Metotab 2,5 mg

Package Leaflet: Information for the User

Metotab 2.5 mg, tablets

Metotab 7.5 mg, tablets

Metotab 10 mg, tablets

Methotrexate

Read all of this leaflet carefully before taking this medicine because it contains important information for you.

• Keep this leaflet. You may need to read it again.
• If you have any further questions, ask your doctor or pharmacist.
• This medicine has been prescribed for you only. Do not pass it on to others. It may harm them, even if their signs of illness are the same as yours.
• If you get any side effects, talk to your doctor or pharmacist. This includes any possible side effects not listed in this leaflet. See section 4.

Contents of the pack and other information

• 1. What Metotab is and what it is used for
• 2. Before you take 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 Metotab is and what it is 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 whose function is to reduce friction in many joints. The inflammatory condition 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 the progression 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. If you have any further questions, ask your doctor, pharmacist, or other healthcare professional and always follow their advice.

2. Before you take Metotab

Important warning about Metotab dosing (methotrexate):

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.
It is very important to read the contents of section 3 of this leaflet carefully.
If you have any questions, you should consult your doctor or pharmacist before taking this medicine.

When not to take Metotab

• if you are allergic to methotrexate or any of the other ingredients of this medicine (listed in section 6),
• if you have severe liver or kidney disease or blood disease,
• if you drink large amounts of alcohol,
• if you have a severe infection, such as tuberculosis or HIV infection, or other immune system disorder,
• if you have ulcers of the mouth, stomach, or intestines,
• if you are pregnant or breastfeeding (see section "Pregnancy, breastfeeding and fertility"),
• if you are to receive a vaccine containing live organisms at the same time.

Warnings and precautions

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

• if you are elderly or in poor general health,
• if you have impaired liver or kidney function,
• if you are dehydrated.

Special precautions for use of Metotab
Methotrexate can temporarily disrupt the production of sperm and egg cells; in most cases, this effect disappears. Methotrexate can cause miscarriage and severe birth defects. Women should avoid becoming pregnant while taking methotrexate and for at least 6 months after stopping treatment. See also section "Pregnancy, breastfeeding and fertility".
Recommended tests and precautions
Severe side effects can occur even with low doses of methotrexate. To detect them in time, your doctor must perform regular tests and laboratory tests.
Before starting treatment
Before starting treatment, a blood test will be performed to check if you have 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 (a blood protein) in the serum and kidney function will be checked, and an assessment for hepatitis (hepatitis virus infection) will be performed. Your doctor may also decide to perform other liver tests, which may include liver imaging or a small tissue sample from the liver for a more detailed assessment. Additionally, your doctor may check for tuberculosis and order a chest X-ray or lung function test.
During treatment
Your 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;
• liver function tests;
• imaging tests to monitor liver condition;
• removal of a small tissue sample from the liver for a more detailed assessment;
• kidney function tests;
• respiratory system tests and, if necessary, lung function tests.

It is very important that you attend these scheduled tests.
If the results of any of these tests show abnormalities, your doctor will adjust the treatment accordingly.
Elderly patients
Elderly patients treated with methotrexate should be closely monitored by their doctor 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 bleeding from the lungs have been reported in patients with underlying rheumatologic disease. If you experience coughing up blood, you should immediately consult your doctor.
Methotrexate can affect the immune system, and some vaccines may not work properly while taking methotrexate. If you have underlying or chronic infections (e.g., shingles, tuberculosis, hepatitis B or C), treatment with methotrexate may cause their exacerbation or worsening. If you have 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.
Lymphoma (lymph node cancer) may occur. In such cases, treatment should be discontinued.
Diarrhea can be a side effect of Metotab and may require discontinuation of treatment. If you experience diarrhea, you should tell your doctor.
In case of swelling, such as facial, tongue, and/or throat swelling, and/or difficulty swallowing or breathing (anaphylactic shock), you should discontinue Metotab and immediately contact your 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 with methotrexate treatment for other diseases. If you, your partner, or caregiver notice new or worsening neurological symptoms, including general muscle weakness, vision disturbances, changes in thinking, memory, and orientation leading to disorientation and personality changes, you should immediately contact your doctor, as these may be symptoms of a very rare, serious brain infection called progressive multifocal leukoencephalopathy (PML).

