Ibuprofen 200mg Tablets
SUMMARY OF PRODUCT CHARACTERISTICS
1. NAME OF THE MEDICINAL PRODUCT
Ibuprofen 200mg Coated Tablets
2 QUALITATIVE AND QUANTITATIVE COMPOSITION
Ibuprofen 200.00 mg
3 PHARMACEUTICAL FORM
Coated tablet
Round white sugar coated tablet.
4 CLINICAL PARTICULARS
4.1 Therapeutic indications
POM:
For relief of mild to moderate rheumatic pain, muscular pain, headache, backache, migraine, period pain, dental pain and neuralgia. Effective in the relief of feverishness.
4.2 Posology and method of administration
For oral administration
To be taken preferably with or after food.
P & GSL:
For short-term use only.
The minimum effective dose should be used for the shortest time necessary to relieve symptoms. The patient should consult a doctor if symptoms persist or worsen, or if the product is required for more than ten days.
Adults, the elderly and children over 12 years 200 mg — 400 mg, up to three times a day as required.
Leave at least four hours between doses and do not take more than 1200 mg in any 24 hour period.
Do not give to children under 12 years of age, except on the advice of a doctor.
POM:
Undesirable effects may be minimised by using the lowest effective dose for the shortest duration necessary to control symptoms (see section 4.4).
Adults and Children over 12 years
One or two tablets - every 4 hours, not more than 3 times in any 24 hour period.
Do not exceed 6 tablets daily
Do not give to children under 12 years of age, except on the advice of a doctor.
Elderly: The elderly are at increased risk of the serious consequences of adverse reactions. If an NSAID is considered necessary, the lowest effective dose should be used and for the shortest possible duration. The patient should be monitored regularly for gastrointestinal bleeding during NSAID therapy.
4.3 Contraindications
Ibuprofen should not be administered to patients with bleeding disorders.
Hypersensitivity to any of the constituents.
NSAIDs are contraindicated in patients who have previously shown hypersensitivity reactions (e.g. asthma, rhinitis, angioedema or urticaria) in response to ibuprofen, aspirin or other non-steroidal anti-inflammatory drugs.
Severe hepatic and renal failure (See section 4.4 — Special warnings and precautions for use).
During the last trimester of pregnancy (See section 4.6 — Pregnancy and lactation).
Active or previous peptic ulcer.
History of upper gastrointestinal bleeding or perforation related to previous NSAIDs therapy.
Use with concomitant NSAIDs including cyclo-oxygenase-2 specific inhibitors (See section 4.5 Interactions).
Severe heart failure.
4.4 Special warnings and precautions for use
In all patients:
Undesirable effects may be minimised by using the lowest effective dose for the shortest duration necessary to control symptoms (see section 4.2, and GI and cardiovascular risks below).
Elderly:
The elderly have an increased frequency of adverse reactions to NSAIDs, especially gastrointestinal bleeding and perforation which may be fatal (See section 4.2 Posology and administration).
Respiratory disorders:
Caution is required if administered to patients suffering from, or with a previous history of, bronchial asthma since NSAIDs have been reported to precipitate bronchospasm in such patients.
Renal and Hepatic Impairment:
The administration of an NSAID may cause a dose dependent reduction in prostaglandin formation and precipitate renal failure. Patients at greatest risk of this reaction are those with impaired renal function, cardiac impairment, liver dysfunction, those taking diuretics and the elderly. The dose should be kept as low as possible and renal function should be monitored in these patients. Hepatic impairment is also associated with an increased risk of gastro-intestinal bleeding. (See also Section 4.3 —Contraindications).
Caution in patients with a history of renal or hepatic impairment, as fluid retention and oedema have been reported in association with NSAID therapy.
Cardiovascular and cerebrovascular effects:
Appropriate monitoring and advice are required for patients with a history of hypertension and/or mild to moderate congestive heart failure as fluid retention and oedema have been reported in association with NSAID therapy.
Clinical trial data suggest that use of ibuprofen, particularly at a high dose (2400 mg 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. < 1200 mg daily) is associated with an increased risk of myocardial infarction.
