Metotab 10 mg

Leaflet accompanying the packaging: information for the user

Metotab 2.5 mg, tablets

Metotab 7.5 mg, tablets

Metotab 10 mg, tablets

Methotrexate

You should carefully read the contents of the leaflet before taking the medicine, as it contains important information for the patient.

• You should keep this leaflet, so that you can read it again if you need to.
• If you have any doubts, you should consult a doctor or pharmacist.
• This medicine has been prescribed specifically for you. Do not pass it on to others. The medicine may harm another person, even if their symptoms are the same.
• If the patient experiences any side effects, including any side effects not listed in the leaflet, they should tell their doctor or pharmacist. See section 4.

Table of contents of the leaflet:

• 1. What is Metotab and what is it used for
• 2. Important information before taking Metotab
• 3. How to take Metotab
• 4. Possible side effects
• 5. How to store Metotab
• 6. Contents of the pack and other information

1. What is Metotab and what is it used for

Metotab is indicated for the treatment of:

• Severe, active rheumatoid arthritis in adult patients.
• Severe and generalized psoriasis, particularly of the plaque type, in adult patients who do not respond to standard treatment.

Rheumatoid arthritis (RA) is a chronic disease of the joints and connective tissue, characterized by inflammation of the synovial membranes (membranes in the joints). The synovial membranes produce fluid, the function of which is to reduce friction in many joints. The inflammatory state causes thickening of the synovial membrane and swelling of the joint.
Psoriasis is a common, chronic skin disease, characterized by the appearance of red patches covered with thick, dry, silvery, adherent scales.
Metotab modifies and slows down the course of the disease.
Methotrexate, which is a component of Metotab, may also be approved for the treatment of other diseases not listed in this leaflet. In case of further doubts, you should consult a doctor, pharmacist or other healthcare professional and always follow their recommendations.

2. Important information before taking Metotab

Important warning regarding Metotab (methotrexate) dosing:

In the treatment of rheumatoid arthritis and psoriasis, Metotab should be taken only once a week.
Taking too high a dose of Metotab (methotrexate) can be fatal.
You should carefully read the contents of point 3 of this leaflet.
If you have any questions, you should consult a doctor or pharmacist before taking this medicine.

When not to take Metotab

• if the patient is allergic to methotrexate or any of the other ingredients of this medicine (listed in point 6),
• if the patient has severe liver or kidney disease or blood disease,
• if the patient drinks large amounts of alcohol,
• if the patient has a severe infection, such as tuberculosis or HIV infection, or another immunodeficiency syndrome,
• if the patient has ulcers in the mouth, stomach or intestines,
• if the patient is pregnant or breastfeeding (see "Pregnancy, breastfeeding and fertility"),
• if the patient is to receive a vaccine containing live microorganisms at the same time.

Warnings and precautions

Before starting treatment with Metotab, you should discuss it with your doctor or pharmacist:

• if the patient is elderly or in poor general condition,
• if the patient has impaired liver or kidney function,
• if the patient is dehydrated.

Special precautions for the use of Metotab
Methotrexate temporarily disrupts the production of sperm and egg cells; in most cases, this effect disappears. Methotrexate may cause miscarriage and severe birth defects. Female patients should avoid becoming pregnant while taking methotrexate and for at least 6 months after the end of treatment. See also "Pregnancy, breastfeeding and fertility".
Recommended tests and precautions
Severe side effects may occur even after small doses of methotrexate.
To detect them in time, the doctor must perform control tests and laboratory tests.
Before starting treatment
Before starting treatment, a blood test will be performed to check if the patient has a sufficient number of blood cells. Blood tests will also be performed to assess liver function and check for hepatitis. Additionally, the level of albumin (blood protein) in the serum and kidney function will be checked, and an assessment for hepatitis (hepatitis virus infection) will be performed. The doctor may also decide to perform other liver tests, which may include liver imaging or taking a small tissue sample from the liver for a more detailed assessment. Additionally, the doctor may check for tuberculosis and order a chest X-ray or lung function test.
During treatment
The doctor may perform the following tests:

• examination of the mouth and throat to detect mucosal changes, such as inflammation or ulcers;
• blood tests/morphology and assessment of methotrexate levels in the blood serum;
• blood tests to monitor liver function;
• imaging tests to monitor liver condition;
• taking a small tissue sample from the liver for a more detailed assessment;
• blood tests to monitor kidney function;
• respiratory system tests and, if necessary, lung function tests.

