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 methotrexate
1. What Injexate is and what it is used for
Injexate contains methotrexate as active substance.
Methotrexate is a substance with the following properties:
- it interferes with the growth of certain cells in the body that are formed quickly
- it reduces the activity of the immune system (the body’s own defense system)
- it has anti-inflammatory effects.
Injexate is for the treatment of:
- Rheumatoid arthritis (RA) in adult patients. RA is a chronic disease characterized by inflammation of the synovial membranes. These membranes produce a fluid that acts as a lubricant for many joints. Inflammation causes the skin to thicken and the joint to swell.
- Polyarthritic forms of severe, active juvenile idiopathic arthritis when treatment with NSAIDs (non-steroidal anti-inflammatory drugs) has not helped. Juvenile arthritis affects children and adolescents under 16 years of age.
- Severe psoriatic arthritis in adult patients (psoriatic arthritis is a type of arthritis with sores or changes ( lesions ) on the skin and nails, especially at the joints of the fingers and toes).
- Severe psoriasis when other types of treatments have not worked ( psoriasis is a common, chronic skin disease characterized by red spots covered with thick, dry, silvery, stuck scales).
- Crohn’s disease in adult patients ( Crohn’s disease is a type of inflammatory bowel disease that causes symptoms such as abdominal pain, diarrhea, vomiting or weight loss).
Indicate changes and delays in the course of the disease.
Methotrexate contained in Injexate may also be approved for the treatment of other conditions not mentioned in this product information. Ask your doctor, pharmacist, or other healthcare professional if you have any further questions, and always follow their instructions.
2. What you need to know before using Injexate
Do not use Injexate if you:
- is allergic to methotrexate or any of the other ingredients of this medicine (listed in section 6)
- have severe liver or kidney disease or blood disease
- regularly drink large amounts of alcohol
- have a severe infection , e.g. tuberculosis , HIV or other immune deficiency syndromes
- have sores in the mouth, stomach ulcers or ulcers in the intestines
- should be vaccinated with live vaccines at the same time.
- if you are pregnant or breast-feeding (see section “Pregnancy, breast-feeding and fertility”)
Warnings and cautions
Talk to your doctor or pharmacist before taking Injexate if:
- you are older or if you generally feel sick and weak
- you have liver problems
- you suffer from dehydration (fluid loss).
Acute hemorrhage from the lungs of patients with the underlying rheumatic disease has been reported with methotrexate. If you get symptoms such as saliva blood or bloody cough, contact your doctor immediately.
Special precautions for treatment with Injexate
Methotrexate temporarily affects sperm and egg production, an effect that in most cases decreases after the end of treatment. Methotrexate can cause miscarriage and severe congenital malformations. You must avoid becoming pregnant while using methotrexate and for at least 6 months after stopping treatment. See also the section “Pregnancy, breastfeeding and fertility”.
Recommended follow-up examinations and safety measures:
Even when Injexate is given in low doses, serious side effects can occur. For them to be detected in time, the doctor must perform checks and laboratory tests.
Before treatment:
Before starting treatment, you will be given blood samples to check that you have enough blood cells, test your liver function, check serum albumin (a protein in the blood) and kidney function. The doctor will also check if you have tuberculosis (a contagious disease in combination with small lumps in the affected tissue ) and have you have a lung X-ray.
During treatment:
You will undergo the following tests at least once a month for the first six months and at least every three months thereafter:
- Examination of the mouth and throat to see if there are changes in the mucous membrane
- Blood tests
- Control of liver function
- Control of renal function
- Respiratory monitoring and, if necessary, lung function test
Inactive, chronic infections (eg herpes zoster [shingles], tuberculosis, hepatitis B or C) may flare up during treatment with methotrexate.
Radiation-induced dermatitis (inflammation of the skin) and sun damage may recur during treatment with methotrexate (recall reaction). Psoriasis lesions can get worse if you are exposed to UV radiation during treatment with methotrexate.
Enlarged lymph nodes ( lymphoma ) can occur and then the treatment must be stopped.
Diarrhea can be a toxic effect of Injexate and requires discontinuation of treatment. If you have diarrhea, you should consult a doctor.
Certain brain diseases (encephalopathy/leukoencephalopathy) have been reported in cancer patients treated with methotrexate. Such side effects cannot be ruled out when methotrexate is used to treat other diseases.
Other medicines and Injexate
Tell your doctor or pharmacist if you are taking, have recently taken, or might take any other medicines.
