Package Insert: Information for the User

Celecoxib OPKO100 mg Hard EFG Capsules

Celecoxib OPKO200 mg Hard EFG Capsules

Read this package insert carefully before starting to take 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, pharmacist, or nurse.
• 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, pharmacist, or nurse even if they are not listed in this package insert. See section 4.

1. What isCelecoxib OPKOand what is it used for

2. What you need to know before starting to takeCelecoxib OPKO

3. How to takeCelecoxib OPKO

4. Possible adverse effects

5. Storage ofCelecoxib OPKO

6. Contents of the package and additional information

Celecoxib OPKObelongs to a class of medications known as nonsteroidal anti-inflammatory drugs (NSAIDs), specifically 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.Celecoxib OPKOacts by reducing the production of prostaglandins, thereby reducing pain and inflammation.

Celecoxib OPKOis indicated in adults for relieving the symptoms ofrheumatoid arthritis, osteoarthritis, and ankylosing spondylitis.

The medication will start to take effect a few hours after taking the first dose, but you may not experience a complete effect until several days have passed.

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

Do not takeCelecoxib OPKO

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

• 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 a 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, or bleeding in the stomach or intestines
• if you have previously experienced any of the following symptoms as a result of taking acetylsalicylic acid or any other nonsteroidal anti-inflammatory drug (NSAID): asthma, nasal polyps, severe nasal congestion or rhinorrhea, or allergic symptoms such as skin rash with itching, 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 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 decrease in blood flow to the brain; also known as a "mini-stroke"), angina, or obstruction of the blood vessels to the heart or brain
• if you have or have had peripheral artery disease or if you have been operated on to remove the arteries in your legs

Warnings and precautions

Consult your doctor or pharmacist before starting to takeCelecoxib OPKO:

• if you have previously had a stomach or intestinal ulcer or bleeding (do not take Celecoxib OPKO 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 antiplatelet therapies
• if you are receiving medications to reduce blood clotting (e.g., warfarin/anticoagulant analogs or new oral anticoagulants, e.g., apixaban)
• if you are receiving corticosteroids (e.g., prednisone)
• if you are taking Celecoxib OPKO at the same time as other non-acetylsalicylic acid NSAIDs 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 Celecoxib OPKO 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 on it.

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 onset of the event was reported, most severe liver reactions occurred in the first month of treatment.

Celecoxib OPKO 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 and breastfeeding).

TakingCelecoxib OPKOwith other medications

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)

Celecoxib OPKO can be taken with low doses of acetylsalicylic acid (75 mg daily or less). Ask your doctor for advice 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

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

Breastfeeding

Celecoxib OPKO should not be used during breastfeeding.

Fertility

NSAIDs, including Celecoxib OPKO, 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 Celecoxib OPKO before driving or operating machinery. If you feel dizzy or drowsy after taking Celecoxib OPKO, do not drive or operate machinery until these effects pass.

Celecoxib OPKO contains lactose

This medication contains lactose (a type of sugar). If your doctor has told you that you have a lactose intolerance, consult with them before taking this medication.

Celecoxib OPKO contains sodium

This medication contains less than 1 mmol ofsodium(23 mg) per dose; that is, 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. If you think or believe that the action ofCelecoxib OPKOis 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 takeCelecoxib OPKOfor longer than necessary to control symptoms.

Administration form:

Celecoxib is for oral use.The capsules are taken at any time of the day, with or without food. However, try to take each dose of celecoxib at the same time every day.

If you have difficulty swallowing the capsules: you can spread the entire content of the capsule on a teaspoon 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 water approximately 240 ml.

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:

For arthritisthe recommended dose is 200mg per day, if necessary, your doctor may increase it up to a maximum of 400 mg.

The dose is usually:

• one capsule of 200mg once a day or
• one capsule of 100mg twice a day.

For rheumatoid arthritis: the recommended dose is 200mg per day, taken in 2 separate doses, if necessary, your doctor may increase it up to a maximum of 400 mg.

The dose is usually:

• one capsule of 100mg twice a day.

For ankylosing spondylitis:the recommended dose is 200mg per day, if necessary, your doctor may increase it up to a maximum of 400 mg.

The dose is usually:

• one capsule of 200mg once a day or
• one capsule of 100mg twice a day.

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

Patients over 65 years, 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:

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

If you take moreCelecoxib OPKOthan you should

If you accidentally take too much medication, inform your doctor or pharmacist or contact the nearest hospital's emergency service for advice.

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 takeCelecoxib OPKO

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 withCelecoxib OPKO

The abrupt interruption of treatment withCelecoxibOPKOmay cause a worsening of symptoms. Do not stop taking Celecoxib OPKO unless your doctor tells you to. Your doctor will indicate that you reduce the dose over a few days before interrupting 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 tookCelecoxib OPKO. The side effects marked with an asterisk (*) occurred in patients takingCelecoxib OPKOfor the prevention of colon polyps. Patients included in these studies tookCelecoxib OPKOat high doses and for a prolonged period of time.

If you experience any of the following side effects, discontinue treatment withCelecoxib OPKOand inform your doctor immediately:

If you have:

- an allergic reaction such as skin rash, facial swelling, wheezing, 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 (feeling unwell), diarrhea, jaundice (your skin or the white of your eyes appears yellow).

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

- Increase in blood pressure, including worsening of existing high blood pressure*

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

- Heart attack*

- Fluid retention with swelling of ankles, legs, and/or hands

- Urinary tract infection

- Difficulty breathing*, sinusitis (inflammation and infection of the nasal sinuses, obstruction or pain of the nasal sinuses), stuffy nose 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*

- Headache

- Nausea (feeling unwell)

- Joint pain.

