Metoject Pen 10 mg solution for injection in pre-filled pen

Package Leaflet: Information for the User

Introduction

Package Leaflet: Information for the User

MetojectPEN 7.5mg solution for injection in a pre-filled pen

MetojectPEN 10mg solution for injection in a pre-filled pen

MetojectPEN 12.5mg solution for injection in a pre-filled pen

MetojectPEN 15mg solution for injection in a pre-filled pen

MetojectPEN 17.5mg solution for injection in a pre-filled pen

MetojectPEN 20mg solution for injection in a pre-filled pen

MetojectPEN 22.5mg solution for injection in a pre-filled pen

MetojectPEN 25mg solution for injection in a pre-filled pen

MetojectPEN 27.5mg solution for injection in a pre-filled pen

MetojectPEN 30mg solution for injection in a pre-filled pen

metotrexate

Read all of this leaflet carefully before you start using this medicine, because it contains important information for you.

• Keep this leaflet, as you may need to read it again.
• If you have any questions, ask your doctor or pharmacist.
• This medicine has been prescribed for you only, and you should not give it to other people, even if they have the same symptoms as you, because it may harm them.
• If you experience any adverse effects, talk to your doctor or pharmacist, even if they are possible adverse effects not listed in this leaflet. See section 4.

Contents of this leaflet

1. What Metoject PEN is and what it is used for
2. What you need to know before using Metoject PEN
3. How to use Metoject PEN
4. Possible side effects
5. How to store Metoject PEN
6. Contents of the pack and other information

1. What Metoject PEN is and what it is used for

Metoject PEN is indicated for the treatment of:

• active rheumatoid arthritis in adult patients,
• severe active polyarticular juvenile idiopathic arthritis in children and adolescents, when the response to non-steroidal anti-inflammatory drugs (NSAIDs) has been inadequate,
• moderate to severe psoriasis in adult patients, and severe psoriatic arthritis in adults,
• mild to moderate Crohn's disease in adult patients when adequate treatment with other medications is not possible.

Rheumatoid arthritis (RA) is a chronic collagen disease characterized by inflammation of the synovial membranes (joint membranes). These membranes produce a fluid that acts as a lubricant in many joints. Inflammation causes thickening of the membrane and joint swelling.

Juvenile arthritis affects children and adolescents under 16 years of age. The polyarticular forms are indicated when five or more joints are affected within the first six months of the disease.

Psoriasis is a common, chronic skin disease characterized by red patches covered with thick, dry, silvery, adherent scales.

Psoriatic arthritis is a type of arthritis associated with psoriatic skin and nail lesions, particularly affecting the joints of the fingers and toes.

Metoject PEN modifies and slows the progression of the disease.

Crohn's disease is a type of inflammatory bowel disease that can affect any part of the gastrointestinal tract, causing symptoms such as abdominal pain, diarrhea, vomiting, or weight loss.

2. What you need to know before using Metoject PEN

Do not use Metoject PEN

• if you are allergic to methotrexate or to any of the other ingredients of this medicine (listed in section 6),
• if you have severe liver or kidney disease or blood disorders,
• if you regularly consume large amounts of alcohol,
• if you have a serious infection, such as tuberculosis, HIV or other immunodeficiency syndromes,
• if you have mouth ulcers, gastric or intestinal ulcers,
• if you are pregnant or breastfeeding (see section "Pregnancy, breastfeeding and fertility"),
• if you are receiving vaccines made with attenuated microorganisms at the same time.

Warnings and precautions

Talk to your doctor or pharmacist before starting Metoject PEN

• if you are elderly or generally feel unwell and weak,
• if you have problems with liver function,
• if you have dehydration (loss of fluids),
• if you have diabetes mellitus and are being treated with insulin.

Special precautionary measures for treatment with Metoject PEN

Methotrexate temporarily affects the production of sperm and ova, which is reversible in most cases. Methotrexate may cause miscarriages and severe birth defects. If you are a woman, you must avoid becoming pregnant while taking methotrexate and for at least 6 months after stopping treatment. If you are a man, you must avoid fathering a child while receiving methotrexate and for at least 3 months after the end of treatment. See also section "Pregnancy, breastfeeding and fertility".

Follow-up tests and recommended precautions

Even when methotrexate is used at low doses, serious adverse reactions may occur. To detect them early, your doctor will perform examinations and laboratory monitoring tests.

