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نشرة الممارس الصحي نشرة معلومات المريض بالعربية نشرة معلومات المريض بالانجليزية صور الدواء بيانات الدواء
  SFDA PIL (Patient Information Leaflet (PIL) are under review by Saudi Food and Drug Authority)

Relexib is used in adults for the relief of signs and symptoms of rheumatoid arthritis, osteoarthritis and ankylosing spondylitis.

Relexib belongs to a group of medicines called nonsteroidal anti-inflammatory drugs (NSAID), and specifically a sub-group known as cyclooxygenase-2 (COX-2) inhibitors. Your body makes prostaglandins that may cause pain and inflammation. In conditions such as rheumatoid arthritis and osteoarthritis your body makes more of these. Relexib acts by reducing the production of prostaglandins, thereby reducing the pain and inflammation.

You should expect your medicine to start working within hours of taking the first dose, but you may not experience a full effect for several days.


You have been prescribed Relexib by your doctor. The following information will help you get the best results with Relexib. If you have any further questions please ask your doctor or pharmacist.

Do not take Relexib
Tell your doctor if any of the following are true for you as patients with these conditions should not take Relexib.

  • 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 a group of medicines called “sulfonamides” (e.g., some antibiotics used to treat infections)
  • if you currently have an ulcer in your stomach or intestines, or bleeding in your stomach or intestines
  • if as a result of taking acetylsalicylic acid or any other anti-inflammatory and pain-relieving medicine (NSAID) you have had asthma, nose polyps, severe nose congestion, or an allergic reaction such as an itchy skin rash, swelling of the face, lips, tongue or throat, breathing difficulties or wheezing
  • if you are pregnant. If you can become pregnant during ongoing treatment you should discuss methods of contraception with your doctor
  • if you are breast-feeding
  • if you have severe liver disease
  • if you have severe kidney disease
  • if you have an inflammatory disease of the intestines such as ulcerative colitis or Crohn’s disease
  • if you have heart failure, established ischaemic heart disease, or cerebrovascular disease, e.g., you have been diagnosed with a heart attack, stroke, or transient ischaemic attack (temporary reduction of blood flow to the brain; also known as “mini-stroke”), angina, or blockages of blood vessels to the heart or brain
  • if you have or have had problems with your blood circulation (peripheral arterial disease) or if you have had surgery on the arteries of your legs

Warnings and precautions
Talk to your doctor or pharmacist before taking Relexib:

  • if you have previously had an ulcer or bleeding in your stomach or intestines. (Do not take Relexib if you currently have an ulcer or bleeding in your stomach or intestine)
  • if you are taking acetylsalicylic acid (even at low dose for heart protective purposes)
  • if you are taking antiplatelet therapies
  • if you use medicines to reduce blood clotting (e.g., warfarin/warfarin like anticoagulants or novel oral anti-clotting medicines, e.g., apixaban)
  • if you use medicines called corticosteroids (e.g., prednisone)
  • if you are using Relexib at the same time as other non-acetylsalicylic NSAIDs such as ibuprofen or diclofenac. The use of these medicines together should be avoided
  • if you smoke, have diabetes, raised blood pressure or raised cholesterol
  • if your heart, liver or kidneys are not working well your doctor may want to keep a regular check on you
  • if you have fluid retention (such as swollen ankles and feet)
  • if you are dehydrated, for instance due to sickness, diarrhoea or the use of diuretics (used to treat excess fluid in the body)
  • if you have had a serious allergic reaction or a serious skin reaction to any medicines
  • if you feel ill due to an infection or think you have an infection, as Relexib may mask a fever or other signs of infection and inflammation
  • if you are over 65 years of age your doctor will want to monitor you regularly
  • the consumption of alcohol and NSAIDs may increase the risk of gastrointestinal problems

As with other NSAIDs (e.g., ibuprofen or diclofenac) this medicine may lead to an increase in blood pressure, and so your doctor may ask to monitor your blood pressure on a regular basis.

Some cases of severe liver reactions, including severe liver inflammation, liver damage, liver failure (some with fatal outcome or requiring liver transplant), have been reported with celecoxib. Of the cases that reported time to onset, most severe liver reactions occurred within one month of start of treatment.

Relexib may make it more difficult to become pregnant. You should inform your doctor if you are planning to become pregnant or if you have problems to become pregnant (see section on Pregnancy and breast-feeding).

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

  • Dextromethorphan (used to treat coughs)
  • ACE inhibitors, angiotensin II antagonists, beta blockers and diuretics (used for high blood pressure and heart failure)
  • Fluconazole and rifampicin (used to treat fungal and bacterial infections)
  • Warfarin or other warfarin like medicines (blood-thinning” agents that reduce blood clotting) including newer medicines like apixaban
  • Lithium (used to treat some types of depression)
  • Other medicines to treat depression, sleep disorders, high blood pressure or an irregular heartbeat
  • Neuroleptics (used to treat some mental disorders)
  • Methotrexate (used to treat rheumatoid arthritis, psoriasis and leukaemia)
  • 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 for immune system suppression e.g., after transplants)

Relexib can be taken with low dose acetylsalicylic acid (75 mg or less daily). Ask your doctor for advice before taking both medicines together.

Pregnancy, breast-feeding and fertility
If you are pregnant or breast-feeding, think you may be pregnant or are planning to have a baby, ask your doctor or pharmacist for advice before taking this medicine.

Pregnancy
Relexib must not be used by women who are pregnant or can become pregnant (i.e., women of child bearing potential who are not using adequate contraception) during ongoing treatment. If you become pregnant during treatment with Relexib you should discontinue the treatment and contact your doctor for alternative treatment.

Breast-feeding
Relexib must not be used during breast-feeding.

Fertility
NSAIDs, including Relexib, may make it more difficult to become pregnant. You should tell your doctor if you are planning to become pregnant or if you have problems becoming pregnant.

Driving and using machines
You should be aware of how you react to Relexib before you drive or operate machinery. If you feel dizzy or drowsy after taking Relexib, do not drive or operate machinery until these effects wear off.

Relexib contains lactose
Relexib contains lactose (a type of sugar). If you have been told by your doctor that you have an intolerance to some sugars, contact your doctor before taking this medicinal product.


Always take this medicine exactly as your doctor or pharmacist has told you. Check with your doctor or pharmacist if you are not sure. If you think or feel that the effect of Relexib is too strong or too weak, talk to your doctor or pharmacist.

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

Method of administration:
Relexib 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 Relexib at the same time each day.

If you have difficulty swallowing capsules: The entire capsule contents can be sprinkled onto a level teaspoon of semi-solid food (such as cool or room temperature applesauce, rice gruel, yogurt or mashed banana) and swallowed immediately with a drink approximately 240 ml of water.

To open the capsule, hold upright to contain the granules at the bottom then gently squeeze the top and twist to remove, taking care not to spill the contents. Do not chew or crush the granules.

Contact your doctor within two weeks of starting treatment if you do not experience any benefit.

The recommended dose is:

For osteoarthritis, the recommended dose is 200 mg each day, increased by your doctor to a maximum of 400 mg, if needed.

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 each day, increased by your doctor to a maximum of 400 mg, if needed.

The dose is usually:

  • one 100 mg capsule twice a day.

For ankylosing spondylitis, the recommended dose is 200 mg each day, increased by your doctor to a maximum of 400 mg, if needed.

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.

The elderly, especially those with a weight less than 50 kg: if you are over 65 years of age and especially if you weigh less than 50 kg, your doctor may want to monitor you more closely.

You should not take more than 400 mg per day.

Use in children
Relexib is for adults only, it is not for use in children.

If you take more Relexib than you should
You should not take more capsules than your doctor tells you to. If you take too many capsules contact your doctor, pharmacist or hospital and take your medicine with you.

If you forget to take Relexib
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 forgotten dose.

If you stop taking Relexib
Suddenly stopping your treatment with Relexib may lead to your symptoms getting worse. Do not stop taking Relexib unless your doctor tells you to. Your doctor may tell you to reduce the dose over a few days before stopping completely.

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


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

The side effects listed below were observed in arthritis patients who took celecoxib. Side effects marked with an asterisk (*) are listed below at the higher frequencies that occurred in patients who took celecoxib to prevent colon polyps. Patients in these studies took celecoxib at high doses and for a long duration.

If any of the following happen, stop taking Relexib and tell your doctor immediately:
If you have:

  • an allergic reaction such as skin rash, swelling of the face, wheezing or difficulty breathing
  • heart problems such as pain in the chest
  • severe stomach pain or any sign of bleeding in the stomach or intestines, such as passing black or bloodstained stools, or vomiting blood
  • a skin reaction such as rash, blistering or peeling of the skin
  • liver failure (symptoms may include nausea (feeling sick), diarrhoea, jaundice (your skin or the whites of your eyes look yellow)). 

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 build up with swollen ankles, legs and/or hands
  • Urinary infections
  • Shortness of breath*, sinusitis (sinus inflammation, sinus infection, blocked or painful sinuses), blocked or runny nose, sore throat, coughs, colds, flu-like symptoms
  • Dizziness, difficulty sleeping
  • Vomiting*, stomach ache, diarrhoea, indigestion, wind
  • Rash, itching
  • Muscle stiffness
  • Difficulty swallowing*
  • Headache
  • Nausea (feeling sick)
  • Painful joints
  • Worsening of existing allergies
  • Accidental injury

Uncommon: may affect up to 1 in 100 people

  • Stroke*
  • Heart failure, palpitations (awareness of heart beat), fast heart rate
  • Abnormalities in liver-related blood tests
  • Abnormalities in kidney-related blood tests
  • Anaemia (changes in red blood cells that can cause fatigue and breathlessness)
  • Anxiety, depression, tiredness, drowsiness, tingling sensations (pins and needles)
  • High levels of potassium in blood test results (can cause nausea (feeling sick), fatigue, muscle weakness or palpitations)
  • Impaired or blurred vision, ringing in the ears, mouth pain and sores, difficulty hearing*
  • Constipation, burping, stomach inflammation (indigestion, stomach ache or vomiting), worsening of inflammation of the stomach or intestine
  • Leg cramps
  • Raised itchy rash (hives)
  • Eye inflammation
  • Difficulty breathing
  • Skin discolouration (bruising)
  • Chest pain (generalised pain not related to the heart)
  • Face swelling

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

  • Ulcers (bleeding) in the stomach, gullet or intestines; or rupture of the intestine (can cause stomach ache, fever, nausea, vomiting, intestinal blockage), dark or black stools, inflammation of the pancreas (can lead to stomach pain), inflammation of the gullet (oesophagus)
  • Low levels of sodium in the blood (a condition known as hyponatraemia)
  • Reduced number of white blood cells (which help to protect the body from infection) or blood platelets (increased chance of bleeding or bruising)
  • Difficulty coordinating muscular movements
  • Feeling confused, changes in the way things taste
  • Increased sensitivity to light
  • Loss of hair
  • Hallucinations
  • Bleeding in the eye
  • Acute reaction that may lead to lung inflammation
  • Irregular heartbeat
  • Flushing
  • Blood clot in the blood vessels in the lungs. Symptoms may include sudden breathlessness, sharp pains when you breathe or collapse
  • Bleeding of the stomach or intestines (can lead to bloody stools or vomiting), inflammation of the intestine or colon
  • Severe liver inflammation (hepatitis). Symptoms may include nausea (feeling sick), diarrhoea, jaundice (yellow discolouration of the skin or eyes), dark urine, pale stools, bleeding easily, itching or chills
  • Acute kidney failure
  • Menstrual disturbances
  • Swelling of the face, lips, mouth, tongue or throat, or difficulty swallowing

