Relcofen (Ibuprofen)

1. Name Of The Medicinal Product

IBUPROFEN TABLETS BP 200mg and 400mg

2. Qualitative And Quantitative Composition

Ibuprofen Tablets BP 200mg:

Each tablet contains 200mg Ibuprofen PhEur.

Ibuprofen Tablets BP 400mg:

Each tablet contains 400mg Ibuprofen PhEur.

3. Pharmaceutical Form

Pink sugar-coated tablets.

4. Clinical Particulars

4.1 Therapeutic Indications

POM product:

Ibuprofen is a non-steroidal anti-inflammatory agent with analgesic and antipyretic activity. It is indicated for:

1) The treatment of rheumatoid arthritis, osteoarthritis, ankylosing spondylitis and other non-rheumatoid (seronegative) arthropathies.

2) The treatment of non-articular rheumatic conditions and soft-tissue injuries including capsulitis, tenosynovitis, bursitis, low-back pain, strains and sprains.

P product (Relcofen):

For the relief of rheumatic and muscular pain, backache, migraine, headache, period pain, neuralgia, dental pain, feverishness, symptoms of colds and influenza.

4.2 Posology And Method Of Administration

Posology

POM product:

Adults and children over 12 years: The recommended dosage is 1200-1800mg daily in divided doses. In acute or severe conditions the dosage may be increased until the acute phase has been brought under control, providing the dosage does not exceed 2400mg in any 24 hour period. The 600mg tablet offers a convenient dosage form where higher dosages are required. Some patients may be maintained on 600-1200mg daily.

Elderly: The elderly are at increased risk of the serious consequences of adverse reactions. If an NSAID is considered necessary, the lowest dose should be used and the patient should be monitored for GI bleeding for 4 weeks following initiation of NSAID therapy.

Children under 12 years: Not recommended.

P product (Relcofen):

Dosage: Adults, the elderly and children over 12 years: 1 tablet three times a day swallowed whole with water. The dose should not be repeated more frequently than every four hours and no more than 3 tablets in any 24 hour period. To be taken preferably with or after food.

Not suitable for children under 12 years.

Method of Adminstration

For oral use.

4.3 Contraindications

A known hypersensitivity to ibuprofen or any other ingredients in the product; patients with a known history of, or active, peptic ulceration. Ibuprofen should not be given to patients in whom aspirin or other NSAIDs induce the symptoms of asthma, rhinitis, angioedema or urticaria.

4.4 Special Warnings And Precautions For Use

Bronchospasm may be precipitated in patients suffering from, or with a previous history of, bronchial asthma; therefore ibuprofen should be used with extreme caution in these patients. Fluid retention and oedema have been reported in association with ibuprofen; therefore the drug should be used with caution in patients with a history of cardiac decompensation or hypertension.

Undesirable effects may be minimised by using the minimum effective dose for the shortest possible duration.

The elderly are at increased risk of the serious consequences of adverse reactions.

Ibuprofen should be given under close supervision to patients with a history of upper gastrointestinal tract disease.

As with other NSAIDs, long-term administration of ibuprofen to animals has resulted in renal papillary necrosis and other abnormal renal pathology. In humans, there have been reports of acute interstitial nephritis with haematuria, proteinuria, and occasionally nephrotic syndrome.

A second form of renal toxicity has been seen in patients with prerenal conditions leading to a reduction in renal blood flow or blood volume, where the renal prostaglandins have a supportive role in the maintenance of renal perfusion. In these patients, administration of a NSAID may cause a dose dependent reduction in prostaglandin formation and may precipitate overt renal decompensation. Patients at greatest risk of this reaction are those with impaired renal function, heart failure, liver dysfunction, those taking diuretics and the elderly. Cessation of NSAID therapy is typically followed by recovery to the pre-treatment state.

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

OTC & POM Label Warning

The label will state: Do not use if you have ever had a stomach ulcer or are allergic to ibuprofen or aspirin. If you are allergic to are taking any other painkiller, pregnant, or suffer from asthma speak to your doctor before taking ibuprofen. Do not exceed the stated dose. Keep out of the reach of children. If symptoms persist, consult your doctor.

