METHOTREXATE 25MG/ML SOLUTION FOR INJECTION

Active substance: METHOTREXATE

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hameln

Patient information leaflet

Read all of this patient information leaflet carefully; it contains important information about the drug.
• Keep this leaflet. You may need to read it again.
• If you have further questions, please ask your doctor or your pharmacist.
• This product has been prescribed for you personally and must not be passed on to anyone else.
In this leaflet:
1. What Methotrexate 25 mg/ml solution for injection is and what it is used for
2. Before receiving Methotrexate 25 mg/ml solution for injection
3. How Methotrexate 25 mg/ml solution for injection is administered
4. Possible side effects
5. Storing Methotrexate 25 mg/ml solution for injection

Methotrexate 25 mg/ml solution for injection
Each 1 ml of this sterile solution for injection contains
methotrexate sodium equivalent to 25 milligrams of active
substance methotrexate.
Other ingredients are sodium hydroxide, sodium chloride,
water for injections and nitrogen.
Marketing Authorisation Holder:
hameln pharma

Manufacturer:
Haupt Pharma Wolfratshausen GmbH
Pfaffenrieder Str. 5
82515 Wolfratshausen, Germany

1. What Methotrexate 25 mg/ml solution for injection
is and what it is used for
Methotrexate 25 mg/ml solution for injection is a yellow
and sterile solution in clear glass vials.
Methotrexate is one of a group of medicines known as
antimetabolites. It is used in the treatment of cancer as
well as psoriasis including psoriatic arthritis. It stops a
substance called dihydrofolate reductase from working.
This substance is an enzyme, which is important in “cell
growth (replication)”. By inhibiting the enzyme, cancer
cells will eventually “die”.
Methotrexate helps patients with psoriasis by killing the
cells in the skin that are growing too fast. It is these rapidly
growing cells that cause the raised patches of skin in
psoriasis.
Pack sizes:
The solution for injection is available in
• packs of 1, 5 or 10 vial(s) containing 2 ml solution. This
corresponds to 50 mg of active substance methotrexate
per vial.
• packs of 1, 5 or 10 vial(s) containing 20 ml solution.
This corresponds to 500 mg of active substance
methotrexate per vial.
• packs of 1 or 5 vial(s) containing 40 ml solution.
This corresponds to 1,000 mg of active substance
methotrexate per vial.
• a pack of 1 vial containing 200 ml solution. This
corresponds to 5,000 mg of active substance
methotrexate per vial.
2. Before receiving Methotrexate 25 mg/ml solution
for injection
2.1 You should not receive Methotrexate 25 mg/ml
solution for injection
• if you have ever had any allergic reaction to methotrexate
or any of the ingredients of this product
• if you have severe problems with your kidneys
• if you have severe problems with your liver, including
alcoholic liver disease, abnormal blood counts, fibrosis,
cirrhosis or recent active hepatitis
• if you suffer from alcoholism
• if you have any serious blood disorders (anaemia, a
reduction in white cell number (leucopenia) or platelet
number (thrombocytopenia))
• if you have an active infection
• if you have a medical condition, or are receiving
medication, which lowers your resistance to infection
• if you are pregnant or intend to become pregnant, or
are breast-feeding, as the drug can harm unborn and
breast-fed infants.
2.2 Take special care with Methotrexate 25 mg/ml
solution for injection
• if you have impaired respiratory function
• if you have mild to moderate kidney or liver problems, or
a mild to moderate blood disorder
• if you have diarrhoea
• if you have ulcers in your mouth, stomach or intestine
(large bowel)
• if you have ascites (collection of liquid in the free
abdominal cavity) and/or pleural effusions (collection of
liquid in the pleural cavity)