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

  • Serious allergic reactions (including potentially fatal anaphylactic shock)
  • Serious skin conditions such as Stevens-Johnson syndrome, exfoliative dermatitis and toxic epidermal necrolysis (can cause rash, blistering or peeling of the skin) and acute generalised exanthematous pustulosis (symptoms include the skin becoming red with swollen areas covered in numerous small pustules)
  • A delayed allergic reaction with possible symptoms such as rash, swelling of the face, fever, swollen glands, and abnormal test results (e.g., liver, blood cell (eosinophilia, a type of raised white blood cell count))
  • Bleeding within the brain causing death
  • Meningitis (inflammation of the membrane around the brain and spinal cord)
  • Liver failure, liver damage and severe liver inflammation (fulminant hepatitis) (sometimes fatal or requiring liver transplant). Symptoms may include nausea (feeling sick), diarrhoea, jaundice (yellow discolouration of the skin or eyes), dark urine, pale stools, bleeding easily, itching or chills
  • Liver problems (such as cholestasis and cholestatic hepatitis, which may be accompanied by symptoms such as discoloured stools, nausea and yellowing of the skin or eyes)
  • Inflammation of the kidneys and other kidney problems (such as nephrotic syndrome and minimal change disease, which may be accompanied by symptoms such as water retention (oedema), foamy urine, fatigue and a loss of appetite)
  • Worsening of epilepsy (possible more frequent and/or severe seizures)
  • Blockage of an artery or vein in the eye leading to partial or complete loss of vision
  • Inflamed blood vessels (can cause fever, aches, purple blotches on the skin)
  • A reduction in the number of red and white blood cells and platelets (may cause tiredness, easy bruising, frequent nose bleeds and increased risk of infections)
  • Muscle pain and weakness
  • Impaired sense of smell
  • Loss of taste

Not known: frequency cannot be estimated from the available data

  • Decreased fertility in females, which is usually reversible on discontinuation of the medicine

In clinical studies not associated with arthritis or other arthritic conditions, where celecoxib was taken at doses of 400 mg per day for up to 3 years, the following additional side effects have been observed:

Common: may affect up to 1 in 10 people

  • Heart problems: angina (chest pain)
  • Stomach problems: irritable bowel syndrome (can include stomach ache, diarrhoea, indigestion, wind)
  • Kidney stones (which may lead to stomach or back pain, blood in urine), difficulty passing urine
  • Weight gain

Uncommon: may affect up to 1 in 100 people

  • Deep vein thrombosis (blood clot usually in the leg, which may cause pain, swelling or redness of the calf or breathing problems)
  • Stomach problems: stomach infection (which can cause irritation and ulcers of the stomach and intestines)
  • Lower limb fracture
  • Shingles, skin infection, eczema (dry itchy rash), pneumonia (chest infection (possible cough, fever, difficulty breathing))
  • Floaters in the eye causing blurred or impaired vision, vertigo due to inner ear troubles, sore, inflamed or bleeding gums, mouth sores
  • Excessive urination at night, bleeding from piles/ haemorrhoids, frequent bowel movements
  • Fatty lumps in skin or elsewhere, ganglion cyst (harmless swellings on or around joints and tendons in the hand or foot), difficulty speaking, abnormal or very heavy bleeding from the vagina, breast pain
  • High levels of sodium in blood test results

If you get any side effects, talk to your doctor or pharmacist. This includes any possible side effects not listed in this leaflet.


Keep out of the reach and sight of children.
Do not store above 30°C.
Do not use this medicine after the expiry date which is stated on the blister and carton. The expiry date refers to the last day of that month.
Do not throw away any medicines via wastewater or household waste. Ask the pharmacist how to throw away medicines you no longer use. These measures will help protect the environment.


The active substance is celecoxib.
1 capsule contains 100 mg or 200 mg celecoxib.

The other ingredients are:
Lactose monohydrate, hydroxypropyl cellulose, crospovidone, povidone, sodium lauryl sulfate, magnesium stearate.
Capsule shells contain gelatin, titanium dioxide, water and sodium lauryl sulfate.
Printing ink contains shellac, propylene glycol, FD&C blue no. 2 & aluminium lake (100 mg capsule), yellow iron oxide (200 mg capsule).


Relexib is available as hard capsules. White opaque with ‘C5’ imprinted on a blue band on the cap and ‘100mg’ imprinted on a blue band on the body (Relexib 100 mg). White opaque with ‘C6’ imprinted on a yellow band on the cap and ‘200mg’ imprinted on a yellow band on a body (Relexib 200 mg). The capsules are packaged blisters. Relexib is packaged in cardboard boxes containing 20 capsules (10 capsules x 2 blisters).

Saudi Pharmaceutical Industries
P.O. Box No.: 355127, Riyadh 11383
Kingdom of Saudi Arabia.
Tel: (+96611) 2650450, 2650354
Fax: (+96611) 2650383
Email: info@saudi-pharma.net 

Manufacturer
Macleods Pharmaceuticals Limited
Block N-2, Village Theda,
Post Office Lodhimajra, Tehsil Baddi,
Distt. Solan, Himachal Pradesh - 174101, India.

Secondary packaging and batch release manufacturer
Saudi Pharmaceutical Industries
P.O. Box No.: 355127, Riyadh 11383
Kingdom of Saudi Arabia.


12/2021
  نشرة الدواء تحت مراجعة الهيئة العامة للغذاء والدواء (اقرأ هذه النشرة بعناية قبل البدء في استخدام هذا المنتج لأنه يحتوي على معلومات مهمة لك)

يستخدم ريليكسيب عند البالغين لتخفيف علامات وأعراض التهاب المفاصل الروماتويدي والفصال العظمي (التهاب العظام والمفاصل) والتهاب الفقار الروماتويدي (التهاب الفقار المقسط).

ينتمي ريليكسيب إلى مجموعة دوائية تدعى الأدوية المضادة للالتهاب غير الستيرويدية، وبالتحديد إلى مجموعة فرعية تعرف بمثبطات إنزيم سيكلو أكسيجيناز-2. يقوم جسمك بإنتاج مركبات البروستاغلاندين التي يمكن أن تسبب الألم والالتهاب. وفي حالات مثل التهاب المفاصل الروماتويدي والفصال العظمي فإن جسمك يقوم بإنتاج كميات أكبر من هذه المواد.

يعمل ريليكسيب من خلال تقليل إنتاج مركبات البروستاغلاندين، وبالتالي يحد من الألم والالتهاب. ينبغي أن تتوقع أن يبدأ دواؤك بالعمل خلال ساعات من تناول الجرعة الأولى، ولكن قد لا تلاحظ المفعول الكامل إلا بعد عدة أيام.

لقد وصف لك طبيبك ريليكسيب. المعلومات التالية ستساعدك في الحصول على أفضل النتائج من استخدام ريليكسيب. إذا كانت لديك أية أسئلة أخرى فاسأل طبيبك أو الصيدلي.

موانع تناول ريليكسيب
أخبر طبيبك إذا كان أي مما يلي ينطبق على حالتك لأن المرضى الذين يعانون من هذه الحالات ينبغي ألا يتناولوا ريليكسيب:

  • إن كان لديك حساسية من سيليكوكسيب أو أي من المكونات الأخرى لهذا الدواء (المدرجة في القسم 6).
  • إذا حدثت لديك ردود فعل تحسسية تجاه مجموعة دوائية تدعى "مركبات السلفوناميد" (مثل بعض المضادات الحيوية التي تستخدم لمعالجة العدوى)
  • إذا كنت تعاني في الوقت الحالي من قرحة في معدتك أو أمعائك او نزيف في معدتك أو أمعائك
  • إذا عانيت من حدوث الربو أو السلائل الأنفية (الزوائد اللحمية الأنفية) أو احتقان شديد بالأنف أو رد فعل تحسسي مثل طفح جلدي مصحوب بحكة أو تورم في الوجه أو الشفاه أو اللسان أو الحلق أو صعوبة في التنفس أو أزيز وذلك نتيجة لتناول حمض الأسيتيل ساليسيليك (الأسبرين) أو أي دواء آخر مضاد للالتهاب ومسكن للألم (دواء مضاد للالتهاب غير ستيرويدي)
  • إذا كنت حاملاً. إذا كان هناك احتمال بأن تصبحي حاملاً أثناء المعالجة فينبغي أن تستشيري طبيبك عن طرق منع الحمل
  • إذا كنت مرضعة
  • إذا كنت تعاني من مرض كبدي شديد
  • إذا كنت تعاني من مرض كلوي شديد
  • إذا كنت تعاني من مرض التهابي في الأمعاء مثل التهاب القولون التقرحي أو مرض كرون
  • إذا كنت تعاني من فشل القلب أو من مرض قلب إقفاري مؤكد أو مرض وعائي دماغي، مثلاً تم تشخيصك سابقاً بنوبة قلبية أو سكتة أو نوبة إقفارية عابرة (انخفاض مؤقت في تدفق الدم إلى الدماغ؛ يعرف أيضاً باسم "السكتة الدماغية الطفيفة") أو ذبحة أو انسداد في الأوعية الدموية المؤدية إلى القلب أو الدماغ
  • إذا كنت تعاني أو عانيت سابقاً من مشاكل في الدورة الدموية (مرض شرياني محيطي) أو إذا خضعت لجراحة في شرايين ساقيك 

الاحتياطات عند استخدام ريليكسيب
أبلغ الطبيب أو الصيدلي قبل تناول ريليكسيب:

  • إذا عانيت فيما مضى من قرحة أو نزيف في معدتك أو أمعائك. (لا تتناول ريليكسيب إذا كنت تعاني في الوقت الحالي من قرحة أو نزيف في معدتك أو أمعائك)
  • إذا كنت تتناول حمض الأستيل ساليسيليك (حتى وإن كان بجرعة منخفضة بهدف وقاية القلب)
  • إذا كنت تتناول علاجات مضادة للصفيحات
  • إذا كنت تستخدم أدوية لتقليل تجلط الدم (مثل الوارفارين/مضادات التخثر المشابهة للوارفارين أو مضادات التخثر الفموية الجديدة مثل أبيكسابان)
  • إذا كنت تستخدم أدوية تدعى الكورتيكوستيرويدات (الستيرويدات القشرية) (مثل بريدنيزون)
  • إذا كنت تستخدم ريليكسيب في الوقت نفسه مع دواء آخر مضاد للالتهاب غير ستيرويدي وليس من مركبات الأستيل ساليسيليك مثل ايبوبروفين أو ديكلوفيناك. يجب تجنب استخدام هذه الأدوية معاً
  • إذا كنت مدخناً أو مصاباً بمرض السكري أو تعاني من ارتفاع ضغط الدم أو ارتفاع الكوليستيرول
  • إذا كان لديك خلل في وظائف القلب أو الكبد أو الكلى، فقد يرغب طبيبك في إجراء فحوصات لك بشكل مستمر ومنتظم
  • إذا كنت تعاني من احتباس السوائل (مثل تورم الكاحلين والقدمين)
  • إذا كنت تعاني من الجفاف، مثلاً بسبب المرض أو الإسهال أو استخدام مدرات البول (تستخدم لمعالجة زيادة السوائل في الجسم)
  • إذا كنت قد عانيت من رد فعل تحسسي خطير أو رد فعل جلدي خطير تجاه أي دواء
  • إذا كنت تشعر بالمرض بسبب عدوى أو تعتقد بأنك مصاب بعدوى، حيث أن ريليكسيب قد يخفي الحمى أو العلامات الأخرى للعدوى والالتهاب
  • إذا كنت بعمر أكبر من 65 سنة فسيرغب طبيبك بمراقبت حالتك بشكل منتظم
  • قد يؤدي تناول الكحول والأدوية المضادة للالتهاب غير الستيرويدية إلى زيادة خطر التعرض للمشاكل الهضمية

كما هول الحال مع الأدوية الأخرى المضادة للالتهاب غير الستيرويدية (مثل ايبوبروفن أو ديكلوفيناك) فإن هذا الدواء قد يؤدي إلى زيادة في ضغط الدم وبالتالي فإن طبيبك قد يطلب منك مراقبة ضغط الدم بشكل منتظم.

