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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)

 

· Orotix® contains the active substance etoricoxib. Orotix® is one of a group of medicines called selective

COX-2 inhibitors. These belong to a family of medicines called non-steroidal anti-inflammatory drugs

(NSAIDs).

What is Orotix® used for?

· Orotix® helps to reduce the pain and swelling (inflammation) in the joints and muscles of people 16 years of age and older with osteoarthritis, rheumatoid arthritis, ankylosing spondylitis and gout.

· Orotix® is also used for the short term treatment of moderate pain after dental surgery in people 16 years

of age and older.

What is osteoarthritis?

Osteoarthritis is a disease of the joints. It results from the gradual breakdown of cartilage that cushions the ends of the bones. This causes swelling (inflammation), pain, tenderness, stiffness and disability.

What is rheumatoid arthritis?

Rheumatoid arthritis is a long term inflammatory disease of the joints. It causes pain, stiffness, swelling, and increasing loss of movement in the joints it affects. It may also cause inflammation in other areas of the body. What is gout?

Gout is a disease of sudden, recurring attacks of very painful inflammation and redness in the joints. It is caused by deposits of mineral crystals in the joint.

What is ankylosing spondylitis?

Ankylosing spondylitis is an inflammatory disease of the spine and large joints.


Do not take Orotix®:

· If you are allergic (hypersensitive) to etoricoxib or any of the other ingredients of this medicine.

· If you are allergic to non-steroidal anti-inflammatory drugs (NSAIDs), including aspirin and COX-2 inhibitors.

· If you have a current stomach ulcer or bleeding in your stomach or intestines.

· If you have serious liver disease.

· If you have serious kidney disease.

· If you are or could be pregnant or are breast-feeding.

· If you are under 16 years of age.

· If you have inflammatory bowel disease, such as Crohn’s Disease, Ulcerative Colitis, or Colitis.

· If you have high blood pressure that has not been controlled by treatment (check with your doctor or nurse if you are not sure whether your blood pressure is adequately controlled).

· If your doctor has diagnosed heart problems including heart failure (moderate or severe types), angina

(chest pain).

· If you have had a heart attack, bypass surgery, peripheral arterial disease (poor circulation in legs or feet due to narrow or blocked arteries).

· If you have had any kind of stroke (including mini-stroke, transient ischaemic attack or TIA). Etoricoxib may

slightly increase your risk of heart attack and stroke and this is why it should not be used in those who have already had heart problems or stroke.

If you think any of these are relevant to you, do not take the tablets until you have consulted your doctor.

Take Special care with Orotix®

Talk to your doctor or pharmacist before taking Orotix®:

· If you have a history of stomach bleeding or ulcers.

· If you are dehydrated, for example by a prolonged bout of vomiting or diarrhea.

· If you have swelling due to fluid retention.

· If you have a history of heart failure, or any other form of heart disease.

· If you have a history of high blood pressure. Orotix® can increase blood pressure in some people, especially in high doses, and your doctor will want to check your blood pressure from time to time.

· If you have any history of liver or kidney disease.

· If you are being treated for an infection. Orotix® can mask or hide a fever, which is a sign of infection.

· If you have diabetes, high cholesterol, or are a smoker. These can increase your risk of heart disease.

· If you are a woman trying to become pregnant.

· If you are over 65 years of age.

If you are not sure if any of the above apply to you, talk to your doctor before taking Orotix® to see if this medicine is suitable for you.

Orotix® works equally well in older and younger adult patients. If you are over 65 years of age, your doctor will want to appropriately keep a check on you. No dosage adjustment is necessary for patients over 65 years of age.

Children and adolescents

Do not give this medicine to children and adolescents under 16 years of age.

Other medicines and Orotix®

Tell your doctor or pharmacist if you are taking, have recently taken or might take any other medicines, includ- ing medicines obtained without a prescription.

In particular if you are taking any of the following medicines, your doctor may want to monitor you to check that your medicines are working properly, once you start taking Orotix®:

· Medicines that thin your blood (anticoagulants), such as warfarin.

· Rifampicin (an antibiotic).

· Methotrexate (a drug used for suppressing the immune system, and often used in rheumatoid arthritis).

· Ciclosporin or tacrolimus (drugs used for suppressing the immune system).

· Lithium (a medicine used to treat some types of depression).

· Medicines used to help control high blood pressure and heart failure called ACE inhibitors and angiotensin receptor blockers, examples include enalapril and ramipril, and losartan and valsartan.

· Diuretics (water tablets).

· Digoxin (a medicine for heart failure and irregular heart rhythm).

· Minoxidil (a drug used to treat high blood pressure).

· Salbutamol tablets or oral solution (a medicine for asthma).

· Birth control pills (the combination may increase your risk of side effects).

· Hormone replacement therapy (the combination may increase your risk of side effects).

· Aspirin, the risk of stomach ulcers is greater if you take Orotix® with aspirin.

· Aspirin for prevention of heart attacks or stroke:

Orotix® can be taken with low-dose aspirin. If you are currently taking low-dose aspirin to prevent heart attacks or stroke, you should not stop taking aspirin until you talk to your doctor.

· Aspirin and other non-steroidal anti-inflammatory drugs (NSAIDs):

do not take high dose aspirin or other anti-inflammatory medicines while taking Orotix®. Orotix® with food and drink

The onset of the effect of Orotix® may be faster when taken without food.

Pregnancy, breast-feeding and fertility Pregnancy

Orotix® tablets must not be taken during pregnancy. If you are pregnant or think you could be pregnant, or if you are planning to become pregnant, do not take the tablets. If you become pregnant, stop taking the tablets and consult your doctor. Consult your doctor if you are unsure or need more advice.

Breast-feeding

It is not known if etoricoxib is excreted in human milk. If you are breast-feeding, or planning to breast-feed, consult your doctor before taking Orotix®. If you are using Orotix®, you must not breast-feed.

Fertility

Orotix® is not recommended in women attempting to become pregnant.

Driving and using machines

Dizziness and sleepiness have been reported in some patients taking Orotix®.

Do not drive if you experience dizziness or sleepiness.

Do not use any tools or machines if you experience dizziness or sleepiness.

Orotix® contains lactose

If you have been told by your doctor that you are unable to tolerate some sugars, contact your doctor before taking this medicinal product.


Always take this medicine exactly as your doctor has told you. You should check with your doctor or pharmacist if you are not sure.

Do not take more than the recommended dose for your condition. Your doctor will want to discuss your treat- ment from time to time. It is important that you use the lowest dose that controls your pain and you should not take Orotix® for longer than necessary. This is because the risk of heart attacks and strokes might increase after prolonged treatment, especially with high doses.

There are different strengths available for this medicinal product and depending on your disease your doctor will prescribe the tablet strength that is appropriate for you.

The recommended dose is:

Osteoarthritis

The recommended dose is 30 mg once a day, increase to a maximum of 60 mg once a day if needed.

Rheumatoid arthritis

The recommended dose is 60 mg once a day, increased to a maximum of 90 mg once a day if needed.

Acute pain conditions

Orotix® should be used only for the acute painful period.

Ankylosing spondylitis

The recommended dose is 60 mg once a day, increased to a maximum of 90 mg once a day if needed.

Gout

The recommended dose is 120 mg once a day which should only be used for the acute painful period, limited to a maximum of 8 days treatment.

Postoperative dental surgery pain

The recommended dose is 90 mg once daily, limited to a maximum of 3 days treatment.

People with liver problems

• If you have mild liver disease, you should not take more than 60 mg a day.

• If you have moderate liver disease, you should not take more than 30 mg a day.

Use in children and adolescents

Orotix® should not be taken by children or adolescents under 16 years of age.

Elderly

No dose adjustment is necessary for elderly patients. As with other medicines, caution should be exercised in elderly patients.

Method of administration

Orotix® is for oral use. Take the tablets once a day. Orotix® can be taken with or without food.

If you take more Orotix® than you should

You should never take more tablets than the doctor recommends. If you do take too many Orotix® tablets, you should seek medical attention immediately.

If you forget to take Orotix®

It is important to take Etoricoxib as your doctor has prescribed. If you miss a dose, just resume your usual schedule the following day. Do not take a double dose to make up for the forgotten tablet.

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.

If you develop any of these signs you should stop Orotix® and talk to your doctor immediately:

· Shortness of breath, chest pains, or ankle swelling appear or if they get worse.

· Yellowing of the skin and eyes (jaundice) – these are signs of liver problems.

· Severe or continual stomach pain or your stools become black.

· An allergic reaction- which can include skin problems such as ulcers or blistering, or swelling of the face, lips, tongue, or throat which may cause difficulty in breathing.

The frequency of possible side effects listed below is defined using the following convention: Very common (affects more than 1 user in 10)

Common (affects 1 to 10 users in 100)

Uncommon (affects 1 to 10 users in 1,000)

Rare (affects 1 to 10 users in 10,000)

Very rare (affects less than 1 user in 10,000)

The following side effects can occur during treatment with Orotix®:

Very common

· Stomach pain.

Common

· Dry socket (inflammation and pain after a tooth extraction).

· Swelling of the legs and/or feet due to fluid retention (oedema).

· Dizziness, headache.

· Palpitations (fast or irregular heartbeat), irregular heart rhythm (arrhythmia).

· Increased blood pressure.

· Wheezing or shortness of breath (bronchospasms).

· Constipation, wind (excessive gas), gastritis (inflammation of the lining of the stomach), heartburn, diarrhea, indigestion (dyspepsia)/stomach discomfort, nausea, being sick (vomiting), inflammation of the oesophagus, mouth ulcers.

· Changes in blood tests related to your liver.

· Bruising.

· Weakness and fatigue, flu-like illness.

Uncommon

· Gastroenteritis (inflammation of the gastrointestinal tract that involves both the stomach and small intestine/ stomach flu), upper respiratory infection, urinary tract infection.

· Changes in laboratory values (decreased number of red blood cells, decreased number of white blood cells,

platelets decreased).

· Hypersensitivity (an allergic reaction including hives which may be serious enough to require immediate medical attention).

· Appetite increases or decreases, weight gain.

· Anxiety, depression, decreases in mental sharpness; seeing, feeling or hearing things that are not there (hallucinations).

· Taste alteration, inability to sleep, numbness or tingling, sleepiness.

· Blurred vision, eye irritation and redness.

· Ringing in the ears, vertigo (sensation of spinning while remaining still).

· Abnormal heart rhythm (atrial fibrillation), fast heart rate, heart failure, feeling of tightness, pressure or heavi- ness in the chest (angina pectoris), heart attack.

· Flushing, stroke, mini-stroke (transient ischaemic attack), severe increase in blood pressure. inflammation of

the blood vessels.

· Cough, breathlessness, nose bleed.

· Stomach or bowel bloating, changes in your bowel habits, dry mouth, stomach ulcer, inflammation of the stomach lining that can become serious and may lead to bleeding, irritable bowel syndrome, inflammation of the pancreas.

