Summary of medicine characteristics - IBUCALM 400 MG TABLETS, IBUPROFEN 400 MG TABLETS BP
1 NAME OF THE MEDICINAL PRODUCT
Ibuprofen Tablets BP 400mg
Ibucalm 400mg Tablets
2 QUALITATIVE AND QUANTITATIVE COMPOSITION
Each tablet contains: Ibuprofen 400mg
3 PHARMACEUTICAL FORM
4. Clinical particulars4.1. Therapeutic indications
4.2 Posology and method of administration
Undesirable effects may be minimised by using) the lowest effective dose should be used for the shortest duration necessary to relieve symptoms (see section 4.4)
For oral administration and short-term use only.
Adults, the elderly and children over 12 years:
The lowest effective dose should be used for the shortest duration necessary to relieve symptoms. If this medicinal product is required for more than 3 days, or if symptoms worsen, a doctor should be consulted. The patient should consult a pharmacist or doctor if symptoms persist or worsen, or if the product is required for more than 10 days.
Adults, the elderly and children over 12 years:
One tablet to be taken three times a day as required. These tablets should be taken with water. Leave at least four hours between doses and do not take more than 1200mg (3 tablets) in any 24hour period.
Not to be given to children under 12 years of age.
4.3. Contraindications
Hypersensitivity to Ibuprofen or any of the excipients in the product.
Patients who have previously shown hypersensitivity reactions (e.g. asthma, rhinitis, angioedema or urticaria) in response to 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.
Severe hepatic failure, renal failure or heart failure NYHA class
IV (See section 4.4)
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 are at an increased risk of the serious consequences of adverse reactions to NSAIDs especially gastrointestinal bleeding and perforation which may be fatal.
There is a risk of renal impairment in dehydrated children and adolescents.
Caution is required in patients with certain conditions:
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 (see section 4.5).
SLE as well as mixed connective tissue disease:
Systemic lupus erythematosus and mixed connective tissue disease due to increased risk of aseptic meningitis (see section 4.8).
Renal:
Renal impairment as renal function may further deteriorate (see section 4.3 and 4.8)
Hepatic:
Hepatic dysfunction (see section 4.3 and 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 renal function may deteriorate and fluid retention, hypertension and oedema have been reported in association with NSAID therapy (see section 4.5).
Clinical studies suggest that use of ibuprofen, particularly at high dose (2400mg daily) 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 arterial thrombotic events.
Impaired female fertility:
There is some 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 anytime during treatment, with or without warning symptoms or a previous history of serious GI events including ulcerative colitis, Crohn’s Disease.
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, selective serotonin uptake
| inhibitors or anti-platelet agents such as aspirin (See Section 4.5 Interactions). When GI bleeding or ulceration occurs in patients receiving Ibuprofen, the treatment should be withdrawn immediately. Dermatological: Sever skin reactions: 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. Acute generalised exanthematous pustulosis (AGEP) has been reported in relation to ibuprofen-containing products. Ibuprofen should be discontinued, at the first appearance of signs and symptoms of severe skin reactions, such as skin rash, mucosal lesions, or any other sign of hypersensitivity. Masking of symptoms of underlying infections Ibuprofen can mask symptoms of infection, which may lead to delayed initiation of appropriate treatment and thereby worsening the outcome of the infection. This has been observed in bacterial community acquired pneumonia and bacterial complications to varicella. When Ibuprofen is administered for fever or pain relief in relation to infection, monitoring of infection is advised. In nonhospital settings, the patient should consult doctor if symptoms persist or worsen. This medicine contains less than 1 mmol sodium (23mg) per 200mg caplet, that is to say essentially ‘sodium-free’. 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 ingredients of the product, aspirin or other related painkillers ■ Are taking other NSAID painkillers, or aspirin with a daily dose above 75mg ■ Are in the last 3 months of pregnancy 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, liver, heart, 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
Aspirin: Unless low-dose aspirin (not above 75mg daily) has been advised by a doctor, as this may increase the risk of adverse reactions (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:
Avoid concomitant use of two or more NSAIDs as this may increase the risk of adverse effects (see section 4.4)
Anticoagulants: NSAIDs may enhance the effects of anti-coagulants, such as warfarin (See Section 4.4).
Antihypertensives and diuretics: NSAIDs may diminish the effect of these drugs. Diuretics can increase the risk of nephrotoxicity of NSAIDs.
Corticosteroids: Corticosteroids may increase the risk of adverse reactions especially of the gastrointestinal tract (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 a potential for an increase in plasma
methotrexate. Ciclosporin: Increased risk of nephrotoxicity.
Mifepristone: NSAIDs should not be used for 8–12 days after Mifepristone administration as NSAIDs can reduce the effect 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
Whilst no teratogenic effects have been demonstrated in animal experiments, the use of Ibuprofen in pregnancy should, if possible, be avoided during the first
6 months of pregnancy.
