Coricib 30 Mg/60 Mg/90 Mg/120 Mg Film-Coated Tablets

CORICIB is indicated for:

• symptomatic relief of osteoarthritis (OA) and rheumatoid arthritis (RA).
• treatment of ankylosing spondylitis (AS).
• treatment of acute gouty arthritis.
• short term relief of acute pain, treatment limited to a maximum period of 8 days.
• treatment of primary dysmenorrhoea.
• treatment of moderate to severe acute post-operative pain associated with dental surgery.

The decision to prescribe CORICIB should be based on an assessment of the individual patient's overall risks (see section 4.4).

Posology

Osteo-arthritis (OA): The recommended dose is 30 mg* once daily. In some patients with insufficient relief from symptoms, the dose may be increased to 60 mg once daily.

Rheumatoid Arthritis (RA): The recommended dose is 90 mg once daily. In some patients, 60 mg once daily may provide adequate therapeutic benefit.

Ankylosing Spondylitis (AS): The recommended dose is 90 mg once daily. In some patients, 60 mg once daily may provide adequate therapeutic benefit.

Short term relief of Acute Pain: The recommended dose is 90 mg or 120 mg once daily, limited to a maximum of 8 days treatment.

Acute Gouty Arthritis: The recommended dose is 120 mg once daily, limited to a maximum of 8 days treatment.

Primary Dysmenorrhoea: The recommended dose is 120 mg once daily.

Post-operative Dental Pain: The recommended dose is 90 mg once daily.

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 should not exceed 90 mg daily. The dose for ankylosing spondylitis should not exceed 90 mg daily. The dose for acute gout should not exceed 120 mg daily. The dose for acute pain and primary dysmenorrhoea should not exceed 120 mg daily. The dose for postoperative acute dental surgery pain should not exceed 90 mg daily.

As the cardiovascular risks of CORICIB 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 (see section 4.4.).

Special populations

Elderly No dosage adjustment in CORICIB is necessary for the elderly. Although the elderly may be more susceptible to renal, gastrointestinal and cardiovascular adverse effects (see section 4.4). When using CORICIB in the elderly and in patients with renal, hepatic or cardiac dysfunction, medically appropriate supervision should be intensified. If these patients show deterioration during treatment, appropriate measures should be taken, including discontinuation of CORICIB.

Hepatic Insufficiency In patients with mild hepatic insufficiency (Child Pugh score 5 to 6), a dose of 60 mg once daily should not be exceeded. In patients with moderate hepatic insufficiency (Child-Pugh score 7 to 9), the dose should be reduced; a dose of 60 mg every other day should not be exceeded, administration of CORICIB 30 mg* once daily can also be considered. Clinical experience is limited particularly in patients with moderate hepatic dysfunction. There are no clinical or pharmacokinetic data in patients with severe hepatic insufficiency (Child-Pugh score > 9), therefore the use of CORICIB is contraindicated in these patients (see section 4.3 and 5.2).

Renal Insufficiency No dosage adjustment is necessary for patients with lesser degrees of renal insufficiency (creatinine clearance u2265 30 mL/min). The use of CORICIB in patients with creatinine clearance < 30 mL/min is contraindicated (see section 4.3).

Method of administration

CORICIB is administered orally. CORICIB may be taken with or without food. CORICIB should be administered for the shortest duration possible and the lowest effective daily dose should be used.

CORICIB is contraindicated in:

• patients with known hypersensitivity to any of the excipients of CORICIB (see section 6.1)
• patients with active peptic ulceration or gastrointestinal (GI) bleeding
• patients with severe hepatic dysfunction (Child-Pugh score > 9 or serum albumin < 25 g/litre)
• patients with severe renal impairment (estimated creatinine clearance < 30 mL/min)
• patients who have developed signs of asthma, acute rhinitis, nasal polyps, angioedema or urticaria following the administration of aspirin or other non-steroidal anti-inflammatory drugs (NSAIDs) including etoricoxib, as contained in CORICIB
• uncontrolled hypertension
• pregnancy and lactation, avoid prescribing NSAIDs such as CORICIB after 20 weeks as it may cause rare kidney problems in unborn babies (see section 4.4)
• children and adolescents under 16 years of age
• patients with inflammatory bowel disease
• patients with congestive heart failure (NYHA II -IV)
• established ischaemic heart disease, peripheral arterial disease and/or cerebrovascular disease (see section 4.4).

When using CORICIB in the elderly and in patients with renal, hepatic or cardiac dysfunction, medically appropriate supervision should be intensified. If patients show deterioration during treatment, appropriate measures should be taken, including discontinuation of CORICIB.

