CELECOXIB OPKO 100 mg HARD CAPSULES

Introduction

Package Leaflet: Information for the User

Celecoxib OPKO100 mg hard capsules EFG

Celecoxib OPKO200 mg hard capsules EFG

Read all of this leaflet carefully before you start taking 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, pharmacist, or nurse.
• 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, pharmacist, or nurse. This includes any possible side effects not listed in this leaflet. See section 4.

Contents of the pack:

1. What is Celecoxib OPKO and what is it used for
2. What you need to know before you take Celecoxib OPKO
3. How to take Celecoxib OPKO
4. Possible side effects
5. Storing Celecoxib OPKO
6. Contents of the pack and other information

1. What is Celecoxib OPKO and what is it used for

Celecoxib OPKO belongs to a group of medicines called non-steroidal anti-inflammatory drugs (NSAIDs), and more specifically to the subgroup known as selective cyclooxygenase-2 (COX-2) inhibitors. Your body produces prostaglandins that can cause pain and inflammation. In conditions such as rheumatoid arthritis or osteoarthritis, your body produces them in larger quantities. Celecoxib OPKO works by reducing the production of prostaglandins, thus reducing pain and inflammation.

Celecoxib OPKO is indicated in adults to relieve the signs and symptoms of rheumatoid arthritis, osteoarthritis, and ankylosing spondylitis.

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

2. What you need to know before you take Celecoxib OPKO

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

Do not takeCelecoxib OPKO

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

• if you are allergic to celecoxib or any of the other ingredients of this medicine (listed in section 6)
• if you have had an allergic reaction to any medicine 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 after taking acetylsalicylic acid or any other non-steroidal anti-inflammatory and analgesic drug (NSAID): asthma, nasal polyps, severe nasal congestion, or allergic symptoms such as skin rash with itching, swelling of the face, lips, tongue, or throat, 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 failure, diagnosed ischemic heart disease, or cerebrovascular disease, e.g., you have been diagnosed with a heart attack, stroke, or transient ischemic attack (temporary reduction in blood flow to the brain; also known as a "mini-stroke"), angina pectoris, or obstruction of the blood vessels to the heart or brain
• if you have or have had circulation problems (peripheral arterial disease) or if you have had surgery on the arteries in your legs

Warnings and precautions

Consult your doctor or pharmacist before takingCelecoxib 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 cardiac protector)
• if you are taking antiplatelet therapies
• if you are receiving medications to reduce blood coagulation (e.g., warfarin/anticoagulants similar to warfarin or new oral anticoagulants, e.g., apixaban)
• if you are taking corticosteroids (e.g., prednisone)
• if you are taking Celecoxib OPKO at the same time as other non-acetylsalicylic NSAIDs such as ibuprofen or diclofenac. The combined use of these medications should be avoided
• if you are a smoker, have diabetes, high blood pressure, or high cholesterol
• if your heart, liver, or kidneys do not function properly, your doctor may want to monitor you regularly
• if you have fluid retention (such as 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 can increase the risk of gastrointestinal problems

Like other anti-inflammatory drugs (e.g., ibuprofen or diclofenac), this medicine may increase your blood pressure, so your doctor may perform periodic blood pressure checks.

Some cases of severe liver reactions have been reported with celecoxib, including severe liver inflammation, liver damage, liver failure (some with a fatal outcome or requiring liver transplantation). Of the cases where the start of the event was reported, most severe liver reactions occurred within the first month of treatment.

Celecoxib OPKO may make it more difficult to become pregnant. You should inform your doctor if you plan to become pregnant or if you are having difficulty becoming pregnant (see section Pregnancy and breastfeeding).

TakingCelecoxib OPKOwith other medicines

Tell your doctor or pharmacist if you are taking, have recently taken, or might take any other medicines:

• Dextromethorphan (used to treat cough)
• ACE inhibitors or angiotensin II receptor antagonists, beta-blockers, and diuretics (medicines used to treat high blood pressure and heart failure)
• Fluconazole and rifampicin (used to treat bacterial and fungal infections)
• Warfarin or other warfarin-like anticoagulants (agents that reduce blood clot formation), including newer oral anticoagulants such as apixaban
• Lithium (used to treat some types of depression)
• Other medicines used to treat depression, sleep disorders, high blood pressure, or irregular heartbeat
• Antipsychotics (used to treat some mental disorders)
• Methotrexate (used in rheumatoid arthritis, psoriasis, and leukemia)
• Carbamazepine (used to treat epilepsy/seizures and some forms of pain or depression)
• Barbiturates (used to treat epilepsy/seizures and some sleep disorders)
• Ciclosporin and tacrolimus (used to suppress the immune system, e.g., after transplants)

Celecoxib OPKOcan be taken with low doses of acetylsalicylic acid (75 mg daily or less). Ask your doctor for advice before taking both medicines 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 medicine.

Pregnancy

Celecoxib OPKO should not be used by pregnant women or women who may become pregnant (i.e., women of childbearing potential who do not use adequate contraception) during treatment. If you become pregnant during treatment with Celecoxib OPKO, you should stop 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 more difficult to become pregnant. You should inform your doctor if you plan to become pregnant or if you are having difficulty becoming pregnant (see section Pregnancy and breastfeeding).

