QUINUX 20 mg/0.8 mL Injectable Solution in Pre-filled Syringe

Introduction

Package Leaflet: Information for the Patient

QUINUX 20 mg/0.8 ml solution for injection in a pre-filled syringe

Methotrexate

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

• Keep this leaflet, you may need to read it again.
• If you have any further questions, ask your doctor or pharmacist.
• This medicine has been prescribed for you only. Do not pass it on to others. It may harm them, even if their signs of illness are the same as yours.
• If you get any side effects, talk to your doctor or pharmacist. This includes any possible side effects not listed in this leaflet. See section 4.

Contents of the pack

1. What Quinux is and what it is used for
2. What you need to know before you use Quinux
3. How to use Quinux
4. Possible side effects
5. Storing 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:

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

Quinux is indicated for the treatment of:

• active rheumatoid arthritis in adult patients,
• severe active polyarticular forms of juvenile idiopathic arthritis (JIA), when the response to non-steroidal anti-inflammatory drugs (NSAIDs) has not been adequate,
• severe recalcitrant and disabling 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 disease of the connective tissue, 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 of age. 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 and toes.

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

Quinux modifies and slows down the progression of the disease.

2. What you need to know before you use 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 diseases,
• if you regularly drink large amounts of alcohol,
• if you have a severe infection, such as tuberculosis, HIV, or other immunodeficiency syndromes,
• if you have an ulcer in the mouth, stomach ulcer, or intestinal ulcer,
• if you are pregnant or breastfeeding (see section "Pregnancy, breastfeeding, and fertility"),
• if you are receiving live vaccines at the same time.

Warnings and precautions

Consult your doctor or pharmacist before starting treatment with Quinux:

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

Acute pulmonary hemorrhage has been reported with methotrexate in patients with underlying rheumatologic disease. If you cough up blood or spit up blood, you should contact your doctor immediately.

Follow-up tests and recommended 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 check-ups.

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). Additionally, the concentration of serum albumin (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 involve imaging of your liver and others may require a small tissue sample from your liver to examine it more closely. 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:

• examination of the mouth and throat to detect changes in the mucous membranes, such as inflammation or ulceration,
• blood tests/complete blood count with 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 to examine it more closely,
• blood tests to monitor 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 the results of vaccinations.

It can also affect the results of immunological tests. It can exacerbate chronic inactive infections (e.g., herpes zoster ["shingles"], tuberculosis, hepatitis B or C). During treatment with Quinux, you should not receive live vaccines.

Methotrexate can make your 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 sunscreen with a high protection factor.

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

A increase in lymph node size (lymphoma) may occur, and in such cases, treatment should be discontinued.

Diarrhea can be a toxic effect of Quinux that requires discontinuation of treatment. If you have diarrhea, talk to your doctor.

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

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

Special precautions for treatment with Quinux

Methotrexate temporarily affects sperm and egg production, which is reversible in most cases. Methotrexate can cause abortions and severe birth defects. If you are a woman, you must avoid becoming pregnant while using 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 treated with methotrexate should be closely monitored by a doctor so that possible side effects can be detected as soon as possible.

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

Other medicines and Quinux

Tell your doctor or pharmacist if you are using, have recently used, or might use any other medicines.

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, such as leflunomide
• Antibiotics (medicines that prevent or combat certain infections), such as tetracyclines, chloramphenicol, non-absorbable broad-spectrum antibiotics, penicillins, glycopeptides, sulfonamides (medicines that contain sulfur and prevent or combat certain infections), ciprofloxacin, and cefalotin
• Non-steroidal anti-inflammatory drugs (NSAIDs) 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., metamizol [synonyms novaminsulfon and dipyrone] for severe pain and/or fever)
• Medicines that can cause adverse effects on the bone marrow, such as trimethoprim-sulfamethoxazole (an antibiotic) and pyrimethamine
• Sulfasalazine (an antirheumatic)
• Azathioprine (an immunosuppressant that is sometimes used in the treatment of severe rheumatoid arthritis)
• Mercaptopurine (a cytostatic)
• 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)
• Hypoglycemic agents (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.

Live vaccines should be avoided.