· Swelling of the face, skin rash or itchy skin, redness of the skin.

· Muscle cramp/spasm, muscle pain/stiffness.

· High levels of potassium in your blood, changes in blood or urine tests relating to your kidney, serious kidney problems.

· Chest pain.

Rare

· Angioedema (an allergic reaction with swelling of the face, lips, tongue and/or throat which may cause difficulty in breathing or swallowing, which may be serious enough to require immediate medical attention)/ anaphylactic/anaphylactoid reactions including shock (a serious allergic reaction that requires immediate medical attention).

· Confusion, restlessness.

· Liver problems (hepatitis).

· Low blood levels of sodium.

· Liver failure, yellowing of the skin and/or eyes (jaundice).

· Severe skin reactions.

If any of the side effects get serious or if you notice any side effects not listed in this leaflet, please tell your doctor or pharmacist.


Keep out of the reach and sight of children.

Do not use Orotix® after the expiry date (EXP) which is stated on the blister and the carton. The expiry date refers to the last day of that month.

Orotix®tablets: Store below 30°C.

Medicines should not be disposed of via wastewater or household waste. Ask your pharmacist how to dispose of medicines no longer required. These measures will help to protect the environment.


The active substance is Etoricoxib.

The other ingredients are: Lactose monohydrate , microcrystalline Cellulose, croscarmellose sodium, povidone K30, colloidal silicone dioxide, magnesium stearate, opadry OY-L White , yellow iron oxide, FD&C Blue #2 lake, polyethylene glycol.


Orotix® 60 mg Tablets Light greenish blue, 7.0 mm round normal biconvex film coated tablet scored on one face and engraved with Phl on the other one, packed in Alu/Alu blister, intended for oral use. Pack size: 7 tablets in Alu / Alu blister.2 blisters/pack. 10 tablets in Alu/Alu blister.3 blisters/pack. Orotix® 90 mg Tablets Light greenish blue 8.2 mm round normal biconvex film coated tablet engraved with PhI on one face, packed in Alu/Alu blister, intended for oral use. Pack size: 7 tablets in Alu/Alu blister.2 blisters/pack. 10 tablets in Alu/Alu blister.3 blisters/pack. Orotix® 120 mg Tablets Light greenish blue 9 mm round normal biconvex film coated tablet engraved with PhI on one face, packed in Alu/Alu blister, intended for oral use. Pack size: 7 tablets in Alu/Alu blister.1 blister/pack. 10 tablets in Alu/Alu blister.1 blister/pack. To report any side effect(s): • Saudi Arabia: The National Pharmacovigilance and Drug Safety Center (NPC): Fax: +966-11-205-7662 Call NPC at +966-11-2038222, Exts: 2317-2356-2340. Reporting hotline: 19999 E-mail: npc.drug@sfda.gov.sa Website: www.sfda.gov.sa/npc • United Arab of Emirates: Pharmacovigilance and Medical Device Section P.O. Box: 1853, Tel: 80011111 Email: pv@moh.gov.ae Drug Department, Ministry of Health & Prevention Dubai-UAE. • Other GCC States: Please contact the relevant competent authority.

Pharma International Company Amman - Jordan

Tel: 00962-6-5158890 / 5157893

Fax: 00962-6-5154753

Email: marketing@pic-jo.com

This leaflet does not contain all the information about your medicine. If you have any questions or are not sure about anything, ask your doctor or pharmacist.


01/2020
  نشرة الدواء تحت مراجعة الهيئة العامة للغذاء والدواء (اقرأ هذه النشرة بعناية قبل البدء في استخدام هذا المنتج لأنه يحتوي على معلومات مهمة لك)

ما هو أوروتكس®؟

· يحتوي أوروتكس® على المادة الفعالة إتوريكوكسيب. وينتمي إلى مجموعة من الادوية تعرف بمثبطات سايكلو أوكسجينيز2- الانتقائية،

التي تنتمي إلى مجموعة من الأدوية تعرف بمضادة الالتهاب غير الستيرويدية.

ما هي استخدامات أوروتكس®؟

· يستعمل أوروتكس® لتخفيف الالام والتورم )الالتهاب( في المفاصل و العضلات عند الأشخاص الذين تبلغ أعمارهم 16 عاما فما فوق

والذين يعانون من التهاب عظمي مفصلي، التهاب المفاصل الروماتزمي،التهاب الفقار القسطي، و النقرس.

· يستعمل أوروتكس® أيضا للعالج قصير الأمد للألم المتوسط بعد الخضوع لجراحة في الأسنان عند الأشخاص الذين تبلغ أعمارهم

16 عاما فما فوق.

يجب أن يعتمد قرار وصف مثبطات سايكلو أوكسجينيز2- االنتقائية على تقييم جميع المخاطر التي من الممكن حصولها للمريض.

ما هو الالتهاب العظمي المفصلي؟

الالتهاب العظمي المفصلي هو مرض يصيب المفاصل، ينتج عن تحلل تدريجي للغضروف الذي يحمي نهايات العظام، وهذا يسبب تورم

)التهاب(، ألم، ألم عند اللمس، تصلب و عدم قدرة على الحركة.

ما هو التهاب المفاصل الروماتزمي؟

التهاب المفاصل الروماتزمي هو مرض التهابي طويل الأمد يصيب المفاصل، يسبب ألم، تصلب، تورم وزيادة في عدم القدرة على

تحرك المفاصل التي يؤثر عليها. قد يسبب أيضاً التهاب في مناطق أخرى من الجسم.

ما هو النقرس؟

النقرس هو مرض يظهر على شكل نوبات مفاجئة، و متكررة الحدوث الحمرار والتهاب مؤلم جداً في المفاصل، ينتج عن ترسب بلورات

الاملاح  المعدنية في المفصل.

ما هو التهاب الفقار القسطي؟

التهاب الفقار القسطي هو مرض التهابي يصيب العمود الفقري و المفاصل الكبيرة.

 الحالات التي يجب أن لا تأخذ فيها أوروتكس
• إذا كنت تعاني من تحسس )فرط الحساسية( ل إتوريكوكسبأو أي من المكونات الأخرى في هذا الدواء.
. • إذا كنت تعاني من الحساسية للأدوية غير الستيرويدية المضادة للالتهاب، بما في ذلك الأسبرين ومثبطات سايكلو أوكسجينيز- 2
• إذا كنت تعاني حالياً من قرحة المعدة أو نزيف في المعدة أو الأمعاء.
• إذا كنت تعاني من مرض خطير في الكبد.
• إذا كنت تعاني من مرض خطير في الكلى.
• إذا كنت حامل أو من المتوقع حصول حمل لديك أو إذا كنت مرضعة.
• إذا كان عمرك يقل عن 16 عاماً.
• إذا كنت تعاني من مرض التهابي في الأمعاء، مثل مرض كرون، التهاب القولون التقرحي، أو التهاب القولون.
• إذا كنت تعاني من ارتفاع ضغط الدم الذي لا يتم السيطرة عليه عن طريق العلاج )تأكد من الطبيب أو الممرض إذا لم تكن متأكداً إن كان
قد يتم السيطرة على ضغط الدم لديك بشكل كاف(.
• إذا قام الطبيب بتشخيص إصابتك بمشاكل في القلب بما في ذلك قصور عضلة القلب )أنواع متوسطة أو حادة(، ذبحة )ألم الصدر(.
•  إذا عانيت في السابق من نوبة قلبية، عملية الترقيع التحويلية للشرايين التاجية، مرض الشرايين الطرفية )ضعف تدفق الدورة الدموية
في الأرجل أو الأقدام نتيجة لتضيق أو انسداد الشرايين(.
•  إذا عانيت في السابق من أي نوع من السكتة الدماغية )بما في ذلك السكتة الدماغية التي تستمر لفترة قصيرة، النوبة المؤقتة الناتجة عن
توقف تدفق الدم إلى الدماغ لفترة قصيرة(. قد يزيد إتوريكوكسببنسبة بسيطة من خطورة التعرض للنوبة القلبية و السكتة الدماغية، لذلك
يجب عدم استعماله للأشخاص الذين عانوا في السابق من مشاكل قلبية أو سكتة دماغية.
إذا كنت تعتقد بأن أي من المذكور في الأعلى ينطبق عليك، لا تتناول الأقراص إلى أن تستشير طبيبك.
® الاحتياطات الخاصة عند استعمال أوروتكس
:® تحدث مع الطبيب أو الصيدلاني قبل تناول أوروتكس
• إذا عانيت في السابق من نزيف أو تقرحات في المعدة.
• إذا كنت تعاني من الجفاف، مثلاً نوبة مطولة من القيء أو الإسهال.
• إذا كنت تعاني من التورم نتيجة لاحتباس السوائل.
• إذا عانيت في السابق من قصور عضلة القلب، أو أي شكل آخر من أمراض القلب.
إلى ارتفاع ضغط الدم لدى بعض الأشخاص، خصوصاً عند ® • إذا عانيت في السابق من ارتفاع ضغط الدم، حيث قد يسبب أوروتكس
تناوله بجرعات عالية، و سيطلب الطبيب مراقبة ضغط الدم لديك من وقت لآخر.
• إذا عانيت في السابق من مرض في الكبد أو الكلى.
ارتفاع درجة الحرارة، التي تعد علامة على وجود التهاب. ® • إذا كنت تخضع لعلاج التهاب معين، حيث قد يخفي أوروتكس
• إذا كنت تعاني من داء السكري، ارتفاع مستوى الكوليسترول، أو كنت مدخن، هذا قد يزيد ذلك من خطورة التعرض لأمراض قلبية.
• إذا كنت امرأة تخططين للحمل.
• إذا كان عمرك يزيد عن 65 عاماً.
إذا لم تكن متأكداً إذا كان أي من الأعلى ينطبق عليك، أخبر طبيبك قبل تناول أوروتكس لمعرفة إذا كان هذا الدواء مناسب لك. 
® أوروتكس يعمل بشكل مماثل عند المرضى كبار السن و البالغين الشباب. إذا كان عمرك يزيد عن 65 عاماً ، سيقوم الطبيب بمراقبتك
بشكل جيد. لا يوجد حاجة لتعديل الجرعة للمرضى الذين تزيد أعمارهم عن 65 عاماً.
الأطفال و المراهقون
لا تقم بإعطاء هذا الدواء للأطفال و المراهقين الذين تقل أعمارهم عن 16 عاماً.
® أدوية أخرى مع أوروتكس
أخبر الطبيب أو الصيدلي إذا كنت تتناول، تناولت مؤخراً أو من الممكن أن تتناول أي أدوية أخرى، بما في ذلك الأدوية التي يتم الحصول
عليها بدون وصفة طبية.
بشكل خاص إذا كنت تتناول أي من الأدوية التالية، سيقوم الطبيب بمراقبتك للتأكد من الأدوية التي تتناولها تعمل بشكل مناسب، عند
 البدء بتناول أوروتكس:
• الأدوية التي تعمل على الوقاية من تجلط الدم )مضادات التجلط(، مثل وارفارين.
• ريفامبيسين )مضاد حيوي(.
• ميثوتريكسيت )دواء يستعمل لتثبيط جهاز المناعة، و يستعمل غالباً لعلاج التهاب المفاصل الروماتزمي(.
• سايكلوسبورين أو تاكروليمس )أدوية تستعمل لتثبيط جهاز المناعة(.
• ليثيوم )دواء يستعمل لعلاج أنواع معينة من الاكتئاب(.
• أدوية تستعمل للمساعدة في ضبط ارتفاع ضغط الدم و قصور عضلة القلب تعرف بمثبطات الإنزيم المحول للأنجيوتنسين و حاصرات
مستقبل الأنجيوتنسين، تتضمن الأمثلة إنالابريل و راميبريل، ولوسارتان و فالسارتان.
• مدرات البول )أقراص الماء(.
• ديجوكسين )دواء يستعمل لقصور عضلة القلب و عدم انتظام نبضات القلب(.
• مينوكسيديل )دواء يستعمل لعلاج ارتفاع ضغط الدم(.
• سالبيوتامول أقراص أو محلول الشرب )دواء يستعمل لعلاج الربو(.
• أقراص تنظيم النسل )قد يزيد تناولها بشكل متزامن من خطر التعرض للآثار الجانبية(.
• العلاج البديل بالهرمونات )قد يزيد تناولها بشكل متزامن من خطر التعرض للآثار الجانبية(.
• الأسبرين، يزداد خطر الإصابة بتقرحات المعدة عند تناول أوروتكس مع الأسبرين. 
• تناول الأسبرين للوقاية من الإصابة بنوبات قلبية أو سكتة دماغية:
من الممكن تناول أوروتكس بالتزامن مع جرعة منخفضة من الأسبرين. إذا كنت تتناول حالياً جرعة منخفضة من الأسبرين للوقاية من 
الإصابة بنوبات قلبية أو سكتة دماغية، يجب عدم التوقف عن تناول الأسبرين إلى أن تستشير الطبيب.
•  تناول الأسبرين بالتزامن مع الأدوية الأخرى غير الستيرويدية المضادة للالتهاب:
-لا تتناول جرعة عالية من الأسبرين أو الأدوية الأخرى غير الستيرويدية المضادة للالتهاب خلال فترة تناول أوروتكس
-تناول أوروتكس مع الطعام والشراب
 قد يكون بدء مفعول أوروتكس أسرع عند تناوله بدون الطعام. 
الحمل، الرضاعة الطبيعية والخصوبة
الحمل
يجب عدم تناول أقراص أوروتكس خلال فترة الحمل. إذا كنت حاملا، تعتقدين أنك حامل، أو تخططين للحمل، لا تتناول الأقراص.  إذا 
حصل الحمل، توقفي عن تناول الأقراص واستشيري طبيبك. استشيري طبيبك إذا لم تكوني متأكدة أو تحتاجين للمزيد من الاستفسار.
الرضاعة الطبيعية
من غير المعروف إذا كان إتوريكوكسب يفرز في حليب الثدي. إذا كنت مرضعة، أو تخططين للإرضاع، استشيري الطبيب قبل تناول ® أوروتكس
® إذا كنت تستعملين أوروتكس يجب عدم الإرضاع. ، .
الخصوبة
لا يوصى باستعمال أوروتكس للمرأة التي تحاول الحمل.
القيادة و استخدام الآلات
تم تسجيل حدوث شعور بدوار و نعاس عند بعض الأشخاص الذين يتناولون أوروتكس
تجنب قيادة المركبات إذا حصل لديك شعور بالدوار أو النعاس.
تجنب استعمال أي أدوات أو آلات إذا حصل لديك شعور بالدوار أو النعاس.
 يحتوي أوروتكس على اللاكتوز 
إذا أخبرت من قبل الطبيب أنك تعاني من عدم القدرة على تحمل بعض أنواع السكريات، قم بالاتصال مع الطبيب قبل البدء بتناول هذا
الدواء.

