Why Is Etoricoxib Banned?

Is it safe to take etoricoxib?

My Account Area – The Patient Information Leaflet (PIL) is the leaflet included in the pack with a medicine. Last updated on emc: 16 Feb 2022 Etoricoxib 30 mg film-coated tablets Etoricoxib 60 mg film-coated tablets Etoricoxib 90 mg film-coated tablets Etoricoxib 120 mg film-coated tablets

Keep this leaflet. You may need to read it again.If you have any further questions, ask your doctor or pharmacist.This medicine has been prescribed for you only. Do not pass it on to others. It may harm them, even if their signs of illness are the same as yours.If you get any side effects, talk to your doctor or pharmacist. This includes any possible side effects not listed in this leaflet. See section 4.

1. What etoricoxib is and what it is used for 2. What you need to know before you take etoricoxib 3. How to take etoricoxib 4. Possible side effects 5. How to store etoricoxib 6. Contents of the pack and other information The name of your medicine is Etoricoxib film-coated tablets (referred to as etoricoxib throughout this leaflet).

The active substance etoricoxib which belongs to a group of medicines called selective COX-2 inhibitors. These belong to a family of medicines called non-steroidal anti-inflammatory drugs (NSAIDs). Etoricoxib 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.

Etoricoxib is also used for the short term treatment of moderate pain after dental surgery in people 16 years of age and older. 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. 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.

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

if you are allergic to etoricoxib or any of the other ingredients of this medicine (listed in section 6).if you are allergic to non-steroidal anti-inflammatory drugs (NSAIDs), including acetylsalicylic acid and COX-2 inhibitors (see Possible Side Effects, section 4).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 (see ‘Pregnancy, breast-feeding and fertility’).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 you with 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. Talk to your doctor or pharmacist before taking etoricoxib if:

you have a history of stomach bleeding or ulcers.you are dehydrated, for example by a prolonged bout of vomiting or diarrhoea.you have swelling due to fluid retention.you have a history of heart failure, or any other form of heart disease.you have a history of high blood pressure. Etoricoxib 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.you have any history of liver or kidney disease.you are being treated for an infection. Etoricoxib can mask or hide a fever, which is a sign of infection.you have diabetes, high cholesterol, or are a smoker. These can increase your risk of heart disease.you are a woman trying to become pregnant.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 etoricoxib to see if this medicine is suitable for you. Etoricoxib 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.

medicines that thin your blood (anticoagulants), such as warfarinrifampicin (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 valsartandiuretics (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)acetylsalicylic acid, the risk of stomach ulcers is greater if you take etoricoxib with acetylsalicylic acid.acetylsalicylic acid for prevention of heart attacks or stroke: Etoricoxib can be taken with low-dose acetylsalicylic acid. If you are currently taking low-dose acetylsalicylic acid to prevent heart attacks or stroke, you should not stop taking acetylsalicylic acid until you talk to your doctoracetylsalicylic acid and other non-steroidal anti-inflammatory drugs (NSAIDs): do not take high dose acetylsalicylic acid or other anti-inflammatory medicines while taking etoricoxib.

The onset of the effect of etoricoxib may be faster when taken without food. 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 Etoricoxib must not be taken during pregnancy.

1. If you are pregnant or think you may be pregnant or are planning to have a baby, do not take the tablets.
2. If you become pregnant, stop taking the tablets and consult your doctor.
3. Consult your doctor if you are unsure or need more advice.
4. 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 etoricoxib. If you are taking etoricoxib, you must not breast-feed. Fertility Etoricoxib is not recommended in women attempting to become pregnant. Dizziness and sleepiness have been reported in some patients taking etoricoxib.

Do not drive if you experience dizziness or sleepiness. Do not use any tools or machines if you experience dizziness or sleepiness. Always take this medicine exactly as your doctor has told you. 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 treatment from time to time. It is important that you use the lowest dose that controls your pain and you should not take etoricoxib for longer than necessary. This is because the risk of heart attacks and strokes might increase after prolonged treatment, especially with high doses.

1. 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.
2. The recommended dose is: Osteoarthritis The recommended dose is 30 mg once a day, increased 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. Ankylosing spondylitis The recommended dose is 60 mg once a day, increased to a maximum of 90 mg once a day if needed. Acute pain conditions Etoricoxib should be used only for the acute painful period.

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. 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. Etoricoxib should not be taken by children or adolescents under 16 years of age. No dose adjustment is necessary for elderly patients. Caution should be exercised in elderly patients.

1. Etoricoxib is for oral use.
2. Take the tablets once a day.
3. Etoricoxib can be taken with or without food.
4. You should never take more tablets than the doctor recommends.
5. If you do take too many etoricoxib tablets, you should seek medical attention immediately.
6. 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 a 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.

shortness of breath, chest pain, 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 following side effects can occur during treatment with etoricoxib: Very common (may affect more than 1 in 10 people)

stomach pain.

Common (may affect up to 1 in 10 people)

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, diarrhoea, 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 (may affect up to 1 in 100 people)

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, non-specific ECG changes, feeling of tightness, pressure or heaviness 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, increased levels of uric acid and creatine phosphokinase,chest pain.

Rare (may affect up to 1 in 1,000 people)

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 (these reactions can involve ulcers of the mouth, throat, nose and genitals; the rash may progress to widespread blistering and peeling of the skin).

If you get any side effects, talk to your doctor or pharmacist or nurse. This includes any possible side effects not listed in this leaflet. You can also report side effects directly via the Yellow Card Scheme at: www.mhra.gov.uk/yellowcard. By reporting side effects you can help provide more information on the safety of this medicine.

Eep this medicine out of the sight and reach of children. Do not use this medicine after the expiry date which is stated on the pack after EXP. The expiry date refers to the last day of that month. This medicine does not require any special storage conditions. Do not throw away any medicines via wastewater or household waste.

Ask your pharmacist how to throw away medicines you no longer use. These measures will help protect the environment. The active substance is etoricoxib. Each film-coated tablet contains 30, 60, 90 or 120 mg of etoricoxib. The other ingredients are: Tablet core: Calcium hydrogen phosphate, anhydrous; Cellulose microcrystalline; Croscarmellose sodium; Silica colloidal anhydrous; Talc; Magnesium stearate Film coat: Hypromellose; Hydroxypropylcellulose; Macrogol 6000; Talc; Titanium dioxide E171 The 60 mg tablets also contain brown ferric oxide E172, the 90 mg tablets also contain yellow ferric oxide E172 and 120 mg tablets also contain red ferric oxide E172.

