Risk Management Plan Etoricoxib film-coated tablets

Transcription

1 VI.2 Elements for a Public Summary VI.2.1 Overview of disease epidemiology Osteoarthritis (OA): OA is a condition in which the cartilage of the joints is broken down. This causes stiffness, pain and leads to loss of function. Joints often affected are hands, knees, back and hips 9,15. OA as a disease is complex and likely results from a combination of factors such as aging, injury, and genetics 4,19. Known risk factors for OA of the knee are obesity, prior knee injury and repetitive bending. Treatment consists of physical exercise, medication and surgery when all other treatments fail. OA is a common joint disorder and usually begins between the ages of 40 and 50 years. By the age of 80 years almost all people have OA to some extent 9,15. The proportion of people having the disease varies across countries and populations 5. Rheumatoid arthritis (RA): RA is a condition in which joints are inflamed often leading to the destruction of it. RA is an autoimmune disease (the immune system attacks healthy tissue by accident). Symptoms include swelling, stiffness and pain of joints. In general patients may experience fatigue, malaise and weakness. Any joint can be affected but usually it begins with inflammation of small joints in hands and feet, elbows and ankles. Hips, knees and shoulders are commonly affected too 10,16. Risk factors for RA are both genetic and non-genetic. Non-genetic factors include smoking, diet, infection and changes in the hormonal environment in women (e.g. pregnancy, birth control pills) 3. Treatment consists of medicines and surgical treatments. Furthermore rest, a healthy diet, and physical treatments are applied as conservative measures. Worldwide, approximately 1% of the population develops RA. This proportion is regardless of race or country of origin. Women are two to three times more often affected than men. RA usually appears between the ages of 35 and 50 years. However it may occur at any age 10,16. Ankylosing spondylitis (AS): AS is characterized by inflammation of the skeleton, large joints and spine. Not only the skeleton is involved but the heart and eyes may also get inflamed. Its cause is not known. The most common symptoms are back pain and early morning stiffness that is relieved by activity. General symptoms include loss of appetite, low-grade fever, weight loss, excessive fatigue, and anemia 7,11. Risk factors are both environmental and genetic; AS patients are predominantly young men 17. Treatment aims at relieving back pain and joint pain through exercise and medications. Men are three times more often affected than women. It most commonly develops between the ages of 20 and 40 years 7,11. Gout: Gout is a disease of sudden, recurring attacks of very painful inflammation and redness in the joints... caused by deposits of mineral crystals in the joint 1. Symptoms include sudden occurrences of severe pain in one or more joints, inflammation of the joint with visible skin discolouration and tightness and shininess of the skin. More general symptoms may include fever, fast heart rate, chills and malaise 8,14. Increased blood pressure, kidney problems, increased blood cholesterol and lipids, diabetes, early menopause, diabetes, being overweight and also alcohol use increase the risk of the occurrence of gout and/or gout flares 6. The condition is treated with medicines, and to prevent further attacks life style Document number (version): RMP.NUS (3.0) Page 11 of 47

2 should be amended to exclude alcohol intake, losing weight and dietary adjustments. Gout usually develops during middle age in men and after menopause in women occurring more often in men than women and runs in families. Although gout is rarely seen in younger people, it is often more severe when occurring before the age of 30 years 8,14. Dental surgery: A common tooth problem concerns cavities caused by plaque. Furthermore teeth may be lost due to oral disease (e.g problems with gum or inflammation) or injuries and may have to be removed and/or replaced by artificial teeth 12,13. Fifteen (15) to 20 percent of people between the ages of suffer from severe gum disease. Risk factors for poor oral health include a bad diet, smoking, use of alcohol and poor dental cleaning 18. VI.2.2 Summary of treatment benefits Osteoarthritis (OA): Treatment of patients with OA with etoricoxib has shown to be beneficial. Etoricoxib 60 mg once daily provided significant improvements in pain and disease status. Effects of etoricoxib were observed as off the second day of therapy and were maintained for up to 52 weeks. Placebo-controlled studies with etoricoxib (30 mg once daily) demonstrated superior efficacy over a 12 week treatment period 2. Rheumatoid arthritis (RA): Treatment of RA patients with etoricoxib 90 mg once daily has shown significant improvements in pain, inflammation, and mobility and were maintained over a 12-week treatment period 2. Ankylosing spondylitis (AS): Treatment of patients with AS with etoricoxib 90 mg once daily has shown significant improvements in spine pain, inflammation, stiffness and function and were observed as early as the second day of therapy after initiation of treatment and were maintained throughout a 52-week treatment period 2. Gout: Etoricoxib 120 mg once daily showed beneficial effects compared to indomethacin 50 mg three times daily in patients with moderate to extreme joint pain and inflammation as a result of attacks of acute gouty arthritis. Pain relief was observed over an eight-day treatment period and as early as four hours after initiation of treatment 2. Postoperative dental pain: A clinical study with etoricoxib 90 mg once daily for up to three days was performed with the aim to assess postoperative dental pain. Etoricoxib showed beneficial effects in the subgroup of patients showing moderate pain at baseline. Evaluating total pain relief over the first six hours, etoricoxib 90 mg demonstrated a similar pain relieving effect compared to other pain medication, i.e. ibuprofen 600 mg, and a greater effect compared to paracetamol/codeine (600 mg/60 mg) and placebo 2. Document number (version): RMP.NUS (3.0) Page 12 of 47