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تناول هذا الدواء دائما كما أخبرك طبيبك. يجب عليك التحقق من طبيبك أو الصيدلي إذا لم تكن متأكدا من كيفية استخدام الدواء.
لا تتناول أكثر من الجرعة الموصى بها لعلاج حالتك. سيقوم الطبيب بمناقشة علاجك من وقت لآخر. من الضروري أن تستعمل أقل جرعة تسيطر على الألم لديك و يجب عدم تناول أوروتكس لفترة أطول من تلك التي تحتاجها. و ذلك لأنه قد تزداد خطورة الإصابة 
بالنوبات القلبية و السكتات الدماغية بعد العلاج طويل الأمد، خصوصاً عند تناول جرعات عالية.
الجرعة الموصى بها هي:
الالتهاب العظمي المفصلي
الجرعة الموصى بها هي 30 ملغم مرة واحدة يومياً، يتم زيادتها عند الحاجة إلى 60 ملغم مرة واحدة يومياً كحد أقصى.
التهاب المفاصل الروماتزمي
الجرعة الموصى بها هي 60 ملغم مرة واحدة يومياً، يتم زيادتها عند الحاجة إلى 90 ملغم مرة واحدة يومياً كحد أقصى.
حالات الألم الحادة
يجب استعمال أوروتكس فقط لعلاج فترة الألم الحاد. 
التهاب الفقار القسطي
الجرعة الموصى بها هي 60 ملغم مرة واحدة يومياً، يتم زيادتها عند الحاجة إلى 90 ملغم مرة واحدة يومياً كحد أقصى.
النقرس
الجرعة الموصى بها هي 120 ملغم مرة واحدة يومياً التي يجب استعمالها فقط لعلاج فترة الألم الحاد، ويجب استعماله لمدة محددة تصل
لغاية 8 أيام كحد أقصى.
الألم الذي يحدث بعد جراحة الأسنان
الجرعة الموصى بها هي 90 ملغم مرة واحدة يومياً، لمدة محددة تصل لغاية 3 أيام كحد أقصى.
الأشخاص الذين يعانون من مشاكل في الكبد
• إذا كنت تعاني من مرض معتدل في الكبد، يجب عدم تناول أكثر من 60 ملغم يومياً.
• إذا كنت تعاني من مرض متوسط في الكبد، يجب عدم تناول أكثر من 30 ملغم يومياً.
الاستعمال للأطفال والمراهقين
يجب عدم تناول أوروتكس من قبل الأطفال والمراهقين الذين تقل أعمارهم عن 16 عاماً. 

كبار السن
لا حاجة لتعديل الجرعة للمرضى كبار السن. كما هو الحال عند استعمال الأدوية الأخرى، يجب توخي الحذر عند المرضى كبار السن.
طريقة الاستعمال
أوروتكس هو للاستعمال عن طريق الفم. تناول الأقراص مرة واحدة يومياً. من الممكن تناول أوروتكس مع أو بدون تناول الطعام.
إذا تناولت أوروتكس أكثر مما يجب  
، ® يجب عدم تناول أكثر من الجرعة الموصى بها من قبل الطبيب. إذا تناولت أكثر من الجرعة الموصى بها من أقراص أوروتكس
يجب طلب الرعاية الطبية فوراً.
® إذا نسيت تناول أوروتكس
من المهم تناول أوروتكس كما وصف الطبيب. إذا نسيت تناول جرعة، فقط استمر بتناوله كالمعتاد في اليوم التالي. لا تتناول جرعة مضاعفة لتعويض الجرعة التي نسيتها.
إذا كان لديك أية أسئلة أخرى عن استعمال هذا الدواء، اسأل طبيبك أو الصيدلي.

مثل جميع الأدوية، ويمكن لهذا الدواء أن يتسبب في آثار جانبية، على الرغم من أنها لا تحصل عند الجميع.

 إذا حصل لديك أي من العلامات التالية، يجب التوقف عن تناول أوروتكس و التحدث مع طبيبك فوراً:

• قصور في النفس، آلام الصدر، ظهور تورم في الكاحل أو إذا ازداد التورم سوءاً.
• اصفرار الجلد و العيون )يرقان(، هذه علامات على حدوث مشاكل في الكبد.
• ألم حاد أو مستمر في المعدة أو أصبح لون البراز أسود.
• تفاعل تحسسي، و الذي قد يتضمن مشاكل جلدية مثل تقرحات أو تنفط، أو تورم الوجه، الشفاه، اللسان، أو الحلق و قد يسبب صعوبة
في التنفس.
تم تصنيف تكرار الآثار الجانبية المحتملة المذكورة في الأسفل باستعمال الترتيب التالي:
شائعة جداً )تؤثر على أكثر من 1 من كل 10 أشخاص(
شائعة )تؤثر على 1 إلى 10 من كل 100 شخص(
غير شائعة )تؤثر على 1 إلى 10 من كل 1000 شخص(
نادرة )تؤثر على 1 إلى 10 من كل 10000 شخص(
نادرة جداً )تؤثر على أقل من 1 من كل 10000 شخص(