تم الإبلاغ عن بعض حالات التفاعلات الكبدية الشديدة مع استخدام سيليكوكسيب بما في ذلك التهاب كبدي شديد وتلف كبدي وفشل كبدي (بعضها مميتة أو تستدعي زراعة الكبد). من تلك الحالات التي تم الإبلاغ عن وقت بدايتها فقد حدثت معظم التفاعلات الكبدية الشديدة خلال شهر واحد من بداية المعالجة.

قد يجعل ريليكسيب حدوث الحمل أكثر صعوبة. يجب أن تخبري طبيبك إذا كنت تخططين للحمل أو إذا كنت تواجهين مشاكل في حدوث الحمل (انظري قسم الحمل والرضاعة).

التداخلات الدوائية من إعطاء ريليكسيب مع أي أدوية أخرى
أبلغ الطبيب أو الصيدلي إذا كنت تتناول أو تناولت مؤخراً أو تنوي أن تتناول أدوية أخرى:

  • ديكستروميتورفان (يستخدم لمعالجة الكحة (السعال))
  • مثبطات الإنزيم المحول للأنجيوتنسين ومضادات الأنجيوتنسين 2 وحاصرات مستقبلات بيتا ومدرات البول (تستخدم لارتفاع ضغط الدم وفشل القلب)
  • فلوكونازول وريفامبيسين (يستخدمان لمعالجة العدوى بالفطريات والجراثيم)
  • وارفارين أو الأدوية الأخرى المشابهة لوارفارين ("مسيلات الدم" مواد تقلل من تجلط الدم) بما في ذلك الأدوية الأحدث مثل أبيكسابان
  • الليثيوم (يستخدم لمعالجة بعض أنواع الاكتئاب)
  • أدوية أخرى لمعالجة الاكتئاب أو اضطرابات النوم أو ارتفاع ضغط الدم أو عدم انتظام نبضات القلب
  • مضادات الذهان (تستخدم لمعالجة بعض الاضطرابات النفسية)
  • ميثوتريكسات (يستخدم لمعالجة التهاب المفاصل الروماتويدي والصدفية وابيضاض الدم (اللوكيميا))
  • كربامازيبين (يستخدم لمعالجة الصرع/الاختلاجات وبعض أنواع الألم أو الاكتئاب)
  • الباربيتورات (تستخدم لمعالجة الصرع/الاختلاجات وبعض اضطرابات النوم)
  • سيكلوسبورين وتاكروليموس (يستخدمان لتثبيط (كبت) الجهاز المناعي كما هو الحال بعد زرع الأعضاء)

يمكن أن يتم يتناول ريليكسيب مع جرعة منخفضة من حمض الأستيل ساليسيليك (75 ملغ أو أقل يومياً). استشر طبيبك قبل تناول كلا الدوائين معاً.

الحمل والرضاعة والخصوبة
إذا كنت حاملاً أو مرضعة أو تعتقدين بأنك حامل أو تخططين للحمل فاستشيري الطبيب أو الصيدلي قبل تناول هذا الدواء.

الحمل
يجب عدم استخدام ريليكسيب من قبل النساء الحوامل أو اللاتي يمكن أن تصبحن حوامل (أي النساء القادرات على الإنجاب ولا تستخدمن وسيلة منع حمل مناسبة) أثناء سير المعالجة. إذا أصبحت حاملاً أثناء المعالجة بريليكسيب فينبغي أن تتوقفي عن المعالجة وتتواصلي مع طبيبك للحصول على معالجة بديلة.

الرضاعة
يجب ألا يستخدم ريليكسيب أثناء الرضاعة.

الخصوبة
قد تجعل الأدوية المضادة للالتهاب غير الستيرويدية بما في ذلك ريليكسيب حدوث الحمل أصعب. يجب أن تخبري طبيبك إذا كنت تخططين للحمل أو إذا كنت تواجهين مشاكل في حدوث الحمل.

تأثير ريليكسيب على القيادة واستخدام الآلات
يجب عليك الانتباه إلى كيفية استجابتك تجاه استخدام ريليكسيب قبل أن تقوم بالقيادة أو تشغيل الآلات. إذا شعرت بالدوخة أو النعاس بعد تناول ريليكسيب فلا تقم بالقيادة أو تشغيل الآلات حتى تزول هذه التأثيرات.

ريليكسيب يحتوي على اللاكتوز
يحتوي ريليكسيب على اللاكتوز (نوع من السكريات). إذا أخبرك طبيبك بأن لديك عدم تحمل لبعض السكريات فتواصل مع طبيبك قبل تناول هذا المستحضر الدوائي.

https://localhost:44358/Dashboard

دائماً تناول هذا الدواء تماماً كما أخبرك به الطبيب أو الصيدلي. إن لم تكن متأكداً من كيفية الاستخدام، ارجع إلى طبيبك أو الصيدلي. إذا كنت تعتقد أو تشعر بأن تأثير ريلكسيب قوي جداً أو ضعيف جداً فأبلغ طبيبك أو الصيدلي.

سيخبرك طبيبك بالجرعة التي ينبغي أن تتناولها. وبما أن الأعراض الجانبية المرتبطة بمشاكل قلبية قد تزداد مع الجرعة ومدة الاستخدام، فمن المهم أن تستخدم أقل جرعة للسيطرة على الألم وينبغي عليك ألا تتناول ريليكسيب لمدة أطول من اللازم للسيطرة على الأعراض.

طريقة الاستخدام:
ريليكسيب للاستخدام عن طريق الفم. يمكن تناول الكبسولات في أي وقت من اليوم مع الطعام أو دونه. على أية حال، حاول أن تتناول جرعة ريليكسيب في الوقت نفسه كل يوم.

إذا كنت تواجه صعوبة في بلع الكبسولات: يمكن نثر كامل محتوى الكبسولة على ملعقة صغيرة من طعام شبه صلب (مثل صلصة التفاح أو عصيدة الأرز أو الزبادي أو الموز المهروس بحيث يكون الطعام بارداً أو بدرجة حرارة الغرفة) ويتم بلعها مباشرة مع شرب حوالي 240 مل من الماء.

لفتح الكبسولة، امسكها بوضع قائم حتى تنزل الحبيبات إلى الأسفل ثم قم بالضغط برفق على الجزء العلوي وقم بتدويره لإزالته، واحرص ألا تنسكب المحتويات. لا تمضغ أو تسحق الحبيبات.

اتصل بطبيبك خلال أسبوعين من بداية المعالجة إذا لم تشعر بأي تحسن.

الجرعة الموصى بها هي:
لمعالجة الفصال العظمي (االتهاب العظام والمفاصل)، الجرعة الموصى بها 200 ملغ يومياً تتم زيادتها من قبل طبيبك إلى 400 ملغ بحد أقصى عند الضرورة.

تكون الجرعة عادة:

  • كبسولة واحدة 200 ملغ مرة يومياً؛ أو
  • كبسولة واحدة 100 ملغ مرتان يومياً.

لمعالجة التهاب المفاصل الروماتويدي، الجرعة الموصى بها 200 ملغ يومياً، تتم زيادتها من قبل طبيبك إلى 400 ملغ بحد أقصى عند الضرورة.

تكون الجرعة عادة:

  • كبسولة واحدة 100 ملغ مرتان يومياً.

لمعالجة التهاب الفقار الروماتويدي (التهاب الفقار المقسط)، الجرعة الموصى بها 200 ملغ يومياً تتم زيادتها من قبل طبيبك إلى 400 ملغ بحد أقصى عند الضرورة.

تكون الجرعة عادة:

  • كبسولة واحدة 200 ملغ مرة يومياً؛ أو
  • كبسولة واحدة 100 ملغ مرتان يومياً.

مشاكل الكبد أو الكلية: احرص على أن يكون طبيبك على علم فيما إذا كنت تعاني من مشاكل في الكبد أو الكلية فقد تحتاج إلى جرعة أقل.

كبار السن، وبخاصة الذين تقل أوزانهم عن 50 كغ: إذا كنت بعمر أكثر من 65 سنة وبخاصة إذا كنت تزن أقل من 50 كغ، فإن طبيبك قد يرغب في مراقبة حالتك عن كثب.

يجب ألا تتناول أكثر من 400 ملغ يومياً.

الاستخدام عند الأطفال
ريليكسيب للبالغين فقط، وليس للاستخدام عند الأطفال. 

إذا تناولت ريليكسيب أكثر من اللازم
ينبغي ألا تتناول كبسولات أكثر مما وصف لك طبيبك. إذا تناولت كبسولات أكثر من اللازم فاتصل بطبيبك أو الصيدلي أو المستشفى وخذ دوائك معك.

إذا نسيت أن تتناول ريليكسيب
إذا نسيت أن تتناول كبسولة، فقم بتناولها بمجرد أن تتذكرها. لا تتناول جرعة مضاعفة لتعويض الجرعة الفائتة.

إذا توقفت عن تناول ريليكسيب
قد يؤدي توقفك المفاجئ عن المعالجة بريليكسيب إلى تفاقم الأعراض. لا تتوقف عن تناول ريليكسيب مالم يخبرك طبيبك بذلك. قد يطلب منك طبيبك تقليل الجرعة على مدى عدة أيام قبل التوقف التام.

إذا كان لديك أي أسئلة أخرى عن استخدام هذا الدواء، اسأل الطبيب أو الصيدلي.

كما هو الحال في كل الأدوية، هذا الدواء يمكن أن يتسبب بأعراض جانبية، بالرغم من أنها قد لا تحدث للجميع.

لوحظت الأعراض الجانبية المدرجة أدناه عند مرضى التهاب المفاصل الذين تناولوا سيليكوكسيب. الأعراض الجانبية المشار إليها بعلامة نجمية (*) مدرجة أدناه عند التكرار الأعلى الذي حدث لدى المرضى الذين تناولوا سيليكوكسيب للوقاية من السلائل (الزوائد) القولونية. تناول المرضى المشاركون في هذه الدراسات جرعات عالية من سيليكوكسيب لمدة طويلة.