Patients with uncontrolled hypertension, congestive heart failure, established ischaemic heart disease, peripheral arterial disease, and/or cerebrovascular disease should only be treated with ibuprofen after careful consideration. Similar consideration should be made before initiating longer-term treatment of patients with risk factors for cardiovascular events (e.g. hypertension, hyperlipidaemia, diabetes mellitus, smoking).
Gastrointestinal bleeding, ulceration and perforation:
GI 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 GI events.
Patients with a history of GI toxicity, particularly when elderly, should report any unusual abdominal symptoms (especially GI bleeding) particularly in the initial stages of treatment.
Caution should be advised in patients receiving concomitant medications which could increase the risk of gastrotoxicity or bleeding, such as corticosteroids, or anticoagulants such as warfarin or anti-platelet agents such as aspirin (See section 4.5 Interactions).
When GI bleeding or ulceration occurs in patients receiving ibuprofen, 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 these conditions may be exacerbated (See section 4.8 — Undesirable effects).
SLE and mixed connective tissue disease:
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 — Undesirable effects).
Female fertility:
The use of ibuprofen 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 ibuprofen should be considered.
P & GSL :
The label will include:
Read the enclosed leaflet before taking this product.
Do not take if you
• have or have ever had a stomach ulcer, perforation or bleeding
• are allergic to ibuprofen or any other ingredient of the product, aspirin or other related painkillers
• are taking other NSAID) painkillers, or aspirin with a daily dose above 75 mg
• are in the last three months of pregnancy
Speak to a pharmacist or your doctor before taking this product if you
• have asthma, liver, heart, kidney or bowel problems
• are in the first six months of your pregnancy
If symptoms persist or worsen, consult your doctor.
Do not exceed the stated dose. Keep out of reach of children
4.5 Interaction with other medicinal products and other forms of interaction
Care should be taken in patients treated with any of the following drugs as interactions have been reported in some patients.
Other analgesics: Avoid concomitant use of two or more NSAIDs, including aspirin (unless low-dose aspirin, not above 75mg daily, has been advised by a doctor) as this may increase the risk of adverse effects (See section 4.3 Contraindications).
Experimental data suggest that ibuprofen may inhibit the effect of low dose aspirin on platelet aggregation when they are dosed concomitantly. However, the limitations of these data and the uncertainties regarding extrapolation of ex-vivo data to the clinical situation imply that no firm conclusions can be made for regular ibuprofen use, and no clinically relevant effect is considered to be likely for occasional ibuprofen use (see section 5.1).
Alcohol: Increased risk of gastro-intestinal bleeding or ulceration in susceptible patients.
Anticoagulants: NSAIDs may enhance the effects of anticoagulants such as warfarin and heparin (See section 4.4 — Special warnings and precautions for use).
Antidepressants: Moclobemide may enhance the effect of ibuprofen. Selective serotonin re-uptake inhibitors (SSRJs) may increase the risk of gastro-intestinal bleeding and ulceration.
Antidiabetics: May enhance the hypoglycaemic effects of sulphonylureas.
Antiepileptics: May enhance the effects of phenytoin by inhibiting its metabolism.
Antihypertensives: Reduced antihypertensive effect of antihypertensives, including ACE inhibitors, angiotensin-II antagonists, beta-blockers and vasodilators; increased monitoring of the effectiveness of antihypertensive therapy may be necessary. Increased risk of nephrotoxicity, renal impairment and hyperkalaemia with ACE inhibitors and of renal impairment and hyperkalaemia with angiotensin-II antagonists.
Antiplatelet drugs: Increased risk of bleeding with clopidogrel and ticlopidine.
Antivirals: Increased risk of haematological toxicity with zidovudine. There is evidence of an increased risk of haemarthroses and haematoma in HIV(+) haemophiliacs receiving concurrent treatment with zidovudine and ibuprofen.
Ritonavir may increase plasma concentrations of ibuprofen.
Cardiac glycosides: NSAIDs may exacerbate cardiac failure, reduce GFR and increase plasma glycoside levels.
Ciclosporin: Increased risk of nephrotoxicity.
