Ibuprofen 400mg Tablets
SUMMARY OF PRODUCT CHARACTERISTICS
1 NAME OF THE MEDICINAL PRODUCT
Ibuprofen 400mg Tablets
2 QUALITATIVE AND QUANTITATIVE COMPOSITION
Ibuprofen 400mg For excipients, see 6.1
3 PHARMACEUTICAL FORM
Pink biconvex film coated tablets (tablets) marked with “I 400” on one side.
4 CLINICAL PARTICULARS
4.1 Therapeutic indications
Rheumatic or muscular pain, pain of non-serious arthritic conditions, backache, neuralgia, migraine, headache, dental pain, dysmenorrhoea, feverishness and symptoms of colds and influenza.
4.2 Posology and method of administration
For oral administration and 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 10 days.
UAdults, the elderly and children over 12 years:
One tablet with water up to three times a day, as required. Take with or after food. Leave at least 4 hours between doses and do not take more than three tablets in any 24 hour period.
4.3 Contraindications
Hypersensitivity to ibuprofen or any of the constituents in the product.
Previous hypersensitivity reactions (e.g. asthma, rhinitis, angioedema or urticaria) in response to aspirin or other non-steroidal anti-inflammatory drugs.
Active or previous peptic ulcer (two or more distinct episodes of proven ulceration or bleeding).
History of upper gastrointestinal bleeding or perforation, related to previous NSAIDs therapy.
Severe hepatic failure, renal failure or heart failure (See section 4.4 Special warnings and precautions for use).
Last trimester of pregnancy (see section 4.6 Pregnancy and lactation).
Bleeding disorders.
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 are at increased risk of the serious consequences of adverse reactions.
Respiratory:
Bronchospasm may be precipitated in patients suffering from or with a previous history of bronchial asthma or allergic disease. The possibility of cross-sensitivity with aspirin and other NSAIDs should be borne in mind.
Other NSAIDs:
The use Ibuprofen with concomitant NSAIDs including cyclo oxygenase 2 selective inhibitors should be avoided (see section 4.5).
SLE and mixed connective tissue disease:
Systemic lupus erythematous and mixed connective tissue disease - increased risk of aseptic meningitis (see section 4.8).
Renal:
Renal impairment as renal function may further deteriorate (see sections 4.3 and section 4.8). There is a risk of renal impairment in dehydrated children and adolescents
Hepatic:
Hepatic dysfunction (see section 4.3 and section 4.8)
Cardiovascular and cerebrovascular effects
Caution (discussion with 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 trial and epidemiological data suggest that use of ibuprofen, particularly at high doses (2400mg 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. < 1200mg daily) is associated with an increased risk of myocardial infarction.
Impaired female fertility:
There is limited evidence that drugs which impair 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 the 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 gastrotoxicity or bleeding, such as corticosteroids, or anticoagulants such as warfarin (prothrombin time should be monitored daily for the first few days of combined treatment) or antiplatelet agents such as aspirin (see section 4.5).
When GI bleeding or ulceration occurs in patients receiving ibuprofen, the treatment should be withdrawn immediately.
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 NSAIDSs (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.
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 NSAID painkillers, or aspirin with a daily dose above 75 mg
• Talk to your pharmacist or doctor before taking this product if you:
o Have or have had asthma, diabetes, high cholesterol, high blood pressure a stroke, liver, heart, kidney or bowel problems o Are a smoker o Are pregnant
Do not exceed the stated dose. If symptoms persist or worsen, or if new symptoms occur, consult your doctor or pharmacist.
4.5 Interaction with other medicinal products and other forms of interaction
Ibuprofen should not be used in combination with:
Aspirin: Unless low dose aspirin (not above 75 mg daily) has been advised by a doctor, as this may increase the risk of adverse effects (see section 4.4)
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).
Other NSAIDS including cyclooxygenase-2 selective inhibitors as these may increase the incidence of adverse effects (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 Special warnings and precautions)
Anti-platelet agents and Selective serotonin reuptake inhibitors (SSRIs): increased risk of gastrointestinal bleeding (see section 4.4).
Antihypertensives and diuretics: NSAIDs may diminish the effect of these drugs.
In some patients with compromised renal function (e.g. dehydrated patients or elderly patients with compromised renal function) the co-administration of an ACE inhibitor or Angiotensin II antagonist and agents that inhibit cyclo-oxygenase may result in further deterioration of renal function, including possible acute renal failure, which is usually reversible.