2008_018_03_PB_Methotrexate 25 m1 1

• if you are receiving or intend to receive any vaccine, as
methotrexate can reduce their effect
• if you have had radio- or chemotherapy before
(especially of the pelvis), or are receiving radiotherapy
concurrently
• if you have an impaired general condition (if you feel
weak or infirm)
• if you are of advanced age
• if Methotrexate 25 mg/ml solution for injection is given
to very young children.
Please consult your doctor, even if these statements were
applicable to you at any time in the past.
2.3 Interactions with other drugs
Please inform your doctor if you are taking or have recently
taken any other medicines, even those not prescribed.
Medications which can be influenced by or can
influence the effect of methotrexate negatively:
• pain-killers such as salicylates (e.g. aspirin), amidopyrine
derivatives, phenylbutazone and leflunomide
• diphenylhydantoins (e.g. phenytoin, an antiepileptic
agent)
• barbiturates and tranquillisers (sedative agents)
• antibiotics (medication against bacteria), e.g.
tetracyclines, penicillins, chloramphenicol, cotrimoxazole
and sulphonamides
• cytostatics
(medication
against
cancer),
e.g.
doxorubicin, mercaptopurine, procarbazine, cisplatin,
L-asparaginase and 5-fluorouracil
• Disease-modifying antirheumatic drugs (DMARD; drugs
that are used to treat rheumatoid arthritis)
• probenecid (uricosuric agent used in the prophylaxis of
gout)
• p-aminobenzoic acid (used in sun creams)
• non-steroidal anti-inflammatory drugs (NSAIDs;
medications against "rheumatism", e.g. indomethacin,
ibuprofen)
• anti-folate drugs (e.g. nitrous oxide or co-trimoxazole)
• p-aminohippuric acid (substance to check kidney
function)
• pyrimethamine (medication against malaria)
• cholestyramine (lipid-lowering agent)
• acitretin or other retinoids (for psoriasis or skin
disorders)
• theophylline (used mainly in bronchial asthma)
• erythrocyte concentrates (for blood transfusion)
• nitrous oxide-based anaesthetics
• omeprazole (used in the therapy of gastric ulcers)
• sulphasalazine (for ulcerative colitis)
• tetrahydrofolic acid preparations
• oral antidiabetics (medications to treat diabetes) and
diuretics (increase urine output)
• hypoglycaemics (lower blood sugar levels)
• other medicinal products with nephrotoxic and
hepatotoxic potential (incl. alcohol)
• vaccinations
• azathioprine (an immunosuppressive drug)
• vitamin preparations containing folic acid or its
derivates
Please note that these statements may also apply to
products used some time ago or at some time in the
future.
2.4 Pregnancy
Do not take Methotrexate 25 mg/ml solution for injection
if you are pregnant because it causes a variety of
malformations or even the death of the foetus. Women
must not get pregnant during treatment with Methotrexate
25 mg/ml solution for injection. If you get pregnant
during treatment with Methotrexate 25 mg/ml solution for
injection, please inform your doctor immediately!
Special indications for contraception:
Methotrexate temporarily influences sperm and egg
production. During treatment and up to 6 months
after treatment is stopped, you must practice effective
contraception. In this respect, it is of no importance
whether the male or the female partner takes Methotrexate
25 mg/ml solution for injection!

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2.5 Breast-feeding
Do not take Methotrexate 25 mg/ml solution for injection
during breast-feeding, since methotrexate is excreted into
the breast milk. Methotrexate can seriously harm breastfed infants.
3. How Methotrexate 25 mg/ml solution for injection
is administered
Your doctor or nurse will give you Methotrexate 25 mg/
ml solution for injection injecting it either into the
central nervous system (intraventricular or intrathecal
administration only for the 2 ml vial), into one of your veins
(e.g. as bolus or infusion), arteries, or a muscle.
During your treatment, you will have a number of tests,
such as regular blood tests to check that appropriate
blood levels of methotrexate are attained and that your
kidneys are eliminating excess drug properly. Other tests
are performed routinely at the start and during the course
of therapy (e.g. chest X-ray, liver function test, full blood
count and urinalysis).
Your doctor may instruct you to take sodium bicarbonate
or acetazolamide tablets while receiving your injections
to help make sure that methotrexate is not concentrated
in the kidneys. If you receive methotrexate in high doses,
you will receive calcium folinate as well to lessen the
side effects of methotrexate. Your doctor will decide on
a suitable dose for you. Doses vary considerably and
will depend on the underlying disease. It is possible that
you will only get methotrexate. In the case of cancer, it is
also possible that you will receive so-called combination
therapy in which you must take several medications.
Your body weight, age, general condition of health, your
response to the drug and whether other medicines are
required at the same time will also influence the dose you
receive.
4. Possible Side Effects
Like all medicines Methotrexate 25 mg/ml solution for
injection can have side effects:
Methotrexate has the potential for serious, sometimes
fatal toxicity. Because the toxic reactions can occur at
any time during therapy, your doctor should observe you
closely and must inform you of early signs and symptoms
of toxicity.
If you think you have an infection, a sore throat, fever
or chills during treatment, you should tell your doctor
immediately.
The most common undesirable effects are ulcerative
stomatitis, leucopenia, nausea, and abdominal
discomfort.
Unwanted effects of Methotrexate 25 mg/ml solution
for injection are
• Blood picture changes - e.g. your vulnerability for
infections may increase, you may suffer from unusual
bleeding or bruising and you may observe signs of
anaemia (weakness, tiredness, difficulties in breathing)
• disorders of the mouth, stomach and intestines like
mucositis (mucus membrane inflammation, e.g.
inflammation of the gums, tongue, throat, mouth,
intestines as well as ulcerations), lack of appetite,
feeling sick, vomiting, diarrhoea, unusual bleeding from
the mouth, stomach and intestines, inflammation of the
pancreas, increased risk of perforation, melaena (red to
black stools), malabsorption (disturbances of uptake of
nutrition with consequences such as body weight loss),
and toxic megacolon (severe complication with massive
dilatation of the colon and severe pain, for example)
• renal failure, impairment of renal function, inflammation
of the urinary bladder, blood in the urine, reduced or
faulty formation of sperm and egg cells, menstrual
dysfunction (periods may become less frequent or even
stop completely), infertility, abortion, malformations of
the foetus and pain or difficulty in passing urine
• damage to the liver such as fibrosis (increase in the
connective tissue), cirrhosis (transformation of the tissue
with hardening and abolition of the normal structure of
the organ), hepatitis (inflammation of the liver), acute
liver cell death, fatty degeneration of the liver or other
histologic (tissue) changes in the liver
• damage to the lungs such as inflammation and fibrosis
(increase in the connective tissue); the pulmonary
toxicity may manifest as fever, cough (especially dry
and nonproductive), difficulties or increase in the
frequency of breathing, chest pain, hypoxaemia (lack of
oxygen in the blood), and/or abnormal findings on chest
radiography and/or tests of respiratory function, and
infections.
• adverse reactions of the skin such as formation of
blisters, becoming red and inflamed, loss of skin tissue,
vasculitis (inflammation of blood vessels), rash, itching,
nettle rash, photosensitivity, pigmentary changes
(discolouration of the skin), telangiectasia (expansion

