Package Insert: Information for the Patient

Meticel 200 mg Hard Capsules EFG

Celecoxib

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

• Keep this package insert as you may need to read it again.
• If you have any questions, consult your doctor or pharmacist.
• This medication has been prescribed only for you and should not be given 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.Seesection4.

Meticel is indicatedin adultsto relieve the symptoms and signs ofrheumatoid arthritis, osteoarthritis, and ankylosing spondylitis.

Meticel belongs to a class of medications known as nonsteroidal anti-inflammatory drugs (NSAIDs), and specifically to the subgroup known as selective cyclooxygenase-2 (COX-2) inhibitors. The body produces prostaglandins that can cause pain and inflammation. In conditions such as rheumatoid arthritis or osteoarthritis, the body produces them in greater quantities. Meticel acts by reducing the production of prostaglandins, thereby reducing pain and inflammation.

You should wait for this medication to start taking effect a few hours after taking the first dose, but you may not experience a complete effect for several days.

Your doctor has prescribed Meticel. The following information will help you get better results with Meticel. If you have any other questions, please ask your doctor or pharmacist.

Do not take Meticel

Inform your doctor if any of the following circumstances affect you, as patients with these conditions should not take Meticel.

• if you are allergic to celecoxib or any of the other components of this medication (listed in section 6)
• if you have had any allergic reaction to any medication in the group called “sulfonamides” (e.g. some antibiotics used to treat infections)
• if you currently have a stomach or intestinal ulcer or bleeding
• if you have previously experienced any of the following symptoms as a result of taking acetylsalicylic acid or any other anti-inflammatory medication: asthma, nasal polyps, severe nasal congestion, or allergic symptoms such as skin rash with itching, facial swelling, lips, tongue, or throat swelling, difficulty breathing, or wheezing
• if you are pregnant. If you can become pregnant during treatment, you should discuss the use of contraceptive methods with your doctor
• if you are breastfeeding your child
• if you have severe liver disease
• if you have severe kidney disease
• if you have inflammatory bowel disease such as ulcerative colitis or Crohn's disease
• if you have heart failure, diagnosed coronary artery disease, or cerebrovascular disease, for example, if you have been diagnosed with a heart attack, stroke, or transient ischemic attack (temporary reduction in blood flow to the brain; also known as “mini-stroke”), angina, or obstruction of blood vessels to the heart or brain
• if you have or have had circulation problems (peripheral arterial disease) or if you have been operated on to clear the arteries in your legs

Warnings and precautions

Consult your doctor before starting to take Meticel:

• if you have previously had a stomach or intestinal ulcer or bleeding (Do not take Meticel if you currently have a stomach or intestinal ulcer or bleeding)
• if you are taking acetylsalicylic acid (even at low doses as a heart protector)
• if you are taking medications to reduce blood clotting (e.g. warfarin/anticoagulant analogs or oral anticoagulants, e.g. apixaban)
• if you are taking corticosteroids (e.g. prednisone)
• if you are taking Meticel at the same time as other non-acetylsalicylic acid anti-inflammatory medications such as ibuprofen or diclofenac. You should avoid using these medications together
• if you are a smoker, have diabetes, high blood pressure, or high cholesterol
• if your heart, liver, or kidneys are not functioning well, your doctor may want to monitor you regularly
• if you have fluid retention (e.g. swollen feet or ankles)
• if you are dehydrated, for example, due to a disease with vomiting, diarrhea, or the use of diuretics (used to treat excess fluid in the body)
• if you have had a severe allergic reaction or a severe skin reaction to any medication
• if you feel unwell due to an infection or think you have an infection, as taking Meticel may mask fever or other signs of infection and inflammation
• if you are over 65 years old, your doctor may want to monitor you regularly
• the consumption of alcohol and NSAIDs may increase the risk of gastrointestinal problems

Like other anti-inflammatory medications (e.g. ibuprofen or diclofenac), this medication may increase your blood pressure, so your doctor will be able to perform regular checks.

Some cases of severe liver reactions with celecoxib have been reported, including severe liver inflammation, liver damage, and liver failure (some with fatal outcome or requiring liver transplant).Of the cases in which the event was reported when it started, most of the severe liver reactions occurred in the first month of treatment.