Etoricoxib 30 mg film-coated tablets: White to off white round biconvex film-coated tablets, approx.6 mm in diameter. Etoricoxib 60 mg film-coated tablets: Light brown round biconvex film-coated tablets, approx.8 mm in diameter. Etoricoxib 90 mg film-coated tablets: Light yellow round biconvex film-coated tablets, approx.9 mm in diameter.

Etoricoxib 120 mg film-coated tablets: Light pink round biconvex film-coated tablets, approx.10 mm in diameter. Etoricoxib 30 mg film-coated tablets 7, 20, 28, 50, 98 and 100 film-coated tablets Etoricoxib 60 and 90 mg film-coated tablets 7, 14, 20, 28, 50, 100 film-coated tablets Etoricoxib 120 mg film-coated tablets 5, 7, 14, 20, 28, 50 and 100 film-coated tablets Not all pack sizes may be marketed.

Why is etoricoxib banned in UK?

Etoricoxib belongs to the selective COX-2 inhibitor class of drugs and may be associated with an increased risk of coronary and cerebrovascular thrombotic events, heart failure, hypertension, and oedema (compared with placebo and some non-steroidal anti-inflammatory drugs).

What are the harmful effects of etoricoxib?

About ETORICOXIB – ETORICOXIB belongs to a group of medications called ‘non-steroidal anti-inflammatory drugs (NSAIDs) used to treat pain, swelling and inflammation in osteoarthritis, rheumatoid arthritis, ankylosing spondylitis and gout in people greater than 16 years of age.

1. Besides this, it is also used to treat moderate pain after dental surgery.
2. Osteoarthritis is a degenerative bone disease in which the tissue supporting the joints wears down.
3. Rheumatoid arthritis is a condition in which the immune system attacks its tissue leading to joint pain and inflammation.
4. Ankylosing spondylitis is the inflammation of the spine and large joints.

Gout is characterized by pain and inflammation in the joints due to the deposition of uric acid crystals. ETORICOXIB contains ‘etoricoxib’, which works by blocking the release of a chemical messenger called prostaglandin, produced by COX-2, which is responsible for pain, swelling and inflammation.

ETORICOXIB acts at the affected area and acts specifically at the pain site. The benefit of COX-2 inhibitors is that they protect the stomach lining from the ulcer effect caused by other painkillers, ibuprofen and aspirin. ETORICOXIB is available in tablet form and injection. Take an oral form of ETORICOXIB as advised by your doctor.

A healthcare professional will give the injection form of ETORICOXIB, do not self-administer. Common side-effects of ETORICOXIB are stomach pain, dry socket, swelling of the legs, dizziness, headache, palpitations (pounding heart), increased blood pressure, shortness of breath, constipation, flatulence, gastritis (inflammation of the lining of the stomach), heartburn, diarrhoea, indigestion (dyspepsia), nausea, vomiting, inflammation of the oesophagus (food pipe), mouth ulcers, general weakness and flu-like illness (fever, cold, cough, or sore throat).

Do not take ETORICOXIB if you are allergic to etoricoxib, other pain killers or other ingredients. Inform your doctor if you have ulcers or bleeding in your stomach, severe liver and/or kidney impairment, colitis (inflammation of the large intestine), uncontrolled blood pressure, or heart problems such as chest pain, heart attack or heart failure and stroke.

Do not take it if you are under 16 years of age, pregnant, planning to become pregnant or breastfeeding. Inform your doctor if you are dehydrated (because of vomiting or diarrhoea), have oedema (swelling due to fluid retention), have an infection, diabetes (high blood sugar) and high cholesterol, are a smoker or have an age above 65 years.

Is etoricoxib still banned in the US?

After using Arcoxia – Note: Arcoxia has not been approved by the FDA for the U.S. market. Keep your tablets in the blister pack until it is time to take them. If you take the tablets out of the blister pack they may not keep well. Keep Arcoxia in a cool dry place where the temperature stays below 30 degrees C (86 degrees F).

Why is etoricoxib not approved in usa?

Journal List Ann Saudi Med v.28(2); Mar-Apr 2008 PMC6074531

As a library, NLM provides access to scientific literature. Inclusion in an NLM database does not imply endorsement of, or agreement with, the contents by NLM or the National Institutes of Health. Learn more: PMC Disclaimer | PMC Copyright Notice Ann Saudi Med.2008 Mar-Apr; 28(2): 141–142.

The selective COX-2 nonsteroidal anti-inflammatory drug etoricoxib ( Arcoxia ) was approved in Saudi Arabia in 2003 and re-registered in February 2007. The drug is now available in 63 countries worldwide. In April 2007, a U.S. Food and Drug Administration (FDA) advisory committee voted 20 to 1 not to recommend the approval of etoricoxib based on the drug’s cardiovascular (CV) risks and its association with an exacerbation of hypertension.1 All information discussed by FDA advisory committees must be made available to the public before meetings.

The advisory committee discussion documents, known as briefing documents, for the etoricoxib meeting can be found on the FDA’s Web site at: http://www.fda.gov/ohrms/dockets/ac/07/briefing/2007-4290b1-01-FDA.pdf, Data presented at the committee meeting did not exclude the possibility of an over six-fold increase in CV risk with etoricoxib compared to naproxen.2 The original marketing application for etoricoxib was filed with the FDA in October 2001.

• In March 2002, the drug’s manufacturer withdrew the application to allow for the submission of additional data.
• The marketing application was again delayed in June 2002 when the FDA asked for additional acute pain efficacy and CV risk safety data.
• The FDA issued an approvable letter in October 2004 asking for additional safety and efficacy data before making a final decision on the drug’s marketing application.

In February 2005, two years prior to the approval of etoricoxib in Saudi Arabia, the FDA convened a meeting to review the safety of the COX-2 drugs, including etoricoxib. In the briefing documents for this meeting was an FDA safety review of etoricoxib and an analysis of the Etoricoxib vs.

Diclofenac Sodium Gastrointestinal Tolerability and Effectiveness (EDGE) trial.3 The EDGE results were originally presented at the American College of Rheumatology meeting in October 2004. The media reported that etoricoxib showed a significantly better gastrointestinal safety profile than diclofenac and no CV risk signal.4 The EDGE trial 5 was not published until February 2007, at the same time the drug was re-registered in Saudi Arabia and over 28 months after public release of the results at the ACR meeting in October 2004.

