SUMMARY OF PRODUCT CHARACTERISTICS

1 NAME OF THE MEDICINAL PRODUCT

Nurofen Max Strength Joint & Back Pain Relief 512mg tablets

2    QUALITATIVE AND QUANTITATIVE COMPOSITION

Ibuprofen 400 mg (as sodium dihydrate).

Also contains the following excipients:

carmellose sodium

xylitol

sucrose

For a full list of excipients, see Section 6.1.

3    PHARMACEUTICAL FORM

Tablet

A white to off-white, biconvex, round, sugar coated tablet printed with an identifying logo in red on one face.

4    CLINICAL PARTICULARS

4.1    Therapeutic indications

For the symptomatic relief of mild to moderate pain, such as headache, backache, period pain, dental pain, neuralgia, rheumatic and muscular pain, the pain of non-serious arthritis, migraine, cold and flu symptoms, sore throat and fever.

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 between 12 and 18 years 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 tablet, up to three times a day as required.

Adults: Take one tablet, up to three times a day as required.

Leave at least four hours between doses and do not take more than 1200mg in any 24 hour period.

Not for use by children under 12 years of age.

Elderly: No special dosage modifications are required (see Section 4.4).

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, angioderma 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 also section 4.4). Last trimester of pregnancy

4.4 Special warnings and precautions for use

Undesirable effects may be minimised by using the lowest effective dose for the shortest possible 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, Undesirable effects)

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 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 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 any time 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 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 NSAIDSs (see Section 4.8). Patients appear to be at highest risk of 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. Nurofen Max Strength Joint & Back Pain Relief 512mg tablets should be discontinued at the first appearance of skin rash, mucosal lesions, or any other sign of hypersensitivity.

Advice for patients with sugar-related disorders:

Patients with rare hereditary problems of fructose intolerance, glucose-galactose malabsorption or sucrase-isomaltase insufficiency should not take this medicine.

Advice for patients on a controlled sodium diet:

Each tablet contains 48.6 mg (approximately 2.12 mmol) sodium. This should be considered in patients whose overall intake of sodium must be markedly restricted.

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 or are dehydrated

•    are a smoker

•    are pregnant

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 not be used 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 (ACE inhibitors and Angiotensin II Antagonists) and diuretics since NSAIDs may diminish the effects 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.

•    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). These can increase the 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 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.

4.6 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, Nurofen should not be given unless clearly necessary. If Nurofen 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; the mother and the neonate, at the end of the 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, Nurofen is contraindicated during the third trimester of pregnancy.

Lactation/Breastfeeding:

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

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 (>1/1000 to <1/100), rare (>1/10,000 to <1/1000), very rare (<1/10,000) and 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 effects 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 use of ibuprofen (particularly at a high dose 2400mg/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		Hypersensitivity reactions consisting of1:
Disorders	Uncommon	Urticaria and pruritus
	Very rare	Severe hypersensitivity reactions.
		Symptoms could be facial, tongue and laryngeal swelling, dyspnoea, tachycardia, hypotension (anaphylaxis, angioedema or severe shock).
	Not Known	Respiratory tract reactivity comprising asthma, aggravated asthma, bronchospasm or dyspnoea.
Nervous System	Uncommon	Headache
Disorders	Very rare	Aseptic meningitis2
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 (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 such as bullous reactions including Stevens- Johnson syndrome, erythema multiforme and toxic epidermal necrolysis can occur.
Renal and Urinary Disorders	Very rare	Acute renal failure, papillary necrosis, especially in long-term use, associated with increased serum urea and oedema.
	Not Known	Renal insufficiency
Investigations	Very rare	Decreased haemoglobin levels

Description of Selected Adverse Reactions

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 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

Pharmacotherapeutic group: propionic acid derivative ATC Code: M01A E01

Ibuprofen is an NSAID that has demonstrated its efficacy in the common animal experimental inflammation models by inhibition of prostaglandin synthesis. In humans, ibuprofen reduces inflammatory pain, swellings and fever. Furthermore, ibuprofen reversibly inhibits platelet aggregation.

The clinical efficacy of ibuprofen has been demonstrated in pain associated with headache, toothache and dysmenorrhoea and fever; furthermore in patients with pain and fever associated with cold and flu and in pain models such as sore throat, muscular pain or soft tissue injury and backache.

A study in dental pain has shown that patients experienced statistically significant pain relief in 15 minutes after the administration of 2 x Nurofen Express 256mg Tablets, compared with placebo. In this study, significantly more patients achieved meaningful pain relief after administration of 2 x Nurofen Express 256mg Tablets than after administration of paracetamol tablets (96.3% vs 67.9%). These patients also achieved significantly greater reduction in pain intensity and greater pain relief over 6 hours compared with patients receiving paracetamol. Using measures of distractibility, patients receiving sodium ibuprofen experienced significantly greater benefit than those receiving placebo.

Clinical evidence demonstrates that ibuprofen, in the form of salts such as ibuprofen sodium and ibuprofen lysine, acts significantly faster than standard ibuprofen acid tablets for the relief of mild-moderate pain.

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 (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 diffuses into the synovial fluid.

Peak plasma concentration of ibuprofen occurs 1 - 2 hours after administration of ibuprofen acid. However, ibuprofen is more rapidly absorbed from the gastrointestinal tract following the administration of Nurofen Express 256mg Tablets, with peak plasma concentration occurring approximately 35 minutes 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.

Preclinical safety data

No relevant information, additional to that contained elsewhere in the SPC.

6.1    List of excipients Tablet core

Croscarmellose sodium (E468)

Xylitol (E967)

Microcrystalline cellulose (E460)

Magnesium stearate (E572)

Colloidal anhydrous silica (E551)

Coating ingredients Carmellose sodium (E466),

Talc (E553b),

Acacia spray dried (E414),

Sucrose,

Titanium dioxide (E171),

Macrogol 6000 powder,

Tablet printing

Red Printing Ink

The ink contains the following residual materials after application: shellac (E904), iron oxide red (E172), Propylene Glycol (E1520), Ammonium Hydroxide (E527) and Simethicone.

6.2    Incompatibilities

Not applicable.

6.3    Shelf life

2 years.

6.4    Special precautions    for    storage

Store in the original package.

6.5    Nature and contents of container

A push through laminate blister tray consisting of opaque, white 250 micron PVC with 40 gsm or 90 gsm polyvinylidene chloride (PVdC), heat-sealed to 20 micron aluminium foil.

The blister trays are packed into either a cardboard carton or a plastic, moulded acrylonitrile butadiene styrene (ABS) case.

Each carton may contain 2, 3, 4, 5, 6, 8, 10, 12, 14, 15, 16, 18, 20, 24, 28, 30, 32, 36, 48, 96 tablets.

Not all packs will be marketed.

6.6 Special precautions for disposal

Not applicable.

7    MARKETING AUTHORISATION HOLDER

Reckitt Benckiser (UK) Ltd, Dansom Lane, Hull HU8 7DS UK

8    MARKETING AUTHORISATION NUMBER(S)

00063/0412

9    DATE OF FIRST AUTHORISATION/RENEWAL OF THE AUTHORISATION

03/06/2008

10 DATE OF REVISION OF THE TEXT

16/03/2016