Ibuprofen Tablets 200mg
SUMMARY OF PRODUCT CHARACTERISTICS
1 NAME OF THE MEDICINAL PRODUCT
Ibuprofen Tablets 200mg
2 QUALITATIVE AND QUANTITATIVE COMPOSITION
Ibuprofen BP 200.0mg
3 PHARMACEUTICAL FORM
Tablet
4 CLINICAL PARTICULARS
4.1 Therapeutic indications
Rheumatic and muscular pain, backache, neuralgia, migraine, headache, dental pain, dysmenorrhoea, feverishness, symptoms of cold and influenza.
4.2 Posology and method of administration
The tablets should be swallowed with or after food.
Adults, the elderly and children over 12 years: 1 or 2 tablets, up to three times a day as required. The dose should not be repeated more frequently than every four hours and no more than 6 tablets in any 24-hour period.
If in adolescents this medicinal product is required for more than 3 days, or if symptoms worsen a doctor should be consulted.
Children: Do not give to children under 12 years.
4.3 Contraindications
Patients with a hypersensitivity to the active substance or to any of the excipients.
NSAIDs are contraindicated in patients who have previously shown hypersensitivity reactions (e.g. asthma, rhinitis, or urticaria) in response to ibuprofen, aspirin, or other non-steroidal anti-inflammatory drugs
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).
Severe heart failure. 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 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.
Other NSAIDs
The use of Ibuprofen with concomitant NSAIDs, including cyclooxygenase-2 selective inhibitors, should be avoided due to the potential for additive effects (see section 4.5).
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
Bronchospasm may be precipitated in patients suffering from, or with a history of, bronchial asthma or allergic disease.
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 mild to moderate congestive heart failure as hypertension, 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 (2400mg daily) and in long term treatment may be associated with a small increase risk of arterial thrombotic events (for example myocardial infarction or stroke). Overall, epidemiological studies do not suggest that a 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, and 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
Hepatic:
Hepatic dysfunction (see sections 4.3 and 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 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. 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 systematic 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.
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.
Label Warnings:
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, to any of the ingredients, or to aspirin or other
related painkillers
• are taking other NSAID pain killers or aspirin with a daily dose above 75mg
Speak to a pharmacist or your doctor before taking 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, or if new symptoms occur, consult your doctor or pharmacist.
4.5 Interaction with other medicinal products and other forms of interaction Ibuprofen (like other NSAIDs) should be avoided in combination with:
Aspirin: unless low-dose aspirin (not above 75mg daily) has been advised by a doctor as this may increase the risk of adverse reactions.
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 effects is considered to be likely for occasional ibuprofen use (see section 5.1).
Other NSAIDs 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).
Ibuprofen should be used with caution in combination with:
Corticosteroids: Increased risk of gastro-intestinal bleeding and ulceration with NSAIDs (see section 4.4).
Anti-hypertensives and diuretics (e.g. ACE inhibitors, Beta Blockers): Since NSAIDs may diminish the effects of these drugs. In some patients with compromised renal function (e.g. dehydrated patients or elderly patients with compromised renal function) the coadministration 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.
Anticoagulants: Increased risk of haemorrhage, prothrombin time should be monitored daily for the first few days of combined treatment. NSAIDs may enhance the effects of anti-coagulants.
Anti-platelet agents and selective serotonin reuptake inhibitors (SSRIs): Increased risk of gastrointestinal bleeding with NSAIDs (see section 4.4).
Cardiac glycosides: NSAIDs may exacerbate cardiac failure, reduce GFR and increase plasma cardiac glycoside levels.
Lithium: There is evidence for potential increase in plasma levels of Ciclosporin: Increased risk of nephrotoxicity.
Methotrexate (cytotoxics): There is evidence for the potential increase in plasma levels of methotrexate
Mifepristone: NSAIDs should not be used for 8-12 days after mifepristone administration as
NSAIDs can reduce the effects of mifepristone.