The briefing documents for the February 2005 advisory committee meeting suggested that the drug does not offer a unique therapeutic advantage over existing drugs used for the treatment of osteoarthritis and may be associated with a significantly greater risk of CV adverse events compared to other agents.3 The question must be raised, if the February 2005 briefing documents were accessed by the Saudi Arabian drug regulatory authorities during the 2007 re-registration review of etoricoxib, would the drug have remained on the market in Saudi Arabia? In summary, FDA briefing documents may contain rigorous analyses of unpublished data or data whose publication was delayed.

Should I take etoricoxib every day?

My Account Area – The Patient Information Leaflet (PIL) is the leaflet included in the pack with a medicine. Last updated on emc: 04 Oct 2022 ARCOXIA ® 30 mg film-coated tablets ARCOXIA ® 60 mg film-coated tablets ARCOXIA ® 90 mg film-coated tablets ARCOXIA ® 120 mg film-coated tablets etoricoxib

Keep this leaflet. You may need to read it again.If you have any further questions, ask your doctor or pharmacist.This medicine has been prescribed for you only. Do not pass it on to others. It may harm them, even if their signs of illness are the same as yours. If you get any side effects, talk to your doctor or pharmacist. This includes any possible side effects not listed in this leaflet. See section 4.

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

ARCOXIA contains the active substance etoricoxib. ARCOXIA 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).

ARCOXIA 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.ARCOXIA is also used for the short-term treatment of moderate pain after dental surgery in people 16 years of age and older.

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. 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. 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.

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

if you are allergic (hypersensitive) to etoricoxib or any of the other ingredients of this medicine (listed in section 6) if you are allergic to non-steroidal anti-inflammatory drugs (NSAIDs), including aspirin and COX-2 inhibitors (see Possible Side Effects, section 4) 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 (see ‘Pregnancy, breast-feeding, and fertility’) 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. Talk to your doctor or pharmacist before taking ARCOXIA if:

You have a history of stomach bleeding or ulcers. You are dehydrated, for example by a prolonged bout of vomiting or diarrhoea. You have swelling due to fluid retention. You have a history of heart failure, or any other form of heart disease. You have a history of high blood pressure. ARCOXIA 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. You have any history of liver or kidney disease. You are being treated for an infection. ARCOXIA can mask or hide a fever, which is a sign of infection. You have diabetes, high cholesterol, or are a smoker. These can increase your risk of heart disease. You are a woman trying to become pregnant. 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 ARCOXIA to see if this medicine is suitable for you. ARCOXIA 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. Do not give this medicine to children and adolescents under 16 years of age. Tell your doctor or pharmacist if you are taking, have recently taken or might take any other medicines, including 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 ARCOXIA:

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 ARCOXIA with aspirin.

aspirin for prevention of heart attacks or stroke: ARCOXIA 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 doctoraspirin and other non-steroidal anti-inflammatory drugs (NSAIDs): do not take high dose aspirin or other anti-inflammatory medicines while taking ARCOXIA.

The onset of the effect of ARCOXIA may be faster when taken without food. Pregnancy ARCOXIA 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 ARCOXIA is excreted in human milk. If you are breast-feeding, or planning to breast-feed, consult your doctor before taking ARCOXIA. If you are using ARCOXIA, you must not breast-feed.

Fertility ARCOXIA is not recommended in women attempting to become pregnant. Dizziness and sleepiness have been reported in some patients taking ARCOXIA. Do not drive if you experience dizziness or sleepiness. Do not use any tools or machines if you experience dizziness or sleepiness.

1. If you have been told by your doctor that you have an intolerance to some sugars, contact your doctor before taking this medicine.
2. This medicine contains less than 1 mmol sodium (23 mg) per film-coated tablet, that is to say essentially ‘sodium-free’.
3. 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 treatment from time to time. It is important that you use the lowest dose that controls your pain and you should not take ARCOXIA 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. Ankylosing spondylitis The recommended dose is 60 mg once a day, increased to a maximum of 90 mg once a day if needed. Acute pain conditions Etoricoxib should be used only for the acute painful period.

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,

ARCOXIA tablets should not be taken by children or adolescents under 16 years of age. No dose adjustment is necessary for elderly patients. As with other medicines, caution should be exercised in elderly patients. Method of administration ARCOXIA is for oral use.

• Take the tablets once a day.
• ARCOXIA can be taken with or without food.
• You should never take more tablets than the doctor recommends.
• If you do take too many ARCOXIA tablets, you should seek medical attention immediately.
• It is important to take ARCOXIA 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.

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 ARCOXIA: 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, diarrhoea, 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 heaviness 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 you get any side effects, talk to your doctor or pharmacist. This includes any possible side effects not listed in this leaflet. You can also report side effects directly via the Yellow Card Scheme at: www.mhra.gov.uk/yellowcard or search for MHRA Yellow Card in the Google Play or Apple App Store.

By reporting side effects, you can help provide more information on the safety of this medicine. Keep this medicine out of the sight and reach of children. Do not use this medicine after the expiry date which is stated on the carton. The expiry date refers to the last day of that month. Bottles: Keep the container tightly closed in order to protect from moisture.

Blisters: Store in the original package in order to protect from moisture. Do not throw away any medicines via wastewater or household waste. Ask your pharmacist how to throw away medicines you no longer use. These measures will help protect the environment.

The active substance is etoricoxib. Each film coated tablet contains 30, 60, 90 or 120 mg of etoricoxib. The other ingredients are: Core: calcium hydrogen phosphate (anhydrous), croscarmellose sodium, magnesium stearate, microcrystalline cellulose. Tablet coating: carnauba wax, lactose monohydrate, hypromellose, titanium dioxide (E171), triacetin. The 30-, 60- and 120-mg tablets also contain yellow ferric oxide (E172, colouring agent) and indigo carmine lake (E132, colouring agent).