Paediatric population CORICIB is contraindicated in children and adolescents under 16 years of age (see section 4.3).

CORICIB may predispose to cardiovascular events, gastrointestinal events or cutaneous reactions which may be fatal. Clinical trials suggest that the selective COX-2 inhibitor class of medicines, such as CORICIB, are associated with an increased risk of arterial thrombotic events (especially myocardial infarction (MI)) and stroke). Long-term administration of NSAIDs such as CORICIB, has resulted in renal papillary necrosis and other renal injury. Renal prostaglandins may play a compensatory role in the maintenance of renal perfusion. Therefore, under conditions of compromised renal perfusion, administration of CORICIB 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 liver cirrhosis. Monitoring of renal and hepatic function in such patients is indicated.

Caution should be used when initiating treatment with CORICIB in patients with dehydration. It is advisable to rehydrate patients prior to starting therapy with CORICIB.

Fluid retention, oedema and hypertension have been reported in patients taking CORICIB. All non-steroidal anti-inflammatory drugs (NSAIDs), including CORICIB, can be associated with new onset or recurrent congestive heart failure. 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 CORICIB should be taken.

CORICIB may be associated with more frequent and severe hypertension than other NSAIDs and other selective COX-2 inhibitors. Therefore special attention should be paid to blood pressure monitoring during treatment with CORICIB. If blood pressure rises significantly, alternative treatment should be considered.

Reported clinical studies suggest that the selective COX-2 inhibitor class of medicines such as etoricoxib, are associated with an increased risk of thrombotic events [especially myocardial infraction (MI) and stroke]. As the cardiovascular risks of selective COX-2 inhibitors such as etoricoxib as contained in CORICIB 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.

Patients with significant risk factors for cardiovascular events (e.g. hypertension, hyperlipidaemia, diabetes mellitus, smoking) should only be treated with CORICIB after careful consideration. CORICIB is not a substitute for aspirin for cardiovascular prophylaxis because of its lack of effect on platelets. Because CORICIB does not inhibit platelet aggregation, anti-platelet therapies should not be discontinued and if indicated, should be considered in patients at risk for or with a history of cardiovascular or other thrombotic events. There is no evidence that concurrent use of aspirin mitigates the increased risk of serious cardiovascular thrombotic events associated with CORICIB. For more details, refer to section on interactions (section 4.5).

Serious skin reactions, some of them fatal, including exfoliative dermatitis, Stevens-Johnson syndrome, and toxic epidermal necrolysis, have been reported in association with the use of selective COX-2 inhibitors such as etoricoxib during post-marketing surveillance. Serious hypersensitivity reactions (such as anaphylaxis and angioedema) have been reported in patients receiving etoricoxib (see section 4.8). Selective COX-2 inhibitors, such as CORICIB have been associated with an increased risk of skin reactions in patients with a history of any allergy. CORICIB should be discontinued at the first appearance of skin rash, mucosal lesions or any other sign of hypersensitivity.

When using CORICIB in the elderly and in patients with renal, hepatic or cardiac dysfunction, medically appropriate supervision should be intensified. If these patients show deterioration during treatment, appropriate measures should be taken, including discontinuation of CORICIB.

Gastrointestinal effects Upper gastrointestinal complications [perforations, ulcers or bleedings (PUBs)], some of them resulting in fatal outcome, have occurred in patients treated with etoricoxib. Caution is advised with treatment of patients at risk of developing a gastrointestinal complication with CORICIB; the elderly, patients using any other NSAIDs or aspirin (acetylsalicylic acid) concomitantly or patients with a prior history of gastrointestinal disease, such as perforation, ulceration and gastrointestinal bleeding. There is an increase in risk of gastrointestinal adverse effects (gastrointestinal ulceration or other gastrointestinal complications) when CORICIB is taken concomitantly with aspirin (even at low doses).

Elevations of alanine aminotransferase (ALT) and/or aspartate aminotransferase (AST) (approximately 3 or more times the upper limit of normal) have been reported in approximately 1 % of patients in clinical trials, treated for up to 1 year with etoricoxib 60 mg and 90 mg daily.

Any patient with symptoms and/or signs suggesting liver dysfunction, or in whom an abnormal liver function test has occurred, should be evaluated for persistently abnormal liver function tests. If persistently abnormal liver function tests (3 times the upper limit of normal) are detected, CORICIB should be discontinued.