Metotab and other medicines

Tell your doctor or pharmacist about all medicines you are taking, have recently taken, or might take.
The effectiveness of Metotab may be altered when taken with certain other medicines:

• antibiotics, such as 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 drugs (NSAIDs)or salicylates[pain-relieving and/or anti-inflammatory medicines, such as acetylsalicylic acid, diclofenac, and ibuprofen or pyrazole];
• probenecid(used to treat gout);
• weak organic acids, such as loop diuretics(diuretics);
• medicines that can harm bone marrow, such as trimethoprim-sulfamethoxazole (an antibiotic) or pyrimethamine;
• other medicines used to treat rheumatoid arthritis, such as leflunomide, sulfasalazine, and azathioprine;
• cytostatic agentssuch as mercaptopurine;
• retinoids(medicines used to treat psoriasis and other skin diseases);
• theophylline(a medicine used to treat asthma and other lung diseases);
• certain stomach medicines, such as omeprazole and pantoprazole;
• blood sugar-lowering medicines(hypoglycemic agents).

Vitamin preparations containing folatemay reduce the effectiveness of treatment and should only be taken on the advice of a doctor.
During treatment with Metotab, live vaccines should be avoided.

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 can 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 pregnant women or those planning to become pregnant do not take methotrexate. If you are of childbearing age, you should confirm that you are not pregnant before starting treatment, taking appropriate measures, such as a pregnancy test. You should avoid becoming pregnant while taking methotrexate and for at least 6 months after stopping treatment, using reliable contraception during this time (see also section "Warnings and precautions").
If you become pregnant while taking Metotab, or if you think you may be pregnant, you should consult your doctor as soon as possible. You should receive advice on the possible harmful effects of treatment on the baby.
If you plan to become pregnant, you should consult your doctor, who may refer you to a specialist for advice before starting treatment.
Male fertility
Available data do 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 can be genotoxic, meaning it can cause genetic mutations. Methotrexate can affect sperm and cause birth defects. Therefore, men should avoid fathering a child and should not donate sperm while taking methotrexate and for at least 6 months after stopping treatment.
Breastfeeding
You should stop breastfeeding before and during treatment with Metotab.

Driving and using machines

While taking Metotab, you may experience side effects from the central nervous system, such as fatigue and dizziness. In some cases, this may adversely 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.
You are responsible for deciding whether you are fit to drive or perform tasks that require increased attention. The medicines you take can affect your ability to do so, due to their effects or side effects. The description of the effect and side effects of this medicine is given in other sections of the leaflet. You should read all the information in this leaflet and, if you have any questions, consult your doctor or pharmacist.

Metotab contains lactose monohydrate

If you have been told that you have an intolerance to some sugars, you should contact your doctor before taking this medicine.

3. How to take Metotab

Recommended dose:

Dose for rheumatoid arthritis and psoriasis:
Take Metotab only once a week.
You and your doctor will decide which day of the week you will take the medicine.
This medicine should always be taken exactly as prescribed by your doctor. If you are unsure, consult your doctor or pharmacist.
The dose of Metotab will be determined by your doctor, tailored to your individual needs.
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 will be decided by your doctor.
If you feel that the effect of Metotab is too strong or too weak, you should consult your doctor or pharmacist.

Taking a higher dose of Metotab than recommended

Follow your doctor's instructions for dosing. Do not change the dose of the medicine yourself.
If you suspect that you have taken a higher dose of Metotab than recommended, you should immediately contact your doctor, who will decide on the appropriate treatment depending on the severity of the overdose.