Meticel may make it difficult to become pregnant. You should inform your doctor if you plan to become pregnant or if you have difficulty becoming pregnant (see Pregnancy, Breastfeeding, and Fertility sections)

Other medications and Meticel

Inform your doctor or pharmacist if you are taking, have taken recently, or may need to take any other medication:

• Dextromethorphan (used to treat cough)
• ACE inhibitors or angiotensin II receptor antagonists, beta-blockers, and diuretics (medications used to treat hypertension and heart failure)
• Fluconazole and rifampicin (used to treat infections caused by bacteria and fungi)
• Warfarin or other warfarin analogs (agents that reduce blood clotting), including newer medications such as apixaban
• Lithium (used to treat some types of depression)
• Other medications used to treat depression, sleep disorders, high blood pressure, or irregular heartbeat
• Neuroleptics (used to treat some mental disorders)
• Methotrexate (used in rheumatoid arthritis, psoriasis, and leukemia)
• Carbamazepine (used to treat epilepsy/convulsions and some types of pain or depression)
• Barbiturates (used to treat epilepsy/convulsions and some sleep disorders)
• Ciclosporin and tacrolimus (used to treat immunosuppression, e.g. after transplants)

Meticel can be taken with low doses of acetylsalicylic acid (75 mg daily or less). Please consult your doctor before taking both medications together.

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 medication.

Pregnancy
Meticel should not be used by pregnant women or women who may become pregnant (i.e. women of childbearing age who do not use an adequate contraceptive method) during treatment. If you become pregnant during treatment with Meticel, you should discontinue treatment and contact your doctor for alternative treatment.

Breastfeeding

Meticel should not be used during breastfeeding.

Fertility

NSAIDs, including Meticel, may make it difficult to become pregnant. You should inform your doctor if you plan to become pregnant or if you are having difficulty becoming pregnant.

Driving and operating machinery

You should know how you react to Meticel before driving or operating machinery. If you feel dizzy or drowsy after taking Meticel, do not drive or operate machinery until these effects pass.

Meticel contains lactose

This medication contains lactose. If your doctor has told you that you have an intolerance to certain sugars, consult with them before taking this medication.

Follow exactly the administration instructions of this medication as indicated by your doctor. In case of doubt, consult your doctor or pharmacist again. If you think or believe that Meticel's action is too strong or weak, inform your doctor or pharmacist.

Your doctor will indicate the dose you should take. Since the risk of adverse effects associated with heart problems may increase with the dose and duration of treatment, it is essential to use the lowest dose that controls your pain and do not take Meticel for longer than necessary to control symptoms.

Administration Form

Meticel must be administered orally. The capsules are taken at any time of the day with or without food. However, try to take each dose of Meticel at the same time every day.

If you have difficulty swallowing the capsules: you can spread the entire content of the capsule on a spoonful of some semi-solid food (such as apple sauce, rice, yogurt, or mashed banana at room temperature) and swallow it immediately with a glass of approximately 240 ml of water.

To open the capsule, hold it in a vertical position to keep the granules at the bottom; then press the top and turn it to extract it, being careful not to spill the content.Do not chew or crush the granules.

Contact your doctor if, after two weeks since the start of treatment, you do not experience an improvement.

The recommended dose is:

The usual dose for the treatment of osteoarthritisis 200 mg per day, if necessary, your doctor may increase it up to a maximum of 400 mg.

The usual dose is:

• one 200 mg capsuleonce a day.

The usual dosefor the treatment of rheumatoid arthritisis 200 mg per day (administered in 2 doses), if necessary, your doctor may increase it up to a maximum of 400 mg:

The usual dose is:

• one 100 mg capsule twice a day(this 100 mg dose of celecoxib twice a day cannot be administered with this medication. For this treatment regimen, there are other medications with a concentration of 100 mg of celecoxib. Please consult your doctor).

Theusual doseforthe treatment of ankylosing spondylitisis 200 mg per day, if necessary, your doctor may increase it up to a maximum of 400 mg.

The usual dose is:

one 200 mg capsuleonce a day.

Problems with the kidneys or liver:make sure your doctor knows if you have problems with the liver or kidneys since you may need a lower dose.

Patients over 65 years old, especially those weighing less than 50 kg:your doctor may want to monitor you more closely if you are over 65 years old and especially if you weigh less than 50 kg.

You should not take more than 400 mg of celecoxib per day.

Use in children

Meticel is only for adults, it is not indicated for children.

If you take more Meticel than you should

You should not take more capsules than indicated by your doctor. If you take more capsules than you have been told, consult your doctor, pharmacist, or hospital immediately and bring the medication with you.

In case of overdose or accidental ingestion, consult your doctor or pharmacist immediately or call the Toxicological Information Service (phone 91 562 04 20), indicating the medication and the amount taken.