CORICIB may mask fever and other signs of inflammation or infection. Due to inhibition of prostaglandin synthesis, fluid retention and oedema have been reported in patients taking etoricoxib as contained in CORICIB; therefore CORICIB should be used with caution in patients with compromised cardiac function, and other conditions predisposing to or worsened by fluid retention. Patients with pre-existing congestive heart failure or hypertension should be closely monitored.

All non-steroidal anti-inflammatory drugs (NSAIDs), including CORICIB, can be associated with new onset or recurrent congestive heart failure (see section 4.8).

The use of CORICIB is not recommended in fertile women attempting to conceive.

Neonatal renal impairment and Oligohydramnios: The use of nonsteroidal anti-inflammatory drugs (NSAIDs) such as CORICIB around 20 weeks gestation or later in pregnancy may cause fetal renal dysfunction leading to oligohydramnios and, in some cases, neonatal renal impairment. Complications of prolonged oligohydramnios may include limb contractures and delayed lung maturation. In some reported post marketing cases of impaired neonatal renal function, invasive procedures such as exchange transfusion or dialysis were required. If NSAID treatment is determined necessary, limit use to the lowest effective dose and shortest duration possible. Avoid prescribing NSAIDs at 20 weeks and later in pregnancy because of the additional risk of premature closure of the fetal ductus arteriosus. Consider ultrasound monitoring of amniotic fluid if NSAID treatment extends beyond 48 hours. Discontinue the NSAID if oligohydramnios occurs (see section 4.3 and 4.6).

Drug Reaction with Eosinophillia and Systemic Symptoms (DRESS) has been reported in patients taking NSAIDs such as CORICIB. Some of these events have been fatal or life-threatening. DRESS typically, although not exclusively, presents with fever, rash, lymphadenopathy, and/or facial swelling. Other clinical manifestations may include hepatitis, nephritis, haematological abnormalities, myocarditis, or myositis. Sometimes symptoms of DRESS may resemble an acute viral infection. Eosinophillia is often present. Because this disorder is variable in its presentation, other organ systems not noted here may be involved. It is important to note that early manifestations of hypersensitivity, such as fever or lymphadenopathy, may be present even though rash is not evident. If such signs or symptoms are present, discontinue CORICIB and evaluate the patient immediately.

Lactose: CORICIB 30, 60, 90 and 90 mg tablets contain 1,05 ; 2,10; 3,15 and 4,20 mg lactose, respectively. Patients with rare hereditary problems of galactose intolerance, total lactase deficiency or glucose-galactose malabsorption should not take CORICIB.

Ciclosporin and tacrolimus: Co-administration of ciclosporin or tacrolimus with any NSAID, including CORICIB, may increase the nephrotoxic effect of ciclosporin or tacrolimus. Renal function should be monitored when CORICIB and either of these medicines is used in combination.

Warfarin: 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). Standard monitoring of INR values should be conducted when therapy with CORICIB is initiated or changed in patients receiving warfarin or similar medicines.

Rifampicin: Co-administration of etoricoxib with rifampicin, a potent inducer of hepatic metabolism, produced a 65 % decrease in etoricoxib plasma area under the curve (AUC). This interaction should be considered when CORICIB is co-administered with rifampicin.

Methotrexate: Two reported studies investigated the effects of etoricoxib 60 mg, 90 mg or 120 mg administered once daily for 7 days, in patients receiving once-weekly methotrexate doses of 7,5 mg to 20 mg for rheumatoid arthritis. Etoricoxib at 60 mg and 90 mg had no effect on methotrexate plasma concentrations (as measured by AUC) or renal clearance. ln one reported study, etoricoxib 120 mg had no effect on methotrexate plasma concentrations (as measured by AUC) or renal clearance. In the other study, etoricoxib 120 mg increased methotrexate plasma concentrations by 28 % (as measured by AUC) and reduced renal clearance of methotrexate by 13 %. Monitoring for methotrexate-related toxicity should be considered, when CORICIB at doses > 90 mg daily and methotrexate are administered concomitantly.

Diuretics, Angiotensin Converting Enzyme (ACE) Inhibitors and Angiotensin Receptor Blockers (ARBs): Reports suggest that non-selective NSAIDs and COX-2 selective inhibitors such as etoricoxib, as contained in CORICIB may diminish the antihypertensive effect of diuretics, ACE inhibitors and Angiotensin Receptor Blockers (ARBs). This interaction should be given consideration in patients taking CORICIB concomitantly with these medicines. In patients with compromised renal function (e.g. elderly patients or patients who are volume depleted, including those on diuretic therapy) who are being treated with CORICIB, the co-administration of ACE inhibitors or ARBs may result in a further deterioration of renal function, including possible acute renal failure. These effects may be reversible. Therefore, the combination should be administered with caution, especially in the elderly and in patients with impaired renal function. Patients should be adequately hydrated and consideration should be given to monitoring of renal function after initiation of concomitant therapy, and periodically thereafter.