قد تحدث الآثار الجانبية التالية خلال فترة العلاج بأوروتكس
شائعة جداً
• ألم المعدة.
شائعة
• تجويف جاف )التهاب و ألم في اللثة ما بعد خلع الأسنان(.
• تورم الأرجل و/أو الأقدام نتيجة لاحتباس السوائل )وذمة(.
• شعور بالدوار، صداع.
• خفقان )نبضات قلب سريعة أو غير منتظمة(، عدم انتظام نبضات القلب )اللانظمية(.
• ارتفاع ضغط الدم.
• أزيز تنفسي أو قصور النفس )تشنج قصبي(.
• إمساك، انتفاخ البطن )زيادة الغازات(، التهاب المعدة )التهاب بطانة المعدة(، حرقة المعدة، إسهال، عسر الهضم/شعور بعدم الراحة
في منطقة المعدة، شعور بالغثيان، قيء، التهاب المريء، تقرحات الفم.
• تغيرات في نتائج فحوصات الدم المتعلقة بالكبد.
• كدمات.
• شعور بالضعف و التعب، مرض يشبه الإنفلونزا.
غير شائعة
• التهاب المعدة و الأمعاء )التهاب الجهاز المعدي المعوي الذي يتضمن كل من المعدة و الأمعاء الدقيقة/ التهاب المعدة الفيروسي(،
التهاب الجهاز التنفسي العلوي، التهاب الجهاز البولي.
• تغيرات في قيم نتائج الفحوصات المخبرية )انخفاض عدد خلايا الدم الحمراء، خلايا الدم البيضاء، و الصفيحات الدموية(.
• فرط الحساسية )تفاعل تحسسي يتضمن الشرى الذي قد يكون خطيراً و يتطلب رعاية طبية فورية(.
• زيادة أو نقصان الشهية للطعام، زيادة الوزن.
• قلق، اكتئاب، انخفاض التيقظ العقلي، رؤية أو سماع أو الإحساس بأشياء غير موجودة في الواقع )هلوسات(.
• تغير في حاسة التذوق، عدم القدرة على النوم، تنمل أو إحساس بوخز خفيف، شعور بالنعاس.
• ضبابية الرؤية، احمرار وتهيج العين.
• رنين في الأذن، ترنح )شعور بالدوران(.
• عدم انتظام نبضات القلب )رجفان أذيني(، تسارع معدل نبضات القلب، قصور عضلة القلب، شعور بضيق، شعور بضغط أو ثقل في
الصدر )ذبحة صدرية(، نوبة قلبية.
• احمرار الوجه، سكتة دماغية، سكتة دماغية تستمر لفترة قصيرة )نوبة مؤقتة ناتجة عن توقف تدفق الدم إلى الدماغ لفترة قصيرة(،
زيادة حادة في ضغط الدم، التهاب الأوعية الدموية.
• سعال، ضيق التنفس، نزيف الأنف.
• انتفاخ في المعدة أو الأمعاء، تغيرات في حركة الأمعاء، جفاف الفم، قرحة المعدة، التهاب بطانة المعدة الذي قد يصبح خطيراً و يؤدي
إلى النزيف، متلازمة الأمعاء المتهيجة )القولون العصبي(، التهاب البنكرياس.
• تورم الوجه، طفح أو حكة في الجلد، احمرار الجلد.
• تشنج عضلي، تصلب/ألم عضلي.
• ارتفاع مستويات البوتاسيوم في الدم، تغيرات في فحوصات الدم أو البول المتعلقة بالكلى، مشاكل خطيرة في الكلى.
• ألم الصدر.
نادرة
• وذمة وعائية )تفاعل تحسسي يؤدي إلى تورم الوجه، الشفاه، اللسان و/أو الحلق مما يسبب صعوبة في التنفس أو البلع، و الذي قد
يكون خطيراً و يتطلب رعاية طبية فورية(/تفاعلات تآقية تتضمن صدمة )تفاعل تحسسي خطير يتطلب رعاية طبية فورية(.
• ارتباك، شعور بعدم الراحة.
• مشاكل في الكبد )التهاب الكبد(.
• انخفاض مستويات الصوديوم في الدم.
• قصور وظيفة الكبد، اصفرار الجلد و/أو العيون )يرقان(.
• تفاعلات جلدية حادة.
إذا كان أي من الآثار الجانبية جدية أو إذا لاحظت أية آثار جانبية غير المذكورة في هذه النشرة، يرجى إخبار الطبيب أو الصيدلي.

 

يحفظ بعيدا عن متناول الأطفال و نظرهم.
لا تستخدم أقراص أوروتكس بعد تاريخ انتهاء الصلاحية المذكورعلى الشريط و العلبة الخارجية. 
تاريخ الانتهاء يشير إلى اليوم الأخير من ذلك الشهر.
أوروتكس أقراص: يحفظ بدرجة حرارة دون 30 °م.
يجب أن لا يتم التخلص من الأدوية عن طريق مياه الصرف الصحي أو النفايات المنزلية. اسأل الصيدلي عن كيفية التخلص من الأدوية
التي لم تعد مطلوبة. وسوف تساعد هذه التدابير في حماية البيئة.

المادة الفعالة هي إتوريكوكسيب.

المكونات الأخرى غير الفعالة هي: لاكتوز أحادي الإماهة، ميكروكريستالين سيليلوز، كروسكارميللوز صوديوم، بوفيدون K30

ثاني أكسيد السيليكون الغروي، ستيرات المغنيسيوم، أوبادري أبيض ، أكسيد الحديد الأصفر، لون أزرق #2 FD &C 

بولي ايثيلين جلايكول.

أقراص أوروتكس 60 ملغم

أقراص مغلفة بفيلم دائرية الشكل محدبة الوجهين قطرها 7.0 مم، ذات لون أزرق فاتح مخضر ، قابلة للتقسيم على أحد الأوجه و
و معبأة في أشرطة ألومنيوم /ألومنيوم، معدة للاستخدام عن طريق الفم. ، محفور على الوجه الآخر PhI
حجم العبوة: 7 أقراص داخل كل شريط ألومنيوم /ألومنيوم. شريطين/علبة.
10 أقراص داخل كل شريط ألومنيوم/ألومنيوم. 3 أشرطة/علبة.

 

أقراص أوروتكس 90 ملغم

 أقراص مغلفة بفيلم دائرية الشكل محدبة الوجهين قطرها 8.2 مم، ذات لون أزرق فاتح مخضر،محفور على أحد الأوجه PhI
معبأة في أشرطة ألومنيوم /ألومنيوم، معدة للاستخدام عن طريق الفم.
حجم العبوة: 7 أقراص داخل كل شريط ألومنيوم /ألومنيوم. شريطين/علبة.
10 أقراص داخل كل شريط ألومنيوم/ألومنيوم. 3 أشرطة/علبة.

 

أقراص أوروتكس 120 ملغم

أقراص مغلفة دائرية الشكل محدبة الوجهين قطرها 9 مم، ذات لون زرق فاتح مخضر، محفور على أحد الأوجه PhI
معبأة في أشرطة ألومنيوم /ألومنيوم، معدة للاستخدام عن طريق الفم.
حجم العبوة: 7 أقراص داخل شريط ألومنيوم /ألومنيوم. شريط/علبة.
10 أقراص داخل كل شريط ألومنيوم/ألومنيوم. شريط/علبة.

 

 

 

للإبلاغ عن أي أعراض جانبية:

المملكة العربية السعودية:

المركز الوطني للتيقظ والسلامة الدوائية

+ 966 -11- 205-7662  :فاكس

للإتصال بالإدارة التنفيذية للتيقظ وإدارة الأزمات

+ 966 -11- 2038222 :هاتف

2317 - 2356 - 2340 :تحويلة

الخط الساخن: 19999 البريد الالكتروني: npc.drug@sfda.gov.sa الموقع االلكتروني: www.sfda.gov.sa/npc

اإلمارات العربية المتحدة:

قسم اليقظة الدوائية والأجهزة الطبية ص.ب: 1853، هاتف: 80011111

البريد الإكترونيpv@moh.gov.ae: قسم الأدوية، وزارة الصحة و وقاية المجتمع

دبي- الإمارات العربية المتحدة.

• دول الخليج الأخرى:

الرجاء الاتصال بالمؤسسات والهيئات الوطنية في كل دولة.

الشركة الدولية للدواء
عمان - الأردن
الهاتف: 00962-6-5158890 / 5157893

فاكس:00962-6-5154753

بريد الكتروني: marketing@pic-jo.com

هذه النشرة لا تحتوي على جميع المعلومات عن المستحضر. إذا كان لديك أية أسئلة أو لم تكن متأكدا من أي شيء، اسأل طبيبك أو
الصيدلي.

01/2020
 Read this leaflet carefully before you start using this product as it contains important information for you

Orotix® 60 mg film-coated tablets. Orotix® 90 mg film-coated tablets. Orotix® 120 mg film-coated tablets. Etoricoxib 60 mg film-coated tablets. Etoricoxib 90 mg film-coated tablets. Etoricoxib 120 mg film-coated tablets.

Orotix® 60 mg Tablets: Each tablet contains 60 mg etoricoxib Orotix® 90 mg Tablets: Each tablet contains 90 mg etoricoxib. Orotix® 120 mg Tablets: Each tablet contains 120 mg etoricoxib. For a full list of excipients, see section 6.1.

Orotix® tablets are film coated tablets. Orotix® 60 mg Tablets Light greenish blue 7.0mm round normal biconvex film coated tablet scored on one face and engraved with PhI on the other one, packed in Alu/Alu blister, intended for oral use. Pack size: 7 tablets in Alu / Alu blister.2 blisters/pack. 10 tablets in Alu/Alu blister.3 blisters/pack. Orotix® 90 mg Tablets Light greenish blue 8.2 mm round normal biconvex film coated tablet engraved with PhI on one face, packed in Alu/Alu blister, intended for oral use. Pack size: 7 tablets in Alu/Alu blister. 2 blisters/pack. 10 tablets in Alu/Alu blister.3 blisters/pack. Orotix® 120 mg Tablets Light greenish blue 9 mm round normal biconvex film coated tablet engraved with PhI on one face, packed in Alu/Alu blister, intended for oral use. 7 tablets in Alu/Alu blister.1 blister/pack. 10 tablets in Alu/Alu blister.1 blister/pack.

Orotix® is indicated in adults and adolescents 16 years of age and older for the symptomatic relief of osteoarthritis (OA), rheumatoid arthritis (RA), ankylosing spondylitis, and the pain and signs of inflammation associated with acute gouty arthritis.
Orotix® is indicated in adults and adolescents 16 years of age and older for the short-term treatment of moderate pain associated with dental surgery.
The decision to prescribe a selective COX-2 inhibitor should be based on an assessment of the individual patient's overall risks (see sections 4.3, 4.4).


Posology As the cardiovascular risks of etoricoxib 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 recommended dose is 30 mg once daily. In some patients with insufficient relief from symptoms, an increased dose of 60 mg once daily may increase efficacy. In the absence of an increase in therapeutic benefit, other therapeutic options should be considered. Rheumatoid arthritis The recommended dose is 60 mg once daily. In some patients with insufficient relief from symptoms, an increased dose of 90 mg once daily may increase efficacy. Once the patient is clinically stabilised, down-titration to a 60 mg once daily dose may be appropriate. In the absence of an increase in therapeutic benefit, other therapeutic options should be considered. Ankylosing spondylitis The recommended dose is 60 mg once daily. In some patients with insufficient relief from symptoms, an increased dose of 90 mg once daily may increase efficacy. Once the patient is clinically stabilized, down-titration to a 60 mg once daily dose may be appropriate. In the absence of an increase in therapeutic benefit, other therapeutic options should be considered. Acute pain conditions For acute pain conditions, etoricoxib should be used only for the acute symptomatic period. Acute gouty arthritis The recommended dose is 120 mg once daily. In clinical trials for acute gouty arthritis, etoricoxib was given for 8 days. Postoperative dental surgery pain The recommended dose is 90 mg once daily, limited to a maximum of 3 days. Some patients may require other postoperative analgesia in addition to Orotix® during the three day treatment period. Doses greater than those recommended for each indication have either not demonstrated additional efficacy or have not been studied. Therefore: The dose for OA should not exceed 60 mg daily. The dose for RA and ankylosing spondylitis should not exceed 90 mg daily. The dose for acute gout should not exceed 120 mg daily, limited to a maximum of 8 days treatment. The dose for postoperative acute dental surgery pain should not exceed 90 mg daily, limited to a maximum of 3 days. Special populations Elderly patients
No dosage adjustment is necessary for elderly patients. As with other drugs, caution should be exercised in elderly patients (see section 4.4). Patients with hepatic impairment Regardless of indication, in patients with mild hepatic dysfunction (Child-Pugh score 5-6) a dose of 60 mg once daily should not be exceeded. In patients with moderate hepatic dysfunction (Child-Pugh score 7-9), regardless of indication, the dose of 30 mg once daily should not be exceeded. Clinical experience is limited particularly in patients with moderate hepatic dysfunction and caution is advised. There is no clinical experience in patients with severe hepatic dysfunction (Child-Pugh score ≥10); therefore, its use is contra-indicated in these patients (see sections 4.3, 4.4 and 5.2). Patients with renal impairment No dosage adjustment is necessary for patients with creatinine clearance ≥30 ml/min (see section 5.2). The use of etoricoxib in patients with creatinine clearance <30 ml/min is contra-indicated (see sections 4.3 and 4.4). Paediatric population Etoricoxib is contra-indicated in children and adolescents under 16 years of age (see section 4.3). Method of administration Orotix® is administered orally and may be taken with or without food. The onset of the effect of the medicinal product may be faster when Orotix® is administered without food. This should be considered when rapid symptomatic relief is needed.