of small superficial blood vessels in the skin), acne,
formation of boils, point-like or small flat bleeding, an
increase in rheumatic nodules, loss of hair, worsening
of psoriasis (with concomitant UV therapy), increased
colouration or inflammation or detachment of the nails,
a "recall" of radiation dermatitis (inflammation of the
skin) and sunburn
• leucoencephalopathy (inflammation of the brain),
manifested by ventricular enlargement (expansion of
the fluid spaces inside the brain), confusion, shaking,
irritability, sleepiness, ataxia (disturbance of balance
and co-ordination), dementia, feeling sick, fever, and
occasionally seizures or coma, significant intellectual
deficit, headache, drowsiness, speech disorder,
incomplete palsy affecting one or both sides of the
body, fits, dizziness, vomiting, mental disturbance,
pain, muscle weakness, paraesthesia (pins-andneedles sensation), subtle cognitive dysfunction (easily
disturbed attention), mood swings, unusual sensations
in the head, and even death
• unwanted reactions of the eyes like swelling,
inflammation of the eyelid edges, conjunctivitis
(inflammation of the eye conjunctiva), unusual formation
of tears, photophobia, and impairment of vision
• allergic reactions, cerebral oedema (swelling of the
brain), haematoma, nodulosis (formation of nodules
under the skin), loss of interest in sex / impotence,
chills, fever without any detectable cause, decreased
resistance to infection, upper respiratory tract infection,
abnormal tissue cell changes, metabolic disorders,
hyperuricaemia (increased blood levels of uric acid,
possibly leading to gout), diabetes, osteoporosis and
other bone disorders, including aseptic necrosis of the
femoral head (loss of bone tissue in the hip joint), pains
in the joints, muscle pain, malaise and undue fatigue,
development of the breast gland in males, ringing in
the ears, sweating, vaginal discomfort, in rare cases
pericarditis (inflammation of the outer lining of the
heart), pericardial effusion and tamponing (collection of
fluid and blood, respectively, in the space between the
outer lining of the heart and the heart muscle), low blood
pressure, complications resulting from the formation of
blood clots in veins and arteries, tumour lysis syndrome
(renal failure due to massive destruction of rapidly
growing tumour cells) and even sudden death
• in cases of acute lymphocytic leukaemia, methotrexate
can cause pain in the left epigastric region (the area
overlying the stomach, below the left lower border of the
rib cage; inflammation of the space above the spleen
due to destruction of the leukaemic cells)
• other possible complications from administration into
the central nervous system include Guillain-Barré
syndrome (inflammation of the central nervous system),
nerve palsies, and cerebellar dysfunction, arachnoiditis
(inflammation of one of the membranes surrounding the
spinal cord) manifested as headache, back pain, neck
stiffness, and/or fever, subacute myelopathy (disorder
affecting the spinal cord) manifested as complete or
incomplete palsy of the lower limbs (paraparesis or
paraplegia).
There have been reports on the manifestation of
lymphomas which were, in some cases, reversible after
discontinuing methotrexate therapy. The potential of
metho­trexate to produce other cancers in humans has
been evaluated in several studies, but the results do not
confirm a cancerogenic risk.
You should inform your doctor immediately if you notice
any unwanted effects.
If you notice any side effects not mentioned in this patient
information leaflet, or if you are unsure of the effect of this
product, please consult your doctor or pharmacist.
5. Storing Methotrexate 25 mg/ml solution for
injection
• Keep the medicine out of the reach and sight 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.
• Methotrexate 25 mg/ml solution for injection should not
be used after the expiry date printed on the label.
• Any unused product or waste should be disposed of
in accordance with local requirements for example by
incineration.
Remember this medicine is for you only. Only a doctor or
a nurse can give you the injection.
Date of last revision of the text: April 2008

721 458 UK 2

2008_018_03_PB_Methotrexate 25 m2 2

31.03.2008 16:36:11

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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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