ZELSIGLAT 100 mg Capsules

Contents of the leaflet

1. Leaflet accompanying the packaging: patient information
2. Zelsiglat, 100 mg, hard capsules
3. Zelsiglat, 200 mg, hard capsules
   1. You should carefully read the contents of the leaflet before taking the medicine, as it contains important information for the patient.
   2. Table of contents of the leaflet
4. What is Zelsiglat and what is it used for
5. Important information before taking Zelsiglat
   1. When not to take Zelsiglat:
   2. Warnings and precautions
   3. Zelsiglat and other medicines
   4. Pregnancy, breastfeeding, and fertility
   5. Driving and using machines
   6. Zelsiglat contains lactose (a type of sugar)
   7. Zelsiglat contains sodium
6. How to take Zelsiglat
   1. Use in children
   2. Taking more than the recommended dose of Zelsiglat:
   3. Missing a dose of Zelsiglat
   4. Stopping treatment with Zelsiglat
7. Possible side effects
   1. The following side effects have been observed in patients with arthritis taking celecoxib. Side effects marked with an asterisk (*) occurred more frequently in patients taking celecoxib for the
   2. If you experience any of the following symptoms, you should stop taking Zelsiglat and inform your doctor immediately:
   3. Very common: may affect more than 1 in 10 people
   4. Common: may affect up to 1 in 10 people
   5. Uncommon: may affect up to 1 in 100 people
   6. Rare: may affect up to 1 in 1,000 people
   7. Very rare: may affect up to 1 in 10,000 people
   8. Frequency not known: frequency cannot be estimated from the available data
   9. In clinical trials not related to arthritis or other joint diseases, in which celecoxib was taken at a dose of 400 mg per day for up to 3 years, the following additional side effects were observed:
   10. Common: may affect up to 1 in 10 people
   11. Uncommon: may affect up to 1 in 100 people
   12. Reporting side effects
8. How to store Zelsiglat
9. Contents of the pack and other information
   1. What Zelsiglat contains
   2. What Zelsiglat looks like and contents of the pack
   3. Marketing authorization holder:
   4. Manufacturer/Importer:
   5. This medicinal product is authorized in the Member States of the European Economic Area under the following names:
   7. Date of last revision of the leaflet: 09.2021

Leaflet accompanying the packaging: patient information

Zelsiglat, 100 mg, hard capsules

Zelsiglat, 200 mg, hard capsules

Celecoxib

You should carefully read the contents of the leaflet before taking the medicine, as it contains important information for the patient.

• You should keep this leaflet, so that you can read it again if you need to.
• If you have any further questions, you should 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 symptoms are the same as yours.
• If you experience any side effects, including those not listed in this leaflet, you should tell your doctor, pharmacist, or nurse. See section 4.

Table of contents of the leaflet

• 1. What is Zelsiglat and what is it used for
• 2. Important information before taking Zelsiglat
• 3. How to take Zelsiglat
• 4. Possible side effects
• 5. How to store Zelsiglat
• 6. Contents of the pack and other information

1. What is Zelsiglat and what is it used for

Zelsiglat belongs to a group of medicines called non-steroidal anti-inflammatory drugs (NSAIDs), and more specifically to a subgroup of medicines called cyclooxygenase-2 (COX-2) inhibitors. The human body produces prostaglandins, which can cause pain and inflammation. In diseases such as rheumatoid arthritis and osteoarthritis, the amount of prostaglandins produced increases. Zelsiglat works by inhibiting the production of prostaglandins, thus reducing pain and inflammation.
Zelsiglat is used in adults for the treatment of symptoms of rheumatoid arthritis, osteoarthritis, and ankylosing spondylitis.
The patient should feel the effect of the medicine within a few hours of taking the first dose, but the full effect may only be felt after several days.

2. Important information before taking Zelsiglat

Zelsiglat has been prescribed by your doctor. The following information will help you get the best results from taking Zelsiglat. If you have any further questions, you should ask your doctor or pharmacist.

When not to take Zelsiglat:

You should inform your doctor if you have any of the following conditions that are contraindications to taking Zelsiglat.

