Cataflam D, Cataflam Sachets 50 mg Dispersible Tablets

As short-term symptomatic relief in the following acute conditions:

• Painful musculoskeletal conditions.
• Non articular rheumatism.
• Acute attacks of gout.
• Painful post-operative and post-traumatic inflammation and swelling, pain following dental surgery.
• Flare-up of osteoarthritis.
• Symptomatic treatment of primary dysmenorrhoea.
• Classical migraine attacks.

Adults

The dose should be the lowest effective dose given for the shortest possible duration. The recommended initial daily dose is 100 mg to 150 mg. In milder cases, 50 to 100 mg daily is usually sufficient. The total daily dosage should generally be divided into 2 to 3 separate doses. The maximum daily dose is 150 mg.

In migraine an initial dose of 50 mg should be taken at the first signs of an impending attack. In cases where pain relief within 2 hours after the first dose is not sufficient, a further dose of 50 mg may be taken. If needed, a further dose of 50 mg may be taken after 4 to 6 hours, not exceeding a total dose of 150 mg per day.

In primary dysmenorrhoea, the daily dose should be individually adjusted and is generally 50 to 150 mg. A dose of 50 to 100 mg should be given initially and, if necessary, increased over the course of several menstrual cycles up to a maximum of 150 mg/day. Treatment should be started on appearance of the first symptoms and, depending on the symptomatology, continued for a few days.

Children and adolescents

Because of its available dosage strength, CATAFLAM is not recommended for use in children and adolescents below 14 years of age. For adolescents aged 14 or over, a total daily dose of 50 to 100 mg is usually sufficient. The total daily dose should generally be divided in 2 to 3 doses. The maximum daily dose of 150 mg should not be exceeded. The use of CATAFLAM in migraine attacks has not been established in children.

The Elderly

The lowest effective dose should be used, caution is indicated, especially for frail elderly patients or those with a low body weight (see section 4.4).

Administration

CATAFLAM D dispersible tablets should preferably be taken on an empty stomach. CATAFLAM D dispersible tablets should be dropped into a glass of water and the liquid stirred to aid dispersion before swallowing. Since a proportion of the active substance may remain in the glass after swallowing, it is advisable to rinse the glass with a small amount of water and to swallow again. The dispersible tablets must not be divided or chewed.

The contents of CATAFLAM SACHETS powder for oral solution should be dissolved with stirring in a glass of natural (non-carbonated) water. The solution may remain somewhat cloudy, but this should not influence the efficacy of the preparation. The solution should be swallowed preferably before meals.

• Gastric or intestinal ulcer, bleeding or perforation.
• Known hypersensitivity to the active substance or to any of the excipients.
• CATAFLAM is also contraindicated in asthmatic patients in whom attacks of asthma, urticaria, or acute rhinitis are precipitated by acetylsalicylic acid or by other NSAIDs.
• CATAFLAM should not be used in patients with porphyria.
• Pregnancy and lactation (see section 4.6)
• Hepatic and renal failure (see section 4.4).
• Heart failure, established ischaemic heart disease and/or cerebrovascular disease (stroke) and peripheral arterial disease.

Gastrointestinal bleeding, ulceration or perforation, which can be fatal, have been reported with all NSAIDs, including CATAFLAM and may occur at any time during treatment, with or without warning symptoms or a previous history of serious gastrointestinal events. They generally have more serious consequences in the elderly. If gastrointestinal bleeding or ulceration occurs in patients receiving CATAFLAM, the medicinal product should be discontinued.

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 NSAIDs, including CATAFLAM (see section 4.8). Patients appear to be at highest risk of these reactions early in the course of therapy, the onset of the reaction occurring in the majority of cases within the first month of treatment. CATAFLAM should be discontinued at the first appearance of skin rash, mucosal lesions or any other sign of hypersensitivity.

Allergic reactions, including anaphylactic/anaphylactoid reactions, may occur without earlier exposure to CATAFLAM.

CATAFLAM may mask the signs and symptoms of infection.

The concomitant use of CATAFLAM with systemic NSAIDs including cyclooxygenase-2 selective inhibitors should be avoided due to the potential for additive undesirable effects (see section 4.5).

Caution is indicated in the elderly on basic medical grounds. In particular, it is recommended that the lowest effective dose be used in frail elderly patients or those with a low body weight.

