Package Insert: Information for the Patient

CelecoxibCombix200 mg Hard EFG Capsules

Read this package insert carefully before taking 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 who may 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.

CelecoxibCombixis indicated in adults for relieving the symptoms and signs ofrheumatoid arthritis, osteoarthritis, and ankylosing spondylitis.

CelecoxibCombixcontains celecoxib as the active ingredient and belongs to a class of medications known as nonsteroidal anti-inflammatory drugs (NSAIDs), specifically the subgroup known as 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. CelecoxibCombixacts by reducing the production of prostaglandins, thereby reducing pain and inflammation.

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

Do not take CelecoxibCombix

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

• if you are allergic to celecoxib or any of the other components of this medication (including those 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 hemorrhage.
• 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 itchy skin rash, facial swelling, lip, 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.
• 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 problems such as: heart failure, diagnosed ischemic heart disease, or cerebrovascular disease, e.g. you have been diagnosed with a heart attack, stroke, or transient ischemic attack (temporary decrease in blood flow to the brain; also known as “mini-stroke”), angina pectoris, 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 on the arteries of your legs

Warnings and precautions

Consult your doctor or pharmacist before starting to take CelecoxibCombix:

• if you have previously had a stomach or intestinal ulcer or hemorrhage (Do not take celecoxibif you currently have a stomach or intestinal ulcer or hemorrhage).
• if you are taking acetylsalicylic acid (even at low doses as a heart protector)
• if you are receiving medications to reduce blood clotting (e.g. warfarin)
• if you are taking celecoxib at the same time as other non-acetylsalicylic acid anti-inflammatory medications such as ibuprofen or diclofenac. You should avoid concurrent use of these medications
• 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 an illness 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 celecoxib can mask fever or other signs of infection and inflammation
• if you are over 65 years old, your doctor may want to monitor you regularly.

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).Most of the severe liver reactions occurred in the first month of treatment.
CelecoxibCombixmay 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 and breastfeeding).

Children and adolescents

Celecoxib is only for adults, not for children.

Taking CelecoxibCombixwith other medications

Some medications may affect the effect of other medications. Inform your doctor or pharmacist if you are using, have used recently, or may need to use any other medication.

• Dextromethorphan (used to treat cough)
• ACE inhibitors or angiotensin II receptor antagonists (medications used to treat hypertension and heart failure)
• Diuretics (used to eliminate excess fluid from the body)
• Fluconazole and rifampicin (used to treat infections caused by bacteria and fungi)
• Warfarin or other oral anticoagulants (agents that reduce blood clotting)
• 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 suppress the immune system, e.g. after transplants)

Celecoxib 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.

CelecoxibCombixshould 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 celecoxib, you should discontinue treatment and contact your doctor for alternative treatment.
CelecoxibCombixshould not be taken during breastfeeding.

Driving and operating machinery

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

CelecoxibCombixcontains lactose. If your doctor has told you that you have an intolerance to certain sugars, consult with him 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 the action of celecoxib is too strong or too 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 celecoxib for longer than necessary to control your symptoms.

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

The recommended dose is:

For the treatment of arthritis

The usual dose is 200 mg per day (1 capsule of 200 mgonce a day).

If necessary, your doctor may increase the dose up to a maximum of 400 mg (1 capsule of 200 mgtwice a day).

For the treatment of rheumatoid arthritis

The usual dose is 200 mg per day (1 capsule of 100 mgtwice a day. This initial recommended dose of 100 mg twice a day cannot be administered with this medication. Please consult your doctor).

If necessary, your doctor may increase it up to a maximum of 400 mg (1 capsule of 200 mgtwice a day).

For the treatment of ankylosing spondylitis

The usual dose is 200 mg per day (1 capsule of 200 mgonce a day).
If necessary, your doctor may increase it up to a maximum of 400 mg (1 capsule of 200 mgtwice a dayortwocapsulesof200mgonceaday).

Maximum daily dose

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

Patients with kidney or liver problems

Make sure your doctor knows if you have kidney or liver problems 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.

Use in children

Celecoxib is only for adults, not indicated for children.

Administration form

This medication is taken orally. The capsules must be swallowed whole with a glass of water. The capsules are taken at any time of the day, with or without food. However, try to take each dose of CelecoxibCombixat the same hour every day.

If you take more CelecoxibCombixthan 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 ingested.

If you forgot to take CelecoxibCombix

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 CelecoxibCombix

Stopping treatment abruptly with celecoxib may cause a worsening of symptoms. Do not stop taking celecoxib 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, this medication may cause side effects, although not everyone will experience them.

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

Stop taking celecoxib and immediately inform your doctor if you experience any of the following side effects:

• A hypersensitivity reaction such as skin rash, facial swelling, wheezing, or difficulty breathing.
• Cardiovascular 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)

Frequent side effects (may affect more than 1 in 10 people):

• Increased 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 runny nose, sore throat, cough, cold, flu-like symptoms
• Dizziness, difficulty sleeping
• Vomiting*, stomach pain, diarrhea, indigestion, gas
• Rash, itching
• Muscle stiffness
• Difficulty swallowing*
• Worsening of existing allergies

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

• Stroke*
• Heart failure, palpitations (perception of heartbeats), tachycardia (rapid heart rate)
• Worsening of high blood pressure
• 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
• Elevated potassium levels in blood test results (may cause nausea, fatigue, muscle weakness, or palpitations)
• Blurred or altered vision, tinnitus (ringing in the ears), mouth pain and ulcers, difficulty hearing*
• Constipation, belching, stomach inflammation (indigestion, stomach pain, or vomiting), worsening of stomach or intestinal inflammation
• Leg cramps
• Rash with itching and elevation (urticarial hives)

