Nurofen Express 200mg Liquid Capsules
SUMMARY OF PRODUCT CHARACTERISTICS
1 NAME OF THE MEDICINAL PRODUCT
Ibuprofen 200mg Liquicaps
Nurofen Express 200mg Liquid Capsules
Nurofen 200mg Liquid Capsules
2 QUALITATIVE AND QUANTITATIVE COMPOSITION
Each capsule, soft contains Ibuprofen 200 mg.
Excipients:
Sorbitol
Lecithin (E322)
Ponceau 4R (E124)
For a full list of excipients see 6.1.
3 PHARMACEUTICAL FORM
Capsule, soft.
A clear red oval soft gelatin capsule printed with an identifying logo in white.
4 CLINICAL PARTICULARS
4.1 Therapeutic indications
Adults and children over 12 years:
Ibuprofen 200mg Liquicaps are indicated for the symptomatic relief of rheumatic or muscular pain, backache, neuralgia, migraine, headache, dental pain, dysmenorrhoea, feverishness colds and influenza symptoms
4.2 Posology and method of administration
For oral administration and short-term use only.
Adults, the elderly and children and adolescents between 12 and 18 years:
Undesirable effects may be minimised by using the lowest effective dose for the shortest duration necessary to control symptoms (see section 4.4).
If in children and adolescents this medicinal product is required for more than 3 days, or if symptoms worsen a doctor should be consulted.
Adults should consult a doctor if symptoms persist or worsen, or if the product is required for more than 10 days.
Children and Adolescents between 12 and 18 years: Take one or two capsules, up to three times a day as required.
Adults: Take one or two capsules, up to three times a day as required.
Leave at least 4 hours between doses.
Do not take more than 6 capsules in any 24 hour period.
4.3 Contraindications
Patients with a known hypersensitivity to ibuprofen or any other constituent of the medicinal product.
Patients who have previously shown hypersensitivity reactions (e.g. asthma, rhinitis, angioedema, or urticaria) in response to aspirin or other non-steroidal antiinflammatory drugs (NSAIDs).
Patients with a history of, or existing gastrointestinal ulceration/perforation or bleeding, including that associated with NSAIDs. (See Section 4.4)
Patients with severe hepatic failure, severe renal failure or severe heart failure (NYHA Class IV). See also Section 4.4
Use with concomitant NSAIDs, including cyclo-oxygenase-2 specific inhibitors -increased risk of adverse reactions (see section 4.5)”
During the last trimester of pregnancy as there is a risk of premature closure of the fetal 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 4.6).
This product contains Lecithin. If you are allergic to peanut or soya, do not take this product.
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.
Respiratory:
Bronchospasm may be precipitated in patients suffering from, or with a 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 the use of ibuprofen, particularly at a high dose (2400 mg/day) may be associated with a small increased risk of arterial thrombotic (for example myocardial infarction or stroke). Overall, epidemiological studies do not suggest that low dose ibuprofen (e.g.< 1200mg/day) is associated in 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.
lmpaired female fertility:
There is some evidence that drugs which inhibit cyclo-oxygenase/ prostaglandin synthesis may cause impairment of female fertility by an effect on ovulation. This is reversible on 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 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 complaicated 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 enclosed leaflet before taking this product Do not take if you:
• have (or have had two or more episodes of ) a stomach ulcer, perforation or bleeding
• are allergic to ibuprofen, to any of the ingredients, or to aspirin or other painkillers
• are taking other NSAID pain killers or aspirin with a daily dose above 75mg
Speak to a pharmacist or your doctor before taking if you:
• have or have had asthma, diabetes, high cholesterol, high blood pressure, a stroke, heart, liver, kidney or bowel problems
• Are a smoker
• Are pregnant
This product contains Sorbitol. Patients with rare hereditary problems of fructose intolerance should not take this medicine.
Contains 50.5 mg of sorbitol per dose, a source of 12.6 mg of fructose per dose.
If symptoms persist or worsen, or if new symptoms occur, consult your doctor or pharmacist.
4.5 Interaction with other medicinal products and other forms of interaction Ibuprofen (like other NSAIDs) should be avoided in combination with:
• Aspirin (acetylsalicylic acid): Concomitant administration of ibuprofen and acetylsalicylic acid is not generally recommended because of the potential of increased adverse effects, unless low-dose aspirin (not above 75mg daily) has been advised by a doctor (see Section 4.4).
Experimental data suggest that ibuprofen may competitively inhibit the effect of low dose aspirin (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:
• Corticosteroids: as these may increase the risk of gastrointestinal ulceration or bleeding (see Section 4.4)
• Antihypertensives and diuretics: since NSAIDs may diminish the effects of these drugs. Diuretics can increase the risk of nephrotoxicity of NSAIDs.
• Anticoagulants. NSAIDs may enhance the effects of anti-coagulants, such as warfarin (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 increase in plasma levels of lithium.
