Migraine Relief 342 Mg Film-Coated Tablets
SUMMARY OF PRODUCT CHARACTERISTICS
1 NAME OF THE MEDICINAL PRODUCT
Migraine Relief 342 mg Film-coated Tablets
2 QUALITATIVE AND QUANTITATIVE COMPOSITION
Each tablet contains 342 mg of ibuprofen lysine (equivalent to ibuprofen 200 mg).
For the full list of excipients, see section 6.1.
3 PHARMACEUTICAL FORM
Film-coated tablet.
White to off-white, film-coated, round, biconvex, bevelled edge tablet imprinted with “M” over “IL1” in black ink on one side of the tablet and blank on the other side.
4 CLINICAL PARTICULARS
4.1 Therapeutic indications
For the relief of headache and migraine pain.
4.2 Posology and method of administration
Posology
Adults, the elderly and children over 12 years:
1 or 2 tablets up to three times a day as required. Leave at least four hours between doses and do not take more than 6 tablets in any 24 hour period.
Undesirable effects may be minimised by using the lowest effective dose for the shortest duration necessary to control symptoms (see section 4.4). The patient should consult a doctor if symptoms persist or worsen, or if the product is required for more than 10 days.
Paediatric population
Migraine Relief is not recommended in children under 12 years old.
If in children aged from 12 years and in adolescents this medicinal product is required for more than 3 days, or if symptoms worsen a doctor should be consulted.
Elderly patients
No special dose adjustment is necessary. Elderly patients should be monitored particularly carefully due to the possible undesirable effect profile (see section 4.4).
Patients with sensitive stomachs
Patients with sensitive stomachs should take Migraine Relief during a meal.
Patients with renal or hepatic deficiency
Patients with renal or hepatic deficiency should first consult a doctor before taking Migraine Relief.
Method of administration:
For oral administration and short-term use only. Migraine Relief tablets are swallowed whole with plenty of water. Do not chew the tablets.
4.3 Contraindications
Migraine Relief is contraindicated in patients:
- with hypersensitivity to the active substance or to any of the excipients listed in section 6.1,
- who have previously shown hypersensitivity reactions (e.g. angioedema, rhinitis, urticaria or asthma) in response to aspirin or other non-steroidal anti-inflammatory drugs (NSAIDs),
- with active or a history of recurrent peptic ulcer/haemorrhage (two or more distinct episodes of proven ulceration or bleeding),
- with history of gastrointestinal bleeding or perforation, related to previous NSAIDs therapy,
- with severe hepatic insufficiency, severe renal insufficiency or severe heart failure (NYHA Class IV) (see section 4.4),
- during the last trimester of pregnancy (see section 4.6).
4.4 Special warnings and precautions for use
Taking ibuprofen with the lowest effective dose for the shortest period required to alleviate symptoms reduces the risk of adverse reactions (see effects on gastrointestinal tract and circulatory system).
Elderly:
The elderly have an increased frequency of adverse reactions to NSAIDs especially gastrointestinal 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:
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.
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) 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. < 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 or 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, have 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 ulcers, 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 the 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.
The label will include:
Read the package leaflet before use.
For rapid relief of headache and migraine pain.
This medicine is used for the rapid relief of headaches and migraine pain.
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 of the other ingredients of this medicine, aspirin or other related painkillers
• are taking other NSAID painkillers, or aspirin, with a daily dose above 75 mg.
Speak to a pharmacist or your doctor before taking this product if you:
• have or have ever had asthma, diabetes, high cholesterol, high blood pressure, a stroke, heart, liver, kidney or bowel problems
• are a smoker
• are pregnant
Dosage:
For oral administration and short-term use only.
Adults, the elderly and children aged 12 years or older: Take 1 or 2 tablets with water, up to three times a day as required.
Leave at least four hours between doses.
Do not take more than 6 tablets in 24 hours.
Do not give to children under 12 years.
You should not take this medicine for longer than 10 days. If symptoms persist or worsen, consult your doctor.