- Worsening of existing allergies

- Accidental injury

Rare side effects: may affect up to 1 in 1,000 patients:

- Ulcers (bleeding) in the stomach, throat, or intestines; or intestinal rupture (may cause stomach pain, fever, nausea, vomiting, intestinal obstruction), dark or black stools, inflammation of the pancreas (may cause stomach pain), inflammation of the esophagus

- Low sodium levels in blood test results (a condition known as hyponatremia)

- Decreased white blood cell count and platelet count (may cause fatigue, easy bruising, frequent nosebleeds, and increased risk of infections)

- Difficulty in muscle coordination of movements

- Feeling of confusion, taste alterations

- Increased sensitivity to light

- Hair loss

- Hallucinations

- Eye bleeding

- Acute reaction that may lead to pulmonary inflammation

- Irregular heart rhythm

- Rubor

- Blood clots in the pulmonary blood vessels. Symptoms may include sudden difficulty breathing, sharp chest pain, or collapse

- Bleeding in the stomach or intestines (may cause stools or vomit with blood), intestinal or colon inflammation

- Severe liver inflammation (hepatitis). Symptoms may include nausea (feeling unwell), diarrhea, jaundice (your skin or the white of your eyes appears yellow), dark urine, pale stools, easy bruising, itching, or chills

- Acute kidney failure

- Menstrual disorders

- Swelling in the face, lips, mouth, tongue, or throat, wheezing, or difficulty swallowing

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

- Severe allergic reactions (including potential life-threatening 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 delayed allergic reaction with possible symptoms such as rash, facial swelling, fever, swollen lymph nodes, and abnormalities in clinical tests (e.g., liver, blood cells (eosinophilia, a type of increased blood cell count)

- Brain bleeding that causes death

- Meningitis (inflammation of the membrane surrounding the brain and spinal cord)

- Liver failure, liver damage, and severe liver inflammation (hepatitis fulminant) (sometimes with fatal outcome or requiring liver transplant). Symptoms may include nausea (feeling unwell), diarrhea, jaundice (your skin or the white of your eyes appears yellow), dark urine, pale stools, easy bruising, itching, or chills

- Liver 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 kidney 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 that leads to partial or complete loss of vision

- Inflammation of blood vessels (may cause fever, pain, and purple spots on the skin)

- Decreased red and white blood cell count and platelet count (may cause fatigue, easy bruising, frequent nosebleeds, and increased risk of infections)

- Muscle pain and weakness

- Alteration of taste

- Loss of taste

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

- Decreased female fertility, which is usually reversible, and is usually reversible if discontinued

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

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

- Heart 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 patients:

- Deep vein thrombosis (blood clotting usually in the leg, which may cause pain, swelling, or redness of the calf or problems 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 that cause vision disturbance or blurred vision, vertigo due to inner ear problems, ulcers, inflammation, or bleeding of the gums, mouth ulcers

- Nocturia (excessive nighttime urination), frequent nosebleeds, frequent bowel movements

- Lipomas (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 that does not appear in this leaflet. You can also report them directly through the Spanish System for the 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 use this medication after the expiration date that appears on the packaging, bottle, and blister pack, after CAD. The expiration date is the last day of the month indicated.

Do not store at a temperature above 30°C.

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

Composition ofCelecoxib OPKO

The active ingredient is celecoxib.

Each hard capsule contains 100 mg or 200 mg of celecoxib.

The other components (excipients) are:

monohydrate lactose, hydroxypropyl cellulose, crospovidone, povidone, sodium lauryl sulfate, magnesium stearate. The capsule coating contains titanium dioxide (E171), gelatin, and sodium lauryl sulfate. The printing ink contains shellac lacquer, propylene glycol, strong ammonia solution, aluminum lake FD&C blue (100 mg dose) and yellow iron oxide (200 mg dose).

Appearance of the product and contents of the package

Celecoxib OPKO 100 mg:The hard gelatin capsules, size 4, have an opaque white cap and a blue band with the imprint "C5" and an opaque white body with a blue band and the inscription "100 mg", filled with white to almost white powder.

Celecoxib OPKO 200 mg:The hard gelatin capsules, size 2, have an opaque white cap and a yellow band with the imprint “C6” and an opaque white body with a blue band and the inscription “200 mg”, filled with white or almost white powder.

This medicine may be presented in PVC/PVDC/Aluminum blisters containing 20, 40, 50, 60, and 100 hard capsules (100 mg dose) and 10, 20, 30, 50, and 100 hard capsules (200 mg dose).

Only some package sizes may be commercially available.

Marketing Authorization Holder

OPKO HEALTH SPAIN, S.L.U.

Pl. Europa 13-15, 08908

L’Hospitalet de Llobregat (Barcelona)

Spain

Responsible for manufacturing

Macleods Pharma UK Limited

Wynyard Park House,

Wynyard Avenue,

Wynyard, Billingham,

TS22 5TB, United Kingdom

or

Synoptis Industrial Sp. z o.o

ul. Rabowicka 15,

Swarzedz, 62-020,

Poland

or

Laboratori Fundació Dau

C/ C, 12-14 Pol. Ind. Zona Franca

08040, Barcelona,

Spain.

This medicine is authorized in the member states of the European Economic Area with the following names:

Spain:Celecoxib OPKO100 mg/200 mg hard capsules EFG

Germany:Celecoxib Heumann 100 mg/200 mg Hartkapseln

Italy:Celecoxib Maxmind 100 mg/200 mg rigid capsules

United Kingdom:Celecoxib 100 mg/200 mg capsules, hard

Last review date of this leaflet: March 2023

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/