Ibuprofen 200mg/5ml Oral Suspension
SUMMARY OF PRODUCT CHARACTERISTICS
1 NAME OF THE MEDICINAL PRODUCT
Ibuprofen 200 mg/5 ml Oral Suspension
2 QUALITATIVE AND QUANTITATIVE COMPOSITION
Each 5ml contains 200mg of Ibuprofen.
Excipients:
Liquid Maltitol 4.25g/5ml
For full list of excipients, see section 6.1
3 PHARMACEUTICAL FORM
Oral Suspension
4 CLINICAL PARTICULARS
4.1 Therapeutic indications
Children under 12 years
Rheumatic or muscular pain, headache, dental pain, feverishness (including postimmunisation pyrexia), symptoms of cold and influenza.
Over 12 years
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).
For infants aged 3 - 5 months medical advice should be sought if symptoms worsen or not later than 24 hours if symptoms persist.
If in children aged from 6 months and in adolescents this medicinal product is required for more than 3 days, or if symptoms worsen a doctor should be consulted.
Leave at least four hours between doses and do not take more than the recommended amount in any 24 hour period.
Not to be given to children under 3 months of age, except on the advice of a doctor This product should only be given to infants who weigh more than 5kg.
If the child’s (aged over 6 months) symptoms persist for more than 3 days, consult your doctor promptly. For children aged 3 to 6 months, medical advice should be sought promptly after 24 hours symptoms persist.
The daily dosage for children is 20- 30mg/kg bodyweight in divided doses. Using the dosing device provided this can be achieved as follows:
3 to 6 months (weighing more than 5 kg): 1.25ml (50mg), up to 3 times in 24 hours.
6 to 12 months (weighing 8-10 kg): 1.25ml (50mg), up to 3 to 4 times in 24 hours.
1 to 4 years (weighing 10-15 kg): 2.5ml (100mg), up to 3 times in 24 hours.
4 to 7 years (weighing 15-20 kg): 3.75ml (150mg), up to 3 times in 24 hours.
7 to 12 years (weighing 20-40 kg): 5 ml (200mg), up to 3 times in 24 hours.
Over 12 years: 5 ml (200mg) to 10ml (400mg) up to three times in 24 hours (maximum daily dose 1200mg)
Post-immunisation pyrexia in infants
1.25ml as a single dose repeated once after 6 hours if necessary.
No more than 2 doses in 24 hours. If fever is not reduced, consult a doctor.
This product is intended for short term use only. Only the lowest dose for the shortest time necessary to relieve symptoms should be used.
Children over 6 months to 12 years should not take Ibuprofen 200mg/5ml Oral Suspension for longer than 3 days unless your doctor tells you to.
Those aged 12 years or over should not take Ibuprofen 200mg/5ml Oral Suspension for longer 10 days unless your doctor tells you to.
Impaired renal function
In patients with mild or moderate reduction of renal function, the dose should be kept as low as possible for the shortest duration necessary to control symptoms and renal function monitored . (For patients with severe renal failure see section 4.3)
Impaired liver function
In patients with mild or moderate reduction of liver function the dose should be kept as low as possible for the shortest duration necessary to control symptoms and hepatic function monitored. (For patients with severe liver failure see section 4,3)
If symptoms persist or worsen consult your doctor.
4.3 Contraindications
Hypersensitivity to ibuprofen or any of the excipients in the product.
Patients with a history of bronchospasm asthma, rhinitis, or urticaria associated with the intake of aspirin (acetylsalicylic acid) or other non-steroidal anti-inflammatory drugs (NSAIDs).
History of gastrointestinal bleeding or perforation, related to NSAID’s therapy.
Severe heart failure (NYHA Class IV).
Last trimester of pregnancy (see section 4.6).
Patients with rare hereditary problems of fructose intolerance should not take this medicine.
Active or history of recurrent peptic ulcer/haemorrhage (two or more distinct episodes of proven ulceration or bleeding).
Severe hepatic failure, severe renal failure or severe heart failure or coronary heart disease (see section 4.4).
Suspected haemopoietic disorder.
Cerebrovascular or other active bleeding.