Lithium: CORICIB may increase plasma lithium levels. This interaction should be given consideration in patients taking CORICIB concomitantly with lithium.

Aspirin: In a reported study in healthy subjects, at steady state, etoricoxib 120 mg once daily had no effect on the anti-platelet activity of aspirin (81 mg once daily). CORICIB may be used concomitantly with aspirin at doses used for cardiovascular prophylaxis (low-dose aspirin). However, concomitant administration of low-dose aspirin with CORICIB increases the rate of gastrointestinal ulceration, and other complications compared to use of etoricoxib alone. Concomitant administration of CORICIB with doses of aspirin above those for cardiovascular prophylaxis or with other NSAIDs should be avoided (see section 4.4) Concurrent use of aspirin does not mitigate the increased risk of serious cardiovascular thrombotic events associated with CORICIB.

Oral Contraceptives: Etoricoxib 60 mg given concomitantly with an oral contraceptive containing 35 u03bcg ethinyl estradiol (EE) and 0,5 mg to 1 mg norethindrone (NET) for 21 days, increased the steady state AUC 0-24h of EE by 37 %. Etoricoxib 120 mg given with the same oral contraceptive concomitantly or separated by 12 hours, increased the steady state AUC 0-24h of EE by 50 % to 60 %; however, (NET) concentrations generally did not increase to a clinically relevant degree. This increase in EE concentration should be considered when selecting an appropriate oral contraceptive for use with CORICIB. An increase in EE exposure can increase the incidence of adverse events associated with oral contraceptives (e.g. venous thromboembolic events in women at risk).

Furosemide: Reported clinical studies have shown that NSAIDs such as etoricoxib, as contained in CORICIB reduce the natriuretic and antihypertensive effect of furosemide and thiazides in patients. This response has been attributed to inhibition of renal prostaglandin synthesis.

Hormone Replacement Therapy: Administration of etoricoxib 120 mg with hormone replacement therapy consisting of conjugated oestrogens (0,625 mg conjugated oestrogens for 28 days, increased the mean steady state AUC 0-24h of unconjugated oestrone (41 %), equilin (76 %) and 17-beta-estradiol (22 %). The effect of the recommended chronic doses of etoricoxib (60 mg and 90 mg) has not been studied. The effects of etoricoxib 120 mg on the exposure (AUC 0-24h) to these oestrogenic components of conjugated oestrogens were less than half of those observed, when conjugated oestrogens was administered alone, and the dose was increased from 0,625 mg to 1,25 mg. The clinical significance of these increases is unknown, and higher doses of conjugated oestrogens were not studied in combination with etoricoxib.

Effects of etoricoxib on medicines metabolised by sulfotransferases: Etoricoxib is an inhibitor of human sulfotransferase activity, particularly SULT1E1, and has been shown to increase the serum concentrations of ethinyl oestradiol. While knowledge about effects of multiple sulfotransferases is presently limited and the clinical consequences for many medicines are still being examined, it may be prudent to exercise care when administering CORICIB concurrently with other medicines primarily metabolised by human sulfotransferases (e.g. oral salbutamol and minoxidil).

Etoricoxib 120 mg once daily for 10 days in healthy volunteers did not alter the steady state plasma AUC 0-24h or renal elimination of digoxin. There was an increase in digoxin C max (approximately 33 %) (See section 4.3).

Other: In interaction studies, etoricoxib did not have clinically significant effects on the pharmacokinetics of prednisone/prednisolone. Antacids do not have clinically significant effects on the pharmacokinetics of CORICIB. 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).

CORICIB is contraindicated in pregnancy and lactation (see section 4.3)

Pregnancy CORICIB, as in other medicines inhibiting prostaglandin synthesis may cause uterine inertia and premature ductus arteriosis during the last trimester of pregnancy. Pregnant women should not use CORICIB at 20 weeks or later unless specifically advised to do so by health care professional because these medicines may cause foetal renal dysfunction (see section 4.3 and 4.4)

Breastfeeding: Mothers on CORICIB should not breastfeed their infants.

Fertility: The use of CORICIB is not recommended in fertile women attempting to conceive.

