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METHOFILL 20 MG SOLUTION FOR INJECTION IN PRE-FILLED INJECTOR

Active substance(s): METHOTREXATE / METHOTREXATE

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Package leaflet: Information for the user

Methofill 7.5 mg solution for
injection in pre-filled injector
Methofill 10 mg solution for
injection in pre-filled injector
Methofill 12.5 mg solution for
injection in pre-filled injector
Methofill 15 mg solution for
injection in pre-filled injector
Methofill 17.5 mg solution for
injection in pre-filled injector
Methofill 20 mg solution for
injection in pre-filled injector
Methofill 22.5 mg solution for
injection in pre-filled injector
Methofill 25 mg solution for
injection in pre-filled injector
Methofill 27.5 mg solution for
injection in pre-filled injector
Methofill 30 mg solution for
injection in pre-filled injector
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
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 or pharmacist or
nurse. This includes any possible side effects not listed in this
leaflet. See section 4.
What is in this leaflet:
1. What Methofill is and what it is used for
2. What you need to know before you use Methofill
3. How to use Methofill
4. Possible side effects
5. How to store Methofill
6. Contents of the pack and other information

1. What Methofill is and what it is used for
Methofill contains methotrexate as active substance
Methotrexate is a substance with following properties:
• it interferes with the growth of certain cells in the body that
reproduce quickly
• it reduces the activity of the immune system (the body’s own
defence mechanism)
• it has anti-inflammatory effects
Methofill is indicated for the treatment of
• Rheumatoid arthritis (RA) in adult patients- (RA) is a chronic
disease, characterised by inflammation of the joint membranes.
These membranes produce a fluid which acts as a lubricant for
many joints. The inflammation causes thickening of the
membrane and swelling of the joint.
• Polyarthritic forms of severe active juvenile idiopathic arthritis
when treatment with nonsteroidal anti-inflammatory drugs
(NSAIDs) have not helped. (Juvenile arthritis concerns children
and adolescents less than 16 years.)
• Severe Psoriatic arthritis in adult patients (psoriatic arthritis is a
kind of arthritis with psoriatric lesions of the skin and nails,
especially at the joints of fingers and toes.)
• Severe Psoriasis which has not responded to other forms of
treatment (psoriasis is a common chronic skin disease,
characterised by red patches covered by thick, dry, silvery,
adherent scales.)
• Crohn’s Disease in adult patients (Crohn’s Disease is a type of
inflammatory bowel disease causing symptoms such as
abdominal pain, diarrhoea, vomiting or weight loss.)
Methofill modifies and slows down the progression of the disease.

2. What you need to know before you use
Methofill
Do not use Methofill if you:
• are allergic to methotrexate or any of the other ingredients of this
medicine (listed in section 6),
• suffer from severe liver or kidney diseases or blood diseases.
• regularly drink large amounts of alcohol.
• suffer from a severe infection, e.g. tuberculosis, HIV or other
immunodeficiency syndromes.
• suffer from mouth ulcers, stomach ulcer or intestinal ulcer.
• are pregnant or breast-feeding.
• receive vaccinations with live vaccines at the same time.
Warnings and precautions
Talk to your doctor or pharmacist or nurse before taking Methofill if:
• you are elderly or if you feel generally unwell and weak.
• you have liver problems
• you suffer from dehydration (water loss).
Recommended follow-up examinations and safety measures:
Even when Methofill is administered in low doses, severe side
effects can occur. In order to detect them in time, check-ups and
laboratory tests have to be carried out by your doctor.
Before therapy:
Before starting the treatment, blood samples will be taken in order
to check that you have enough blood cells, tests to check your liver
function, serum albumin (a protein in the blood) and kidney
function. Your doctor will also check if you suffer from tuberculosis
(infectious disease in combination with little nodules in the affected
tissue) and a chest X-ray will be taken.

