Patient Information: Package Insert

QUINUX15 mg/0.6 ml pre-filled syringe solution

Methotrexate

Read this entire package insert carefully before starting to use this medication, as it contains important information for you.

• Keep this package insert, as you may need to refer to it again.
• If you have any questions, consult your doctor or pharmacist.
• This medication has been prescribed only for you, and you should not give it to others, even if they have the same symptoms as you, as it may harm them.
• If you experience any adverse effects, consult your doctor or pharmacist, even if they are not listed in this package insert. See section 4.

• What is Quinuxand how is it used
• What you need to know before starting to use Quinux
• How to use Quinux
• Possible adverse effects
• Storage of Quinux
• Contents of the package and additional information

Quinux contains methotrexate as the active ingredient.

Methotrexate is a substance with the following properties:

• interferes with the growth of certain cells in the body that reproduce quickly,
• reduces the activity of the immune system (the body's defense mechanism),
• has anti-inflammatory effects.

Quinux is indicated for the treatment of:

• active rheumatoid arthritis in adult patients,
• severe active polyarticular juvenile idiopathic arthritis (JIA), when the response to nonsteroidal anti-inflammatory drugs (NSAIDs) has not been adequate,
• severe and debilitating psoriasis that does not respond adequately to other treatments 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 the membrane to thicken and the joint to swell.

Juvenile arthritis affects children and adolescents under 16 years old. Polyarticular forms are indicated if there is involvement of 5 or more joints in the first 6 months of the disease.

Psoriatic arthritis is a type of arthritis with psoriatic lesions on the skin and nails, especially in the joints of the fingers of the hands and feet.

Poriasis is a chronic and frequent skin disease characterized by red patches covered with thick, dry, silver, and adherent scales.

Quinux modifies and delays the progression of the disease.

No use Quinux

• if you are allergic to methotrexate or any of the other ingredients in this medicine (listed in section 6),
• if you havesevere liver or kidney disease or blood disorders,
• if you regularly take large amounts of alcohol,
• if you havea severe infection, for example, tuberculosis, HIV or other immunodeficiency syndromes,
• if you havea mouth ulcer, stomach 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 havealtered liver function,
• if you have dehydration (loss of fluids) problems.

A severe lung haemorrhage has been reported in patients with underlying rheumatological disease treated with methotrexate. If you notice blood when coughing or spitting, you should contact your doctor immediately.

Recommended follow-up tests and safety measures

Even when Quinux is administered at low doses, serious side effects can occur. To detect them in time, your doctor will need to perform blood tests and checks.

Before starting treatment with Quinux

Before starting treatment, you will have blood tests to check that you have enough blood cells and tests to check liver function and to see if you have hepatitis (liver infection). In addition, your liver function, albumin serum concentration (a blood protein), hepatitis status, and kidney function will be checked. Your doctor may also decide to perform other liver tests, some of which may be images of your liver and others may require a small sample of liver tissue for closer examination. Your doctor may also check if you have tuberculosis (an infectious disease with small nodules in the affected tissue) and may perform a chest X-ray or lung function test.

During treatment

Your doctor may perform the following tests:

• oral and throat examination to detect changes in mucous membranes, such as inflammation or ulceration,
• blood test/haemogram with blood cell count and measurement of serum methotrexate levels,
• blood test to check liver function,
• imaging tests to check liver condition,
• small sample of liver tissue extracted for closer examination,
• blood test to check kidney function,
• review of the respiratory system and, if necessary, lung function test.

It is very important that you attend these scheduled tests.

If the results of any of these tests are notable, your doctor will adjust your treatment accordingly.

Methotrexate can affect the immune system and vaccine results.

It can also affect the results of immunological tests. It can intensify chronic inactive infections (e.g. herpes zoster [“culebrillas”], tuberculosis, hepatitis B or C). During treatment with Quinux, do not receive vaccines made with attenuated microorganisms.

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

During treatment with methotrexate, dermatitis caused by radiation and sunburn (recall reactions) may reappear. Psoriatic lesions may intensify during UV radiation (ultraviolet radiation) and simultaneous administration of methotrexate.

Lymph node enlargement (lymphoma) may occur, and in this case, treatment should be suspended.

Diarhoea can be a toxic effect of Quinux that requires suspension of treatment. If you have diarrhoea, talk to your doctor.