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

a) Summary of the safety profile 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; hepatotoxicity including hepatic failure, and pancreatitis. In clinical studies, a higher incidence of adverse experiences was seen in older patients compared to younger patients.

b) Tabulated summary of adverse reactions

System organ class (SOC) Frequency Adverse reaction Infections and infestations Frequent Less frequent Alveolar osteitis Gastroenteritis, upper respiratory infection, urinary tract infection Blood and lymphatic system disorders Less frequent Frequency unknown Anaemia (primarily associated with gastrointestinal bleeding), leukopenia Thrombocytopenia Immune system disorders Less frequent Frequency unknown Hypersensitivity reactions, angioedema, anaphylactic/anaphylactoid reactions including shock Metabolism and nutrition disorders Frequent Less frequent Oedema/fluid retention Appetite increase or decrease, weight gain Psychiatric disorders Less frequent Frequency unknown Anxiety, depression, mental acuity decreased Confusion, hallucinations, restlessness Nervous system disorders Frequent Less frequent Frequency unknown Dizziness, headache Insomnia, paraesthesia/ hypaesthesia Dysgeusia, somnolence Eye disorders Less frequent Conjunctivitis Frequency unknown Blurred vision Ear and labyrinth disorders Less frequent Tinnitus, vertigo Cardiac disorders Frequent Less frequent Frequency unknown Palpitations Atrial fibrillation, congestive heart failure, non-specific EGG changes, myocardial infarction, angina Aggravated hypertension, dysrhythmia cardiovascular thrombotic events and tachycardia Vascular disorders Frequent Less frequent Frequency unknown Hypertension Flushing, cerebrovascular incidents (stroke), transient ischaemic attack, vasculitis Hypertensive crisis, peripheral oedema Respiratory, thoracic and mediastinal disorders Less frequent Frequency unknown Cough, dyspnoea, epistaxis Bronchospasm Gastrointestinal disorders Frequent Less frequent Frequency unknown Gastrointestinal disorders (e.g. abdominal pain, flatulence, heartburn), diarrhoea, dyspepsia, epigastric discomfort, nausea Abdominal distension, acid reflux, bowel movement pattern change, constipation, dry mouth, gastroduodenal ulcer, irritable bowel syndrome, oesophagitis, oral ulcer, vomiting, gastritis, pancreatitis Peptic ulcers including gastro-intestinal perforation and bleeding (mainly in the elderly) Hepato-biliary disorders Frequent Frequency unknown Increased ALT and AST Hepatitis, jaundice, hepatic failure Skin and subcutaneous tissue disorders Frequent Less frequent Frequency unknown Ecchymosis Facial oedema, pruritus, rash, erythema Urticaria, Stevens Johnson syndrome, toxic epidermal necrolysis, fixed drug eruption, Drug Reaction with Eosinophillia and Systemic Symptoms (DRESS) [see Warnings and Precautions] Musculoskeletal, connective tissue and bone disorders Less frequent Muscular cramp/spasm, musculoskeletal pain/stiffness Renal and urinary disorders Less frequent Frequency unknown Proteinuria, increased serum creatinine Renal insufficiency, including renal failure (see section 5.2) nephrotoxicity including interstitial nephritis and nephrotic syndrome General disorders and administration site conditions Frequent Less frequent Asthenia/fatigue, flu like disease Chest pain Investigations Less frequent Increased blood urea, increased creatine phosphokinase, decreased haematocrit, decreased haemoglobin, hyperkalaemia, decreased leukocytes, decreased platelets, increased uric acid, decreased blood sodium.

c) Description of selected adverse reactions CORICIB may cause foetal renal dysfunction leading to oligohydramnios and, in some cases, neonatal renal impairment. These adverse outcomes are reported, on average, after days to weeks of treatment, although oligohydramnios has been infrequently reported as soon as 48 hours after NSAID initiation. Oligohydramnios is often, but not always, reversible with treatment discontinuation (see section 4.3 and 4.4).

Reporting of suspected adverse reactions Reporting suspected adverse reactions after authorisation of the medicine is important. It allows continued monitoring of the benefit/risk balance of the medicine. Health care providers are asked to report any suspected adverse reactions to SAHPRA via the Med Safety APP (Medsafety X SAHPRA) and eReporting platform (who-umc.org) found on SAHPRA website. Suspected adverse reactions can also be reported directly to the Holder of certificate of registration via email: [email protected] or tel: +27(0) 12 643 2000.

The most frequently observed adverse experiences were gastrointestinal events, renovascular events. In the event of overdose, it is reasonable to employ the usual supportive measures e.g. remove unabsorbed material from the gastrointestinal 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.