Significant dehydration (caused by vomiting, diarrhoea or insufficient fluid intake).
4.4 Special warnings and precautions for use
Undesirable effects may be minimised by using the minimum effective dose for the shortest possible duration necessary to control symptoms (see section 4.2 GI and cardiovascular risks below)
Patients treated with NSAIDs long term should undergo regular medical supervision to monitor for adverse events
Eldery:
The elderly have an increased frequency of adverse reactions to NSAIDs especially gastrointestinal bleeding and perforation which may be fatal.
Other NSAIDs:
The use of Ibuprofen 200 mg/5 ml Oral Suspension with concomitant NSAIDs including cylooxygenase-2 selective inhibitors should be avoided (see section 4.5)
SLE and mixed connective tissue disease:
Systemic lupus erythematosus and mixed connective tissue disease - increased risk of aseptic meningitis (see section 4.8).
Asthmatic patients are to seek their doctor’s advice before using ibuprofen (see below)
Renal:
Renal impairment as renal function may further deteriorate (see sections 4.3 and 4.8).
There is a risk of renal impairment in dehydrated children and adolescents.
Administration of NSAIDs such as Ibuprofen may cause dose dependent renal toxicity in patients with reduced renal blood flow or blood volume where renal prostaglandins support the maintenance of renal perfusion. Patients at risk of this reaction include those with impaired renal function, heart failure or liver dysfunction. This is of particular importance in hypertension and/or cardiac impairment as renal function may deteriorate and/or fluid retention occur. Caution is therefore required in the use of Ibuprofen in such patients.
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 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 (2400 mg/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. <1200 mg/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 (2400 mg/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 (2400 mg/day) are required.
Respiratory:
Ibuprofen should be used with caution in patients with bronchial asthma or allergic disease, since such patients may have NSAID - sensitive asthma which has been associated with severe bronchospasm.
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.
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.
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 acetylsalicylic acid, or other medicinal products likely to increase gastrointestinal risk (see below and section 4.5).
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.
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. Ibuprofen 200mg/5ml Oral Suspension should be discontinued at the first appearance of skin rash, mucosal lesion, or any other sign of hypersensitivity.
Exceptionally, varicella can be at the origin of serious cutaneous and soft tissues infectious complications. To date, the contributing role of NSAIDs in the worsening of these infections cannot be ruled out. Thus, it is advisable to avoid use of Ibuprofen Oral Suspension in case of varicella (Chicken pox).
During the prolonged use of analgesics headaches may occur which must should not be treated with elevated doses of the medicinal product. In general the habitual intake of analgesics, particularly the combination use of different analgesic substances, may cause permanent renal damage and a risk of renal failure (analgesics nephropathy). This risk may be increased under physical strain associated with loss of salt and dehydration therefore it should be avoided.
Ibuprofen may temporarily inhibit the blood platelet function (thrombocyte aggregation) and prolong the bleeding time. Patients with coagulation defects or on anticoagulant therapy should be observed carefully.
In case of prolonged treatment with ibuprofen a periodical monitoring of hepatic and renal function as well as the blood count is necessary, especially in high risk patients.
Consumption of alcohol should be avoided since it may intensify side effects of NSAIDs, especially if affecting the gastrointestinal tract or the central nervous system.
Severe acute hypersensitivity reactions (for example anaphylactic shock) are observed very rarely. At the first signs of a hypersensitivity reaction after taking/administering Ibuprofen, therapy must be stopped. Medically required measures, in line with the symptoms, must be initiated by specialist personnel.
Caution is required in the following patients;
- patients with congenital disorder of porphyrim metabolism (e.g. acute intermittent porphyria)
- patients who are dehydrated
- patients directly after major surgical procedures
Patients with rare hereditary problems of fructose intolerance should not take this medicine
4.5 Interaction with other medicinal products and other forms of interaction Ibuprofen should be avoided in combination with:
Acetylsalicylic acid (Aspirin): Concomitant administration of ibuprofen and acetylsalicylic acid is not generally recommended because of the potential of increased adverse effects (see section 4.4).