ARCOXIA tablets are available in four strengths: 30 mg blue-green, apple-shaped, biconvex film coated tablets marked ‘ACX 30′ on one side and ‘101′ on the other.60 mg dark green, apple-shaped, biconvex film coated tablets marked ‘ARCOXIA 60′ on one side and ‘200′ on the other.90 mg white, apple-shaped, biconvex film coated tablets marked ‘ARCOXIA 90′ on one side and ‘202′ on the other.120 mg pale-green, apple-shaped, biconvex film coated tablets marked ‘ARCOXIA 120′ on one side and ‘204′ on the other.30 mg: Pack sizes of 2, 7, 14, 20, 28, 49, 98 tablets or multi-packs containing 98 (2 packs of 49) tablets in blisters.60 mg: Pack sizes of 2, 5, 7, 10, 14, 20, 28, 30, 50, 84, 98, 100 tablets or multi-packs containing 98 (2 packs of 49) tablets in blisters; or 30 and 90 tablets in bottles with desiccant containers.

The desiccant (one or two containers) in the bottle, used to keep the tablets dry, should not be swallowed.90 and 120 mg: Pack sizes of 2, 5, 7, 10, 14, 20, 28, 30, 50, 84, 100 tablets or multi-packs containing 98 (2 packs of 49) tablets in blisters; or 30 and 90 tablets in bottles with desiccant containers.

The desiccant (one or two containers) in the bottle, used to keep the tablets dry, should not be swallowed.60, 90 and 120 mg: Aluminium/aluminium blisters (unit doses) in packs of 5, 50 or 100 tablets. Not all pack sizes may be marketed. Marketing Authorisation Holder Organon Pharma (UK) Limited The Hewett Building 14 Hewett Street London EC2A 3NP United Kingdom Manufacturer Merck Sharp & Dohme B.V.

Waarderweg 39 2031 BN Haarlem The Netherlands This medicinal product is authorised in the Member States of the EEA under the following names: Belgium, Luxemburg Arcoxia 30 mg, 60 mg, 90 mg, 120 mg, comprimés pelliculés Denmark, Estonia, Arcoxia Iceland, Norway Ireland, United Kingdom ARCOXIA 30, 60, 90 or 120 mg film-coated tablets Austria Arcoxia 30 mg, 60 mg, 90 mg, 120 mg-Filmtabletten Czech Rep.

ARCOXIA 30 mg, 60 mg, 90 mg potahované tablety Cyprus, Malta ARCOXIA 60, 90, 120 mg film-coated tablets Finland Arcoxia 30, 60, 90 ja 120 mg tabletti, kalvopäällysteinen France ARCOXIA 30, 60 mg comprimé pelliculé Germany ARCOXIA 30/60/90/120 mg Filmtabletten Greece ARCOXIA 30 mg, 60 mg, 90 mg,120 mg film-coated tablets Hungary Arcoxia 30 mg, 60 mg, 90 mg, 120 mg filmtabletta Italy ARCOXIA 30, 60, 90, 120 mg compresse rivestite con film Latvia Arcoxia 30 mg, 60 mg, 90 mg un 120 mg apvalkotās tabletes Lithuania Arcoxia 30, 60, 90, 120 mg plėvele dengtos tabletės Netherlands Arcoxia 30 mg, 60 mg, 90 mg, 120 mg, filmomhulde tabletten Poland ARCOXIA 30 mg, 60 mg, 90 mg, 120 mg tabletki powlekane Portugal ARCOXIA 30 mg, 60 mg, 90 mg, 120 mg comprimidos revestidos por película Slovakia ARCOXIA 30 mg, 60 mg, 90 mg, 120 mg Slovenia Arcoxia 30/60/90/120 mg filmsko obložene tablete Spain ARCOXIA 30, 60, 90 y 120 mg comprimidos recubiertos con película Sweden Arcoxia 30 mg, 60 mg, 90 mg och 120 mg filmdragerade tabletter This leaflet was last revised in April 2022.

Can I take etoricoxib long term?

Etoricoxib is used for long-term treatment (taken for 3-months and more) and short-term treatment (taken for 1 to 3 weeks).

Is etoricoxib safer than ibuprofen?

Conclusion: Low-dose etoricoxib with low-dose paracetamol has comparable analgesic efficacy with better safety than therapeutic dose ibuprofen and low-dose paracetamol.

Can you drink alcohol while taking etoricoxib?

Alcohol – Q: Can I consume alcohol with Etoricoxib? A: Do not drink alcohol during treatment with Etoricoxib. Etoricoxib and alcohol consumption increase the risk of bleeding from stomach and intestine.

When should I stop taking etoricoxib?

Things you must do – If you become pregnant while taking ARCOXIA, tell your doctor immediately. If you get an infection while taking ARCOXIA, tell your doctor. ARCOXIA may hide fever and may make you think, mistakenly, that you are better or that that your infection is less serious than it might be.

1. If you notice any of the following, tell your doctor immediately: vomiting blood or material that looks like coffee grounds, bleeding from the back passage, black sticky bowel motions (stools), or bloody diarrhoea These symptoms may occur at any time during use and without warning.
2. Any symptoms that could indicate a severe allergic reaction such as inability to breath or a serious skin reaction which may occur without warning You may need urgent medical attention.

If any of the following symptoms: serious skin rash, shortness of breath, chest pains or ankle swelling, appear or worsen, stop your treatment with ARCOXIA and consult a doctor, as soon as is practical. If you are about to be started on any new medicine, tell your doctor and pharmacist that you are taking ARCOXIA.

Additional things to be aware of while taking ARCOXIA: ARCOXIA works equally well in older and younger adult patients. Adverse experiences may occur at a higher incidence in older patients compared to younger patients. If you are elderly (i.e., over 65 years of age), your doctor will want to keep a regular check on you.

No dosage adjustment is necessary for older patients. If you have kidney, liver or heart disease, your doctor will want to keep a regular check on you. Your doctor will want to discuss your treatment from time to time. It is important that you use the lowest dose that controls your pain and you should not take ARCOXIA for longer than necessary.

Is etoricoxib cardiac risk?

Background – Etoricoxib belongs to the selective COX-2 inhibitor class of drugs and may be associated with an increased risk of coronary and cerebrovascular thrombotic events, heart failure, hypertension, and oedema (compared with placebo and some non-steroidal anti-inflammatory drugs).

Does etoricoxib affect sleep?

