Ibuprofen 600mg Tablets
SUMMARY OF PRODUCT CHARACTERISTICS
1 NAME OF THE MEDICINAL PRODUCT
Ibuprofen 600mg Tablets BP
2 QUALITATIVE AND QUANTITATIVE COMPOSITION
Ibuprofen 600mg.
For excipients, see 6.1.
3 PHARMACEUTICAL FORM
Film coated tablet.
Pink oblong film coated tablet.
4 CLINICAL PARTICULARS
4.1 Therapeutic indications
Relief of mild to moderate pain; rheumatoid arthritis; ankylosing spondylitis; osteoarthritis; sero-negative arthropathies; pain relief of peri-articular disorders; pain relief of soft tissue injuries.
4.2 Posology and method of administration
For oral administration. Swallow the tablets with a drink of water, preferably with or after food.
Adults: Take one tablet to start, followed by one tablet every 6 hours if necessary. Do not take more than 4 tablets in any 24 hour period.
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 GI bleeding during NSAID therapy.
Children: Not recommended.
Undesirable effects may be minimised by using the lowest effective dose for the shortest duration necessary to control symptoms (see section 4.4)
4.3 Contraindications
Contraindicated in those with known hypersensitivity to ibuprofen or to any of the other constituents. Should not be given to patients with active, or history of recurrent peptic ulcer/haemorrhage (two or more distinct episodes of proven ulceration or bleeding) and to patients in whom ibuprofen, aspirin or other non-steroidal anti-inflammatory drugs induce hypersensitivity reactions (e.g. asthma, rhinitis, angioedema or urticaria).
Severe heart failure (NYHA Class IV), hepatic failure and renal failure (see section 4.4).
During the last trimester of pregnancy (see section 4.6)
History of gastrointestinal bleeding or perforation, related to previous NSAIDs therapy.
Ibuprofen should not be given to patients with conditions involving an increased tendency to bleeding.
4.4 Special warnings and precautions for use
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).
As with other NSAIDs, ibuprofen may mask the signs of infection.
The use of ibuprofen with concomitant NSAIDs including cyclooxygenase-2 selective inhibitors should be avoided due to the increased risk of ulceration or bleeding (see section 4.5).
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).
Paediatric _ population
There is a risk of renal impairment in dehydrated children and adolescents. 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 cause bronchospasm in such patients.
Cardiovascular, 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. Renal function should be monitored in these patients (see also section 4.3).
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 studies suggest that use of ibuprofen, particularly at a high dose (2400mg/day) 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/day) is associated with an increased risk of arterial thrombotic events.
Patients with uncontrolled hypertension, congestive heart failure (NYHA II-III), established ischaemic heart disease, peripheral arterial disease, and/or cerebrovascular disease should only be treated with ibuprofen after careful consideration and high doses (2400 mg/day) should be avoided.
Careful consideration should also be exercised before initiating long-term treatment of patients with risk factors for cardiovascular events (e.g. hypertension, hyperlipidaemia, diabetes mellitus, smoking), particularly if high doses of ibuprofen (2400 mg/day) are required.
Renal effects
Caution should be used when initiating treatment with ibuprofen in patients with considerable dehydration.
As with other NSAIDs, long-term administration of ibuprofen has resulted in renal papillary necrosis and other renal pathologic changes. Renal toxicity has also been seen in patients in whom renal prostaglandins have a compensatory role in the maintenance of renal perfusion. In these patients administration of an NSAID may cause a dose-dependent reduction in prostaglandin formation and, secondarily, in renal blood flow, which 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 ACE inhibitors and the elderly. Discontinuation of NSAID therapy is usually followed by recovery to the pretreatment state.
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.
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 (see section 4.3), 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 (see below and section 4.5).
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 ulceration or bleeding, such as oral corticosteroids, anticoagulants such as warfarin, selective serotonin-reuptake inhibitors or anti-platelet agents such as aspirin (see section 4.5)
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).
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 below and section 4.8).
Dermatological:
Serious skin reactions, 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 (see section 4.8). Patients appear to be at highest risk for 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. Ibuprofen should be discontinued at the first appearance of skin rash, mucosal lesions, or any other sign of hypersensitivity.
Haematological effects
Ibuprofen, like other NSAIDs, can interfere with platelet aggregation and has been shown to prolong bleeding time in normal subjects.
Aseptic meningitis
Aseptic meningitis has been observed on rare occasions in patients on ibuprofen therapy. Although it is probably more likely to occur in patients with systemic lupus erythematosus and related connective tissue diseases, it has been reported in patients who do not have an underlying chronic disease.
Impaired 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.
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.
Anti-hypertensives, beta-blockers and diuretics: NSAIDs may reduce the effect of anti-hypertensives, such as ACE inhibitors, beta-blockers and diuretics.
Diuretics can also increase the risk of nephrotoxicity of NSAIDs.
Cardiac glycosides: NSAIDs may exacerbate cardiac failure, reduce GFR and increase plasma cardiac glycoside levels.
Colestyramine: The concomitant administration of ibuprofen and colestyramine may reduce the absorption of ibuprofen in the gastrointestinal tract. However, the clinical significance is unknown.