Corticosteroids: Increased risk of gastro-intestinal ulceration and gastro-intestinal bleeding. (See section 4.4 — Special warnings and precautions for use)
Diuretics: Reduced diuretic and antihypertensive effects. Possibility of hyperkalaemia with potassium-sparing diuretics. Diuretics can increase the risk of nephrotoxicity of NSAlDs.
Lithium: Decreased elimination of lithium.
Methotrexate: Decreased elimination of methotrexate.
Mifepristone: NSAIDs should not be used for 8-12 days after mifepristone administration as NSAIDs can reduce the effect of mifepristone.
Muscle Relaxants: Reduced excretion of baclofen (increased risk of toxicity).
Pentoxyfylline: May increase risk of gastrointestinal bleeding; avoid concomitant use.
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.
Tacrolimus: Possible increased risk of nephrotoxicity when NSAIDs are given with tacrolimus.
4.6 Pregnancy and lactation
Congenital abnormalities have been reported in association with NSAID administration in man; however, these are low in frequency and do not appear to follow any discernible pattern. In view of the known effects of NSAIDs on the foetal cardiovascular system (risk of closure of the ductus arteriosus and persistent pulmonary hypertension in the neonate), use in the last trimester of pregnancy is contraindicated. The onset of labour may be delayed and the duration increased with an increased bleeding tendency in both mother and child. (See section 4.3 Contraindications). NSAIDs should not be used during the first two trimesters of pregnancy or labour unless the potential benefit to the patient outweighs the potential risk to the foetus.
Lactation:
In the limited studies so far available, NSAIDs can appear in breast milk in very low concentrations. NSAIDs should, if possible, be avoided when breastfeeding.
See section 4.4 Special warnings and precautions for use, regarding female fertility.
4.7 Effects on ability to drive and use machines
Undesirable effects such as dizziness, drowsiness, fatigue and visual disturbances are possible after taking NSAIDs. If affected, patients should not drive or operate machinery.
4.8 Undesirable effects
P & GSL
Hypersensitivity reactions have been reported and these may consist of:
a) non-specific allergic reactions and anaphylaxis
b) respiratory tract reactivity, e.g. asthma, aggravated asthma, bronchospasm or dyspnoea.
c) various skin reactions e.g., pruritus, urticaria,, angioedema and more rarely exfoliative and bullous dermatoses (including epidermal necrolysis and erythema multiforme).
The following list of adverse effects relates to those experienced with ibuprofen as OTC doses, for short term use. In the treatment of chronic conditions, under longterm treatment, additional adverse effects may occur.
Hypersensitivity reactions:
Uncommon: Hypersensitivity reactions with urticaria and pruritus.
Very rare: Severe hypersensitivity reaction. Symptoms could be: facial, tongue and laryngeal swelling, dyspnoea, tachycardia, hypotension, (anaphylaxis, angioedema or severe shock).
Exacerbation of asthma and bronchospasm.
Gastrointestinal:
Uncommon: abdominal pain, nausea and dyspepsia.
Rare: diarrhoea, flatulence, constipation and vomiting.
Very rare: peptic ulcer, perforation or gastrointestinal haemorrhage, sometimes fatal particularly in the elderly. Exacerbation of ulcerative colitis and Crohn’s disease (See section 4.4).
Nervous System: Uncommon: Headache
Renal:
Very rare: Acute renal failure, papillary necrosis, especially in long-term use, associated with increased serum urea and oedema.
Hepatic:
Very rare: liver disorders.
Haematological:
Very rare: Haematopoietic disorders (anaemia, leucopenia, thrombocytopenia, pancytopenia, agranulocytosis). First signs are: fever, sore throat, superficial mouth ulcers, flu-like symptoms, severe exhaustion, unexplained bleeding and bruising.
Skin:
Uncommon: Various skin rashes
Very rare: Severe forms of skin reactions such as erythema multiforme and epidermal necrolysis can occur.