Before starting treatment

Before starting treatment, you will have blood tests to check that you have sufficient blood cells. You will also have blood tests to assess liver function and to determine whether you have hepatitis. In addition, serum albumin (a blood protein), hepatitis status (liver infection), and kidney function will be monitored. Your doctor may also decide to perform further liver tests; some of these may involve imaging of the liver, while others may require taking a small sample of liver tissue for more detailed examination. Your doctor may also check for tuberculosis, and you may have a chest X-ray or a lung function test.

During treatment

Your doctor may perform the following examinations:

• Examination of the oral cavity and pharynx to identify changes in the mucous membrane, such as inflammation or ulceration.
• Blood tests/blood counts with measurement of blood cell counts and serum methotrexate levels.
• Blood tests to monitor liver function.
• Imaging tests to monitor liver function.
• Taking a small tissue sample from the liver for more detailed examination.
• Blood tests to monitor kidney function.
• Monitoring of the respiratory tract and, if necessary, a lung function test.

It is very important that you attend these scheduled examinations.

If any of these test results are abnormal, your doctor will adjust your treatment accordingly.

Elderly patients

Elderly patients receiving methotrexate should be closely monitored by a doctor to detect possible adverse effects as early as possible.

Age-related decline in liver and kidney function and low body stores of folic acid in the elderly require a relatively low dose of methotrexate.

Other precautions

Acute pulmonary haemorrhage has been reported with methotrexate in patients with underlying rheumatological disease. If you notice blood when coughing or spitting, contact your doctor immediately.

Methotrexate may affect the immune system and vaccination outcomes. It may also affect the results of immunological tests. It may reactivate inactive chronic infections (such as herpes zoster ["shingles"], tuberculosis, hepatitis B or C). During treatment with Metoject PEN, you must not receive vaccines made with attenuated microorganisms.

Methotrexate may make your skin more sensitive to sunlight. Avoid strong sunlight and do not use sunbeds or ultraviolet lamps without medical advice. To protect your skin from intense sunlight, wear suitable clothing or use a high-protection sunscreen.

During treatment with methotrexate, radiation-induced dermatitis and sunburns may reappear (memory reactions). Psoriatic lesions may worsen during UV radiation and simultaneous administration of methotrexate.

An increase in the size of lymph nodes (lymphoma) may occur, and in such cases, treatment must be discontinued.

Diarrhoea may be an adverse effect of Metoject PEN and requires discontinuation of treatment. If you have diarrhoea, speak to your doctor.

Certain brain disorders (encephalopathy/leukoencephalopathy) have been reported in cancer patients treated with methotrexate. The occurrence of these adverse effects cannot be ruled out when methotrexate is used to treat other diseases.

If you, your partner or your caregiver notice the onset or worsening of neurological symptoms such as general muscle weakness, visual disturbances, changes in thinking, memory and orientation causing confusion, or personality changes, contact your doctor immediately, as these may be symptoms of a very rare serious brain infection called progressive multifocal leukoencephalopathy (PML).

Using Metoject PEN with other medicines

Inform your doctor or pharmacist if you are taking, have recently taken or might need to take any other medicines. Keep this in mind also for medicines you may take in the future.

The effect of treatment may be affected if Metoject PEN is administered at the same time as certain medicines:

• Antibiotics such as: tetracyclines, chloramphenicol, non-absorbable broad-spectrum antibiotics, penicillins, glycopeptides, sulfonamides, ciprofloxacin and cephalothin (medicines to prevent or treat certain infections).
• Non-steroidal anti-inflammatory drugs or salicylates (medicines for pain or inflammation such as acetylsalicylic acid, diclofenac and ibuprofen or pyrazolones).
• Metamizole (synonyms: novaminsulfone and dipyrone) (medicine for severe pain and/or fever).
• Probenecid (medicine for gout).
• Weak organic acids such as loop diuretics.
• Medicines that may cause adverse effects on the bone marrow, such as trimethoprim-sulfamethoxazole (an antibiotic) and pyrimethamine.
• Other medicines used to treat rheumatoid arthritis such as leflunomide, sulfasalazine and azathioprine.
• Cyclosporine (to suppress the immune system).
• Mercaptopurine (a cytostatic medicine).
• Retinoids (medicines for psoriasis and other skin diseases).
• Theophylline (medicine for bronchial asthma and other lung diseases).
• Some medicines for stomach discomfort such as omeprazole and pantoprazole.
• Hypoglycaemics (medicines used to reduce blood sugar levels).

Vitamins containing folic acid may alter the effect of your treatment and should only be taken on the advice of your doctor.