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 embryfoetal 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 oligohydroamniosis;
the mother and the neonate, at the end of the 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/Breastfeeding
In the limited studies so far available, NSAIDs can appear in the breast milk in very low concentrations and is unlikely to affect the breast-fed infant adversely.
See section 4.4 Special warnings and precautions for use, regarding female fertility.
4.7 Effects on ability to drive and use machines
Dizziness, drowsiness, visual disturbances or headaches are possible undesirable effects after taking NSAIDs, if affected, patients should not drive or operate machinery.
4.8 Undesirable effects
Adverse events which have been associated with Ibuprofen are given below, listed by system organ class and frequency. Frequencies are defined as: very common (>1/10), common (>1/100 to <1/10), uncommon (>1/1000 to <1/100), rare (>1/10,000 to <1/1000), very rare (<1/10,000) and not known (cannot be estimated from the available data). Within each frequency grouping, adverse events are presented in order of decreasing seriousness.
The list of the following adverse events 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 events 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), (see section 4.4).
|
System Organ Class |
Frequency |
Adverse Event |
|
Blood and lymphatic system disorders |
Very rare: |
Haematopoietic disorders (anaemia, leucopenia, thrombocytopenia, pancytopenia, agranulocytosis), neutropenia First signs are: fever, sore throat, superficial mouth ulcers, flu-like symptoms, severe exhaustion, unexplained bleeding and bruising. |
|
Immune system |
Hypersensitivity reactions consisting of1: | |
|
disorders |
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 |
Uncommon |
Headache |
|
disorders |
Very rare |
2 Aseptic meningitis |
|
Not known |
Optic neuritis, paraesthesia, dizziness, somnolence. | |
|
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. Ulcerative stomatitis, gastritis, pancreatitis | |
|
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, toxic nephropathy (interstitial nephritis, nephritic syndrome) | |
|
Investigations |
Very rare |
Decreased haemoglobin levels |
|
Psychiatric disorders |
Not known |
Depression, confusional state, hallucination |
|
Eye disorders |
Not known |
Visual disturbances |
|
Ear and labyrinth disorders |
Not known |
Tinnitus, vertigo |
|
General disorders and administration site conditions |
Not known |
Malaise, fatigue |
Description of Selected Adverse Reactions
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 poisioning, toxicity is seen in the central nervous system, manifesting as drowsiness, occasionally excitation and disorientation and 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.
Therapeutic measures
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
ATC Code: M01AE01
Ibuprofen is a propionic acid derivative NSAID that has demonstrated its efficacy by inhibition of prostaglandin synthesis. In humans, ibuprofen reduces pain, swellings and fever. Furthermore, ibuprofen reversibly inhibits platelet aggregation.
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 like for occasional ibuprofen use.
5.2 Pharmacokinetic properties
Ibuprofen is rabidly 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.
Elimination half-life 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, starch, povidone, croscarmellose sodium, microcrystalline cellulose, alginic acid, magnesium stearate, sodium lauryl sulphate, sucrose, E171, E127, sodium starch glycollate, Opaseal (polyvinyl acetate phthalate, stearic acid (E570)).
6.2 Incompatibilities
None known
6.3 Shelf life
3 years
6.4 Special precautions for storage
Store in a cool dry place protected from moisture below 25°C.
6.5 Nature and contents of container
Cartons of blister packs containing 12 or 16 tablets.
6.6 Special precautions for disposal
Not applicable.
7 MARKETING AUTHORISATION HOLDER
Ennogen Pharma Limited Unit G4,
Riverside Industrial Estate,
Riverside Way,
Dartford DA1 5BS UK
8 MARKETING AUTHORISATION NUMBER(S)
PL 40147/0045
DATE OF FIRST AUTHORISATION/RENEWAL OF THE AUTHORISATION
24/02/2009
10
DATE OF REVISION OF THE TEXT
04/10/2016
Hypersensitivity reactions have been reported following treatment with ibuprofen. These may consist of (a) nonspecific 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).