Methotrexate 2mg/ml Oral Solution

Package leaflet: Information for the user

Methotrexate 2mg/ml Oral Solution

1. What Methotrexate Oral Solution is and what it is used for

The full name of your medicine is Methotrexate 2mg/ml Oral Solution. In this leaflet the shorter name methotrexate is used.

Methotrexate belongs to a group of medicines called ‘cytotoxics’ which are most commonly used to kill cells and tumours. It is also known as an immunosuppressant which affects the reproduction of the body’s cells and reduces the activity of the immune system.

Methotrexate can be given alone or in combination to treat:

• Severe active rheumatoid arthritis in adults.
• Polyarthritic forms (when five or more joints are affected) of active, severe juvenile idiopathic arthritis (JIA) in adolescents and children aged 3 years and over when the response to non-steroidal anti-inflammatory drugs (NSAIDs) has been inadequate.
• Acute Lymphocytic Leukaemia (ALL) in children and adults
• Malignant trophoblastic tumours
• Severe psoriasis. It is usually used for patients who have tried other treatments but their condition has not improved.

You should consult your doctor if you are unsure why you have been given Methotrexate 2mg/ml Oral Solution.

2. What you need to know before you take Methotrexate Oral Solution

3. How to take Methotrexate Oral Solution

Important warning about the dose of methotrexate:

Use methotrexate only once a week for the treatment of arthritis (including juvenile idiopathic arthritis or JIA) and psoriasis. Using too much of 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.

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

Taking this medicine

• This medicine contains 2 milligram (mg) of Methotrexate in each 1 millilitre (ml) of solution.
• Take this medicine by mouth.
• Patients with rheumatoid arthritis or psoriasis and children with juvenile idiopathic arthritis (JIA) will usually take their medicine orally once a week on the same day each week. Daily administration in non-oncological indications can lead to serious toxic effects.
• Do not take more medicine more often than your doctor has told you to.
• Always use the syringe supplied with the pack, or as directed by your doctor, nurse or pharmacist.
• Methotrexate can be taken with or without food. When you have taken your dose, drink some water and swallow it to ensure you have taken you full dose and there is no methotrexate left in your mouth.
• If you are a parent or care giver administering the medicine, wash your hands before and after administering a dose. Wipe up spillages immediately. To decrease the risk of exposure disposable gloves should be used when handling methotrexate
• Women who are pregnant, planning to be or breastfeeding should not handle methotrexate
• Parents / care givers and patients should be advised to keep methotrexate out of the reach and sight of children, preferably in a locked cupboard. Accidental ingestion can be lethal for children.
• Keep the bottle tightly closed to protect the integrity of the product and minimise the risk of accidental spillage.

Measuring your dose

Instructions for use

• Open the bottle: press the cap and turn it anticlockwise (Figure 1).
• Separate the syringe adaptor from the syringe and insert the adaptor securely into the bottle neck (Figure 2).
• Take the syringe and put it in the adaptor opening (Figure 3).
• Turn the bottle upside down (Figure 4).
• Fill the syringe with a small amount of solution by pulling the plunger down (Figure 4A). Then push the plunger upward in order to remove any possible bubbles (Figure 4B). Finally, pull the plunger down to the graduation mark corresponding to the quantity in millilitres (ml) prescribed by your doctor. The top flat edge of the plunger should be in line with the graduation mark you are measuring to (Figure 4C).
• Turn the bottle the right way up (Figure 5A).
• Remove the syringe from the adaptor (Figure 5B).
• Put the end of the syringe into your mouth and push the plunger slowly back in to take the medicine.
• Close the bottle with the plastic screw cap - leave the syringe adaptor in the bottle.
• Wash the syringe with warm ‘soapy’ water and rinse well. Hold the syringe under water and move the plunger up and down several times to make sure the inside of the syringe is clean. Let the syringe dry completely before you use that syringe again for dosing. Store the syringe in a hygienic place with the medicine (Figure 6).

WASH YOUR HANDS THOROUGHLY with soap and warm water.

How much to take

Recommended dose:

Dose in rheumatoid arthritis

Take methotrexate only once a week.

Adults

• The usual dose is 7.5mg to 15mg (3.75 – 7.5ml), once a week on the same day each week.
• Your doctor may adjust the dose to suit you according to your response to treatment and side effects.
• If you are elderly, your doctor may give you lower doses.

Dose in polyarthritic forms of juvenile idiopathic arthritis

Use methotrexate once a week.

Children and adolescents:

The doctor will calculate the dose required from the child’s body surface area (m²), and the dose is expressed as mg/m².

Dose in psoriasis

Take methotrexate only once a week.

Adults and the Elderly

• The usual dose is 10mg to 25mg (5ml – 12.5ml), once a week on the same day each week.
• Your doctor may adjust the dose to suit you according to your response to treatment and side effects.

Children and adolescents:

Not recommended for use in children and adolescents.