Driving and using machines

You should know how you react to Celecoxib OPKO before driving or using machinery. If you feel dizzy or drowsy after taking Celecoxib OPKO, do not drive or operate machinery until these effects have passed.

CelecoxibOPKOcontains lactose

This medicine contains (a type of sugar). If your doctor has told you that you have an intolerance to some sugars, consult with them before taking this medicine.

CelecoxibOPKOcontains sodium

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

3. How to take Celecoxib OPKO

Follow exactly the administration instructions of this medicine given by your doctor or pharmacist. If you are unsure, consult your doctor or pharmacist again. If you think the effect of Celecoxib OPKO is too strong or too weak, tell your doctor or pharmacist.

Your doctor will tell you what dose to take. Since the risk of side effects associated with heart problems may increase with the dose and duration of treatment, it is important that you use the lowest dose that controls your pain and do not take Celecoxib OPKO for longer than necessary to control the symptoms.

Method of administration:

Celecoxib is for oral use.The capsules can be 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 sprinkle the entire contents of the capsule into a level teaspoon of some semi-solid food (such as apple sauce, rice, yogurt, or mashed banana, cold or at room temperature) and swallow it immediately with a glass of water of approximately 240 ml.

To open the capsule, hold it in a vertical position to keep the granules at the bottom; then squeeze the top and twist it to remove it, being careful not to spill the contents. Do not chew or crush the granules.

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

The recommended dose is:

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

The dose is usually:

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

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

The dose is usually:

• one 100 mg capsule twice a day

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

The dose is usually:

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

Kidney or liver problems:make sure your doctor knows if you have liver or kidney problems, as you may need a lower dose.

Patient 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, especially if you weigh less than 50 kg.

Do not take more than 400 mg of celecoxib per day.

Use in children:

Celecoxib is for adults only; it is not indicated in children.

If you take moreCelecoxib OPKOthan you should

If you accidentally take too much medicine, tell your doctor or pharmacist or contact the nearest hospital emergency department for advice.

In case of overdose or accidental ingestion, consult your doctor or pharmacist immediately or call the Toxicology Information Service, phone: 91 562 04 20, indicating the medicine and the amount ingested.

If you forget to takeCelecoxib OPKO

If you forget to take a capsule, take it as soon as you remember. Do not take a double dose to make up for forgotten doses.

If you stop takingCelecoxib OPKO

Stopping treatment with Celecoxib OPKOabruptly may cause a worsening of symptoms. Do not stop taking Celecoxib OPKO unless your doctor tells you to. Your doctor will tell you to reduce the dose over a few days before stopping treatment completely.

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

4. Possible Adverse Effects

Like all medicines, this medicine can cause adverse effects, although not all people suffer from them.

The adverse effects mentioned below were observed in patients with arthritis who tookCelecoxib OPKO. The adverse effects marked with an asterisk (*) occurred in patients who tookCelecoxib OPKOfor the prevention of colon polyps. The patients included in these studies tookCelecoxib OPKOat high doses and for a prolonged period of time.

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

If you have:

• a allergic reaction such as skin rash, swelling of the face, 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 stained with blood, or blood in the vomit.
• a skin reaction such as rash, blisters or peeling of the skin.
• liver failure (symptoms may include nausea, diarrhea, jaundice (yellowing of the skin or eyes).

Very frequent adverse effects: may affect more than 1 in 10 patients:

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

Frequent adverse effects: may affect up to 1 in 10 patients:

• Heart attack*
• Fluid retention with swelling of ankles, legs and/or hands
• Urinary tract infection
• Difficult breathing*, sinusitis (inflammation and infection of the paranasal sinuses, obstruction or pain of the paranasal 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 of discomfort)
• Pain in the joints.
• Worsening of existing allergies
• Accidental injury

Uncommon adverse effects: may affect up to 1 in 100 patients:

• Stroke*
• Heart failure, palpitations (perception of heartbeat), accelerated heartbeat
• Abnormalities in blood tests related to the liver
• Abnormalities in blood tests related to the kidneys
• Anemia (changes in red blood cells that can cause fatigue and difficulty breathing)
• Anxiety, depression, fatigue, numbness, tingling sensation
• High levels of potassium in blood test results (can cause nausea, fatigue, muscle weakness or palpitations)
• Blurred or altered vision, ringing in the ears, mouth pain or ulcers, difficulty hearing*
• Constipation, belching, stomach inflammation (indigestion, stomach pain or vomiting), worsening of stomach or intestinal inflammation
• Leg cramps
• Rash with itching and relief (urticarial habon)
• Eye inflammation
• Difficulty breathing
• Discoloration of the skin (bruises)
• Chest pain (generalized pain not related to the heart)
• Swelling of the face