If you forgot to take Meticel

If you forgot to take a capsule, take it as soon as you remember. Do not take a double dose to compensate for the missed doses.

If you interrupt the treatment with Meticel

Stopping the treatment with Meticel abruptly may cause a worsening of symptoms. Do not stop taking Meticel unless your doctor tells you to. Your doctor will indicate that you reduce the dose over a few days before stopping treatment completely.

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

Like all medications,thismedicationmay cause side effects, although not everyone will experience them.

The side effects listed below were observed in patients with arthritis who tookcelecoxib. The side effects marked with an asterisk (*) occurred in patients takingcelecoxibfor the prevention of colon polyps and have been classified based on the highest frequency of occurrence. Patients included in these studies tookcelecoxibat high doses and for a prolonged period of time.

If you experience any of the following side effects, discontinue treatment with Meticel and inform your doctor immediately:

If you have:

• a skin rash, facial swelling, hives, or difficulty breathing.
• heart problems, such as chest pain
• severe stomach pain or any sign of bleeding in the stomach or intestines, such as dark urine or stools with blood, or blood in the vomit.
• a skin reaction, such as rash, blisters, or skin peeling.
• liver failure (symptoms may include nausea, diarrhea, jaundice, dark urine, pale stools, easy bruising, or itching)

Very common side effects:may affect more than 1 in 10people:

• Increased blood pressure, including worsening of existing high blood pressure*

Common side effects:may affect up to 1 in 10 people:

• Myocardial infarction*
• Fluid retention with swelling of ankles, legs, and/or hands
• Urinary tract infection
• Difficulty breathing*, sinusitis (inflammation and infection of the paranasal sinuses, obstruction or pain of the paranasal sinuses), nasal congestion or discharge, sore throat, cough, cold, flu-like symptoms
• Dizziness, difficulty sleeping
• Vomiting*, stomach pain, diarrhea, indigestion, gas
• Rash, itching
• Muscle stiffness
• Difficulty swallowing*
• Headache
• Nausea (sensation of discomfort)
• Joint pain
• Worsening of existing allergies
• Accidental injury

Rare side effects:may affect up to 1 in 100 people:

• Stroke*
• Cardiac insufficiency, palpitations (perception of heartbeats), tachycardia
• Abnormal liver function test results
• Abnormal kidney function test results
• Anemia (changes in red blood cells that may cause fatigue and difficulty breathing)
• Anxiety, depression, fatigue, numbness, tingling
• High potassium levels in blood test results (may cause nausea, fatigue, muscle weakness, or palpitations)
• Blurred or altered vision, tinnitus, mouth pain and ulcers, difficulty hearing*
• Constipation, belching, stomach inflammation (indigestion, stomach pain, or vomiting), worsening of stomach or intestinal inflammation
• Leg cramps
• Urticarial hives (hives with itching and raised lesions)
• Eye inflammation
• Difficulty breathing
• Decoloration of the skin (cardenales)
• Chest pain (generalized pain not related to the heart)
• Facial swelling

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

• Ulcers (bleeding) in the stomach, esophagus, or intestines; or intestinal rupture (may cause stomach pain, fever, nausea, vomiting, intestinal obstruction), dark or black stools, pancreatitis (may cause stomach pain), pharyngitis (may cause difficulty swallowing)
• Low sodium levels in the blood (a condition known as hyponatremia)
• Decreased white blood cell and platelet count (increases the risk of bleeding and cardenales)
• Difficulty in muscle coordination of movements
• Confusion, altered taste
• Increased sensitivity to light
• Hair loss
• Alucinations
• Eye hemorrhage
• Acute reaction that may lead to pulmonary inflammation
• Irregular heartbeat
• Rubefaction
• Pulmonary embolism (blood clots in the lungs). Symptoms may include sudden difficulty breathing, sharp chest pain, or collapse.
• Stomach or intestinal hemorrhage (may cause stools or vomit with blood), intestinal or colon inflammation
• Severe liver inflammation (hepatitis). Symptoms may include nausea, diarrhea, jaundice, dark urine, pale stools, easy bruising, itching, or chills
• Acute kidney failure
• Menstrual disorders
• Facial, lip, mouth, tongue, or throat swelling or difficulty swallowing