إذا حدثت أي من الأعراض التالية فتوقف عن تناول ريليكسيب وأخبر طبيبك على الفور:
إذا عانيت من:

  • رد فعل تحسسي مثل طفح جلدي أو تورم في الوجه أو أزيز أو صعوبة في التنفس
  • مشاكل قلبية مثل ألم في الصدر
  • ألم شديد في المعدة أو أي علامة لنزيف في المعدة أو الأمعاء مثل خروج براز أسود أو ملطخ بالدم أو تقيؤ الدم
  • رد فعل جلدي مثل طفح أو بثور أو تقشر الجلد
  • فشل الكبد (قد تشتمل الأعراض على الغثيان أو الإسهال أو اليرقان (حيث يبدو جلدك أو بياض عينيك باللون الأصفر)).

شائعة جداً: قد تؤثر على أكثر من 1 من بين 10 أشخاص

  • ارتفاع ضغط الدم بما في ذلك تفاقم ارتفاع ضغط الدم الموجود بالفعل*

شائعة: قد تؤثر على 1 من بين 10 أشخاص

  • نوبة قلبية*
  • تراكم السوائل مع تورم الكاحلين و/أو الساقين و/أو اليدين
  • عدوى بولية
  • ضيق التنفس*، التهاب الجيوب (التهاب الجيوب، عدوى الجيوب، انسداد أو ألم في الجيوب)، انسداد أو سيلان الأنف، التهاب الحلق، كحة (سعال)، برد، أعراض شبيهة بالانفلونزا
  • دوخة، صعوبة النوم
  • قيء*، ألم في المعدة، إسهال، عسر هضم، غازات
  • طفح، حكة
  • تصلب (تيبس) العضلات
  • صعوبة البلع*
  • صداع
  • غثيان
  • ألم في المفاصل
  • تفاقم حالات الحساسية الموجودة بالفعل
  • إصابات عرضية

غير شائعة: قد تؤثر على 1 من بين 100 شخص

  • سكتة*
  • فشل القلب، خفقان (الشعور بنبضات القلب)، سرعة نبضات القلب
  • شذوذ في اختبارات الدم المتعلقة بالكبد
  • شذوذ في اختبارات الدم المتعلقة بالكلية
  • فقر دم (تغيرات في خلايا الدم الحمراء الذي يمكن أن يسبب التعب وضيق التنفس)
  • قلق، اكتئاب، إرهاق، نعاس، إحساس بالوخز (كالإبر والدبابيس)
  • ارتفاع مستويات الكالسيوم في نتائج اختبار الدم (يمكن أن يسبب الغثيان أو التعب أو ضعف العضلات أو الخفقان)
  • ضعف الرؤية أو عدم وضوح الرؤية (تغيم الرؤية)، طنين في الأذنين، ألم وتقرحات في الفم، صعوبة في السمع*
  • إمساك، تجشؤ، التهاب المعدة (عسر هضم أو ألم في المعدة أو قيء)، تفاقم التهاب المعدة أو الأمعاء
  • تشنج الساق
  • طفح جلدي مثير للحكة (شرى)
  • التهاب العين
  • صعوبة التنفس
  • تغير لون الجلد (تكدم)
  • ألم في الصدر (ألم عام غير متعلق بالقلب)
  • تورم الوجه

نادرة: قد تؤثر على 1 من بين 1000 شخص

  • قرحات (نزيف) في المعدة أو المريء أو الأمعاء؛ أو تمزق الأمعاء (يمكن أن يسبب ألماً في المعدة، حمى، غثياناً، قيئاً، انسداد الأمعاء)، براز غامق أو أسود، التهاب البنكرياس (يمكن أن يؤدي إلى ألم في المعدة)، التهاب المريء
  • انخفاض مستويات الصوديوم في الدم (وهي حالة تعرف بنقص صوديوم الدم)
  • نقص في عدد خلايا الدم البيضاء (التي تساعد في حماية الجسم من العدوى) أو صفيحات الدم (زيادة احتمالات النزيف أو التكدم)
  • صعوبة تنسيق الحركات العضلية
  • الشعور بالارتباك، تغير في طريقة تذوق الأشياء
  • زيادة الحساسية تجاه الضوء
  • تساقط الشعر
  • هلوسات
  • نزيف في العين
  • رد فعل حاد قد يؤدي إلى التهاب الرئة
  • عدم انتظام نبضات القلب
  • تورد (توهج)
  • تجلط الدم في الأوعية الدموية في الرئتين. قد تشتمل الأعراض على ضيق تنفس مفاجئ أو آلام حادة عند التنفس أو هبوط
  • نزيف في المعدة أو الأمعاء (يمكن أن يؤدي إلى براز ملطخ بالدم أو قيء)، التهاب الأمعاء أو القولون
  • التهاب كبدي شديد. قد تشتمل الأعراض على غثيان أو إسهال أو يرقان (تبدل لون الجلد أو بياض العينين إلى الأصفر) أو بول غامق أو براز باهت أو سهولة حدوث النزيف أو حكة أو قشعريرة
  • فشل كلية حاد
  • اضطرابات في الحيض
  • تورم الوجه أو الشفاه أو الفم أو اللسان أو الحلق، أو صعوبة البلع

نادرة جداً: قد تؤثر على 1 من بين 10000 شخص

  • ردود فعل تحسسية خطيرة (بما في ذلك صدمة تحسسية يحتمل أن تكون مميتة)
  • حالات جلدية خطيرة مثل متلازمة ستيفنز-جونسون والتهاب الجلد التقشري وتقشر الأنسجة المتموتة البشروية التسممي (يمكن أن يسبب طفحاً أو بثوراً أو تقشر الجلد) وكثرة البثرات الطفحية المعممة الحاد (تشتمل الأعراض على احمرار الجلد مع وجود مناطق متورمة مغطاة بالعديد من البثور الصغيرة)
  • رد فعل تحسسي متأخر مع احتمال حدوث أعراض مثل الطفح وتورم الوجه والحمى وتورم الغدد وشذوذ في نتائج الاختبارات (مثل اختبارات الكبد وخلايا الدم (كثرة اليوزينات (الحمضات) وأحد أنواع زيادة عدد خلايا الدم البيضاء))
  • نزيف في الدماغ يسبب الوفاة
  • التهاب السحايا (التهاب الغشاء حول الدماغ والحبل النخاعي (الشوكي))
  • فشل الكبد، تلف الكبد والتهاب شديد في الكبد (التهاب الكبد الخاطف) (يكون في بعض الأحيان مميتاً أو يتطلب زراعة الكبد). قد تشتمل الأعراض على غثيان أو إسهال أو يرقان (تبدل لون الجلد أو بياض العينين إلى الأصفر) أو بول غامق أو براز باهت أو سهولة حدوث النزيف أو حكة أو قشعريرة
  • مشاكل في الكبد (مثل الركود الصفراوي والتهاب الكبد الركودي، ويمكن أن يترافقا بأعراض مثل تبدل لون البراز وغثيان واصفرار الجلد أو العينين)
  • التهاب الكلى ومشاكل كلوية أخرى (مثل المتلازمة الكلوية ومرض التبدل الأدنى ويمكن أن يترافقا بأعراض مثل احتباس الماء (وذمة) وبول رغوي وتعب وفقد الشهية)
  • تفاقم حالة الصرع (احتمالية حدوث النوبات بتكرار أكثر و/أو أكثر شدة)
  • انسداد شريان أو وريد في العين يؤدي إلى فقد بصر جزئي أو تام
  • التهاب الأوعية الدموية (يمكن أن يسبب حمى، ألماً، بقعاً بنفسجية على الجلد)
  • نقص في عدد خلايا الدم الحمراء والبيضاء والصفيحات (يمكن أن يسبب تعباً وسهولة حدوث الكدمات ونزيفاً متكرراً في الأنف وزيادة خطر العدوى)
  • ألم وضعف في العضلات
  • ضعف حاسة الشم
  • فقدان التذوق

غير معروف: لا يمكن تقدير التكرار من خلال البيانات المتاحة

  • انخفاض الخصوبة عند الإناث والذي يكون قابلاً للعكس غالباً عند التوقف عن تناول الدواء

لوحظت الأعراض الجانبية التالية من خلال دراسات سريرية غير مرتبطة بالتهاب المفاصل أو حالات المفاصل الأخرى، حيث تم تناول سيليكوكسيب بجرعات 400 ملغ يومياً لمدة 3 سنوات:
شائعة: قد تؤثر على 1 من بين 10 أشخاص

  • مشاكل في القلب: ذبحة (ألم في الصدر)
  • مشاكل في المعدة: متلازمة القولون المتهيج (يمكن أن تشتمل على ألم في المعدة، إسهال، عسر هضم، غازات)
  • حصيات في الكلية (يمكن أن تؤدي إلى ألم في المعدة أو الظهر، ظهور دم في البول)، صعوبة التبول
  • زيادة الوزن

غير شائعة: قد تؤثر على 1 من بين 100 شخص

  • خثار في وريد عميق (الخثار الوريدي العميق) (تجلط الدم عادة في الساق ويمكن أن يسبب ألماً أو تورم أو احمرار الربلة أو مشاكل في التنفس)
  • مشاكل في المعدة: عدوى في المعدة (يمكن أن تسبب تهيجاً وقرحاً في المعدة والأمعاء)
  • كسر في الطرف السفلي
  • هربس نطاقي، عدوى جلدية، إكزيمة (طفح جاف مسبب للحكة)، التهاب الرئة (عدوى في الصدر (احتمال حدوث كحة (سعال)، حمى، صعوبة في التنفس))
  • ظهور أجسام طافية (عوائم) في العين تسبب عدم وضوح الرؤية (تغيم الرؤية) أو ضعف الرؤية، دوار بسبب مشاكل في الأذن الداخلية، قرحة أو التهاب أو نزيف اللثة، تقرحات فموية
  • زيادة التبول في الليل، نزيف البواسير، حركات معوية متكررة
  • ظهور كتل دهنية في الجلد أو في أي مكان آخر، أكياس عقدية (ورم حميد على أو حول المفاصل والأوتار في اليد أو القدم)، صعوبة في الكلام، نزيف غير طبيعي أو شديد من المهبل، ألم في الثدي
  • مستويات مرتفعة من الصوديوم في نتائج اختبار الدم

إن كان لديك أعراض جانبية أو لاحظت أعراضاً جانبية غير مذكورة في هذه النشرة، فضلاً أبلغ الطبيب أو الصيدلي.

يحفظ بعيداً عن متناول ومرأى الأطفال.
يخزن عند حرارة لا تزيد عن 30°م.
لا تستخدم هذه الدواء بعد تاريخ انتهاء الصلاحية الموضح على الشريط والعبوة الكرتونية. يشير تاريخ انتهاء الصلاحية على آخر يوم من الشهر.
لا تتخلص من الدواء عن طريق رميه في مياه الصرف الصحي أو النفايات المنزلية. اسأل الصيدلي عن كيفية التخلص من الدواء إذا لم تعد بحاجته. هذه الإجراءات ستساعد في حماية البيئة.

المادة الفعالة هي سيليكوكسيب.
تحتوي كل كبسولة على 100 ملغ أو 200 ملغ من سيليكوكسيب.