 Hypersensitivity to the active substance or to any of the excipients listed in section 6.1.  Active peptic ulceration or active gastro-intestinal (GI) bleeding.  Patients who, after taking acetylsalicylic acid or NSAIDs including COX-2 (cyclooxygenase-2) inhibitors, experience bronchospasm, acute rhinitis, nasal polyps, angioneurotic oedema, urticaria, or allergic-type reactions.  Pregnancy and lactation (see sections 4.6 and 5.3).  Severe hepatic dysfunction (serum albumin <25 g/l or Child-Pugh score ≥10).  Estimated renal creatinine clearance <30 ml/min.  Children and adolescents under 16 years of age.  Inflammatory bowel disease.  Congestive heart failure (NYHA II-IV).  Patients with hypertension whose blood pressure is persistently elevated above 140/90 mmHg and has not been adequately controlled.  Established ischaemic heart disease, peripheral arterial disease, and/or cerebrovascular disease.

Gastrointestinal effects Upper gastrointestinal complications [perforations, ulcers or bleedings (PUBs)], some of them resulting in fatal outcome, have occurred in patients treated with etoricoxib. 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 acetylsalicylic acid
concomitantly or patients with a prior history of gastrointestinal disease, such as ulceration and GI bleeding. There is a further increase in the risk of gastrointestinal adverse effects (gastrointestinal ulceration or other gastrointestinal complications) when etoricoxib 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). Cardiovascular effects Clinical trials suggest that the selective COX-2 inhibitor class of drugs may be associated with a risk of thrombotic events (especially myocardial infarction (MI) and stroke), relative to placebo and some NSAIDs. As the cardiovascular risks of etoricoxib 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 4.2, 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 etoricoxib 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 effect. Therefore antiplatelet therapies should not be discontinued (see sections above, 4.5 and 5.1.). Renal effects Renal prostaglandins may play a compensatory role in the maintenance of renal perfusion. Therefore, under conditions of compromised renal perfusion, administration of etoricoxib may cause a reduction in prostaglandin formation and, secondarily, in renal blood flow, and thereby impair renal function. Patients at greatest risk of this response are those with pre-existing significantly impaired renal function, uncompensated heart failure, or cirrhosis. Monitoring of renal function in such patients should be considered. Fluid retention, oedema and hypertension As with other medicinal products known to inhibit prostaglandin synthesis, fluid retention, oedema and hypertension have been observed in patients taking etoricoxib. All Nonsteroidal Anti-inflammatory Drugs (NSAIDs), including etoricoxib, can be associated with new onset or recurrent congestive heart failure. For information regarding a dose related response for etoricoxib see section 5.1. Caution should be exercised in patients with a history of cardiac failure, left ventricular dysfunction, or hypertension and in patients with pre-existing oedema from any other reason. If there is clinical evidence of deterioration in the condition of these patients, appropriate measures including discontinuation of etoricoxib should be taken. Etoricoxib may be associated with more frequent and severe hypertension than some other NSAIDs and selective COX-2 inhibitors, particularly at high doses. Therefore, hypertension should be controlled before treatment with etoricoxib (see section 4.3) and special attention should be paid to blood pressure monitoring during treatment with etoricoxib. Blood pressure should be monitored within two weeks after initiation of treatment and periodically thereafter. If blood pressure rises significantly, alternative treatment should be considered. Hepatic effects Elevations of alanine aminotransferase (ALT) and/or aspartate aminotransferase (AST) (approximately three or more times the upper limit of normal) have been reported in
approximately 1% of patients in clinical trials treated for up to one year with etoricoxib 30, 60 and 90 mg daily. Any patients with symptoms and/or signs suggesting liver dysfunction, or in whom an abnormal liver function test has occurred, should be monitored. If signs of hepatic insufficiency occur, or if persistently abnormal liver function tests (three times the upper limit of normal) are detected, etoricoxib should be discontinued. General If during treatment, patients deteriorate in any of the organ system functions described above, appropriate measures should be taken and discontinuation of etoricoxib therapy should be considered. Medically appropriate supervision should be maintained when using etoricoxib in the elderly and in patients with renal, hepatic, or cardiac dysfunction. Caution should be used when initiating treatment with etoricoxib in patients with dehydration. It is advisable to rehydrate patients prior to starting therapy with etoricoxib. 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 NSAIDs and some selective COX-2 inhibitors during post-marketing surveillance (see section 4.8). Patients appear to be at highest risk for these reactions early in the course of therapy with the onset of the reaction occurring in the majority of cases within the first month of treatment. Serious hypersensitivity reactions (such as anaphylaxis and angioedema) have been reported in patients receiving etoricoxib (see section 4.8). Some selective COX-2 inhibitors have been associated with an increased risk of skin reactions in patients with a history of any drug allergy. Etoricoxib should be discontinued at the first appearance of skin rash, mucosal lesions, or any other sign of hypersensitivity. Etoricoxib may mask fever and other signs of inflammation. Caution should be exercised when co-administering etoricoxib with warfarin or other oral anticoagulants (see section 4.5). The use of etoricoxib, as with any medicinal product known to inhibit cyclooxygenase / prostaglandin synthesis, is not recommended in women attempting to conceive (see sections 4.6, 5.1, and 5.3). Orotix® tablets contain lactose. Patients with rare hereditary problems of galactose intolerance, the Lapp lactase deficiency or glucose-galactose malabsorption should not take this medicine.


Pharmacodynamic interactions Oral anticoagulants: In subjects stabilised on chronic warfarin therapy, the administration of etoricoxib 120 mg daily was associated with an approximate 13% increase in prothrombin time International Normalised Ratio (INR). Therefore, patients receiving oral anticoagulants should be closely monitored for their prothrombin time INR, particularly in the first few days when therapy with etoricoxib is initiated or the dose of etoricoxib is changed (see section 4.4). Diuretics, ACE inhibitors and Angiotensin II Antagonists: NSAIDs may reduce the effect of diuretics and other antihypertensive drugs. In some patients with compromised renal function (e.g. dehydrated patients or elderly patients with compromised renal function) the co-administration of an ACE inhibitor or Angiotensin II antagonist and agents that inhibit cyclo-oxygenase may result in further deterioration of renal function, including possible acute renal failure, which is usually reversible. These interactions should be considered in patients taking
etoricoxib concomitantly with ACE inhibitors or angiotensin II antagonists. 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. Acetylsalicylic Acid: In a study in healthy subjects, at steady state, etoricoxib 120 mg once daily had no effect on the anti-platelet activity of acetylsalicylic acid (81 mg once daily). Etoricoxib can be used concomitantly with acetylsalicylic acid at doses used for cardiovascular prophylaxis (low-dose acetylsalicylic acid). However, concomitant administration of low-dose acetylsalicylic acid with etoricoxib may result in an increased rate of GI ulceration or other complications compared to use of etoricoxib alone. Concomitant administration of etoricoxib with doses of acetylsalicylic acid above those for cardiovascular prophylaxis or with other NSAIDs is not recommended (see sections 5.1 and 4.4.). Cyclosporin and tacrolimus: Although this interaction has not been studied with etoricoxib, coadministration of cyclosporin or tacrolimus with any NSAID may increase the nephrotoxic effect of cyclosporin or tacrolimus. Renal function should be monitored when etoricoxib and either of these drugs is used in combination. Pharmacokinetic interactions The effect of etoricoxib on the pharmacokinetics of other drugs Lithium: NSAIDs decrease lithium renal excretion and therefore increase lithium plasma levels. If necessary, monitor blood lithium closely and adjust the lithium dosage while the combination is being taken and when the NSAID is withdrawn. Methotrexate: Two studies investigated the effects of etoricoxib 60, 90 or 120 mg administered once daily for seven days in patients receiving once-weekly methotrexate doses of 7.5 to 20 mg for rheumatoid arthritis. Etoricoxib at 60 and 90 mg had no effect on methotrexate plasma concentrations or renal clearance. In one study, etoricoxib 120 mg had no effect, but in the other study, etoricoxib 120 mg increased methotrexate plasma concentrations by 28% and reduced renal clearance of methotrexate by 13%. Adequate monitoring for methotrexate-related toxicity is recommended when etoricoxib and methotrexate are administered concomitantly. Oral contraceptives: Etoricoxib 60 mg given concomitantly with an oral contraceptive containing 35 micrograms ethinyl estradiol (EE) and 0.5 to 1 mg norethindrone for 21 days increased the steady state AUC0-24hr of EE by 37%. Etoricoxib 120 mg given with the same oral contraceptive concomitantly or separated by 12 hours, increased the steady state AUC0-24hr of EE by 50 to 60%. This increase in EE concentration should be considered when selecting an oral contraceptive for use with etoricoxib. An increase in EE exposure can increase the incidence of adverse events associated with oral contraceptives (e.g., venous thrombo-embolic events in women at risk). Hormone Replacement Therapy (HRT): Administration of etoricoxib 120 mg with hormone replacement therapy consisting of conjugated estrogens (0.625 mg PREMARINTM) for 28 days, increased the mean steady state AUC0-24hr of unconjugated estrone (41%), equilin (76%), and 17-β-estradiol (22%). The effect of the recommended chronic doses of etoricoxib (30, 60, and 90 mg) has not been studied. The effects of etoricoxib 120 mg on the exposure (AUC0-24hr) to these estrogenic components of PREMARIN were less than half of those observed when PREMARIN was administered alone and the dose was increased from 0.625 to 1.25 mg. The clinical significance of these increases is unknown, and higher doses of PREMARIN were not studied in combination with etoricoxib. These increases in estrogenic concentration should be
taken into consideration when selecting post-menopausal hormone therapy for use with etoricoxib because the increase in oestrogen exposure might increase the risk of adverse events associated with HRT. Prednisone/prednisolone: In drug-interaction studies, etoricoxib did not have clinically important effects on the pharmacokinetics of prednisone/prednisolone. Digoxin: Etoricoxib 120 mg administered once daily for 10 days to healthy volunteers did not alter the steady-state plasma AUC0-24hr or renal elimination of digoxin. There was an increase in digoxin Cmax (approximately 33%). This increase is not generally important for most patients. However, patients at high risk of digoxin toxicity should be monitored for this when etoricoxib and digoxin are administered concomitantly. Effect of etoricoxib on drugs metabolised by sulfotransferases Etoricoxib is an inhibitor of human sulfotransferase activity, particularly SULT1E1, and has been shown to increase the serum concentrations of ethinyl estradiol. While knowledge about effects of multiple sulfotransferases is presently limited and the clinical consequences for many drugs are still being examined, it may be prudent to exercise care when administering etoricoxib concurrently with other drugs primarily metabolised by human sulfotransferases (e.g., oral salbutamol and minoxidil). Effect of etoricoxib on drugs metabolised by CYP isoenzymes Based on in vitro studies, etoricoxib is not expected to inhibit cytochromes P450 (CYP) 1A2, 2C9, 2C19, 2D6, 2E1 or 3A4. In a study in healthy subjects, daily administration of etoricoxib 120 mg did not alter hepatic CYP3A4 activity as assessed by the erythromycin breath test. Effects of other drugs on the pharmacokinetics of etoricoxib The main pathway of etoricoxib metabolism is dependent on CYP enzymes. CYP3A4 appears to contribute to the metabolism of etoricoxib in vivo. In vitro studies indicate that CYP2D6, CYP2C9, CYP1A2 and CYP2C19 also can catalyse the main metabolic pathway, but their quantitative roles have not been studied in vivo. Ketoconazole: Ketoconazole, a potent inhibitor of CYP3A4, dosed at 400 mg once a day for 11 days to healthy volunteers, did not have any clinically important effect on the single-dose pharmacokinetics of 60 mg etoricoxib (43% increase in AUC). Voriconazole and Miconazole: Co-administration of either oral voriconazole or topical miconazole oral gel, strong CYP3A4 inhibitors, with etoricoxib caused a slight increase in exposure to etoricoxib, but is not considered to be clinically meaningful based on published data. Rifampicin: Co-administration of etoricoxib with rifampicin, a potent inducer of CYP enzymes, produced a 65% decrease in etoricoxib plasma concentrations. This interaction may result in recurrence of symptoms when etoricoxib is co-administered with rifampicin. While this information may suggest an increase in dose, doses of etoricoxib greater than those listed for each indication have not been studied in combination with rifampicin and are therefore not recommended (see section 4.2). Antacids: Antacids do not affect the pharmacokinetics of etoricoxib to a clinically relevant extent.