Lithium: decreased elimination of lithium.
Methotrexate: NSAIDs may inhibit the tubular secretion of methotrexate and reduce clearance of methotrexate.
Ciclosporin: increased risk of nephrotoxicity.
Mifepristone: A decrease in the efficacy of the medicinal product can theoretically occur due to the antiprostaglandin properties of NSAIDs. Limited evidence suggests that co-administration of NSAIDs on the day of prostaglandin administration does not adversely influence the effects of mifepristone or the prostaglandin on cervical ripening or uterine contractility and does not reduce the clinical efficacy of medicinal termination of pregnancy
Other analgesics and cyclooxygenase-2 selective inhibitors: avoid concomitant use of two or more NSAIDs, including Cox-2 inhibitors as this may increase the risk of adverse effects (see section 4.4).
Acetylsalicylic acid: Concomitant administration of ibuprofen and acetylsalicylic acid is not generally recommended because of the potential of increased adverse effects.
Experimental data suggest that ibuprofen may competitively inhibit the effect of low dose acetylsalicylic acid on platelet aggregation when they are dosed concomitantly. Although there are uncertainties regarding extrapolation of these data to the clinical situation, the possibility that regular, long-term use of ibuprofen may reduce the cardioprotective effect of low-dose acetylsalicylic acid cannot be excluded. No clinically relevant effect is considered to be likely for occasional ibuprofen use (see section 5.1).
Corticosteroids: increased risk of gastrointestinal bleeding or ulceration with NSAIDs (see section 4.4).
Anticoagulants: NSAIDs may enhance the effects of anticoagulants, such as warfarin (see section 4.4).
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.
Sulfonylureas: NSAIDs may potentiate the effects of sulfonylurea medications. There have been rare reports of hypoglycaemia in patients on sulfonylurea medications receiving ibuprofen.
Anti-platelet agents and selective serotonin reuptake inhibitors (SSRIs): increased risk of gastrointestinal bleeding with NSAIDs (see section 4.4).
Tacrolimus: possible increased risk of nephrotoxicity when NSAIDs are given with tacrolimus.
Zidovudine: increased risk of haematological toxicity when NSAIDs are given with zidovudine. There is evidence of an increased risk of haemarthroses and haematoma in HIV (+) haemophiliacs receiving concurrent treatment with zidovudine and ibuprofen.
Aminoglycosides: NSAIDs may decrease the excretion of aminoglycosides.
Herbal extracts: Ginkgo biloba may potentiate the risk of bleeding with NSAIDs.
CYP2C9 inhibitors: Concomitant administration of ibuprofen with CYP2C9 inhibitors may increase the exposure to ibuprofen (CYP2C9 substrate). In a study with voriconazole and fluconazole (CYP2C9 inhibitors), an increased S(+)-ibuprofen exposure by approximately 80 to 100% has been shown. Reduction of the ibuprofen dose should be considered when potent CYP2C9 inhibitors are administered concomitantly, particularly when high-dose ibuprofen is administered with either voriconazole or fluconazole.
4.6 Pregnancy and lactation
Pregnancy:
Congenital abnormalities have been reported in association with NS AID 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), use in the last trimester of pregnancy is contraindicated. The onset of labour may be delayed and duration of labour increased with an increased bleeding tendency in both mother and child (see section 4.3). 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 concentration. 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
Infections and infestations: rhinitis and 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).
Blood and lymphatic system disorders: leucopenia, thrombocytopenia, pancytopenia, neutropenia, agranulocytosis, aplastic anaemia and haemolytic anaemia.
Immune system disorders: 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, pruritus, urticaria, purpura, angiodema and more rarely exfoliative and bullous dermatoses (including Stevens-Johnson syndrome, toxic epidermal necrolysis and erythema multiforme).
Psychiatric disorders: insomnia, anxiety, depression, confusion, hallucinations.
Nervous system disorders: optic neuritis, headaches, paraesthesia, dizziness and drowsiness.
Eye disorders: visual disturbances, toxic optic neuropathy.
Ear and labyrinth disorders: hearing impaired, tinnitus and vertigo.
Cardiac disorders and vascular disorders: oedema, hypertension and cardiac failure have been reported in association with NSAID treatment.
Clinical studies suggest that use of ibuprofen, particularly at a high dose (2400 mg/day) may be associated with a small increased risk of arterial thrombotic events (for example myocardial infarction or stroke) (see section 4.4).
Gastrointestinal disorders: the most commonly observed adverse events are gastro- intestinal in nature. Peptic ulcers, perforation or GI bleeding, sometimes fatal, particularly in the elderly, may occur (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) have been reported following administration. Less frequently, gastritis has been observed. Gastrointestinal perforation has been rarely reported with ibuprofen use. Pancreatitis has also been reported very rarely.
Hepatobiliary disorders: abnormal liver function, hepatic failure, hepatitis and jaundice.
Skin and subcutaneous tissue disorders: various skin rashes, bullous reactions including Stevens-Johnson syndrome and toxic epidermal necrolysis (very rare). Photosensitivity.