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

• Ulcers (bleeding) in the stomach, throat, or intestines; or intestinal rupture (may cause stomach pain, fever, nausea, vomiting, intestinal obstruction), dark or black stools, throat inflammation (may cause difficulty swallowing), pancreatic inflammation (may cause stomach pain)
• Decreased white blood cell count (which helps protect the body from infections) and platelet count (increases the risk of bleeding and petechiae)
• Difficulty with muscle coordination of movements
• Confusion, altered taste
• Increased sensitivity to light
• Hair loss

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

• Cerebral hemorrhage leading to death
• Severe allergic reactions (including potential anaphylactic shock) that may cause skin rash, facial swelling, lips, mouth, tongue, or throat swelling, wheezing, or difficulty breathing; difficulty swallowing
• Gastrointestinal hemorrhage (may cause stools or vomit with blood), intestinal or colon inflammation, nausea
• 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 (hairy, red, and swollen area with numerous small pustules)
• A delayed hypersensitivity 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))
• Liver failure, severe liver damage, and liver inflammation (sometimes with fatal outcome or requiring liver transplant). Symptoms may include nausea, diarrhea, jaundice, dark urine, pale stools, easy bruising, or itching
• Renal problems (possible kidney failure, kidney inflammation)
• Pulmonary embolism (blood clots in the lungs' blood vessels). Symptoms may include sudden difficulty breathing, sharp chest pain, or collapse (circulatory obstruction of the pulmonary vessels)
• Irregular heart rhythm
• Meningitis (inflammation of the membrane surrounding the brain and spinal cord)
• Hallucinations
• Worsening of epilepsy (seizures possibly more frequent and/or severe)
• Severe vascular inflammation (may cause fever, pain, and purplish spots on the skin)
• Obstruction of an artery or vein in the eye leading to partial or complete vision loss, conjunctival inflammation, hemorrhage
• Decreased red and white blood cell count and platelet count (may cause fatigue, frequent nosebleeds, easy bruising, and increased risk of infections)
• Chest pain -Altered sense of taste
• Decoloration of the skin (petechiae), muscle pain and weakness, joint pain
• Menstrual disorders
• Headache, flushing
• Low sodium levels in blood test results (may cause loss of appetite, headache, nausea, muscle cramps, and weakness)

The side effects reported in clinical trials in which celecoxib was administered at a dose of 400 mg per day for more than 3 years in patients with non-arthritis-related diseases or other arthritic conditions were:

Frequent side effects (may affect up to 1 in 10 people):

• Cardiovascular problems: angina pectoris (chest pain)
• Gastrointestinal problems: irritable bowel syndrome (may include abdominal pain, diarrhea, indigestion, and gas)
• Kidney stones (which 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 (which may cause stomach irritation or ulcers in the stomach and intestines)
• Lower limb fractures
• Herpes, skin infection, eczema (dry, itchy rash), pneumonia (chest infection, possibility of cough, fever, difficulty breathing)
• Flies in the eye causing vision disturbance or blurred vision, vertigo due to inner ear problems, ulcers, inflammation, or bleeding of the gums, mouth ulcers
• Excessive nighttime urination, heavy menstrual bleeding, frequent bowel movements
• Fatty lumps in the skin or other areas, ganglion cyst (non-painful inflammation in the joints or tendons or around them, in the hand or foot) difficulty speaking, abnormal or very heavy vaginal bleeding, chest pain
• Elevated 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 leaflet. You can also report them directly through the Spanish System for the Pharmacovigilance of Medicinal Products 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.

No special storage conditions are required.

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

Medications should not be disposed of through drains or in the trash. Dispose of the packaging and medications you no longer need at the SIGRE collection pointat the pharmacy. If in doubt, ask your pharmacist how to dispose of the packaging and medications you no longer need. By doing so, you will help protect the environment.

Composition of CelecoxibCombix

• The active ingredient is celecoxib. Each capsule contains 200 mg of celecoxib.
• The other components (excipients) are: lactose monohydrate, sodium lauryl sulfate, povidone K-30, sodium croscarmelloseand magnesium stearate. The capsule coating contains: gelatin, titanium dioxide (E171),sodium lauryl sulfateandwater.The printing ink contains: shellac lacquer (E904), iron oxide black (E172), anhydrous ethanol, propylene glycol, isopropyl alcohol, butyl alcohol and potassium hydroxide (E525).

Appearance of the product and contents of the packaging

Hard, opaque, white capsules with the mark “200” printed in black ink on the capsule body.inblackink.

OPA/AL/PVC-Aluminum (standard and perforated) blisters and PVC/PVDC-Aluminum (standard and perforated) blisters.

Packages containing 20 and 30 capsules.

Only some package sizes may be marketed.

Marketing Authorization Holder

Combix, S.L.U.

C/ Badajoz, 2. Edificio 2.

28223 Pozuelo de Alarcón (Madrid)

Spain

Responsible for Manufacturing

Zydus France

ZAC Les Hautes Patures

Parc dactivités des Peupliers

25 Rue des Peupliers

92000 Nanterre

France

or

Centre Spécialités Pharmaceutiques

ZAC des Suzots

35 rue de la Chapelle

63450 Saint Amant Tallende

France

Last review date of this leaflet:March 2014

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