It is very important for the patient to attend these scheduled tests.
If the results of any of these tests show abnormalities, the doctor will adjust the treatment accordingly.
Elderly patients
Elderly patients treated with methotrexate should be under close medical supervision to quickly detect any possible side effects.
Age-related disorders of liver and kidney function and low folate levels in the elderly require the use of relatively low doses of methotrexate.
Other precautions
During treatment with methotrexate, cases of acute pulmonary bleeding have been reported in patients with underlying rheumatologic disease. If the patient experiences hemoptysis, i.e., coughing up sputum with blood, they should immediately consult a doctor.
Methotrexate may affect the immune system, and some vaccines may not work properly while taking methotrexate. If the patient has latent or chronic infections (e.g., shingles, tuberculosis, hepatitis B or C), treatment with methotrexate may cause their exacerbation or worsening.
If the patient has previously had skin problems after radiation therapy (radiation dermatitis) and sunburn, these symptoms may recur during treatment with methotrexate (recall reaction). Exposure to UV radiation during treatment with methotrexate may exacerbate psoriatic lesions.
Lymph node enlargement (lymphoma) may occur. In such cases, treatment should be discontinued.
Diarrhea may be a side effect of Metotab and requires discontinuation of treatment. If the patient experiences diarrhea, they should tell their doctor.
In case of swelling, e.g., of the face, tongue, and/or throat, and/or difficulty swallowing or breathing (anaphylactic shock), the patient should discontinue Metotab and immediately consult a doctor.
In patients with cancer treated with methotrexate, cases of certain brain disorders (encephalopathy/leukoencephalopathy) have been reported. It cannot be excluded that such side effects may occur in the treatment of other diseases.
If the patient, their partner, or caregiver notices new or worsening neurological symptoms, including general muscle weakness, vision disturbances, changes in thinking, memory, and orientation leading to disorientation and personality changes, they should immediately consult a doctor, as these may be symptoms of a very rare, serious brain infection called progressive multifocal leukoencephalopathy (PML).

Metotab and other medicines

You should tell your doctor or pharmacist about all medicines you are currently taking or have recently taken, as well as any medicines you plan to take.
The effectiveness of Metotab may be affected if you take certain other medicines:

• antibiotics, e.g., tetracyclines, chloramphenicol, non-absorbable broad-spectrum antibiotics, penicillins, glycopeptides, sulfonamides, ciprofloxacin, and cephalothin (medicines used to prevent and treat certain infections);
• non-steroidal anti-inflammatory drugsor salicylates[pain-relieving and/or anti-inflammatory medicines, e.g., acetylsalicylic acid, diclofenac, and ibuprofen or pyrazole];
• probenecid(used to treat gout);
• weak organic acids such as loop diuretics(diuretics);
• medicines that may harm bone marrow, e.g., trimethoprim-sulfamethoxazole (an antibiotic) or pyrimethamine;
• other medicines used to treat rheumatoid arthritis, e.g., leflunomide, sulfasalazine, and azathioprine;
• mercaptopurine (a cytostaticmedicine);
• retinoids (medicines used to treat psoriasisand other skin diseases);
• theophylline (a medicine used to treat asthmaand other lung diseases);
• certain stomach medicines, e.g., omeprazole and pantoprazole;
• medicines that lower blood sugar levels(hypoglycemic medicines).

Vitamin preparations containing folinic acidmay reduce the effectiveness of treatment and should only be taken on the advice of a doctor.
While taking Metotab, you should avoid vaccinations with live vaccines.