المكونات الأخرى:
لاكتوز أحادي الماء، هيدروكسي بروبيل سلولوز، كروس بوفيدون، بوفيدون، صوديوم لوريل سلفات، ستيارات المغنيزيوم.
يحتوي غلاف الكبسولة على جيلاتين، ثنائي أكسيد التيتانيوم، ماء، صوديوم لوريل سلفات.
يحتوي حبر الطباعة على شيلاك (صمغ)، بروبيلين غليكول، لون أزرق رقم 2 (مطابق لقانون الغذاء والدواء ومواد التجميل الأمريكي) وصباغ الألمنيوم (كبسولات 100 ملغ)، أكسيد الحديد الأصفر (كبسولات 200 ملغ).

ريليكسيب متوفر بشكل كبسولات صلبة.
كبسولات بيضاء عاتمة مطبوع عليها ‘C5‘ على شريط أزرق على الغطاء و‘100mg‘ على شريط أزرق على الجسم (ريليكسيب 100 ملغ).
كبسولات بيضاء عاتمة مطبوع عليها ‘C6‘ على شريط أصفر على الغطاء و‘200mg‘ على شريط أصفر على الجسم (ريليكسيب 200 ملغ).
الكبسولات معبأة في أشرطة.
يتوفر ريليكسيب في عبوات كرتونية تحتوي على 20 كبسولة (شريطان × 10 كبسولات)

مالك رخصة التسويق
الشركة السعودية للصناعات الصيدلانية
صندوق بريد رقم: 355127، الرياض 11383
المملكة العربية السعودية.
هاتف: 2650354، 2650450 (96611+)
فاكس: 2650383 (96611+)
بريد إلكتروني: info@saudi-pharma.net 

المصنع
ماكلويدز فارماسوتيكال ليميتد
الكتلة رقم 2، بلدة ثيدا
مكتب بريد لوديماجرا، تهسيل بادي
حي سولان، هيماتشال براديش – 174101، الهند 

المصنع المسؤول عن التغليف الثانوي والإفراج عن التشغيلات
الشركة السعودية للصناعات الصيدلانية
صندوق بريد رقم: 355127، الرياض 11383
المملكة العربية السعودية.

12/2021
 Read this leaflet carefully before you start using this product as it contains important information for you

Relexib 200 mg Capsules.

Each capsule contains 200 mg celecoxib. Excipient with known effect Lactose (each capsule contains 33.8 mg lactose monohydrate; see section 4.4). For the full list of excipients, see section 6.1.

Capsule. Size ‘2’ capsules having white opaque cap and white opaque body with ‘C6’ imprinted on a yellow band on the cap and ‘200mg’ imprinted on a yellow band on a body.

Relexib is indicated in adults for the symptomatic relief in the treatment of osteoarthritis, rheumatoid arthritis and ankylosing spondylitis.

The decision to prescribe a selective cyclooxygenase-2 (COX-2) inhibitor should be based on an assessment of the individual patient's overall risks (see sections 4.3 and 4.4).


Posology
As the cardiovascular (CV) risks of celecoxib may increase with dose and duration of exposure, the shortest duration possible and the lowest effective daily dose should be used. The patient's need for symptomatic relief and response to therapy should be re-evaluated periodically, especially in patients with osteoarthritis (see sections 4.3, 4.4, 4.8 and 5.1).

Osteoarthritis
The usual recommended daily dose is 200 mg taken once daily or in two divided doses. In some patients, with insufficient relief from symptoms, an increased dose of 200 mg twice daily may increase efficacy. In the absence of an increase in therapeutic benefit after two weeks, other therapeutic options should be considered.

Rheumatoid arthritis
The initial recommended daily dose is 200 mg taken in two divided doses. The dose may, if needed, later be increased to 200 mg twice daily. In the absence of an increase in therapeutic benefit after two weeks, other therapeutic options should be considered.

Ankylosing spondylitis
The recommended daily dose is 200 mg taken once daily or in two divided doses. In a few patients, with insufficient relief from symptoms, an increased dose of 400 mg once daily or in two divided doses may increase efficacy. In the absence of an increase in therapeutic benefit after two weeks, other therapeutic options should be considered.

The maximum recommended daily dose is 400 mg for all indications.

Special populations
Elderly
As in younger adults, 200 mg per day should be used initially. The dose may, if needed, later be increased to 200 mg twice daily. Particular caution should be exercised in elderly with a body weight less than 50 kg (see sections 4.4 and 5.2).

Paediatric population
Celecoxib is not indicated for use in children.

CYP2C9 poor metabolisers
Patients who are known, or suspected to be CYP2C9 poor metabolisers based on genotyping or previous history/experience with other CYP2C9 substrates should be administered celecoxib with caution as the risk of dose-dependent adverse effects is increased. Consider reducing the dose to half the lowest recommended dose (see section 5.2).

Hepatic impairment
Treatment should be initiated at half the recommended dose in patients with established moderate liver impairment with a serum albumin of 25 – 35 g/l. Experience in such patients is limited to cirrhotic patients (see sections 4.3, 4.4 and 5.2).

Renal impairment
Experience with celecoxib in patients with mild or moderate renal impairment is limited, therefore such patients should be treated with caution (see sections 4.3, 4.4 and 5.2).

Method of administration
Oral use
Relexib may be taken with or without food. For patients who have difficulty swallowing capsules, the contents of a celecoxib capsule can be added to applesauce, rice gruel, yogurt or mashed banana. To do so, the entire capsule contents must be carefully emptied onto a level teaspoon of cool or room temperature applesauce, rice gruel, yogurt or mashed banana and should be ingested immediately with 240 ml of water. The sprinkled capsule contents on applesauce, rice gruel or yogurt are stable for up to 6 hours under refrigerated conditions (2 – 8°C). The sprinkled capsule contents on mashed banana should not be stored under refrigerated conditions and should be ingested immediately.


Hypersensitivity to the active substance or to any of the excipients listed in section 6.1. Known hypersensitivity to sulfonamides. Active peptic ulceration or gastrointestinal (GI) bleeding. Patients who have experienced asthma, acute rhinitis, nasal polyps, angioneurotic oedema, urticaria or other allergic-type reactions after taking acetylsalicylic acid (aspirin) or other non-steroidal anti-inflammatory drugs (NSAIDs) including COX-2 inhibitors. In pregnancy and in women of childbearing potential unless using an effective method of contraception (see section 4.6). Celecoxib has been shown to cause malformations in the two animal species studied (see sections 4.6 and 5.3). The potential for human risk in pregnancy is unknown, but cannot be excluded. Breast-feeding (see sections 4.6 and 5.3). Severe hepatic dysfunction (serum albumin <25 g/l or Child-Pugh score ≥10). Patients with estimated creatinine clearance <30 ml/min. Inflammatory bowel disease. Congestive heart failure (NYHA II-IV). Established ischaemic heart disease, peripheral arterial disease and/or cerebrovascular disease.

Gastrointestinal (GI) effects
Upper and lower gastrointestinal complications (perforations, ulcers or bleedings [PUBs]), some of them resulting in fatal outcome, have occurred in patients treated with celecoxib. Caution is advised with treatment of patients most at risk of developing a gastrointestinal complication with NSAIDs; the elderly, patients using any other NSAID or antiplatelet drugs (such as acetylsalicylic acid), or glucocorticoids concomitantly, patients using alcohol, or patients with a prior history of gastrointestinal disease, such as ulceration and GI bleeding.

There is further increase in the risk of gastrointestinal adverse effects for celecoxib (gastrointestinal ulceration or other gastrointestinal complications), when celecoxib is taken concomitantly with acetylsalicylic acid (even at low doses). A significant difference in GI safety between selective COX-2 inhibitors + acetylsalicylic acid vs. NSAIDs + acetylsalicylic acid has not been demonstrated in long-term clinical trials (see section 5.1).

Concomitant NSAID use
The concomitant use of celecoxib and a non-aspirin NSAID should be avoided.

Cardiovascular effects
Increased number of serious cardiovascular (CV) events, mainly myocardial infarction, has been found in a long-term placebo-controlled study in subjects with sporadic adenomatous polyps treated with celecoxib at doses of 200 mg BID and 400 mg BID compared to placebo (see section 5.1).

As the cardiovascular risks of celecoxib may increase with dose and duration of exposure, the shortest duration possible and the lowest effective daily dose should be used. NSAIDs, including COX-2 selective inhibitors, have been associated with increased risk of cardiovascular and thrombotic adverse events when taken long term. The exact magnitude of the risk associated with a single dose has not been determined, nor has the exact duration of therapy associated with increased risk. The patient's need for symptomatic relief and response to therapy should be re-evaluated periodically, especially in patients with osteoarthritis (see sections 4.2, 4.3, 4.8 and 5.1).

Patients with significant risk factors for cardiovascular events (e.g. hypertension, hyperlipidaemia, diabetes mellitus, smoking) should only be treated with celecoxib after careful consideration (see section 5.1).

COX-2 selective inhibitors are not a substitute for acetylsalicylic acid for prophylaxis of cardiovascular thrombo-embolic diseases because of their lack of antiplatelet effects. Therefore, antiplatelet therapies should not be discontinued (see section 5.1).

Fluid retention and oedema
As with other medicinal products known to inhibit prostaglandin synthesis, fluid retention and oedema have been observed in patients taking celecoxib. Therefore, celecoxib should be used with caution in patients with history of cardiac failure, left ventricular dysfunction or hypertension, and in patients with pre-existing oedema from any other reason, since prostaglandin inhibition may result in deterioration of renal function and fluid retention. Caution is also required in patients taking diuretic treatment or otherwise at risk of hypovolaemia.

Hypertension
As with all NSAIDS, celecoxib can lead to the onset of new hypertension or worsening of pre-existing hypertension, either of which may contribute to the increased incidence of cardiovascular events. Therefore, blood pressure should be monitored closely during the initiation of therapy with celecoxib and throughout the course of therapy.

Hepatic and renal effects
Compromised renal or hepatic function and especially cardiac dysfunction are more likely in the elderly and therefore medically appropriate supervision should be maintained.

NSAIDs, including celecoxib, may cause renal toxicity. Clinical trials with celecoxib have shown renal effects similar to those observed with comparator NSAIDs. Patients at greatest risk for renal toxicity are those with impaired renal function, heart failure, liver dysfunction, those taking diuretics, angiotensin converting enzyme (ACE)-inhibitors, angiotensin II receptor antagonists, and the elderly (see section 4.5). Such patients should be carefully monitored while receiving treatment with celecoxib.

Some cases of severe hepatic reactions, including fulminant hepatitis (some with fatal outcome), liver necrosis and, hepatic failure (some with fatal outcome or requiring liver transplant), have been reported with celecoxib. Among the cases that reported time to onset, most of the severe adverse hepatic events developed within one month after initiation of celecoxib treatment (see section 4.8).

If during treatment, patients deteriorate in any of the organ system functions described above, appropriate measures should be taken and discontinuation of celecoxib therapy should be considered.

CYP2D6 inhibition
Celecoxib inhibits CYP2D6. Although it is not a strong inhibitor of this enzyme, a dose reduction may be necessary for individually dose-titrated medicinal products that are metabolised by CYP2D6 (see section 4.5).

CYP2C9 poor metabolisers
Patients known to be CYP2C9 poor metabolisers should be treated with caution (see section 5.2).