My Account Area – The Patient Information Leaflet (PIL) is the leaflet included in the pack with a medicine. Last updated on emc: 16 Feb 2022 Etoricoxib 30 mg film-coated tablets Etoricoxib 60 mg film-coated tablets Etoricoxib 90 mg film-coated tablets Etoricoxib 120 mg film-coated tablets

Keep this leaflet. You may need to read it again.If you have any further questions, ask your doctor or pharmacist.This medicine has been prescribed for you only. Do not pass it on to others. It may harm them, even if their signs of illness are the same as yours.If you get any side effects, talk to your doctor or pharmacist. This includes any possible side effects not listed in this leaflet. See section 4.

1. What etoricoxib is and what it is used for 2. What you need to know before you take etoricoxib 3. How to take etoricoxib 4. Possible side effects 5. How to store etoricoxib 6. Contents of the pack and other information The name of your medicine is Etoricoxib film-coated tablets (referred to as etoricoxib throughout this leaflet).

The active substance etoricoxib which belongs to a group of medicines called selective COX-2 inhibitors. These belong to a family of medicines called non-steroidal anti-inflammatory drugs (NSAIDs). Etoricoxib 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.

Etoricoxib is also used for the short term treatment of moderate pain after dental surgery in people 16 years of age and older. 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. 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.

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

if you are allergic to etoricoxib or any of the other ingredients of this medicine (listed in section 6).if you are allergic to non-steroidal anti-inflammatory drugs (NSAIDs), including acetylsalicylic acid and COX-2 inhibitors (see Possible Side Effects, section 4).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 (see ‘Pregnancy, breast-feeding and fertility’).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 you with 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. Talk to your doctor or pharmacist before taking etoricoxib if:

you have a history of stomach bleeding or ulcers.you are dehydrated, for example by a prolonged bout of vomiting or diarrhoea.you have swelling due to fluid retention.you have a history of heart failure, or any other form of heart disease.you have a history of high blood pressure. Etoricoxib 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.you have any history of liver or kidney disease.you are being treated for an infection. Etoricoxib can mask or hide a fever, which is a sign of infection.you have diabetes, high cholesterol, or are a smoker. These can increase your risk of heart disease.you are a woman trying to become pregnant.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 etoricoxib to see if this medicine is suitable for you. Etoricoxib 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.

medicines that thin your blood (anticoagulants), such as warfarinrifampicin (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 valsartandiuretics (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)acetylsalicylic acid, the risk of stomach ulcers is greater if you take etoricoxib with acetylsalicylic acid.acetylsalicylic acid for prevention of heart attacks or stroke: Etoricoxib can be taken with low-dose acetylsalicylic acid. If you are currently taking low-dose acetylsalicylic acid to prevent heart attacks or stroke, you should not stop taking acetylsalicylic acid until you talk to your doctoracetylsalicylic acid and other non-steroidal anti-inflammatory drugs (NSAIDs): do not take high dose acetylsalicylic acid or other anti-inflammatory medicines while taking etoricoxib.

The onset of the effect of etoricoxib may be faster when taken without food. 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 Etoricoxib must not be taken during pregnancy.

If you are pregnant or think you may be pregnant or are planning to have a baby, 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 etoricoxib. If you are taking etoricoxib, you must not breast-feed. Fertility Etoricoxib is not recommended in women attempting to become pregnant. Dizziness and sleepiness have been reported in some patients taking etoricoxib.

Do not drive if you experience dizziness or sleepiness. Do not use any tools or machines if you experience dizziness or sleepiness. Always take this medicine exactly as your doctor has told you. 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 treatment from time to time. It is important that you use the lowest dose that controls your pain and you should not take etoricoxib 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, increased 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. Ankylosing spondylitis The recommended dose is 60 mg once a day, increased to a maximum of 90 mg once a day if needed. Acute pain conditions Etoricoxib should be used only for the acute painful period.

• 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.
• 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. Etoricoxib should not be taken by children or adolescents under 16 years of age. No dose adjustment is necessary for elderly patients. Caution should be exercised in elderly patients.

• Etoricoxib is for oral use.
• Take the tablets once a day.
• Etoricoxib can be taken with or without food.
• You should never take more tablets than the doctor recommends.
• If you do take too many etoricoxib tablets, you should seek medical attention immediately.
• 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 a 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.

shortness of breath, chest pain, 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 following side effects can occur during treatment with etoricoxib: Very common (may affect more than 1 in 10 people)

stomach pain.

Common (may affect up to 1 in 10 people)

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, diarrhoea, 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 (may affect up to 1 in 100 people)

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, non-specific ECG changes, feeling of tightness, pressure or heaviness 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, increased levels of uric acid and creatine phosphokinase,chest pain.

Rare (may affect up to 1 in 1,000 people)

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 (these reactions can involve ulcers of the mouth, throat, nose and genitals; the rash may progress to widespread blistering and peeling of the skin).

If you get any side effects, talk to your doctor or pharmacist or nurse. This includes any possible side effects not listed in this leaflet. You can also report side effects directly via the Yellow Card Scheme at: www.mhra.gov.uk/yellowcard. By reporting side effects you can help provide more information on the safety of this medicine.

• Eep this medicine out of the sight and reach of children.
• Do not use this medicine after the expiry date which is stated on the pack after EXP.
• The expiry date refers to the last day of that month.
• This medicine does not require any special storage conditions.
• Do not throw away any medicines via wastewater or household waste.

Ask your pharmacist how to throw away medicines you no longer use. These measures will help protect the environment. The active substance is etoricoxib. Each film-coated tablet contains 30, 60, 90 or 120 mg of etoricoxib. The other ingredients are: Tablet core: Calcium hydrogen phosphate, anhydrous; Cellulose microcrystalline; Croscarmellose sodium; Silica colloidal anhydrous; Talc; Magnesium stearate Film coat: Hypromellose; Hydroxypropylcellulose; Macrogol 6000; Talc; Titanium dioxide E171 The 60 mg tablets also contain brown ferric oxide E172, the 90 mg tablets also contain yellow ferric oxide E172 and 120 mg tablets also contain red ferric oxide E172.

1. Etoricoxib 30 mg film-coated tablets: White to off white round biconvex film-coated tablets, approx.6 mm in diameter.
2. Etoricoxib 60 mg film-coated tablets: Light brown round biconvex film-coated tablets, approx.8 mm in diameter.
3. Etoricoxib 90 mg film-coated tablets: Light yellow round biconvex film-coated tablets, approx.9 mm in diameter.