diclofenac and ibuprofen or pyrazole)
• Probenecid (medicine against gout)
• Weak organic acids like loop diuretics (“water tablets”)
• Medicines, which may have adverse effects on the bone marrow,
e.g. trimethoprim-sulphamethoxazole (an antibiotic) and
pyrimethamine
• Other medicines used to treat rheumatoid arthritis such as
leflunomide, sulphasalazine and Azathioprine
• Mercaptopurine (a cytostatic agent)
• Retinoids (medicine against psoriasis and other dermatological
diseases)
• Theophylline (medicine against bronchial asthma and other lung
diseases)
• Some medicines against stomach trouble)
• Hypoglycaemics (medicines that are used to lower the blood sugar)
Vitamins containing folic acid may impair the effect of your
treatment and should only be taken when advised by your doctor.
Vaccination with live vaccine should be avoided. Methotrexate may
affect your immune system and vaccination results.
Methofill with food, drink and alcohol
Alcohol as well as large amounts of coffee, caffeine-containing soft
drinks and black tea should be avoided during treatment with
Methofill.
Pregnancy, breast-feeding and fertility
You must not take Methofill during pregnancy. There is a risk of
harm to the foetus and miscarriage. Men and women should use
an effective method of birth control during treatment and during a
further six months after treatment with Methofill 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.
Breast-feeding has to be stopped prior to and during treatment
with Methofill.
Driving and using machines
Treatment with Methofill may cause adverse reactions affecting the
central nervous system, e.g. tiredness and dizziness. Thus the
ability to drive a vehicle and/or to operate machines may, in certain
cases, be compromised. If you feel tired or drowsy you should not
drive or use machines.
Methofill contains sodium
This medicinal product contains less than 1 mmol sodium (23 mg)
per dose, i.e. essentially “sodium-free”.

3. How to use Methofill
Always take this medicine exactly as your doctor has told you.
Check with your doctor or pharmacist if you are not sure.
Your doctor decides on the dosage, which is adjusted individually.
Usually it takes 4 – 8 weeks before there is any effect of the
treatment.
Methofill is administered subcutaneously (under the skin) by or
under the supervision of a physician or healthcare staff as an
injection once a week only. Together with your doctor you decide
on a suitable weekday each week on which you receive your
injection.
Use in children and adolescents
The doctor decides on the appropriate dose in children and
adolescents with polyarthritic forms of juvenile idiopathic arthritis.
Methofill is not recommended in children less than 3 years of age
due to insufficient experience in this age group.
Method and duration of administration
Methofill is injected once weekly!
The duration of the treatment is determined by the treating
physician. Treatment of rheumatoid arthritis, juvenile idiopathic
arthritis, psoriasis vulgaris, psoriatic arthritis and Crohn’s disease
with Methofill is a long-term treatment.
Methotrexate should only be prescribed by physicians, who are
familiar with the various characteristics of the medicinal product
and its mode of action. If considered appropriate, the treating
physician can, in selected cases, delegate subcutaneous
administration to the patient.
Patients must be educated to use the proper injection technique.
Under no circumstances should you try to inject Methofill yourself
before you have received such training.
For single use only. Please note that all of the contents have to be
used.
The manner of handling and disposal must be consistent with that
of other cytostatic preparations in accordance with local
requirements. Pregnant health care personnel should not handle
and/or administer Methofill.
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.
Instructions for use:
Please read these instructions in full before using Methofill
pre-filled injector. This injector requires training by a healthcare
professional before use.
For any problem or question, contact your doctor, pharmacist or
nurse.
Before you begin
• Choose a clean, well-lit space to administer your medication.
• Check expiration date on package. Do not use if expiration date
has passed.
• Gather an alcohol swab and a sharps container
Preparation

During therapy:
You will have the following tests at least once a month during the
first six months and at least every three months thereafter:
• Examination of the mouth and throat for alterations of the mucosa
• Blood tests
• Check if your liver is working properly
• Check if your kidneys are working properly
• Check of respiratory system and if necessary lung function test

• Wash hands with soap under warm running water.

Inactive, chronic infections (e.g. herpes zoster [shingles],
tuberculosis, hepatitis B or C) may flare up during methotrexate
treatment.
Radiation induced dermatitis and sun-burn can reappear under
methotrexate therapy (recall-reaction). Psoriatic lesions can
become worse if you are exposed to UV-irradiation during
treatment with methotrexate.
Enlarged lymph nodes (lymphoma) may occur and therapy must
then be stopped.