Vaccination with vaccines made with attenuated microorganisms must be avoided.

Using Metoject PEN with food, drinks and alcohol

During treatment with Metoject PEN, consumption of alcohol and large quantities of coffee, caffeinated soft drinks and black tea should be avoided.

Pregnancy, breastfeeding and fertility

Pregnancy

Do not use Metoject PEN during pregnancy or if you are trying to become pregnant. Methotrexate may cause birth defects, harm the foetus or cause miscarriages. It is associated with malformations of the skull, face, heart and blood vessels, brain and limbs. Therefore, it is very important that methotrexate is not administered to pregnant patients or those planning to become pregnant.

In women of childbearing age, pregnancy must be ruled out by appropriate measures, for example, 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 contraceptive methods throughout this time (see also section "Warnings and precautions").

If you become pregnant during treatment or suspect you may be pregnant, consult your doctor as soon as possible. You should be provided with information about the risk of harmful effects on the child during treatment.

If you wish to become pregnant, consult your doctor, who may refer you to a specialist to provide information before the planned start of treatment.

Breastfeeding

Discontinue breastfeeding before and during treatment with Metoject PEN.

Male fertility

Available data do not indicate an increased risk of malformations or miscarriages if the father takes a methotrexate dose below 30 mg/week. However, this risk cannot be completely ruled out. Methotrexate may be genotoxic, meaning it may cause genetic mutations. Methotrexate may affect sperm production and cause birth defects. Therefore, you must avoid fathering a child or donating semen while taking methotrexate and for at least 3 months after stopping treatment.

Driving and using machines

Treatment with Metoject PEN may cause adverse reactions affecting the central nervous system, such as fatigue and dizziness. Therefore, the ability to drive or use machines may, in some cases, be impaired. If you feel tired or drowsy, you should not drive or use machines.

Metoject PEN contains sodium

This medicine contains less than 1 mmol of sodium (23 mg) per dose; this is essentially "sodium-free".

3. How to use Metoject PEN

Important warning about the dose of Metoject PEN (methotrexate):

Use Metoject PEN only once a week for the treatment of rheumatoid arthritis, juvenile idiopathic arthritis, psoriasis, psoriatic arthritis, and Crohn's disease. Overuse of Metoject PEN (methotrexate) can be fatal. Please read section 3 of this leaflet very carefully. If you have any doubts, consult your doctor or pharmacist before using this medicine.

Always follow exactly the instructions for use of this medicine as given by your doctor. In case of doubt, please consult your doctor or pharmacist again.

Your doctor will determine the dose, which will be individually adjusted. Normally, it takes between 4 and 8 weeks for the treatment to take effect.

The Metoject PEN injection is administered subcutaneously (under the skin) by, or under the supervision of, a doctor or healthcare professional only once a week. Together with your doctor, you will choose a day of the week suitable for you to receive the injection.

Use in children and adolescents

The doctor will decide the appropriate dose for children and adolescents with polyarticular forms of juvenile idiopathic arthritis.

Metoject PEN is not recommended for use in children under 3 years of age due to limited experience in this age group.

Duration and method of administration

! Metoject PEN is injected once a week !

The treating doctor will decide the duration of treatment. Treatment of rheumatoid arthritis, juvenile idiopathic arthritis, psoriasis vulgaris, psoriatic arthritis, and Crohn's disease with Metoject PEN is long-term therapy.

At the beginning of treatment, Metoject PEN may be administered by medical staff. However, your doctor may decide that you can learn to self-inject Metoject PEN. You will receive appropriate training for this.

Under no circumstances should you attempt to self-inject unless you have been properly trained to do so.

Please read the "Instructions for use" at the end of this leaflet for guidance on how to correctly use Metoject PEN.

Please note that the entire content must be used.

Handling and disposal of the medicine and the pre-filled pen must comply with local regulations. Healthcare personnel who are pregnant must not handle or administer Metoject PEN.

Methotrexate must not come into contact with the skin surface or mucous membranes. If contact occurs, the affected area should be immediately rinsed with copious amounts of water.

If you use more Metoject PEN than you should

If you use more Metoject PEN than prescribed, consult your doctor immediately.

If you suspect that you (or someone else) has administered too much Metoject PEN, contact your doctor, go immediately to the nearest hospital, or call the Toxicology Information Service at telephone number 91 562 04 20. They will determine which measures to take depending on the severity of the poisoning. Take the medicine with you if you go to the doctor or to a hospital.

If you forget to use Metoject PEN

Do not use a double dose to make up for a missed dose.