Pregnancy No clinical data on exposed pregnancies are available for etoricoxib. Studies in animals have shown reproductive toxicity (see section 5.3). The potential for human risk in pregnancy is unknown. Etoricoxib, as with other medicinal products inhibiting prostaglandin synthesis, may cause uterine inertia and premature closure of the ductus arteriosus during the last trimester. Etoricoxib is contraindicated in pregnancy (see section 4.3). If a woman becomes pregnant during treatment, etoricoxib must be discontinued. Breast-feeding It is not known whether etoricoxib is excreted in human milk. Etoricoxib is excreted in the milk of lactating rats. Women who use etoricoxib must not breast feed (see sections 4.3 and 5.3). Fertility The use of etoricoxib, as with any drug substance known to inhibit COX-2, is not recommended in women attempting to conceive.


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


Summary of the safety profile

In clinical trials, etoricoxib was evaluated for safety in 9,295 individuals, including 6,757 patients with OA, RA, chronic low back pain or ankylosing spondylitis (approximately 600 patients with OA or RA were treated for one year or longer).

In clinical studies, the undesirable effects profile was similar in patients with OA or RA treated with etoricoxib for one year or longer.

In a clinical study for acute gouty arthritis, patients were treated with etoricoxib 120 mg once daily for eight days. The adverse experience profile in this study was generally similar to that reported in the combined OA, RA, and chronic low back pain studies.

In a cardiovascular safety outcomes programme of pooled data from three active comparator controlled trials, 17, 412 patients with OA or RA were treated with etoricoxib (60 mg or 90 mg) for a mean duration of approximately 18 months. The safety data and details from this programme are presented in section 5.1.

 

In clinical studies for acute postoperative dental pain following surgery including 614 patients treated with etoricoxib (90 mg or 120 mg), the adverse experience profile in these studies was generally similar to that reported in the combined OA, RA, and chronic low back pain studies.

 

Tabulated list of adverse reactions

The following undesirable effects were reported at an incidence greater than placebo in clinical trials in patients with OA, RA, chronic low back pain or ankylosing spondylitis treated with etoricoxib 30 mg, 60 mg or 90 mg up to the recommended dose for up to 12 weeks; in the MEDAL Programme studies for up to 3½ years; in short term acute pain studies for up to 7 days; or in post-marketing experience (see Table 1):

 

Table 1:

System Organ Class

Adverse Reactions

Frequency Category*

 

Infections and infestations

alveolar osteitis

Common

 

gastroenteritis, upper respiratory infection, urinary tract infection

Uncommon

Blood and lymphatic system disorders

anaemia (primarily associated with gastrointestinal bleeding), leukopenia, thrombocytopenia

Uncommon

Immune system disorders

hypersensitivity ß

Uncommon

 

angioedema/anaphylactic

/anaphylactoid reactions including shock

Rare

Metabolism and nutrition disorders

oedema/fluid retention

Common

 

appetite increase or decrease, weight gain

Uncommon

Psychiatric disorders

anxiety, depression, mental acuity decreased, hallucinations

Uncommon

 

confusion, restlessness

Rare

Nervous system disorders

dizziness, headache

Common

 

dysgeusia, insomnia, paresthaesia/hypaesthesia, somnolence

Uncommon

Eye disorders

blurred vision, conjunctivitis

Uncommon

Ear and labyrinth disorders

tinnitus, vertigo

Uncommon

Cardiac disorders

palpitations, arrhythmia

Common

 

atrial fibrillation, tachycardia, congestive heart failure, non-specific ECG changes, angina pectoris, myocardial infarction§

Uncommon

Vascular disorders

hypertension

Common

 

flushing, cerebrovascular accident§, transient ischaemic attack, hypertensive crisis, vasculitis

Uncommon

Respiratory, thoracic and mediastinal disorders

bronchospasm

Common

 

cough, dyspnoea, epistaxis

Uncommon

Gastrointestinal disorders

abdominal pain

Very common

 

Constipation, flatulence, gastritis, heartburn/acid reflux, diarrhea, dyspepsia/epigastric discomfort, nausea, vomiting, oesophagitis, oral ulcer

Common

 

 

abdominal distention, bowel movement pattern change, dry mouth, gastroduodenal ulcer, peptic ulcers including gastrointestinal perforation and bleeding, irritable bowel syndrome, pancreatitis

Uncommon

Hepatobiliary disorders

ALT increased, AST increased

Common

 

hepatitis

Rare

 

hepatic failure, jaundice

Rare

Skin and subcutaneous tissue disorders

ecchymosis

Common

 

facial oedema, pruritus, rash, erythema, urticaria

Uncommon

 

Stevens-Johnson syndrome, toxic epidermal necrolysis, fixed drug eruption

Rare

Musculoskeletal and connective tissue disorders

muscular cramp/spasm, musculoskeletal pain/stiffness

Uncommon

Renal and urinary disorders

proteinuria, serum creatinine increased, renal failure/renal insufficiency(see section 4.4)

Uncommon

General disorders and administration site conditions

asthenia/fatigue, flu-like disease

Common

 

chest pain

Uncommon

Investigations

blood urea nitrogen increased, creatine phosphokinase increased, hyperkalaemia, uric acid increased

Uncommon

 

blood sodium decreased

Rare

*Frequency Category: Defined for each Adverse Experience Term by the incidence reported in the clinical trials data base: Very Common (≥1/10), Common (≥1/100 to <1/10), Uncommon (≥1/1000 to <1/100), Rare (≥1/10,000 to <1/1000), Very Rare (<1/10,000).

‡ This adverse reaction was identified through post-marketing surveillance. Its reported frequency has been estimated based upon the highest frequency observed across clinical trial data pooled by indication and approved dose.

†The frequency category of “Rare” was defined per the Summary of Product Characteristics (SmPC) guidance (rev. 2, Sept 2009) on the basis of an estimated upper bound of the 95% confidence interval for 0 events given the number of subjects treated with etoricoxib in the analysis of the Phase III data pooled by dose and indication (n=15,470).

ß Hypersensitivity includes the terms "allergy", "drug allergy", "drug hypersensitivity", "hypersensitivity", "hypersensitivity NOS", "hypersensitivity reaction" and "nonspecific allergy".

§Based on analyses of long-term placebo and active controlled clinical trials, selective COX-2 inhibitors have been associated with an increased risk of serious thrombotic arterial events,

 

Text Box: including myocardial infarction and stroke. The absolute risk increase for such events is unlikely to exceed 1% per year based on existing data (uncommon).

The following serious undesirable effects have been reported in association with the use of

NSAIDs and cannot be ruled out for etoricoxib: nephrotoxicity including interstitial nephritis and nephrotic syndrome.

 

To report any side effect(s):

•Saudi Arabia:

The National Pharmacovigilance and Drug Safety Center (NPC):

Fax: +966-11-205-7662

Call NPC at +966-11-2038222, Exts: 2317-2356-2340.

Reporting hotline: 19999

E-mail: npc.drug@sfda.gov.sa Website: www.sfda.gov.sa/npc

•United Arab of Emirates:

Pharmacovigilance and Medical Device Section P.O. Box: 1853 , Tel: 80011111

Email : pv@moh.gov.ae

Drug Department, Ministry of Health & Prevention Dubai-UAE.

•Other GCC States:

Please contact the relevant competent authority..


In clinical studies, administration of single doses of etoricoxib up to 500 mg and multiple doses up to 150 mg/day for 21 days did not result in significant toxicity. There have been reports of acute overdosage with etoricoxib, although adverse experiences were not reported in the majority of cases. The most frequently observed adverse experiences were consistent with the safety profile for etoricoxib (e.g. gastrointestinal events, cardiorenal events). In the event of overdose, it is reasonable to employ the usual supportive measures, e.g., remove unabsorbed material from the GI tract, employ clinical monitoring, and institute supportive therapy, if required. Etoricoxib is not dialysable by haemodialysis; it is not known whether etoricoxib is dialysable by peritoneal dialysis.


Pharmacotherapeutic group: Anti-inflammatory and antirheumatic products, non-steroids, coxibs, ATC code: M01 AH05

 

Mechanism of Action

Etoricoxib is an oral, selective cyclo-oxygenase-2 (COX-2) inhibitor within the clinical dose range.

