Zelsiglat

Package leaflet: Information for the patient

Zelsiglat, 100 mg, hard capsules
Zelsiglat, 200 mg, hard capsules
Celecoxib
Please read this leaflet carefully before using the medicine, as it contains important information for the patient.

• Keep this leaflet for future reference.
• If you have any questions, consult your doctor or pharmacist.
• This medicine has been prescribed for a specific individual. Do not share it with others. This medicine may harm others, even if their symptoms are similar.
• If you experience any adverse reactions, including those not listed in this leaflet, inform your doctor, pharmacist or nurse. See section 4.

Leaflet contents

1. What Zelsiglat is and what it is 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 Zelsiglat is and what it is used for

Zelsiglat belongs to a group of medicines called non-steroidal anti-inflammatory drugs (NSAIDs), and more specifically to a subgroup known as cyclooxygenase-2 (COX-2) inhibitors. The human body produces prostaglandins, which can cause pain and inflammation. In conditions such as rheumatoid arthritis and osteoarthritis, the production of prostaglandins increases. Zelsiglat works by inhibiting the production of prostaglandins, thereby reducing pain and inflammation.
Zelsiglat is used in adults to treat the objective and subjective symptoms of rheumatoid arthritis, osteoarthritis, and ankylosing spondylitis.
You should feel the effect of the medicine within a few hours of taking the first dose, but full effect may not be apparent until after several days.

2. Important information before using Zelsiglat

Zelsiglat has been prescribed by your doctor. The following information will help you achieve the best possible results from treatment with Zelsiglat. If you have any further questions, please consult your doctor or pharmacist.

When not to use Zelsiglat:

Inform your doctor if you have any of the following conditions, which are contraindications for the use of Zelsiglat:

• if you are allergic to celecoxib or any of the other ingredients of this medicine (listed in section 6);
• if you have hypersensitivity to sulfonamides (e.g. certain antibiotics used to treat infections);
• if you have active peptic ulcer disease or gastrointestinal bleeding;
• if you have previously experienced asthma, nasal polyps, rhinitis, or allergic reactions (such as itchy rash, facial swelling, swelling of lips, tongue or throat, breathing difficulties or wheezing) after taking acetylsalicylic acid (aspirin) or other non-steroidal anti-inflammatory drugs (NSAIDs);
• if you are pregnant. If you are of childbearing potential while on therapy, discuss 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, ischemic heart disease, or cerebrovascular disease (e.g. patients who have had a heart attack, stroke, transient ischemic attack [temporary reduction in blood flow to the brain, so-called mini-stroke], angina pectoris, or arterial blockages in the heart or brain);
• if you have current or past circulatory disorders (peripheral vascular disease), or if you have undergone arterial surgery in the legs.

Warnings and precautions

Before starting Zelsiglat, discuss the following with your doctor or pharmacist:

• if you have previously had peptic ulcer disease or gastrointestinal bleeding (do not use Zelsiglat in patients with active peptic ulcer disease or gastrointestinal bleeding);
• if you are taking acetylsalicylic acid (aspirin), even in low doses for cardiovascular protection;
• if you are taking antiplatelet drugs;
• if you are taking anticoagulants (e.g. warfarin, warfarin derivatives, or newer oral anticoagulants such as apixaban);
• if you are taking corticosteroids (e.g. prednisone);
• if you plan to use other NSAIDs together with Zelsiglat, such as ibuprofen or diclofenac (other than acetylsalicylic acid). Concomitant use of these drugs should be avoided;
• if you smoke, have diabetes, high blood pressure, or elevated cholesterol levels;
• if you have heart, liver, or kidney problems; your doctor may recommend regular monitoring;
• if you have fluid retention (e.g. swelling of ankles or feet);
• if you are dehydrated due to illness, diarrhea, or use of diuretics (medicines used to treat fluid overload);
• if you have experienced a severe allergic reaction or severe skin reaction to any medicine;
• if you have an infection or suspect you may have an infection, as Zelsiglat may mask fever or other signs of infection or inflammation;
• if you are over 65 years of age; your doctor may recommend regular monitoring.

If you consume alcohol or use other NSAIDs, your risk of gastrointestinal side effects may increase.

Like other NSAIDs (e.g. ibuprofen or diclofenac), this medicine may lead to increased blood pressure; therefore, your doctor may recommend regular blood pressure monitoring.