Etoricoxib 120 mg film-coated tablets: Light pink round biconvex film-coated tablets, approx.10 mm in diameter. Etoricoxib 30 mg film-coated tablets 7, 20, 28, 50, 98 and 100 film-coated tablets Etoricoxib 60 and 90 mg film-coated tablets 7, 14, 20, 28, 50, 100 film-coated tablets Etoricoxib 120 mg film-coated tablets 5, 7, 14, 20, 28, 50 and 100 film-coated tablets Not all pack sizes may be marketed.

Is etoricoxib toxic to the liver?

3.3. Evidence of Hepatotoxicity – Clinically significant evidence of hepatotoxicity was found in 8 studies, which accounted for 44.4%. It was found that almost all studies reported AST or ALT, which indicates hepatotoxicity. According to the criteria adopted in this study for hepatotoxicity, 7 of 8 studies (87.5%) demonstrated the elevation of either AST or ALT, or both enzymes, >3 × ULN during the study period (Table 3 and supplement 3 ; Table 2 for full information). One study did not report the magnitude of elevated AST or ALT enzymes but reported liver-related discontinuation, One study assessed liver injury using both AST and ALP elevations, Diclofenac and etoricoxib showed >5 × ULN of aminotransferase elevations. In addition, 2 diclofenac studies reported Hy’s cases, It was found that most studies used high doses of diclofenac, around 100–150 mg, except for 1 study that used a lower dose, in SoluMatrix dosage form, In 3 studies, it was found that diclofenac users discontinued the drug due to liver-related injury, In 8 studies with clinically significant hepatotoxicity (Table 3 ), the drug that caused hepatotoxicity in 1 study did not in our interest which was fenbufen, For the remaining 7 studies, the drugs that caused hepatotoxicity were diclofenac (6 studies), celecoxib (2 studies), and etoricoxib (1 study). Of the total of 789 patients who received celecoxib, from 4 studies, only 2 patients (0.002%) had ALT > 3 × ULN and 1 patient (0.0013%) had liver-related discontinuation. Hence, the hepatotoxicity events ranged from 0.13 to 0.38 (×10 −2 ). Only 1 study reported hepatotoxicity events from etoricoxib, which were in the range of 0.005–0.930 (×10 −2 ). Of those 17,412 total samples, 162 patients (0.009%) had aminotransferase elevation > 3 × ULN, 1 patient (0.00005%) had Hy’s case, and 57 patients (0.0032%) had liver-related discontinuation. Compared with 2 drugs mentioned above, diclofenac had the highest proportion of hepatotoxic events which ranged from 0.015 to 4.3 (×10 −2 ). Patients with AST elevation > 3 × ULN were found in 395/19998 (0.02%), ALT elevation > 3 × ULN in 864/19998 (0.04%), AST/ALT elevation > 3 × ULN in 19/19998 (0.001%), and Hy’s case in 3/19998 (0.0002%), in addition to liver-related discontinuation and hospitalization in 492/19998 (0.024%) and 4/19998 (0.0002%), respectively (Table 4 and Figure 2 ).

Can etoricoxib damage kidneys?

Conclusion – Even a short duration of treatment with the new COX-2 inhibitor etoricoxib may have the potential to precipitate renal failure and life-threatening hyperkalemia when administered to selected patients. The importance of considering a patient’s existing diet, medications and systemic status before writing a new prescription that may interfere with the potassium physiology cannot be overstressed.

Can etoricoxib damage liver?

Summary and Conclusions – All the NSAIDs had been associated with some form of liver toxicity, etoricoxib being the safest in the present study, followed by Ibuprofen which showed to have excellent safety profile. The liver toxicity is less often than the gastrointestinal adverse effects, but might have significant morbidity if overlooked. The usual underreporting is due to lack of understanding and physicians probable associate the liver effects more commonly with alcohol or with acetaminophen. Because of low frequency of liver toxicity it is virtually difficult to study the risk factors and etiology of the liver toxicity purely due to NSAIDs. Increased awareness and recognition will lead to better patient treatment and subsequent outcome in a timely intervention pattern. Timely intervention would lead to reversal of liver toxicity, considering the enormous capacity of liver to be regenerative. The risk factors cannot be termed of true risk factors due to NSAIDs alone as they do not represent the only population receiving NSAIDs and further studies and large sample size of each of subgroups of NSAIDs are required to establish toxicity on liver purely due to NSAIDs use. NSAIDs induced liver toxicity must be kept in mind by physicians in patients with isolated impaired function test in otherwise health individual who is on NSAIDs; Under reporting is common because many of the patients may not disclose the fact to their physicians as it is not prescription drug. Prompt recognition and withdrawal of culprit drug reduces the liver risk and avoids chronic consequences.

Is etoricoxib banned in Canada?

Science A newer arthritis drug leads to fewer stomach side-effects than older drugs, according to a new study. A newer arthritis drug leads slightly fewer stomach side-effects than older drugs, according to a new study. People with arthritis often take non-steroidal anti-inflammatories or NSAIDS over a long term.

A newer class of NSAIDS called COX-2 inhibitors cause fewer gastrointestinal side-effects such as ulcers and stomach bleedingthan other NSAIDs such as Aspirin and ibuprofen. In the Feb.10 issue of the medical journal The Lancet, researchers analyzed the results of three clinical trials comparing Merck & Co.’s drug etoricoxib, sold as Arcoxia, to diclofenac, sold in Canada as Voltaren.

Etoricoxib is not approved for use in Canada. “Our results indicate that the rate of clinically important upper-gastrointestinal events was lower with the COX-2 selective inhibitor etoricoxib than it was with the traditional NSAID diclofenac,” said Prof.

Loren Laine of the University of Southern California Keck School of Medicine in Los Angeles. The nearly 35,000 study participants had rheumatoid arthritis or osteoarthritis. To mirror how the drugs are prescribed in real life, participants were encourage to take a proton pump inhibitor with the drugs to protect against gastrointestinal side-effects, and those with risk factors for heart disease were urged to take low-dose Aspirin.

Overall, there were fewer ulcers in people taking the new drug and more of those peoplecontinued to take the treatment, the researchers found. Merck employees performed the statistical analysis, which was independently confirmed by the Frontier Science Foundation.