These interactions should be considered in patients taking a coxib concomitantly with ACE inhibitors or angiotensin II antagonists. Therefore, the combination should be administered with caution, especially in the elderly. Patients should be adequately hydrated and consideration should be given to monitoring of renal function after initiation of concomitant therapy, and periodically thereafter. Diuretics can increase the risk of nephrotoxicity of NSAIDs.
Cardiac Glycosides: NSAIDs may exacerbate heart failure, reduce GFR and increase plasma cardiac glycoside concentration.
Ciclosporin: Increased risk of nephrotoxicity.
Corticosteroids: May increase the risk of adverse reactions in the gastrointestinal tract (see section 4.4 Special warnings)
Lithium: There is evidence for potential increases in plasma levels of lithium.
Mifepristone: NSAIDs should not be used for 8-12 days after mifepristone administration as NSAIDs can reduce the effect of mifepristone.
Methotrexate: There is evidence for the potential increase in plasma levels of methotrexate.
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.
Quinolone antibiotics: Animal data indicate that NSAIDs can increase the risk of convulsions associated with quinolone antibiotics. Patients taking NSAIDs and quinolones may have an increased risk of developing convulsions.
4.6 Fertility, pregnancy and lactation
Pregnancy:
Inhibition of prostaglandin synthesis may adversely affect the pregnancy and/or the embryo/foetal development. Data from epidemiological studies suggest an increased risk of miscarriage and of cardiac malformation and gastroschisis after use of a prostaglandin synthesis inhibitor in early pregnancy. The absolute risk for cardiovascular malformation was increased from less than 1%, up to approximately 1.5 %. The risk is believed to increase with dose and duration of therapy. In animals, administration of a prostaglandin synthesis inhibitor has been shown to result in increased pre- and post-implantation loss 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 and 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:
- Cardiopulmonary toxicity (with premature closure of the ductus arteriosus and pulmonary hypertension);
- Renal dysfunction, which may progress to renal failure with oligo-hydroamniosis;
the mother and the neonate, at the end of pregnancy, to:
- Possible prolongation of bleeding time, an anti-aggregating effect which may occur even at very low doses.
- Inhibition of uterine contractions resulting in delayed or prolonged labour. Consequently, Ibuprofen is contraindicated during the third trimester of pregnancy. Lactation:
In limited studies ibuprofen appears in the breast milk in very low concentrations and is unlikely to affect the breast-fed infant adversely.
Fertility:
See section 4.4 regarding female fertility.
4.7 Effects on ability to drive and use machines
None at the recommended doses and duration of therapy.
4.8 Undesirable effects
The following terminologies have been used to classify the occurrence of undesirable effects:
Very common (>1/10); Common (>1/100 to <1/10); Uncommon (>1/1000 to <1/100), Rare (>1/10000 to <1/1000); Very rare (<1/10000); not known (cannot be estimated from the available data).
The list of the following adverse effects relates to those experienced with ibuprofen at OTC doses, from short-term use. In chronic conditions, under long-term treatment, additional adverse effects may occur.
The adverse events observed most often are gastrointestinal in nature. Adverse events are mostly dose-dependent, in particular the risk of occurrence of gastrointestinal bleeding is dependent on the dosage range and duration of treatment.
Clinical trial and epidemiological data suggest that use of ibuprofen, particularly at high doses (2400mg daily) and in long-term treatment may be associated with a small increased risk of arterial thrombotic events (for example myocardial infarction or stroke).