Severe liver disease, including severe hepatitis, liver damage, and liver failure (sometimes fatal or requiring liver transplantation), has been reported during celecoxib treatment.

In cases where the time between starting treatment and onset of liver disease was known, most serious liver adverse events occurred within one month of initiating therapy.

Zelsiglat may cause difficulties in becoming pregnant. You should inform your doctor if you are planning pregnancy or experiencing fertility problems (see section Pregnancy and breastfeeding).

Zelsiglat and other medicines

Tell your doctor or pharmacist about all medicines you are currently taking, have recently taken, or 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 (anticoagulants used to prevent blood clots), including newer generation anticoagulants such as apixaban,
• lithium (used to treat certain types of depression),
• other medicines used to treat depression, sleep disorders, high blood pressure, or cardiac arrhythmias,
• neuroleptics (used to treat certain psychiatric disorders),
• 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 suppress the immune system, e.g. after organ transplants).

Zelsiglat may be used with low-dose acetylsalicylic acid (aspirin), 75 mg or lower daily doses. Consult your doctor before taking both medicines together.

Pregnancy, breastfeeding, and fertility

If you are pregnant or breastfeeding, think you may be pregnant, or plan to have a baby, consult your doctor or pharmacist before taking this medicine.

Pregnancy

Zelsiglat must not be used in pregnant women or in women who may become pregnant (e.g. women of childbearing potential who are not using effective contraception) during treatment. If you become pregnant while taking Zelsiglat, stop taking Zelsiglat immediately and contact your doctor to discuss alternative treatment options.

Breastfeeding

Zelsiglat must not be used in women who are breastfeeding.

Fertility

NSAIDs, including Zelsiglat, may impair fertility. You should inform your doctor if you are planning to become pregnant or are experiencing fertility problems.

Driving and operating machinery

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

Zelsiglat contains lactose (a type of sugar)

If you have been previously diagnosed with an intolerance to certain sugars, consult your doctor before taking this medicine.

Zelsiglat contains sodium

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

3. How to use Zelsiglat

This medicine should always be taken exactly as your doctor or pharmacist has told you. If you are unsure,
you should contact your doctor or pharmacist. If you feel that the effect of Zelsiglat is too strong or too weak,
you should consult your doctor or pharmacist.
Your doctor will inform you what dose of the medicine to take. Since the risk of heart-related
side effects may increase with dose and duration of treatment, it is important to use Zelsiglat at the lowest
effective dose that controls your pain, and for no longer than necessary to control your symptoms.

Administration method
Zelsiglat should be taken orally. Capsules may be taken at any time of day, with or without food. However,
it is recommended that you take Zelsiglat at the same time each day.
If you have difficulty swallowing the capsules: Empty the entire contents of the capsule onto a spoon
containing a semi-solid food (e.g. cool or room temperature applesauce, rice cereal, yoghurt, or mashed banana)
and swallow immediately, followed by approximately 240 ml of water.
To open the capsule, hold it upright so that the granules inside are at the bottom. Then gently squeeze
the cap and twist it off carefully to avoid spilling the contents. Do not chew or crush the granules.
If you do not notice any benefit within two weeks of starting treatment, you should contact your doctor.

Recommended dose
Osteoarthritis: The recommended dose is 200 mg once daily. Your doctor may increase the dose to a
maximum of 400 mg daily, if necessary.
The recommended dose is:

• one 200 mg capsule once daily, or
• one 100 mg capsule twice daily.

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

• one 100 mg capsule twice daily.

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

• one 200 mg capsule once daily, or
• one 100 mg capsule twice daily.

Kidney or liver function impairment: Make sure your doctor is aware of any kidney or liver problems,
as a lower dose may be required.
Elderly patients, especially those weighing less than 50 kg: In patients aged 65 years and older,
particularly those weighing less than 50 kg, your doctor may recommend regular monitoring.
Do not take more than 400 mg of celecoxib per day.

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

Taking more Zelsiglat than recommended:
Do not take more capsules than prescribed by your doctor. If you take too many capsules, contact your
doctor or pharmacist immediately, or go to hospital. Bring the medicine with you.

If you miss a dose of Zelsiglat
If you forget to take a capsule, take it as soon as you remember. Do not take a double dose to make up
for a missed dose.