• Choose injection site (Abdomen or thigh if a patient is injecting
himself/herself, with the additional option of the back of the arm if
a Healthcare Provider or caregiver is assisting them)

Diarrhoea can be a toxic effect of Methofill and requires an
interruption of therapy. If you suffer from diarrhoea please speak to
your doctor.
Certain brain disorders (encephalopathy/ leukoencephalopathy)
have been reported in cancer patients receiving
methotrexate.Such side effects cannot be excluded when
methotrexate is used to treat other diseases.
Other medicines and Methofill
Tell your doctor or pharmacist if you are taking, have recently
taken or might take any other medicines.

• Clean injection site: use an alcohol swab to wipe site clean. Allow
to air dry.
1. Pre-Injection

The effect of the treatment may be affected if Methofill is
administered at the same time as certain other drugs:
• Antibiotics such as: tetracyclines, chloramphenicol, and
non-absorbable broad-spectrum antibiotics, penicillines,
glycopeptides, sulphonamides, ciprofloxacin and cefalotin
(medicines to prevent/fight certain infections)
• Non-steroidal anti-inflammatory drugs or salicylates (medicines
against pain and/or inflammation such as acetylsalicylic acid,

• Inspect liquid in window. Check for any changes in colour,
cloudiness or large particles.

• Headache, tiredness, drowsiness
• Reduced blood cell formation with decrease in white and/or red
blood cells and/or platelets (leukopenia, anaemia,
thrombocytopenia)

• Remove bottom cap: Twist and pull bottom cap to remove. Keep
hands away from needle guard after cap is removed. Do not
recap. Dispose of bottom cap immediately. Do not inject if you
drop the pre-filled injector after removing cap.
• Inject within 5 minutes of removing bottom cap.
2. Injection

• Place the injector straight onto your skin (about 90 degrees).

• Push the handle straight down: The medicine will be injected as
you push. Do this at a speed that is comfortable for you.
• Do not lift the injector during injection.

Uncommon: may affect up to 1 in 100 people
• Throat inflammation, inflammation of the bowels, vomiting
• Increased sensitivity to light, loss of hair, increased number of
rheumatic nodules, shingles, inflammation of blood vessels,
herpes-like skin rash, hives
• Onset of diabetes mellitus
• Dizziness, confusion, depression
• Decrease in serum albumin
• Decrease in the number of blood cells and platelets
• Inflammation and ulcer of the urinary bladder or vagina, reduced
kidney function, disturbed urination
• Joint pain, muscle pain, osteoporosis (reduction of bone mass)
Rare: may affect up to 1 in 1,000 people
• Increased skin pigmentation, acne, blue spots due to vessel
bleeding
• Allergic inflammation of blood vessels, fever, red eyes, infection,
wound-healing impairment, decreased number of anti-bodies in
the blood
• Visual disturbances
• Inflammation of the sac around the heart, accumulation of fluid in
the sac around the heart
• Low blood pressure
• Lung fibrosis, shortness of breath and bronchial asthma,
accumulation of fluid in the sac around the lung
• Electrolyte disturbances
Very rare: may affect up to 1 in 10,000 people
• Profuse bleeding, toxic megacolon (acute toxic dilatation of the
gut)
• Increased pigmentation of the nails, inflammation of the cuticles,
furunculosis (deep infection of hair follicles), visible enlargement
of small blood vessels
• Impaired vision, pain, loss of strength or sensation of numbness
or tingling in arms and legs, changes in taste (metallic taste),
convulsions, paralysis, severe headache with fever
• Retinopathy (noninflammatory eye disorder)
• Loss of sexual drive, impotence, male breast enlargement
(gynaecomastia), defective sperm formation, menstrual disorder,
vaginal discharge
• Enlargement of lymphatic nodes (lymphoma)
Not Known: frequency cannot be estimated from the available data:
• Leukoencephalopathy (a disease of the white brain substance)

• Injection is completed when the handle has been pushed down
as far as possible, you hear a click and the orange body is no
longer visible.

