Ibuprofen 100 Mg Chewable Capsules Soft
SUMMARY OF PRODUCT CHARACTERISTICS
1 NAME OF THE MEDICINAL PRODUCT
Ibuprofen 100 mg, chewable capsules, soft
2 QUALITATIVE AND QUANTITATIVE COMPOSITION
Each chewable capsule, soft contains 100 mg Ibuprofen.
Excipient with known effect:
Glucose, 358.1 mg per chewable capsule Sucrose, 251.6 mg per chewable capsule
For the full list of excipients, see section 6.1.
3 PHARMACEUTICAL FORM
Chewable capsule, soft.
A light to dark yellow, square shaped chewable soft gelatin capsule with a hashtag (#) print in white ink. Typical dimensions of the soft gelatin capsule are approximately 5 to 8 mm in width and approximately 15 to 17 mm in length.
4 CLINICAL PARTICULARS
4.1 Therapeutic indications
For the symptomatic treatment of mild to moderate pain such as headache, period pain, dental pain and fever and pain associated with the common cold.
4.2 Posology and method of administration
For oral administration.
The product should be chewed before swallowing For 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).
Children from 7 to 12 years
For pain, fever and symptoms of cold and influenza: The daily dosage of Ibuprofen is 20-30 mg/kg bodyweight in divided doses. This can be achieved as follows:
Children 7 - 9 years: Two capsules may be taken 3 times in 24 hours.
Children 10 - 12 years: Three capsules may be taken 3 times in 24 hours.
Doses should be given approximately every 6 to 8 hours, (or with a minimum of 6 hours between each dose if required).
Not suitable for children under 7 years of age.
If in children this medicinal product is required for more than 3 days, or if symptoms worsen a doctor should be consulted.
Adolescents 12 to 18 years
Take up to 2 or 4 capsules, up to three times a day as required. Leave at least six hours between doses.
Do not take more than 12 capsules in any 24 hour period.
The minimum effective dose should be used for the shortest time necessary to relieve symptoms.
If in adolescents this medicinal product is required for more than 3 days, or if symptoms worsen a doctor should be consulted.
Adults
Take up to 2 or 4 capsules, up to three times a day as required. Leave at least six hours between doses.
Do not take more than 12 capsules in any 24 hour period.
The minimum effective dose should be used for the shortest time necessary to relieve symptoms.
If the product is required for more than 10 days, or if the symptoms worsen the patient should consult a doctor.
4.3 Contraindications
Hypersensitivity to ibuprofen or any of the constituents 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 upper gastrointestinal bleeding or perforation, related to previous NSAIDs therapy.
Severe hepatic failure, renal failure or heart failure (NYHA Class IV) (See section 4.4, Special warnings and precautions for use).
Last trimester of pregnancy (See section 4.6 Pregnancy and lactation).
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.
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 (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 Undesirable effects).
Porphyrin metabolism:
Caution is required in patients with congenital disorder of porphyrin metabolism (e.g. acute intermittent porphyria).
Renal:
Renal impairment as renal function may further deteriorate (See section 4.3 Contraindications and Section 4.8 Undesirable effects).
Hepatic:
Hepatic dysfunction (See section 4.3 Contraindications and Section 4.8 Undesirable effects).
Surgery:
Caution is required directly after major surgery.
Allergy:
Caution is required in patients who react allergically to other substances, as an increased risk of hypersensitivity reactions occurring also exists for them on use of Ibuprofen.
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.
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 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 4.5).
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.
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 in case of varicella.
Platelet Junction:
As NSAIDs can interfere with platelet function, they should be used with caution in patients with idiopathic thrombocytopenic purpura (ITP), intracranial haemorrhage and bleeding diathesis.
This product contains glucose. Patients with rare hereditary problems of galactose intolerance e.g. galacotosaemia, or glucose-galactose malabsorption should not take this medicine.
This product contains sucrose. Patients with rare hereditary problems of fructose intolerance, glucose-galactose malabsorption or sucrase-isomaltase insufficiency should not take this medicine.
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). Concomitant administration of ibuprofen and aspirin 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 aspirin 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 (aspirin) 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 as this may increase the risk of adverse effects (see section 4.4).
Ibuprofen should be used with caution in combination with:
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.
In particular, concomitant use of potassium-sparing diuretics may increase the risk of hyperkalaemia.