If you stop treatment with Metoject PEN

If you interrupt treatment with Metoject PEN, consult your doctor immediately.

If you feel that the effect of Metoject PEN is too strong or too weak, consult your doctor or pharmacist.

4. Possible adverse effects

Like all medicines, this medicine can cause adverse effects, although not everyone will experience them.

The frequency and severity of adverse effects depend on the dose and frequency of administration. It is important that your doctor performs regular check-ups, as serious adverse effects may occur even with the lowest doses. Your doctor will carry out tests to detect abnormalities in the blood (such as low white blood cell count, low platelet count or lymphoma) and changes in the kidneys and liver.

If you experience any of the following symptoms, contact your doctor immediately, as they may indicate a serious, potentially life-threatening adverse effect requiring urgent specific treatment:

• Persistent dry cough, without phlegm, difficulty breathing, and fever; these may be signs of lung inflammation [frequent]
• blood in sputum or when coughing; these may be signs of pulmonary hemorrhage [frequency not known]
• signs of liver damage such as yellowing of the skin or whites of the eyes; methotrexate may cause chronic liver injury (hepatic cirrhosis), scarring of the liver (hepatic fibrosis), fatty degeneration of the liver [all uncommon], inflammation of the liver (acute hepatitis) [rare], and liver failure [very rare]
• allergic symptoms such as skin rash, including skin itching, swelling of the hands, feet, ankles, face, lips, mouth or throat (which may cause difficulty swallowing or breathing), and feeling faint; these may be signs of severe allergic reactions or anaphylactic shock [rare]
• signs of kidney damage such as swelling of the hands, ankles or feet, or changes in urination frequency, reduced (oliguria) or absent (anuria) urine output; these may be signs of kidney failure [rare]
• signs of infection, e.g., fever, chills, aches, sore throat; methotrexate may make you more susceptible to infections. Serious infections such as a specific type of pneumonia (Pneumocystis jirovecii pneumonia) or blood poisoning (sepsis) may occur [rare]
• symptoms such as weakness on one side of the body (stroke) or pain, swelling, redness and unusual warmth in one leg (deep vein thrombosis); this may occur when a dislodged blood clot causes blockage of a blood vessel (thromboembolic event) [rare]
• fever and severe deterioration in your general condition, or sudden fever accompanied by sore throat or mouth pain, or urinary problems; methotrexate may cause a sudden drop in certain white blood cells (agranulocytosis) and severe myelosuppression [very rare]
• unexpected bleeding, e.g., bleeding gums, blood in urine, vomiting blood, or bruising, which may be signs of a severe decrease in platelets caused by serious episodes of bone marrow suppression [very rare]
• symptoms such as severe headache, often combined with fever, neck stiffness, nausea, vomiting, disorientation, and sensitivity to light, which may indicate inflammation of the membranes surrounding the brain (acute aseptic meningitis) [very rare]
• certain brain disorders (encephalopathy/leukoencephalopathy) have been reported in cancer patients treated with methotrexate; these adverse effects cannot be ruled out when methotrexate treatment is used for other diseases; signs of such brain disorders may include mental status changes, movement disorders (ataxia), visual disturbances, or memory problems [frequency not known]
• severe skin rash or blistering of the skin (this may also affect the mouth, eyes, and genitals); these may be signs of a condition called Stevens-Johnson syndrome or toxic epidermal necrolysis (Lyell's syndrome) [very rare]

The following are other adverse effects that may occur:

Very common: may affect more than 1 in 10 people

• Inflammation of the lining of the mouth, indigestion, nausea, loss of appetite, abdominal pain.
• Abnormal results in liver function tests (ASAT, ALAT, bilirubin, alkaline phosphatase).

Common: may affect up to 1 in 10 people

• Mouth ulcers, diarrhea.
• Rash, skin redness, itching.
• Headache, fatigue, drowsiness.
• Decreased production of blood cells, resulting in reduced numbers of white blood cells, red blood cells, or platelets.

Uncommon: may affect up to 1 in 100 people

• Sore throat.
• Inflammation of the intestine, vomiting, inflammation of the pancreas, black or tarry stools, gastrointestinal ulcers and bleeding.
• Sunburn-like reactions due to increased skin sensitivity to sunlight, hair loss, increase in the number of rheumatoid nodules, skin ulcer, shingles (herpes zoster), inflammation of blood vessels, herpes-like rash, hives.
• Onset of diabetes mellitus.
• Dizziness, confusion, depression.
• Decreased serum albumin.
• Decreased number of all blood cells and platelets.
• Inflammation and ulceration of the urinary bladder or vagina, reduced kidney function, urinary disorders.
• Joint pain, muscle pain, reduced bone mass.

