SUMMARY OF PRODUCT CHARACTERISTICS

1    NAME OF THE MEDICINAL PRODUCT

Sudafed Sinus Pressure & Pain Tablets

2    QUALITATIVE AND QUANTITATIVE    COMPOSITION

Active Ingredients    mg/tablet

Ibuprofen Ph Eur    200

Pseudoephedrine Hydrochloride BP    30

3    PHARMACEUTICAL FORM

Tablet for oral administration.

4    CLINICAL PARTICULARS

4.1    Therapeutic indications

For symptomatic relief in conditions where both the decongestant action of Pseudoephedrine Hydrochloride and the analgesic and/or anti-inflammatory action of Ibuprofen are required e.g. nasal and/or sinus congestion with headache, pain, fever and other symptoms of the common cold or influenza.

4.2    Posology and method of administration

For oral administration

Adults, the elderly and young persons over 12 years: 1 or 2 tablets every 4 - 6 hours to a maximum of 6 tablets in 24 hours.

Not to be given to children under the age of 12.

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.

4.3 Contraindications

Hypersensitivity to ibuprofen or any of the ingredients.

Patients who have or have previously suffered from severe heart failure, circulatory problems, renal failure, severe hepatic failure, hypertension, diabetes, phaeochromocytoma, or closed angle glaucoma. (see Section 4.4 Special warnings and precautions for use).

This product is contraindicated in patients who have previously shown hypersensitivity reactions (e.g. asthma, rhinitis, angioedema or urticaria) in response to aspirin or other non-steroidal anti-inflammatory drugs. Active or previous peptic ulcer (two or more distinct episodes of proven ulceration or bleeding).

History of gastrointestinal bleeding or perforation, related to previous NSAIDs therapy.

Use with concomitant NSAIDs including cyclo-oxygenase specific inhibitors (see Section 4.5 Interactions). Patients taking other painkillers or decongestants. Patients receiving tricyclic antidepressants. Patients currently receiving, or have had within the last two weeks received, monoamine oxidase inhibitors.

During the last trimester of pregnancy (see Section 4.6 Pregnancy and lactation).

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 are at increased risk of the serious consequences of adverse reactions, 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.

The use of Non-Drowsy Sudafed Dual Relief Max 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)

Caution is required in patients with hypertension and/or cardiac, or hepatic impairment since renal function may deteriorate and/or fluid retention occur.

Renal:

Renal impairment as renal function may further deteriorate (see Section 4.3 Contraindications and Section 4.8 Undesirable effects).

Hepatic:

Hepatic dysfunction (See section 4.3 Contraindications and Section 4.8 Undesirable effects)

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 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.

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 9see 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 serious GI events.

The risk of GI bleeding, ulceration or perforation is higher with increasing NSAID doses, in patients with 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 when elderly, should report any unusual abdominal symptoms (especially GI bleeding) particularly in the early 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, or anticoagulants such as warfarin, selective serotonin reuptake inhibitors or anti-platelet agents such as aspirin (see Section 4.5 Interactions).

Where 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. Non-Drowsy Sudafed Dual Relief Max should be discontinued at the first appearance of skin rash, mucosal lesions, or any other sign of hypersensitivity.

Patients suffering from asthma, hypertension, heart disease, diabetes, thyroid disease or prostatic hypertrophy should consult their doctor before using this product. NonDrowsy Sudafed Dual Relief Max should not be taken with other decongestants or analgesics.

The label will state;

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 or have had asthma, diabetes, high cholesterol, high blood pressure, a stroke, heart, liver, kidney or bowel problems.

•    Are a smoker.

•    Are pregnant.

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).

Experimental data suggest that ibuprofen may inhibit the effect of low dose aspirin on platelet aggregation when they are dosed concomitantly. 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 (see section 5.1).

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:

Anticoagulants: NSAIDs may enhance the effects of anti-coagulants, such as warfarin (see Section 4.4).

Antihypertensives and diuretics: NSAIDs may diminish the effect of these drugs. Diuretics can increase the risk of nephrotoxicity of NSAIDs.

Corticosteroids: may increase the risk of adverse reactions in the gastrointestinal tract (see Section 4.4 Special warnings.)

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.

Methotrexate: there is a potential for an increase in plasma methotrexate.

Ciclosporin: increased risk of nephrotoxicity.

Mifepristone: NSAID 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: 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.

Pseudoephedrine

Pseudoephedrine may interact with the actions of other sympathomimetic drugs and the antibacterial agent furazolidine. The action of Pseudoephedrine may be reduced by guanethidine, reserpine or methyldopa and may be reduced or enhanced by tricyclic antidepressants. Pseudoephedrine may reduce the action of guanethidine and may increase the possibility or arrhythmias in patients taking digitalis, quinidine or tricyclic antidepressants.

4.6 Pregnancy and lactation

There have been reports of foetal maldevelopment in animals following the use of Pseudoephedrine. Whilst no teratogenic effects have been demonstrated in animal studies Non-Drowsy Sudafed Dual Relief Max should 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 arterisus 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). Both Pseudoephedrine and to a lesser degree Ibuprofen pass into breast milk. In limited studies, ibuprofen appears in the breast milk in very low

concentration and is unlikely to affect the breast-fed infant adversely. The product should therefore not be used during pregnancy, or during lactation except under the supervision of a doctor.