Immune System:
In patients with existing auto-immune disorders (such as systemic lupus erythematosus, mixed connective tissues) during treatment with ibuprofen, single cases of symptoms of aseptic meningitis, such as stiff neck, headache, nausea, vomiting, fever or disorientation have been observed (See section 4.4)
POM:
Gastro-intestinal:
The most commonly-observed adverse events are gastrointestinal in nature. Peptic ulcers, perforation or GI bleeding, sometimes fatal, may occur, particularly in the elderly (See section 4.4). Nausea, vomiting, diarrhoea, flatulence, constipation, dyspepsia, abdominal pain, melaena, haematemesis, ulcerative stomatitis, exacerbation of colitis and Crohn’s disease (See section 4.4 Special warnings and precautions for use) have been reported following administration. Less frequently, gastritis and pancreatitis have been observed.
Hypersensitivity:
Hypersensitivity reactions have been reported following treatment with NSAIDs. These may consist of (a) fever, non-specific allergic reaction and anaphylaxis (b) respiratory tract reactivity comprising asthma, aggravated asthma, bronchospasm or dyspnoea, or (c) assorted skin disorders, including rashes of various types, pruritus, urticaria, purpura, angioedema and, more rarely, exfoliative and bullous dermatoses (including epidermal necrolysis,-erythema multiforme and Stevens Johnson syndrome).
Respiratory:
Bronchospasm in asthmatic patients, alveolitis.
Cardiovascular:
Oedema, hypertension, and cardiac failure, have been reported in association with NSAID treatment. Fluid retention may precipitate congestive heart failure in elderly patients. Clinical trial and epidemiological data suggest that use of ibuprofen, particularly at high dose (2400 mg daily), and in long term treatment may be associated with a small increased risk of arterial thrombotic events (for example myocardial infarction or stroke) (see section 4.4).
Other adverse events reported less commonly include:
Renal:
Prolonged excessive use may cause nephrotoxicity in various forms, including interstitial nephritis, haematuria, papillary necrosis, nephrotic syndrome and renal failure (especially with pre-existing renal impairment).
Hepatic:
Abnormal liver function, jaundice, hepatitis.
Neurological & special senses:
Visual disturbances, optic neuritis, headache, paraesthesia, reports of aseptic meningitis (especially in patients with existing auto-immune disorders, such as systemic lupus erythematosus, mixed connective tissue disease), with symptoms such as stiff neck, headache, nausea, vomiting, fever or disorientation (See section 4.4), depression, nervousness, insomnia, confusion, hallucinations, tinnitus, vertigo, dizziness, malaise, fatigue and drowsiness.
Haematological:
Thrombocytopenia, neutropenia, agranulocytosis, aplastic anaemia and haemolytic anaemia, prolonged bleeding time, eosinophilia.
Dermatological:
Photosensitivity has also been reported (see Hypersensitivity for other skin reactions).
4.9 Overdose
In children ingestion of more than 400 mg/kg may cause symptoms. In adults the dose response effect is less clear cut. The half-life in overdose is 1.5 — 3 hours.
Symptoms:
Most patients who have ingested clinically important amounts of NSAIDs will develop no more than nausea, vomiting, epigastric pain, or more rarely diarrhoea. Dizziness, tinnitus, fainting, headache and gastrointestinal bleeding are also possible. In more serious poisoning, toxicity is seen in the central nervous system, manifesting as drowsiness, occasionally excitation and disorientation or coma.
Occasionally patients develop convulsions. In serious poisoning metabolic acidosis may occur and the prothrombin time/INR may be prolonged, probably due to interference with the actions of circulating clotting factors. Acute renal failure and liver damage may occur. Exacerbation of asthma is possible in asthmatics.
Management:
Management should be symptomatic and supportive and include the maintenance of a clear airway and monitoring of cardiac and vital signs until stable. Consider oral administration of activated charcoal if the patient presents within one hour of ingestion of a potentially toxic amount. Alternatively, in adults, gastric lavage should be considered within one hour of ingestion of a potentially life-threatening overdose.
Good urine output should be ensured.
Renal and liver function should be closely monitored.
Patients should be observed for at least four hours after ingestion of potentially toxic amounts. Frequent or prolonged convulsions should be treated with intravenous diazepam or lorazepam. Give bronchodilators for asthma.
Other measures may be indicated by the patient’s clinical condition.