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

• Ulcers (bleeding) in the stomach, throat or intestines; or rupture of the intestine (can cause stomach pain, fever, nausea, vomiting, intestinal obstruction), dark or black stools, pancreatitis (can cause stomach pain), esophagitis (inflammation of the esophagus)
• Low levels of sodium in blood test results (a disease known as hyponatremia)
• Decreased number of white blood cells and platelets (increases the possibility of bleeding and bruising)
• Difficulty in muscular coordination of movements
• Feeling of confusion, taste disturbances
• Increased sensitivity to light
• Hair loss
• Hallucinations
• Eye bleeding
• Acute reaction that can lead to pulmonary inflammation
• Irregular heartbeat
• Redness of the skin
• Blood clots in the blood vessels of the lungs. Symptoms may include sudden difficulty breathing, sharp pain when breathing or collapse
• Bleeding in the stomach or intestine (can cause stools or vomit with blood), inflammation of the intestine or colon
• Severe liver inflammation (hepatitis). Symptoms may include nausea, diarrhea, jaundice (yellowing of the skin and eyes), darkened urine, pale stools, ease of bleeding, itching or chills
• Acute kidney failure
• Menstrual disorders
• Swelling in the face, lips, mouth, tongue or throat, wheezing or difficulty swallowing

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

• Severe allergic reactions (including potentially fatal anaphylactic shock)
• Severe skin reactions such as Stevens-Johnson syndrome, exfoliative dermatitis and toxic epidermal necrolysis (can cause rash, blistering or peeling of the skin) and acute generalized exanthematous pustulosis (symptoms include redness of the skin with swollen areas and numerous small pustules)
• A late allergic reaction with possible symptoms such as rash, swelling of the face, fever, swollen glands and abnormalities in clinical test results (e.g. liver, blood cells (eosinophilia, a type of increase in blood cell count)
• Bleeding in the brain that causes death
• Meningitis (inflammation of the membrane that surrounds the brain and spinal cord)
• Liver failure, liver damage and severe liver inflammation (fulminant hepatitis) (sometimes with fatal outcome or requiring liver transplant). Symptoms may include nausea, diarrhea, jaundice (yellowing of the skin and eyes), darkened urine, pale stools, ease of bleeding, itching or chills
• Liver problems (such as cholestasis and cholestatic hepatitis, which may be accompanied by symptoms such as discolored stools, nausea and yellowing 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, 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 the blood vessels (can cause fever, pain, purple spots on the skin)
• Decrease in the number of red and white blood cells and platelets (can cause fatigue, ease of bruising, frequent nosebleeds and increased risk of infections)
• Muscle pain and weakness
• Taste disturbance
• Loss of taste

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

• Decreased fertility in women, which is normally reversible if the medication is discontinued

Adverse effects observed in clinical trials in which celecoxib was administered at doses of 400 mg per day for a period of up to 3 years, in patients who had diseases unrelated to arthritis or other arthritic conditions, were:

Frequent adverse effects: may affect up to 1 in 10 patients:

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

Uncommon adverse effects: may affect up to 1 in 100 patients:

• Deep vein thrombosis (blood clotting generally in the leg, which can cause pain, swelling or redness of the calf or breathing problems)
• Stomach problems: stomach infection (which can cause irritation or ulcers in the stomach and intestine)
• Fracture of lower limbs
• Herpes, skin infection, eczema (dry rash with itching), pneumonia (infection in the chest (possibility of cough, fever, difficulty breathing))
• Floaters in the eye that cause vision disturbance or blurred vision, vertigo due to problems in the inner ear, ulcers, inflammation or bleeding of the gums, ulcers in the mouth
• Excessive urination at night, bleeding from hemorrhoids, frequent bowel movement
• Fat bumps on the skin or other places, ganglion cyst (painless inflammation in the joints or tendons or around them, in the hand or foot), difficulty speaking, abnormal or very heavy vaginal bleeding, chest pain
• High levels of sodium in blood test results

Reporting of adverse effects

If you experience any type of adverse effect, consult your doctor or pharmacist, even if it is a possible adverse effect that is not listed in this prospectus. 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. Conservation of Celecoxib OPKO

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

Do not use this medicine 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.

Medicines should not be thrown away through wastewater or household waste. Deposit the packaging and medicines that you no longer need at the SIGRE collection point in the pharmacy. In case of doubt, ask your pharmacist how to dispose of the packaging and medicines that you no longer need. This way, you will help protect the environment.

6. Package contents and additional information

Composition of Celecoxib OPKO

The active ingredient is celecoxib.

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

The other components (excipients) are:

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

Appearance of the product and package contents

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

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

This medicine may be presented in PVC/PVDC/Aluminum blister packs 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 marketed.

Marketing authorization holder

OPKO HEALTH SPAIN, S.L.U.

Pl. Europa 13-15, 08908

L’Hospitalet de Llobregat (Barcelona)

Spain

Manufacturer

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 under the following names:

Spain: Celecoxib OPKO 100 mg/200 mg hard capsules EFG

Germany: Celecoxib Heumann 100 mg/200 mg hard capsules

Italy: Celecoxib Maxmind 100 mg/200 mg hard capsules

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

Date of the last revision of this prospectus: March 2023

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