RUPAN 200 Tablet

Ibuprofen is indicated for its analgesic and anti-inflammatory effects in the treatment rheumatoid arthritis (including juvenile rheumatoid arthritis or Still’s disease) ankylosing spondylitis, osteoarthritis and other non-rheumatoid (seronegative) arthropathies.

In the treatment of non-articular rheumatic conditions, Ibuprofen is indicated in periarticular conditions, Ibuprofen is indicated in periarticular conditions such as frozen shoulder (capsulitis), bursitis, tendonitis, tenosynovitis and low back pain. Ibuprofen can also be used in soft tissue injuries such as strains and sprains.

Ibuprofen is also indicated for its analgesic effect in the relief of mild to moderate pain, including dysmenorrhoea, dental and post-operative pain and for the symptomatic relief of headache including migraine headache.

DOSAGE AND ADMINISTRATION

Undesirable effects may be minimized by using the lowest effective dose for the shortest duration necessary to control symptoms

Adults

The recommended dosage of Ibuprofen is 1200-1800mg daily in divided doses. Some patients can be maintained on 600-1200mg daily. In severe or acute conditions, it can be advantageous to increase the dosage until the acute phase is brought under control, provided that the total daily dose does not exceed 2400mg in divided doses.

Children

The daily dosage of Ibuprofen is 20mg/kg body weight in divided doses.

Up to 40mg/kg body weight per day in divided doses may be given in juvenile rheumatoid arthritis.

The total daily dose should not exceed 500mg in individuals with body weight of 30kg or less.

In the event of gastro-intestinal complaints, RUPAN 200mg may be given with food or milk.

Not recommended for children weighing less than 7kg.

(See the package insert about the details below.)

Elderly

Hepatic impairment

Renal impairment

- Hypersensitivity to ibuprofen or any other of the tablet ingredients

- Patients, with or without chronic asthma, in whom attacks of asthma, urticaria or acute rhinitis are precipitated by aspirin or other NSAIDs

- History of gastrointestinal bleeding or perforation, related to previous NSAIDs therapy

- Active or history of recurrent peptic ulcer/ haemorrhage (two or more distinct episodes of proven ulceration or bleeding)

- In patients with severe heart failure

- Severe renal impairment

- Severe coagulation disorders

- Pregnancy (last trimester)

- Lactation

- Children less than 7kg

Gastrointestinal: The most commonly-observed adverse events are gastrointestinal in nature. Peptic ulcers, perforation or GI bleeding, sometimes fatal, particularly in the elderly, may occur. Nausea, vomiting, diarrhoea, flatulence, constipation, dyspepsia, abdominal pain, melaena, haematemesis, ulcerative stomatitis, exacerbation of colitis and Crohn’s disease have been reported following ibuprofen administration. Less frequently, gastritis, duodenal ulcer, gastric ulcer and gastrointestinal perforation have been observed. Epidemiological data indicate that of the seven most widely-used oral, non-aspirin NSAIDs, ibuprofen presents the lowest risk of upper gastrointestinal toxicity.

Hypersensitivity: See the package insert about the details.

Cardiovascular: See the package insert about the details.

The following adverse effects are reported less commonly (<1%), and causality is not always established:

Dermatological: Photosensitivity

Haematological: Agranulocytosis, aplastic and haemolytic anaemia, neutropenia and thrombocytopenia

Hepatic: Liver function abnormalities, hepatitis and jaundice.

Renal: Various forms of nephrotoxicity: interstitial nephritis, nephrotic syndrome and renal failure;

Neurological/sensory: Confusion, depression, dizziness, drowsiness, fatigue, malaise, hallucinations, headaches, optic neuritis, paresthesia, tinnitus, vertigo and visual disturbances.

Care should be taken in patients treated with any of the following drugs as interactions have been reported in some patients.

(See the package insert about the details below.)

Antihypertensives

Diuretics

Anticoagulants (Coumarin type)

Antiplatelet agents and selective serotonin reuptake inhibitors (SSRIs)

Other analgesics

Cardiac glycosides

Corticosteroids

Cyclosporin

Lithium

Methotrexate

Mifepristone

Quinolone antibiotics

Whilst no teratogenic effects have been demonstrated in animal toxicology studies, the use of ibuprofen during pregnancy should, if possible, be avoided. Congenital abnormalities have been reported in association with ibuprofen administration in man; however, these are low infrequency and do not appear to follow any discernible pattern. In view of the known effects of NSAIDs on the foetal cardiovascular system (closure of ductus arteriosus), use in late pregnancy should be avoided.

In the limited studies so far available, ibuprofen appears in the breast milk in very low concentrations and is unlikely to adversely affect the breast-fed infant.

Undesirable effects may be minimized by using the minimum effective dose for the shortest duration necessary to control symptoms

The use of RUPAN 200 with concomitant NSAIDs including COX-2 selective inhibitors should be avoided.

The elderly have an increased frequency of adverse reactions to NSAIDs especially gastrointestinal bleeding and perforation which may be fatal.