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: as a results of synergistic effects, avoid concomitant use of two or more NSAIDs as this may increase the risk of adverse effects (see section 4.4). Co-adminstration of ibuprofen with other NSAIDs should therefore be avoided (see section 4.4)
Ticlopidine: NSAIDs should not be combined with ticlopidine due to a risk of an additive effect in the inhibition of the platelet function.
Methotrexate: There is a potential for an increase in plasma methotrexate.
Ibuprofen should be used with caution in combination with:
Anticoagulants: NSAIDs may enhance the effects of anticoagulants, such as warfarin or heparin (see section 4.4). In case of simultaneous treatments, monitoring of the coagulation state is recommended.
Diuretics, ACE inhibitors, beta-receptor blocking medicines and angiotensin-II antagonists: NSAIDs may reduce the effect of diuretics and other antihypertensive 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, beta-receptor blocking medicines or angiotensin-II antagonists and agents that inhibit cyclo-oxygenase may result in further deterioration of renal function, including possible acute renal failure, which is usually reversible. 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.
The concomitant administration of ibuprofen and potassium-sparing diuretics may lead to hyperkalaemia.
Sulphonylureas:
Clinical investigations have shown interactions between NSAIDs and antidiabetics (sulphonylureas). Although interactions between ibuprofen and sulphonylureas have not been described to date, a check of blood-glucose values is recommended as a precaution on concomitant intake.
Probenecid and sulfinpyrazone:
Medicinal products that contain probenecid or sulfinpyrazone may delay the excretion of ibuprofen.
Corticosteroids: May increase the risk of adverse reactions in the gastrointestinal tract (see section 4.4 Special warnings).
Anti-platelets 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 increased plasma glycoside levels.
Ciclosporin: Increased risk of nephrotoxicity.
Tacrolimus: Possible increased risk of nephrotoxicity when NSAIDs are given with tacrolimus.
Lithium, Phenytoin: There is evidence for potential increase in plasma levels of these active ingredients. Checking the serum lithium levels is necessary and it is recommended to check the serum phenytoin levels.
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 quinolone may have increased risk of developing convulsions.
Ritonavir: May increase the plasma concentrations of NSAIDs.
Moclobemide: Enhances the effect of ibuprofen.
Captopril: Experimental studies indicate that ibuprofen counteracts the effect of captopril on increased sodium excretion.
Aminoglycosides: NSAIDs can slow down the elimination of aminoglycosides and increase their toxicity.
Cholestyramine: Concomitant treatment with cholestyramine and ibuprofen results in prolonged and reduced (25%) absorption of ibuprofen. The medicinal products should be administered with at least one hour interval.
Alcohol, bisphosphonates and oxpentifylline (pentoxyflline): May potentiate the GI side-effects and the risk of bleeding and ulceration.
Baclofen: Elevated baclofen toxicity.
4.6 Fertility, Pregnancy and lactation
Pregnancy
Inhibition of prostaglandin synthesis may adversely affect the pregnancy and/or the embryo/fetal 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-fetal 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 trimesters 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 trimesters 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 fetus 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 concentration and is unlikely to affect breast-fed infants adversely. If, however, longer treatment is prescribed, early weaning should be considered.
Fertility:
The use of ibuprofen may impair 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.
4.7 Effects on ability to drive and use machines
None expected at recommended dose and duration of therapy
4.8 Undesirable effects
The following frequencies are taken as a basis when evaluating undesirable effects:
Very common: Common: Uncommon: Rare:
Very rare:
Not known:
> 1/10
> 1/100 to < 1/10
> 1/1,000 to < 1/100
> 1/10,000 to < 1/1,000 < 1/10,000
cannot be estimated from the available data
With the following adverse drug reactions, it must be accounted for that they are predominantly dose-dependent and vary interindividually.
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 administration. Less frequently, gastritis has been observed.
Particularly the risk of gastrointestinal bleeding occurring is dependent on the dose range and the duration of use.
Clinical studies suggest that use of ibuprofen (particularly at high doses 2400mg/day) may be associated with a small increased risk of arterial thrombotic events (for example myocardial infarction or stroke) (see section 4.4).
