Coxflam 7,5 / 15 mg Tablets

COXFLAM is indicated for the symptomatic relief of painful and/or inflammatory conditions, including musculoskeletal and joint disorders such as osteoarthritis, rheumatoid arthritis, acute sciatica and ankylosing spondylitis.

Posology
Use the lowest effective dose for the shortest possible duration of treatment.
Adults
Rheumatoid arthritis: 15 mg meloxicam once daily. The dose may be reduced to 7,5 mg daily according to the therapeutic response.
Osteo-arthritis: 7,5 mg meloxicam once daily. In severe cases: 15 mg meloxicam once daily.
Ankylosing spondylitis: 15 mg once daily.
Acute sciatica: 7,5 mg once daily. The dose may be increased to 15 mg once daily according to the therapeutic response.
Special populations
Elderly and other patients with increased risk for adverse reactions: 7,5 mg meloxicam daily initially. Careful patient monitoring is recommended.
Dialysis patients: Do not exceed 7,5 mg meloxicam daily. Maximum recommended dose: 15 mg meloxicam once daily.
Paediatric population
Children under 12 years of age: Contraindicated (see section 4.3). Safety and efficacy have not been established.
Method of administration
COXFLAM should be taken with water, with or after a meal. Noticeable improvement in severe conditions may require 1 to 2 weeks of continuous use.

COXFLAM is contraindicated in:
u2022 Patients with a known hypersensitivity to meloxicam or any of the excipients in COXFLAM (see section 6.1) any other non-steroidal anti-inflammatory medicines (NSAIDs) or to aspirin. The potential for cross sensitivity to aspirin and other NSAIDs exists.
u2022 Patients with a history of allergic reactions (such as skin rashes, urticaria, rhinitis, asthma, angioedema and anaphylactic shock) induced by aspirin or other NSAIDs.
u2022 Patients with aspirin-induced nasal polyps, associated with bronchospasm.
u2022 Patients with peptic ulcerations or bleeding of the gastrointestinal tract, active inflammatory bowel disease (Crohnu2019s disease or ulcerative colitis), severe hepatic insufficiency, non-dialysed severe renal insufficiency, recent cerebrovascular bleeding or established systemic bleeding disorders, peripheral arterial disease, established ischaemic heart disease and uncontrolled heart failure.
u2022 The treatment of peri-operative pain in the setting of coronary artery bypass graft (CABG) surgery.
u2022 Patients whose renal functions are being maintained by prostaglandins. These may include patients on diuretics and patients with impaired circulation, renal vascular disease and heart failure (see section 4.5).
u2022 Children under the age of 12 years, as NSAIDs may produce a high degree of gastrointestinal toxicity in children.
u2022 Pregnancy (see section 4.6).

COXFLAM may predispose to cardiovascular events, gastrointestinal events, or cutaneous reactions which may be fatal. There appears to be a higher risk for cardiovascular events with higher doses and longer duration of treatment. Caution is advised when COXFLAM is prescribed to patients with cardiovascular risk factors e.g. hypertension, diabetes, smoking and hypercholesterolaemia. Gastrointestinal tract (GIT) side effects such as gastrointestinal ulceration and bleeding, are more likely to occur in the elderly, and are more likely to be of a serious nature. Patients with a history of ulcers and the elderly are more susceptible to GIT side effects with increasing doses. GIT side effects may occur at any time during treatment with or without warning symptoms or a previous history of serious gastrointestinal events. Patients with a history of upper GIT disease and symptoms should be monitored and COXFLAM treatment should be stopped if peptic ulceration or GIT bleeding occurs. Serious skin reactions, which can be fatal, may occur. Skin reactions including Stevens-Johnson syndrome, toxic epidermal necrolysis and exfoliative dermatitis have been reported. The highest risk for occurrence of skin reactions is within the first weeks of treatment. COXFLAM should be discontinued if a mucocutaneous adverse event arises and the patient should be monitored.
Because of its lack of platelet effects, COXFLAM is not a substitute for aspirin for cardiovascular prophylaxis. Patients with pre-existing congestive heart failure or hypertension should be closely monitored as fluid retention and oedema have been reported. COXFLAM should be given with care to patients with a history of gastrointestinal disease such as Crohn's disease, gastro-oesophageal reflux disease, ulcerative colitis, angiodysplasia or hiatus hernia as the condition may be exacerbated (see section 4.2). Serious life-threatening hypersensitivity reactions have occurred with the use of NSAIDs. The risk/benefit should be considered in patients with mild allergic reactions, such as urticaria, skin rash and allergic rhinitis, induced by aspirin or other NSAIDs (see section 4.2). Due to inhibition of prostaglandin synthesis, fluid retention and oedema have been observed in patients taking COXFLAM, therefore COXFLAM should be used with caution in patients with compromised cardiac function and other conditions predisposing to, or worsened by, fluid retention. Renal prostaglandins play an important supportive role in the maintenance of renal perfusion. The inhibition of renal prostaglandin synthesis may precipitate overt renal decompensation which is typically followed by recovery to pre-treatment state upon discontinuation of treatment. Patients at risk of such a reaction include elderly, dehydrated patients, those with congestive cardiac failure, liver cirrhosis or dysfunction, nephrotic syndrome and overt renal disease, those on concurrent diuretics, sartans, angiotensin-II receptor antagonist or ACE-inhibitor treatment or those that are hypovolaemic (regardless the cause). In such patients careful monitoring of diuresis and the kidney function at the start of treatment is recommended. Age-related renal function impairment may increase the risk of NSAID-induced renal and hepatic toxicity, as well as the possible accumulation of the medication. Elderly patients should therefore be carefully monitored. In rare instances NSAIDs may cause interstitial nephritis, glomerulonephritis, papillary necrosis and the nephrotic syndrome. The dose of COXFLAM should be restricted to 7,5 mg daily in haemodialysed patients with terminal kidney disease. Patients with mild or moderate renal impairment (creatinine clearance > 25 mL/min) or clinically stable liver cirrhosis do not require dose reduction. Occasional elevations of serum transaminases or other indicators of liver function have been reported. In most cases these have been small and transient increases above the normal range. If the abnormality is significant or persistent, COXFLAM treatment should be discontinued and appropriate medical action taken. In view of COXFLAMu2019s inherent potential to cause fluid and electrolyte retention and its interference with the natriuretic effects of diuretics, heart failure or hypertension may be precipitated or exacerbated in susceptible patients. Caution should be used when prescribing COXFLAM to patients with haemorrhagic disorders (coagulation or platelet function disorders or haemophilia) or patients on anticoagulants as the bleeding time may be prolonged because of suppressed platelet aggregation (see section 4.5). These patients should be carefully monitored and the associated risk considered. COXFLAM should be used with caution in patients with infections, since meloxicam may mask symptoms like fever and inflammation. COXFLAM should not be used during pregnancy and lactation (see section 4.3 and 4.6). Risk of renal tubular acidosis and hypokalaemia are associated with non-steroidal anti-inflammatory medicine (NSAID) usage. Lactose COXFLAM contains lactose monohydrate. Patients with rare hereditary conditions of galactose intolerance e.g., galactosaemia, Lapp lactase deficiency, glucose-galactose malabsorption should not take COXFLAM.

