Methotrexate 25 Mg/Ml Solution For Injection/Infusion
PACKAGE LEAFLET: INFORMATION FOR THE PATIENT
Methotrexate 25 mg/ml solution for injection/infusion methotrexate
Read all of this leaflet carefully before you start using 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. This includes any possible side effects not listed in this leaflet..
What is in this leaflet
1. What Methotrexate 25 mg/ml solution for injection/infusion is and what it is used for
2. What you need to know before you use Methotrexate 25 mg/ml solution for injection/infusion
3. How to use Methotrexate 25 mg/ml solution for injection/infusion
4. Possible side effects
5. How to store Methotrexate 25 mg/ml solution for injection/infusion
6. Contents of the pack and other information
1. What Methotrexate 25 mg/ml solution for injection/infusion is and what it
is used for
Methotrexate is a substance with the following properties:
- it interferes with the growth of tumour cells in the body that reproduce quickly (anti-tumour agent)
- it reduces undesired reactions of the body’s own defence mechanism (immunosuppressant), and
- it has anti-inflammatory effects.
Methotrexate is used to treat cancer, such as:
• lymphatic leukaemia (disease of the blood or bone marrow with increased number of white blood cells)
• breast cancer
• bone cancer (osteosarcoma)
• head and neck cancer
• gynaecologic cancer (choriocarcinoma, trophoblastic disease - tumour development directly associated with pregnancy)
• cancer of the lymphatic system (Non-Hodgkin's lymphoma).
2. What you need to know before you use Methotrexate 25 mg/ml solution for injection/infusion
Do not use Methotrexate 25 mg/ml solution for injection/infusion if:
• you are allergic to methotrexate or any of the other ingredients of this medicine (listed in section 6)
• you have significant kidney disease
• you have significant liver disease
• you have increased alcohol consumption
• you have disorders of the blood-forming system
• you have severe or existing infections
• you have gastrointestinal ulcers or ulcers of the oral cavity
• you are pregnant or breast-feeding (see section “Pregnancy, breast-feeding and fertility”)
You should not be given live vaccines during treatment with Methotrexate 25 mg/ml solution for injection/infusion.
Tell your doctor before you use Methotrexate 25 mg/ml solution for injection/infusion if you think any of the above applies to you.
Warnings and precautions
Take special care with Methotrexate 25 mg/ml solution for injection/infusion if you:
• have diabetes mellitus treated with insulin
• have inactive, prolonged infections (e.g. tuberculosis, hepatitis B or C, shingles (herpes zoster))
• have problems with your lung function
• have/had any liver or kidney disease
• experience any sign or symptoms suggestive of infection, e.g. fever
• have abnormal accumulation of liquid in the abdomen or in the cavity between the lungs and chest wall (ascites, pleural effusions)
• are dehydrated or suffer from conditions leading to dehydration (vomiting, diarrhoea, stomatitis).
Inform your doctor in case any of the above applies to you.
You should avoid solarium and direct sun light during treatment, as the skin is more sensitive.
Methotrexate may be genotoxic. This means that the medicine may cause genetic mutation. Methotrexate can affect sperm and egg production with the potential to cause birth defects. You and your partner must avoid conception (becoming pregnant or fathering children) if currently receiving methotrexate and for at least six months after your treatment with methotrexate has stopped. See also section “Pregnancy, breast-feeding and fertility”.
Since treatment with methotrexate may lead to infertility, it might be advisable for male patients to look into the possibility of sperm preservation before starting treatment.
Even if Methotrexate 25 mg/ml solution for injection/infusion is administered at low dosage, severe side effects can occur. In order to diagnose them early, regular monitoring by the doctor at short-term intervals is necessary.
Before treatment is started your doctor may carry out blood tests, and also to check how well your kidneys and liver are working. You may also have a chest X-ray. Further tests may also be done during and after treatment. Do not miss appointments for blood tests.
If the results of any of these tests are abnormal, treatment will only be resumed when all readings are back to normal.
Other medicines and Methotrexate 25 mg/ml solution for injection/infusion
Tell your doctor or pharmacist if you are taking, have recently taken, or might take any other medicines including medicines, obtained without a prescription and herbal or natural medicinal products. Remember to tell your doctor about your treatment with Methotrexate 25 mg/ml solution for injection/infusion, if you are prescribed another medicine while the treatment is still ongoing.
It is especially important to tell your doctor if you are using:
- other treatments for rheumatoid arthritis or psoriasis such as leflunomide, sulphasalazine (also used for ulcerative colitis), salicylates such as acetylsalicylic acid, phenylbutazone, or amidopyrine
- alcohol (should be avoided)
- live vaccinations
- azathioprine (used to prevent rejection after an organ transplant)
- retinoids (used to treat psoriasis and other skin disorders)
- anticonvulsant drugs (prevent fits)
- cancer treatments
- barbiturates (sleeping injection)
- tranquillisers
- oral contraceptives
- probenecid (for gout)
- antibiotics
- pyrimethamine (used to prevent and treat malaria)
- vitamin preparations, which contain folic acid
- proton-pump inhibitors (used to treat severe heartburn or ulcers)
- theophylline (used to treat asthma).
