 × 625 mg orally every 3 hours or IV) or acetazolamide (500 mg orally 4 times a day) to increase diuresis and alkalinize urine to a pH value of 6.5–7.0) . When intrathecal and intraventricular administration of Methotrexate "Ebewe" 100 mg/ml, it must be diluted. The maximum recommended concentration is 5 mg/ml. Experiments have revealed the teratogenic effect of methotrexate, so it is recommended to prescribe it to women of reproductive age only if the benefits of the drug outweigh the possible risks. If methotrexate is prescribed during pregnancy for the treatment of cancer or if the patient becomes pregnant during therapy, she should be warned of the possible harm to the fetus. Methotrexate is excreted in breast milk, so breastfeeding should be discontinued during treatment with methotrexate. Depending on individual sensitivity, the drug may adversely affect the ability to drive vehicles and operate machinery.

Contraindications for Metoject

The medicine should not be used if there is hypersensitivity to the components. It should also not be used when:

• Alcohol abuse.
• Diseases of the liver and kidneys.
• Hematopoiesis disorders.
• The presence of ulcerative lesions in the gastrointestinal tract and in the oral cavity.
• Vaccinations (due to a decrease in the immune response, vaccination should be carried out only six months after stopping treatment).
• Acute and chronic infections (including recent illnesses).
• Autoimmune diseases.

Caution should be used if there is:

• Herpes.
• Pleural and peritoneal effusions.
• Ascites.
• Gout.
• Obstructive diseases of the digestive system.
• Dehydration of the body (impaired water balance increases the toxicity of the products).
• Asthenia.
• High concentration of bilirubin.
• Vomiting and diarrhea.
• History of chemical and radiation therapy.

They try not to prescribe Metoject to older people, since their liver and kidney function may be impaired. In particular, Metoject and Methotrexate are not used for UC (nonspecific ulcerative colitis).

Side effects of Methotrexate

On the part of the digestive system, manifestations of ulcerative stomatitis, anorexia, gingivitis, pharyngitis, nausea are possible; in rare cases - diarrhea, melena, enteritis, pancreatitis, liver necrosis, cirrhosis, fatty atrophy, periportal liver fibrosis. The hematopoietic system may respond with leukopenia, anemia, and thrombocytopenia. Central nervous system - feeling of fatigue, dizziness; in rare cases - headache, aphasia, drowsiness, convulsions. Reproductive system - violation of oogenesis and spermatogenesis, oligospermia, menstrual irregularities, decreased libido, impotence. Urinary system - hematuria, cystitis, severe renal dysfunction. The following allergic reactions may occur: chills, decreased resistance to infection; in rare cases - urticaria, toxic epidermal necrolysis, Stevens-Johnson syndrome. Dermatological reactions - skin rash, photosensitivity, pigmentation disorders, acne, furunculosis.

If any negative reactions of the body to the drug occur, you should immediately consult a doctor.

Use in pregnant and lactating women

What's the difference here? Methoject and Methotrexate should not be taken during pregnancy and lactation.

"Methoject" is toxic to the fetus and can lead to serious developmental disorders and even death. It tends to accumulate in breast milk, which can also negatively affect the baby’s health.

If pregnancy occurs while taking the drug, there may be undesirable consequences for the child. Therefore, careful contraception is necessary during therapy.

We compare the drugs Metoject and Methotrexate Ebeve. What is the difference has become clearer. Let's figure it out further.

Interaction of Metoject with other means

The simultaneous use of Metoject and other drugs leads to either an increase in toxicity or a decrease in the therapeutic effect. If you need to combine any means, it is better to inform a specialist about this.

"Methoject" should be taken with caution with:

• Hepatotoxic drugs.
• Drugs that inhibit hematopoiesis.
• Drugs that affect the bone marrow.
• Alcoholic drinks.
• Antibiotics.
• NSAIDs and salicylates.

The prohibited list of medications is quite long. It must be remembered that interaction with Metoject will cause very severe toxic poisoning of the body (death is not excluded). Sometimes this can lead to skin cancer.

Green tea and coffee are also prohibited, as well as drinks with purine alkaloids, theophylline and caffeine. The reason for this is poor compatibility with methotrexate. It can significantly delay their elimination.

It should be noted that during therapy, the use of vitamin complexes and preparations containing folates is indicated, since they reduce toxic properties.

Which drug to choose - Metoject and Methotrexate? What's better? More on this later.

Side effects

Side effects can be different, but most often the organs of the gastrointestinal tract are affected. The frequency and severity with which they occur depends on the dose and individual characteristics of the organism.

The main side effects are:

• Stomatitis.
• Nausea.
• Depression.
• Anemia.
• Dermatitis.
• Headache and dizziness.
• Increased sweating and fever.
• Allergies and anaphylactic shock.
• Pericarditis.
• Thromboembolism.
• Interstitial pneumonia.
• Various infectious diseases.

Sometimes:

• Vomiting.
• Baldness.
• Vasculitis.
• Pharyngitis.
• Paresthesia of the lower extremities, fingers and toes.

Very rarely:

• Convulsions and paralysis.
• Visual impairment.
• Pulmonary insufficiency.
• Myalgia.
• Osteoporosis.