Corticosteroids: As these may increase the risk of gastrointestinal ulceration or bleeding (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 and phenytoin: There is evidence for potential increases in plasma levels of these medicinal products when co-administered with ibuprofen. If used correctly, monitoring of the plasma concentrations of lithium or phenytoin is usually not needed.
Probenecid and sulfinpyrazon: Medicinal products that contain probenecid or sulfinpyrazon may delay the excretion of ibuprofen.
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 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.
Oral hypoglycemic agents: Inhibition of metabolism of sulfonylurea drugs, prolonged half-life and increased risk of hypoglycaemia.
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 malformations and gastroschisis after use of prostaglandin synthesis inhibitors in early pregnancy. 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 (see section 4.3).
Breastfeeding
Ibuprofen and its metabolites pass only in low concentrations into breast milk. Since harmful effects to infants have not become known to date, interruption of breastfeeding is usually not necessary during short-term treatment with the recommended dose (see section 4.2).
Fertility
There is some evidence that drugs which inhibit cylooxygenase/prostglandin synthesis may cause impairment of female fertility by an effect on ovulation. This is reversible on withdrawal of treatment.
See section 4.4 regarding female fertility.
4.7 Effects on ability to drive and use machines
Ibuprofen has no expected influence at recommended doses and duration of therapy.
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, eg asthma, aggravated asthma, bronchospasm, dyspnoea
(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)
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.
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.
Gastrointestinal:
The most commonly observed adverse events are gastrointestinal in nature.
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.
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. 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.
Skin:
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 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).
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 maintainance 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: M01A E01 Propionic acid derivative NSAID
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 aspirin 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 acetyl salicylic acid (aspirin) dosing (81 mg), a decreased effect of acetylsalicylic acid (aspirin) 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 (aspirin) 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 about 2 hours.
In limited studies, ibuprofen appears in the breast milk in very low concentrations.
5.3 Preclinical safety data
The sub-chronic and chronic toxicity of ibuprofen in animal experiments showed up mainly in form of lesions and ulcerations in the gastro-intestinal tract. In vitro and in vivo studies gave no clinically relevant evidence of a mutagenic potential of ibuprofen. In studies in rats and mice no evidence of carcinogenic effects of ibuprofen was found. Ibuprofen led to an inhibition of ovulation in rabbits and impaired implantation in various animal species (rabbit, rat, mouse). Experimental studies in rats and rabbits have shown that ibuprofen crosses the placenta. Following administration of maternotoxic doses, an increased rate of malformations (ventricular septal defects) occurred in the progeny of rats.
6 PHARMACEUTICAL PARTICULARS
6.1 List of excipients
Gelatin Purified water Glucose, liquid Sucrose
Fumaric acid (E297)
Sucralose Citric acid (E330)
Acesulfame K (E950)
Disodium edetate Glycerin
Natural Orange Flavour*
*The flavour contains: (R)-p-mentha-1,8-diene (d-limonene), Ethyl acetate and Alpha-Pinene
Capsule _ printing
Opacode White NS-78-18011**
**The ink contains: Purified water, titanium dioxide (E171), propylene glycol, isopropyl alcohol, HPMC 2910/hypromellose 3cP (E464)
Processing Aids Medium Chain Triglycerides Isopropyl alcohol Lecithin Stearic acid
6.2 Incompatibilities
Not applicable.
6.3 Shelf life
15 months.
6.4 Special precautions for storage
Do not store above 30°C.
6.5 Nature and contents of container
Blisters formed of PVC/PE/PVdC/Al packed into cartons.
Each carton may contain 2, 4, 6, 8, 10, 12, 14, 16, 18, 20, 22, 24, 26, 28, 30, or 32 capsules.
Not all pack sizes may be marketed.
Special precautions for disposal
6.6
No special requirements.
7 MARKETING AUTHORISATION HOLDER
Patheon Softgels B.V. (trading as Banner Pharmacaps Europe) De Posthoornstraat 7 5048 AS Tilburg The Netherlands
8 MARKETING AUTHORISATION NUMBER(S)
PL 14338/0006
9 DATE OF FIRST AUTHORISATION/RENEWAL OF THE AUTHORISATION
14/11/2013
10 DATE OF REVISION OF THE TEXT
13/05/2016