• if you are allergic to celecoxib or any of the other ingredients of this medicine (listed in section 6);
• if you have been diagnosed with hypersensitivity to sulfonamide medicines (e.g. certain antibiotics used to treat infections);
• if you have active stomach or intestinal ulcers, or bleeding from the stomach or intestines;
• if you have experienced asthma, nasal polyps, nasal congestion, or allergic reactions (such as itching rash, facial swelling, lip swelling, tongue swelling, or throat swelling, difficulty breathing, or wheezing) after taking acetylsalicylic acid (aspirin) or other anti-inflammatory and pain-relieving medicines (NSAIDs);
• if you are pregnant. If you may become pregnant during treatment, you should discuss contraception 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, ischemic heart disease, or cerebrovascular disease, e.g. patients who have been diagnosed with myocardial infarction, stroke, or transient ischemic attack (temporary reduction in blood flow to the brain, so-called mini-stroke), angina pectoris, or blockage of coronary or cerebral blood vessels.
• if you have had or have circulatory disorders (peripheral arterial disease), or if you have had a procedure on the arteries of the legs.

Warnings and precautions

Before starting treatment with Zelsiglat, you should discuss it with your doctor or pharmacist:

• if you have had stomach or intestinal ulcers, or bleeding from the stomach or intestines in the past (do not take Zelsiglat if you have active stomach or intestinal ulcers, or bleeding from the stomach or intestines);
• if you are taking acetylsalicylic acid (aspirin), even in small doses for heart protection;
• if you are taking antiplatelet agents;
• if you are taking blood-thinning medicines (e.g. warfarin/anticoagulant derivatives of warfarin or new-generation anticoagulants, e.g. apixaban);
• if you are taking corticosteroid medicines (e.g. prednisone);
• if you plan to take other NSAIDs with Zelsiglat, such as ibuprofen or diclofenac (other than acetylsalicylic acid). You should avoid taking these medicines at the same time;
• if you smoke, have diabetes, high blood pressure, or high cholesterol levels;
• if you have heart, liver, or kidney problems; your doctor may recommend regular check-ups;
• if you have fluid retention (such as swelling of the ankles or feet);
• if you are dehydrated due to illness, diarrhea, or taking diuretic medicines (used to treat excess fluid in the body);
• if you have had a severe allergic reaction or severe skin reaction to any medicine;
• if you have an infection or suspect you have an infection, as Zelsiglat may mask fever or other signs of infection or inflammation;
• if you are over 65 years old; your doctor may recommend regular check-ups;

If you consume alcohol or take NSAIDs, it may increase the risk of gastrointestinal disorders.
Like other NSAIDs (e.g. ibuprofen or diclofenac), this medicine may lead to increased blood pressure, so your doctor may recommend regular blood pressure check-ups.
During treatment with celecoxib, cases of severe liver disease have been reported, including severe hepatitis, liver damage, and liver failure (sometimes fatal or requiring liver transplantation).
In cases where the period preceding the onset of the disease was known, most severe liver-related adverse events occurred within a month of starting treatment.
Zelsiglat may cause difficulties in becoming pregnant. Female patients should inform their doctor if they plan to become pregnant or are having trouble becoming pregnant (see section Pregnancy and breastfeeding).

Zelsiglat and other medicines

You should tell your doctor or pharmacist about all medicines you are currently taking or have recently taken, as well as any medicines you plan to take:

• dextromethorphan (used to treat cough),
• ACE inhibitors, angiotensin II receptor antagonists, beta-blockers, and diuretics (used to treat high blood pressure and heart failure),
• fluconazole and rifampicin (used to treat fungal and bacterial infections),
• warfarin or other warfarin derivatives (blood-thinning medicines used to prevent blood clotting), including new-generation medicines such as apixaban,
• lithium (used to treat certain types of depression),
• other medicines used to treat depression, sleep disorders, high blood pressure, or heart rhythm disorders,
• antipsychotics (used to treat certain mental illnesses),
• methotrexate (used to treat rheumatoid arthritis, psoriasis, and leukemia),
• carbamazepine (used to treat epilepsy/seizures and certain types of pain or depression),
• barbiturates (used to treat epilepsy/seizures and certain sleep disorders),
• cyclosporine and tacrolimus (used to weaken the immune system, e.g. after transplants).

Zelsiglat can be taken with low doses of acetylsalicylic acid (aspirin), 75 mg or less per day. You should consult your doctor before taking both medicines at the same time.