Because of its lack of platelet effects, COXFLAM is not a substitute for aspirin for cardiovascular prophylaxis. There is no consistent evidence that concurrent use of aspirin mitigates the increased risk of serious cardiovascular thrombotic events associated with COXFLAM. An increased risk of gastrointestinal ulceration and bleeding may occur with the concurrent administration of two or more NSAIDs (including aspirin), due to the synergistic action produced. The concomitant use of corticosteroids may increase the incidence of upper gastrointestinal toxicity. The effects of oral anticoagulants, such as coumarin, indandion derivates or systemically administered heparin, thrombolytics and selective serotonin reuptake inhibitors may lead to an increased risk of bleeding by inhibition of platelet function.
Meloxicam is bound in the gastrointestinal tract by cholestyramine, and this leads to a faster elimination of COXFLAM. Increased plasma concentrations of lithium (via decreased renal excretion of lithium) and methotrexate (via decreased renal tubular secretion of methotrexate) may be present with concomitant use of COXFLAM. The plasma levels of these medicines should be carefully monitored if treatment with COXFLAM is unavoidable. The hematologic toxicity of methotrexate may be increased. Strict monitoring of the blood cell count is therefore advised. Acute renal insufficiency may occur in patients who are dehydrated. Patients who receive concurrent diuretics should be adequately hydrated and their renal function carefully monitored. There may be an increased risk of nephrotoxicity when administered concomitantly with angiotensin converting enzyme inhibitors, angiotensin-II receptor antagonists, ciclosporin and diuretics. An increased risk of hyperkalaemia may be present with angiotensin converting enzyme inhibitors, angiotensin-II receptor antagonists, NSAIDs, heparins, ciclosporin, tacrolimus, trimethoprim and potassium-sparing diuretics. The effect of some anti-hypertensive agents, such as u00df-blockers, ACE-inhibitors, vasodilators and diuretics, may be affected due to the inhibition of vasodilating prostaglandins. The concurrent administration of COXFLAM and quinolones may cause convulsions. The effect of phenytoin, and sulphonylurea anti-diabetics may be enhanced by COXFLAM. Prolonged concurrent use of COXFLAM and paracetamol may increase the risk of adverse renal effects. Potassium supplements may increase the risk of gastrointestinal side effects. NSAIDs may decrease the efficacy of intra-uterine devices. Concomitant treatment with probenecid leads to reduced excretion and thereby increased effects of COXFLAM. COXFLAM should not be used in combination with tacrolimus. COXFLAM is eliminated almost entirely by hepatic metabolism, of which approximately two thirds are mediated by cytochrome (CYP) P450 enzymes (CYP 2C9 major pathway and CYP 3A4 minor pathway) and one third by other pathways, such as peroxidase oxidation. The potential for a pharmacokinetic interaction should be taken into account when COXFLAM and medicines known to inhibit, or to be metabolised by CYP 2C9 and/or CYP 3A4 are administered concurrently. No significant medicine interaction exists between cimetidine, furosemide, digoxin and antacids. Simultaneous use of COXFLAM and alcohol increases the risk of bleeding.

