Flenodic 25 mg or 100 mg Tablets

FLENODIC (diclofenac sodium) is indicated for the symptomatic treatment of:

• Rheumatoid arthritis and osteoarthrosis. It is also used to treat ankylosing spondylitis and spondyarthritis.
• Post-operative and post-traumatic pain associated with inflammation and swelling.
• Pain associated with dental surgery.
• Treatment of the symptoms of primary dysmenorrhoea.

Posology

The maximum recommended daily dose for FLENODIC in any dosage form is 150 mg. FLENODIC should be taken with food and the tablets should be swallowed whole. Use the lowest effective dose for the shortest possible duration of treatment.

FLENODIC 25 Tablets (enteric-coated)

The usual initial daily dose is 100 to 150 mg: in mild cases, FLENODIC treatment should be initiated with 75 mg to 100 mg per day. In general, the daily dose should be divided into two or three fractional doses. For the treatment of primary dysmenorrhoea, the dosage should be adapted to meet individual requirements. The daily dosage should be in the range of 50 to 150 mg. Treatment should begin at the onset of symptoms and continue for a few days.

FLENODIC 100 SR Tablets

One tablet to be taken daily. If the symptoms most commonly occur at night or in the morning, the FLENODIC should be taken at night.

Paediatric population

FLENODIC is not recommended for use in children.

Method of administration

FLENODIC tablets are administered orally.

FLENODIC (diclofenac sodium) is absolutely contraindicated in:

• Patients with active or recent history of peptic ulcer.
• Patients with known or suspected hypersensitivity to diclofenac, other non-steroidal anti-inflammatory medicines, or any of the excipients in FLENODIC listed in section 6.1.
• Asthmatic patients in whom aspirin and other prostaglandin synthetase inhibitors have induced attacks of asthma, acute rhinitis or urticarial.
• Pregnancy and lactation.
• Patients with porphyria.
• Heart failure, established ischaemic heart disease and/or cerebrovascular disease (stroke) and peripheral arterial disease.
• History of gastrointestinal perforation, ulceration or bleeding (PUBs) related to previous NSAIDs, including FLENODIC.
• Active or history of recurrent ulcer/haemorrhage/perforations.

Caution is required in patients with a history of hypertension and/or heart failure as fluid retention and oedema have been reported in association with FLENODIC therapy. In view of the FLENODICu2019s inherent potential to cause fluid retention, heart failure may be precipitated in some compromised patients.

Caution is required in patients with significant risk factors for cardiovascular events (e.g., hypertension, hyperlipidaemia, diabetes mellitus, smoking) and should only be treated with FLENODIC after careful consideration. Patients should see a medical practitioner immediately if the patients experience the signs and symptoms of a serious arteriothrombotic event (e.g. chest pain, shortness of breath, weakness, slurring of speech), which can occur without warnings.

Elderly: The elderly have an increased frequency of adverse reactions to NSAIDs including FLENODIC, especially gastrointestinal perforation, ulceration and bleeding (PUBs) which may be fatal. Elderly patients receiving FLENODIC should be closely monitored, and the dosage reduced if necessary. The lowest effective dose should be used in the elderly, frail and low body mass patients.

The risk of gastrointestinal perforation, ulceration or bleeding (PUBs) is higher with increasing doses of FLENODIC, in patients with a history of ulcers, and the elderly. Medical supervision is also required for patients with pre-existing dyshaemopoiesis or disorders of blood coagulation.

Gastrointestinal bleeding or perforation may present at any time during FLENODIC treatment. This can present with or without warning symptoms or a previous history. When gastrointestinal bleeding or ulceration occurs in patients receiving FLENODIC, treatment with FLENODIC should be stopped.

To reduce the risk of gastrointestinal toxicity in patients with a history of peptic ulcers, haemorrhage, perforation and in the elderly, the lowest effective dose should be used. Combination therapy with protective medicines (e.g. proton pump inhibitors) should be considered for these patients as well as for patients that requires concomitant use of medicines containing a low dose acetylsalicylic acid or other medicines that is likely to increase gastrointestinal risk (see section 4.5).