Pregnancy, breastfeeding, and fertility

If you are pregnant or breastfeeding, think you may be pregnant, or plan to have a child, you should ask your doctor or pharmacist for advice before taking this medicine.
Pregnancy
You should not take Zelsiglat if you are pregnant or may become pregnant (e.g. women of childbearing age who do not use effective contraception) during treatment. If you become pregnant during treatment with Zelsiglat, you should stop taking Zelsiglat and contact your doctor to determine an alternative treatment method.
Breastfeeding
You should not take Zelsiglat if you are breastfeeding.
Fertility
NSAIDs, including Zelsiglat, may make it more difficult to become pregnant. Female patients should tell their doctor if they plan to become pregnant or are having trouble becoming pregnant.

Driving and using machines

Before driving or operating machinery, you should observe how Zelsiglat affects you. If you experience dizziness or drowsiness after taking Zelsiglat, you should not drive or operate machinery until these symptoms have resolved.

Zelsiglat contains lactose (a type of sugar)

If you have been diagnosed with intolerance to some sugars, you should contact your doctor before taking Zelsiglat.

Zelsiglat contains sodium

The medicine contains less than 1 mmol (23 mg) of sodium per capsule, which means it is considered "sodium-free".

3. How to take Zelsiglat

This medicine should always be taken exactly as directed by your doctor or pharmacist. If you are unsure, you should ask your doctor or pharmacist. If you feel that the effect of Zelsiglat is too strong or too weak, you should ask your doctor or pharmacist.
Your doctor will inform you about the dose you should take. Since the risk of side effects related to heart problems may increase with the dose and duration of treatment, it is essential to take Zelsiglat at the lowest effective dose that controls pain and for no longer than necessary to control symptoms.
Method of administration
Zelsiglat should be taken orally.Capsules can be taken at any time of day, with or without food. However, it is recommended that you take Zelsiglat at the same time every day.
In case of difficulty swallowing capsules: You should pour the entire contents of the capsule onto a spoon containing a semi-solid food (e.g. cold or room-temperature apple sauce, rice cereal, yogurt, or mashed banana) and swallow immediately, followed by about 240 ml of water.
To open the capsule, you should hold it upright so that the granule contents are at the bottom. Then, you should gently squeeze the cap and twist it to remove it, being careful not to spill the contents. The granules should not be chewed or crushed.
If you do not observe any benefits within two weeks of starting treatment, you should contact your doctor.
Recommended dose
Osteoarthritis:the recommended dose is 200 mg per day. Your doctor may increase the dose to a maximum of 400 mg if necessary.
The recommended dose is:

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

Rheumatoid arthritis:the recommended dose is 200 mg per day. Your doctor may increase the dose to a maximum of 400 mg if necessary.
The recommended dose is:

• one 100 mg capsule twice a day.

Ankylosing spondylitis:the recommended dose is 200 mg per day. Your doctor may increase the dose to a maximum of 400 mg if necessary.
The recommended dose is:

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

Impaired renal or hepatic function:you should ensure that your doctor knows about any liver or kidney function disorders, as a lower dose may be necessary.
Elderly patients, particularly those with a body weight of less than 50 kg:in patients over 65 years old, particularly those with a body weight of less than 50 kg, your doctor may recommend regular monitoring. You should not take more than 400 mg of celecoxib per day.

Use in children

Zelsiglat should only be used in adults; it should not be used in children.

Taking more than the recommended dose of Zelsiglat:

You should not take more capsules than recommended by your doctor. If you have taken too many capsules, you should contact your doctor or pharmacist or go to the hospital. You should take the medicine with you.

Missing a dose of Zelsiglat

If you forget to take a capsule, you should take it as soon as you remember. You should not take a double dose to make up for a missed dose.

Stopping treatment with Zelsiglat

Suddenly stopping treatment with Zelsiglat may worsen existing symptoms. You should not stop taking Zelsiglat unless your doctor advises you to do so. Your doctor may recommend gradually reducing the dose over several days before completely stopping treatment.
If you have any further questions about taking this medicine, you should ask your doctor or pharmacist.

4. Possible side effects

Like all medicines, Zelsiglat can cause side effects, although not everybody gets them.

The following side effects have been observed in patients with arthritis taking celecoxib. Side effects marked with an asterisk (*) occurred more frequently in patients taking celecoxib for the

prevention of colon polyps. In this study, patients took celecoxib at high doses and for a long period.

If you experience any of the following symptoms, you should stop taking Zelsiglat and inform your doctor immediately:

• allergic reaction, such as rash, facial swelling, wheezing, or difficulty breathing,
• heart problems, such as chest pain,
• severe stomach pain or signs of bleeding from the stomach or intestines, such as black or blood-stained stools or vomiting blood,
• skin reactions, such as rash, blistering, or peeling of the skin,
• liver failure (symptoms may include nausea, diarrhea, yellowing of the skin or eyes, dark urine, pale stools, bleeding, itching, or chills).

