Flarin 200 Mg Soft Capsules
SUMMARY OF PRODUCT CHARACTERISTICS
1 NAME OF THE MEDICINAL PRODUCT
Flarin 200 mg soft capsules
2 QUALITATIVE AND QUANTITATIVE COMPOSITION
Ibuprofen 200 mg per capsule, soft.
Excipient(s) with a known effect:
Brilliant blue (E133) and allura red (E129)
For the full list of excipients see section 6.1.
3 PHARMACEUTICAL FORM
Capsule, soft
Oval red and blue capsules, containing a solid white lipid capsule fill and printed with “Flarin” in white on the capsule shell.
4 CLINICAL PARTICULARS
4.1 Therapeutic indications
For the relief of rheumatic or muscular pain, pain of non-serious arthritic conditions, backache, neuralgia, migraine, headache, dental pain, dysmenorrhea, feverishness, symptoms of colds and influenza.
4.2 Posology and method of administration
For oral administration and short-term use only. Do not chew.
Undesirable effects may be minimised by using the lowest effective dose for the shortest duration necessary to control symptoms (see section 4.4).
Children under 12 years:
Not recommended.
Adults, the elderly and children over 12 years
If in adolescents (age range > 12 years to 18 < years) this medicinal product is required for more than 3 days, or if symptoms worsen a doctor should be consulted.
The patient over 18 years old should consult a doctor if symptoms persist or worsen, or if the product is required for more than 10 days.
Take one or two capsules (200 mg - 400 mg), up to three times a day as required.
Leave at least four hours between doses and do not take more than 1200 mg in any 24 hour period.
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 heart failure (NYHA Class IV), renal failure or hepatic failure (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 have an increased frequency of adverse reactions to NSAIDs, especially GI bleeding and perforation which may be fatal.
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).
Renal:
There is a risk of renal impairment in dehydrated adolescents.
Renal impairment as renal function may further deteriorate (See sections 4.3 and 4.8).
Hepatic:
Hepatic dysfunction (See sections 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.
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 NSAIDs 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 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, StevensJohnson 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.
Patients with rare hereditary problems of fructose intolerance should not take this medicine because of the presence of sorbitol.
4.5 Interaction with other medicinal products and other forms of interaction
Ibuprofen should be avoided in combination with:
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:
Acetylsalicylic acid: Concomitant administration of ibuprofen and acetylsalicylic acid 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 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 cannot be excluded. No clinically relevant effect is considered to be likely for occasional ibuprofen use (see section 5.1).
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: Increased 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: 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 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 mother and child (See section 4.3).
In limited studies, ibuprofen appears in the breast milk in 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
The most commonly observed adverse events are gastrointestinal in nature. Hypersensitivity reactions have been reported and these may consist of:
(a) Non-specific allergic reactions and anaphylaxis
(b) Respiratory tract reactivity, e.g. asthma, aggravated asthma, bronchospasm, dyspnoea
(c) Various skin reactions, e.g. pruritus, urticaria, angioedema and more rarely exfoliative and bullous dermatoses (including epidermal necrolysis and erythema multiforme)
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) (see section 4.4).
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 long-term treatment, additional adverse effects may occur. Treatment related adverse reactions are listed below by MedDRA system organ class and frequency. The following convention has been utilised for the classification of frequency: very common > 1/10; common > 1/100 to < 1/10, uncommon > 1/1,000 to < 1/100; rare > 1/10,000 to < 1/1,000; very rare < 1/10,000 and not known (cannot be estimated from the available data).
|
MedDRA Standard System Organ Class |
Adverse Reactions |
Frequency |
|
Blood and lymphatic system disorders |
Haematopoietic disorders (anaemia, leucopenia, thrombocytopenia, pancytopenia, agranulocytosis). First signs are: fever, sore throat, superficial mouth ulcers, flu-like symptoms, severe exhaustion, unexplained bleeding and |
Very rare |
|
bruising. | ||
|
Immune system disorders |
Hypersensitivity reactions with urticaria and pruritus. |
Uncommon |
|
Severe hypersensitivity reactions. Symptoms could be: facial, tongue and laryngeal swelling, dyspnoea, tachycardia, hypotension, (anaphylaxis, angioedema or severe shock). Exacerbation of asthma and bronchospasm. |
Very rare | |
|
Nervous system disorders |
Headache |
Uncommon |
|
Aseptic meningitis1 |
Very rare | |
|
Cardiac disorders |
Cardiac failure, hypertension and oedema |
Not known |
|
Gastrointestinal disorders |
Abdominal pain, nausea and dyspepsia. |
Uncommon |
|
Diarrhoea, flatulence, constipation and vomiting. |
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). |
Very rare | |
|
Hepatobiliary disorders |
Liver disorders. |
Very rare |
|
Skin and subcutaneous tissue disorders |
Various skin rashes |
Uncommon |
|
Severe forms of skin reactions such as bullous reactions, including Stevens-Johnson syndrome, erythema multiforme and toxic epidermal necrolysis can occur. |
Very rare | |
|
Renal and urinary disorders |
Acute renal failure, papillary necrosis, especially in long-term use, associated with increased serum urea and oedema. |
Very rare |
|
1 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).
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
ATC code M01AE01
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 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 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
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
There are no preclinical safety data of relevance additional to that contained elsewhere in the SmPC.
6 PHARMACEUTICAL PARTICULARS
6.1 List of excipients
Capsule contents Macrogol 400 Hard Fat
Glycerol monolinoleate
Hard fat and glycerol monolinoleate are lipids, which are long chain fatty acids from a vegetable source.
Capsule shell
Gelatin Sorbitol Purified water Brilliant Blue (E133)
Allura Red (E129)
Capsule printing ink
Purified water
Titanium dioxide
Propylene glycol
Isopropyl alcohol
HPMC 2910/Hypromellose 3cP
6.2 Incompatibilities
Not applicable.
6.3 Shelf life
24 months.
6.4 Special precautions for storage
Do not store above 25°C. Store in the original package.
6.5 Nature and contents of container
A blister pack consisting of opaque, white 250 micron polyvinyl chloride (PVC)/30 micron polyethylene, coated with 90 g/m2 polyvinylidene chloride (PVDC), heat sealed to 20 micron aluminium foil. The blisters are packed into cardboard cartons.
Package size(s): 4, 10, 16 or 30 capsules per carton.
Not all pack sizes may be marketed.
6.6 Special precautions for disposal
No special requirements.
Any unused product or waste material should be disposed of in accordance with local requirements.
7 MARKETING AUTHORISATION HOLDER
infirst HEALTHCARE Ltd.
Central Point
45 Beech Street London EC2Y 8AD
8 MARKETING AUTHORISATION NUMBER(S)
PL 42459/0002
9 DATE OF FIRST AUTHORISATION/RENEWAL OF THE AUTHORISATION
15/09/2014
10 DATE OF REVISION OF THE TEXT
10/12/2015