MAXTREX TABLETS 10.0 MG - patient leaflet, side effects, dosage

Maxtrex®

methotrexate

Read all of this leaflet carefully before you

start 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, pharmacist or nurse.
• 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, pharmacist or nurse. This includes any possible side effects not listed in this leaflet. See section 4.

• 1. What Maxtrex Tablets are and what they are used for

• 2. What you need to know before you take Maxtrex

• 3. How to take Maxtrex

• 4. Possible side effects

• 5. How to store Maxtrex

• 6. Contents of the pack and other information

1. What Maxtrex Tablets are and what they are used for

Maxtrex Tablets contain the active ingredient methotrexate. Methotrexate is referred to as a cytotoxic, most commonly used to kill cells in tumours.

Maxtrex Tablets can also be used to treat severe, uncontrolled psoriasis. It is usually used for patients who have tried other treatments but their condition has not improved.

Methotrexate helps patients with psoriasis by killing the cells in the skin, which are growing too quickly. It is these fast growing cells, which cause the raised patches of skin in psoriasis.

Maxtrex is used to treat a wide range of tumours, in particular:

• acute leukaemias,
• Non-Hodgkin’s lymphoma,
• soft tissue and bone sarcomas,
• solid tumours like breast, lung, head and neck, bladder, cervical, ovarian and testicular cancer.

Maxtrex can be given alone or in combination with other medicines.

You should consult your doctor if you are unsure why you have been given Maxtrex 10 mg Tablets.

You must talk to a doctor if you do not feel better or if you feel worse.

2. what you need to know before you take maxtrex

Your doctor may perform several tests such as blood tests, x-rays and physical examinations before treatment with Maxtrex tablets is started, and at regular intervals during treatment.

Do not take Maxtrex Tablets if you:

• are allergic to methotrexate, or any of the other ingredients of this medicine (listed in section 6).
• are breast-feeding and additionally, for non-oncologic indications (for non-cancer treatment) if you are pregnant (see section on Pregnancy, breast-feeding and fertility). You and your partner should avoid conception (becoming pregnant or fathering children) ilQli for at least three months after your treatment with rQM methotrexate has stopped.
• have severe liver problems (including fibrosis, cirrhosis and recent or active hepatitis).
• have severe kidney problems, including conditions requiring kidney dialysis.
• have any serious blood problems including serious anaemia and clotting problems.
• have an alcohol dependency.
• have a medical condition or are receiving medication which lowers your resistance to infection.
• are taking antibiotics which prevent the production of folic acid (vitamin B9) such as co-trimoxazole, which are used to treat bacterial infections.
• have an active infectious disease (e.g. fever, chills, joint pain).
• are being treated with live vaccines.
• ulcer of the oral cavity and gut.
• inflammation of mouth or lips.

Warnings and precautions

Talk to your doctor, pharmacist or nurse before taking Maxtrex Tablets if you have any of the following conditions. This will help them decide if Maxtrex Tablets are suitable for you:

• have any mild or moderate kidney disease,
• have a stomach ulcer or ulcerative colitis (inflammation and ulceration of the gut),
• have any blood disorders or anaemia,
• have diarrhoea,
• have gastro-intestinal (digestive) problems,
• have severe mouth ulcers,
• diabetes mellitus,
• have severe mouth ulcers,
• have or have ever suffered from mental illness,
• received or you are receiving radiotherapy (x-ray treatment) or UV radiation,
• have received any vaccinations recently or you are due to have any, as methotrexate can reduce their effect,
• have any symptoms or signs of infection,
• have excess fluid, between the lungs and chest wall (pleural effusion) or abdominal swelling (ascites) causing breathlessness,
• develop a persistent cough or develop shortness of breath as it may be associated with serious lung disease,
• have or have ever had liver damage, dependence on alcohol or abnormal liver function tests,
• have diabetes and are being treated with insulin,
• have an inactive chronic infection, such as herpes zoster, tuberculosis, hepatitis B or C,
• special care is also needed in children, the elderly and in those who are in poor physical condition,
• methotrexate temporarily affects sperm and egg production. Methotrexate can cause miscarriage and severe birth defects. You and your partner should avoid having a baby if you are being given methotrexate at the time and for at least 6 months after the end of your treatment with methotrexate. See also section “Pregnancy, breast-feeding and fertility”.