Rare: may affect up to 1 in 1,000 people

• Inflammation of gum tissue.
• Increased skin pigmentation, acne, skin bruising due to bleeding from blood vessels (ecchymosis, petechiae), allergic inflammation of blood vessels.
• Decreased number of antibodies in the blood.
• Infection (including reactivation of inactive chronic infections), red eyes (conjunctivitis).
• Mood changes (mood disturbances).
• Visual disturbances.
• Inflammation of the sac surrounding the heart, fluid accumulation in the sac around the heart, obstruction of heart filling due to fluid in the sac surrounding the heart.
• Low blood pressure.
• Scarring of lung tissue (pulmonary fibrosis), breathing difficulty and bronchial asthma, fluid accumulation in the sac surrounding the lung.
• Stress fracture.
• Electrolyte imbalances.
• Fever, impaired wound healing.

Very rare: may affect up to 1 in 10,000 people

• Acute toxic dilation of the intestine (toxic megacolon).
• Increased nail pigmentation, inflammation of the nail folds (acute paronychia), deep infection of hair follicles (furunculosis), visible enlargement of small blood vessels.
• Pain, loss of strength, or numbness and tingling sensations/reduced sensitivity to stimuli, taste disturbances (metallic taste), seizures, paralysis, meningism.
• Visual impairment, non-inflammatory eye disorder (retinopathy).
• Loss of sexual appetite, impotence, male breast enlargement, altered sperm formation (oligospermia), menstrual disorders, vaginal discharge.
• Enlargement of lymph nodes (lymphoma).
• Lymphoproliferative disorders (excessive increase in white blood cells).

Frequency not known: cannot be estimated from available data

• Increase in certain white blood cells.
• Nosebleeds.
• Protein in urine.
• Feeling of weakness.
• Jaw bone damage (secondary to excessive increase in white blood cells).
• Tissue damage at the injection site.
• Skin redness and peeling.
• Swelling.

Subcutaneous administration of methotrexate is well tolerated locally. Only mild local skin reactions (such as burning sensation, erythema, swelling, color change, severe itching, pain) were observed, which decreased during treatment.

Reporting of adverse effects

If you experience any adverse effect, consult your doctor or pharmacist, even if it is a possible adverse effect not listed in this leaflet. You may also report them directly via the Spanish Pharmacovigilance System for Human Medicinal Products: www.notificaRAM.es. By reporting adverse effects, you can help provide more information on the safety of this medicine.

5. Storage of Metoject PEN

Keep this medicine out of the sight and reach of children.

Store below 25 °C. Do not freeze.

Store the pre-filled pens in their outer packaging to protect them from light.

Do not use this medicine after the expiry date stated on the carton and on the pre-filled pen after EXP. The expiry date refers to the last day of the month indicated.

Medicines must not be disposed of via wastewater or household waste. Dispose of containers and unused medicines at the SIGRE collection point at your pharmacy. If you are unsure how to dispose of unused containers or medicines, please consult your pharmacist. This will help protect the environment.

6. Contents of the pack and other information

Composition of MetojectPEN

• The active substance is methotrexate.

1 pre-filled pen containing 0.15 ml of solution contains 7.5 mg of methotrexate.
1 pre-filled pen containing 0.2 ml of solution contains 10 mg of methotrexate.
1 pre-filled pen containing 0.25 ml of solution contains 12.5 mg of methotrexate.
1 pre-filled pen containing 0.3 ml of solution contains 15 mg of methotrexate.
1 pre-filled pen containing 0.35 ml of solution contains 17.5 mg of methotrexate.
1 pre-filled pen containing 0.4 ml of solution contains 20 mg of methotrexate.
1 pre-filled pen containing 0.45 ml of solution contains 22.5 mg of methotrexate.
1 pre-filled pen containing 0.5 ml of solution contains 25 mg of methotrexate.
1 pre-filled pen containing 0.55 ml of solution contains 27.5 mg of methotrexate.
1 pre-filled pen containing 0.6 ml of solution contains 30 mg of methotrexate.

• The other components are sodium chloride, sodium hydroxide, and hydrochloric acid for pH adjustment, and water for injections.

Nature of the medicinal product and contents of the pack

This medicine is presented as an injectable solution in a pre-filled pen.
The solution is transparent yellow-brown in colour.