Pre-existing asthma: In patients with asthma, seasonal allergic rhinitis, swelling of the nasal mucosa (i.e. nasal polyps), chronic obstructive pulmonary diseases or chronic infections of the respiratory tract (especially if linked to allergic rhinitis-like symptoms), reactions to CATAFLAM like asthma exacerbations (so-called intolerance to analgesics / analgesics-asthma), angioedema or urticaria are more frequent than in other patients. Therefore, special precaution is recommended in such patients (readiness for emergency). This is applicable as well for patients who are allergic to other substances, e.g. with skin reactions, pruritus or urticaria.

Gastrointestinal effects: Close medical surveillance is imperative, and particular caution should be exercised when prescribing CATAFLAM in patients with symptoms indicative of gastrointestinal (GI) disorders or with a history suggestive of gastric or intestinal ulceration, bleeding or perforation (see section 4.8). The risk of GI bleeding is higher with increasing CATAFLAM doses and in patients with a history of ulcer, particularly if complicated with haemorrhage or perforation and in the elderly. To reduce the risk of GI toxicity in patients with a history of ulcer, particularly if complicated with haemorrhage or perforation, and in the elderly, the treatment should be initiated and maintained at the lowest effective dose. Patients with a history of GI toxicity, particularly the elderly, should report any unusual abdominal symptoms (especially GI bleeding). Caution is recommended in patients receiving concomitant medications which could increase the risk of ulceration or bleeding, such as systemic corticosteroids, anticoagulants, anti-platelet agents or selective serotonin-reuptake inhibitors (see section 4.5).

Close medical surveillance and caution should also be exercised in patients with ulcerative colitis or Crohnu2019s disease, as their condition may be exacerbated (see section 4.8)

Hepatic effects: Close medical surveillance is required when prescribing CATAFLAM to patients with impaired hepatic function, as their condition may be exacerbated. Values of one or more liver enzymes may increase. During prolonged treatment with CATAFLAM, regular monitoring of hepatic function is indicated as a precautionary measure. If abnormal liver function tests persist or worsen, if clinical signs or symptoms consistent with liver disease develop, or if other manifestations occur (e.g. eosinophilia, rash), CATAFLAM should be discontinued. Hepatitis may occur with the use of CATAFLAM without prodromal symptoms.

NSAIDs, including diclofenac, may be associated with increased risk of gastro-intestinal anastomotic leak. Close medical surveillance and caution are recommended when using CATAFLAM after gastro-intestinal surgery.

Renal effects: As fluid retention and oedema have been reported in association with CATAFLAM therapy, particular caution is called for in patients with impaired cardiac or renal function, history of hypertension, the elderly, patients receiving concomitant treatment with diuretics or medicinal products that can significantly impact renal function, and in those patients with substantial extracellular volume depletion from any cause, e.g. before or after major surgery (see section 4.3). Monitoring of renal function is recommended as a precautionary measure when using CATAFLAM in such cases. Discontinuation of therapy is usually followed by recovery to the pre-treatment state.

Haematological effects: During prolonged treatment with CATAFLAM, monitoring of the blood count is recommended. CATAFLAM may temporarily inhibit platelet aggregation. Patients with defects of haemostasis should be carefully monitored.

Cardiovascular effects: Treatment with NSAIDs including CATAFLAM, may be associated with an increased risk of serious cardiovascular thrombotic events (including myocardial infarction and stroke). The lowest effective dose of CATAFLAM, should be used for the shortest possible duration. Treatment with CATAFLAM is contraindicated in patients with established cardiovascular disease (congestive heart failure, established ischemic heart disease, peripheral arterial disease) or uncontrolled hypertension. Patients should remain alert for the signs and symptoms of serious arteriothrombotic events (e.g. chest pain, shortness of breath, weakness, slurring of speech), which can occur without warning. Patients should be instructed to see a physician immediately in case of such an event.

The following interactions include those observed with CATAFLAM and/or other pharmaceutical forms of diclofenac.