4.5 Interaction with other medicinal products and other forms of interaction
The following drug interactions have been identified for ibuprofen acid. Ibuprofen (like other NSAIDs) should be avoided in combination with:
Acetylsalicylic acid: Concomitant administration of ibuprofen and acetylsalicylic acid is not generally recommended because of the potential for increased adverse effects, unless low-dose acetylsalicylic acid (not above 75 mg daily) has been advised by a doctor (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: 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 anticoagulants, such as warfarin (see section 4.4).
Antihypertensives (ACE-inhibitors and Angiotensin II Antagonists) and diuretics: since NSAIDs may diminish the effect of these 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 or Angiotensin II antagonist and agents that inhibit cyclo-oxygenase may result in further deterioration of renal function, including possible acute renal failure, which is usually reversible. These interactions should be considered in patients taking a coxib concomitantly with ACE inhibitors or angiotensin II antagonists. 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. 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 levels of 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
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 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 embryofoetal 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 oligohydroamniosis
At the end of the pregnancy the mother and the neonate may be exposed 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. Breast-feeding
In limited studies, ibuprofen appears in breast milk in very low concentration and is unlikely to affect the breast fed infant adversely.
Fertility
See section 4.4 regarding female fertility.
4.7 Effects on ability to drive and use machines
Ibuprofen lysine has no or negligible influence on the ability to drive and use machines.
4.8 Undesirable effects
Adverse events which have been associated with ibuprofen are given below, listed by system organ class and frequency. Frequencies are defined as:
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
Not known (cannot be estimated from the available data)
Within each frequency grouping, adverse events are presented in order of decreasing seriousness.
The list of the following adverse effects relates to those experienced with Ibuprofen at OTC doses (maximum 1200mg per day) for short-term use. In the treatment of chronic conditions, under long-term treatment, additional adverse events may occur.
The most commonly observed adverse events are gastrointestinal in nature. Adverse events are mostly dose-dependent, in particular the risk of occurrence of gastrointestinal bleeding is dependent on the dosage range and duration of treatment.
Clinical studies suggest that the 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).
|
System Organ Class |
Frequency |
Adverse event |
|
Blood and lymphatic system disorders |
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 |
|
Immune system disorders |
Uncommon Very rare |
Hypersensitivity reactions consisting of1: Urticaria and pruritus Severe hypersensitivity reactions. |
|
Not known |
Symptoms could be: facial, tongue and laryngeal swelling, dyspnoea, tachycardia, hypotension, (anaphylaxis, angioedema or severe shock) Respiratory tract reactivity comprising asthma, aggravated asthma, bronchospasm or dyspnoea | |
|
Nervous system |
Uncommon |
Headache |
|
disorders | ||
|
Very rare |
Aseptic meningitis 2 | |
|
Cardiac disorders |
Not known |
Cardiac failure and oedema |
|
Vascular disorders |
Not known |
Hypertension |
|
Gastrointestinal |
Uncommon |
Abdominal pain, nausea, dyspepsia |
|
disorders | ||
|
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. | |
|
Not known |
Exacerbation of colitis and Crohn’s disease (see section 4.4) | |
|
Hepatobiliary disorders |
Very rare |
Liver disorders |
|
Skin and subcutaneous |
Uncommon |
Various skin rashes |
|
tissue disorders | ||
|
Very rare |
Severe forms of skin reactions including Stevens-Johnson syndrome, erythema multiforme and toxic epidermal necrolysis can occur | |
|
Renal and urinary |
Very rare |
Acute renal failure, papillary necrosis, |
|
disorders |
especially in long-term use, associated with increased serum urea and oedema | |
|
Not known |
Renal insufficiency | |
|
Investigations |
Very rare |
Decreased haemoglobin levels |
1. Hypersensitivity reactions have been reported following treatment with ibuprofen. These may consist of (a) non-specific allergic reactions and anaphylaxis, (b) respiratory tract activity comprising asthma, aggravated asthma, bronchospasm, dyspnoea or (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).
