Quinux 10 mg/0.4 ml solution for injection in pre-filled syringe

Package leaflet: Information for the user

Introduction

Package leaflet: information for the patient

QUINUX 10 mg/0,4 ml solution for injection in pre-filled syringe

Methotrexate

Read the entire 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, consult your doctor or pharmacist, even if they are adverse effects not listed in this leaflet. See section 4.

Contents of the leaflet

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

1. What Quinux is and what it is used for

Quinux contains methotrexate as the active substance.

Methotrexate is a substance with the following properties:

• interferes with the growth of certain rapidly dividing cells in the body,
• reduces the activity of the immune system (the body's own defence mechanism),
• has anti-inflammatory effects.

Quinux is indicated for the treatment of:

• active rheumatoid arthritis in adult patients,
• polyarticular forms of active severe juvenile idiopathic arthritis (JIA) when the response to non-steroidal anti-inflammatory drugs (NSAIDs) has been inadequate,
• severe, recalcitrant, disabling psoriasis that is not adequately responsive to other therapies such as phototherapy, PUVA (psoralen + UVA radiation), and retinoids, and severe psoriatic arthritis in adult patients.

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. Polyarticular forms are defined by involvement of five or more joints within the first six months of the disease.

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

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

Quinux modifies and slows the progression of the disease.

2. What you need to know before using Quinux

Do not use Quinux

• if you are allergic to methotrexate or 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 severe infection, such as tuberculosis, HIV, or other immunodeficiency syndromes,
• if you have a mouth ulcer, gastric ulcer, or intestinal ulcer,
• 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

Consult your doctor or pharmacist before starting to use Quinux:

• if you are elderly or generally feel unwell and weak,
• if you have impaired liver function,
• if you have dehydration (loss of body fluids).

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

Follow-up tests and recommended safety measures

Even when Quinux is administered at low doses, serious adverse effects may occur. To detect them early, your doctor must perform blood tests and check-ups.

Before starting Quinux treatment

Before starting treatment, you will have blood tests to ensure you have sufficient blood cells, and tests to assess liver function and check for hepatitis (liver infection). Additionally, serum albumin levels (a blood protein), hepatitis status, and kidney function will be monitored. Your doctor may also decide to perform other liver tests, some of which may include imaging of your liver, while others may require a small tissue sample from the liver for closer examination. Your doctor may also check for tuberculosis (an infectious disease associated with small nodules in affected tissue) and may perform a chest X-ray or lung function test.

During treatment

Your doctor may perform the following examinations:

• examination of the mouth and throat to detect mucosal changes such as inflammation or ulceration,
• blood tests/hematological analysis including blood cell count and measurement of serum methotrexate levels,
• blood tests to monitor liver function,
• imaging tests to monitor liver condition,
• a small tissue sample taken from the liver for closer examination,
• blood tests to monitor kidney function,
• respiratory system examination and, if necessary, lung function testing.

It is very important that you attend these scheduled examinations.

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

Methotrexate can affect the immune system and the response to vaccinations.

It may also affect the results of immunological tests. It can reactivate chronic latent infections (e.g., herpes zoster ["shingles"], tuberculosis, hepatitis B or C). During treatment with Quinux, you must not receive vaccines made with attenuated microorganisms.

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

During treatment with methotrexate, radiation-induced dermatitis and sunburn may reappear (recall reactions). Psoriatic lesions may worsen during UV radiation (ultraviolet radiation) and concomitant administration of methotrexate.

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

Diarrhea may be a toxic effect of Quinux requiring treatment discontinuation. If you experience diarrhea, speak with your doctor.

Encephalopathy (a brain disorder) and leukoencephalopathy (a specific disorder of the brain's white matter) have been reported in cancer patients receiving methotrexate. These disorders cannot be ruled out when methotrexate is used to treat other conditions.

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

Special precautionary measures for Quinux treatment

Methotrexate temporarily affects sperm and egg production, 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 taking methotrexate and for at least 3 months after stopping treatment. See also section "Pregnancy, breastfeeding and fertility".

Elderly patients

Elderly patients receiving methotrexate should be closely monitored by a doctor so that potential side effects can be detected as early as possible.

Age-related decline in liver and kidney function, as well as low body reserves of folic acid in older age, require a relatively low dose of methotrexate.

Other medicines and Quinux

Inform your doctor or pharmacist if you are taking, have recently taken, or might need to take any other medicines.