Missing a dose of Metotab

Do not take a double dose to make up for a missed dose. Consult your doctor and take the prescribed dose as soon as possible, and then take one dose per 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 can occur even with low doses of the medicine, it is essential that your doctor regularly monitors your health. Your 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 are related to 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 [common];
• Coughing up blood;[frequency not known];
• Signs of liver damage, such as yellowing of the skin and eyes;methotrexate can cause chronic liver damage (liver cirrhosis), scarring of liver tissue (liver fibrosis), fatty liver degeneration [all uncommon], acute liver inflammation (acute hepatitis) [rare], and liver failure [very rare];
• Allergic reaction symptoms, such as skin rash, including red, itchy skin, swelling of 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 hands, feet, or ankles, or changes in urination frequency or decreased urine output;these may be symptoms of kidney failure [rare];
• Signs of infection, such as fever, chills, malaise, sore throat;methotrexate can increase the risk of infections. Severe infections, such as a certain type of pneumonia (Pneumocystis jirovecii pneumonia) and blood poisoning (sepsis), may occur [rare];
• 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 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, accompanied by sore throat or mouth ulcers;methotrexate can cause a sharp decrease in the number of white blood cells (agranulocytosis) and severe suppression of bone marrow function [very rare];
• Unexpected bleeding, such as bleeding from the gums, 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 bone marrow suppression [very rare];
• Symptoms, such as severe headache with fever, stiff neck, nausea, vomiting, disorientation, and sensitivity to light;these may 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 with methotrexate treatment for other diseases. Symptoms of these brain disorders include altered mental state, movement disorders (ataxia), vision disturbances, or memory disturbances[frequency not known];
• 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 affect more than 1 in 10 people)

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

Common (may affect up to 1 in 10 people)

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

Uncommon (may affect up to 1 in 100 people)

• Sore throat.
• Intestinal inflammation, vomiting, pancreatitis, black or tarry stools, gastrointestinal ulcers and bleeding.
• Increased sensitivity to light, hair loss, increased number of rheumatoid nodules, skin ulcers, shingles, blood vessel inflammation, skin rash resembling herpes, hives.
• Onset of diabetes.
• Dizziness, impaired thinking (cognitive impairment), disorientation, depression.
• Decreased albumin levels in the blood.
• 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 affect up to 1 in 1,000 people)

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

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

• Sudden, severe swelling of the large intestine (toxic megacolon).
• Worsening of nail discoloration, inflammation of the nail bed (acute paronychia), deep infection of the hair follicles (furunculosis), visible dilation 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 meningitis.
• Impaired vision, non-inflammatory eye disease (retinopathy).
• Decreased sex drive, impotence, breast enlargement in men, disorders of sperm production (oligospermia), disorders of egg production, disorders of sperm production, 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.
• Protein in the urine.
• Feeling of weakness.
• Bleeding from the lungs.
• Bone damage in the jaw (due to overproduction of white blood cells).
• Redness and peeling of the skin.
• Swelling.

Reporting side effects

If you experience any side effects, including those not listed in this leaflet, you should tell your doctor, pharmacist, or nurse. You can also report side effects directly to the Pharmacovigilance Department, Office for Registration of Medicinal Products, Medical Devices, and Biocidal Products:
Jerozolimskie Avenue 181C, 02-222 Warsaw, Poland, Tel.: +48 22 49-21-301, Fax: +48 22 49-21-309,
Website: https://smz.ezdrowie.gov.pl.
You can also report side effects to the marketing authorization holder.
By reporting side effects, you can help provide more information on the safety of this medicine.

5. How to store Metotab

Keep this medicine out of the sight and reach of children.
There are no special storage instructions for this medicine.
Do not use Metotab after the expiry date stated on the packaging after "EXP". The expiry date refers to the last day of that month.
Medicines should not be disposed of via wastewater or household waste. Ask your pharmacist how to dispose of medicines no longer required. These measures 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 (as methotrexate disodium).
• The other ingredients are lactose monohydrate, maize 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 only for marking purposes.
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