Acute bleeding from the lungs in patients with underlying rheumatologic disease has been reported with methotrexate. If you experience symptoms of spitting or coughing up blood you should contact your doctor immediately.

If you, your partner or your caregiver notice new onset or worsening of neurological symptoms including general muscle weakness, disturbance of vision, changes in thinking, memory and orientation leading to confusion and personality changes contact your doctor immediately because these may be symptoms of a very rare, serious brain infection called progressive multifocal leukoencephalopathy (PML). Recommended follow-up examinations and precautions Even if methotrexate is used in low doses, serious side effects can occur. In order to detect them in time, your doctor must perform monitoring examinations and laboratory tests.

Prior to the start of therapy:

Before you start treatment, your blood will be checked to see if you have enough blood cells. Your blood will also be tested to check your liver function and to find out if you have hepatitis. Furthermore, serum albumin (a protein in the blood), hepatitis (liver infection) status and kidney function will be checked. The doctor may also decide to run other liver tests, some of these may be images of your liver and others may need a small sample of tissue taken from the liver in order to examine it more closely. Your doctor may also check to see if you have tuberculosis and they may X-ray your chest or perform a lung function test.

During the treatment:

Your doctor may perform the following examinations: – examination of the oral cavity and the pharynx for changes in the mucous membrane such as inflammation or ulceration

• – blood tests/ blood count with number of blood cells and measurement of serum methotrexate levels

• – blood test to monitor liver function – imaging tests to monitor liver condition – small sample of tissue taken from the liver in order to examine it more closely

• – blood test to monitor kidney function

• – respiratory tract monitoring and, if necessary, lung function test

It is very important that you appear for these scheduled examinations.

If the results of any of these tests are conspicuous, your doctor will adjust your treatment accordingly.

Elderly patients

Elderly patients under treatment with methotrexate should be monitored closely by a physician so that possible side effects can be detected as early as possible. Age-related impairment of liver and kidney function as well as low body reserves of the vitamin folic acid in old age require a relatively low dosage of methotrexate.

Other medicines and Maxtrex Tablets

Tell your doctor or pharmacist if you are taking, have recently taken, or might take any other medicines. This includes the following medicines, as the effect of Maxtex Tablets may be altered when they are taken at the same time:

• vaccinations / live virus vaccines
• ibuprofen, indomethacin (NSAID’s, non-steroidal anti-inflammatory drugs) which are used for pain or inflammation
• aspirin or similar medicines (known as salicylates)
• diuretics (water tablets)
• medicines used/taken for diabetes
• antibiotics (used to treat bacterial infections e.g. chloramphenicol, penicillin, sulfonamides, co-trimoxazole, trimethoprim / sulfamethoxazole, ciprofloxacin and tetracyclines)
• thiazides (a group of diuretics for fluid retention e.g. bendroflumethi­azide)
• hypoglycaemics (used for lowering blood sugar levels e.g. metformin)
• p-aminobenzoic acid, acitretin (used to treat psoriasis or skin disorders)
• diphenylhydantoins, phenytoin (used to treat epilepsy) probenicid, sulfinpyrazone (used to treat gout) acitretin (a medicine used to treat psoriasis)
• theophylline (medicine used in the treatment of asthma)
• pantoprazole (medicines used to reduce the production of stomach acid)
• radiotherapy
• vitamin preparations containing folic acid or similar products
• nitrous oxide (a gas used in general anaesthesia)
• levetiracetam (a medicine used to treat seizures in epilepsy) loop diuretics (used to treat hypertension and oedema) sulfasalazine, leflunomide (used to treat arthritis)
• cisplatin (used in chemotherapy)
• omeprazole, pantoprazole (used to treat indigestion, stomach acid and ulcers)
• theophylline (used to treat asthma, bronchitis, emphysema)
• mercaptopurine (used to treat acute lymphocytic leukaemia) cyclosporine (used in organ transplantation).

Please tell your doctor or pharmacist if you are taking or have recently taken any other medicines, including medicines obtained without a prescription.