Oedema, hypertension, and cardiac failure, have been reported in association with NSAID treatment.
The list of the following undesirable effects comprises all undesirable effects that have become known under treatment with ibuprofen, also those under high-dose long-term therapy in rheumatism patients. The stated frequencies, which extend beyond very rare reports, refer to the short-term use of daily doses up to a maximum of 1200 mg ibuprofen for oral dosage forms and a maximum of 1800 mg for suppositories (= 60 ml oral suspension of Ibuprofen Oral Suspension maximum daily dose for adults and children older than 12 years).
Infections and infestations:
Very rare: exacerbation of infection-related inflammations (e.g. development of necrotising fasciitis) coinciding with the use of non-steroidal anti-inflammatory drugs has been described. This is possibly associated with the mechanism of action of the non-steroidal anti-inflammatory drugs.
If signs of an infection occur or get worse during use of this product, the patient is therefore recommended to go to a doctor without delay. It is to be investigated whether there is an indication for an anti-infective/antibiotic therapy.
Very rare: the symptoms of aseptic meningitis with neck stiffness, headache, nausea, vomiting, fever or consciousnesses clouding have been observed under ibuprofen. Patients with autoimmune disorders (SLE, mixed connective-tissue disease) appear to be predisposed.
Blood and lymphatic system disorders:
Very rare: Haematopoietic disorders (anaemia, leucopenia, thrombocytopenia, pancytopenia, and agranulocytosis). First signs are: fever, sore throat, superficial mouth ulcers, flu-like symptoms, severe exhaustion, unexplained bleeding and bruising. In such cases, the patient should be advised to discontinue the medicine immediately, to avoid any self-medication with analgesics or antipyretics and to consult a physician.
The blood count should be checked regularly in long-term therapy
Immune system disorders:
Uncommon: Hypersensitivity reactions with skin rash and pruritis, as well as asthma attacks (possibly with drop in blood pressure).
The patient is to be instructed to inform a doctor at once and no longer to take Ibuprofen in this case.
Very rare: Severe general hypersensitivity reactions.
They may present as facial oedema, swelling of the tongue, swelling of the internal larynx with constriction of the airways, respiratory distress, racing heart, drop in blood pressure up to life-threatening shock.
If one of these symptoms occurs, which can happen even on first use, the immediate assistance of a doctor is required.
Psychiatric disorders:
Very rare: psychotic reactions, depression
Nervous system disorders:
Uncommon: central nervous disturbances such as headache, dizziness, sleeplessness, agitation, irritability or tiredness.
Eye disorders:
Uncommon: visual disturbances.
Ear and labyrinth disorders:
Rare: tinnitus.
Cardiac disorders
Very rare: palpitations, heart failure, myocardial infarction.
Vascular disorders:
Very rare: arterial hypertension.
Gastrointestinal disorders:
Common: gastro-intestinal complaints such as pyrosis, abdominal pain, nausea, vomiting, flatulence, diarrhoea, constipation and slight gastro-intestinal blood losses that may cause anaemia in exceptional cases.
Uncommon: gastrointestinal ulcers, potentially with bleeding and perforation. Ulcerative stomatitis, exacerbation of colitis and Crohn's disease (see section 4.4), gastritis.
Very rare: oesophagitis, pancreatitis, formation of intestinal, diaphragm-like strictures.
The patient is to be instructed to withdraw the medicinal product and to go to a doctor immediately if severe pain in the upper abdomen or melaena or haematemesis occurs.
Hepatobiliary disorders:
Very rare: Hepatic dysfunction, hepatic damage, particularly in long-term therapy, hepatic failure, acute hepatitis.
Skin and subcutaneous tissue disorders:
Uncommon: Various skin rashes, photosentivity
Very rare: Severe forms of skin reactions such as bullous reactions, including Stevens - Johnson syndrome, erythema multiforme and toxic epidermal necrolysis alopecia.
In exceptional cases, severe skin infections and soft-tissue complications may occur during a varicella infection (see also "Infections and infestations").
Renal and urinary disorders:
Rare: renal tissue damage (papillary necrosis), particularly in long-term therapy, increased serum uric acid concentration in the blood.