During the 3rd trimester, Ibuprofen is contraindicated as there is a risk of premature closure of the foetal ductus arteriosus with possible persistent pulmonary hypertension. The onset of labour may be delayed and the duration increased with an increased bleeding tendency in both the mother and child. (See Section 4.3).
In limited studies, Ibuprofen appears in breast milk in a very low concentration and is unlikely to affect the breast-fed infant adversely.
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 therapy.
4.8. Undesirable effects
Hypersensitivity reactions have been reported and these may consist of: –
■ Non-specific allergic reaction and anaphylaxis,
■ Respiratory tract reactivity, e.g. asthma, aggravated asthma, bronchospasm, dyspnoea or
■ Various skin reactions, e.g. pruritis, 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 longterm treatment, additional adverse effects may occur.
Infections and infestations:
Very rare: Aseptic meningitis
Immune system reactions:
Uncommon: hypersensitivity reactions with urticaria and pruritus.
Very rare:
Exacerbation of asthma and bronchospasm.
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.
Severe hypersensitivity reactions: Symptoms could be: facial, tongue and larynx swelling, dyspnoea, tachycardia, hypotension (anaphylaxis, angioedema or severe shock).
Psychiatric disorders:
Very rare: Nervousness.
Gastrointestinal disorders:
The most commonly-observed adverse events are gastrointestinal in nature. Uncommon: Abdominal pain, abdominal distension, nausea and 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). Mouth ulceration.
Exacerbation of ulcerative colitis and Crohn’s disease (See Section 4.4)
Nervous system:
Uncommon: Headache
Eye disorders:
Very rare: Visual disturbance
Ear and labyrinth disorders:
Very rare: Tinnitus and vertigo
Renal and urinary disorders:
Very rare: Acute renal failure, papillary necrosis, especially in long-term use, associated with increased serum urea and oedema. Haematuria, interstitial nephritis, nephrotic syndrome, proteinuria.
Hepatobiliary disorders:
Very rare: Liver disorders, especially in long-term treatment, hepatitis and jaundice.
Haematological:
Very rare: Haematopoietic disorders (anaemia, leucopenia, thrombocytopenia, pancytopenia, granulocytosis). First signs are: fever, sore throat, superficial mouth ulcers, flu-like symptoms, severe exhaustion, unexplained bleeding and bruising.
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.
Not known:
Drug reaction with eosinophilia and systemic symptoms (DRESS syndrome) Acute generalised exanthematous pustulosis (AGEP)
Cardiovascular disorders:
Very rare: Cardiac failure.
Clinical trial and epidemiological data suggest that use of ibuprofen (particularly at high doses 240mg 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).
Vascular disorders:
Very rare: Hypertension
Respiratory, thoracic and mediastinal disorders:
Very rare: Asthma, bronchospasm, dyspnoea and wheezing.
General disorders:
Very rare: Oedema, peripheral oedema.
Investigations:
Very rare: Decreased haematocrit and haemoglobin levels.
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 or search for MHRA Yellow Card in the Google Play or Apple App Store.
4.9. Overdose
In children ingestion of more than 400mg/kg may cause symptoms. In adults the dose response effect is less clear cut. The half life in overdose 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 vertigo, headache, respiratory depression, dyspnoea, 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
Ibuprofen is a propionic acid derivative NSAID that has demonstrated its efficacy by inhibition of prostaglandin synthesis. In human ibuprofen reduces inflammatory 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 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 to 2 hours. These times may vary with different dosage forms.
The half-life of Ibuprofen is about 2 hours.
In limited studies, Ibuprofen appears in breast milk in very low concentrations.
5.3 Preclinical safety data
6 PHARMACEUTICAL PARTICULARS
6.1 List of excipients
Colloidal anhydrous silica, potato starch, povidone, microcrystalline cellulose, alginic acid, magnesium stearate, sodium lauryl sulphate, sodium starch glycollate, croscarmellose sodium, hypromellose, glycerol and Mastercote Pink FA 2481 (titanium dioxide E171, carmine E120, hydroxypropylmethyl cellulose E464)
6.2 Incompatibilities
6. PHARMACEUTICAL PARTICULARS
6.3 Shelf life
2 years
6.4 Special precautions for storage
Do not store above 25°C. Store in the original package (blisters) or keep the container tightly closed (plastic containers).
6.5 Nature and contents of container
Cartons of 12, 16, 24, 48 and 96 tablets in blister packs of Aluminium foil/PVC.
6.6 Special precautions for disposal
7. MARKETING AUTHORISATION HOLDER
8 MARKETING AUTHORISATION NUMBER(S)
PL 08977/0017