Stopping Zelsiglat
Stopping Zelsiglat suddenly may cause your symptoms to worsen. Do not stop taking Zelsiglat unless
your doctor tells you to. Your doctor may advise gradually reducing the dose over several days before
completely stopping treatment.

If you have any further 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 everyone will experience them.
The adverse effects listed below have been observed in patients with arthritis taking celecoxib. Adverse effects marked with an asterisk (*) listed
below occurred more frequently in patients taking celecoxib for the prevention of colorectal polyps. In this study, patients took celecoxib at high
doses and for a prolonged period.
If any of the symptoms listed below occur, stop taking Zelsiglat immediately and contact your doctor:

• allergic reaction, such as rash, facial swelling, wheezing or difficulty breathing,
• heart problems, e.g. chest pain,
• severe abdominal pain or any signs of gastrointestinal bleeding, such as black or bloody stools or vomiting blood,
• skin reactions, such as rash, blistering or peeling of the skin,
• liver failure (symptoms may include: nausea (feeling sick), diarrhoea, jaundice (yellowing of the skin or whites of the eyes)).

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

• heart attack*
• fluid retention with oedema of ankles, legs and (or) hands
• urinary tract infections
• shortness of breath*, sinusitis (sinus inflammation, sinus infection, stuffy or painful sinuses), stuffy nose or runny nose, sore throat, cough, cold, flu-like symptoms
• dizziness, difficulty sleeping
• vomiting*, abdominal pain, diarrhoea, indigestion, bloating with gas
• rash, itching
• muscle stiffness
• difficulty swallowing*
• headache
• nausea (feeling sick)
• joint pain
• worsening of pre-existing allergic symptoms
• accidental injuries

Uncommon: may affect up to 1 in 100 people

• stroke*
• heart failure, palpitations (awareness of heartbeat), rapid heartbeat
• abnormal blood test results relating to liver function
• abnormal blood test results relating to kidney function
• anaemia (changes in red blood cell count; may cause fatigue and breathlessness)
• restlessness, depression, fatigue, drowsiness, tingling sensation
• high potassium levels in the blood (may cause nausea (feeling sick), fatigue, muscle weakness or palpitations)
• blurred or impaired vision, ringing in the ears, mouth pain and inflammation, hearing disturbances*
• constipation, belching, stomach inflammation (indigestion, abdominal pain or vomiting), worsening of stomach or intestinal inflammation
• leg cramps
• raised itchy rash (urticaria)
• eye inflammation
• breathing difficulties
• skin discolouration (bruising)
• chest pain (general pain unrelated to the heart)
• facial swelling

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

• stomach, oesophagus or intestinal ulceration (bleeding) or intestinal perforation (which may cause abdominal pain, fever, nausea, vomiting, gastrointestinal obstruction), tarry or black stools, pancreatitis (which may cause abdominal pain), oesophagitis
• low sodium levels in the blood (a condition called hyponatraemia)
• decreased white blood cell count (which help protect the body against infections) or platelet count (increased risk of bleeding or bruising)
• movement coordination disorders
• disorientation, taste disturbances
• light sensitivity
• hair loss
• hallucinations
• bleeding inside the eye
• acute reaction which may lead to lung inflammation
• irregular heartbeat
• hot flushes
• blood clots in blood vessels of the lungs. Symptoms may include sudden breathlessness, sharp pain when breathing or collapse
• bleeding from the stomach or intestines (which may lead to bloody stools or vomiting), intestinal or colonic inflammation
• severe liver inflammation. Symptoms may include nausea (feeling sick), diarrhoea, jaundice (yellowing of the skin or whites of the eyes), dark urine, pale stools, bleeding, itching or chills
• acute kidney failure
• menstrual disorders
• swelling of the face, lips, mouth, tongue or throat or difficulty swallowing