Pregnancy
COXFLAM is contraindicated in pregnancy (see section 4.3). In early pregnancy, an increased risk of miscarriage, cardiac malformation and gastrochisis exists. Regular use of NSAIDs during the third trimester of pregnancy may result in premature closure of the foetal ductus arteriosus in utero, renal dysfunction with possible renal failure with oligohydramnios and persistent pulmonary hypertension of the newborn. The inhibition of prostaglandin synthesis may prolong bleeding time and inhibit uterine contractions at the end of pregnancy. The onset of labour may be delayed and its duration increased. Use of NSAIDs, such as COXFLAM, around 20 weeks gestation or later in pregnancy may cause a rare but serious foetal renal dysfunction leading to oligohydramnios and, in some cases, neonatal renal impairment. Complications of prolonged oligohydramnios include limb contractures and delayed lung maturation, which may require invasive procedures such as exchange transfusion or dialysis, in some cases.
Breastfeeding
It is not known whether COXFLAM is excreted in breast milk, however NSAIDs are known to pass into breast milk. Therefore, the use of COXFLAM during breastfeeding is not advised.
Fertility
COXFLAM may reduce female fertility and is not recommended in women attempting to conceive. Women who have difficulties conceiving, or who are undergoing investigation of infertility should not use COXFLAM.

The effects on ability to drive and use machinery has not been studied with meloxicam, but should vertigo, visual disturbances, drowsiness or other central nervous system disturbances occur, it would be advisable to refrain from these activities.

Blood and lymphatic system disorders
Less frequent: Anaemia, abnormal blood count, leukopenia and thrombocytopenia. Frequency unknown: Agranulocytosis. Concomitant administration of other potentially myelotoxic medicines, in particular methotrexate, can be a predisposing factor for the onset of cytopenia.
Immune system disorders
Less frequent: Allergic reactions. Frequency unknown: Anaphylactic reactions, anaphylactoid reaction and other immediate hypersensitivity.
Metabolism and nutrition disorders
Frequency unknown: Hypokalaemia.
Psychiatric disorders
Less frequent: Altered mood and nightmares. Frequency unknown: Disorientation and confusion.
Nervous system disorders
Frequent: Headache. Less frequent: Dizziness, somnolence. Frequency unknown: Cerebrovascular incidents (strokes) and insomnia.
Eye disorders
Less frequent: Visual disturbances (including blurred vision) and conjunctivitis.
Ear and labyrinth disorders
Less frequent: Tinnitus and vertigo.
Cardiac disorders
Less frequent: Palpitations. Frequency unknown: Peripheral oedema, dysrhythmia, tachycardia, congestive cardiac failure, myocardial infarction, cardiovascular thrombotic events.
Vascular disorders
Less frequent: Increased blood pressure, flushing. Frequency unknown: Aggravated hypertension and hypertension.
Respiratory, thoracic and mediastinal disorders
Less frequent: Asthma in individuals allergic to aspirin or other NSAIDs.
Gastrointestinal disorders
Frequent: Dyspepsia, nausea, diarrhoea, vomiting, constipation, flatulence and abdominal pain. Less frequent: Gastrointestinal perforation, gastroduodenal ulcer, colitis, oesophagitis, gastritis, eructation, occult or macroscopic gastrointestinal haemorrhage and stomatitis. Frequency unknown: Melaena, Crohnu2019s disease, peptic ulcers, haematemesis. Potentially fatal side effects include gastrointestinal ulceration or perforation and haemorrhage.
Hepatobiliary disorders
Less frequent: Hepatitis, abnormal liver function tests (e.g. raised bilirubin or transaminases).
Skin and subcutaneous tissue disorders
Less frequent: Dermatitis bullous, erythema multiforme, urticaria, Stevens-Johnson syndrome, toxic epidermal necrolysis, pruritus, rash and angioedema. Frequency unknown: Photosensitivity reaction.
Renal and urinary disorders
Less frequent: Micturition disorders (including acute urinary retention), acute renal failure, sodium and water retention, hyperkalaemia and abnormal renal function parameters (increased serum creatinine and/or serum urea) may occur. Frequency unknown: Renal tubular acidosis.
General disorders and administration site conditions
Less frequent: Oedema including oedema of the lower limbs.

Prolonged use at higher than recommended doses may result in severe hypokalaemia and renal tubular acidosis. Symptoms may include reduced level of consciousness and generalised weakness (see section 4.4 and section 4.8). Treatment is symptomatic and supportive. Standard measures of gastric evacuation should be used in alert patients. Clinical trials have shown that cholestyramine accelerates the elimination of meloxicam. Accelerated removal of meloxicam by 4 g oral doses of cholestyramine given three times a day was demonstrated in a clinical trial.