Renal and urinary disorders: impaired renal function and nephrotoxicity in various forms, including interstitial nephritis, nephrotic syndrome, renal failure, papillary necrosis.
General disorders and administration site conditions: malaise, fatigue. Reporting of suspected adverse reactions:
Reporting suspected adverse reactions after authorisation of the medicinal product is important. It allows continued monitoring of the benefit/risk balance of the medicinal product. Healthcare professionals are asked to report any suspected adverse reactions via the Yellow Card Scheme at: www.mhra.gov.uk/yellowcard.
4.9 Overdose symptoms, emergency procedures, antidotes
Toxicity
Signs and symptoms of toxicity have generally not been observed at doses below 100 mg/kg in children or adults. However, supportive care may be needed in some cases. Children have been observed to manifest signs and symptoms of toxicity after ingestion of 400 mg/kg or greater.
a) Symptoms
Most patients who have ingested significant amounts of ibuprofen will manifest symptoms within 4 to 6 hours. The most frequently reported symptoms of overdose include nausea, vomiting, abdominal pain, lethargy and drowsiness. Central nervous system (CNS) effects include headache, tinnitus, dizziness, convulsion, and loss of consciousness. Nystagmus, metabolic acidosis, hypothermia, renal effects, gastrointestinal bleeding, coma, apnoea, diarrhoea and depression of the CNS and respiratory system have also been rarely reported. Disorientation, excitation, fainting and cardiovascular toxicity, including hypotension, bradycardia and tachycardia have been reported. In cases of significant overdose, renal failure and liver damage are possible. Large overdoses are generally well tolerated when no other drugs are being taken.
b) Therapeutic measures
Patients should be treated symptomatically as required.
Within one hour of ingestion of a potentially toxic amount, activated charcoal should be considered. 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. Other measures may be indicated by the patients clinical condition.
5.1 Pharmacodynamic properties
Ibuprofen is a phenylpropionic acid derivative which has analgesic, antiinflammatory and antipyretic actions.
Experimental data suggest that ibuprofen may competitively inhibit the effect of low dose acetylsalicylic acid on platelet aggregation when they are dosed concomitantly. Some pharmcodynamic studies show that when single doses of ibuprofen 400mg were taken within 8 h before or within 30 min after immediate release acetylsalicyclic acid dosing (81mg), a decreased effect of acetylsalicylic acid on the formation of thromboxane or platelet aggregation occurred. Although there are uncertainties regarding extrapolation of these data to the clinical situation, the possibility that regular, long-term use of ibuprofen may reduce the cardioprotective effect of low-dose acetylsalicylic acid cannot be excluded. No clinically relevant effect is considered to be likely for occasional ibuprofen use (see section 4.5).
5.2 Pharmacokinetic properties
Ibuprofen is absorbed from the gastro-intestinal tract and peak plasma concentrations occur about 1 to 2 hours after ingestion. It is extensively bound to plasma proteins and has a half-life of about 2 hours. It is rapidly excreted in the urine as metabolites and their conjugates. About 1% is excreted in the urine as unchanged ibuprofen and about 14% as conjugated ibuprofen.
5.3 Preclinical safety data
No data of relevance which is additional to that already included in other sections of the SPC.
6 Pharmaceutical particulars
6.1 List of Excipients
Maize Starch
Microcrystalline Cellulose Croscarmellose Sodium Povidone
Colloidal Anhydrous Silica Alginic Acid Sodium Laurilsulfate Sodium Starch Glycollate Magnesium Stearate
Coating:
(Using individual coating powder ingredients) :
Hydroxypropylcellulose Hydroxypropylmethylcellulose Polyethylene Glycol 400 Erythrosine Aluminium Lake (E127)
Titanium Dioxide (E171)
(Using single ingredient coating powder):
Opadry 20B640005 Pink [contains Hydroxypropylcellulose, Hydroxypropylmethylcellulose, Polyethylene Glycol 400, Erythrosine Aluminium Lake (E127) and Titanium Dioxide (E171)]
6.2 Incompatibilities
Not applicable.
6.3 Shelf life
3 years.
6.4 Special precautions for storage
Do not store above 25 °C. Store in the original container.
Keep the container tightly closed.
Blister: Do not store above 25°C. Store in the original package.
6.5 Nature and contents of container
PP or HDPE tablet containers of 50, 100 250 or 500 tablets.
Plastic tablet containers of 50 tablets.
Blister comprised of Aluminium foil (20pm) and PVC (250 pm) enclosed in an outer carton containing 84 tablets.
Not all pack sizes may be marketed.
6.6 Special precautions for disposal
Not applicable.
7 MARKETING AUTHORISATION HOLDER
Dalkeith Laboratories Ltd
2 Park Street
Woburn
Bedfordshire
MK17 9PG
8 MARKETING AUTHORISATION NUMBER(S)
PL 17496/0019
9 DATE OF FIRST AUTHORISATION/RENEWAL OF THE AUTHORISATION
19/03/2002 / 03/07/2008
10 DATE OF REVISION OF THE TEXT
23/03/2016