The effect of the treatment can be affected if Injexate is given at the same time as certain other medicines:
- Antibiotics , e.g. tetracyclines , chloramphenicol and non-absorbable broad-spectrum antibiotics, penicillins , glycopeptides, sulfonamides , ciprofloxacin and cefatolin (medicines to prevent / fight certain infections )
- Non-steroidal anti-inflammatory drugs or salicylates (medicines for pain and / or inflammation such as acetylsalicylic acid , diclofenac , ibuprofen or pyrazole)
- Probenecid (medicine for gout )
- Weak organic acids as loop‑ diuretics (” diuretic tablets”)
- Drugs that can have side effects on the bone marrow , e.g. trimethoprim ‑ sulfamethoxazole (an antibiotic ) and pyrimethamine
- Other drugs used to treat rheumatoid arthritis , such as leflunomide, sulfasalazine and azathioprine
- Mercaptopurine (a cytostatic agent)
- Retinoids (medicines for psoriasis and other dermatological diseases)
- Theophylline (medicine for bronchial asthma and other lung diseases)
- Some medicines for stomach problems such as omeprazole and pantoprazole
- Hypoglycaemic drugs (drugs used to lower blood sugar)
Vitamins that contain folic acid can weaken the effect of your treatment and should only be taken when your doctor prescribes it.
Vaccination with live vaccines must be avoided.
Inject with food, drink and alcohol
Avoid alcohol and large amounts of coffee, soft drinks containing caffeine, and black tea during treatment with Injexate.
Pregnancy, breastfeeding and fertility
Pregnancy
Do not use Injexate during pregnancy or if you are trying to get pregnant. Methotrexate can cause congenital malformations, birth defects, and miscarriages. It is associated with malformations of the skull, face, heart and blood vessels, brain and arms, and legs. It is therefore very important that methotrexate is not given to pregnant patients or patients planning to become pregnant. Infertile women, pregnancy must be ruled out by appropriate measures, e.g. a pregnancy test before starting treatment. You must avoid becoming pregnant while taking methotrexate and for at least 6 months after stopping treatment, using reliable contraception during this time (see also section “Warnings and precautions”).
If you become pregnant during treatment or suspect you may be pregnant, talk to your doctor as soon as possible. You should be offered medical advice on the risk of harmful effects on the child due to the treatment.
If you wish to become pregnant, consult your doctor, who may refer you to specialist advice before the planned start of treatment.
Fertility in men
Available data do not indicate an increased risk of malformations or miscarriages if the father takes less methotrexate than 30 mg/week. However, risk cannot be completely ruled out. Methotrexate may be genotoxic. This means that the drug can cause gene mutation. Methotrexate can affect sperm production and can cause congenital malformations. Therefore, you should avoid getting a woman pregnant and donating sperm while taking methotrexate and for at least 6 months after stopping treatment.
Breast-feeding must be stopped before and during treatment with Injexate.
Driving and using machines
Treatment with Injexate can cause side effects that affect the central nervous system, e.g. fatigue and dizziness. The ability to drive and/or use machines may in some cases be impaired. If you feel drowsy, do not drive or use machines.
You are responsible for assessing whether you are fit to drive a motor vehicle or perform work that requires sharpened attention. One of the factors that can affect your ability in these respects is the use of drugs due to their effects and/or side effects. Descriptions of these effects and side effects can be found in other sections. Read all the information in this leaflet for guidance. If you are not sure, talk to your doctor or pharmacist.
Injexate contains sodium
This medicine contains less than 1 mmol sodium (23 mg) per dose, ie essentially ‘sodium-free.
3. How to use Injexate
Always take this medicine exactly as your doctor has told you. Ask your doctor or pharmacist if you are unsure.
The doctor will decide on a dose, which will be adjusted individually for you. It usually takes 4-8 weeks before you see any effect of the treatment.
Injexate is given subcutaneously (under the skin) as an injection only once a week. It is given by or under the supervision of a doctor or healthcare professional. Together with the doctor, you decide on a suitable day of the week each week when you receive an injection.
| Important warning regarding dosing one of Injexate (methotrexate): Injexate should only be used once a week in the treatment of rheumatoid arthritis, juvenile idiopathic arthritis, psoriatic arthritis, psoriasis, and Crohn’s disease. Using too much Injexate (methotrexate) can be life-threatening. Read section 3 of this leaflet very carefully. If you have any further questions on the use of this product, ask your doctor or pharmacist. |
Use for children and adolescents
The doctor will determine the appropriate dose for children and adolescents with polyarthritic forms of juvenile idiopathic arthritis.
Injexate is not recommended for children under 3 years of age due to insufficient experience in this age group.
Method of administration and duration of treatment
Injexate is given as an injection once a week!
The duration of treatment is determined by the attending physician. Treatment of rheumatoid arthritis, juvenile idiopathic arthritis, psoriasis Vulgaris, psoriatic arthritis, and Crohn’s disease with Injexate is a long-term treatment.
Methotrexate should only be prescribed by a doctor who knows the different properties of the drug and its mechanism of action. If deemed appropriate, the treating physician may, in selected cases, entrust the subcutaneous administration to the patient.