Very common: may affect more than 1 in 10 people

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

Common: may affect up to 1 in 10 people

• myocardial infarction*
• fluid retention with swelling of the ankles, legs, and (or) hands
• urinary tract infections
• shortness of breath*, sinusitis (sinus infection, sinusitis, feeling of blocked or painful sinuses), stuffy nose or runny nose, sore throat, cough, common cold, flu-like symptoms
• dizziness, difficulty sleeping
• vomiting*, stomach pain, diarrhea, indigestion, bloating with gas
• rash, itching
• muscle stiffness
• difficulty swallowing*
• headache
• nausea
• joint pain
• worsening of existing allergic symptoms
• accidental injuries

Uncommon: may affect up to 1 in 100 people

• stroke*
• heart failure, palpitations (feeling of heartbeat), rapid heartbeat
• abnormal liver function test results
• abnormal kidney function test results
• anemia (changes in red blood cell count; may cause fatigue and shortness of breath)
• anxiety, depression, fatigue, drowsiness, tingling sensation
• high potassium levels in the blood (may cause nausea, fatigue, weakness, or palpitations)
• vision disturbances or blurred vision, ringing in the ears, mouth pain or inflammation, hearing disturbances*
• constipation, belching, stomach inflammation (indigestion, stomach pain, or vomiting), worsening of stomach or intestinal inflammation
• leg cramps
• hives (itchy rash)
• eye inflammation
• breathing difficulties
• skin discoloration (bruising)
• chest pain (general chest pain not related to the heart)
• facial swelling

Rare: may affect up to 1 in 1,000 people

• ulceration (bleeding) of the stomach, esophagus, or intestines; or perforation of the intestines (which can cause stomach pain, fever, nausea, vomiting, bowel obstruction), black or tarry stools, pancreatitis (which can cause stomach pain), esophagitis
• low sodium levels in the blood (a condition called hyponatremia)
• decreased white blood cell or platelet count (which can increase the risk of infection or bleeding)
• coordination disorders
• disorientation, taste disturbances
• increased sensitivity to light
• hair loss
• hallucinations
• bleeding into the eye
• severe reaction, which can lead to pneumonia
• irregular heartbeat
• hot flashes
• blood clots in the blood vessels of the lungs. Symptoms may include sudden shortness of breath, stabbing pain while breathing, or collapse
• bleeding from the stomach or intestines (which can lead to black or blood-stained stools or vomiting blood), intestinal or colon inflammation
• severe liver disease. Symptoms may include nausea, diarrhea, yellowing of the skin or eyes, dark urine, pale stools, bleeding, itching, or chills
• acute kidney failure
• menstrual disorders
• facial swelling, lip swelling, tongue swelling, or throat swelling, or difficulty swallowing

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

• severe allergic reactions (including anaphylactic shock, which can be fatal)
• severe skin diseases, such as Stevens-Johnson syndrome, toxic epidermal necrolysis, and drug rash with eosinophilia and systemic symptoms (DRESS) (which can cause rash, blistering, or peeling of the skin) and acute generalized exanthematous pustulosis (which can cause red, swollen areas of skin with many small blisters)
• delayed allergic reaction with possible symptoms such as rash, facial swelling, fever, swollen lymph nodes, and abnormal test results (e.g. liver, blood (eosinophilia, a type of increased white blood cell count))
• intracranial bleeding, which can be fatal
• meningitis (inflammation of the membranes surrounding the brain and spinal cord)
• liver failure, liver damage, and severe hepatitis (sometimes fatal or requiring liver transplantation); symptoms may include nausea, diarrhea, yellowing of the skin or eyes, dark urine, pale stools, bleeding, itching, or chills
• liver problems (such as cholestasis and cholestatic hepatitis, which may be accompanied by symptoms such as pale stools, nausea, or yellowing of the skin or eyes)
• kidney problems (such as nephritis and nephrotic syndrome, which may be accompanied by symptoms such as fluid retention, foamy urine, fatigue, or loss of appetite)
• worsening of epilepsy (which may cause more frequent or severe seizures)
• closure of the artery or vein of the retina, leading to partial or complete loss of vision
• inflammation of blood vessels (which can cause fever, pain, purpura)
• decreased red, white blood cell, and platelet count (which can cause weakness, easy bruising, frequent nosebleeds, increased risk of infection)
• muscle pain and weakness
• smell disturbances
• taste disturbances