Skin and systemic hypersensitivity reactions
Serious skin reactions, some of them fatal, including exfoliative dermatitis, Stevens-Johnson syndrome, and toxic epidermal necrolysis, have been reported very rarely in association with the use of celecoxib (see section 4.8). Patients appear to be at highest risk for these reactions early in the course of therapy: the onset of the reaction occurring in the majority of cases within the first month of treatment. Serious hypersensitivity reactions (including anaphylaxis, angioedema and drug rash with eosinophilia and systemic symptoms (DRESS), or hypersensitivity syndrome), have been reported in patients receiving celecoxib (see section 4.8). Patients with a history of sulfonamide allergy or any drug allergy may be at greater risk of serious skin reactions or hypersensitivity reactions (see section 4.3). Celecoxib should be discontinued at the first appearance of skin rash, mucosal lesions, or any other sign of hypersensitivity.

General
Celecoxib may mask fever and other signs of inflammation.

Use with oral anticoagulants
In patients on concurrent therapy with warfarin, serious bleeding events, some of them fatal, have been reported. Increased prothrombin time (INR) with concurrent therapy has been reported. Therefore, this should be closely monitored in patients receiving warfarin/coumarin-type oral anticoagulants, particularly when therapy with celecoxib is initiated or celecoxib dose is changed (see section 4.5). Concomitant use of anticoagulants with NSAIDS may increase the risk of bleeding. Caution should be exercised when combining celecoxib with warfarin or other oral anticoagulants, including novel anticoagulants (e.g. apixaban, dabigatran, and rivaroxaban).

Excipients
Relexib 200 mg capsules contain lactose (33.8 mg). Patients with rare hereditary problems of galactose intolerance, the Lapp lactase deficiency or glucose-galactose malabsorption should not take this medicine.


Pharmacodynamic interactions
Anticoagulants
Anticoagulant activity should be monitored particularly in the first few days after initiating or changing the dose of celecoxib in patients receiving warfarin or other anticoagulants since these patients have an increased risk of bleeding complications. Therefore, patients receiving oral anticoagulants should be closely monitored for their prothrombin time INR, particularly in the first few days when therapy with celecoxib is initiated or the dose of celecoxib is changed (see section 4.4). Bleeding events in association with increases in prothrombin time have been reported, predominantly in the elderly, in patients receiving celecoxib concurrently with warfarin, some of them fatal.

Anti-hypertensives
NSAIDs may reduce the effect of anti-hypertensive medicinal products including ACE-inhibitors, angiotensin II receptor antagonists, diuretics and beta-blockers. As for NSAIDs, the risk of acute renal insufficiency, which is usually reversible, may be increased in some patients with compromised renal function (e.g. dehydrated patients, patients on diuretics, or elderly patients) when ACE-inhibitors, angiotensin II receptor antagonists, and/or diuretics are combined with NSAIDs, including celecoxib (see section 4.4). Therefore, the combination should be administered with caution, especially in the elderly. Patients should be adequately hydrated and consideration should be given to monitoring of renal function after initiation of concomitant therapy, and periodically thereafter.

In a 28-day clinical study in patients with lisinopril-controlled Stage I and II hypertension, administration of celecoxib 200 mg BID resulted in no clinically significant increases, when compared to placebo treatment, in mean daily systolic or diastolic blood pressure as determined using 24-hour ambulatory blood pressure monitoring. Among patients treated with celecoxib 200 mg BID, 48% were considered unresponsive to lisinopril at the final clinic visit (defined as either cuff diastolic blood pressure >90 mmHg or cuff diastolic blood pressure increased >10% compared to baseline), compared to 27% of patients treated with placebo; this difference was statistically significant.

Ciclosporin and tacrolimus
Co-administration of NSAIDs and ciclosporin or tacrolimus may increase the nephrotoxic effect of ciclosporin or tacrolimus, respectively. Renal function should be monitored when celecoxib and any of these medicinal products are combined.

Acetylsalicylic acid
Celecoxib can be used with low-dose acetylsalicylic acid but is not a substitute for acetylsalicylic acid for CV prophylaxis. In the submitted studies, as with other NSAIDs, an increased risk of gastrointestinal ulceration or other gastrointestinal complications compared to use of celecoxib alone was shown for concomitant administration of low-dose acetylsalicylic acid (see section 5.1).

Pharmacokinetic interactions
Effects of celecoxib on other medicinal products

CYP2D6 inhibition
Celecoxib is an inhibitor of CYP2D6. The plasma concentrations of medicinal products that are substrates of this enzyme may be increased when celecoxib is used concomitantly. Examples of medicinal products which are metabolised by CYP2D6 are antidepressants (tricyclics and SSRIs), neuroleptics, anti-arrhythmic medicinal products, etc. The dose of individually dose-titrated CYP2D6 substrates may need to be reduced when treatment with celecoxib is initiated or increased if treatment with celecoxib is terminated.

Concomitant administration of celecoxib 200 mg twice daily resulted in 2.6-fold and 1.5-fold increases in plasma concentrations of dextromethorphan and metoprolol (CYP2D6 substrates), respectively. These increases are due to celecoxib inhibition of the CYP2D6 substrate metabolism.

CYP2C19 inhibition
In vitro studies have shown some potential for celecoxib to inhibit CYP2C19 catalysed metabolism. The clinical significance of this in vitro finding is unknown. Examples of medicinal products which are metabolised by CYP2C19 are diazepam, citalopram and imipramine.

Methotrexate
In patients with rheumatoid arthritis celecoxib had no statistically significant effect on the pharmacokinetics (plasma or renal clearance) of methotrexate (in rheumatologic doses). However, adequate monitoring for methotrexate-related toxicity should be considered when combining these two medicinal products.

Lithium
In healthy subjects, co-administration of celecoxib 200 mg twice daily with 450 mg twice daily of lithium resulted in a mean increase in Cmax of 16% and in area under the curve (AUC) of 18% of lithium. Therefore, patients on lithium treatment should be closely monitored when celecoxib is introduced or withdrawn.

Oral contraceptives
In an interaction study, celecoxib had no clinically relevant effects on the pharmacokinetics of oral contraceptives (1 mg norethisterone/35 micrograms ethinylestradiol).

Glibenclamide/tolbutamide
Celecoxib does not affect the pharmacokinetics of tolbutamide (CYP2C9 substrate), or glibenclamide to a clinically relevant extent.

Effects of other medicinal products on celecoxib
CYP2C9 poor metabolisers

In individuals who are CYP2C9 poor metabolisers and demonstrate increased systemic exposure to celecoxib, concomitant treatment with CYP2C9 inhibitors such as fluconazole could result in further increases in celecoxib exposure. Such combinations should be avoided in known CYP2C9 poor metabolisers (see sections 4.2 and 5.2).

CYP2C9 inhibitors and inducers
Since celecoxib is predominantly metabolised by CYP2C9 it should be used at half the recommended dose in patients receiving fluconazole. Concomitant use of 200 mg single dose of celecoxib and 200 mg once daily of fluconazole, a potent CYP2C9 inhibitor, resulted in a mean increase in celecoxib Cmax of 60% and in AUC of 130%. Concomitant use of inducers of CYP2C9 such as rifampicin, carbamazepine and barbiturates may reduce plasma concentrations of celecoxib.

Ketoconazole and antacids
Ketoconazole or antacids have not been observed to affect the pharmacokinetics of celecoxib.

Paediatric population
Interaction studies have only been performed in adults.


Pregnancy
Studies in animals (rats and rabbits) have shown reproductive toxicity, including malformations (see sections 4.3 and 5.3). Inhibition of prostaglandin synthesis might adversely affect pregnancy. Data from epidemiological studies suggest an increased risk of spontaneous abortion after use of prostaglandin synthesis inhibitors in early pregnancy. The potential for human risk in pregnancy is unknown, but cannot be excluded. Celecoxib, as with other medicinal products inhibiting prostaglandin synthesis, may cause uterine inertia and premature closure of the ductus arteriosus during the last trimester.

During the second or third trimester of pregnancy, NSAIDs including celecoxib may cause fetal renal dysfunction which may result in reduction of amniotic fluid volume or oligohydramnios in severe cases. Such effects may occur shortly after treatment initiation and are usually reversible.

Celecoxib is contraindicated in pregnancy and in women who can become pregnant (see sections 4.3 and 4.4). If a woman becomes pregnant during treatment, celecoxib should be discontinued.

Breast-feeding
Celecoxib is excreted in the milk of lactating rats at concentrations similar to those in plasma. Administration of celecoxib to a limited number of lactating women has shown a very low transfer of celecoxib into breast milk. Women who take Relexib should not breastfeed.

Fertility
Based on the mechanism of action, the use of NSAIDs, including celecoxib, may delay or prevent rupture of ovarian follicles, which has been associated with reversible infertility in some women.


Patients who experience dizziness, vertigo or somnolence while taking Relexib should refrain from driving or operating machinery.


Adverse reactions are listed by system organ class and ranked by frequency in Table 1, reflecting data from the following sources:

● Adverse reactions reported in osteoarthritis patients and rheumatoid arthritis patients at incidence rates greater than 0.01% and greater than those reported for placebo during 12 placebo- and/or active-controlled clinical trials of duration up to 12 weeks at celecoxib daily doses from 100 mg up to 800 mg. In additional studies using non-selective NSAID comparators, approximately 7400 arthritis patients have been treated with celecoxib at daily doses up to 800 mg, including approximately 2300 patients treated for 1 year or longer. The adverse reactions observed with celecoxib in these additional studies were consistent with those for osteoarthritis and rheumatoid arthritis patients listed in Table 1.

● Adverse reactions reported at incidence rates greater than placebo for subjects treated with celecoxib 400 mg daily in long-term polyp prevention trials of duration up to 3 years (the Adenoma Prevention with Celecoxib (APC) and Prevention of Colorectal Sporadic Adenomatous Polyps (PreSAP) trials; see section 5.1, Cardiovascular safety – long-term studies involving patients with sporadic adenomatous polyps).

● Adverse drug reactions from post-marketing surveillance as spontaneously reported during a period in which an estimated >70 million patients were treated with celecoxib (various doses, durations, and indications). Even though these were identified as reactions from post-marketing reports, trial data was consulted to estimate frequency. Frequencies are based on a cumulative meta-analysis with pooling of trials representing exposure in 38102 patients.