The trial was designed to address cardiovascular side-effects, not gastrointestinal ones, Joost Drenth and Freek Verheugt of Radboud University Nijmegen, Netherlands, said in an accompanying commentary. “Though eterocoxib reduced upper-gastrointestinal events, the effect was only small, as 259 patients need to be treated to prevent one uncomplicated gastrointestinal event,” the pair wrote.

The real question is whether a COX-2 inhibitor such as etoricoxib is safer than an NSAID when a proton pump inhibitor is added, Drenth and Verheugt said. Taking an older NSAID with a proton pump inhibitormight be cheaper and potentially less harmful to the heart, although a randomized clinical trial is needed to test the idea.

How long can you take etoricoxib 60 mg?

My Account Area – 1. Name of the medicinal product Etoricoxib 60 mg film-coated tablets 2. Qualitative and quantitative composition Each film-coated tablet contains 60 mg of etoricoxib. For the full list of excipients, see section 6.1.3. Pharmaceutical form Film-coated tablet Light brown round biconvex film-coated tablets, approx.8 mm in diameter.4. Clinical particulars 4.1 Therapeutic indications Etoricoxib 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. Etoricoxib 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).4.2 Posology and method of administration 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 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. 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 etoricoxib 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. Caution should be exercised in elderly patients (see section 4.4). 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). 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 Etoricoxib is administered orally and may be taken with or without food. The onset of the effect of the medicinal product may be faster when etoricoxib is administered without food. This should be considered when rapid symptomatic relief is needed.4.3 Contraindications 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 140/90mmHg and has not been adequately controlled. Established ischaemic heart disease, peripheral arterial disease, and/or cerebrovascular disease.4.4 Special warnings and precautions for use Gastrointestinal effects Upper gastrointestinal complications, 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).4.5 Interaction with other medicinal products and other forms of interaction 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.). Ciclosporin and tacrolimus Although this interaction has not been studied with etoricoxib, coadministration of ciclosporin or tacrolimus with any NSAID may increase the nephrotoxic effect of ciclosporin 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 PREMARIN TM ) 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.4.6 Fertility, pregnancy and lactation 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 active substance known to inhibit COX-2, is not recommended in women attempting to conceive.4.7 Effects on ability to drive and use machines Patients who experience dizziness, vertigo or somnolence while taking etoricoxib should refrain from driving or operating machinery.4.8 Undesirable effects Summary of the safety profile In clinical trials, etoricoxib was evaluated for safety in 9295 individuals, including 6757 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, diarrhoea, 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, 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. 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 via the Yellow Card Scheme at: www.mhra.gov.uk/yellowcard.4.9 Overdose 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.5. Pharmacological properties 5.1 Pharmacodynamic properties Pharmacotherapeutic group: Anti-inflammatory and antirheumatic products, non-steroids, coxibs, ATC code: M01AH05 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 1000 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 7111 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 4086 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 acetylsalicylic acid 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 150mg were similar.

Table 2: Rates of Confirmed Thrombotic CV Events (Pooled MEDAL Programme)
	Etoricoxib (N=16819) 25836 Patient-Years	Diclofenac (N=16483) 24766 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 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= 17412 on etoricoxib and 17289 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 edema-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 acetylsalicylic acid (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 vs.2.78 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 3100 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).5.2 Pharmacokinetic properties 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 120 l 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).5.3 Preclinical safety data 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 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 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 (90mg). 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.6. Pharmaceutical particulars 6.1 List of excipients Tablet core: Calcium hydrogen phosphate, anhydrous Cellulose microcrystalline Croscarmellose sodium Silica colloidal anhydrous Talc Magnesium stearate Film coat: Hypromellose Hydroxypropylcellulose Macrogol 6000 Talc Titanium dioxide E171 The 60 mg tablets also contain brown ferric oxide E172.6.2 Incompatibilities Not applicable.6.3 Shelf life 2 years 6.4 Special precautions for storage This medicinal product does not require any special storage conditions.6.5 Nature and contents of container Blisters of laminate OPA-ALU-PVC and aluminium foil in pack size of 7, 14, 20, 28, 50, 100 film-coated tablets. Not all pack sizes may be marketed.6.6 Special precautions for disposal and other handling No special requirements. Any unused medicinal product or waste material should be disposed of in accordance with local requirements.7. Marketing authorisation holder Zentiva Pharma UK Limited 12 New Fetter Lane London EC4A 1JP United Kingdom 8. Marketing authorisation number(s) PL 17780/0725 9. Date of first authorisation/renewal of the authorisation 29 March 2016 10. Date of revision of the text

Does etoricoxib cause weight gain?

Etoricoxib treatment reduced the body weight gain in both control and HF diet–fed rats. However, food and water intake were not changed among the groups studied. The increased body weight in HF diet–fed rats could be explained by the increased calorie intake than the control rats (Table 2).

How does etoricoxib make you feel?

Important information to know about etoricoxib – ▪️ It can be taken by adults aged 16 years and over. It’s not suitable for children under 16 and women who are pregnant, trying for a baby or breastfeeding. ▪️ Don’t take Arcoxia if you have a stomach ulcer or bleeding in your gut, inflammatory bowel disease, uncontrolled high blood pressure, heart disease or if you’ve ever had a stroke.

▪️ The most common side effects are stomach ache, indigestion, wind, feeling sick, diarrhoea, constipation, headache, feeling tired or dizzy, wheezing, palpitations and increased blood pressure. ▪️ Stop taking Arcoxia and see your doctor if you get any sign of bleeding in your gut, for example vomiting blood and/or passing black/tarry/bloodstained stools.

▪️ It’s fine to drink alcohol in moderation while you’re taking Arcoxia. ▪️ Never take more than the dose prescribed by your doctor. If you think this medicine is not working for you, consult your doctor.

How many hours does etoricoxib last?

Etoricoxib – Etoricoxib (MK-663) is a dipyridinyl derivative that contains a phenyl group attached to the central ring. Etoricoxib is highly selective for COX-2 (IC 50 ratio, 344; see Table 40.2 ), with substantial distribution into tissue and 92% bound to plasma.152 It is distributed rapidly, with the peak concentration being reached within 1 to 2 hours, and has an elimination half-life of approximately 22 hours.153 Etoricoxib is metabolized via cytochrome P-450–dependent oxidation, which results in prolonged elimination in patients with liver disease.