• Lithium: If used concomitantly, CATAFLAM may raise plasma concentrations of lithium. Monitoring of the serum lithium levels is recommended.
• Digoxin: If used concomitantly, CATAFLAM may raise plasma concentrations of digoxin. Monitoring of the serum digoxin levels is recommended.
• Diuretics and antihypertensive agents: Concomitant use of CATAFLAM with diuretics or antihypertensive agents (e.g. beta-blockers, angiotensin converting enzyme (ACE) inhibitors) may cause a decrease in their antihypertensive effect. Therefore, the combination should be administered with caution and patients, especially the elderly, should have their blood pressure periodically monitored. Patients should be adequately hydrated and consideration should be given to monitoring of renal function after initiation of concomitant therapy and periodically thereafter, particularly for diuretics and ACE inhibitors due to the increased risk of nephrotoxicity. (see section 4.4).
• Medicines known to cause hyperkalaemia: Concomitant use of CATAFLAM with potassium sparing diuretics, ciclosporin, tacrolimus or trimethoprim may be associated with increased serum potassium levels, which should be monitored frequently (see section 4.4).
• Other NSAIDs and corticosteroids: Concomitant administration of CATAFLAM and other systemic NSAIDs or corticosteroids may increase the frequency of gastrointestinal undesirable effects (see section 4.4).
• Anticoagulants and anti-platelet medicines: The bioavailability of CATAFLAM is reduced by acetylsalicylic acid, and that of acetylsalicylic acid by CATAFLAM, when the two agents are administered together. Caution is recommended since concomitant administration could increase the risk of bleeding (see section 4,4). There are reports of an increased risk of haemorrhage in patients receiving CATAFLAM and anticoagulants concomitantly. Close monitoring of such patients is therefore recommended.
• Selective serotonin reuptake inhibitors (SSRIs): Concomitant administration of CATAFLAM and SSRIs may increase the risk of gastrointestinal bleeding (see section 4.4).
• Antidiabetics: There have been isolated reports of both hypoglycaemic and hyperglycaemic effects necessitating changes in the dosage of the antidiabetic agents during treatment with CATAFLAM. For this reason, monitoring of the blood glucose level is recommended as a precautionary measure during concomitant therapy. There have been isolated reports of metabolic acidosis when diclofenac was co-administered with metformin, especially in patients with pre-existing renal impairment.
• Methotrexate: Caution is recommended when CATAFLAM is administered less than 24 hours before or after treatment with methotrexate, since blood concentrations of methotrexate may rise and the toxicity of this substance be increased.
• Ciclosporin: CATAFLAM may increase the nephrotoxicity of ciclosporin due to the effect on renal prostaglandins. Therefore, it should be given at doses lower than those that would be used in patients not receiving ciclosporin.
• Quinolone antibacterials: There have been isolated reports of convulsions which may have been due to concomitant use of quinolones and NSAIDs.
• Potent CYP2C9 inhibitors: Caution is recommended when co-prescribing CATAFLAM with potent CYP2C9 inhibitors (such as voriconazole), which could result in a significant increase in peak plasma concentrations and exposure to CATAFLAM due to inhibition of CATAFLAM metabolism.
• Phenytoin: When using phenytoin concomitantly with CATAFLAM, monitoring of phenytoin plasma concentrations is recommended due to an expected increase in exposure to phenytoin.
• CYP2C9 inducers: Caution is recommended when co-prescribing diclofenac with CYP2C9 inducers (such as rifampicin), which could result in a significant decrease in plasma concentration and exposure to diclofenac.

Pregnancy
CATAFLAM should not be used during pregnancy. CATAFLAM during the third trimester of pregnancy is contraindicated as uterine inertia and/or premature closure of the ductus arteriosus may occur (see section 4.3). Use in pregnancy at 20 weeks gestation or later 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.

Lactation
CATAFLAM passes into the breast milk. Mothers on CATAFLAM should not breastfeed their infants.

Fertility
The use of CATAFLAM may impair female fertility and is not recommended in women attempting to conceive. In women who have difficulties conceiving or who are undergoing investigation of infertility, withdrawal of CATAFLAM should be considered.

CATAFLAM may have an effect on the patientu2019s ability to drive and use machines. Patients experiencing visual disturbances, dizziness, vertigo, somnolence or other central nervous system disturbances while taking diclofenac should refrain from driving or using machines.

Adverse reactions (Table 1) are ranked under heading of frequency, the most frequent first, using the following convention: common (u2265 1/100, < 1/10); uncommon (u2265 1/1,000, < 1/100); rare (u2265 1/10,000, < 1/1,000); very rare (< 1/10,000), including isolated reports. The following undesirable effects include those reported with CATAFLAM D dispersible tablets and/or other pharmaceutical forms of diclofenac, with either short-term or long-term use.

Table 1

Blood and lymphatic system disorders
Very rare: Thrombocytopenia, leucopenia, anaemia (including haemolytic and aplastic anaemia), agranulocytosis.