Metotab with food, drink, and alcohol

While taking Metotab, you should avoid drinking alcohol and excessive amounts of coffee, caffeine-containing beverages, and black tea.

Pregnancy, breastfeeding, and fertility

Pregnancy
Do not take Metotab if you are pregnant or trying to become pregnant. Methotrexate may cause birth defects, harm the unborn baby, or cause miscarriage.
This is associated with developmental abnormalities of the skull, face, heart, and blood vessels, brain, and limbs. Therefore, it is very important that female patients who are pregnant or planning to become pregnant do not take methotrexate. If the patient is of childbearing age, it is essential to confirm that she is not pregnant before starting treatment, by taking appropriate measures, e.g., performing a pregnancy test. The patient should avoid becoming pregnant while taking methotrexate and for at least 6 months after the end of treatment, using reliable contraceptive methods throughout this time (see also "Warnings and precautions").
If the patient becomes pregnant while taking methotrexate or suspects that she may be pregnant, she should consult her doctor as soon as possible. The patient should receive advice on the possible harmful effects of treatment on the baby.
If the patient plans to become pregnant, she should consult her doctor, who may refer her to a specialist for advice before planned treatment begins.
Male fertility
Available evidence does not indicate an increased risk of birth defects or miscarriages after the father has taken methotrexate at a dose below 30 mg/week. However, this risk cannot be entirely excluded. Methotrexate may be genotoxic, meaning it may cause genetic mutations. Methotrexate may affect sperm and cause birth defects. Therefore, male patients should avoid fertilizing their partner and should not donate sperm while taking methotrexate and for at least 6 months after the end of treatment.
Breastfeeding
Before starting treatment and while taking Metotab, you should stop breastfeeding.

Driving and using machines

While taking Metotab, you may experience side effects such as fatigue and dizziness. In some cases, this may negatively affect your ability to drive or perform tasks that require increased attention. If you experience fatigue or drowsiness, you should not drive or operate machinery.
The patient is responsible for deciding whether they are fit to drive or perform tasks that require increased attention. Medicines taken by the patient, due to their effect or side effects, are one of the factors that may affect their ability to perform these tasks safely. The description of the medicine's effect and side effects is presented in other sections of the leaflet. You should read all the information contained in this leaflet, and if you have any doubts, you should consult a doctor or pharmacist.

Metotab contains lactose monohydrate

If you have previously been diagnosed with intolerance to some sugars, you should consult your doctor before taking the medicine.

3. How to take Metotab

Recommended dose:

Dose in rheumatoid arthritis and psoriasis:
Take Metotab only once a week.
The patient, in agreement with their doctor, will determine which day of the week they will take the medicine.
This medicine should always be taken according to the doctor's recommendations. If you have any doubts, you should consult a doctor or pharmacist.
The dose of Metotab is determined by the doctor, individually tailored to the needs of each patient.
Metotab usually starts working after 4-8 weeks in the case of rheumatoid arthritis and after 2-6 weeks in the case of psoriasis. The duration of treatment is determined by the doctor.
If you feel that the effect of Metotab is too strong or too weak, you should consult a doctor or pharmacist.

Taking a higher dose of Metotab than recommended

You should follow the doctor's recommendations regarding dosing. Do not change the dose of the medicine on your own.
If you suspect that you have taken a higher dose of Metotab than recommended, you should immediately consult the doctor who is treating you, who will decide on the appropriate treatment depending on the severity of the poisoning.

Missing a dose of Metotab

Do not take a double dose to make up for a missed dose. You should consult a doctor and take the prescribed dose as soon as possible, and then take the dose once a week.