Subcutaneous application of methotrexate is locally well tolerated.
Only mild local skin reactions (such as burning sensations,
erythema, swelling, discolouration, severe itching, pain) were
observed, decreasing during therapy.
Reporting of side effects
If you get any side effects, talk to your doctor, pharmacist or nurse.
This includes any possible side effects not listed in this leaflet.
You can also report side effects directly via (see details below). By
reporting side effects you can help provide more information on the
safety of this medicine.

• Lift straight up: The yellow band indicates that the needle guard
is locked.
3. Disposal

For UK- You can also report side effects directly via Yellow Card
Scheme, Website: www.mhra.gov.uk/yellowcard.
For Ireland- You can also report side effects directly via
HPRA Pharmacovigilance
Earlsfort Terrace
IRL - Dublin 2
Tel: +353 1 6764971
Fax: +353 1 6762517
Website: www.hpra.ie
e-mail: medsafety@hpra.ie

5. How to store Methofill
Keep this medicine out of the sight and reach of children.
• Dispose of the used Methofill pre-filled injector: Place injector in
an approved sharps container. Regulations vary by region. Check
with your doctor or pharmacist for proper disposal instructions.
Do not dispose of injector in household trash.
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 or someone around you is injured by the needle, consult
your doctor immediately and do not use this Methofill pre-filled
injector.
If you use more Methofill than you should
If you use more Methofill than you should, talk to your doctor
immediately.
If you forget to use Methofill
Do not take a double dose to make up for a forgotten dose.
If you stop using Methofill
If you stop using Methofill, talk to your doctor immediately.

4. Possible side effects
Like all medicines, this medicine can cause side effects, although
not everybody gets them.
The frequency as well as the degree of severity of the side effects
depends on the dosage level and the frequency of administration.
As severe side effects may occur even at low dosage, it is
important that you are monitored regularly by your doctor. Your
doctor will do tests to check for abnormalities developing in the
blood (such as low white blood cells, low platelets, lymphoma) and
changes in the kidneys and the liver.
Tell your doctor immediately if you experience any of the
following symptoms, as these may indicate a serious, potentially
life-threatening side effect, which require urgent specific treatment:
• persistent dry, non-productive cough, shortness of breath
and fever; these may be signs of an inflammation of the lungs
(pneumonia) [common]
• symptoms of liver damage such as yellowing of the skin and
whites of the eyes; methotrexate can cause chronic liver damage
(liver cirrhosis), formation of scar tissue of the liver (liver fibrosis),
fatty degeneration of the liver [all uncommon], inflammation of the
liver (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 in swallowing or
breathing) and feeling you are going to faint; these may be
signs of severe allergic reactions or an anaphylactic shock [rare]
• symptoms of kidney damage such as swelling of the hands,
ankles or feet or changes in frequency of urination or
decrease or absence of urine; these may be signs of kidney
failure [rare]
• symptoms of infections, e.g. fever, chills, achiness, sore
throat; methotrexate can make you more susceptible to
infections. Severe infections like a certain type of pneumonia
(Pneumocystis carinii pneumonia) or blood poisoning (sepsis)
may occur [rare]
• severe diarrhoea, vomiting blood and black or tarry stools;
these symptoms may indicate a severe complication of the
gastrointestinal system caused by methotrexate e.g.
gastrointestinal ulcers [rare]
• symptoms associated with the blockage (occlusion) of a
blood vessel by a dislodged blood clot (thromboembolic
event) such as weakness of one side of the body (stroke) or
pain, swelling, redness and unusual warmth in one of your
legs (deep vein thrombosis); methotrexate can cause
thromboembolic events [rare]
• fever and serious deterioration of your general condition, or
sudden fever accompanied by a sore throat or mouth, or
urinary problems; methotrexate can cause a sharp fall in white
blood cells (agranulocytosis) and severe bone marrow
suppression [very rare]
• unexpected bleeding, e.g. bleeding gums, blood in the urine,
vomiting blood or bruising, these can be signs of a severely
reduced number of blood platelets caused by severe courses of
bone marrow depression [very rare]
• severe skin rash or blistering of the skin (this can also affect
your mouth, eyes and genitals); these may be signs of the
conditions called Stevens Johnson syndrome or burned skin
syndrome (toxic epidermal necrolysis) [very rare]
In the following, please find the other side effects that may occur:
Very common: may affect more than 1 in 10 people
• Mouth inflammation, indigestion, nausea (feeling sick), loss of
appetite
• Increase in liver enzymes
Common: may affect up to 1 in 10 people
• Mouth ulcers, diarrhoea
• Rash, reddening of the skin, itching