Using Quinux with food, drinks, and alcohol

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

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 can cause birth defects, harm the fetus, 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, any possibility of pregnancy should be excluded with 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 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 harmful effects on the child during treatment.

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

Since methotrexate can be genotoxic, it is recommended that all women who wish to become pregnant consult a genetic counseling center, if possible, before treatment, and men should be informed about the possibility of preserving sperm before starting treatment.

Breastfeeding

Breastfeeding should be discontinued during treatment with Quinux.

Male fertility

Available data do not indicate an increased risk of malformations or miscarriages 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, which means it can cause genetic mutations. Methotrexate can affect sperm production and cause birth defects. Therefore, you must avoid fathering a child or donating sperm while taking methotrexate and for at least 3 months after stopping treatment.

Driving and using machines

Treatment with Quinux can cause adverse reactions that affect the central nervous system, such as fatigue and dizziness. Therefore, the ability to drive or use machines may be affected in certain cases. If you feel tired or drowsy, you should not drive or use machines.

Quinux contains sodium

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

3. How to use Quinux

Follow the instructions for administration of this medicine exactly as prescribed by your doctor or pharmacist. If you are unsure, consult your doctor or pharmacist again.

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

The injection of Quinux 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 that is suitable for you to receive the injection. Quinux can be injected intramuscularly (into a muscle) or subcutaneously (under the skin).

Use in children and adolescents

The doctor decides what dose is suitable 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 long-term treatment.

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

See the instructions for use at the end of the leaflet.

The handling and disposal of the product will be carried out 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 skin or mucous membranes. If it does, the affected area should be rinsed immediately 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, consult your doctor or pharmacist immediately or call the Toxicology Information Service, phone: 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 all people suffer from them.

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

The most relevant adverse 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 adverse effect with potential vital danger that may require urgent specific treatment:

• Severe pulmonary disorders (symptoms may be general discomfort, irritating and dry cough, difficulty breathing, feeling of lack of air at rest, chest pain, or fever).
• Blood when coughing or spitting.
• Severe blistering or peeling of the skin.
• Unusual bleeding (including vomiting blood) or bruising.
• Severe diarrhea.
• Ulcers in the mouth.
• Black stools.
• Blood in the urine or stools.
• Small red spots on the skin.
• Fever.
• Yellowing of the skin (jaundice).
• Pain or difficulty urinating.
• Thirst and/or frequent need to urinate.
• Seizures (convulsions).
• Loss of consciousness.
• Blurred vision or decreased vision.

The following adverse effects may occur:

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

• Mouth inflammation, indigestion, nausea (vomiting), 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 formation of red blood cells with decreased number of white blood cells, red blood cells, or platelets (leukopenia, anemia, thrombocytopenia).

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

• Throat inflammation, intestinal inflammation, vomiting.
• Reactions similar to sunburn due to increased skin sensitivity to sunlight, hair loss, increased number of rheumatic nodules, shingles, blood vessel inflammation, herpes-like rash, hives.
• Onset of diabetes mellitus.
• Dizziness, confusion, depression.
• Inflammation and ulceration of the urinary bladder or vagina, decreased renal function, urinary disorders.
• Pain in the joints, muscle pain, osteoporosis (reduction of 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, alterations in wound healing, decrease in the number of antibodies in the blood.
• Visual disturbances.
• Inflammation of the sac around the heart, accumulation of fluid in the sac around the heart.
• Low blood pressure.
• Pulmonary fibrosis, pneumonia caused by a specific microorganism (Pneumocystis carinii pneumonia), respiratory difficulty, and bronchial asthma, accumulation of fluid in the sac around the lung.
• Electrolyte disturbances.