4. Possible side effects

Like all medicines, Metotab can cause side effects, although not everybody gets them.
The frequency and severity of side effects depend on the dose and frequency of administration of Metotab. Since severe side effects may occur even after small doses of the medicine, it is essential that the doctor regularly monitors the patient's health. The doctor will perform tests to rule out abnormalitiesin blood parameters (e.g., low white blood cell count, low platelet count, lymphoma) and changes in the kidneys and liver.
The most important side effects concern the hematopoietic system and the gastrointestinal tract.
You should immediately tell your doctorif you experience any of the following symptoms, as they may indicate severe, potentially life-threatening side effects that require urgent treatment:

• Persistent dry cough without expectoration, shortness of breath, and fever;these may be symptoms of pneumonia [frequent];
• Hemoptysis, i.e., coughing up sputum with blood[frequency unknown];
• Signs of liver damage, such as yellowing of the skin and whites of the eyes; methotrexate may cause chronic liver damage (liver cirrhosis), scarring of liver tissue (liver fibrosis), fatty liver degeneration [all not very common], acute liver inflammation (acute hepatitis) [rare], and liver failure [very rare];
• Allergy symptoms such as skin rash, including red, itchy skin, swelling of the hands, feet, ankles, face, lips, mouth, or throat (which may cause difficulty swallowing or breathing) and a feeling of impending fainting;these may be symptoms of severe allergic reactions or anaphylactic shock [rare];
• Signs of kidney damage, such as swelling of the hands, ankles, or feet, or changes in urine frequency or decreased urine output (oliguria) or absence of urine (anuria);these may be symptoms of kidney failure [rare];
• Infection symptoms, such as fever, chills, malaise, sore throat;methotrexate may increase the risk of infections. Severe infections such as a certain type of pneumonia (Pneumocystis jirovecii pneumonia) and blood poisoning with bacteria and their toxins (sepsis) [rare] may occur;
• Symptoms such as weakness or partial paralysis of one side of the body (stroke) or pain, swelling, redness, and unusual warmth in one leg (deep vein thrombosis);these symptoms may be related to the displacement of a blood clot and blockage of a blood vessel (thromboembolic event) [rare];
• Fever and severe deterioration of general health or sudden fever, which is accompanied by sore throat or mouth sores;methotrexate may cause a sharp decrease in the number of white blood cells (agranulocytosis) and severe suppression of bone marrow function [very rare];
• Unexpected bleeding, e.g., bleeding from the nose, blood in the urine, vomiting, or appearance of bruises;these may be symptoms of a significant decrease in the number of platelets caused by severe suppression of bone marrow function [very rare];
• Symptoms such as severe headache with accompanying fever, stiff neck, nausea, vomiting, disorientation, and sensitivity to lightmay indicate meningitis (aseptic meningitis) [very rare];
• in patients with cancer treated with methotrexate, cases of certain brain disorders (encephalopathy/leukoencephalopathy) have been reported. It cannot be excluded that such side effects may occur in the treatment of other diseases. Symptoms of such brain disorders include altered mental state, movement disorders (ataxia), vision disturbances, or memory disturbances[frequency unknown];
• Severe skin rash or blisters on the skin (which may also occur in the mouth, eyes, and genital area);these may be symptoms of Stevens-Johnson syndrome or toxic epidermal necrolysis (Lyell's syndrome) [very rare].

The following are other side effects that may occur:

Very common (may occur in more than 1 in 10 people)

• Mouth ulcers, nausea, vomiting, loss of appetite, abdominal pain.
• Abnormal liver function test results (AST, ALT, bilirubin, alkaline phosphatase).

Common (may occur in up to 1 in 10 people)

• Mouth ulcers, diarrhea.
• Skin rash, redness of the skin, itching.
• Headache, fatigue, drowsiness.
• Decreased production of blood cells with decreased white blood cell count, decreased red blood cell count, decreased platelet count.

Uncommon (may occur in up to 1 in 100 people)

• Sore throat.
• Intestinal inflammation, vomiting, pancreatitis, black and tarry stools, gastrointestinal ulcers and bleeding.
• Increased sensitivity to light, hair loss, increased number of rheumatoid nodules, skin ulcers, shingles, vasculitis, skin rash resembling herpes, hives.
• Onset of diabetes.
• Dizziness, impaired cognitive function (cognitive impairment), disorientation, depression.
• Decreased albumin levels in the blood serum.
• Decreased production of all blood cells and platelets.
• Urinary tract inflammation or ulcers, decreased kidney function, urinary disorders.
• Joint pain, muscle pain, decreased bone density.