 

Across clinical pharmacology studies, etoricoxib produced dose-dependent inhibition of COX- 2 without inhibition of COX-1 at doses up to 150 mg daily. Etoricoxib did not inhibit gastric prostaglandin synthesis and had no effect on platelet function.

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 man but its relevance to ulcer healing has not been established.

 

Clinical efficacy and safety Efficacy

In patients with osteoarthritis (OA), etoricoxib 60 mg once daily provided significant improvements in pain and patient assessments of disease status. These beneficial effects were observed as early as the second day of therapy and maintained for up to 52 weeks. Studies with etoricoxib 30 mg once daily demonstrated efficacy superior to placebo over a 12 week treatment period (using similar assessments as the above studies). In a dose ranging study, etoricoxib 60 mg demonstrated significantly greater improvement than 30 mg for all 3 primary endpoints over 6 weeks of treatment. The 30 mg dose has not been studied in osteoarthritis of hands.

In patients with rheumatoid arthritis (RA), etoricoxib 60 mg and 90 mg once daily both provided significant improvements in pain, inflammation, and mobility. In studies evaluating the 60 mg and 90 mg dose, these beneficial effects were maintained over the 12-week treatment periods. In a study evaluating the 60 mg dose compared to the 90 mg dose, etoricoxib 60 mg once daily and 90 mg once daily were both more effective than placebo. The 90 mg dose was superior to the 60 mg dose for Patient Global Assessment of Pain (0-100mm visual analogue scale), with an average improvement of -2.71 mm (95% CI: -4.98 mm, -0.45 mm).

In patients experiencing attacks of acute gouty arthritis, etoricoxib 120 mg once daily over an eight-day treatment period, relieved moderate to extreme joint pain and inflammation comparable to indomethacin 50 mg three times daily. Pain relief was observed as early as four hours after initiation of treatment.

In patients with ankylosing spondylitis, etoricoxib 90 mg once daily provided significant improvements in spine pain, inflammation, stiffness and function. The clinical benefit of etoricoxib was observed as early as the second day of therapy after initiation of treatment and was maintained throughout the 52-week treatment period. In a second study evaluating the 60 mg dose compared to the 90 mg dose, etoricoxib 60 mg daily and 90 mg daily demonstrated similar efficacy compared to naproxen 1,000 mg daily. Among inadequate responders to 60 mg daily for 6 weeks, dose escalation to 90 mg daily improved spinal pain intensity score (0-100 mm visual analogue scale) compared to continuing on 60 mg daily, with an average improvement of -2.70 mm (95% CI: -4.88 mm, -0.52 mm).

In a clinical study evaluating postoperative dental pain, etoricoxib 90 mg was administered once daily for up to three days. In the subgroup of patients with moderate pain at baseline, etoricoxib 90 mg demonstrated a similar analgesic effect to that of ibuprofen 600 mg (16.11 vs. 16.39; P=0.722), and greater than that of paracetamol/codeine 600 mg/60 mg (11.00; P<0.001) and

 

placebo (6.84; P<0.001) as measured by total pain relief over the first 6 hours (TOPAR6). The proportion of patients reporting rescue medication usage within the first 24 hours of dosing was 40.8% for etoricoxib 90 mg, 25.5% for ibuprofen 600 mg Q6h, and 46.7% for paracetamol/codeine 600 mg/60 mg Q6h compared to 76.2% for placebo. In this study, the median onset of action (perceptible pain relief) of 90 mg etoricoxib was 28 minutes after dosing.

 

Safety

Multinational Etoricoxib and Diclofenac Arthritis Long-term (MEDAL) Programme

The MEDAL Programme was a prospectively designed Cardiovascular (CV) Safety Outcomes Programme of pooled data from three randomized, double-blind active comparator controlled trials, the MEDAL study, EDGE II and EDGE.

The MEDAL Study, was an endpoint driven CV Outcomes study in 17,804 OA and 5,700 RA patients treated with etoricoxib 60 (OA) or 90 mg (OA and RA) or diclofenac 150 mg daily for a mean period of 20.3 months (maximum of 42.3 months, median 21.3 months). In this trial, only serious adverse events and discontinuations due to any adverse events were recorded.

The EDGE and EDGE II studies compared the gastrointestinal tolerability of etoricoxib versus diclofenac. The EDGE study included 7,111 OA patients treated with a dose of etoricoxib 90 mg daily (1.5 times the dose recommended for OA) or diclofenac 150 mg daily for a mean period of 9.1 months (maximum 16.6 months, median 11.4 months). The EDGE II study included 4,086 RA patients treated with etoricoxib 90 mg daily or diclofenac 150 mg daily for a mean period of 19.2 months (maximum 33.1 months, median 24 months).

In the pooled MEDAL Programme, 34,701 patients with OA or RA were treated for a mean duration of 17.9 months (maximum 42.3 months, median 16.3 months) with approximately 12,800 patients receiving treatment for more than 24 months. Patients enrolled in the Programme had a wide range of cardiovascular and gastrointestinal risk factors at baseline. Patients with a recent history of myocardial infarction, coronary artery bypass grafting or percutaneous coronary intervention within 6 months preceding enrollment were excluded. Use of gastroprotective agents and low dose aspirin were permitted in the studies.

Overall Safety:

There was no significant difference between etoricoxib and diclofenac in the rate of cardiovascular thrombotic events. Cardiorenal adverse events were observed more frequently with etoricoxib than with diclofenac, and this effect was dose-dependent (see specific results below). Gastrointestinal and hepatic adverse events were observed significantly more frequently with diclofenac than etoricoxib. The incidence of adverse experiences in EDGE and EDGE II and of adverse experiences considered serious or resulting in discontinuation in the MEDAL study was higher with etoricoxib than diclofenac.

Cardiovascular safety results:

The rate of confirmed thrombotic cardiovascular serious adverse events (consisting of cardiac, cerebrovascular, and peripheral vascular events) was comparable between etoricoxib and diclofenac, and data are summarized in the table below. There were no statistically significant differences in thrombotic event rates between etoricoxib and diclofenac across all subgroups analyzed including patient categories across a range of baseline cardiovascular risk. When considered separately, the relative risks for confirmed thrombotic cardiovascular serious adverse events with etoricoxib 60 mg or 90 mg compared with diclofenac 150 mg were similar.

 
 Text Box: Table 2: Rates of Confirmed Thrombotic CV Events (Pooled MEDAL Programme)

 

 

 

Etoricoxib (N=16,819)

25,836 Patient-Years

Diclofenac (N=16,483)

24,766 Patient-Years

Between                       Treatment Comparison

 

Rate (95% CI)

Rate (95% CI)

Relative Risk (95% CI)

Confirmed Thrombotic Cardiovascular Serious Adverse Events

Per-protocol

1.24 (1.11, 1.38)

1.30 (1.17, 1.45)

0.95 (0.81, 1.11)

Intent-to-treat

1.25 (1.14, 1.36)

1.19 (1.08, 1.30)

1.05 (0.93, 1.19)

Confirmed Cardiac Events

Per-protocol

0.71 (0.61, 0.82)

0.78 (0.68, 0.90)

0.90 (0.74, 1.10)

Intent-to-treat

0.69 (0.61, 0.78)

0.70 (0.62, 0.79)

0.99 (0.84, 1.17)

Confirmed Cerebrovascular Events

Per-protocol

0.34 (0.28, 0.42)

0.32 (0.25, 0.40)

1.08 (0.80, 1.46)

Intent-to-treat

0.33 (0.28, 0.39)

0.29 (0.24, 0.35)

1.12 (0.87, 1.44)

Confirmed Peripheral Vascular Events

Per-protocol

0.20 (0.15, 0.27)

0.22 (0.17, 0.29)

0.92 (0.63, 1.35)

Intent-to-treat

0.24 (0.20, 0.30)

0.23 (0.18, 0.28)

1.08 (0.81, 1.44)

†Events per 100 Patient-Years; CI=confidence interval

N=total number of patients included in Per-protocol population

Per-protocol: all events on study therapy or within 14 days of discontinuation (excluded: patients who took < 75% of their study medication or took non-study NSAIDs >10% of the time).

Intent-to-treat: all confirmed events up to the end of the trial (included patients potentially exposed to non-study interventions following discontinuation of study medication). Total number of patients randomised, n= 17,412 on etoricoxib and 17,289 on diclofenac.

CV mortality, as well as overall mortality, was similar between the etoricoxib and diclofenac treatment groups.

Cardiorenal Events:

Approximately 50% of patients enrolled in the MEDAL study had a history of hypertension at baseline. In the study, the incidence of discontinuations due to hypertension-related adverse events was statistically significantly higher for etoricoxib than for diclofenac. The incidence of congestive heart failure adverse events (discontinuations and serious events) occurred at similar rates on etoricoxib 60 mg compared to diclofenac 150 mg but was higher for etoricoxib 90 mg compared to diclofenac 150 mg (statistically significant for 90 mg etoricoxib vs. 150 mg diclofenac in MEDAL OA cohort). The incidence of confirmed congestive heart failure adverse events (events that were serious and resulted in hospitalisation or a visit to an emergency department) was non-significantly higher with etoricoxib than diclofenac 150 mg, and this effect was dose-dependent. The incidence of discontinuations due to oedema-related adverse events was higher for etoricoxib than diclofenac 150 mg, and this effect was dose-dependent (statistically significant for etoricoxib 90 mg, but not for etoricoxib 60 mg).

The cardiorenal results for EDGE and EDGE II were consistent with those described for the MEDAL Study.

In the individual MEDAL Programme studies, for etoricoxib (60 mg or 90 mg), the absolute incidence of discontinuation in any treatment group was up to 2.6% for hypertension, up to 1.9%

 

for oedema, and up to 1.1% for congestive heart failure, with higher rates of discontinuation observed with etoricoxib 90 mg than etoricoxib 60 mg.

MEDAL Programme Gastrointestinal Tolerability Results:

A significantly lower rate of discontinuations of treatment for any clinical (e.g., dyspepsia, abdominal pain, ulcer) GI adverse event was observed with etoricoxib compared with diclofenac within each of the three component studies of the MEDAL Programme. The rates of discontinuations due to adverse clinical GI events per hundred patient-years over the entire period of study were as follows: 3.23 for etoricoxib and 4.96 for diclofenac in the MEDAL Study;

9.12 with etoricoxib and 12.28 with diclofenac in the EDGE study; and 3.71 with etoricoxib and

4.81 with diclofenac in the EDGE II study.

MEDAL Programme Gastrointestinal Safety Results:

Overall upper GI events were defined as perforations, ulcers and bleeds. The subset of overall upper GI events considered complicated included perforations, obstructions, and complicated bleeding; the subset of upper GI events considered uncomplicated included uncomplicated bleeds and uncomplicated ulcers. A significantly lower rate of overall upper GI events was observed with etoricoxib compared to diclofenac. There was no significant difference between etoricoxib and diclofenac in the rate of complicated events. For the subset of upper GI haemorrhage events (complicated and uncomplicated combined), there was no significant difference between etoricoxib and diclofenac. The upper GI benefit for etoricoxib compared with diclofenac was not statistically significant in patients taking concomitant low-dose aspirin (approximately 33% of patients).

