Ibuprofen 400 Mg Tablets
SUMMARY OF PRODUCTCHARACTERISTICS
1. NAME OF THE MEDICINAL PRODUCT
Ibuprofen 400mg Tablets
2. QUANTITATIVE AND QUALITATIVE COMPOSITION
Each tablet contains Ibuprofen B.P 400mg For a full list of excipients see 6.1
3. PHARMACEUTICAL FORM
Pink colour sugar coated tablets.
4 CLINICAL PARTICULARS
4.1 Therapeutic indications
POM indications: DISPENSING PACK
Ibuprofen is indicated for its analgesic and anti-inflammatory effects in the treatment of 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 such as frozen shoulder (capsulitis), bursitis, tendonitis, tenosynovitis and low back pain; Ibuprofen can also be used in soft tissue injuries such as sprains and strains.
Ibuprofen is also indicated for its analgesic effect in the relief of mild to moderate pain such as dysmenorrhoea, dental and post-operative pain and for symptomatic relief of headache, including migraine headache.
P indications: OTC PACK SIZES
Ibuprofen is indicated for rheumatic or muscular pain, backache, neuralgia, migraine, headache, dental pain, dysmenorrhoea, feverishness, symptoms of colds and influenza.
4.2
Posology and method of administration
Undesirable effects may be minimised by using the lowest effective dose for the shortest duration necessary to control symptoms (see section 4.4).
For POM product:
Adult: The recommended dosage of Ibuprofen is 1200-1800 mg daily in divided doses. Some patients can be maintained on 600-1200 mg 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 2400 mg in divided doses.
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 for the shortest possible duration. The patient should be monitored regularly for GI bleeding during NSAID therapy.
Children: 20mg of Ibuprofen per kg of body weight daily, except that in children weighing less than 30 kg, the total of Ibuprofen given in 24 hours should not exceed 500mg.
Not recommended for children weighing less than 7 kg.
In Juvenile Rheumatoid Arthritis, up to 40 mg/kg of body weight daily in divided doses may be taken.
For P product:
Adults: The recommended dosage of Ibuprofen is 1200-1800 mg daily in divided doses. Some patients can be maintained on 600-1200 mg 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 2400 mg in divided doses.
Children: 20mg of Ibuprofen per kg of body weight daily, except that in children Weighing less than 30 kg, the total dose of Ibuprofen given in 24 hours should not exceed 500mg.
If in adolescents this medicinal product is required for more than 3 days, or if symptoms worsen a doctor should be consulted.
Not indicated for the children less than 12 years of age.
Not recommended for children weighing less than 7 kg.
Elderly: The elderly are at increased risk of 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. If renal or hepatic function is impaired, dosage should be assessed individually.
For oral administration. To be taken preferably with or after food.
4.3 Contraindications
Ibuprofen is contraindicated in patients with hypersensitivity to the active substance or to any of the excipients.
Ibuprofen should not be used in patients who have previously shown hypersensitivity reactions (e.g. asthma, urticaria, angioedema or rhinitis) after taking ibuprofen, aspirin or other NSAIDs.
Ibuprofen is also contraindicated in patients with a history of gastrointestinal bleeding or perforation, related to previous NSAID therapy. Ibuprofen should not be used in patients with active, or history of, recurrent peptic ulcer or gastrointestinal haemorrhage (two or more distinct episodes of proven ulceration or bleeding).
Ibuprofen should not be given to patients with conditions involving an increased tendency to bleeding. Ibuprofen results in deterioration of renal function. The dose should be kept as low as possible and renal function should be monitored.
Ibuprofen is contraindicated in patients with severe heart failure, hepatic failure and renal failure (see section 4.4).
Ibuprofen is contraindicated during the last trimester of pregnancy (see section 4.6).
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).
Patients with rare hereditary problems of galactose intolerance, the Lapp lactose deficiency or glucose-galactose malabsorption should not take this medication.