5 PHARMACOLOGICAL PROPERTIES
5.1 Pharmacodynamic properties
Ibuprofen is a phenylpropionic acid derivative which has analgesic anti-inflammatory and antipyretic actions.
Many possible mechanisms for the action of NSAIDS have been postulated. However, ibuprofen in common with other NSAIDS probably achieves its antiinflammatory effect through inhibition of prostoglandin synthesis at the site of the lesion, thereby preventing the sensitizing of tissue to other pain producing mediators (e.g. histamine, 5-hydroxytryptamine and bradykinin). Most NSAIDS delay normal platelet aggregation by inhibiting thromboxane A2 production.
Experimental data suggest that ibuprofen may inhibit the effect of low dose aspirin on platelet aggregation when they are dosed concomitantly. In one study, when a single dose of ibuprofen 400 mg was taken within 8 hours before or within 30 minutes after immediate release aspirin dosing (81 mg), a decreased effect of aspirin on the formation of thromboxane or platelet aggregation occurred. However, the limitations of these data and the uncertainties regarding extrapolation of ex vivo data to the clinical situation imply that no firm conclusions can be made for regular ibuprofen use, and no clinically relevant effect is considered to be likely for occasional ibuprofen use.
Pharmacokinetic properties
5.2
Ibuprofen is rapidly absorbed following administration and is rapidly distributed throughout the whole body. The excretion is rapid and complete via the kidneys. About 1% is excreted in urine as unchanged ibuprofen and about 14% as conjugated ibuprofen.
Maximum plasma concentrations are reached 45 minutes after ingestion if taken on an empty stomach. When taken with food, peak levels are observed after one to two hours. These times may vary with different dosage forms.
Ibuprofen is extensively bound to plasma proteins and has a half life of about two hours.
In limited studies, ibuprofen appears in the breast milk in very low concentrations.
5.3 Preclinical safety data
The only consistent pathological effect of repeated ibuprofen dose studies in experimental animals was ulceration of the gastrointestinal tract. No evidence of carcinogenicity has been seen in rats. Reproduction studies on white rabbits in the early part of pregnancy showed no treatment related abnormalities, similar satisfactory results were obtained with mice and rats. Cultures of lymphocytes from rheumatic patients taking ibuprofen showed no significant increase in chromosome aberrations.
6 PHARMACEUTICAL PARTICULARS
6.1 List of excipients
Colloidal anhydrous silica Starch (potato)
Povidone
Microcrystalline cellulose Alginic acid Magnesium stearate Sodium lauryl sulphate Sodium starch glycollate
Croscarmellose sodium
Coating Materials
PVAP sealcote (contains polyvinyl acetate phthalate & stearic acid)
Purified talc
Sucrose
Calcium carbonate Acacia
Titanium dioxide (E171)
Carnauba wax
6.2 Incompatibilities
None stated except as in ‘interactions with other medicaments’.
6.3 Shelf life
Three years from date of manufacture.
6.4 Special precautions for storage
Store in a dry place below 25°C
Protect from light
Keep out of the reach of children.
6.5 Nature and contents of container
Blister Pack
Tablets are packed individually in pre-moulded PVC film and sealed with aluminium foil. Pack sizes: 8, 12, 16 (GSL) 8, 12, 16, 24, 32, 48, 56, 64, 72, 84, 96 (P).
Bottles
Tablets are packed into-
Securitainers (polypropylene body & HDPE cap).
Pack sizes: 100, 250, 500, 560, 1000.
Tamper evident bottles (polypropylene body & HDPE child resistant cap). Pack sizes: 25, 50, 250, 500, 560, 1000.
6.6 Special precautions for disposal
Return any left over tablets to the Pharmacist.
7 MARKETING AUTHORISATION HOLDER
Wockhardt UK Ltd,
Ash Road North,
Wrexham,
LL13 9UF,
United Kingdom
8 MARKETING AUTHORISATION NUMBER(S)
PL 29831/0369
9 DATE OF FIRST AUTHORISATION/RENEWAL OF THE AUTHORISATION
14th November 2007
10 DATE OF REVISION OF THE TEXT
07/01/2009