Maxtrex Tablets with food, drink and alcohol Alcohol should be avoided while receiving methotrexate as it increases the risk of liver damage.

Pregnancy, breast-feeding and fertility

If you are pregnant or breast-feeding, think you may be pregnant or are planning to have a baby, ask your doctor or pharmacist for advice before taking this medicine.

Pregnancy

Do not use Maxtrex during pregnancy except if your doctor has prescribed it for oncology treatment. Methotrexate can cause birth defects, harm the unborn child or cause miscarriage. It is associated with malformations of the skull, face, heart and blood vessels, brain, and limbs. It is therefore very important that methotrexate is not given to pregnant women or to women who are planning to become pregnant unless used for oncology treatment.

For non-oncological indications, in women of child-bearing age the possibility of a pregnancy must be ruled out, e.g. by pregnancy tests, before treatment is started.

Do not use Maxtrex if you are trying to become pregnant. You must avoid becoming pregnant during treatment with methotrexate and for at least 6 months after the end of treatment. Therefore, you must ensure that you are taking effective contraception for the whole of this period (see also section “Warnings and precautions”).

If you become pregnant during treatment or suspect you might be pregnant, speak to your doctor as soon as possible. If you do become pregnant during treatment, you should be offered advice regarding the risk of harmful effects on the child through treatment.

If you want to become pregnant, you should speak with your doctor, who may refer you for specialist advice before the planned start of treatment.

Methotrexate can cause birth defects, harm unborn babies or cause miscarriages and so it is very important that it is not given to pregnant patients or patients planning to become pregnant. It may also affect women’s periods; they may become less frequent or stop completely. Methotrexate can affect sperm and egg production with the potential to cause birth defects. You and your partner should avoid conception (becoming pregnant or fathering children) for at least six months after your treatment with methotrexate has stopped. As methotrexate may cause genetic mutations, all women who wish to become pregnant are advised to consult a genetic counselling centre, if possible already prior to therapy, and men should seek advice about the possibility of sperm preservation before starting therapy.

Male fertility

The available evidence does not indicate an increased risk of malformations or miscarriage if the father takes methotrexate less than 30 mg/week. However, a risk cannot be completely excluded and there is no information regarding higher methotrexate doses. Methotrexate can have a genotoxic effect. This means that the medicine can cause genetic mutations. Methotrexate can affect the production of sperm, which is associated with the possibility of birth defects.

You should avoid fathering a child or donating semen during treatment with methotrexate and for at least 6 months after the end of treatment. As treatment with methotrexate at higher doses commonly used in cancer treatment can cause infertility and genetic mutations, it may be advisable for male patients treated with methotrexate doses higher than 30 mg/week to consider sperm preservation before the beginning of treatment (see also section “Warnings and precautions”).

Breast-feeding

Methotrexate passes into breast milk. You should not take Maxtrex Tablets if you are breast-feeding.

Driving and using machines

Maxtrex Tablets may cause some side effects which could affect your ability to drive or use machinery for example drowsiness, loss of co-ordination or blurred vision. If you

experience these symptoms, do not drive or use any tools or machinery. The full list of side effects are listed in section 4. Maxtrex Tablets contain lactose

These tablets contain lactose monohydrate (type of sugar). If you have been told by your doctor that you have an intolerance to some sugars, contact your doctor before taking this medicine.

3. how to take maxtrex

Always take this medicine exactly as your doctor or pharmacist has told you. Check with your doctor or pharmacist if you are not sure. _____________­________________

Important warning about the dose of Maxtrex tablets (methotrexate):

Use Maxtrex tablets only once a week for the treatment of psoriasis. Using too much of Maxtrex tablets (methotrexate) may be fatal. Please read section 3 of this leaflet very carefully. If you have any questions, please talk to your doctor or pharmacist before you take this medicine.

The recommended dose is:

Dosage for psoriasis:

Take Maxtrex only once a week.

Adults

You will usually take your tablets once a week on the same day each week. Patients may be given a test dose of 2.5–5 mg by their doctor first to exclude unexpected toxicities. For severe psoriasis, the dose usually starts at 7.5 – 15 mg per week but may rise to 25 mg per week. The dose must be given all at once. The dose should be adjusted according to your response to treatment and side effects.