At the beginning of treatment, Injexate can be injected by healthcare professionals. However, your doctor may decide that you can learn to inject Injexate yourself. In that case, you will receive instructions on how to proceed. Under no circumstances should you try to inject yourself, unless you have learned how to do it.
For single use only. Note that all content must be used.
Handling and disposal must be consistent with that of other cytostatic preparations by local requirements. Pregnant healthcare professionals should not handle and/or administer Injexate.
Methotrexate should not come into contact with the skin surface or mucous membranes. If this happens, immediately flush the area with plenty of water.
Instructions for use:
Read the entire instruction manual before using the Injexate pre-filled injector. This injector requires you to be trained by healthcare professionals before using it.
Contact a doctor, pharmacist, or nurse if you have any problems or questions.
Before you begin
- Choose a clean, well-lit place to administer the drug.
- Check the expiration date on the packaging. Do not use if the expiration date has passed.
- Bring a spirit dryer and a container for sharp objects.
Preparation
1. Before injection
2. Injection
3. Disposal
Methotrexate should not come into contact with skin or mucous membranes. If this happens, immediately flush the area with plenty of water.
If you or anyone close to you is injured by the needle, consult a doctor immediately and do not use the pre-filled injector.
If you use more Injexate than you should
Contact your doctor immediately if you have used too much Injexate.
If you have ingested too much medicine or if e.g. If a child has ingested the medicine by mistake, contact a doctor, hospital, or the Poison Information Center for risk assessment and advice.
If you forget to use Injexate
Do not take a double dose to make up for a forgotten dose.
If you stop using Injexate
Contact your doctor immediately if you stop using Injexate.
4. Possible side effects
Like all medicines, this medicine can cause side effects, although not everybody gets them.
How often the side effects occur as well as their severity depends on the dose level and how often the medicine is given. As serious side effects can occur even at low doses, you must be checked regularly by your doctor. Your doctor will take samples to check for any abnormal values in your blood (eg low white blood cell count, low platelet count, lymphoma ) and changes in kidney and liver function.
Contact a doctor immediately if you experience any of the following symptoms as they may be signs of a serious, potentially life-threatening side effect, which requires immediate treatment:
- persistent dry, non-productive cough, shortness of breath and fever: these may be signs of pneumonia [common]
- blood in saliva or cough
- symptoms of liver damage such as yellow skin and yellow eye whites: methotrexate may lead to chronic liver damage ( liver cirrhosis ), scar tissue formation in the liver (liver fibrosis), fatty liver [all uncommon] liver inflammation ( acute hepatitis ) [rare] and liver failure [very rare]
- allergic symptoms such as rash including red, itchy skin, swelling of hands, feet, ankles, face, lips, mouth or throat (which may make it difficult to swallow or breathe) and fainting : these may be signs of a severe allergic reaction [rare]
- symptoms of kidney damage such as swelling of the hands, ankles or feet or changes in how often you need to urinate or decreased urine output ( oliguria ) or lack of urine ( anuria ): these may be signs of kidney failure [rare]
- symptoms of infection are, e.g. fever, chills, aches, sore throats: methotrexate may make you more susceptible to infection . Serious infection such as a certain type of pneumonia ( Pneumocystis carinii pneumonia ) or sepsis can occur [rare]
- symptoms such as weakness in one side of the body ( stroke ) or pain, swelling, redness and abnormal heat in a leg (deep vein thrombosis ) : this can happen when a loose blood clot clogs a vessel (thromboembolic event) [rare]
- fever and severe deterioration of your general health or sudden fever with sore throat or mouth, or urination problems: methotrexate may lead to a sudden decrease in the number of certain white blood cells ( agranulocytosis ) and severe bone marrow suppression [very rare]
- unexpected bleeding, e.g. bleeding gums, blood in the urine, vomiting or bruising. This can be a sign of a sharp decrease in the number of platelets caused by severe bone marrow inhibition [very rare]
- symptoms such as very severe headache often combined with fever, stiff neck, nausea, vomiting, confusion and sensitivity to light may indicate inflammation of the meninges ( acute aseptic meningitis ) [very rare]
- Certain brain diseases (encephalopathy / leukoencephalopathy) have been reported in cancer patients receiving methotrexate. Such side effects cannot be ruled out when methotrexate is used to treat other diseases. Signs of this type of brain disease can be altered mental state, movement disorders ( ataxia ), visual disturbances or memory disorders [have been reported]