FLENODIC should be given with caution to patients with a history of gastrointestinal disease (e.g. ulcerative colitis, Crohnu2019s disease, hiatus hernia, gastro-oesophageal reflux disease, angiodysplasia) as the condition may be exacerbated (see section 4.8).

Serious skin reactions, some of them fatal, including exfoliative dermatitis, Stevens-Johnson syndrome, and toxic epidermal necrolysis have been reported. FLENODIC should be discontinued at the first appearance of skin rash, mucosal lesions, or any other sign of hypersensitivity.

Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS) has been reported in patients taking NSAIDs such as FLENODIC. 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. Eosinophilia 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 FLENODIC and evaluate the patient immediately.

In patients with systemic lupus erythematosus (SLE) and mixed connective tissue disorders there may be an increased risk of aseptic meningitis (see section 4.8).

Allergic reactions including anaphylaxis can occur, even without prior exposure. FLENODIC like other medicines that inhibit prostaglandin synthase activity can precipitate bronchospasm. Special precaution is recommended in patients with asthma, seasonal allergic rhinitis, swelling of nasal mucosa, chronic obstructive pulmonary disease or chronic infections of the respiratory tract.

The administration of Nonsteroidal anti-inflammatory drugs (NSAIDu2019s) around 20 weeks or later in pregnant patients may cause serious kidney problems in an unborn baby. This may lead to low levels of amniotic fluid because around 20 weeks of pregnancy the unborn babyu2019s kidneys produces amniotic fluid. Amniotic fluid provides a protective cushion and helps the lungs, digestive system, and muscles of the unborn baby to develop (see section 4.3).

Medicines that inhibit prostaglandin synthesis, like NSAIDu2019s, may adversely affect pregnancy and/or the embryo or foetalu2019s development. The risk is believed to increase with an increased dose and/or duration of therapy.

Regular use of NSAIDs such as FLENODIC during 20 to 40 weeks of pregnancy or the third trimester of pregnancy, may result in premature closure of the foetal ductus arteriosus in utero, and possibly, in persistent pulmonary hypertension of the new-born. The onset of labour may be delayed, and its duration increased.

FLENODIC may cause renal dysfunction, which may progress to renal failure with oligohydroamniosis, and in some cases neonatal renal impairment. Complications of prolonged oligohydramnios may include limb contractures and delayed lung maturation. Oligohydramnios may be reversible with treatment.

Discontinuation and possible prolongation of bleeding time due to the anti-aggregating effect which may occur even at very low doses of FLENODIC.

Severe hypokalaemia and renal tubular acidosis have been reported due to prolonged use of diclofenac as contained in FLENODIC at higher than recommended doses. Presenting signs and symptoms included reduced level of consciousness and generalised weakness. Diclofenac (i.e., FLENODIC) induced renal tubular acidosis should be considered in patients with unexplained hypokalaemia and metabolic acidosis.

Fluid retention and oedema have been reported with NSAID therapy, including diclofenac, particular caution should be taken when FLENODIC is used in patients with hepatic or renal insufficiency. Monitoring of renal function is recommended as a precautionary measure when using FLENODIC in such cases.

Elevations of one or more of the liver enzymes may occur with FLENODIC treatment. Should these abnormal liver functions tests persist or if clinical signs of liver disease develop, FLENODIC should be discontinued. Hepatitis may occur.

Serious interactions have been reported with the concomitant use of FLENODIC and methotrexate. Due to the fact that prostaglandins are important where renal blood flow is concerned, careful monitoring is required for the following patients:

• Patients with impaired hepatic, cardiac or renal function.
• Elderly patients being treated with diuretics.
• Patients with extracellular volume depletion.
• Patients with cirrhosis

Patients receiving long term FLENODIC therapy should undergo periodic blood counts. FLENODIC may reversibly inhibit platelet aggregation (see section 4.5). Patients with haemostasis, bleeding diathesis or haematological abnormalities should be carefully monitored. Patients with collagen disease are at increased risk of developing aseptic meningitis. FLENODIC therapy should be discontinued in patients who experience blurred vision or changes in colour vision.