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).
Gastrointestinal bleeding, ulceration and perforation
GI bleeding, ulceration or perforation, which can be fatal, has been reported with all NSAIDs at anytime 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 gastrointestinal disease, particularly when elderly, should report any unusual abdominal symptoms (especially gastrointestinal 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 ulcerative colitis or Crohn's disease as these conditions may be exacerbated (see section 4.8).
Respiratory disorders
Caution is required if Ibuprofen is administered to patients suffering from, or with a previous history of, bronchial asthma since NSAIDs have been reported to precipitate 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).
Ibuprofen should be given with care to patients with a history of heart failure or hypertension since oedema has been reported in association with ibuprofen administration.
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.
Epidemiological 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 such as 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 arterial thrombotic events, particularly 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).
Renal effects
Caution should be used when initiating treatment with ibuprofen in patients with considerable dehydration. There is a risk of renal impairment in dehydrated children and adolescents.
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.
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 effects
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 of these reactions early in the course of therapy, the onset of the reaction occurring within the first month of treatment in the majority of cases. Brufen 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.
For the P product 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 or taking any other pain killer, 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
Care should be taken in patients treated with any of the following drugs as interactions have been reported in some patients.
Antihypertensives, 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.
Cholestyramine; The concomitant administration of ibuprofen and cholestyramine 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 coadministration 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).
Aspirin: As with other products containing NSAIDs, concomitant administration of ibuprofen and aspirin is not generally recommended because of the potential of increased adverse effects.
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 use (see section 5.1).
Corticosteroids: Increased risk of gastrointestinal ulceration or bleeding 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
Whilst no teratogenic effects have been demonstrated in animal studies, ibuprofen should be avoided during pregnancy. Congenital abnormalities have been reported in association with ibuprofen administration in man; however, these are low in frequency and do not appear to be follow any discernible pattern. In view of the known effects of NSAIDs on the foetal cardiovascular system (a closure of ductus arteriosus) use in pregnancy should be avoided. The onset of labour may be delayed and duration of labour increased.
Inhibition of prostaglandin synthesis may adversely affect the pregnancy and/or embryo/foetal development. Data from epidemiological studies suggest an increased risk of miscarriage and of cardiac malformation and gastroschisis after the use of a prostaglandin synthesis inhibitor in early pregnancy. In animals, the administration of a prostaglandin synthesis inhibitor has been shown to result in increased pre- and post-implantation losses and embryo/foetal lethality. In addition, increased incidences of various malformations, including cardiovascular, have been reported in animals given a prostaglandin synthesis inhibitor during the organogenetic period.
During the first and second trimester of pregnancy, Ibuprofen should not be given unless clearly necessary. If Ibuprofen is used by a woman attempting to conceive, or during the first or second trimester of pregnancy, the dose should be kept as low and duration of treatment as short as possible.
During the third trimester of pregnancy, all prostaglandin synthesis inhibitors may expose the foetus to the following:
• Cardiopulmonary toxicity (with premature closure of the ductus arteriosus and pulmonary hypertension)
• Renal dysfunction, which may progress to renal failure with oligohydramnios.
At the end of pregnancy, prostaglandin synthesis inhibitors may expose the mother and the neonate to the following:
• Possible prolongation of bleeding time
• Inhibition of uterine contractions, which may result in delayed or prolonged labour. Consequently, Brufen is contraindicated during the third trimester of pregnancy.
Lactation
In the limited studies so far available, NSAIDs can appear in the 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
Gastrointestinal disorders: The most commonly observed adverse events are gastrointestinal 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 ibuprofen administration. Less frequently, gastritis has been observed. Gastrointestinal perforation has been rarely reported with ibuprofen use. Pancreatitis has also been reported very rarely.
Immune system disorders: Hypersensitivity reactions have been reported following treatment with NSAIDs. These may consist of (a) 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 Stevens- Johnson syndrome, toxic epidermal necrolysis and erythema multiforme).
