Ibuprofen Tablets Bp 400mg
SUMMARY OF PRODUCT CHARACTERISTICS
1 NAME OF THE MEDICINAL PRODUCT
Ibuprofen Tablets BP 400 mg
2 QUALITATIVE AND QUANTITATIVE COMPOSITION
Ibuprofen BP 400 mg per tablet
3 PHARMACEUTICAL FORM
The product is presented in the form of a pink, sugar coated, deep convex tablet.
4 CLINICAL PARTICULARS
4.1 Therapeutic indications
For the relief of rheumatic or muscular pain, pain of non-serious arthritic conditions, backache, neuralgia, migraine, headache, dental pain, dysmenorrhoea, feverishness, symptoms of colds and influenza.
4.2 Posology and method of administration
For oral administration and short-term use only.
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 the elderly:
The patient should consult a doctor if symptoms persist or worsen, or if the product is required for more than 10 days.
In adolescents (age range > 12 years to < 18 years):
If in adolescents this medicinal product is required for more than 3 days, or if symptoms worsen a doctor should be consulted.
Adults, the elderly and children over 12 years:
1 tablet (400mg), up to three times a day as required.
Leave at least four hours between doses and do not take more than 1200mg in any 24 hour period.
Children under 12 years:
Not recommended for use in children under 12 years of age.
4.3 Contraindications
Hypersensitivity to ibuprofen or to any of the excipients.
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.
Active, or history of recurrent peptic ulcer/haemorrhage (two or more distinct episodes of proven ulceration or bleeding).
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.
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)
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 GI and cardiovascular risks below).
The elderly have an increased frequency of adverse reactions to NSAIDs especially gastrointestinal bleeding and perforation which may be fatal.
Paediatric population:
There is a risk of renal impairment in dehydrated children and adolescents. Respiratory:
Bronchospasm may be precipitated in patients suffering from or with a previous history of bronchial asthma or allergic disease.
Other NSAIDs:
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).
SLE and mixed connective tissue disease:
Systemic lupus erythematosus and mixed connective tissue disease - increased risk of aseptic meningitis (see below and section 4.8).
Renal:
Renal impairment as renal function may further deteriorate (see sections 4.3 and 4.8).
Hepatic:
Hepatic dysfunction (see sections 4.3 and 4.8).
Cardiovascular and cerebrovascular effects:
Caution (discussion with a doctor or pharmacist) is required prior to starting treatment in patients with a history of hypertension and/or heart failure, as fluid retention, hypertension 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 (2400mg/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 (2400mg/day) are required.
Impaired female fertility:
There is limited evidence that drugs which inhibit cyclo-oxygenase/prostaglandin synthesis may cause impairment of female fertility by an effect on ovulation. This is reversible upon withdrawal of treatment.
Gastrointestinal:
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).
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.
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.
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.
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.
Haematological effects:
Ibuprofen, like other NSAIDs, can interfere with platelet aggregation and has been shown to prolong bleeding time in normal subjects.
Patients with rare hereditary problems of fructose intolerance, glucose-galactose malabsorption or sucrase-isomaltase insufficiency should not take this medicine as it contains sucrose.
The label will include:
Read the enclosed leaflet before taking this product.
Do not take if you:
- have (or have had two or more episodes of) 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 75mg
Speak to a pharmacist or your doctor before taking this product if you:
- have or have had asthma, diabetes, high cholesterol, high blood pressure, a stroke, heart, liver, kidney or bowel problems
- are a smoker
- are pregnant
If symptoms persist or worsen, consult your doctor.
4.5 Interaction with other medicinal products and other forms of interaction Ibuprofen should be avoided in combination with:
Acetylsalicylic acid: Unless low-dose aspirin (not above 75mg daily) has been advised by a doctor, 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).
Other NSAIDs including cyclooxygenase-2 selective inhibitors: avoid concomitant use of two or more NSAIDs (including aspirin) as this may result in an increased risk of adverse reactions (see section 4.4).
Ibuprofen should be used with caution in combination with:
Anticoagulants: NSAIDs may enhance the effects of anticoagulants, such as warfarin (see section 4.4).
Anti-hypertensives, beta-blockers and diuretics: NSAIDs may diminish the effect of these drugs. Diuretics can increase the risk of nephrotoxicity of NSAIDs.
Corticosteroids: increased risk of GI bleeding or ulceration (see section 4.4).
Anti-platelet agents and selective serotonin reuptake inhibitors (SSRIs): increased risk of gastrointestinal bleeding (see section 4.4).
Cardiac glycosides: NSAIDs may exacerbate cardiac failure, reduce GFR and increase plasma glycoside levels.
Lithium: There is evidence for potential increases in plasma levels of lithium.
Methotrexate: There is potential for an increase in plasma methotrexate. NSAIDs may inhibit the tubular secretion of methotrexate and reduce the 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.
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.
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.
Colestyramine: The concomitant administration of ibuprofen and colestyramine may reduce the absorption of ibuprofen in the gastrointestinal tract. However, the clinical significance is unknown.
Sulfonylureas: NSAIDs may potentiate the effects of sulfonylurea medications. There have been rare reports of hypoglycaemia in patients on sulfonylurea medications receiving ibuprofen.
Aminoglycosides: NSAIDs may decrease the excretion of aminoglycosides.
Herbal extracts: Ginko 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 Fertility, pregnancy and lactation
Pregnancy:
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 3rd 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:
- inhibition of uterine contraction, which may result in delayed or prolonged labour
- possible prolongation of bleeding time.