NSAIDs: use of two or more NSAIDs concomitantly could result in an increase in side effects.

Anti-hypertensive medicines and diuretics: Concomitant use of FLENODIC, with diuretics or antihypertensive medicines (e.g., beta-blockers, angiotensin converting enzyme) may cause a decrease in their antihypertensive effect because of its inhibition of vasodilatory prostaglandin synthesis.

FLENODIC may raise plasma concentrations of digoxin or lithium when used concomitantly.

Medicines known to cause hyperkalaemia: Concomitant treatment of FLENODIC with potassium-sparing diuretics, ciclosporin, tacrolimus or trimethoprim may increase serum potassium levels.

Corticosteroids: increased risk of gastrointestinal perforation, ulceration or bleeding (PUBs).

Bioavailability of FLENODIC is reduced by acetylsalicylic acid when the two medicines are administered concomitantly (see section 4.4 for more information).

Anti-coagulants: FLENODIC may enhance the effects of anti-coagulants such as warfarin. The patient must be closely monitored due to the increased risk of haemorrhage.

Use of FLENODIC in diabetic patients requires close monitoring of blood sugar and possible alterations in the dosage of hypoglycaemic medicines.

The nephrotoxicity of ciclosporin may be increased when used together with FLENODIC due to the effect on renal prostaglandins.

Methotrexate: FLENODIC can inhibit the tubular renal clearance and hereby may increased levels of methotrexate.

Tacrolimus: May increase the risk of nephrotoxicity.

Quinolone antimicrobials: Interactions between quinolones and diclofenac may cause convulsions. This may occur in patients without or with history of epilepsy or convulsions.

Phenytoin: Concomitant treatment of diclofenac with phenytoin may increase exposure of phenytoin. For this reason it is recommended to monitor phenytoin plasma concentrations.

Colestipol and cholestyramine: The absorption of diclofenac can be delayed or decreased by these medicines. It is recommended to administer diclofenac at least 4 to 6 hours after or one hour before the administration of colestipol or cholestyramine.

Cardiac glycosides: Concomitant use of cardiac NSAIDu2019s, like diclofenac, with glycosides may exacerbate cardiac failure, increase plasma glycoside levels and reduce GFR in patients.

Mifepristone: NSAIDu2019s like diclofenac, should not be used for 8 to 12 days after administration of mifepristone, NSAIDu2019s can reduce mifepristoneu2019s effect.

Potent CYP2C9 inhibitors: Caution is recommended when CYP2C9 is co-administered with FLENODIC, this concomitant use could result in an inhibition of diclofenac metabolism that will significant increase in peak plasma concentration and exposure to diclofenac.

Anti-platelet medicines and selective serotonin reuptake inhibitors (SSRIs): increased risk of gastrointestinal bleeding.

Women of childbearing potential

If FLENODIC is used by a woman attempting to conceive, the dose should be kept as low and duration of treatment as short as possible.

Pregnancy

FLENODIC is contraindicated during pregnancy (see section 4.3). During the third trimester of pregnancy, all prostaglandin synthesis inhibitors may expose the foetus to:

• cardiopulmonary toxicity (with premature closure of the ductus arteriosus and pulmonary hypertension);
• renal dysfunction, which may progress to renal failure with oligo-hydroamniosis;
• the mother and the neonate, at the end of pregnancy, to:
• possible prolongation of bleeding time, an anti-aggregating effect which may occur even at very low doses.
• inhibition of uterine contractions resulting in delayed or prolonged labour.

Breastfeeding

FLENODIC is contraindicated during breastfeeding, due to its ability to pass into the breast milk in small amounts.

Fertility

NSAIDu2019s, like FLENODIC, may impair female fertility and is not recommended in patients attempting to conceive (see section 4.4).