The effect of treatment may be affected if Quinux is taken at the same time as certain medicines:

• Medicines that damage the liver or blood, e.g., leflunomide
• Antibiotics (medicines that prevent or treat certain infections) such as: tetracyclines, chloramphenicol, non-absorbable broad-spectrum antibiotics, penicillins, glycopeptides, sulfonamides (medicines containing sulfur that prevent or treat certain infections), ciprofloxacin, and cephalothin
• Non-steroidal anti-inflammatory drugs or salicylates (medicines for pain or inflammation)
• Probenecid (a medicine for gout)
• Weak organic acids such as loop diuretics or certain medicines used to treat pain and inflammatory diseases (e.g., acetylsalicylic acid, diclofenac, and ibuprofen), and pyrazoles (e.g., metamizole (synonyms: novaminsulfone and dipyrone) for severe pain and/or fever)
• Medicines that may cause adverse effects on the bone marrow, e.g., trimethoprim-sulfamethoxazole (an antibiotic) and pyrimethamine
• Sulfasalazine (an anti-rheumatic medicine)
• Azathioprine (an immunosuppressant sometimes used in the treatment of severe forms of rheumatoid arthritis)
• Mercaptopurine (a cytostatic medicine)
• Retinoids (medicines for psoriasis and other skin diseases)
• Theophylline (a medicine for bronchial asthma and other lung diseases)
• Proton pump inhibitors (medicines for stomach discomfort)
• Hypoglycemics (medicines used to lower blood sugar levels).

Vitamins containing folic acid may alter the treatment effect and should only be taken if advised by your doctor.

Vaccinations with vaccines made from attenuated microorganisms should be avoided.

Use of Quinux with food, drinks, and alcohol

During treatment with Quinux, consumption of alcohol and large amounts of coffee, caffeinated soft drinks, and black tea should be avoided.

Pregnancy, breastfeeding and fertility

If you are pregnant or breastfeeding, think you may be pregnant, or plan to become pregnant, consult your doctor or pharmacist before using this medicine.

Pregnancy

Do not use Quinux during pregnancy or if you are trying to become pregnant. Methotrexate may cause birth defects, harm the fetus, or cause miscarriage. 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 given to pregnant patients or those planning to become pregnant. In women of childbearing age, pregnancy must be ruled out using appropriate measures, such as 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 period (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 for counseling before the planned start of treatment.

Because methotrexate may be genotoxic, all women who wish to become pregnant are advised to consult a genetic counseling center, if possible, before treatment. Men should be informed about the possibility of sperm preservation before starting treatment.

Breastfeeding

Breastfeeding must be discontinued during treatment with Quinux.

Male fertility

Available data do not indicate an increased risk of birth defects or miscarriage 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 can 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 Quinux may cause adverse reactions affecting the central nervous system, such as fatigue and dizziness. Therefore, your ability to drive or operate machinery may, in some cases, be impaired. If you feel tired or drowsy, you should not drive or use machinery.

Quinux contains sodium

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

3. How to use Quinux

Follow exactly the administration instructions for this medicine as indicated by your doctor or pharmacist. If in doubt, consult your doctor or pharmacist again.

Important warning about the dose of Quinux (methotrexate):

Use Quinux only once a week for the treatment of arthritis and psoriasis. Excessive use of Quinux (methotrexate) can be fatal. Read section 3 of this leaflet very carefully. If you have any doubts, consult your doctor or pharmacist before taking this medicine.

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

Quinux injections will be administered or supervised by your 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. Quinux can be injected either intramuscularly (into a muscle) or subcutaneously (under the skin).

Use in children and adolescents

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

Quinux 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

Quinux is injected once a week.

The doctor in charge will decide the duration of treatment. Treatment of rheumatoid arthritis, juvenile idiopathic arthritis, psoriasis vulgaris, and psoriatic arthritis with Quinux is a long-term treatment.

At the beginning of treatment, Quinux may be administered by medical staff. However, your doctor may decide that you can learn to self-inject Quinux. You will receive appropriate training for this. Under no circumstances should you attempt to self-inject unless you have been specifically trained to do so.

Refer to the instructions for use at the end of this leaflet.

Handling and disposal of the product must follow guidelines for other cytotoxic preparations according to local regulations. Healthcare personnel who are pregnant must not handle or administer Quinux.

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

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

If you use more Quinux than you should

In case of overdose or accidental ingestion, contact your doctor or pharmacist immediately or call the Toxicology Information Service at: 91 562 04 20.

If you forget to use Quinux

Do not use a double dose to make up for forgotten doses.

If you have any further questions about the use of this medicine, ask your doctor, pharmacist, or nurse.