The rates per hundred patient-years of confirmed complicated and uncomplicated upper GI clinical events (perforations, ulcers and bleeds (PUBs)) were 0.67 (95% CI 0.57, 0.77) with etoricoxib and 0.97 (95% CI 0.85, 1.10) with diclofenac, yielding a relative risk of 0.69 (95% CI

0.57, 0.83).

The rate for confirmed upper GI events in elderly patients was evaluated and the largest reduction was observed in patients ≥ 75 years of age (1.35 [95% CI 0.94, 1.87] vs. 2.78 [95% CI 2.14, 3.56] events per hundred patient-years for etoricoxib and diclofenac, respectively.

The rates of confirmed lower GI clinical events (small or large bowel perforation, obstruction, or haemorrhage, (POBs)) were not significantly different between etoricoxib and diclofenac.

MEDAL Programme Hepatic Safety Results:

Etoricoxib was associated with a statistically significantly lower rate of discontinuations due to hepatic-related adverse experiences than diclofenac. In the pooled MEDAL Programme, 0.3% of patients on etoricoxib and 2.7% of patients on diclofenac discontinued due to hepatic-related adverse experiences. The rate per hundred patient-years was 0.22 on etoricoxib and 1.84 for diclofenac (p-value was <0.001 for etoricoxib vs. diclofenac). However, most hepatic adverse experiences in the MEDAL Programme were non-serious.

Additional Thrombotic Cardiovascular Safety Data

In clinical studies excluding the MEDAL Programme Studies, approximately 3,100 patients were treated with etoricoxib ≥60 mg daily for 12 weeks or longer. There was no discernible difference in the rate of confirmed serious thrombotic cardiovascular events between patients receiving etoricoxib ≥60 mg, placebo, or non-naproxen NSAIDs. However, the rate of these events was higher in patients receiving etoricoxib compared with those receiving naproxen 500 mg twice daily. The difference in antiplatelet activity between some COX-1 inhibiting NSAIDs and selective COX-2 inhibitors may be of clinical significance in patients at risk of thrombo-embolic events. Selective COX-2 inhibitors reduce the formation of systemic (and therefore possibly

 

endothelial) prostacyclin without affecting platelet thromboxane. The clinical relevance of these observations has not been established.

Additional Gastrointestinal Safety Data

In two 12-week double-blind endoscopy studies, the cumulative incidence of gastroduodenal ulceration was significantly lower in patients treated with etoricoxib 120 mg once daily than in patients treated with either naproxen 500 mg twice daily or ibuprofen 800 mg three times daily. Etoricoxib had a higher incidence of ulceration as compared to placebo.

Renal Function Study in the Elderly

A randomized, double-blind, placebo-controlled, parallel-group study evaluated the effects of 15 days of treatment of etoricoxib (90 mg), celecoxib (200 mg bid), naproxen (500 mg bid) and placebo on urinary sodium excretion, blood pressure, and other renal function parameters in subjects 60 to 85 years of age on a 200-mEq/day sodium diet. Etoricoxib, celecoxib, and naproxen had similar effects on urinary sodium excretion over the 2 weeks of treatment. All active comparators showed an increase relative to placebo with respect to systolic blood pressures; however, etoricoxib was associated with a statistically significant increase at Day 14 when compared to celecoxib and naproxen (mean change from baseline for systolic blood pressure: etoricoxib 7.7 mmHg, celecoxib 2.4 mmHg, naproxen 3.6 mmHg).


Absorption

Orally administered etoricoxib is well absorbed. The absolute bioavailability is approximately 100%. Following 120 mg once-daily dosing to steady state, the peak plasma concentration (geometric mean Cmax = 3.6 µg/ml) was observed at approximately 1 hour (Tmax) after administration to fasted adults. The geometric mean area under the curve (AUC0-24hr) was 37.8 µg•hr/ml. The pharmacokinetics of etoricoxib are linear across the clinical dose range.

Dosing with food (a high-fat meal) had no effect on the extent of absorption of etoricoxib after administration of a 120-mg dose. The rate of absorption was affected, resulting in a 36% decrease in Cmax and an increase in Tmax by 2 hours. These data are not considered clinically significant. In clinical trials, etoricoxib was administered without regard to food intake.

Distribution

Etoricoxib is approximately 92% bound to human plasma protein over the range of concentrations of 0.05 to 5 µg/ml. The volume of distribution at steady state (Vdss) was approximately 1,20l in humans.

Etoricoxib crosses the placenta in rats and rabbits, and the blood-brain barrier in rats.

Biotransformation

Etoricoxib is extensively metabolised with <1% of a dose recovered in urine as the parent drug. The major route of metabolism to form the 6'-hydroxymethyl derivative is catalyzed by CYP enzymes. CYP3A4 appears to contribute to the metabolism of etoricoxib in vivo. In vitro studies indicate that CYP2D6, CYP2C9, CYP1A2 and CYP2C19 also can catalyse the main metabolic pathway, but their quantitative roles in vivo have not been studied.

Five metabolites have been identified in man. The principal metabolite is the 6'-carboxylic acid derivative of etoricoxib formed by further oxidation of the 6'-hydroxymethyl derivative. These principal metabolites either demonstrate no measurable activity or are only weakly active as COX-2 inhibitors. None of these metabolites inhibit COX-1.

Elimination

 

Following administration of a single 25-mg radiolabeled intravenous dose of etoricoxib to healthy subjects, 70% of radioactivity was recovered in urine and 20% in faeces, mostly as metabolites. Less than 2% was recovered as unchanged drug.

Elimination of etoricoxib occurs almost exclusively through metabolism followed by renal excretion. Steady state concentrations of etoricoxib are reached within seven days of once daily administration of 120 mg, with an accumulation ratio of approximately 2, corresponding to a half-life of approximately 22 hours. The plasma clearance after a 25-mg intravenous dose is estimated to be approximately 50 ml/min.

Characteristics in patients

Elderly patients: Pharmacokinetics in the elderly (65 years of age and older) are similar to those in the young.

Gender: The pharmacokinetics of etoricoxib are similar between men and women.

Hepatic impairment: Patients with mild hepatic dysfunction (Child-Pugh score 5-6) administered etoricoxib 60 mg once daily had an approximately 16% higher mean AUC as compared to healthy subjects given the same regimen. Patients with moderate hepatic dysfunction (Child-Pugh score 7-9) administered etoricoxib 60 mg every other day had similar mean AUC to the healthy subjects given etoricoxib 60 mg once daily; etoricoxib 30 mg once daily has not been studied in this population. There are no clinical or pharmacokinetic data in patients with severe hepatic dysfunction (Child-Pugh score ≥10). (See sections 4.2 and 4.3.) Renal impairment: The pharmacokinetics of a single dose of etoricoxib 120 mg in patients with moderate to severe renal insufficiency and patients with end-stage renal disease on haemodialysis were not significantly different from those in healthy subjects. Haemodialysis contributed negligibly to elimination (dialysis clearance approximately 50 ml/min). (See sections 4.3 and 4.4.)

Paediatric patients: The pharmacokinetics of etoricoxib in paediatric patients (<12 years old) have not been studied.

In a pharmacokinetic study (n=16) conducted in adolescents (aged 12 to 17) the pharmacokinetics in adolescents weighing 40 to 60 kg given etoricoxib 60 mg once daily and adolescents >60 kg given etoricoxib 90 mg once daily were similar to the pharmacokinetics in adults given etoricoxib 90 mg once daily. Safety and effectiveness of etoricoxib in paediatric patients have not been established (see section 4.2).


In preclinical studies, etoricoxib has been demonstrated not to be genotoxic. Etoricoxib was not carcinogenic in mice. Rats developed hepatocellular and thyroid follicular cell adenomas at >2- times the daily human dose [90 mg] based on systemic exposure when dosed daily for approximately two years. Hepatocellular and thyroid follicular cell adenomas observed in rats are considered to be a consequence of rat-specific mechanism related to hepatic CYP enzyme induction. Etoricoxib has not been shown to cause hepatic CYP3A enzyme induction in humans.

In the rat, gastrointestinal toxicity of etoricoxib increased with dose and exposure time. In the 14-week toxicity study etoricoxib caused gastrointestinal ulcers at exposures greater than those seen in man at the therapeutic dose. In the 53- and 106-week toxicity study, gastrointestinal ulcers were also seen at exposures comparable to those seen in man at the therapeutic dose. In dogs, renal and gastrointestinal abnormalities were seen at high exposures.

 

Etoricoxib was not teratogenic in reproductive toxicity studies conducted in rats at 15 mg/kg/day (this represents approximately 1.5 times the daily human dose [90 mg] based on systemic exposure). In rabbits, a treatment related increase in cardiovascular malformations was observed at exposure levels below the clinical exposure at the daily human dose (90 mg). However no treatment-related external or skeletal foetal malformations were observed. In rats and rabbits, there was a dose dependent increase in post implantation loss at exposures greater than or equal to 1.5 times the human exposure (see sections 4.3 and 4.6).

Etoricoxib is excreted in the milk of lactating rats at concentrations approximately two-fold those in plasma. There was a decrease in pup body weight following exposure of pups to milk from dams administered etoricoxib during lactation.


Lactose monohydrate , microcrystalline Cellulose, croscarmellose sodium, povidone K30, colloidal silicone dioxide, magnesium stearate, opadry OY-L White , yellow iron oxide, FD&C Blue #2 lake, polyethylene glycol.


Not applicable.


2 years

Store below 30°C.

Store in the original package in order to protect from moisture


1.1   Orotix® 60 mg Tablets

Light greenish blue, 7.Omm round normal biconvex film coated tablet scored on one face and engraved with Phl on the other one, packed in Alu/Alu blister, intended for oral use.

Pack size:

7 tablets in Alu / Alu blister.2 blisters/pack. 10 tablets in Alu/Alu blister.3 blisters/pack.

 

Orotix® 90 mg Tablets

Light greenish blue 8.2 mm round normal biconvex film coated tablet engraved with PhI on one face, packed in Alu/Alu blister, intended for oral use.

Pack size:

7 tablets in Alu/Alu blister. 2 blisters/pack. 10 tablets in Alu/Alu blister.3 blisters/pack.

 

Orotix® 120 mg Tablets

 

Light greenish blue 9 mm round normal biconvex film coated tablet engraved with PhI on one face, packed in Alu/Alu blister, intended for oral use.

Pack size:

7 tablets in Alu/Alu blister.1 blister/pack. 10 tablets in Alu/Alu blister.1 blister/pack

 


No special requirements.


Pharma International Company Amman - Jordan Tel: 00962-6-5158890 / 5157893 Fax: 00962-6-5154753 email: marketing@pic-jo.com

05/2020
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