4.5 Interaction With Other Medicinal Products And Other Forms Of Interaction

In therapeutic doses, no evidence of significant interactions with other commonly used drugs have yet been observed. In common with other NSAIDs, however, ibuprofen should be used with caution in patients receiving oral anticoagulants and diuretics, including frusemide and thiazides. NSAIDs may diminish the effect of anti-hypertensives.

Ibuprofen has been shown to produce a clinically relevant elevation of plasma lithium levels and a reduction in renal lithium clearance in a volunteer study. This effect has been attributed to inhibition of renal prostaglandin synthesis. Therefore, when ibuprofen and lithium are concurrently administered, patients should be carefully observed for signs of lithium toxicity.

Cardiac glycosides: NSAIDs may exacerbate cardiac failure, reduce GFR and increase plasma cardiac glycoside levels.

Methotrexate: Decreases elimination of methotrexate.

Cyclosporin: increased risk of nephrotoxicity with NSAIDs.

Mifepristone: NSAIDs should not be used for 8-12 days after mifepristone administration as NSAIDs can reduce the effects of mifepristone.

Other analgesics: Avoid concomitant use of two or more NSAIDs.

Corticosteroids: Increased risk of GI bleeding.

Quinolone antibiotics: Animal data indicate that NSAIDs can increase the risk of convulsions associated with quinolone antibiotics. Patients taking NSAIDs and quinolones may have an increased risk of developing convulsions.

4.6 Pregnancy And Lactation

Ibuprofen does not appear to be teratogenic in animals; however, the use of ibuprofen in pregnancy should, if possible, be avoided. Congenital abnormalities have been reported in association with ibuprofen administration in man; however, these are low in frequency and do not appear to follow any discernible pattern. Due to the known effects of NSAIDs on the foetal cardiovascular system (closure of the ductus arteriosus), use during late pregnancy should be avoided. As with other drugs known to inhibit prostaglandin synthesis, an increased incidence of dystocia and delayed parturition occurred in rats. The onset of labour may be delayed and duration of labour increased. Ibuprofen appears in breast-milk in very low concentration and is unlikely to adversely affect the breast-fed infant.

4.7 Effects On Ability To Drive And Use Machines

None known.

4.8 Undesirable Effects

Gastrointestinal: abdominal pain, nausea and dyspepsia, occasionally peptic ulcer and gastrointestinal haemorrhage, vomiting, diarrhoea, melaena, haemetemesis, ulcerative stomatitis have been reported following administration. Less frequently, gastritis, duodenal ulcer, gastric ulcer and gastrointestinal perforation have been observed.

Hypersensitivity: hypersensitivity reactions have been reported following treatment with NSAIDs. These may consist of (a) non-specific allergic reactions and anaphylaxis, (b) respiratory tract reactivity comprising asthma, aggravated asthma, bronchospasm or dyspnoea, or (c) assorted skin disorders, including rashes of various types, pruritis, urticaria, purpura, angiodema and, less commonly, bullous dermatoses (including epidermal necrolysis and erythema multiforme).

Cardiovascular: oedema has been reported in association with NSAID treatment.

Other: other adverse effects reported less commonly include:

Renal: nephrotoxicity in various forms, including interstitial nephritis, nephrotic syndrome and renal failure.

Hepatic: abnormal liver function, hepatitis and jaundice.

Neurological and special senses: visual disturbances, optic neuritis, headaches, paraesthesia, depression, confusion, hallucinations, tinnitus, vertigo, dizziness, malaise, fatigue and drowsiness.

Haematological: thrombocytopenia, neutropenia, agranulocytosis, aplastic anaemia and haemolytic anaemia.

Dermatological: photosensitivity.

Other effects: lupus erythematosus syndrome with aseptic meningitis.

4.9 Overdose

Symptoms of headache, vomiting, drowsiness and hypotension.

There is no specific antidote to ibuprofen. Gastric lavage may be carried out and, if necessary, correction of serum electrolytes.

5. Pharmacological Properties

5.1 Pharmacodynamic Properties

Ibuprofen has analgesic, antipyretic and anti-inflammatory properties. Ibuprofen inhibits prostaglandin synthesis.