4. Possible adverse effects

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

The frequency and severity of adverse effects depend on the dose and frequency of administration. It is important that your doctor performs regular monitoring, as serious adverse effects may occur even with the lowest doses. Your doctor will carry out tests to monitor blood abnormalities such as low levels of leukocytes (white blood cells), platelets, lymphoma, and changes in the kidneys and liver.

The most relevant adverse effects associated with the administration of Quinux occur in the blood-forming system and the gastrointestinal tract.

Immediately inform your doctor if you experience any of the following symptoms, as they may indicate a serious adverse reaction with potential life-threatening risk that may require urgent specific treatment:

• Severe pulmonary discomfort (symptoms may include general malaise, dry irritating cough, difficulty breathing, shortness of breath at rest, chest pain, or fever).
• Coughing up blood.
• Severe blistering or peeling of the skin.
• Unusual bleeding (including vomiting blood) or bruising.
• Severe diarrhea.
• Mouth ulcers.
• Black stools.
• Blood in the urine or stools.
• Small red spots on the skin.
• Fever.
• Yellowing of the skin (jaundice).
• Pain or difficulty urinating.
• Excessive thirst and/or frequent need to urinate.
• Seizures.
• Loss of consciousness.
• Blurred vision or decreased vision.

The following adverse effects may occur:

Very common (may affect more than 1 in 10 people):

• Inflammation of the mouth, indigestion, nausea (feeling of needing to vomit), loss of appetite.
• Increased liver enzymes.

Common (may affect up to 1 in 10 people):

• Mouth ulcers, diarrhea.
• Rash, skin redness, itching.
• Headache, fatigue, drowsiness.
• Decreased production of red blood cells with reduced numbers of white blood cells, red blood cells, or platelets (leukopenia, anemia, thrombocytopenia).

Uncommon (may affect up to 1 in 100 people):

• Sore throat, intestinal inflammation, vomiting.
• Sunburn-like reactions due to increased sensitivity of the skin to sunlight, hair loss, increase in rheumatoid nodules, herpes zoster, inflammation of blood vessels, herpes-like rash, urticaria.
• Development of diabetes mellitus.
• Dizziness, confusion, depression.
• Inflammation and ulceration of the urinary bladder or vagina, decreased kidney function, urinary disorders.
• Joint pain, muscle pain, osteoporosis (reduction in bone mass).
• Decrease in serum albumin.

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

• Increased skin pigmentation, acne, bruising due to bleeding from blood vessels.
• Allergic reactions, anaphylactic shock, allergic inflammation of blood vessels, fever, red eyes, infection, blood toxicity, impaired wound healing, decreased number of antibodies in the blood.
• Visual disturbances.
• Inflammation of the sac surrounding the heart, fluid accumulation in the sac around the heart.
• Low blood pressure.
• Pulmonary fibrosis, pneumonia caused by a specific microorganism (Pneumocystis carinii pneumonia), breathing difficulty and bronchial asthma, fluid accumulation in the sac around the lungs.
• Electrolyte disturbances.

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

• Profuse bleeding, toxic megacolon (acute toxic dilation of the intestine).
• Stevens-Johnson syndrome, increased pigmentation of the nails, inflammation of the cuticles, furunculosis (deep infection of hair follicles), visible enlargement of small blood vessels.
• Local injury at the site of administration (formation of sterile abscesses, changes in fatty tissue) following intramuscular or subcutaneous injection.
• Visual disturbances, pain, loss of strength, or numbness or tingling sensation, reduced sensitivity to stimuli, altered taste (metallic taste), seizures, paralysis, severe headache with fever.
• Retinopathy (non-inflammatory eye disorder).
• Sudden drop in white blood cell count, severe bone marrow suppression.
• Lymphoproliferative disorders (excessive increase in white blood cells).
• Loss of sexual appetite, impotence, male breast enlargement (gynecomastia), altered sperm formation, menstrual disorders, vaginal discharge.
• Enlargement of lymph nodes (lymphoma).

Frequency not known (cannot be estimated from available data):

• Leukoencephalopathy (a disease of the brain's white matter).
• Pulmonary hemorrhage.
• Jaw bone damage (secondary to excessive increase in white blood cells).
• Redness and peeling of the skin.
• Tissue damage at the injection site.
• Swelling.

When methotrexate is administered by intramuscular route, local adverse reactions (burning sensation) or lesions (formation of sterile abscesses, destruction of fatty tissue) at the injection site may occur frequently. Subcutaneous administration of methotrexate is well tolerated locally. Only mild local skin reactions have been observed, which decreased during treatment.