- severe skin rash or blistering of the skin (this can also occur in the mouth, eyes and genitals): these may be signs of a condition called Stevens ‑ Johnson syndrome or toxic epidermal necrolysis / Lyell’s syndrome (burning pain in the skin) [very rare]
Listed below are other side effects that may occur:
Very common: may affect more than 1 user in 10
- Inflammation of the oral mucosa, indigestion, nausea, decreased appetite, abdominal pain
- Deviating liver function values (AST / ALT, bilirubin , alkaline phosphatase)
Common: may affect up to 1 in 10 users
- Sores in the mouth, diarrhea
- Rash, redness of the skin, itching
- Headache, fatigue, drowsiness
- Decreased blood cell formation with reduced number of white and / or red blood cells and / or platelets
Uncommon: may affect up to 1 in 100 people
- Inflammation of the pharynx
- Inflammation of the intestines, vomiting, pancreatitis, black or tar-like stools, ulcers and bleeding in the gastrointestinal tract
- Increased photosensitivity, hair loss, increased number of rheumatic nodules, skin ulcers, shingles , inflammation of the blood vessels, herpes-like skin rash, hives
- Occurrence of diabetes mellitus
- Dizziness, confusion, depression
- Decrease in serum albumin
- Reduced number of all blood cells and platelets
- Inflammation and ulcers in the bladder or vagina, impaired kidney function, disturbed urination
- Joint pain, muscle pain, decreased bone mass
Rare: may affect up to 1 in 1,000 users
- Inflammation of the gums
- Increased pigmentation of the skin, acne , bruising of the skin due to vascular bleeding ( ecchymosis , petechiae ), allergic inflammation of blood vessels
- Decreased number of antibodies in the blood
- Infection (incl. Reactivation of inactive chronic infection), red eyes ( conjunctivitis )
- Mood swings (mood swings)
- Visual disturbances
- Inflammation of the pericardium, accumulation of fluid in the pericardium, obstruction of the heart’s blood filling due to fluid around the heart
- Low blood pressure
- Formation of scar tissue in the lung ( pulmonary fibrosis ), shortness of breath and bronchial asthma , accumulation of fluid in the alveoli
- Stress fracture
- Electrolyte disturbances
- Fever, impaired wound healing
Very rare: may affect up to 1 in 10,000 people
- Acute toxic enlargement of the intestine (toxic megacolon)
- Increased pigmentation of the nails, inflammation of the cuticles (acute paronychia), deep infection of the hair follicles ( furunculosis ), visible enlargement of small blood vessels
- Pain, loss of strength or feeling of numbness or tingling / lower sensitivity to stimulation than normal, taste changes (metallic taste), seizures, paralysis, meningism
- Impaired vision, non- inflammatory eye disease ( retinopathy )
- Loss of sexual drive, impotence , breast augmentation in men, insufficient sperm formation (oligospermia), menstrual disorders, discharge from the vagina
- Enlarged lymph nodes ( lymphoma )
- Lymphoproliferative disorders (abnormal growth of white blood cells )
Has been reported: occurs in an unknown number of users
- Increased number of certain white blood cells
- Nasal blood
- Protein in the urine
- Feeling weak
- Bleeding from the lungs
- Bone damage in the jaw (as a result of abnormal growth of white blood cells )
- Tissue destruction at the injection site
- reddening of the skin and scaly skin
- swelling
Subcutaneous administration of methotrexate is well tolerated locally. Only mild skin reactions (such as burning sensation, reddening of the skin, swelling, discoloration, severe itching, pain) have been observed during treatment.
Reporting of side effects
If you get any side effects, talk to your doctor, pharmacist, or nurse. This also applies to any side effects not mentioned in this information. You can also report side effects directly to the Medical Products Agency. By reporting side effects, you can help increase drug safety information.
5. How to store Injexate
Keep this medicine out of the sight and reach of children.
Do not store above 30 ° C.
Store the pre-filled injector in the outer carton. Sensitive to light.
Do not use this medicine after the expiry date which is stated on the carton after EXP and on the label after EXP. The expiration date is the last day of the specified month.
Do not use Injexate if you notice any color change or visible particles.
Medicines should not be disposed of via wastewater or household waste. Ask your pharmacist how to dispose of medicines no longer required. These measures will help to protect the environment.
6. Contents of the packaging and other information
Content declaration
- 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 the medicine looks like and contents of the pack
Injexate 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, multiple packs of 4×1 or 8×1 pre-filled injectors in a carton.
Not all pack sizes may be marketed.
Marketing Authorization Holder and Manufacturer
Marketing Authorisation Holder
Accord Healthcare BV
Winthontlaan 200
3526 KV Utrecht
Netherlands
Manufacturer
Accord Healthcare Limited,
Sage House,
319, Pinner Road,
North Harrow,
Middlesex HA1 4HF,
UK
Wessling Hungary Kft.,
Anonymous u. 6., Budapest, 1045
Hungary
Accord Healthcare Polska Sp.z oo,
ul. Lutomierska 50,95-200 Pabianice, Poland