Reckitt Benckiser Ireland Limited

Nurofen Cold and Flu Film-Coated Tablets

Ibuprofen 200mg

Pseudoephedrine Hydrochloride 30mg

Excipients: Sunset Yellow (E110), up to 16.8 micrograms per tablets.

For a full list of excipients, see section 6.1.

Film coated tablet (Short term: Tablet).

Yellow, circular, biconvex, tablets printed in black with an identifying motif.

For the symptomatic relief of head colds and influenza, including nasal congestion and to ease the pain of sore throats.

Oral Administration

Adults and children over 12 years: Initial dose two tablets, then if necessary two tablets every four hours. Do not exceed six tablets in any 24 hour period.

Elderly: No special dosage modifications are required, unless renal or hepatic function is impaired, in which case dosage should be assessed individually.

Severe heart failure.

History of gastrointestinal bleeding or perforation related to previous NSAIDs therapy. Active, or history of recurrent peptic ulcer/haemorrhage (two or more distinct episodes of proven ulceration or bleeding or other gastrointestinal disorders.

Hypersensitivity to any of the constituents, aspirin, or other NSAIDs.

Use in children under 12 years.

Use in patients taking other sympathomimetic drugs, monoamine oxidox inhibitors, or tricyclic antidepressants.

Patients with a history of bronchospasm, rhinitis or urticaria associated with aspirin or other NSAIDs.

Patients with cardiovascular disease, hypertension, diabetes, phaeochromocytoma, closed angle glaucoma, prostatic enlargement.

The use of Nurofen Cold and Flu Tablets with concomitant NSAIDs including cyclooxygenase-2 selective inhibitors should be avoided.

Undesirable effects may be minimised by using the minimum effective dose for the shortest duration necessary to control symptoms (See section 4.2, and GI and cardiovascular risks below).

Elderly: The elderly have an increased frequency of adverse reactions to NSAIDs especially gastrointestinal bleeding and perforation which may be fatal (see section 4.2)

Gastrointestinal bleeding, ulceration and perforation: GI bleeding, ulceration or perforation, which can be fatal, has been reported with all NSAIDs at any time during treatment, with or without any 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 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. Combination therapy with protective agents (e.g. misoprostol or proton pump inhibitors) should be considered for these patients, and also for patients requiring concomitant low dose aspirin, or other drugs likely to increase gastrointestinal risk (see below and 4.5).

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 Nurofen Cold and Flu, the treatment should be withdrawn.

NSAIDs should be given with care to patients with a history of gastrointestinal disease (ulcerative colitis, Crohn's Disease) as their condition may be exacerbated (see section 4.8 – undesirable 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 and oedema have been reported in association with NSAID therapy.

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.

In patients with renal, cardiac or hepatic impairment caution is required since the use of NSAIDs may result in deterioration of renal function.

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 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 Cold and Flu should be discontinued at the first appearance of skin rash, mucosal lesions, or any other sign of hypersensitivity.

Bronchospasm may be precipitated in patients suffering from, or with a previous history of, bronchial asthma or allergic disease.

Elderly patients are particularly susceptible to the adverse effects of NSAIDs. Prolonged use of NSAIDs in the elderly is not recommended. Where prolonged therapy is required, patients should be reviewed regularly.

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.

It is considered unsafe to take NSAIDs in combination with Warfarin or heparin unless under direct medical supervision.

Care should be taken in patients treated with any of the following drugs as interactions have been reported:

Zidovudine: There is evidence of prolonged bleeding time in patients receiving concurrent treatment with zidovudine and ibuprofen

Anti-hypertensives: reduced anti-hypertensive effect.

Diuretics: reduced diuretic effect. Diuretics can increase the risk of nephrotoxicity of NSAIDs.

Cardiac glycosides: NSAIDs may exacerbate cardiac failure, reduce GFR and increase plasma cardiac glycoside levels.

Lithium: decreased elimination of lithium.

Methotrexate: decreased elimination of methotrexate.

Cyclosporin: increased risk of nephrotoxicity with NSAIDs.

Other NSAIDs: avoid concomitant use of two or more NSAIDs.

Aminoglycosides: reduction in renal function in susceptible individuals, decreased elimination of aminoglycoside and increased plasma concentrations.

Probenecid: reduction in metabolism and elimination of NSAID and metabolites.

Oral hypoglycaemic agents: inhibition of metabolism of sulfonylurea drugs, prolonged half-life and increased risk of hypoglycaemia.

Pseudoephredine should not be used in combination with:

- MAOI therapy or within 14 days of ceasing such treatment.

- Sympathomimetic agents, such as decongestants and appetite suppressants, as it may potentiate their effects.

- The effect of psuedoephedrine may be diminished by guanethidine, reserpine and methyldopa.

- The effect of pseudoephedrine may be diminished/enhanced by tricyclic antidepressants.

Pseudoephedrine may diminish the effects of guanethidine and may increase the possibility or arrhythmias in digitalised patients, or in those receiving quinidine or tricyclic antidepressants.

Experimental data suggest that ibuprofen may inhibit the effect of low dose aspirin on platelets aggregation when they are dosed concomitantly. However, the limitations of these data and the uncertainties regarding the extrapolation of ex vivo data to the clinical situation imply that no firm conclusions can be made for regular ibuprofen use, and no clinically relevant effect is considered to be likely for occasional use (see section 5.1)

This product should be avoided during pregnancy and lactation.

No adverse effects known.

The list of the following adverse effects relates to those experienced with the product at OTC doses, for short-term use. In the treatment of chronic conditions, under long-term treatment, additional adverse effects may occur.