The highest recommended daily dosage for chronic use is 60 to 90 mg; for acute pain, the dose is 120 mg.154 Clinical trials of etoricoxib have demonstrated its analgesic efficacy for various types of arthritis, 155 acute dental pain, 156 dysmenorrhea, and chronic pain conditions such as back pain. Adverse effects include GI, renal, and cardiovascular manifestations.

There is a 40% reduction in the relative risk for GI side effects with etoricoxib in comparison to other NSAIDs. Read full chapter URL: https://www.sciencedirect.com/science/article/pii/B9780323083409000402

Can etoricoxib cure inflammation?

Comparison of an Etoricoxib medicine with a Naproxen –

	Etoricoxib	Naproxen
Composition	Etoricoxib is the active ingredient in this medication. Etoricoxib comes as film-coated tablets in 30, 60, 90, or 120 mg doses.	At a pH of 7, Naproxen sodium is a freely soluble, crystalline solid ranging in colour from white to creamy white.
Uses	In arthritic conditions such as osteoarthritis, ankylosing spondylitis, and rheumatoid arthritis, Etoricoxib reduces inflammation and relieves pain.	Naproxen is a nonsteroidal anti-inflammatory medication (NSAID). It alleviates joint and muscular pain and swelling (inflammation).
Side Effects	Feeling worn out. Diarrhoea or constipation. High blood pressure Stomach pain Fatigue Difficulty breathing	Changes in vision Feeling sleepy and tired Skin Rash Severe indigestion Frequent sore throat

References: https://patient.info/medicine/etoricoxib-for-pain-and-inflammation-arcoxia#nav-5 https://www.medicines.org.uk/emc/product/9317/pil#gref Disclaimer: The information provided here is not meant to substitute an advice from a healthcare professional.

• The information is not intended to cover all the possible uses, side-effects, precautions, and drug interactions.
• This information is not intended to suggest that using a specific drug is suitable, safe, or efficient for you or anyone else.
• The absence of any information or warning regarding the drug should not be interpreted as an implicit guarantee from the organisation.

We strongly advise you to consult a doctor if you have any concerns about the drug and never use the medication without a doctor’s prescription.

Is etoricoxib safer than ibuprofen?

Conclusion: Low-dose etoricoxib with low-dose paracetamol has comparable analgesic efficacy with better safety than therapeutic dose ibuprofen and low-dose paracetamol.

Is etoricoxib cardiac risk?

Background – Etoricoxib belongs to the selective COX-2 inhibitor class of drugs and may be associated with an increased risk of coronary and cerebrovascular thrombotic events, heart failure, hypertension, and oedema (compared with placebo and some non-steroidal anti-inflammatory drugs).

Is etoricoxib toxic to the liver?

3.3. Evidence of Hepatotoxicity – Clinically significant evidence of hepatotoxicity was found in 8 studies, which accounted for 44.4%. It was found that almost all studies reported AST or ALT, which indicates hepatotoxicity. According to the criteria adopted in this study for hepatotoxicity, 7 of 8 studies (87.5%) demonstrated the elevation of either AST or ALT, or both enzymes, >3 × ULN during the study period (Table 3 and supplement 3 ; Table 2 for full information). One study did not report the magnitude of elevated AST or ALT enzymes but reported liver-related discontinuation, One study assessed liver injury using both AST and ALP elevations, Diclofenac and etoricoxib showed >5 × ULN of aminotransferase elevations. In addition, 2 diclofenac studies reported Hy’s cases, It was found that most studies used high doses of diclofenac, around 100–150 mg, except for 1 study that used a lower dose, in SoluMatrix dosage form, In 3 studies, it was found that diclofenac users discontinued the drug due to liver-related injury, In 8 studies with clinically significant hepatotoxicity (Table 3 ), the drug that caused hepatotoxicity in 1 study did not in our interest which was fenbufen, For the remaining 7 studies, the drugs that caused hepatotoxicity were diclofenac (6 studies), celecoxib (2 studies), and etoricoxib (1 study). Of the total of 789 patients who received celecoxib, from 4 studies, only 2 patients (0.002%) had ALT > 3 × ULN and 1 patient (0.0013%) had liver-related discontinuation. Hence, the hepatotoxicity events ranged from 0.13 to 0.38 (×10 −2 ). Only 1 study reported hepatotoxicity events from etoricoxib, which were in the range of 0.005–0.930 (×10 −2 ). Of those 17,412 total samples, 162 patients (0.009%) had aminotransferase elevation > 3 × ULN, 1 patient (0.00005%) had Hy’s case, and 57 patients (0.0032%) had liver-related discontinuation. Compared with 2 drugs mentioned above, diclofenac had the highest proportion of hepatotoxic events which ranged from 0.015 to 4.3 (×10 −2 ). Patients with AST elevation > 3 × ULN were found in 395/19998 (0.02%), ALT elevation > 3 × ULN in 864/19998 (0.04%), AST/ALT elevation > 3 × ULN in 19/19998 (0.001%), and Hy’s case in 3/19998 (0.0002%), in addition to liver-related discontinuation and hospitalization in 492/19998 (0.024%) and 4/19998 (0.0002%), respectively (Table 4 and Figure 2 ).

Can etoricoxib damage liver?

Summary and Conclusions – All the NSAIDs had been associated with some form of liver toxicity, etoricoxib being the safest in the present study, followed by Ibuprofen which showed to have excellent safety profile. The liver toxicity is less often than the gastrointestinal adverse effects, but might have significant morbidity if overlooked. The usual underreporting is due to lack of understanding and physicians probable associate the liver effects more commonly with alcohol or with acetaminophen. Because of low frequency of liver toxicity it is virtually difficult to study the risk factors and etiology of the liver toxicity purely due to NSAIDs. Increased awareness and recognition will lead to better patient treatment and subsequent outcome in a timely intervention pattern. Timely intervention would lead to reversal of liver toxicity, considering the enormous capacity of liver to be regenerative. The risk factors cannot be termed of true risk factors due to NSAIDs alone as they do not represent the only population receiving NSAIDs and further studies and large sample size of each of subgroups of NSAIDs are required to establish toxicity on liver purely due to NSAIDs use. NSAIDs induced liver toxicity must be kept in mind by physicians in patients with isolated impaired function test in otherwise health individual who is on NSAIDs; Under reporting is common because many of the patients may not disclose the fact to their physicians as it is not prescription drug. Prompt recognition and withdrawal of culprit drug reduces the liver risk and avoids chronic consequences.