Rare (may occur in up to 1 in 1,000 people)

• Malabsorption of nutrients, gum inflammation.
• Skin discoloration, acne, blue spots due to bleeding (ecchymoses, purpura), allergic vasculitis.
• Decreased antibody levels in the blood.
• Infection (including reactivation of latent chronic infection), eye redness (conjunctivitis).
• Mood swings.
• Vision disturbances.
• Pericarditis, fluid accumulation in the pericardial sac, impaired heart filling due to fluid in the pericardial sac.
• Low blood pressure.
• Lung tissue scarring (pulmonary fibrosis), shortness of breath and asthma, fluid accumulation in the pleura.
• Fractures due to overuse or bone weakness (stress fractures).
• Electrolyte disturbances.
• Fever, impaired wound healing.

Very rare (may occur in less than 1 in 10,000 people)

• Sudden, severe colon enlargement (toxic megacolon).
• Worsening of nail discoloration, inflammation of the nail folds (acute paronychia), deep infection of hair follicles (furunculosis), visible enlargement of small blood vessels.
• Pain, decreased muscle strength, numbness or tingling, or decreased reaction to stimuli, changes in taste (metallic taste), seizures, paralysis, signs of meningeal irritation.
• Impaired vision, non-inflammatory eye disease (retinopathy).
• Loss of sex drive, impotence, breast enlargement in men, disorders of sperm production (oligospermia), disorders of oogenesis, disorders of spermatogenesis, infertility, menstrual disorders, vaginal discharge.
• Lymph node enlargement (lymphoma).
• Lymphoproliferative disorders (overproduction of white blood cells).

Frequency not known (frequency cannot be estimated from available data)

• Increased white blood cell count.
• Nosebleeds.
• Presence of protein in the urine.
• Feeling of weakness.
• Pulmonary bleeding.
• Jawbone damage (due to overproduction of white blood cells).
• Redness and peeling of the skin.
• Swelling.

Reporting side effects

If you experience any side effects, including any side effects not listed in this leaflet, you should tell your doctor, pharmacist, or nurse. Side effects can be reported directly to the Department of Drug Safety Monitoring of the Office for Registration of Medicinal Products, Medical Devices, and Biocidal Products:
Al. Jerozolimskie 181C, PL-02-222 Warsaw, Tel.: +48 22 49-21-301, Fax: +48 22 49-21-309,
Website: https://smz.ezdrowie.gov.pl .
Side effects can also be reported to the marketing authorization holder.
Reporting side effects will help to gather more information on the safety of the medicine.

5. How to store Metotab

The medicine should be stored out of sight and reach of children.
There are no special storage instructions for the medicine.
Do not take Metotab after the expiry date stated on the packaging after the term "Expiry date". The expiry date refers to the last day of the given month.
Medicines should not be disposed of via wastewater or household waste. You should ask your pharmacist how to dispose of medicines that are no longer needed. This will help protect the environment.

6. Contents of the pack and other information

What Metotab contains

• The active substance of Metotab is methotrexate. The medicine contains 2.5 mg or 7.5 mg or 10 mg of methotrexate (in the form of methotrexate disodium).
• The other ingredients are: lactose monohydrate, pregelatinized starch, magnesium stearate.

What Metotab looks like and contents of the pack

Yellow, slightly speckled, round, biconvex tablets. The 10 mg tablets have a score line, which is intended only for marking.
HDPE or PP bottle with a PP cap, containing 10, 30, 50, or 100 tablets.
Not all pack sizes may be marketed.

Marketing authorization holder and manufacturer

medac Gesellschaft für klinische Spezialpräparate mbH
Theaterstr. 6
22880 Wedel
Germany
Tel. +49 4103 8006 0
Fax: +49 4103 8006 100

Date of last revision of the leaflet: 05/2022