|
System Organ Class |
Frequency |
Adverse Event |
|
Blood and Lymphatic System Disorders |
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. |
|
Immune System Disorders |
Hypersensitivity reactions consisting of1: | |
|
Uncommon |
Urticaria and pruritus | |
|
Very rare |
Severe hypersensitivity reactions. Symptoms could be facial, tongue and laryngeal swelling, dyspnoea, tachycardia, hypotension (anaphylaxis, angioedema or severe shock). | |
|
Not known |
Respiratory tract reactivity comprising asthma, aggravated asthma, bronchospasm or dyspnoea. | |
|
Nervous System Disorders |
Uncommon |
Headache |
|
Very rare |
Aseptic meningitis2 | |
|
Cardiac Disorders |
Not known |
Cardiac failure and oedema |
|
Vascular Disorders |
Not known |
Hypertension |
|
Gastrointestinal Disorders |
Uncommon |
Abdominal pain, nausea, dyspepsia |
|
Rare |
Diarrhoea, flatulence, constipation and vomiting | |
|
Very rare |
Peptic ulcer, perforation or gastrointestinal haemorrhage, melaena, haematemesis, sometimes fatal, particularly in the elderly (see section 4.4). Ulcerative stomatitis, gastritis | |
|
Not known |
Exacerbation of colitis and Crohn’s disease (section 4.4). | |
|
Hepatobiliary Disorders |
Very rare |
Liver disorders |
|
Skin and Subcutaneous Tissue Disorders |
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. | ||
|
Renal and Urinary Disorders |
Very rare |
Acute renal failure, papillary necrosis, especially in long-term use, associated with increased serum urea and oedema. |
|
Not known |
Renal insufficiency | |
|
Investigations |
Very rare |
Decreased haemoglobin levels |
1 Hypersensitivity reactions have been reported following treatment with ibuprofen. These may consist of (a) non-specific allergic reactions and anaphylaxis, (b) respiratory tract activity comprising asthma, aggravated asthma, bronchospasm, 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 and erythema multiforme).
2The pathogenic mechanism of drug-Induced aseptic meningitis is not fully understood. However, the available data on NSAID-related aseptic meningitis points to a hypersensitivity reaction (due to a temporal relationship with drug intake, and disappearance of symptoms after drug discontinuation). Of note, single cases of symptoms of aseptic meningitis (such as stiff neck, headache, nausea, vomiting, fever or disorientation) have been observed during treatment with ibuprofen, in patients with existing auto-immune disorders (such as systemic lupus erythematosus, mixed connective tissue disease).
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
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. Tinnitus, 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 1 hour of ingestion of a potentially toxic amount. If frequent or prolonged, convulsions should be treated with intravenous diazepam or lorazepam. Give bronchodilators for asthma.
5 PHARMACOLOGICAL PROPERTIES
5.1 Pharmacodynamic properties
Pharmacotherapeutic group: Anti-inflammatory and anti-rheumatic products,
nonsteroids, propionic acid derivatives.
ATC code: MO1AE
Ibuprofen is a Phenylpropionic acid derivative NSAID that has demonstrated its efficacy by inhibition of prostoglandin synthesis. In humans ibuprofen reduces inflammatory pain, swelling and fever. Furthermore, ibuprofen reversibly inhibits platelet aggregation.
Clinical evidence demonstrates that when 400mg of ibuprofen are taken, the effects start within 30-40 minutes of dosing, and pain relieving effects can last for up to 8 hours.
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 (81mg), 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.
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 1-2 hours. These times may vary with different dosage forms.
In limited studies, ibuprofen appears in the breast milk in very low concentrations.
5.3 Preclinical safety data
Ibuprofen has been used in general medicine over a long period exceeding 20 years.
6 PHARMACEUTICAL PARTICULARS
6.1 List of excipients
Cores: Pregelatinised starch
Maize starch
Colloidal anhydrous silica Magnesium stearate Coating: Hypromellose Macrogol 6000 Erythrosine lake E127 Titanium dioxide E171 Docusate Sodium
6.2 Incompatibilities
None known
6.3 Shelf life
3 years (Blister)
2 years (container)
6.4
Special precautions for storage
Do not store above 250C. Store in original container/outer carton.
6.5 Nature and contents of container
Tablet containers:
Pack sizes: 21, 100, 250, 500 and 1000 tablets
Packaging composition: Polypropylene container with a low density polyethylene tamper evident lid
Blister Packs:
Pack sizes: 12, 21, 24, 28, 48, 56, 84, 96 and 100
Packaging composition: White rigid PVC and 20um aluminium foil.
Bags:
Pack sizes: 5,000 and 10,000 tablets for bulk supply Packaging composition: Polyethylene free from additives
6.6 Special precautions for disposal
N/A
7 MARKETING AUTHORISATION HOLDER
Relonchem Limited Cheshire House
Gorsey Lane, Widnes, Cheshire WA8 0RP, UK
8 MARKETING AUTHORISATION NUMBER(S)
PL 20395/0080
9 DATE OF FIRST AUTHORISATION/RENEWAL OF THE AUTHORISATION
05/01/2011
10 DATE OF REVISION OF THE TEXT
29/01/2016