Store below 30 °C.
Keep the pre-filled injector in the outer carton in order to protect
from light.
Do not use this medicine after the expiry date which is stated on
the label/carton after EXP. The expiry date refers to the last day of
that month.
Do not use Methofill if you notice any change in colour or visible
particles.
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 Methofill contains
• The active substance is methotrexate.
1 pre-filled injector with 0.15 ml solution contains 7.5 mg
methotrexate.
1 pre-filled injector with 0.20 ml solution contains 10 mg
methotrexate
1 pre-filled injector with 0.25 ml solution contains 12.5 mg
methotrexate
1 pre-filled injector with 0.30 ml solution contains 15 mg
methotrexate
1 pre-filled injector with 0.35 ml solution contains 17.5 mg
methotrexate
1 pre-filled injector with 0.40 ml solution contains 20 mg
methotrexate
1 pre-filled injector with 0.45 ml solution contains 22.5 mg
methotrexate
1 pre-filled injector with 0.50 ml solution contains 25 mg
methotrexate
1 pre-filled injector with 0.55 ml solution contains 27.5 mg
methotrexate
1 pre-filled injector with 0.60 ml solution contains 30 mg
methotrexate
• The other ingredients are sodium chloride, sodium hydroxide (for
pH adjustment) and water for injections.
What Methofill looks like and contents of the pack
Methofill contains a clear, yellow to brown solution.
The following pack sizes are available:
• For 0.15 mL, 0.20 mL, 0.25 mL, 0.30 mL, 0.35 mL, 0.40 mL,
0.45 mL,0.50 mL, 0.55 mL and 0.60 mL: pack of 1, multipacks of
4 (4 packs of 1) or 8 (8 packs of 1) pre-filled injectors in a carton.
Not all pack sizes may be marketed.
Marketing Authorisation Holder and Manufacturer
Marketing Authorisation Holder
Accord Healthcare Limited,
Sage House, 319 Pinner Road,
North Harrow, Middlesex, HA1 4HF,
United Kingdom
Manufacturer
Accord Healthcare Limited,
Sage House, 319 Pinner Road,
North Harrow, Middlesex, HA1 4HF,
United Kingdom
This medicinal product is authorised in the Member States of
the EEA under the following names:
Name of the
Member State
Ireland
Poland
Sweden
United Kingdom

Name of the medicinal product
Methofill 7.5 mg/10 mg/12.5 mg/15 mg/
17.5 mg/20 mg/22.5 mg/25 mg/27.5 mg/30 mg
solution for injection in pre-filled injector
Methofill
Injexate 7.5 mg/10 mg/12.5 mg/15 mg/
17.5 mg/20 mg/22.5 mg/25 mg/27.5 mg/30 mg
injektionsvätska i förfylld injektions
Methofill 7.5 mg/10 mg/12.5 mg/15 mg/
17.5 mg/20 mg/22.5 mg/25 mg/27.5 mg/30 mg
solution for injection in pre-filled injector

This leaflet was last revised in 03/2017.

INP030
10 00000 0 000000

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Source: Medicines and Healthcare Products Regulatory Agency

Disclaimer: Every effort has been made to ensure that the information provided here is accurate, up-to-date and complete, but no guarantee is made to that effect. Drug information contained herein may be time sensitive. This information has been compiled for use by healthcare practitioners and consumers in the United States. The absence of a warning for a given drug or combination thereof in no way should be construed to indicate that the drug or combination is safe, effective or appropriate for any given patient. If you have questions about the substances you are taking, check with your doctor, nurse or pharmacist.

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