Migrafen Tablets
SUMMARY OF PRODUCT CHARACTERISTICS
1 NAME OF THE MEDICINAL PRODUCT
MIGRAFEN Tablets
2 QUALITATIVE AND QUANTITATIVE COMPOSITION
Ibuprofen BP 200 mg
3 PHARMACEUTICAL FORM
Sugar-coated tablet
4
CLINICAL PARTICULARS
4.1 Therapeutic indications
a) For the symptomatic relief of migraine, headaches, rheumatic pain or muscular pain, pain of non serious arthritic conditions backache, lumbago, fibrositis, period pain, dental pain, neuralgia, colds and influenza.
b) Migrafen reduces inflammation and feverishness (lowers body temperature).
4.2 Posology and method of administration
For oral administration and short -term use only.
Adults, the elderly and children over 12 years
200mg - 400mg, up to three times a day as required. To be taken preferably after food.
The minimum effective dose should be used for the shortest time necessary to relieve symptoms. The patient should consult a doctor if symptoms persist or worsen, or if the product is required for more than 10 days.
If in adolescents (between 12 and 18 years) 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 1200 mg in any 24 hour period.
Not to be given to children under 12 years
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 nonsteroidal anti-inflammatory drugs.
Active or previous peptic ulcer.
History of upper gastrointestinal bleeding or perforation, related to previous NSAIDs therapy.
Use with concomitant NSAIDs including cyclo-oxygenase-2 specific inhibitors (See Section 4.5 Interactions).
Severe hepatic failure, renal failure or heart failure (See section 4.4, Special warnings and precautions for use).
Last trimester of pregnancy (See section 4.6 Pregnancy and lactation).
Severe heart failure.
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).
Cardiovascular and cerebrovascular effects
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). Overall, epidemiological studies do not suggest that low dose ibuprofen (e.g. < 1200mg daily) is associated with an increased risk of myocardial infarction.
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.
Acute interstitial nephritis with haematuria, proteinuria and occasionally, nephrotic syndrome has been reported.
In patients with renal, cardiac or hepatic impairment, the elderly and patients taking diuretics, caution is required since the use of NSAIDs may result in deterioration of renal function. Where the renal prostaglandins play a part in the maintenance of renal diffusion; a dose- dependant reduction in prostaglandin formation may result and this may precipitate a renal decompensation. The dose should be kept as low as possible and renal function should be monitored. NSAIDs have been reported to cause nephrotoxicity in various forms and their use can lead to interstitial nephritis, nephritic syndrome and renal failure.
Patients with impaired renal function should be closely monitored and a reduction in dosage should be used in order to avoid drug accumulation because Ibuprofen is eliminated mainly by the kidneys. Similarly, all patients who are at risk of developing renal dysfunction during long-term treatment should be monitored for renal function periodically.
There is a risk of renal impairment in dehydrated children and adolescents.
Hepatic dysfunction (See section 4.3 Contraindications and Section 4.8 Undesirable effects).
Patients should report to their physician if signs or symptoms of gastrointestinal ulceration or bleeding, any eye symptoms such as blurred vision, oedema, weight gain or skin rash are observed. When gastro-intestinal bleeding and peptic ulceration occurs in those patients receiving Ibuprofen, the treatment should be withdrawn.
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.
All patients with a history of upper gastrointestinal tract disease should be kept under close supervision when receiving ‘Migrafen’. Likewise for patients with chronic inflammatory intestinal disease (Ulcerative colitis, Crohn’s disease) - as these conditions may be exacerbated (See section 4.8 Undesirable effects).
GI bleeding, ulceration or perforation, which can be fatal, have been reported for all NSAIDs at anytime during treatment, with or without warning symptoms or a previous history of serious GI events Caution should be advised in patients receiving concomitant medications which could increase the risk of gastrotoxicity or bleeding, e.g. corticosteroids, anticoagulants such as warfarin or anti-platelet agents such as aspirin (see section 4.5 Interactions).
Bronchospasm may be precipitated in patients suffering from or with a previous history of bronchial asthma or allergic disease. Treatment should be discontinued in patients reporting ocular defects such as diminished vision, blurred vision, changes in colour vision or scotomata.
In patients with systemic lupus erythematosus and mixed connective tissue disease there is an increased risk of aseptic meningitis (see section 4.8 Undesirable effects).
There is limited evidence that drugs that inhibit cyclooxygenase/ prostaglandin synthesis may cause impairment of female fertility by an effect on ovulation. This is reversible upon withdrawal of treatment.
The elderly are at increased risk of the serious consequences of adverse reactions.
The label will include:
Read the enclosed leaflet before taking this product.
Do not take if you
• have or have ever had a stomach ulcer, perforation or bleeding
• are allergic to ibuprofen or any other ingredient 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 asthma, liver, heart, kidney or bowel problems
• are in the first 6 months of pregnancy
If symptoms persist or worsen, consult your doctor.
4.5 Interaction with other medicinal products and other forms of interaction Ibuprofen should not be used 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 (See section 4.3 Contraindications).
Other NSAIDS: As these may increase the risk of adverse effects (See section
4.3 Contraindications).
Ibuprofen should be used with caution in combination with:
Anti-coagulant therapy: NSAIDS may enhance the effects of anti-coagulants, such as warfarin (See section 4.4). Ibuprofen has been shown to prolong bleeding time and this prolonged bleeding time may be exaggerated in this category of patient.