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

• Severe bleeding, toxic megacolon (toxic and acute dilation of the intestine).
• Stevens-Johnson syndrome, increased nail pigmentation, inflammation of the cuticles, furunculosis (deep infection of the hair follicles), visible enlargement of small blood vessels.
• Local injury at the injection site (formation of sterile abscesses, changes in fatty tissue) after injection into a muscle or under the skin.
• Visual disturbance, pain, loss of strength or sensation of numbness or tingling/sensitivity to stimuli less than normal, taste disturbances (metallic taste), seizures, paralysis, severe headache with fever.
• Retinopathy (non-inflammatory disorder of the eyes).
• Sudden drop in the number of white blood cells, severe bone marrow depression.
• Lymphoproliferative disorders (excessive increase in white blood cells).
• Loss of sexual appetite, impotence, increased male breast size (gynecomastia), altered sperm formation, menstrual disorders, vaginal discharge.
• Increased size of lymph nodes (lymphoma).

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

• Leukoencephalopathy (a disease of the white matter of the brain).
• Pulmonary hemorrhage.
• Jawbone injury (secondary to excessive increase in white blood cells).
• Redness and peeling of the skin.
• Destruction of tissue at the injection site.
• Swelling.

When methotrexate is administered intramuscularly, local adverse reactions (burning sensation) or injuries (formation of sterile abscesses, destruction of fatty tissue) may frequently occur at the injection site. Subcutaneous administration of methotrexate is well tolerated locally. Only mild local skin reactions were 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 it is a possible adverse effect not listed in this leaflet. You can also report them directly through the Spanish Pharmacovigilance System for Human Use Medicines. https://www.notificaram.es. By reporting adverse effects, you can contribute to providing more information on the safety of this medicine.

5. Storage of Quinux

Keep this medicine out of sight and reach of children.

Do not store above 25°C. Keep 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 expiration date stated on the packaging after CAD. The expiration date is the last day of the month indicated.

Medicines should not be disposed of via wastewater or household waste. Deposit the packaging and medicines you no longer need at the SIGRE collection point in your pharmacy or any other system for collecting medicinal waste. If in doubt, ask your pharmacist how to dispose of the packaging and medicines you no longer need. This will help protect the environment.

6. Package contents and additional information

Composition of Quinux

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

1 pre-filled syringe of 0.8 ml of solution contains 20 mg of methotrexate.

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

Appearance of the product and package contents

The 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 package contains 1 or 4 pre-filled syringe(s) with 0.8 ml of solution, with subcutaneous injection needles attached and alcohol-impregnated cotton balls.

Each package contains 1 or 4 pre-filled syringe(s) with 0.8 ml of solution, with subcutaneous injection needles attached with a safety system and alcohol-impregnated cotton balls.

Only some package sizes may be marketed.

Marketing authorization holder and manufacturer

Marketing authorization holder

Especialidades Farmacéuticas Centrum, S.A.

C/ Sagitario, 14

03006, Alicante

SpainAsacpharma Group

Tel.: 965288160; Fax.: 965286434

Manufacturer

Especialidades Farmacéuticas Centrum, S.A.

C/ Sagitario, 14

03006, Alicante

Spain

Date of the last revision of this leaflet: October 2024.

Detailed information about this medicine is available on the website of the Spanish Agency for 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 application 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 the necessary elements before starting:

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

Wash your hands carefully. Before using it, check the Quinux syringe for visible defects (or cracks).

Injection site

The best places for injection are:

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

• If someone is helping you with the injection, they can also administer the injection in the back of the arm, just below the shoulder.
• Change the injection site for each injection. This can reduce the risk of developing irritations at the injection site.
• Never administer the injection in painful, bruised, red, hardened, or scarred skin. If you have psoriasis, do not attempt to inject directly into lesions or elevated, thickened, red, or scaly skin patches.

Injection of the solution

1. Open the box containing the pre-filled syringe of methotrexate and read the leaflet carefully. Remove the pre-filled syringe from the package at room temperature.
2. Disinfection: select an injection site and disinfect it with the alcohol-impregnated cotton ball. Wait 60 seconds for the disinfectant to dry.

1. Carefully remove the protective plastic cap, gently twisting it 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 quickly insert the needle at a 90-degree angle.

1. Injection: insert the needle fully into the skin fold. Slowly push the plunger and 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 cap will automatically enclose the needle.

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

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

Elimination and other handling

The handling and elimination of the medicine and the pre-filled syringe will be carried out in accordance with local regulations for cytotoxic agents. Pregnant healthcare personnel should not handle or administer Quinux.