3 VI.2.3 Unknowns relating to treatment benefits Extensive post-marketing experience is available with the reference product of etoricoxib. Special populations have been defined in which etoricoxib is not to be used (pregnant and breastfeeding women, children and adolescents under 16 years of age, and patients with particular co-morbidities). VI.2.4 Summary of safety concerns Important identified risks Risk What is known Preventability Problems concerning heart or blood circulation including blood clotting (Thrombotic cardiovascular complications) Problems with digestive tract (Gastrointestinal complications) Heart problems such as changes in rate or rhythm but also heart failure or heart attack, and events involving vasculature such as blood pressure and stroke(-like) events may occur in 1 to 10 users in 1000, with particular rate related events such as palpitations and high blood pressure potentially occurring in 1 to 10 in 100 patients treated with etoricoxib. The class of COX-2 inhibitors (to which etoricoxib belongs) may be associated with a risk of stroke and heart attacks. Cardiovascular risks may be increased with dose and duration of etoricoxib use. Side effects of using etoricoxib related to stomach and intestines may occur in 1 to 10 in 100 users of which aches may occur in more than 1 user in 10. More severe complications (e.g. ulcerations, perforations, bleeding) may occur in 1 to 10 in 1000 users. Ulcerations, perforations and bleedings of the digestive tract with serious outcomes (sometimes even fatal) have occurred with etoricoxib. Risks of these adverse events are increased when etoricoxib is taken together with aspirin (even at low doses). Use the lowest dose for the shortest duration possible. Furthermore etoricoxib should not be used in those patients who have already had heart problems or stroke or uncontrolled high blood pressure. Patients with a history of heart disease, high blood pressure, high blood cholesterol, diabetes or smokers have to discuss their history with their physician before treatment initiation. If patients develop shortness of breath, chest pains, or ankle swelling, or if they get worse while on etoricoxib, etoricoxib should be stopped and a Patients with current stomach or intestinal ulcerations or bleedings or inflammatory bowel diseases should not take etoricoxib. High doses of aspirin (or other antiinflammatory medicines) should not be taken together with etoricoxib. If a patient has a history of stomach bleeding or ulcerations this should be discussed with the physician before treatment initiation. If patients experience severe or continual stomach pain or have black stools while on etoricoxib, etoricoxib should be stopped and a physician should be consulted Document number (version): RMP.NUS (3.0) Page 13 of 47

4 Risk What is known Preventability Problems with heart, kidneys and accumulation of fluids (Cardio-renal risk fluid retention, oedema and hypertension) Severe skin reactions and allergy (Severe skins reactions and hypersensitivity) Severe reactions of the liver (Severe hepatic reactions) Accumulation of fluids may occur in 1 to 10 in 100 users. Severe loss of kidney function may occur in 1 to 10 in 1000 users. All Nonsteroidal Antiinflammatory Drugs (NSAIDs), including etoricoxib, may lead to occurrences/recurrences of heart failure. Serious toxic skin reactions (e.g. severe blistering and shedding of the skin), some of them fatal, have been reported very rarely (less than 1 in users) in association with the use of NSAIDs and some selective COX-2 inhibitors (etoricoxib is classified as selective COX-2 inhibitor). These reactions usually occur within the first month of treatment. Some selective COX-2 inhibitors have been associated with an increased risk of skin reactions in patients with a history of any drug allergy. Liver problems including inflammation of the liver, yellowing of the skin, and loss of liver function (liver failure) may occur rarely (1 to 10 in users). Etoricoxib should not be taken if patients have severe liver or kidney disease or uncontrolled high blood pressure. Patients with a history of accumulation of fluids, high blood blood pressure, or liver of kidney disease should discuss this with their physician before initiating treatment. If patients develop shortness of breath, chest pains, or ankle swelling, or if they get worse while on etoricoxib, etoricoxib should be stopped and a physician should be consulted Patients with allergies to etoricoxib (or other ingredients) or NSAIDs including aspirin and COX-2 inhibitors should not take etoricoxib. Etoricoxib should be stopped if patients develop an allergic reaction, which can include skin problems such as ulcers or blistering, or swelling of the face, lips, tongue, or throat. A Patients with severe liver disease should not take etoricoxib. Patients with a history of liver disease should discuss this with their physician before initiating treatment. If patients develop yellowing of the skin and eyes (jaundice) while on etoricoxib, etoricoxib should be stopped and a Document number (version): RMP.NUS (3.0) Page 14 of 47

5 Important potential risks Risk Pregnancy Off-label use What is known (Including reason why it is considered a potential risk) The effects of etoricoxib on reproduction have been studied in animals and have shown cardiovascular abnormalities in rabbits and loss of implantation of the embryo in rats and rabbits. Pregnant or breastfeeding women should not take etoricoxib. Women trying to become pregnant or planning to breast-feed should consult their physician before treatment is initiated. Etoricoxib is approved for the treatment of osteoarthritis, rheumatoid arthritis, ankylosing spondylitis, gout and short term treatment of moderate pain after dental surgery. Only for these indications beneficial effects have been weighed against the known and potential risks. Missing information Risk None What is known Not applicable VI.2.5 Summary of risk minimisation measures by safety concern All medicines have a Summary of Product Characteristics which provides doctors, pharmacists and other health care professionals with details on how to use the medicine, the risks and recommendations for minimising them. An abbreviated version of this in lay language is provided in the form of the package leaflet. The measures in these documents are known as routine risk minimisation measures. Also the fact that etoricoxib can only be taken by a patient if it has been prescribed by a health care professional, is a routine risk minimisation measure. No additional risk minimisation measures have been proposed. VI.2.6 Planned post authorisation development plan No post-authorization development is planned. VI.2.7 Summary of changes to the over time Not applicable. Document number (version): RMP.NUS (3.0) Page 15 of 47