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

• severe allergic reactions (including anaphylactic shock, which may be fatal)
• severe skin diseases, such as Stevens-Johnson syndrome, exfoliative dermatitis and toxic epidermal necrolysis (which may cause rash, blistering or peeling of the skin), and acute generalised exanthematous pustulosis (symptoms include red, swollen areas of skin with numerous small pustules)
• 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))
• fatal intracranial haemorrhage
• meningitis (inflammation of the membranes covering the brain and spinal cord)
• liver failure, liver damage and severe liver inflammation (fulminant hepatitis) (sometimes fatal or requiring liver transplantation); symptoms may include nausea (feeling sick), diarrhoea, jaundice (yellowing of the skin or whites of the 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 and yellowing of the skin or whites of the eyes)
• kidney inflammation and other kidney problems (such as nephrotic syndrome and microscopic glomerulonephritis, which may be accompanied by symptoms such as fluid retention (oedema), frothy urine, fatigue and loss of appetite)
• worsening of epilepsy (possibly more frequent and (or) more severe seizures)
• blockage of retinal artery or vein, leading to partial or complete loss of vision
• blood vessel inflammation (may cause fever, pain, purplish skin spots)
• decreased red and white blood cell count and platelet count (may cause weakness, easy bruising, frequent nosebleeds, increased risk of infections)
• muscle pain and weakness
• smell disturbances
• loss of taste

Frequency not known: frequency cannot be estimated from available data

• reduced fertility in women, which is usually reversible after stopping treatment

In clinical studies not related to arthritis or other joint diseases,
in which celecoxib was administered at a dose of 400 mg daily for up to 3 years, the following additional adverse effects were observed:
Common: may affect up to 1 in 10 people

• heart-related problems: angina (chest pain)
• stomach-related problems: irritable bowel syndrome (may include abdominal pain, diarrhoea, indigestion, bloating with gas),
• kidney stones (may lead to abdominal or back pain, blood in urine), difficulties with urine flow through the urinary tract
• weight gain

Uncommon: may affect up to 1 in 100 people

• deep vein thrombosis (blood clots most commonly in the legs, which may cause pain, swelling or redness in the calf or breathing problems)
• stomach-related problems: stomach inflammation (which may cause irritation and ulceration of the stomach and intestines)
• lower limb fracture
• shingles, skin inflammation, eczema (dry, itchy rash), pneumonia (infection in the chest area (possible cough, fever, breathing difficulties))
• eye clouding causing blurred or reduced vision, dizziness caused by middle ear disorders, pain, inflammation or bleeding of the gums, mouth ulceration
• excessive urination at night, haemorrhoidal bleeding (haemorrhoids), frequent bowel movements
• lipomas in the skin or other locations, ganglion cysts of tendon sheaths (harmless swellings around joints and tendons of hands or feet), difficulty speaking, altered or very heavy vaginal bleeding, breast pain
• high sodium levels in blood tests

Reporting of adverse effects
If any adverse effects occur, including any not listed
in this leaflet, tell your doctor, pharmacist or nurse. Adverse effects
can be reported directly to the Department of Monitoring Adverse Drug Reactions of the Office for Registration of Medicinal Products, Medical Devices and Biocidal Products, Al. Jerozolimskie 181C, 02-222 Warsaw, tel.: +48 22 49 21 301, fax: +48 22 49 21 309, website: https://smz.ezdrowie.gov.pl.
Adverse effects can also be reported to the marketing authorisation holder.
Reporting adverse effects helps provide more information on the safety of the medicine.

5. How to store Zelsiglat

Keep this medicine out of sight and reach of children.
Do not use this medicine after the expiry date stated on the blister and the carton after:
"EXP". The expiry date refers to the last day of the stated month.
No special storage conditions are required for this medicinal product.
Medicines must not be disposed of via wastewater or household waste. Ask your pharmacist how to dispose of medicines you no longer use. This will help protect the environment.

6. Contents of the package and other information

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

• 100 mg capsules: shellac, indigo carmine (E 132), lake,
• 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 band and a white, opaque body with a blue band marked with the inscription "100", containing white, granular powder.
Zelsiglat 200 mg, hard capsules: hard, gelatin capsules consisting of a white, opaque cap with a yellow band and a white, opaque body with a yellow band marked with the inscription "200", containing white, granular powder.
Zelsiglat 100 mg capsules are packed in white, transparent PVC/Aluminum blisters.
Pack sizes contain 10 and 30 capsules.
Zelsiglat 200 mg capsules are packed in white, transparent PVC/Aluminum blisters.
Pack sizes contain 10 and 30 capsules.
Marketing Authorisation 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 authorised for marketing in the European Economic Area countries under the following names:
Poland Zelsiglat