Anti-hypertensives and diuretics: NSAIDs may diminish the effect of these drugs. Ibuprofen reduces the natriuretic effect of Furosemide and thiazide diuretics. This is thought to be due to the inhibition of renal Prostaglandin synthesis by NSAIDs (including Ibuprofen). Accordingly, patients being treated concomitantly with Ibuprofen and thiazides or Furosemide should be closely monitored.
Aspirin and other NSAID’s: Possible net decrease in anti-inflammatory activity and possible increase in adverse reactions.
Corticosteroids: May increase the risk of adverse reactions in the gastrointestinal tract (See section 4.4 Special warnings).
Lithium: Ibuprofen has been shown to produce an elevation of plasma lithium levels and a reduction in renal lithium clearance. Patients receiving Ibuprofen and Lithium concurrently should be observed for signs of lithium toxicity.
Methotrexate: Enhanced toxicity of methotrexate may ensue due to a reduction of renal tubular secretion of methotrexate.
Zidovudine: There is evidence of an increased risk of haemarthroses and haematoma in HIV (+) haemophiliacs receiving concurrent treatment with zidovudine and ibuprofen.
4.6 Pregnancy and lactation
Whilst no teratogenic effects have been demonstrated in animal studies, Ibuprofen should, if possible, be avoided during the first 6 months of pregnancy.
During the third 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 duration of labour increased with an increased bleeding tendency in both mother and child. (See section 4.3 Contraindications).
Ibuprofen appears in breast milk in very low concentrations 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
‘Migrafen’ does not to affect the ability to drive or use machines at the recommended doses.
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, e.g. asthma, aggravated asthma, bronchospasm or dyspnoea
c) assorted skin disorders, including rashes of various types, pruritis, urticaria, purpura, angiodema and, less commonly, 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 long-term treatment, additional adverse effects may occur.
Gastro-intestinal
Uncommon: Abdominal pain, nausea and dyspepsia.
Rare: diarrhoea, flatulence, constipation and vomiting.
Very rare: peptic ulcer, perforation or gastro-intestinal haemorrhage, sometimes
fatal, particularly in the elderly. Exacerbation of ulcerative colitis and Crohn’s disease (See section 4.4)
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
Renal:
Very rare: Acute renal failure and papillary necrosis which can lead to renal
failure, especially in long term use, associated with increased serum urea and
oedema.
Hypersensitivity reactions:
Uncommon: Hypersensitivity reactions with urticaria and pruritis.
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 has been reported.
Nervous System:
Uncommon: Headache.
Hepatic:
Very rare: liver disorders.
Skin:
Uncommon: Various skin rashes.
Very rare: Severe forms of skin reactions such as erythema multiforme and 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).
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).
Oedema, hypertension, and cardiac failure, have been reported in association with NSAID treatment.
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 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 PHARMACOLOGICAL PROPERTIES
5.1 Pharmacodynamic properties
Ibuprofen is a phenylpropionic acid derivative NSAID that has demonstrated its efficacy by inhibition of prostaglandin synthesis with analgesic, anti-inflammatory and antipyretic actions. Furthermore, ibuprofen reversibly inhibits platelet aggregation.
5.2 Pharmacokinetic properties
Ibuprofen is rapidly absorbed from the gastro-intestinal tract. 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 drug is extensively bound to plasma proteins and has a half-life of about 2 hours. It is rapidly excreted via the kidneys, mainly in the form of metabolites and their conjugates. About 1% is excreted in the urine as unchanged Ibuprofen and about 14% as conjugated Ibuprofen. In limited studies, ibuprofen appears in the breast milk in very low concentrations
Preclinical safety data
5.3
Not applicable.
6 PHARMACEUTICAL PARTICULARS
6.1 List of excipients
Migrafen tablets also contain: Maize starch, talc, crospovidone, colloidal silicone dioxide, magnesium stearate, stearic acid, shellac, povidone, Opalux (contains quinoline yellow E104, erythrosin E127, titanium dioxide E171 and sodium benzoate E211), sucrose, beeswax and carnauba wax.
6.2 Incompatibilities
No known incompatibilities other than those stated in 4.4 and 4.5 above.
6.3 Shelf life
The shelf life of Ibuprofen tablets 200 mg as packaged for sale is: 36 months in plastic containers 24 months in blister-packs
6.4 Special precautions for storage
Store below 25°C in a dry place.
6.5 Nature and contents of container
1. High density polystyrene with polythene lids and/or polypropylene containers with polypropylene or polythene lids and polyurethane or polythene inserts.
Packs of 100 and 500 tablets for the P product.
2. PVC aluminium foil blister packs, composed of 230 micron PVC
glass- clear/bluish rigid PVC (pharmaceutical grade) and 20 micron hard-tempered aluminium foil coated on the dull side with 6.7 gsm heat-seal lacquer and printed on the bright side. The blister strips are enclosed in outer cardboard cartons.
Blister-packs of 12 and 24 tablets for the P product and 12 tablets for the GSL product.
6.6 Special precautions for disposal
No special instructions.
7 MARKETING AUTHORISATION HOLDER
Chelonia Healthcare Limited
Boumpoulinas 11, 3 rd Floor
NICOSIA
CYPRUS
PC. 1060
CYPRUS
8 MARKETING AUTHORISATION NUMBER(S)
PL 33414/0085
DATE OF FIRST AUTHORISATION/RENEWAL OF THE AUTHORISATION
4/12/84 / 24/6/96
10
DATE OF REVISION OF THE TEXT
29/01/2016