Immune system disorders
Rare: Hypersensitivity reactions, anaphylactic and anaphylactoid reactions (including hypotension and shock). Very rare: Angioedema (including face oedema).

Psychiatric disorders
Very rare: Disorientation, depression, insomnia, nightmares, irritability, psychotic disorder.

Nervous system disorders
Common: Headache, dizziness. Rare: Somnolence. Very rare: Disturbances of sensation, paraesthesia, memory impairment, convulsion, anxiety, tremor, aseptic meningitis, taste disturbances, cerebrovascular accident.

Eye disorders
Very rare: Visual impairment, blurred vision, diplopia.

Ear and labyrinth disorders
Common: Vertigo. Very rare: Tinnitus, impaired hearing.

Cardiac disorders
Uncommon: Palpitations, chest pain, cardiac failure, myocardial infarction.

Vascular disorders
Very rare: Hypertension, vasculitis.

Respiratory, thoracic and mediastinal disorders
Rare: Asthma (including dyspnoea). Very rare: Pneumonitis.

Gastrointestinal system disorders
Common: The most commonly observed adverse events are gastrointestinal in nature. Peptic ulcers, perforation or gastrointestinal bleeding, sometimes fatal. Nausea, vomiting, diarrhoea, flatulence, constipation, dyspepsia, abdominal pain, melaena, haematemesis, ulcerative stomatitis, exacerbation of colitis and Crohnu2019s disease, gastritis. Rare: Gastritis, gastrointestinal haemorrhage, haematemesis, haemorrhagic diarrhoea, melaena, gastro-intestinal ulcer (with or without bleeding or perforation). Very rare: Colitis (including haemorrhagic colitis and exacerbation of ulcerative colitis or Crohn's disease), constipation, stomatitis, glossitis, oesophageal disorder, intestinal diaphragm disease diaphragm-like intestinal strictures, pancreatitis.

Hepatobiliary disorders
Common: Transaminases increased (ALT, AST). Rare: Hepatitis, jaundice, liver disorder. Very rare: Fulminant hepatitis, hepatic necrosis, hepatic failure.

Skin and subcutaneous tissue disorders
Common: Rash. Rare: Urticaria. Very rare: Bullous dermatitis, eczema, erythema, erythema multiforme, Stevens-Johnson syndrome, toxic epidermal necrolysis (Lyell's syndrome), exfoliative dermatitis, alopecia, photosensitivity reaction, purpura, Henoch-Schonlein purpura, pruritus.

Renal and urinary disorders
Very rare: Acute renal failure, haematuria, proteinuria, nephrotic syndrome, tubulointerstitial nephritis, renal papillary necrosis.

General disorders and administration site conditions
Common: Injection site reactions, injection site pain, injection site induration, application site irritation (suppositories). Rare: Oedema.

Description of selected adverse drug reactions

Arteriothrombotic events: Meta-analysis and pharmacoepidemiological data point towards a risk of arteriothrombotic events (for example myocardial infarction) associated with the use of diclofenac, and during long-term treatment (see section 4.4).

Visual effects: Visual disturbances such as visual impairment, blurred vision or diplopia appear to be NSAID class effects and are usually reversible on discontinuation. A likely mechanism for the visual disturbances is the inhibition of prostaglandin synthesis and other related compounds that alter regulation of retinal blood flow resulting in potential changes in vision. If such symptoms occur during diclofenac treatment, an ophthalmological examination may be required to exclude other causes.

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 requested to report any suspected adverse drug reactions to SAHPRA via the Med Safety APP (Medsafety X SAHPRA) and eReporting platform (who-umc.org) found on SAHPRA website.

Overdosage can cause symptoms such as vomiting, gastrointestinal haemorrhage, diarrhoea, dizziness, tinnitus or convulsions. In the event of significant poisoning, acute renal failure and liver damage are possible.

Therapeutic measures
Management of acute poisoning with CATAFLAM essentially consists of supportive measures and symptomatic treatment. Supportive measures and symptomatic treatment should be given for complications such as hypotension, renal failure, convulsions, gastrointestinal disorder, and respiratory depression. Special measures such as forced diuresis, dialysis or haemoperfusion are probably of no help in eliminating CATAFLAM due to the high protein binding and extensive metabolism. Activated charcoal may be considered after ingestion of a potentially toxic overdose, and gastric decontamination (e.g. vomiting) after ingestion of a potentially life-threatening overdose.