Encephalopathy (a brain disorder) and leukoencephalopathy (a special disorder of the brain's white matter) have been reported in cancer patients receiving methotrexate treatment. These disorders cannot be ruled out for methotrexate treatment in other diseases.

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

Special precautions for Quinux treatment

Methotrexate temporarily affects sperm and egg production, which is reversible in most cases. Methotrexate can cause severe birth defects and miscarriage. If you are a woman, avoid becoming pregnant while using methotrexate and for at least 6 months after stopping treatment. If you are a man, avoid fathering a child while taking methotrexate and for at least 3 months after stopping treatment. See also section «Pregnancy, breastfeeding and fertility».

Older patients

Older patients on methotrexate treatment should be closely monitored by a doctor to detect any possible side effects as soon as possible.

The age-related deterioration of liver and kidney function, as well as the low body reserves of folic acid in old age, require a relatively low dose of methotrexate.

Other medicines and Quinux

Inform your doctor or pharmacist if you are using, have used recently, or may need to use any other medicine.

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

• Medicines that damage the liver or blood, for example, leflunomide
• Antibiotics (medicines that prevent or combat certain infections) such as:tetracyclines,chloramphenicol,non-absorbable broad-spectrum antibiotics,penicillins,glucopetides,sulfonamides (medicines containing sulfur that prevent or combat certain infections),ciprofloxacin andcephalothin
• Non-steroidal anti-inflammatory drugs orsalicylates (pain and inflammation medicines)
• Probenecid (gout medicine)
• Weak organic acids such as diuretics of the asaor some medicines used to treat pain and inflammatory diseases (e.g. acetylsalicylic acid, diclofenac and ibuprofen) and pyrazoles (e.g. metamizol (synonyms novaminsulfon and dipirona) for intense pain and/or fever)
• Medicines that can cause adverse effects on the bone marrow, for example, trimethoprim-sulfamethoxazole (an antibiotic) and pyrimethamine
• Sulfasalazine (anti-rheumatic)
• Azathioprine (immunosuppressant that is sometimes used to treat severe forms of rheumatoid arthritis)
• Mercaptopurine (cytostatic)
• Retinoids (medicines for psoriasis and other skin diseases)
• Theophylline (medicines for asthma and other lung diseases)
• Inhibitors of the proton pump (medicines for stomach discomfort)
• Hypoglycemics (medicines used to reduce blood sugar levels).

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

Vaccinations with vaccines made with attenuated microorganisms should be avoided.

Use of Quinux with food, drinks and alcohol

During treatment with Quinux, avoid consuming alcohol and large amounts of coffee, caffeinated soft drinks, and black tea.

Pregnancy, breastfeeding and fertility

If you are pregnant or breastfeeding, or if you think you may be 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 can cause birth defects, harm the fetus, or cause miscarriage. It is associated with skull, face, heart, and blood vessel malformations, brain and limb malformations. Therefore, it is very important that methotrexate is not administered to pregnant patients or those planning to become pregnant. In fertile women, any possibility of pregnancy should be excluded with appropriate measures, for example, a pregnancy test before starting treatment. You should avoid becoming pregnant while taking methotrexate and for at least 6 months after stopping treatment, using reliable contraceptive methods during 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 will be offered information about the risk of harm to the child during treatment.

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

As methotrexate may be genotoxic, all women who wish to become pregnant should consult a genetic counselling centre, if possible, before treatment, and men should be informed about the possibility of preserving sperm before starting treatment.

Breastfeeding

Breastfeeding should be suspendedduring treatment with Quinux.

Male fertility

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

Driving and operating machinery

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 be affected in some cases. If you feel tired or drowsy, do not drive or operate machinery.

Quinux contains sodium

This medicine contains less than 1 mmol of sodium (23 mg) per dose unit; it is essentially “sodium-free”.

Follow exactly the administration instructions of this medication indicated by your doctor or pharmacist. In case of doubt, consult your doctor or pharmacist again.

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

The Quinux injection will be administered or supervised by your doctor or healthcare professionalonly once a week. Along with your doctor, you will choose a day of the week that suits you to receive the injection. Quinux can be injected intramuscularly (into a muscle) or subcutaneously (under the skin).

Useinchildrenandadolescents

Your doctor will decide what is the appropriate dose in children and adolescents with polyarticular idiopathic juvenile arthritis.

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

Duration and form of administration

Quinux is injectedonce a week.