Table 1. Adverse drug reactions in celecoxib clinical trials and surveillance experience (MedDRA preferred terms)1,2

 

Adverse Drug Reaction Frequency

System Organ Class

Very Common (≥1/10)

Common

(≥1/100 to

<1/10)

Uncommon

(≥1/1,000 to

<1/100)

Rare

(≥1/10,000 to

<1/1,000)

Very Rare

(<1/10,000)

Frequency Not Known (cannot be estimated from available data)

Infections and infestations

 

Sinusitis, upper respiratory tract infection, pharyngitis, urinary tract infection

 

 

 

 

Blood and lymphatic system disorders

 

 

Anaemia

Leukopenia, thrombo- cytopenia

Pancytopenia4

 

Immune system disorders

 

Hyper- sensitivity

 

 

Anaphylactic shock4, anaphylactic reaction4

 

Metabolism and nutrition disorders

 

 

Hyperkalaemia

 

 

 

Psychiatric disorders

 

Insomnia

Anxiety, depression, fatigue

Confusional state, hallucinations4

 

 

Nervous system disorders

 

Dizziness, hypertonia, headache4

Cerebral infarction1, paraesthesia, somnolence

Ataxia, dysgeusia

Haemorrhage intracranial (including fatal intracranial haemorrhage)4, meningitis aseptic4, epilepsy (including aggravated epilepsy)4, ageusia4, anosmia4

 

Eye disorders

 

 

Vision blurred, conjunctivitis4

Eye haemorrhage4

Retinal artery occlusion4, retinal vein occlusion4

 

Ear and labyrinth disorders

 

 

Tinnitus, hypoacusis1

 

 

 

Cardiac disorders

 

Myocardial infarction1

Cardiac failure, palpitations, tachycardia

Arrhythmia4

 

 

Vascular disorders

Hyper- tension1 (including aggravated hyper- tension)

 

 

Pulmonary embolism4, flushing4

Vasculitis4

 

Respiratory, thoracic, and mediastinal disorders

 

Rhinitis, cough, dyspnoea1

Bronchospasm4

Pneumonitis4

 

 

Gastrointestinal disorders

 

Nausea4, abdominal pain, diarrhoea, dyspepsia, flatulence, vomiting1, dysphagia1

Constipation, gastritis, stomatitis, gastrointestinal inflammation (including aggravation of gastrointestinal inflammation), eructation

Gastro- intestinal haemorrhage4, duodenal ulcer, gastric ulcer, oesophageal ulcer, intestinal ulcer, large intestinal ulcer, intestinal perforation, oesophagitis, melaena, pancreatitis, colitis4

 

 

Hepatobiliary disorders

 

 

Hepatic function abnormal, hepatic enzyme increased (including increased SGOT and SGPT)

Hepatitis4

Hepatic failure4 (sometimes fatal or requiring liver transplant), hepatitis fulminant4 (some with fatal outcome), hepatic necrosis4, cholestasis4, hepatitis cholestatic4, jaundice4

 

Skin and subcutaneous tissue disorders

 

Rash, pruritus (includes pruritus generalised)

Urticaria, ecchymosis4

Angioedema4, alopecia, photo- sensitivity

Dermatitis exfoliative4, erythema multiforme4, Stevens-Johnson syndrome4, toxic epidermal necrolysis4, drug reaction with eosinophilia and systemic symptoms (DRESS)4, acute generalised exanthematous pustulosis (AGEP)4, dermatitis bullous4

 

Musculoskeletal and connective tissue disorders

 

Arthralgia4

Muscle spasms (leg cramps)

 

Myositis4

 

Renal and urinary disorders

 

 

Blood creatinine increased, blood urea increased

Renal failure acute4, hypo-natraemia4

Tubulointerstitial nephritis4, nephrotic syndrome4, glomerulonephritis minimal lesion4

 

Reproductive system and breast disorders

 

 

 

Menstrual disorder4

 

Infertility female (female fertility decreased)3

General disorders and administrative site conditions

 

Influenza-like illness, oedema peripheral/ fluid retention

Face oedema, chest pain4

 

 

 

Injury, poisoning and procedural complications

 

Injury (accidental injury)

 

 

 

 

 

1 Adverse drug reactions that occurred in polyp prevention trials, representing subjects treated with celecoxib 400 mg daily in 2 clinical trials of duration up to 3 years (the APC and PreSAP trials). The adverse drug reactions listed above for the polyp prevention trials are only those that have been previously recognised in the post-marketing surveillance experience, or have occurred more frequently than in the arthritis trials.

2 Furthermore, the following previously unknown adverse reactions occurred in polyp prevention trials, representing subjects treated with celecoxib 400 mg daily in 2 clinical trials of duration up to 3 years (the APC and PreSAP trials):

Common: angina pectoris, irritable bowel syndrome, nephrolithiasis, blood creatinine increased, benign prostatic hyperplasia, weight increased. Uncommon: helicobacter infection, herpes zoster, erysipelas, bronchopneumonia, labyrinthitis, gingival infection, lipoma, vitreous floaters, conjunctival haemorrhage, deep vein thrombosis, dysphonia, haemorrhoidal haemorrhage, frequent bowel movements, mouth ulceration, allergic dermatitis, ganglion, nocturia, vaginal haemorrhage, breast tenderness, lower limb fracture, blood sodium increased.

3 Women intending to become pregnant are excluded from all trials, thus consultation of the trial database for the frequency of this event was not reasonable.

4 Frequencies are based on cumulative meta-analysis with pooling of trials representing exposure in 38102 patients.

In final data (adjudicated) from the APC and PreSAP trials in patients treated with celecoxib 400 mg daily for up to 3 years (pooled data from both trials; see section 5.1 for results from individual trials), the excess rate over placebo for myocardial infarction was 7.6 events per 1,000 patients (uncommon) and there was no excess rate for stroke (types not differentiated) over placebo.

Reporting of suspected adverse reactions
Reporting suspected adverse reactions after authorisation of the medicinal product is important. It allows continued monitoring of the benefit/risk balance of the medicinal product. Healthcare professionals are asked to report any suspected adverse reactions.

To reports any side effect(s):

  • Saudi Arabia:

The National Pharmacovigilance Centre (NPC):

  • Fax: +966 11 205 7662
  • SFDA Call Center: 19999
  • Email: npc.drug@sfda.gov.sa
  • Website: https://ade.sfda.gov.sa
  • Other GCC States:

Please contact the relevant competent authority. 


There is no clinical experience of overdose. Single doses up to 1200 mg and multiple doses up to 1200 mg twice daily have been administered to healthy subjects for nine days without clinically significant adverse effects. In the event of suspected overdose, appropriate supportive medical care should be provided e.g. by eliminating the gastric contents, clinical supervision and, if necessary, the institution of symptomatic treatment. Dialysis is unlikely to be an efficient method of medicinal product removal due to high protein binding.


Pharmacotherapeutic group: Non-steroidal anti-inflammatory and antirheumatic drugs, NSAIDs, Coxibs, ATC code: M01AH01.

Mechanism of action
Celecoxib is an oral, selective, COX-2 inhibitor within the clinical dose range (200 – 400 mg daily). No statistically significant inhibition of COX-1 (assessed as ex vivo inhibition of thromboxane B2 [TxB2] formation) was observed in this dose range in healthy volunteers.

Pharmacodynamic effects
Cyclooxygenase is responsible for generation of prostaglandins. Two isoforms, COX-1 and COX-2, have been identified. COX-2 is the isoform of the enzyme that has been shown to be induced by pro-inflammatory stimuli and has been postulated to be primarily responsible for the synthesis of prostanoid mediators of pain, inflammation, and fever. COX-2 is also involved in ovulation, implantation and closure of the ductus arteriosus, regulation of renal function, and central nervous system functions (fever induction, pain perception and cognitive function). It may also play a role in ulcer healing. COX-2 has been identified in tissue around gastric ulcers in humans but its relevance to ulcer healing has not been established.

The difference in antiplatelet activity between some COX-1 inhibiting NSAIDs and COX-2 selective inhibitors may be of clinical significance in patients at risk of thrombo-embolic reactions. COX-2 selective inhibitors reduce the formation of systemic (and therefore possibly endothelial) prostacyclin without affecting platelet thromboxane.

Celecoxib is a diaryl-substituted pyrazole, chemically similar to other non-arylamine sulfonamides (e.g. thiazides, furosemide) but differs from arylamine sulfonamides (e.g. sulfamethoxizole and other sulfonamide antibiotics).

A dose-dependent effect on TxB2 formation has been observed after high doses of celecoxib. However, in healthy subjects, in small multiple dose studies with 600 mg BID (three times the highest recommended dose) celecoxib had no effect on platelet aggregation and bleeding time compared to placebo.

Clinical efficacy and safety
Several clinical studies have been performed confirming efficacy and safety in osteoarthritis, rheumatoid arthritis and ankylosing spondylitis. Celecoxib was evaluated for the treatment of the inflammation and pain of osteoarthritis of the knee and hip in approximately 4200 patients in placebo and active controlled trials of up to 12 weeks duration. It was also evaluated for treatment of the inflammation and pain of rheumatoid arthritis in approximately 2100 patients in placebo and active controlled trials of up to 24 weeks duration. Celecoxib at daily doses of 200 mg – 400 mg provided pain relief within 24 hours of dosing. Celecoxib was evaluated for the symptomatic treatment of ankylosing spondylitis in 896 patients in placebo and active controlled trials of up to 12 weeks duration. Celecoxib at doses of 100 mg BID, 200 mg QD, 200 mg BID and 400 mg QD in these studies demonstrated significant improvement in pain, global disease activity and function in ankylosing spondylitis.

Five randomised double-blind controlled studies have been conducted including scheduled upper gastrointestinal endoscopy in approximately 4500 patients free from initial ulceration (celecoxib doses from 50 mg – 400 mg BID). In twelve week endoscopy studies celecoxib (100 – 800 mg per day) was associated with a significantly lower risk of gastroduodenal ulcers compared with naproxen (1000 mg per day) and ibuprofen (2400 mg per day). The data were inconsistent in comparison with diclofenac (150 mg per day). In two of the 12-week studies the percentage of patients with endoscopic gastroduodenal ulceration was not significantly different between placebo and celecoxib 200 mg BID and 400 mg BID.

In a prospective long-term safety outcome study (6 to 15 month duration, CLASS study), 5,800 osteoarthritis and 2,200 rheumatoid arthritis patients received celecoxib 400 mg BID (4-fold and 2-fold the recommended osteoarthritis and rheumatoid arthritis doses, respectively), ibuprofen 800 mg TID or diclofenac 75 mg BID (both at therapeutic doses). Twenty-two percent of enrolled patients took concomitant low-dose acetylsalicylic acid (≤325 mg/day), primarily for cardiovascular (CV) prophylaxis. For the primary endpoint complicated ulcers (defined as gastrointestinal bleeding, perforation or obstruction) celecoxib was not significantly different than either ibuprofen or diclofenac individually. Also for the combined NSAID group there was no statistically significant difference for complicated ulcers (relative risk 0.77, 95 % CI 0.41 – 1.46, based on entire study duration). For the combined endpoint, complicated and symptomatic ulcers, the incidence was significantly lower in the celecoxib group compared to the NSAID group, relative risk 0.66, 95 % CI 0.45 – 0.97 but not between celecoxib and diclofenac. Those patients on celecoxib and concomitant low-dose acetylsalicylic acid experienced 4-fold higher rates of complicated ulcers as compared to those on celecoxib alone. The incidence of clinically significant decreases in haemoglobin (>2 g/dL), confirmed by repeat testing, was significantly lower in patients on celecoxib compared to the NSAID group, relative risk 0.29, 95 % CI 0.17 – 0.48. The significantly lower incidence of this event with celecoxib was maintained with or without acetylsalicylic acid use.