• Methotrexate: There is evidence for the potential 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 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 Pregnancy and lactation
Whilst no teratogenic effects have been demonstrated in animal experiments, the use of Ibuprofen 200mg Liquicaps 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 Contraindications).
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 dose 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 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)
The list of the following 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.
Gastrointestinal Uncommon:
Disorders
Rare:
Very rare:
abdominal pain, dyspepsia and nausea.
diarrhoea, flatulence, constipation and vomiting
Peptic ulcer, perforation or gastrointestinal haemorrhage, melaena, haematemesis, sometimes fatal, particularly in the elderly. Ulcerative stomatitis gastritis.
Exacerbation of ulcerative colitis and Crohn’s disease (See section
4.4) (see section 4.4)
|
Nervous |
Uncommon: |
Headache |
|
System |
Very rare |
Aseptic meningitis - single cases have been reported very rarely |
|
Kidney |
Very rare: |
Decrease of urea excretion and oedema can occur. Also, acute renal failure. Papillary necrosis, especially in long-term use, and increased serum urea concentrations have been reported. |
|
Liver |
Very rare: |
Liver disorders, especially in longterm treatment. |
|
Blood |
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 |
Very rare: |
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)
urticaria and pruritus.
Reactions
Very rare severe hypersensitivity reactions.
Symptoms could be: facial, tongue and larynx swelling, dyspnoea, tachycardia, hypotension, (anaphylaxis, angioedema or severe shock).
Exacerbation of asthma and bronchospasm.
Cardiovascular and Cerebrovascular:
Oedema, hypertension, and cardiac failure, have been reported in association with NSAID treatment.
Clinical studies suggest that use of ibuprofen (particularly at a high dose 2400mg/day) 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 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
ATC Code: M01A E01 Propionic acid derivative.
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.
Clinical evidence demonstrates that when 400mg of ibuprofen is taken the pain relieving effects can last for up to 8 hours.
Experimental data suggest that ibuprofen may competitively inhibit the effect of low dose aspirin (acetylsalicylic acid) on platelet aggregation when they are dosed concomitantly. Some pharmacodynamics studies show that when single doses of ibuprofen 400mg were taken within 8 h before or within 30 min after immediate release aspirin (acetylsalicylic acid) dosing (81mg), a decreased effect of ASA (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 relevant effect is considered to be likely for occasional ibuprofen use (see section 4.5).
5.2 Pharmacokinetic properties
Ibuprofen is well absorbed from the gastrointestinal tract. Ibuprofen is extensively bound to plasma proteins.
Ibuprofen 200mg Liquicaps consist of ibuprofen 200 mg dissolved in a hydrophilic solvent inside a gelatin shell. On ingestion, the gelatin shell disintegrates in the gastric juice releasing the solubilised ibuprofen immediately for absorption. The median peak plasma concentration is achieved approximately 30 minutes after administration.
The median peak plasma concentration for Nurofen tablets is achieved approximately 1-2 hours after administration.
Ibuprofen is metabolised in the liver to two major metabolites with primary excretion via the kidneys, either as such or as major conjugates, together with a negligible amount of unchanged ibuprofen. Excretion by the kidney is both rapid and complete.
Elimination half-life is approximately 2 hours.
No significant differences in pharmacokinetic profile are observed in the elderly.
5.3 Preclinical safety data
No relevant information, additional to that contained elsewhere in the SPC
6 PHARMACEUTICAL PARTICULARS
6.1 List of excipients
Macrogol 600
Potassium hydroxide 50% solution (E525)
Gelatin
Sorbitol Liquid, Partially Dehydrated (E420)
Purified Water Ponceau 4R (E124)
Lecithin (E322) or Phosphatidylcholine in Medium Chain Triglycerides Triglycerides , medium chain Ethanol White ink*
The ink contains the following residual materials after application: Titanium Dioxide (E171), Polyvinyl Acetate Phthalate, Macrogol 400, ammonium hydroxide (E527), propylene glycol.
6.2 Incompatibilities
Not applicable.
6.3 Shelf life
24 months.
6.4 Special precautions for storage
Store below 25 °C
6.5 Nature and contents of container
Blisters formed from Opaque Duplex PVC/PVdC 250pm/60gsm heat sealed to 20pm aluminium foil or opaque Tristar (Triplex) PVC/PE/PVdC 250pm/25pm/90gsm heat sealed to 20pm aluminium foil packed into cartons
Each carton may contain 10, 12, 16 in blister strips
Not all packs will be marketed.
6.6 Special precautions for disposal
Not applicable.
7 MARKETING AUTHORISATION HOLDER
Reckitt Benckiser Healthcare (UK) Ltd
Slough
SL1 4AQ
8 MARKETING AUTHORISATION NUMBER(S)
PL 00063/0648
9 DATE OF FIRST AUTHORISATION/RENEWAL OF THE AUTHORISATION
25/01/2008
10 DATE OF REVISION OF THE TEXT
08/01/2016