Very rare: reduced urinary excretion and formation of oedemas, particularly in patients with arterial hypertension or renal insufficiency, nephrotic syndrome, interstitial nephritis that may be accompanied by acute renal insufficiency.
Renal function should therefore be checked regularly.
Investigations
Rare: increase of blood urea nitrogen, serum transaminases and alkaline phosphatase, decrease in haemoglobin and haematocrit values, inhibition of platelet aggregation, prolonged bleeding time, decrease of serum calcium, increase in serum uric acid
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
5.1 Pharmacodynamic properties
Pharmacotherapeutic group: anti-inflammatory and antirheumatic products, non steroids; propionic acid derivatives
ATC Code: M01 AE01
Ibuprofen is a non-steroidal anti-inflammatory drug (NSAID) that in the conventional animal-experiment inflammation models has demonstrated its efficacy by inhibition of prostaglandin synthesis. In humans, ibuprofen reduces inflammatory pain, swellings and fever. Furthermore, ibuprofen reversibly inhibits ADP - and collagen-inducted 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 400 mg were taken within 8 h before or within 30 min after immediate release acetylsalicylic acid (aspirin) dosing (81 mg), 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
Absorption
On oral application ibuprofen is already partly absorbed in the stomach and then completely in the small intestine, peak serum concentrations occurring 1-2 hours after oral administration of a normal-release pharmaceutical form.
Distribution
Ibuprofen is rapidly distributed throughout the whole body. The plasma protein binding is approximately 99%.
Metabolism
Ibuprofen is metabolised in the liver (hydroxylation, carboxylation).
Elimination
Ibuprofen is metabolised in the live into two major metabolites with primary excretion via the kidneys. Either as such or as major conjugates, together with negligible amount of unchanged Ibuprofen, Excretion by the kidney is both rapid and complete. Elimination half life is approximately 2 hours.
5.3 Preclinical safety data
As a well established and widely used product, the pre-clinical safety of ibuprofen is well documented.
The principal findings observed during subchronic and chronic toxicity studies with ibuprofen include gastric damage and ulcers. Any observation made during the in vitro and in vivo studies to investigate the mutagenic potential of ibuprofen were not considered to be clinically significant.
Furthermore no carcinogenic effects have been observed in mice and rats.
Ibuprofen inhibits ovulation in rabbits and impairs implantation in various animal species (rabbit, rat, and mouse). In reprotoxicity studies in rats and rabbits; ibuprofen crossed the placenta. At dose causing toxicity to the mother, malformations (ventricular septal defects) occurred more frequently in the progeny of rats.
6 PHARMACEUTICAL PARTICULARS
6.1 List of excipients
Glycerol Xanthan gum,
Liquid Maltitol,
Polysorbate 80,
Saccharin sodium,
Citric acid monohydrate (for pH-adjustment), Magnesium Aluminium Silicate,
Sodium Benzoate (E211),
Strawberry flavour (contains propylene glycol)
Purified water
6.2 Incompatibilities
Not applicable.
6.3 Shelf life
24 months
In use shelf life: 3 months
6.4 Special precautions for storage
Do not store above 25°C. Store in the original pack.
6.5 Nature and contents of container
An amber glass bottle sealed with child resistant, tamper evident cap. Pack sizes available: 60 ml, 80ml, 100 ml, 150 ml and 200 ml.
Not all pack sizes may be marketed.
A double ended spoon with measures of 1.25ml 2.5ml or 5ml is provided.
6.6 Special precautions for disposal
Shake well before use. Return any left over medicine to the Pharmacist for safe disposal.
7 MARKETING AUTHORISATION HOLDER
Pinewood Laboratories Ltd (trading as Pinewood Healthcare),
Ballymacarbry,
Clonmel,
Co. Tipperary, Ireland.
MARKETING AUTHORISATION NUMBER(S)
8
PL04917/0099
9 DATE OF FIRST AUTHORISATION/RENEWAL OF THE AUTHORISATION
20/10/2011
10 DATE OF REVISION OF THE TEXT
24/12/2015