Children

Not recommended for use in children.

Dosage for treatment of cancer: Adults, the Elderly and Children

• Your doctor should give you a test dose of 5 to 10 mg by injection one week before starting treatment.
• The doctor will calculate the dosage required from your body surface area (m2), and the dose is expressed as mg/m2.
• Maxtrex Tablets are usually given as single doses, not exceeding 30 mg/m2, for up to five days.
• A rest period of at least two weeks is advised between treatments, to allow recovery from any side effects.
• Doses in excess of 100 mg are usually given by injection by your doctor or physician.
• Doses of more than 70 mg/m2 should not be administered without calcium folinate rescue therapy or blood levels of methotrexate being checked 24 to 48 hours after taking your medicine.
• These doses may be reduced if you are receiving other medication. Your doctor will decide the correct dose for you, if you want more information you should ask your doctor.

If you have the impression that the effect of Maxtrex Tablets is too strong or too weak, talk to your doctor or pharmacist.

If you take more Maxtrex Tablets than you should

If you accidentally take too many Maxtrex Tablets contact your doctor at once or go to the nearest hospital casualty department. Always take the labelled medicine package with you, whether there are any Maxtrex Tablets left or not. Overdose symptoms may include easy bruising or bleeding, unusual weakness, mouth sores, nausea, vomiting, black or bloody stools, coughing up blood or vomit that looks like coffee grounds, and decreased urinating.

Inappropriate intake resulting in overdose can sometimes lead to death.

The antidote in case of an overdose is calcium folinate.

If you forget to take Maxtrex Tablets

If you forget to take a dose, take it as soon as you remember if this is within two days. However, if you have missed a dose by more than two days, please contact your doctor for advice. Do not take a double dose to make up for a forgotten dose.

If you stop taking Maxtrex Tablets

Do not stop taking Maxtrex Tablets unless your doctor tells you to. Should you need to stop taking Maxtrex Tablets, your doctor will have decided which is the best method for you.

If you have any further questions on the use of this medicine, ask your doctor, pharmacist or nurse.

4. possible side effects

Like all medicines, this medicine can cause side effects, although not everybody gets them. However, Methotrexate is a very toxic medicine and some patients have died, or become very ill whilst being treated with it.

Tell your doctor immediately if you experience any of the following symptoms after taking this medicine. Although they are very rare, these symptoms can be serious.