See section 4.4 regarding female fertility

4.7 Effects on ability to drive and use machines

None expected at recommended doses and duration of therapy

4.8 Undesirable effects

Hypersensitivity reactions have been reported following treatment with NSAIDs. These may consist of:

a)    Non-specific allergic reactions and anaphylaxis.

b)    Respiratory tract reactivity comprising of asthma, aggravated asthma, bronchospasm or dyspnoea.

c)    Assorted skin disorders, including rashes of various types, pruritus, urticaria, purpura, angioedema, more rarely exfoliative and 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 effects may occur

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

Gastrointestinal:

The most commonly-observed adverse events are gastrointestinal in nature. Uncommon: abdominal pain, nausea and dyspepsia.

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. Exacerbation of ulcerative colitis and Crohn’s disease (see Section 4.4).

Nervous system:

Uncommon: Headache.

Very rare: Aseptic meningitis - single cases have been reported very rarely. Renal:

Very rare: Acute renal failure, papillary necrosis, especially in long-term use, associated with increased serum urea and oedema.

Hepatic:

Very rare: liver disorders.

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.

Dermatological:

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:

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)

Cardiovascular and Cerebrovascular:

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

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).

Adverse events reported with Pseudoephedrine Insomnia, excitability, anxiety, tremor, palpitations, dry mouth, loss of appetite, thirst, chest pains. Less frequently: difficulty in micturition, muscle weakness and hallucinations.

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 of ibuprofen may cause symptoms. In adults the dose response effect is less clear cut. The half life in overdose is 1.5 - 3 hours.

Overdosage may result in nervousness, dizziness, insomnia, headache, vomiting, drowsiness and hypotension.

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 for 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.

Due to the rapid absorption of the two active ingredients from the gastro-intestinal tract, emetics and gastric lavage must be instituted within 4 hours of overdosage to be effective. Oral administration of activated charcoal is effective only if given within one hour. Cardiac status should be monitored and the serum electrolytes measured.

If there are signs of cardiac toxicity, propranolol may be administered intravenously. A slow infusion of a dilute solution of potassium chloride should be initiated in the event of a drop in the serum potassium level. Despite hypokalaemia, the patient is unlikely to be potassium depleted, therefore overload must be avoided. Continued monitoring of the serum potassium is advisable for several hours after administration of the salt. For delirium or convulsions, intravenous administration of diazepam or lorazepamis indicated. Give bronchodilators for asthma.

5.1 Pharmacodynamic properties

Ibuprofen is a non-steroidal anti-inflammatory agent belonging to the Propionic Acid class of drugs. It has analgesic, antipyretic and anti-inflammatory properties. Ibuprofen inhibits prostaglandin synthesis. Pseudoephedrine hydrochloride is a sympathomimetic agent which causes vasoconstriction of nasal mucosa, thereby reducing rhinorrhoea and nasal congestion.

Experimental data suggest that ibuprofen may inhibit the effect of low dose aspirin on platelet aggregation when they are dosed concomitantly. In one study, when a single dose of ibuprofen 400mg was taken within 8 hours before or within 30 minutes after immediate release aspirin dosing (81mg), a decreased effect of aspirin 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 if considered to be likely for occasional ibuprofen use.

5.2 Pharmacokinetic properties

Ibuprofen is rapidly absorbed from the gastrointestinal tract with peak concentrations being achieved 45-90 minutes later. It is over 90% plasma protein bound in the circulation and has a short elimination half-life of 2 hours. Ibuprofen is primarily metabolised in the liver to 2-Hydroxyibuprofen and 2-Carboxyibuprofen. These are excreted in the urine along with approximately 9% of unchanged drug.

In limited studies, Ibuprofen appears in the breast milk in very low concentrations.

Pseudoephedrine hydrochloride is rapidly absorbed from the gastro-intestinal tract with peak plasma levels at 1 - 3 hours. It is partly metabolised in the liver like most sympathomimetics, but is mainly excreted unchanged in the urine.

5.3 Preclinical safety data

None stated.

6.1. List of Excipients

Sucrose Ph Eur Starch Ph Eur Pregelatinised starch NF Croscarmellose sodium NF Microcrystalline cellulose Ph Eur Opalux butterscotch AS-3739*

Stearic acid TP fine powder NF Colloidal anyhydrous silica Ph Eur Opaglos GS-2-0310 (solids)*

Sodium lauryl sulfate Ph Eur Carnauba wax No. yellow powder NF

*The colouring agents contain shellac, iron oxide (yellow, red), acetylated monoglyceride, povidone, sucrose, titanium dioxide, sodium hydroxide, propyl hydroxybenzoate, methyl hydroxybenzoate.

6.2 Incompatibilities

None known.

6.3 Shelf life

3 years.

6.4    Special precautions for storage

Store below 30°C.

6.5    Nature and contents of container

10, 12, 20 or 24 tablets in a blister pack consisting of white opaque PVC (250 pm) bonded to Aluminium foil (20 pm) in cardboard cartons.

Special precautions for disposal