Gastrointestinal Disorders: The most commonly observed adverse events are gastrointestinal in nature. Peptic ulcers, perforation or GI bleeding, sometimes fatal, particularly in the elderly, may occur (see section 4.4).

Nausea, vomiting, diarrhoea, flatulence, constipation, dyspepsia, abdominal pain, melaena, haematemesis, ulcerative stomatitis, exacerbation of colitis and Crohn's disease (see section 4.4 –Special warnings and precautions for use) have been reported following administration. Less frequently, gastritis has been observed.

Abdominal pain, dyspepsia and nausea, diarrhoea, flatulence, constipation and vomiting. Very rarely gastro-intestinal ulcers, sometimes with bleeding and perforation can occur.

Nervous System Disorders: Headache, dizziness, muscle weakness, palpitations and tremors.

Renal and Urinary Disorders: 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. Dysuria

Hepatobiliary Disorders: Liver disorders, especially in long-term treatment.

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, nose and skin bleeding.

Skin and Subcutaneous Disorders: Very rarely severe forms of skin reactions such as erythema multiforme and epidermal necrolysis can occur. Sweating increased. Skin reactions: Bullous reactions inclusing Stevens-Johnson syndrome and toxic epidermal necrolysis (very rare).

Immune System Disorders: 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.

Hypersensitivity Reactions: Hypersensitivity reactions with urticaria and pruritus. Rarely severe hypersensitivity reactions. Symptoms could be: facial, tongue and larynx swelling, dyspnoea, tachycardia, hypotension, (anaphylaxis, angioedema or severe shock). Exacerbation of asthma and bronchospasm.

Cardiac Disorders: Palpitations

Cardiovascular: Oedema, hypertension and cardiac failure have been reported in association with NSAID treatment.

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) (see section 4.4).

Psychiatric Disorders: Restlessness, insomnia, hearing disturbance, anxiety and hallucinations.

General Disorders and Administration Site Conditions: Chest pain and thirst.

Symptoms of overdose include headache, nausea, vomiting, drowsiness, dizziness, thirst, anxiety, restlessness, irritability, fever, sinus tachycardia, sweating, insomnia, dilated pupils, blurred vision, delusions and hallucinations, muscular weakness, difficulty in micturition, tremors, convulsions, coma, respiratory depression, hypertension, supraventricular and ventricular arrhythmias.

Treatment consists of gastric lavage and if necessary correction of serum electrolytes. Symptomatic and supportive treatment should be undertaken, particularly with regard to the cardiovascular and respiratory systems. Convulsions should be controlled with intravenous diazepam. Chlorpromazine may be used to control marked excitement and hallucinations. Severe hypertension may need to be treated with an alpha-receptor blocking drug such as phentolamine. A beta-receptor blocking drug may be required to control cardiac arrhythmias.

Ibuprofen is a propionic acid derivative, having analgesic, anti-inflammatory and antipyretic activity. The therapeutic effects of ibuprofen as a NSAID are thought to result from its inhibitory activity on the enzyme prostaglandin synthetase.

Pseudoephedrine is a sympathommetic agent with direct and indirect effects on adrenergic receptors. It has alpha and beta stimulant adrenergic activity and some stimulant effect on the central nervous system. The sympathomimetic effect of pseudoephredine produces vasoconstriction which in turn relieves nasal congestion.

Experimental data suggest that ibuprofen may inhibit the effect of low dose aspirin on platelets aggregation when they are dosed concomitantly. In one study, when a single dose of ibuprofen 400mg was taken within 8 h before or within 30 min after immediate release aspirin (81mg), a decreased effect of ASA on the formation of thromboxane or platelet aggregation occurred. However, the limitations of these data and the uncertainties regarding extrapolation of ex vivo data to the clinical situation imply that no firm conclusions can be made for regular ibuprofen use, and no clinically relevant effect is considered to be likely for occasional ibuprofen use.

Ibuprofen is rapidly absorbed from the gastrointestinal tract, peak serum concentrations occurring 1 to 2 hours after administration.

Ibuprofen is extensively bound to plasma proteins

Ibuprofen is metabolised in the liver to two major inactive metabolites and these together with unchanged Ibuprofen are excreted by the kidney either as such or as conjugates. The elimination half-life is approximately 2 hours. Excretion by the kidney is both rapid and complete.

Pseudoephredine is absorbed from the gastrointestinal tract and is largely excreted in the urine unchanged, together with small amounts of a hepatic metabolite. It has an elimination half-life of several hours, which may be reduced by acidifying the urine.

No data is available which is of relevance to the consumer.

Core

Calcium phosphate

Microcrystalline cellulose

Povidone

Croscarmellose sodium

Magnesium stearate

Film Coating

Hypromellose

Talc

Opaspray Yellow M-1F-6168 or

Mastercote Yellow FA 0156 containing

Titanium dioxide

Sunset yellow (E110)

Quinilone Yellow

Printing Ink

Black printing ink containing:

Iron oxide black (E172)

Propylene Glycol

Shellac

Not applicable.

3 years.

Do not store above 25°C.

Store in the original package in order to protect from moisture.

A strip pack consisting of a blister tray of white pigmented 250μm PVC/40 gsm PVDC laminate heat-sealed to lacquered 20μm aluminium foil containing 12 tablets. One or two trays packed in a cardboard carton (12 or 24 tablets).

No special requirements.

Reckitt Benckiser Ireland Ltd

7 Riverwalk

Citywest Business Campus

Dublin 24

PA 979/33/1

Date of first authoristaion: 18 April 1994

Date of last renewal: 18 April 2009

January 2012