Reporting of adverse effects

If you experience any type of adverse effect, consult your doctor, pharmacist, or nurse, even if they are possible adverse effects not listed in this leaflet. You may also report them directly via the Spanish Pharmacovigilance System for Human Medicines: https://www.notificaram.es. By reporting adverse effects, you can help provide more information on the safety of this medicine.

5. Storage of Quinux

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

Do not store above 25 °C. Store the pre-filled syringes in the outer packaging to protect them from light. Do not refrigerate or freeze.

Do not use this medicine after the expiry date stated on the packaging 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 unused medicines and their packaging at a SIGRE collection point at your pharmacy or any other medicine waste collection system. If in doubt, ask your pharmacist how to dispose of packaging and medicines you no longer need. This will help protect the environment.

6. Contents of the pack and other information

Composition of Quinux

• The active substance is methotrexate. 1 ml of solution contains 25 mg of methotrexate (equivalent to 27.42 mg of methotrexate disodium).

1 pre-filled syringe of 0.4 ml of solution contains 10 mg of methotrexate.

• The other components are sodium chloride, sodium hydroxide, water for injections.

Appearance of the product and contents of the pack

Quinux pre-filled syringes contain a yellowish, clear solution.

The syringe is equipped with a safety system designed to help prevent needlestick injuries after use.

Each pack contains 1 or 4 pre-filled syringe(s) with 0.4 ml of solution, with attached subcutaneous injection needles and alcohol swabs.

Each pack contains 1 or 4 pre-filled syringe(s) with 0.4 ml of solution, with attached safety-engineered subcutaneous injection needles and alcohol swabs.

Only certain pack sizes may be commercially available.

Marketing Authorization Holder and Manufacturer

Marketing Authorization Holder

Especialidades Farmacéuticas Centrum, S.A.
C/ Sagitario, 14
03006, Alicante
Spain
Asacpharma Group
Tel.: 965288160; Fax.: 965286434

Manufacturer

Especialidades Farmacéuticas Centrum, S.A.
C/ Sagitario, 14
03006, Alicante
Spain

Date of latest revision of this leaflet: October 2024.

Detailed information about this medicine is available on the website of the Spanish Agency of Medicines and Health Products (AEMPS) (http://www.aemps.gob.es)

Instructions for use

Read the instructions carefully before starting to administer the injection, and always use the administration technique advised by your doctor, nurse, or pharmacist.

If you have any problems or questions, contact your doctor, nurse, or pharmacist.

Preparation

Select a clean, flat, and well-lit work surface.

Gather all necessary items before starting:

• 1 pre-filled syringe of Quinux
• 1 alcohol swab (supplied in the pack)

Wash your hands thoroughly. Before use, inspect the Quinux syringe for any visible defects (or cracks).

Injection site

The best sites for injection are:

• the upper thigh,
• the abdomen, except the area around the navel.

• If someone is assisting you with the injection, they may also administer it on the back of the upper arm, just below the shoulder.
• Change the injection site with each dose. This may reduce the risk of developing injection site reactions.
• Never inject into painful, bruised, red, hardened skin, or skin with scars or stretch marks. If you have psoriasis, do not attempt to inject directly into lesions or raised, thickened, red, or scaly skin patches.

Injection of the solution

1. Open the box containing the pre-filled methotrexate syringe and read the leaflet carefully. Remove the pre-filled syringe from its packaging and allow it to reach room temperature.
2. Disinfection: Select an injection site and clean it with the alcohol swab. Wait 60 seconds for the disinfectant to dry.

3. Carefully remove the protective plastic cap by gently twisting it off. Important: Do not touch the needle of the pre-filled syringe.

4. Cannula insertion: With two fingers, pinch a fold of skin and insert the needle quickly at a 90-degree angle.

5. Injection: Fully insert the needle into the skin fold. Slowly push the plunger to inject the liquid under the skin. Hold the skin firmly until the injection is complete. Carefully remove the needle in a straight line.

A protective shield will automatically cover the needle.

Methotrexate must not come into contact with the skin surface or mucous membranes. In case of contamination, immediately rinse the affected area thoroughly with plenty of water.

If you or someone in your household is injured by the needle, consult your doctor immediately and do not use this pre-filled syringe.

Disposal and other handling

Handling and disposal of the medicine and the pre-filled syringe must be carried out in accordance with local regulations for cytotoxic agents. Pregnant healthcare personnel must not handle or administer Quinux.