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

• Severe allergic reactions (including potentially fatal anaphylactic shock)
• Severe skin alterations, such as Stevens-Johnson syndrome, exfoliative dermatitis, and toxic epidermal necrolysis (may cause rash, blistering, or skin peeling) and acute generalized pustular psoriasis (symptoms include skin redness with swollen areas and numerous small pustules)
• A late-onset allergic reaction with possible symptoms such as rash, facial swelling, fever, swollen lymph nodes, and abnormal laboratory test results (e.g., liver, blood cells (eosinophilia, a type of increased white blood cell count))
• Cerebral hemorrhage leading to death
• Meningitis (inflammation of the membrane surrounding the brain and spinal cord)
• Acute liver failure, liver damage, and severe liver inflammation (hepatitis fulminant) (sometimes with fatal outcome or requiring liver transplant). Symptoms may include nausea, diarrhea, jaundice, dark urine, pale stools, easy bruising, itching, or chills
• Hepatic problems (such as cholestasis and cholestatic hepatitis, which may be accompanied by symptoms such as pale stools, nausea, and yellow discoloration of the skin or eyes)
• Kidney inflammation and other renal problems (such as nephrotic syndrome and minimal change disease, which may be accompanied by symptoms such as fluid retention (edema), foamy urine, fatigue, and loss of appetite)
• Worsening of epilepsy (seizures possibly more frequent and/or severe)
• Obstruction of an artery or vein in the eye leading to partial or complete vision loss
• Inflammation of blood vessels (may cause fever, pain, and purplish spots on the skin)
• Decreased red and white blood cell and platelet count (may cause fatigue, easy bruising, frequent nosebleeds, and increased risk of infections)
• Muscle pain and weakness
• Altered sense of taste
• Loss of taste

Side effects of unknown frequency: the frequency cannot be estimated from available data:

• Decreased female fertility, which is normally reversible if medication is discontinued

The side effects reported in clinical trials in whichcelecoxibwas administered at a dose of 400mg per day for1to3 years in patients with non-arthritis-related diseases or other arthritic conditions were:

Common side effects:may affect up to 1 in 10 people:

• Cardiac problems: angina pectoris (chest pain)
• Gastrointestinal problems: irritable bowel syndrome (may include abdominal pain, diarrhea, indigestion, and gas)
• Kidney stones (may cause stomach or back pain, blood in the urine), difficulty urinating
• Weight gain

Rare side effects:may affect up to 1 in 100 people:

• Deep vein thrombosis (blood clotting usually in the leg, which may cause pain, swelling, or redness of the calf or difficulty breathing)
• Gastrointestinal problems: stomach infection (may cause stomach irritation or ulcers in the stomach and intestines)
• Fracture of lower limbs
• Herpes, skin infection, eczema (dry, itchy rash), pneumonia (lung infection, possibility of cough, fever, difficulty breathing)
• Flies in the eye causing visual disturbance or blurred vision, vertigo due to inner ear problems, ulcers, inflammation, or bleeding of the gums, mouth ulcers
• Excessive nighttime urination, vaginal bleeding or hemorrhoids, frequent bowel movements
• Fatty lumps in the skin or other areas, ganglion cyst (inflammation not painful in the joints or tendons or around them, in the hand or foot) difficulty speaking, abnormal or very heavy vaginal bleeding, chest pain
• High sodium levels in blood test results

Reporting of side effects

If you experience any type of side effect, consult your doctor or pharmacist, even if it is a possible side effect not listed 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 medication.

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

Do not usethismedicationafter the expiration date that appears on the packagingafter CAD. The expiration date is the last day of the month indicated.

Do not store at a temperature above 30°C.

Medicines should not be disposed of through drains or in the trash. Dispose of packaging and unused medications at the SIGRE collection pointat the pharmacy. If in doubt, ask your pharmacist how to dispose of packaging and unused medications. By doing so, you will help protect the environment..

Composition of Meticel

• The active principle is celecoxib. Each capsule contains 200 mg of celecoxib.
• The other components are: Lactose monohydrate, sodium lauryl sulfate, povidone K30, sodium croscarmellose, magnesium stearate (see section 2, Meticel contains lactose).

The capsule coating contains gelatin and titanium dioxide (E171).

Appearance of the product and content of the container

Meticel is presented in the form of hard capsules.

The capsules are opaqueof white color.

The capsules are presented in PVC-aluminum blisters.

Meticelis presented in containers containing30 capsules

Holder of the marketing authorization and responsible for manufacturing

Laboratorios Alter, S.A.

Mateo Inurria, 30

28036 Madrid

Spain

Date of the last review of this leaflet: August 2018.

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