Methotrexate 25 mg/ml solution for injection/infusion with food, drink and alcohol
During Methotrexate 25 mg/ml solution for injection/infusion treatment, you should avoid any alcohol consumption as well as excessive consumption of coffee, caffeine-containing beverages or black tea. Also make sure you drink plenty of liquids during treatment with Methotrexate 25 mg/ml solution for injection/infusion, because dehydration (reduction in body water) can increase the toxicity of Methotrexate 25 mg/ml solution for injection/infusion.
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 for advice before taking this medicine.
You must not use Methotrexate 25 mg/ml solution for injection/infusion during pregnancy. Men and women should use an effective method of birth control during treatment and during a further six months after treatment with Methotrexate 25 mg/ml solution for injection/infusion has been discontinued.
In women of child-bearing age, any existing pregnancy must be excluded with certainty by taking appropriate measures e.g. pregnancy test, prior to therapy.
As methotrexate can be genotoxic, 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, see also section “Take special care with Methotrexate 25 mg/ml solution for injection/infusion”.
Breast-feeding
Methotrexate passes into breast milk. Breast-feeding should be stopped prior to and during treatment with Methotrexate 25 mg/ml solution for injection/infusion.
Driving and using machines
Tiredness and dizzinesscan occur during treatment. If affected you should not drive or operate machinery.
Methotrexate 25 mg/ml solution for injection/infusion contains sodium
This medicinal product contains 0.21 mmol (or 4.945 mg) sodium per ml. To be taken into consideration by patients on a controlled sodium diet.
3. How to use Methotrexate 25 mg/ml solution for injection/infusion solution for injection/infusion
Treatment with methotrexate should be initiated by or in consultation with a doctor with considerable experience in cancer treatment. The dose is usually calculated based on various factors e.g. the patient general health and body surface area and the type of disease. The overall duration of treatment and intervals between administrations is decided by the physician.
Methotrexate can be given intramuscularly (in a muscle), intravenously (in a vein), intra-arterially (in an artery and intra-thecally. Higher doses are usually given as an infusion over 24 h, either alone or in combination with other medicinal products used to treat cancer.
Your doctor may instruct you to take sodium bicarbonate or acetazolamide tablets while receiving your medicine to help make sure that methotrexate is not concentrated in the kidnes. If you receive methotrexate in high doses, you will receive calcium folinate as well to lessen the side effects of methotrexate.
Use in children
This medicine should be used with caution in children and in line with standard therapy.
Methotrexate should not come into contact with the surface of the skin or mucosa. In the event of contamination, the affected area must be rinsed immediately with plenty of water.
If you use more Methotrexate 25 mg/ml than you should
Your doctor decides on the dosage, which is given by healthcare staff. Overdose is therefore unlikely.
An overdose of methotrexate can lead to severe toxic reactions.
Overdose symptoms may include easy bruising or bleeding, unusual weakness, mouth sores, nausea, vomiting, black or bloody stools. The antidote in case of an overdose is calcium folinate.
If you forget or stop using Methotrexate 25 mg/ml solution for injection/infusion
You should not interrupt or discontinue Methotrexate 25 mg/ml solution for injection/infusion treatment, unless you have discussed this with your doctor. In case you forget your appointment for next dose, contact your doctor as soon as possible to schedule a new appointment. If you suspect severe side effects, contact your doctor immediately for advice.
If you have any further questions on the use of this product, ask your doctor or pharmacist.
4. Possible Side Effects
Like all medicines Methotrexate 25 mg/ml solution for injection/infusion can cause side effects, although not everybody gets them.
Tell your doctor straight away if you get any sudden wheeziness, difficulty in breathing, swelling of the eyelids, face or lips, rash or itching (especially affecting your whole body).
Serious side effects
If you develop any of the following side effects, contact your doctor immediately:
• lung complaints (symptoms may be general illness; dry, irritating cough; shortness of breath, breathlessness at rest, chest pain, or fever)
• severe peeling or blistering of the skin
• unusual bleeding (including vomiting blood) or bruising
• severe diarrhoea
• ulcers in mouth
• black or tarry stools
• blood in the urine or stools
• tiny red spots on the skin
• fever
• yellowing of the skin (jaundice)
• pain or difficulty in passing urine
• thirst and/or frequent urination
• fits (convulsions)
• loss of consciousness
• blurred or decreased vision.
The following side effects have also been reported.
Very common (more than 1 in 10):
Inflammation of the mouth, indigestion, loss of appetite, nausea (feeling sick), vomiting, tummy pain, inflammation and ulcers in the mouth and throat. Increase in liver enzymes (can be detected by a test carried out by a doctor).
Common (between 1 in 100 and 1 in 10):
Changes in the number of blood cells and platelets (can be detected by a test carried out by a doctor).
Headache, tiredness, sleepiness. Diarrhoea. Measles-like rash (alone), redness, and itching.