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

At the beginning of treatment, Quinux may be injected by medical personnel. However, your doctor may decide that you can learn to inject Quinux yourself. You will receive the necessary training for this. Under no circumstances should you attempt to inject yourself unless you have been taught to do so.

See the usage instructions at the end of the prospectus.

The form of handling and eliminating the product will be done in accordance with the guidelines for other cytotoxic preparations in accordance with local regulations. Pregnant healthcare personnel should not handle or administer Quinux.

Methotrexate should not come into contact with the skin surface or mucous membranes. If it does, the affected area should be washed immediately with plenty of water.

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

IfyouusemoreQuinuxthanyoushould

In case of overdose or accidental ingestion, consult your doctor or pharmacist immediately or call the Toxicological Information Service, phone: 91 562 04 20.

IfyouforgottouseQuinux

Do not use a double dose to compensate for the missed doses.

If you have any other doubts about the use of this medication, ask your doctor, pharmacist, or nurse.

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

The frequency and severity of side effects will depend on the dose and frequency of administration. It is essential that your doctor performs regular checks, as severe side effects can occur even with low doses. Your doctor will perform tests to monitor abnormalities in the blood, such as low white blood cell counts (leukocytes), platelets, lymphoma, and changes in the kidneys and liver.

The most relevant side effects related to the administration of Quinux occur in the blood production system and the digestive tract.

Inform your doctor immediately if you experience any of the following symptoms, as they may indicate a severe side effect with potential life-threatening risk that may require urgent specific treatment:

• Severe respiratory distress (symptoms may include general discomfort, irritating and dry cough, difficulty breathing, feeling of lack of air at rest, chest pain, or fever).
• Bleeding when coughing or sneezing.
• Severe blistering or skin peeling.
• Unusual bleeding (including vomiting blood) or bruises.
• Severe diarrhea.
• Mouth ulcers.
• Black stools.
• Blood in the urine or stools.
• Small red spots on the skin.
• Fever.
• Yellow discoloration of the skin (jaundice).
• Pain or difficulty urinating.
• Thirst and/or frequent urination.
• Seizures (convulsions).
• Loss of consciousness.
• Blurred vision or decreased vision.

The following side effects may occur:

Very common(mayaffectmorethan1in10people):

• Oral inflammation, indigestion, nausea (urge to vomit), loss of appetite.
• Increased liver enzymes.

Common(mayaffectupto1in10people):

• Mouth ulcers, diarrhea.
• Rash, skin redness, itching.
• Headache, fatigue, drowsiness.
• Decreased red blood cell formation with decreased white blood cell, red blood cell, or platelet count (leukopenia, anemia, thrombocytopenia).

Uncommon(mayaffectupto1in100people):

• Throat inflammation, intestinal inflammation, vomiting.
• Reactions similar to sunburn due to increased skin sensitivity to sunlight, hair loss, increased number of rheumatic nodules, herpes zoster, inflammation of blood vessels, herpes-like rash, urticaria.
• Appearance of diabetes mellitus.
• Dizziness, confusion, depression.
• Urinary or vaginal tract inflammation or ulcers, decreased kidney function, urinary disorders.
• Joint pain, muscle pain, osteoporosis (bone mass reduction).
• Decreased serum albumin.

Rare(mayaffectupto1in10,000people):

• Severe bleeding, toxic megacolon (acute and toxic dilation of the intestine).
• Sunburn-like syndrome, increased skin pigmentation, nail pigmentation, skin cuticle inflammation, furunculosis (deep infection of hair follicles), visible enlargement of small blood vessels.
• Local lesion at the injection site (sterile abscess formation, tissue destruction) after intramuscular injection or subcutaneous injection.
• Visual disturbances, pain, loss of strength or numbness/sensitivity to minor stimuli, altered taste (metallic taste), seizures, paralysis, severe headache with fever.
• Retinopathy (non-inflammatory eye disorder).
• Severe decrease in white blood cell count, severe bone marrow depression.
• Lymphoproliferative disorders (excessive increase in white blood cells).
• Loss of sexual appetite, impotence, increased male breast tissue (gynecomastia), altered sperm formation, menstrual disorders, vaginal discharge.
• Enlarged lymph nodes (lymphoma).

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

• Leucoencephalopathy (a disease of the brain's white matter).
• Pulmonary hemorrhage.
• Damage to jaw bones (secondary to excessive white blood cell increase).
• Redness and peeling of the skin.
• Tissue destruction at the injection site.
• Swelling.