Consequently, ibuprofen is contraindicated during the third trimester of pregnancy.
Lactation:
In limited studies so far available, NSAIDs can appear in the breast milk in very low concentration. NSAIDs should, if possible, be avoided when breastfeeding.
See section 4.4 regarding female fertility.
4.7 Effects on ability to drive and use machines
None expected at recommended doses and duration of treatment
4.8 Undesirable effects
Hypersensitivity reactions have been reported and these may consist of:
(a) non-specific allergic reactions and anaphylaxis
(b) respiratory tract reactivity comprising asthma, aggravated asthma, bronchospasm or dyspnoea, or
(c) various skin reactions eg. 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 at OTC doses, for short-term use. In the treatment of chronic conditions, under long-term treatment, additional adverse effects may occur.
Infections and infestations:
Not known: Rhinitis.
Hypersensitivity reactions:
Uncommon: Hypersensitivity reactions with urticaria and pruritus.
Very rare: severe hypersensitivity reactions. Symptoms could be: facial, tongue and laryngeal swelling, dyspnoea, tachycardia, hypotension, (anaphylaxis, angioedema or severe shock).
Exacerbation of asthma and bronchospasm.
Psychiatric disorders:
Not known: Insomnia, anxiety.
Gastrointestinal:
The most commonly observed adverse events are gastrointestinal in nature. Uncommon: abdominal pain, nausea and dyspepsia.
Rare: diarrhoea, flatulence, constipation, vomiting, gastrointestinal perforation.
Very rare: peptic ulcer, perforation or gastrointestinal haemorrhage, melaena, haematemesis, sometimes fatal, particularly in the elderly. Ulcerative stomatitis, gastritis. Exacerbation of colitis and Crohn’s disease (see section 4.4).
Nervous System:
Uncommon: Headache.
Very rare: Aseptic meningitis - single cases have been reported very rarely. Eye disorders:
Not known: Toxic optic neuropathy.
Ear and labyrinth disorders:
Not known: Hearing impaired.
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.
Dermatological:
Uncommon: Various skin rashes.
Very rare: Severe forms of skin reactions such as bullous reactions including Stevens-Johnson Syndrome, erythema multiforme and toxic epidermal necrolysis can occur.
Immune System:
In patients with existing auto-immune disorders (such as systemic lupus erythematosus, mixed connective tissue disease) 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).
Cardiovascular and cerebrovascular:
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).
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
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.
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 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 tinnitus, headache, dizziness, convulsion, and loss of consciousness. Metabolic acidosis may occur and the prothrombin time / INR may be prolonged, probably due to interference with the actions of circulating clotting factors. Exacerbation of asthma is possible in asthmatics. Nystagmus, 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.
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 1 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 patients clinical condition.
5 PHARMACOLOGICAL PROPERTIES
5.1 Pharmacodynamic properties
M01A E01 - Anti-inflammatory & Anti-rheumatic products, Propionic Acid Derivatives
Ibuprofen is a propionic acid derivative NSAID that has demonstrated its efficacy by inhibition of prostaglandin synthesis. In humans ibuprofen reduces inflammatory pain, swellings and fever. Furthermore, ibuprofen reversibly inhibits platelet aggregation.
Experimental data suggest that ibuprofen may competitively inhibit the effect of low dose acetylsalicylic acid on platelet aggregation when they are dosed concomitantly. Some pharmacodynamic studies show that when single doses of ibuprofen 400mg were taken within 8 h before or within 30 min after immediate release acetylsalicylic 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 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 after 1 to 2 hours. These times may vary with different dosage forms. The half life of ibuprofen is approximately 2 hours. In limited studies ibuprofen appears in the breast milk in very low concentrations.
5.3 Preclinical safety data
Not applicable.
6 PHARMACEUTICAL PARTICULARS
6.1 List of excipients
Colloidal Anhydrous Silica Microcrystalline Cellulose Pregelatinised Maize Starch Purified Talc Sodium Starch Glycolate Magnesium Stearate
Coating Sucrose Gum Acacia Purified Talc
Erythrosine Aluminium Lake (E127)
Titanium Dioxide (E171)
Opaglos 6000P (Shellac, Beeswax, Carnauba Wax)
6.2 Incompatibilities
None known
6.3. Shelf life
Opaque plastic containers: 5 years Blister packs: 4 years
6.4 Special precautions for storage
Protect from heat, light and moisture.
Keep out of the reach of children.
6.5 Nature and contents of container
The product marketed in pack sizes of 50 and 100 tablets are packed in opaque plastic containers (securitainers) and/or in opaque plastic containers composed of either, high density polypropylene or high density polyethylene with tamper evident or child resistant tamper evident closure composed of high density polyethylene.
The product is also packed in blister packs of aluminium/opaque PVC, it is subsequently packed in printed boxboard cartons in pack sizes of 28, 42, 56 and 84 tablets.
6.6 Special precautions for disposal
No special instructions for use/handling.
7 MARKETING AUTHORISATION HOLDER
Crescent Pharma Limited.
Units 3 and 4
Quidhampton Business Units Polhampton Lane Overton
Hants RG25 3ED, UK
8 MARKETING AUTHORISATION NUMBER(S)
PL 20416/0089
9 DATE OF FIRST AUTHORISATION/RENEWAL OF THE AUTHORISATION
04/03/2009
10 DATE OF REVISION OF THE TEXT
11/01/2016