• Severe skin rash that causes blistering, (this can affect the mouth and tongue). These may be signs of a condition known as Stevens Johnson Syndrome. Your doctor will stop your treatment in these cases.
• Persistent cough, pain or difficulty breathing, or becoming breathless, methotrexate can cause diseases of the lung e.g. fluid in lungs.
• Spitting or coughing blood; this has been reported for methotrexate used in patients with underlying rheumatologic disease.
• Skin rash and fever with swollen glands, particularly in the first two months of treatment, as these may be signs of a hypersensitivity reaction.
• Sore throat, fever, chills, or achiness; methotrexate can make you more likely to catch infections.
• Loss of coordination, loss of ability to speak or understand speech, weakness and inability to move one side of the body or the whole body, convulsions or fits.
• Swelling of the hands, ankles or feet (which may be a sign of kidney damage).
• Yellowing of the skin and whites of the eye (a sign of liver damage).
• Severe allergic reaction (anaphylactic reaction) -although very rare you may experience a sudden itchy skin rash (hives), swelling of the hands, feet, ankles, face, lips, mouth or throat (which may cause difficulty in swallowing or breathing), wheeze, and you may feel you are going to faint.
• Severe mouth ulcers and ulcers of the gut
• Reduction in red blood cells which can make the skin pale and cause weakness or breathlessness
• Reduction in blood platelets which increase risk of bleeding or bruising
• Lung infection (Pneumonia)
• Drowsiness
• Severe skin reaction
• Inflammation of vessels, often with skin rash
• Itchy skin
• Shingles (Herpes Zoster)
• Ringing in the ears
• Abdominal pain
• Indigestion
• Convulsions
• Loss of coordination
• Asthma
• Confusion
• Liver damage (seen as yellowing of the skin and whites of the eye)
• Liver failure
• Kidney damage
• Low levels of white cell count (leukopenia) and red blood cells and cells that clot blood
• Infection, reduced resistance to infection
• Abnormal red blood cell function
• Lung damage/scarred
• Build-up of excess fluid in the lung
• Build-up of fluid or excess fluid in the double layer around the heart
• Abnormal low blood pressure
• Inability to move
• Inability to move in one half of the body
• Dizziness
• Headaches
• Blurred vision
• Difficulty sleeping
• Raised blood sugar levels (diabetes mellitus)
• Sensation of numbness or tingling, having less sensitivity to stimulation than normal (frequency very rare)
• Change in sense of taste
• Loss of ability to speak or understand speech
• Impaired vision
• Brittle bones
• Muscular pain
• Slow thought process
• Mood alteration
• Black or tarry stools
• Skin ulcers and erosions of inflamed areas, in psoriasis patients
• Damaged skin becomes inflamed on re-exposure to radiation and sunlight
• Reduced ability to become pregnant and reduced ability to father children
• Inflammation of the vagina
• Vaginal bleeding
• Menstrual disorders
• Blood in the urine
• Raised liver enzymes
• Weakening or softening of bones
• Unusual sensations in the head
• Anorexia (eating disorders)
• Loss of interest in, or inability to have sex
• Stomach pains and soreness of the mouth, throat and lips
• Inflamed blood vessels
• Feeling sick, being sick and/or diarrhoea, decreased absorption from intestines
• Irritation or swelling of the vaginal tissues
• Vaginal ulcers
• Pain or difficulty in passing urine
• The need to pass urine more often than usual
• Ulcers in urinary bladder
• Joint and muscle pain
• Chills and fever
• Changes in skin and nail colouration
• Bacteria or fungal infection of hand and feet
• Hair loss
• Red spots on the skin, skin lesions, acne, boils
• Redness and shedding of skin (frequency not known)
• Itchiness and rash
• Sensitivity to light
• Eye infection
• Tiredness and lack of energy
• General feeling of illness
• Other metabolic changes
• Nose bleed (frequency not known)
• Bleeding from the lungs (frequency not known) – this has been reported for methotrexate used in patients with underlying rheumatologic disease
• Lymphoproliferative disorders (excessive growth of white blood cells) (frequency very rare)
• Bone damage in the jaw (secondary to excessive growth of white blood cells) (frequency not known)
• Swelling (frequency not known).

5. how to store maxtrex

Keep this medicine out of the sight and reach of children. Accidental ingestion can be lethal for children.

Keep the blister in the outer carton in order to protect from light

Do not use this medicine after the expiry date which is printed on the carton and label after EXP. The expiry date refers to the last day of that month.

Anyone handling methotrexate should wash their hands after administering a dose. To decrease the risk of exposure, parents and care givers should wear disposable gloves when handling methotrexate.

Do not throw medicines via wastewater or household waste. Ask your pharmacist how to throw away medicines you no longer use. These measures will help protect the environment.

6. contents of the pack and other information

What Maxtrex Tablets contains

The active substance is methotrexate. Each tablet contains 10 mg of the active ingredient methotrexate.

The other ingredients are maize starch, lactose monohydrate (see section 2), pregelatinised starch, polysorbate 80, microcrystalline cellulose, magnesium stearate and purified water.

What Maxtrex Tablets looks like and contents of the pack

Maxtrex 10 mg Tablets are yellow, elongated like a capsule and is scored and printed ‘M10’ on the same side of the tablet.

The tablet has a deeper scoreline to help it to break more easily.

Maxtrex 10 mg Tablets are available in plastic bottles containing 100 tablets.

Not all pack sizes may be marketed.

Marketing Authorisation Holder

Pfizer Limited

Ramsgate Road

Sandwich

Kent CT13 9NJ

United Kingdom

Manufacturer

Orion Corporation,

Orion Pharma

Orionintie 1

FI-02200

Espoo

Finland

For further information please contact Medical Information at Pfizer Limited on 01304 616161.

This leaflet was last revised in 01/2022.

Ref: MX 23_0