When metotrexate is administered intramuscularly, local side effects may occur frequently (burning sensation) or lesions (sterile abscess formation, tissue destruction) at the injection site. Subcutaneous metotrexate administration is well tolerated locally. Only mild local skin reactions were observed, which decreased during treatment.

Reporting of side effects

If you experience any type of side effect, consult your doctor,pharmacistornurse,even if it is a possible side effect that does not appear in this prospectus. You can also report them directly through the Spanish System for Pharmacovigilance of Medicines for Human Use. https://www.notificaram.es. By reporting side effects, you can contribute to providing more information on the safety of this medicine.

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

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

Do not use this medication after the expiration date that appears on the packagingafter CAD. The expiration date is the last day of the month indicated.

Medicines should not be disposed of through drains or in the trash. Dispose of packaging and unused medications at the SIGRE point of the pharmacyoranyothercollectionsystemforpharmaceuticalwaste. If in doubt, ask your pharmacist how to dispose of packaging and unused medications. In this way, you will help protect the environment.

Composition of Quinux

• The active ingredient is methotrexate. 1 ml of solution contains 25 mg of methotrexate(equivalenta27.42mgofmethotrexatedisodium).

1 pre-filled syringe of0.6mlofsolutioncontains15mgofmethotrexate.

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

Appearance of the product and contents of the pack

Quinux pre-filled syringes contain a yellowish and transparent solution.

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

Each pack contains 1 or 4 pre-filled syringes with 0.6 ml of solution, with subcutaneous injection needles attached and alcohol-impregnated cotton balls.

Each pack contains 1 or 4 pre-filled syringes with 0.6 ml of solution, with subcutaneous injection needles attachedwith safety systemand alcohol-impregnated cotton balls.

Only some pack sizes may be marketed.

Marketing Authorization Holder and Responsible Manufacturer

Marketing Authorization Holder

Specialties Pharmaceutical Centrum, S.A.

C/ Sagitario, 14

03006, Alicante

Spain
GroupAsacpharma

Tel.: 965288160; Fax.: 965286434

Responsible Manufacturer

Specialties Pharmaceutical Centrum, S.A.

C/ Sagitario, 14

03006, Alicante

Spain

Last review date of this leaflet: October 2024.

The detailed informationof this medicine is available on the website of the Spanish Agency for Medicines and Medical Devices (AEMPS) (http://www.aemps.gob.es)

Instructions for use

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

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

Preparation

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

Gather all the necessary elements before starting:

• 1 Quinux pre-filled syringe
• 1 alcohol-impregnated cotton ball (supplied in the pack)

Wash your hands thoroughly. Before using it, inspect the Quinux pre-filled syringe for visible defects (or cracks).

Injection site

The best places for injection are:

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

• If someone is helping you with the injection, you can also apply the injection to the back of the arm, just below the shoulder.
• Change the injection site each time. This may reduce the risk of developing skin irritation at the injection site.
• Do not apply the injection to painful, discolored, red, hardened or scarred skin. If you have psoriasis, do not attempt to inject directly into lesions or patches of raised, thickened, red or scaly skin.

Injecting the solution

1. Open the pack containing the pre-filled syringe of methotrexate and read the leaflet carefully. Remove the pre-filled syringe from the pack at room temperature.
2. Disinfection: select a place for the injection and disinfect it with the alcohol-impregnated cotton ball. Leave for 60 seconds to allow the disinfectant to dry.

1. Removecarefullythe plastic protective cap, turn it gently with a movement outward. Important: do not touch the needle of the pre-filled syringe.

1. Insertion of the cannula: with two fingers, form a fold in the skin and insert the needle quickly at an angle of 90 degrees.

1. Injection: insert the needle completely into the skin fold. Push the plunger slowly and inject the liquid under the skin. Hold the skin firmly until the injection is complete. Remove the needle carefully in a straight line.

A protective cap will automatically enclose the needle.

Methotrexate should not come into contact with the skin surface or mucous membranes. In case of contamination, the affected area should be washed immediately with plenty of water.

If you or someone in your environment are injured with the needle, consult your doctor immediately and do not use this pre-filled syringe.

Disposal and other manipulations

The manipulation and disposal of the medicine and the pre-filled syringe will be carried out in accordance with local regulationsforcytotoxic agents. Pregnant healthcare personnel should not handle or administer Quinux.