Patients with a history of gastro-intestinal bleeding or ulceration should be closely supervised. There are reports of bleeding, ulceration and/or perforation of the stomach and small and large intestine in patients administered ibuprofen.

Gastrointestinal bleeding, ulceration or perforation which can be fatal, has been reported with all NSAIDs at any time during treatment, with or without warning symptoms or a previous history of serious gastrointestinal events.

The risk of GI bleeding, ulceration or perforation is higher with increasing NSAID doses, in patients with a history of ulcer, particularly if complicated with haemorrhage or perforation, and in the elderly.

These patients should commence treatment on the lowest dose available. Combination therapy with protective agents (e.g. misoprostol or proton pump inhibitors) should be considered for these patients, and also for patients requiring concomitant low dose aspirin, or other drugs likely to increase gastrointestinal risk.

Patients with a history of GI toxicity, particularly when elderly, should report and unusual abdominal symptoms (especially GI bleeding) particularly in the initial stages of the treatment.

Caution should be advised in patients receiving concomitant medications which could increase the risk of ulceration or bleeding, such as oral corticosteroids, anticoagulants such as warfarin, selective serotonin-reuptake inhibitors or anti-platelet agents such as aspirin.

When GI bleeding or ulceration occurs in patients receiving RUPAN200, the treatment should be withdrawn.

NSAIDs should be given with care to patients with a history of gastrointestinal disease (ulcerative colitis, Crohn’s disease) as their condition may be exacerbated.

Caution is required in patients with renal, hepatic or cardiac impairment since the use of NSIADs may result in deterioration of renal function. The dose should be kept as low as possible and renal function should be monitored in these patients.

Long term administration of ibuprofen, as with other NSAIDs, may cause alterations to renal pathology such as acute interstitial nephritis with haematuria, proteinuria and, occasionally nephrotic syndrome. Patients in whom a pre-renal condition causes real blood flow or blood volume reduction rely on renal prostaglandins to support renal perfusion. Administration of a NSAID to such patients may precipitate overt renal decompensation due to a dose dependent reduction in prostaglandin formation. The risk of this is highest in patients with heart failure, hepatic dysfunction, renal dysfunction, on diuretics and the elderly. Recovery to pre-treatment state usually follows therapy discontinuation.

Patients with significantly impaired renal function should be closely monitored, possibly with reduced dosage to prevent drug accumulation, and, as with other high renal dysfunction risk patients, renal function should be monitored periodically during long term therapy.

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 NSAIDs therapy.

Clinical trial data suggest that use of ibuprofen, particularly at a high dose (2400mg/daily) and in long term treatment may be associated with a small increased risk of arterial thrombotic events (for example myocardial infarction or stroke). Overall, epidemiological studies do not suggest that low dose ibuprofen (e.g.<1200mg daily) is associated with an increased risk of myocardial infarction.

Patients with uncontrolled hypertension, congestive heart failure, established ischaemia heart disease, peripheral arterial disease, and/or cerebrovascular disease should only be treated with ibuprofen after careful consideration. Similar consideration should be made before for cardiovascular events (e.g. hypertension, hyperlipidaemia, diabetes mellitus, and smoking).

As with other NSAIDs, platelet aggregation is inhibited by ibuprofen. As a result, bleeding time may be prolonged, the effect of which may be exaggerated in patients with underlying haemostatic defects. Ibuprofen should be used with caution in patients on anti-coagulant therapy or with intrinsic coagulation defects.

Ibuprofen should be used with extreme caution in patients with bronchial asthma; There are reports of fatal asthmatic and anaphylactic reactions. Approximately 10% of pre-existing asthmatic patients may have aspirin sensitive asthma. In such patients, use of aspirin or cross reacting non-steroidal anti-inflammatory drugs has been associated with severe, and sometimes fatal, bronchospasm. Such patients should not receive ibuprofen, and it should be administered with caution to all patients with pre-existing asthma.

Allergic reactions, including anaphylactoid/anaphylactic reactions, can occur without previous exposure to ibuprofen.

Serious skin reaction, some of them fatal, including exfoliative dermatitis, Stevens-Johnson syndrome, and toxic epidermal necrolysis, have been reported very rarely in association with the use of NSAIDs. Patients appear to be at highest risk of these reactions early in the course therapy, the onset of the reaction occurring in the majority of the cases within the first month of treatment. RUPAN 200 should be discontinued at the first appearance of skin rash, mucosal lesions, or any other sign of hypersensitivity.

The anti-inflammatory and anti-pyretic activity of ibuprofen may diminish inflammation and fever, rendering detection and diagnosis of presumed non infections/inflammatory conditions more difficult.

Discontinuation of therapy is indicated in patients reporting colour vision changes, blurring/diminished vision or scotomata.

Ibuprofen use in the elderly has been associated with cognitive dysfunction.

Patients should be encouraged to report signs or symptoms of gastro-intestinal bleeding or ulceration, vision changes, oedema or weight gain and skin rash.

The use of RUPAN200 may impair female fertility and is not recommended is women attempting to conceive.in women who have difficulties conceiving or who are undergoing investigation of infertility, withdraw of RUPAN200 should be considered.