In a prospective randomised 24 week safety study in patients who were aged ≥60 years or had a history of gastroduodenal ulcers (users of ASA excluded), the percentages of patients with decreases in haemoglobin (≥2 g/dL) and/or haematocrit (≥10%) of defined or presumed GI origin were lower in patients treated with celecoxib 200 mg twice daily (N=2238) compared to patients treated with diclofenac SR 75 mg twice daily plus omeprazole 20 mg once daily (N=2246) (0.2% vs. 1.1% for defined GI origin, p = 0.004; 0.4% vs. 2.4% for presumed GI origin, p = 0.0001). The rates of clinically manifest GI complications such as perforation, obstruction or haemorrhage were very low with no differences between the treatment groups (4 – 5 per group).

Cardiovascular safety – long-term studies involving subjects with sporadic adenomatous polyps
Two studies involving subjects with sporadic adenomatous polyps were conducted with celecoxib i.e., the APC trial (Adenoma Prevention with Celecoxib) and the PreSAP trial (Prevention of Spontaneous Adenomatous Polyps). In the APC trial, there was a dose-related increase in the composite endpoint of CV death, myocardial infarction, or stroke (adjudicated) with celecoxib compared to placebo over 3 years of treatment. The PreSAP trial did not demonstrate a statistically significant increased risk for the same composite endpoint.

In the APC trial, the relative risks compared to placebo for a composite endpoint (adjudicated) of CV death, myocardial infarction, or stroke were 3.4 (95% CI 1.4 – 8.5) with celecoxib 400 mg twice daily and 2.8 (95% CI 1.1 – 7.2) with celecoxib 200 mg twice daily. Cumulative rates for this composite endpoint over 3 years were 3.0% (20/671 subjects) and 2.5% (17/685 subjects), respectively, compared to 0.9% (6/679 subjects) for placebo. The increases for both celecoxib dose groups versus placebo were mainly due to an increased incidence of myocardial infarction.

In the PreSAP trial, the relative risk compared to placebo for this same composite endpoint (adjudicated) was 1.2 (95% CI 0.6 – 2.4) with celecoxib 400 mg once daily compared to placebo. Cumulative rates for this composite endpoint over 3 years were 2.3% (21/933 subjects) and 1.9% (12/628 subjects), respectively. The incidence of myocardial infarction (adjudicated) was 1.0% (9/933 subjects) with celecoxib 400 mg once daily and 0.6% (4/628 subjects) with placebo.

Data from a third long-term study, ADAPT (The Alzheimer's Disease Anti-inflammatory Prevention Trial), did not show a significantly increased CV risk with celecoxib 200 mg BID compared to placebo. The relative risk compared to placebo for a similar composite endpoint (CV death, myocardial infarction, stroke) was 1.14 (95% CI 0.61 – 2.15) with celecoxib 200 mg twice daily. The incidence of myocardial infarction was 1.1% (8/717 patients) with celecoxib 200 mg twice daily and 1.2% (13/1070 patients) with placebo.

Prospective Randomised Evaluation of Celecoxib Integrated Safety vs. Ibuprofen Or Naproxen (PRECISION)
The PRECISION study was a double-blind study of cardiovascular safety in OA or RA patients with or at high risk for cardiovascular disease comparing Celecoxib (200 – 400 mg daily) with Naproxen (750 – 1000 mg daily) and Ibuprofen (1800 – 2400 mg daily). The primary endpoint, Antiplatelet Trialists Collaboration (APTC), was an independently adjudicated composite of cardiovascular death (including hemorrhagic death), non-fatal myocardial infarction or non-fatal stroke. The study was planned with 80% power to evaluate non-inferiority. All patients were prescribed open-label esomeprazole (20 – 40 mg) for gastro protection. Patients who were taking low-dose aspirin were permitted to continue therapy, at baseline nearly half of the subjects were on aspirin. Secondary and tertiary endpoints included cardiovascular, gastrointestinal and renal outcomes. The Average Dose dispensed was 209±37 mg/day for Celecoxib, 2045±246 for Ibuprofen and 852±103 for Naproxen.

Regarding the primary endpoint, Celecoxib, as compared with either naproxen or ibuprofen, met all four pre-specified non-inferiority requirements, see Table 2.

Other independently adjudicated secondary and tertiary endpoints included cardiovascular, gastrointestinal and renal outcomes. Additionally, there was a 4-month substudy focusing on the effects of the three drugs on blood pressure as measured by ambulatory monitoring (ABPM).

Table 2. Primary Analysis of the Adjudicated APTC Composite Endpoint

Intent-To-Treat Analysis (ITT, through month 30)

 

Celecoxib 100 – 200 mg bid

Ibuprofen 600 – 800 mg tid

Naproxen 375 – 500 mg bid

N

8,072

8,040

7,969

Subjects with Events

188 (2.3%)

218 (2.7%)

201 (2.5%)

Pairwise Comparison

Celecoxib vs. Naproxen

Celecoxib vs. Ibuprofen

Ibuprofen vs. Naproxen

HR (95% CI)

0.93 (0.76, 1.13)

0.86 (0.70, 1.04)

1.08 (0.89, 1.31)

Modified Intent-To-Treat Analysis (mITT, on treatment through month 43)

 

Celecoxib 100 – 200 mg bid

Ibuprofen 600 – 800 mg tid

Naproxen 375 – 500 mg bid

N

8,030

7,990

7,933

Subjects with Events

134 (1.7%)

155 (1.9%)

144 (1.8%)

Pairwise Comparison

Celecoxib vs. Naproxen

Celecoxib vs. Ibuprofen

Ibuprofen vs. Naproxen

HR (95% CI)

0.90 (0.72, 1.14)

0.81 (0.64, 1.02)

1.12 (0.889, 1.40)

The results were overall numerically similar in the celecoxib and comparator groups for the secondary and tertiary endpoints and there were overall no unexpected safety findings.

Taken together the PRECISION study indicates that celecoxib at the lowest approved dose of 100 mg twice daily is non-inferior to ibuprofen dosed in the range of 600 mg – 800 mg three times daily or naproxen dosed in the range of 375 mg – 500 mg twice daily with respect to cardiovascular adverse effects. The cardiovascular risks of the NSAID class, including coxibs, are dose-dependent, therefore, the results for celecoxib 200 mg daily on the composite cardiovascular endpoint cannot be extrapolated to dosing regimens using the higher doses of celecoxib.


Absorption
Celecoxib is well absorbed reaching peak plasma concentrations after approximately 2 – 3 hours. Dosing with food (high fat meal) delays absorption of celecoxib by about 1 hour resulting in a Tmax of about 4 hours and increases bioavailability by about 20%.

In healthy adult volunteers, the overall systemic exposure (AUC) of celecoxib was equivalent when celecoxib was administered as intact capsule or capsule contents sprinkled on applesauce. There were no significant alterations in Cmax, Tmax or T1/2 after administration of capsule contents on applesauce.

Distribution
Plasma protein binding is about 97% at therapeutic plasma concentrations and the medicinal product is not preferentially bound to erythrocytes.

Biotransformation
Celecoxib metabolism is primarily mediated via cytochrome P450 2C9. Three metabolites, inactive as COX-1 or COX-2 inhibitors, have been identified in human plasma i.e., a primary alcohol, the corresponding carboxylic acid and its glucuronide conjugate.

Cytochrome P450 2C9 activity is reduced in individuals with genetic polymorphisms that lead to reduced enzyme activity, such as those homozygous for the CYP2C9*3 polymorphism.

In a pharmacokinetic study of celecoxib 200 mg administered once daily in healthy volunteers, genotyped as either CYP2C9*1/*1, CYP2C9*1/*3, or CYP2C9*3/*3, the median Cmax and AUC0-24 of celecoxib on day 7 were approximately 4-fold and 7-fold, respectively, in subjects genotyped as CYP2C9*3/*3 compared to other genotypes. In three separate single dose studies, involving a total of 5 subjects genotyped as CYP2C9*3/*3, single-dose AUC0-24 increased by approximately 3-fold compared to normal metabolisers. It is estimated that the frequency of the homozygous *3/*3 genotype is 0.3 – 1.0% among different ethnic groups.

Patients who are known, or suspected to be CYP2C9 poor metabolisers based on previous history/experience with other CYP2C9 substrates should be administered celecoxib with caution (see section 4.2).

No clinically significant differences were found in PK parameters of celecoxib between elderly African-Americans and Caucasians.

The plasma concentration of celecoxib is approximately 100% increased in elderly women (>65 years).

Compared to subjects with normal hepatic function, patients with mild hepatic impairment had a mean increase in Cmax of 53% and in AUC of 26% of celecoxib. The corresponding values in patients with moderate hepatic impairment were 41% and 146% respectively. The metabolic capacity in patients with mild to moderate impairment was best correlated to their albumin values. Treatment should be initiated at half the recommended dose in patients with moderate liver impairment (with serum albumin 25 – 35 g/l). Patients with severe hepatic impairment (serum albumin <25 g/l) have not been studied and celecoxib is contraindicated in this patient group.

There is little experience of celecoxib in renal impairment. The pharmacokinetics of celecoxib has not been studied in patients with renal impairment but is unlikely to be markedly changed in these patients. Thus caution is advised when treating patients with renal impairment. Severe renal impairment is contraindicated.

Elimination
Celecoxib is mainly eliminated by metabolism. Less than 1% of the dose is excreted unchanged in urine. The inter-subject variability in the exposure of celecoxib is about 10-fold. Celecoxib exhibits dose- and time-independent pharmacokinetics in the therapeutic dose range. Elimination half-life is 8 – 12 hours. Steady state plasma concentrations are reached within 5 days of treatment.


Non-clinical safety data revealed no special hazard for humans based on conventional studies of repeated dose toxicity, mutagenicity or carcinogenicity beyond those addressed in section 4.4, 4.6, and 5.1 of the SPC.

Celecoxib at oral doses ≥150 mg/kg/day (approximately 2-fold human exposure at 200 mg twice daily as measured by AUC0-24), caused an increased incidence of ventricular septal defects, a rare event, and foetal alterations, such as ribs fused, sternebrae fused and sternebrae misshapen when rabbits were treated throughout organogenesis. A dose-dependent increase in diaphragmatic hernias was observed when rats were given celecoxib at oral doses ≥30 mg/kg/day (approximately 6-fold human exposure based on the AUC0-24 at 200 mg twice daily) throughout organogenesis. These effects are expected following inhibition of prostaglandin synthesis. In rats, exposure to celecoxib during early embryonic development resulted in pre-implantation and post-implantation losses, and reduced embryo/foetal survival.

Celecoxib was excreted in rat milk. In a peri-post natal study in rats, pup toxicity was observed.

In a 2 year toxicity study an increase in nonadrenal thrombosis was observed in male rat at high doses.


Capsules content
Lactose monohydrate
Hydroxypropyl cellulose
Crospovidone
Povidone
Sodium lauryl sulfate
Magnesium stearate

Capsule shells
Titanium dioxide
Gelatin
Water
Sodium lauryl sulfate

Printing ink
Shellac
Propylene glycol
Yellow iron oxide


Not applicable.


36 months.

Do not store above 30°C.


Relexib is available as 20 capsules carton pack containing 2 Alu- Clear PVC/PVdc blisters of 10 capsules each.


Any unused medicinal product or waste material should be disposed of in accordance with local requirements.


Saudi Pharmaceutical Industries P.O. Box No.: 355127, Riyadh 11383 Kingdom of Saudi Arabia. Tel: (+96611) 2650450, 2650354 Fax: (+96611) 2650383 Email: info@saudi-pharma.net

12/2021
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