Patients who experience central nervous system reactions should refrain from driving and operating hazardous machinery.

Gastrointestinal System

Frequent Nausea, vomiting, diarrhoea, dyspepsia, abdominal pain, flatulence, anorexia, abdominal cramps and discomfort, eructation and local irritation.

Less frequent Gastritis, gastrointestinal haemorrhage, peptic ulcer with or without perforation, haematemesis, diarrhoea haemorrhagic, melaena, Gastric and duodenal ulcerations with or without bleeding or perforation (sometimes fatal particularly in the elderly). Colitis (including non-specific haemorrhagic colitis and exacerbation of ulcerative colitis or Crohn's disease), constipation, Aphthous stomatitis (including ulcerative stomatitis), glossitis, oesophageal disorder, oesophageal lesions, diaphragm-like intestinal strictures, pancreatitis, gastritis.

Unknown Ischaemic colitis.

Blood and lymphatic system disorders

Less frequent Anaemia secondary to gastrointestinal bleeding, thrombocytopenia, leucopoenia, aplastic anaemia, agranulocytosis, haemolytic anaemia, neutropenia, eosinophilia.

Immune system disorders

Less frequent Hypersensitivity reactions (e.g.: bronchospasm). anaphylactic and anaphylactoid reactions (including hypotension and shock). Angioneurotic oedema (including face oedema).

Respiratory System

Less frequent Asthma (including dyspnoea) in patients sensitive to Acetylsalicylic Acid, pneumonitis.

Psychiatric disorders

Less frequent Disorientation, depression, insomnia, nightmares, irritability, psychotic reactions.

Nervous system disorders

Frequent Headache, dizziness.

Less frequent Somnolence, tiredness, drowsiness, vertigo, paraesthesia, memory disturbance, convulsion, anxiety, tremor, aseptic meningitis, impaired concentration, disturbances of sensation, taste alteration disorders, cerebrovascular accident.

Unknown Confusion, hallucinations, disturbances of sensation, malaise.

Eye disorders

Less frequent Disturbances of vision (blurred vision, diplopia), impaired vision, changes in colour perception, toxic amblyopia.

Unknown Optic neuritis.

Ear and labyrinth disorders

Frequent Vertigo.

Less frequent Tinnitus, impaired hearing.

Cardiac disorders

Less frequent Myocardial infarction, cardiac failure, palpitations, chest pain.

Unknown Kounis syndrome.

Vascular disorders

Less frequent Hypertension, sweating, hypotension, vasculitis.

Hepato-biliary disorders

Frequent Transaminases increased.

Less Frequent Liver function disorders including hepatitis with or without jaundice, hepatotoxicity, liver disorder. Fulminant hepatitis, hepatic necrosis, hepatic failure. Elevation of serum aminotransferase enzymes (SGOT, SGPT).

Skin and subcutaneous tissue disorders

Frequent Rash.

Less frequent Urticaria, skin eruption, eczema, erythema, erythema multiforme, bullous reactions including Stevens-Johnson syndrome, toxic epidermal necrolysis (Lyell's syndrome), dermatitis exfoliative, loss of hair, photosensitivity reaction, purpura including allergic purpura, pruritus.

Frequency unknown Drug Reaction with Eosinophillia and Systemic Symptoms (DRESS) (see section 4.4).

Renal and urinary disorders

Less frequent Acute renal failure, haematuria, proteinuria, nephrotic syndrome, interstitial nephritis, renal papillary necrosis, cystitis.

Frequency unknown Renal tubular acidosis *

Reproductive system and breast disorders

Less frequent Impotence.

General disorders and administration site conditions

Less frequent Oedema, peripheral oedema.

Metabolism and nutrition disorders

Frequency unknown Hypokalaemia*

Description of Selected Adverse Reactions

*Renal tubular acidosis and hypokalaemia have been reported in the post-marketing setting typically following prolonged use of diclofenac at higher than recommended doses.

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. Healthcare 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.

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. There is no specific antidote for FLENODIC.