Frequency not known: frequency cannot be estimated from the available data

• decreased fertility in women, which is usually reversible after treatment is stopped

In clinical trials not related to arthritis or other joint diseases, in which celecoxib was taken at a dose of 400 mg per day for up to 3 years, the following additional side effects were observed:

Common: may affect up to 1 in 10 people

• heart problems: angina pectoris (chest pain)
• stomach problems: irritable bowel syndrome (which may include stomach pain, diarrhea, indigestion, bloating with gas)
• kidney stones (which can cause stomach or back pain, blood in the urine)
• weight gain

Uncommon: may affect up to 1 in 100 people

• deep vein thrombosis (blood clots that occur most commonly in the legs, which can cause pain, swelling, or redness of the calf or breathing problems)
• stomach problems: stomach inflammation (which can cause stomach upset and ulcers)
• lower limb fracture
• shingles, skin inflammation, eczema (dry, itchy rash), pneumonia (chest infection, which may cause cough, fever, difficulty breathing)
• eye clouding causing blurred vision or vision loss, dizziness caused by middle ear disorders, gum pain or inflammation or bleeding, mouth ulcers
• nocturnal urination, hemorrhoidal bleeding (hemorrhoids), frequent bowel movements
• fat deposits in the skin or other locations, ganglion cysts (harmless thickening in the area of joints and tendons of the hands or feet), speech difficulties, changed or very heavy menstrual bleeding, breast pain
• high sodium levels in the blood

Reporting side effects

If you experience any side effects, including those not listed in this leaflet, you should tell your doctor, pharmacist, or nurse. You can report side effects directly to the Department of Adverse Reaction Monitoring of Medicinal Products, Medical Devices, and Biocidal Products, Al. Jerozolimskie 181C, 02-222 Warsaw, phone: +48 22 49 21 301, fax: +48 22 49 21 309, website: https://smz.ezdrowie.gov.pl.
You can also report side effects to the marketing authorization holder.
Reporting side effects will help to gather more information on the safety of this medicine.

5. How to store Zelsiglat

The medicine should be stored out of sight and reach of children.
You should not take this medicine after the expiry date stated on the blister and carton after "EXP". The expiry date refers to the last day of the month.
There are no special precautions for storage of the medicinal product.
Medicines should not be disposed of via wastewater or household waste. You should ask your pharmacist how to dispose of medicines that are no longer needed. This will help protect the environment.

6. Contents of the pack and other information

What Zelsiglat contains

The active substance of Zelsiglat is celecoxib.
Each Zelsiglat 100 mg capsule contains 100 mg of celecoxib.
Each Zelsiglat 200 mg capsule contains 200 mg of celecoxib.
The other ingredients (excipients) are: sodium lauryl sulfate, lactose monohydrate, crospovidone (type A), povidone K29-32, magnesium stearate.
The capsule shell contains: titanium dioxide (E 171), gelatin, sodium lauryl sulfate.
The ink contains:

• 100 mg capsules: shellac, indigo carmine (E 132), lac,
• 200 mg capsules: shellac, yellow iron oxide (E 172).

What Zelsiglat looks like and contents of the pack

Zelsiglat 100 mg, hard capsules: hard, gelatin capsules consisting of a white, opaque cap with a blue stripe and a white, opaque body with a blue stripe marked with "100", containing a white, granular powder.
Zelsiglat 200 mg, hard capsules: hard, gelatin capsules consisting of a white, opaque cap with a yellow stripe and a white, opaque body with a yellow stripe marked with "200", containing a white, granular powder.
Zelsiglat 100 mg capsules are packaged in white, transparent PVC/Aluminum blisters.
The packs contain 10 and 30 capsules.
Zelsiglat 200 mg capsules are packaged in white, transparent PVC/Aluminum blisters.
The packs contain 10 and 30 capsules.

Marketing authorization holder:

Synoptis Pharma Sp. z o.o.
ul. Krakowiaków 65
02-255 Warsaw

Manufacturer/Importer:

Balkanpharma-Dupnitsa AD
3 Samokovsko Shosse Str., Dupnitza 2600
Bulgaria

This medicinal product is authorized in the Member States of the European Economic Area under the following names:

Poland
Zelsiglat

Date of last revision of the leaflet: 09.2021