Cardiac disorders and vascular disorders: Oedema, hypertension and cardiac failure have been reported in association with NSAID treatment. 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 such as myocardial infarction or stroke (see section 4.4).
Other adverse events reported less commonly and for which causality has not necessarily been established include:
Blood and lymphatic system disorders: Leukopenia, thrombocytopenia, neutropenia, agranulocytosis, aplastic anaemia and haemolytic anaemia
Psychiatric disorders: Insomnia, anxiety, depression, confusional state, hallucination
Nervous system disorders: Optic neuritis, headache, paraesthesia, dizziness, somnolence
Infections and infestations: Rhinitis and aseptic meningitis (especially in patients with existing autoimmune disorders, such as systemic lupus erythematosus and mixed connective tissue disease) with symptoms of stiff neck, headache, nausea, vomiting, fever or disorientation (see section 4.4).
Eye disorders: Visual impairment and toxic optic neuropathy
Ear and labyrinth disorders: Hearing impaired, tinnitus and vertigo
Hepatobiliary disorders: Abnormal liver function, hepatic failure, hepatitis and jaundice
Skin and subcutaneous tissue disorders: Bullous reactions, including Stevens-Johnson syndrome and toxic epidermal necrolysis (very rare), and photosensitivity reaction
Renal and urinary disorders: Impaired renal function and toxic nephropathy in various forms, including interstitial nephritis, nephrotic syndrome and renal failure
General disorders and administration site conditions: Malaise, fatigue.
4.9 Overdose
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.
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.
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 patient's clinical condition.
5 PHARMACOLOGICAL PROPERTIES
5.1 Pharmacodynamic properties
Ibuprofen is a propionic acid derivative with analgesic, anti-inflammatory and anti-pyretic activity. The drug's therapeutic effects as an NSAID are thought to result from its inhibitory effect on the enzyme cyclo-oxygenase, which results in a marked reduction in prostaglandin synthesis.
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 400mg 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 like for occasional ibuprofen use.
5.2 Pharmacokinetic properties
NONE STATED
5.3. Preclinical Safety Data
N/A
6. PHARMACEUTICAL PARTICULARS 6.1. List of Excipients
Pregelatinised Starch 100.00mg
Maize Starch 83.00mg
Povidone 25.00mg
Sodium Luaryl Sulphate 2.50mg
Silicon Dioxide 1.50mg
Magnesium Stearate 2.50mg
Coating:
Povidone 2.5mg
Sucrose 152.3mg
Erythrosine Aluminium Lake (E 127) 8.40mg
Purified Talc 42.00mg
Titanium Dioxide 1.20mg
Bees Wax (white) qs
Carnauba Wax
qs
6.2. Incompatibilities
None known
6.3. Shelf-Life
5 years
6.4. Special Precautions for Storage
Do not store above 30C Do not freeze
6.5. Nature and Content of Container
Dispensing pack 500: A plastic securitainer with a double security closure containing Ibuprofen tablets. (POM)
OTC packs- A plastic securitainers with a double security closure. (P)
Pack size includes 100, 50, and 25.
Or
PVC/foil blister pack in carton. (P)
Pack size includes 96, 84, 48, 24, 16 and 12.
20 micron hard-temper aluminium foil printed (bright side) and coated (dull side) with a heat seal lacquer. 250 micron PVC-pharmaceutical grade.
6.6. Instructions for Use, Handling and Disposal
None
7. MARKETING AUTHORISATION HOLDER
Pharmvit Limited 177 Bilton Road
Perivale Greenford Middlesex UB6 7HQ
8. MARKETING AUTHORISATION NUMBER(S)
PL 04556/0023
9 DATE OF FIRST AUTHORISATION/RENEWAL OF THE AUTHORISATION
20/05/2009
10 DATE OF REVISION OF THE TEXT
19/08/2016