Dosage for treatment of cancer:

Adults, the Elderly and Children

• Your doctor should give you a test dose of 5 to10mg 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.
• Methotrexate Oral Solution is usually given as a single dose
  • For malignant tumours, the usual dose is 15mg/m² for 5 days
  • For Acute Lymphoblastic Leukaemia the usual dose is 20 - 40mg/m²
• A rest period of at least two weeks is advised between treatments, to allow recovery from any side effects.
• Doses in excess of 100mg are usually given by injection by a doctor.
• Doses of more than 70mg/m² should not be administered without leucovorin rescue (folinic acid rescue) 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 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. The following side effects may happen with this medicine:

Stop taking methotrexate and see a doctor or go to a hospital straight away if you notice the following serious side effect - you may need urgent medical treatment:

• allergic reaction - the signs may include swelling of your face, lips, tongue or throat, difficulty breathing or swallowing, severe itching of your skin with raised lumps.
• the first signs of life-threatening complications can be: fever, sore throat, mouth ulcers, flu-like symptoms, severe fatigue, nose bleeds and bruising.
• serious heart problems where fluid is filling around the heart affecting the heartbeat
• sepsis, whole body inflammation that can be life-threatening.

Stop taking methotrexate and see a doctor or go to a hospital straight away if you notice the symptoms listed above.

Tell your doctor straight away if you have any of the following side effects:

• a severe skin rash with blisters and peeling skin, particularly around the mouth, nose, eyes and genitals (Stevens Johnson Syndrome) and a more severe form causing severe skin peeling (Toxic Epidermal Necrolysis). Your doctor will stop your treatment in these cases. This is an uncommon side effect.
• persistent dry cough, pain or difficulty breathing or becoming breathless as methotrexate can cause inflammation of the lungs. This is an uncommon side effect.
• spitting or coughing blood (has been reported for methotrexate used in patients with underlying rheumatologic disease).
• skin rash, fever and swollen glands, particularly in the first two months of treatment, as these may be signs of a hypersensitivity reaction.
• 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
• rapid expansion of the large intestines (toxic megacolon). Symptoms may come on suddenly and may include: abdominal pain, bloating of the abdomen, abdominal tenderness, fever, rapid heart rate, shock, bloody diarrhoea. This is a very rare side effect.

The following side-effects have been reported. If any of these cause you problems or if they last for more than one week, you should contact your doctor.

Common: affects 1 to 10 users in 100

• infections
• decrease in white blood cell count which increases your risk of infection
• headache, dizziness and tiredness
• soreness of the mouth, throat and lips, loss of appetite, feeling sick and vomiting, diarrhoea
• raised liver enzymes which may show liver problems.
• mild, red itchy skin rash, hair loss.

Uncommon: affects 1 to 10 users in 1,000

• reduced resistance to infection
• tumours in the lymph nodes, this may be more noticeable under your armpit or in your groin.
• low levels of white and red blood cells
• drowsiness
• nose bleeds
• kidney problems
• irritation or swelling of the vaginal tissues

Rare: affects 1 to 10 users in 10,000

• chickenpox (herpes zoster)
• production of very large red blood cells which leads to tiredness, muscle weakness, weight loss, feeling sick, fast heart beat and tingling or numbness in the hands and feet
• increased risk of diabetes
• feeling depressed or confused
• weakness and loss of movement, sometimes on one side of the body.
• fits
• high blood pressure, blood clots that can lead to strokes, breathlessness
• swelling at the back of the throat, swollen and bleeding gums, swollen tongue, ulcers and bleeding in the digestive tract, inflamed pancreas
• fatty liver, cirrhosis of the liver, and serious liver disorders.
• breakdown of the kidney tissue which may show as back pain
• skin sensitivity to light, acne, flaking inflamed skin, changes in skin colour, red or purple spots on the skin, skin lesions, skin ulcers and breakdown of inflamed areas in patients with psoriasis, discolouration of the nails
• increase in lumps under the skin that are caused in Rheumatoid Arthritis
• loss of interest in or inability to have sex, problems with your periods

Very rare: affects less than 1 user in 10,000

• herpes simples (cold sores), hepatitis
• an immune disorder that reduces antibodies that fight infection. Symptoms include pain, unable to sleep, tiredness and feeling depressed and anxious.
• joint and muscle pain, sensation of numbness or tingling/having less sensitivity to stimulation than normal
• mixing words up when speaking and impaired thinking, loss of contact with reality (psychosis), tingly sensations in the head, pain in the head caused by swelling, ringing in the ears
• change in mood
• conjunctivitis, blurred vision
• dry cough, pneumonia
• swollen pancreas, black or tarry stools
• thread veins in the skin, boils, bruising, nail infection and detachment of the nail.
• weakening or softening of the bones
• pain or difficulty passing urine or increased need to pass urine, blood in the urine, cystitis
• reduced ability to become pregnant or for a man to father children
• vaginal bleeding, swelling of the breasts, particularly in men
• lymphoproliferative disorders (excessive growth of white blood cells).

Not known:

• wide spread cold sores and infections
• haemorrhages and bleeding problems
• impaired vision
• bleeding from the lungs (has been reported for methotrexate used in patients with underlying rheumatologic disease)
• bone damage in the jaw (secondary to excessive growth of white blood cells)
• redness and shedding of skin
• swelling.

If any of the side effects gets serious, or if you notice any side effects not listed in this leaflet, please tell your doctor or pharmacist.

5. How to store Methotrexate Oral Solution

• Keep this medicine out of the sight and reach of children.
• Do not store above 25ºC. Do not refrigerate. Store in the original carton in order to protect from light.
• Do not use 3 months after you first open it. Take it back to the pharmacy.
• Do not use this medicine after the expiry date (month, year) which is stated on the label after EXP. The expiry date refers to the last day of that month.
• Do not use methotrexate if you notice anything wrong with the medicine. Talk to your doctor or pharmacist.
• Any unused medicine should be disposed of in accordance with local requirements for cytotoxics.
• 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 to protect the environment.

6. Contents of the pack and other information