Uncommon (between 1 in 1000 and 1 in 100):
Spinning sensation, confusion, depression, fits. Brain disorder (leukoencephalopathy/enchepalopathy). Lung damage. Ulcers and bleeding in the digestive tract. Liver disorders (can be detected by a test carried out by a doctor), diabetes, decreased blood protein (can be detected by a test carried out by a doctor). Nettle rash (alone), light sensitivity, brown skin, hair loss, increase of rheumatic nodules (lumps of tissues), shingles, painful psoriasis, Joint or muscle pain, brittle bones, inflammation. Ulcers in the bladder (possibly with blood in the urine), painful urination. Severe allergic reactions. Inflammation and ulcers of the vagina.
Rare (between 1 in 1000 and 1 in 10000):
Inflammation of the lining of the heart, fluid around the heart. Severely visual disturbance, mood alterations.
Low blood pressure, blood clots. Sore throat, interruption of breathing, asthma. Inflammation of the digestive tract, bloody stools, inflamed gums, abnormal digestion. Changed colour of nails, acne, red or purple spots.
Bone fracture. Kidney failure, little or no urine produced, waste products in the blood. Very rare (less than 1 in 10000 and unknown):
Infections. Severe failure of the bone marrow (can be detected by a test carried out by a doctor). Swollen glands. Sleeplessness. Pain, muscle weakness, pins and needles, changes in sense of taste (metallic taste), inflammation of the lining of the brain causing paralysis or vomiting. Red eyes, damage to the retina of the eye. Fluid on the lungs. Vomiting blood. Cold sores. Protein in the urine (can be detected by a test carried out by a doctor). Loss of sex drive, problems having an erection, low sperm production, abnormal periods, vaginal discharge, infertility. Infection around a fingernail, severe complication of the digestive tract, fungal infections, boils, dilated small blood vessels in the skin, damage to the blood vessels of the skin. Lumps in the armpit or groin. Slow wound healing.
Other: After injection into a muscle, there may be a burning sensation or damage at the injection site.
If you get any side effects, talk to your doctor. This includes any side effects not listed in this leaflet.
5. How to store Methotrexate 25 mg/ml for injection/infusion
• Keep the medicine out of sight and reach of children.
• Keep the vial in the outer carton in order to protect from light.
• Do not store above 25°C.
• For single dose use only. Discard any unused solution immediately and safely after initial use.
• This medicine should only be administered by a medically qualified person, e.g. a doctor.
• Do not use Methotrexate 25 mg/ml solution for injection/infusion if there are any visible signs of deterioration.
• Do not use Methotrexate 25 mg/ml solution for injection/infusion after the expiry date which is printed on the carton and vial after EXP.
The expiry date refers to the last day of that month.
• Do not throw away any 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 Methotrexate 25 mg/ml solution for injection/infusion contains
The active substance is: methotrexate.
Each 1 ml of this sterile solution for injection/infusion contains 25 milligrams methotrexate.
The other ingredients are: sodium chloride, hydrochloric acid, sodium hydroxide, water for injections.
What Methotrexate 25 mg/ml solution for injection/infusion looks like and contents of the pack
Methotrexate 25 mg/ml solution for injection/infusion is a yellow and sterile solution in clear glass vials.
Each pack contains 5 vials of 2 ml, 4 ml or 10 ml solution.
Each pack contains 1 vial of 40 ml solution.
Not all pack sizes may be marketed.
Marketing Authorisation Holder and Manufacturer
Marketing Authorisation Holder:
Mylan, Potters Bar, Hertfordshire, EN6 1TL, UK Manufacturer:
Agila Specialties Polska Sp.z.o.o.
10, Daniszewska Str 03-230 Warsaw Poland
This leaflet was last revised in 09/2014
The following information is intended for medical or healthcare professionals only
Methotrexate 25 mg/ml solution for injection/infusion solution for injection/infusion may be further diluted with an appropriate preservative-free medium such as glucose solution (5 %) or sodium chloride solution (0.9 %) to an in-use concentration of 2 mg/ml.
With respect to the handling the following general recommendations should be considered: The product should be used and administered only by trained personnel; the mixing of the solutions should take place in designated areas, designed to protect personnel and the environment (e.g. safety cabins); protective clothing should be worn (including gloves, eye protection, and masks if necessary).
The product is for single use only. Discard any unused solution immediately after initial use. Waste should be disposed of carefully in suitable separate containers, clearly labelled as to their contents (as the patient’s body fluids and excreta may also contain appreciable amounts of antineoplastic agents and it has been suggested that they, and material such as bed linen contaminated with them, should also be treated as hazardous waste). Any unused product or waste should be disposed of in accordance with local requirements by incineration. For example, chemical destruction methods (oxidation with e.g., potassium permanganate and sulphuric acid or aqueous alkaline potassium permanganate or sodium hypochlorite) have also been used.
Adequate procedures should be in place for accidental contamination due to spillage; staff exposure to antineoplastic agents should be recorded and monitored.
If a cytotoxic drug should contaminate the skin it should be washed off immediately using copious amounts of running water for at least ten minutes. For example, if eyes are sprayed with cytotoxic material they should be rinsed immediately with copious amounts of water and bathed with sterile sodium chloride solution for at least ten minutes.
Pregnant staff should avoid handling antineoplastic agents.