2. The pathogenic mechanism of drug-induced aseptic meningitis is not fully understood. However, the available data on NSAID-related aseptic meningitis points to a hypersensitivity reaction (due to a temporal relationship with drug intake, and disappearance of symptoms after drug discontinuation). Of note, single cases of symptoms of aseptic meningitis (such as stiff neck, headache, nausea, vomiting, fever or disorientation) have been observed during treatment with ibuprofen, in patients with existing auto-immune disorders (such as systemic lupus erythematosus, mixed connective tissue disease).
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
Website: 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 PHARMACOLOGICAL PROPERTIES
5.1 Pharmacodynamic properties
Pharmacotherapeutic group: anti-inflammatory and antirheumatic products, non-steroids, propionic acid derivative.
ATC code: M01A E01
Mechanism of action
Ibuprofen lysine is the lysine salt of ibuprofen, a propionic acid derivative, having analgesic, anti-inflammatory and antipyretic activity. The therapeutic effects of ibuprofen lysine as a non steroidal anti-inflammatory drug are thought to result from inhibitory activity on prostaglandin synthesis.
Following oral administration, ibuprofen lysine dissociates to ibuprofen acid and lysine. Lysine has no recognised pharmacological activity. The pharmacological properties of ibuprofen lysine, therefore, are the same as those of ibuprofen acid.
Experimental data suggest that ibuprofen may competitively inhibit the effect of low dose acetylsalicylic acid on platelet aggregation when they are dosed concomitantly. Some pharmacodynamics 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
Most pharmacokinetic data obtained following the administration of ibuprofen acid also apply to ibuprofen lysine.
Peak plasma concentrations occur 1-2 hours after administration of ibuprofen acid. However, ibuprofen is more rapidly absorbed from the gastrointestinal tract following the administration of ibuprofen lysine tablets, with peak plasma concentrations occurring approximately 35 minutes after administration in the fasting state.
The elimination half-life of ibuprofen acid is approximately 2 hours.
The drug is extensively bound to plasma proteins.
Ibuprofen is metabolised in the liver to two inactive metabolites and these, together with unchanged ibuprofen, are excreted by the kidney either as such or as conjugates. Excretion by the kidney is both rapid and complete.
No specific difference in pharmacokinetic profile is observed in the elderly.
5.3 Preclinical safety data
No relevant information additional to that contained elsewhere within the SmPC.
PHARMACEUTICAL PARTICULARS
6
6.1 List of excipients
Core tablet
Cellulose, microcrystalline Silica, colloidal anhydrous Crospovidone Povidone
Magnesium stearate Talc (E553b)
Tablet coating
Polyvinyl alcohol hydrolysed Titanium dioxide (E171)
Macrogol Talc (E553b)
Printing Ink Shellac
Iron oxide black (E172)
Ammonium hydroxide (E527).
6.2 Incompatibilities
Not applicable
6.3 Shelf life
3 years
6.4 Special precautions for storage
This medicinal product does not require any special storage conditions.
6.5 Nature and contents of container
Blister pack comprises of white opaque PVC laminated with Aclar on one side and hard tempered aluminium foil coated with VMCH heat seal lacquer on the other side.
or
Cold form blister pack comprises of cold form laminate (aluminium foil laminated to oriented polyamide on one side and laminated to PVC on the other side i.e. OPA / Al / PVC) on one side and hard tempered aluminium foil coated with VMCH heat seal lacquer on the other side.
Blisters are placed in an outer cardboard carton.
Pack sizes: 8, 12, 16 tablets.
Not all pack sizes may be marketed.
6.6 Special precautions for disposal
Not applicable
7 MARKETING AUTHORISATION HOLDER
Generics [UK] Limited t/a Mylan
Station Close
Potters Bar
Hertfordshire
EN6 1TL
United Kingdom
MARKETING AUTHORISATION NUMBER(S)
PL 04569/1453
DATE OF FIRST AUTHORISATION/RENEWAL OF THE AUTHORISATION
04/09/2013
10
DATE OF REVISION OF THE TEXT
02/03/2016