Ibuprofen has prominent anti-inflammatory effect in addition to having analgesic and antipyretic actions. The analgesic effects of ibuprofen are due to both a peripheral and a central effect, and are distinct from its property as an anti-inflammatory drug. Ibuprofen is a potent inhibitor of the enzyme cyclo-oxygenase which thus results in a marked reduction in prostaglandin synthesis.

Ibuprofen also inhibits the synthesis of some lipoxygenase products, especially 11 and 15-monohydroxyeicosatetranoic acid (HETE) but it has no effect on the generation of 5- HETE and leukotriene B4.

Ibuprofen also inhibits the migration of polymorphonuclear leucocytes but the role of this in its anti-inflammatory action is not clear.

Inhibition of prostaglandin biosynthesis prevents their hyperalgesic effect upon sensory nerves. Inhibition of vasodilator prostanoid formation (PGE) diminishes the vascularity and transudation of fluid which are two of the principal manifestations of inflammation.

5.2 Pharmacokinetic Properties

Ibuprofen is rapidly absorbed following administration and is rapidly distributed throughout the whole body. The excretion is rapid and complete via the kidneys.

Maximum plasma concentrations are reached 45 minutes after ingestion if taken on an empty stomach. When taken with food peak levels are observed at 1 to 2 hours. These times may vary with different dosage forms.

The half-life of ibuprofen is about 2 hours.

In limited studies, ibuprofen appears in the breast milk in very low concentrations.

About 1% is excreted in urine as unchanged ibuprofen and about 14% as conjugated ibuprofen.

5.3 Preclinical Safety Data

Not applicable.

6. Pharmaceutical Particulars

6.1 List Of Excipients

Also contains: beeswax, carmellose sodium, colloidal silica, dimethicone, gelatin, hydrochloric acid, kaolin, shellac, sodium lauryl sulphate, sucrose, E127, E170, E171, E172, E211, E322, E414, E460, E463, E553.

6.2 Incompatibilities

None known.

6.3 Shelf Life

Shelf-life

Three years from the date of manufacture.

Shelf-life after dilution/reconstitution

Not applicable.

Shelf-life after first opening

Not applicable.

6.4 Special Precautions For Storage

Store below 25°C in a dry place.

6.5 Nature And Contents Of Container

The product containers are rigid injection moulded polypropylene or injection blow-moulded polyethylene containers with polyfoam wad or polyethylene ullage filler and snap-on polyethylene caps or child-resistant closures; in case any supply difficulties should arise the alternative is amber glass containers with screw caps. An alternative closure for polyethylene containers is a polypropylene, twist on, push down and twist off child-resistant, tamper-evident lid.

OTC packs include a child-resistant closure.

The product may also be supplied in blister packs in cartons:

a) Carton: Printed carton manufactured from white folding box board.

b) Blister pack: (i) 250µm white rigid PVC. (ii) Surface printed 20µm hard temper aluminium foil with 5-7g/M² PVC and PVdC compatible heat seal lacquer on the reverse side.

Pack sizes: 28s, 56s, 60s, 84s, 100s, 112s, 168s, 250s, 500s, 1000s.

OTC pack sizes: 12s, 20s, 24s, 48s, 96s.

Product may also be supplied in bulk packs, for reassembly purposes only, in polybags contained in tins, skillets or polybuckets filled with suitable cushioning material. Bulk packs are included for temporary storage of the finished product before final packaging into the proposed marketing containers.

Maximum size of bulk packs: 28,000 (200mg); 16,000 (400mg).

6.6 Special Precautions For Disposal And Other Handling

Not applicable.

Administrative Data

7. Marketing Authorisation Holder

Alpharma Limited (Trading style: Alpharma, Cox Pharmaceuticals)

Whiddon Valley

BARNSTAPLE

N Devon EX32 8NS

8. Marketing Authorisation Number(S)

PL 0142/0304 (200mg)

PL 0142/0305 (400mg)

9. Date Of First Authorisation/Renewal Of The Authorisation

26.10.90 (Renewed 1/00)

10. Date Of Revision Of The Text

October 2002