SUMMARY OF PRODUCT CHARACTERISTICS

1    NAME OF THE MEDICINAL PRODUCT

Ibuprofen and Phenylephrine Hydrochloride 200mg/6.1mg Tablets Galpharm Pain Relief & Decongestant 200mg/6.1mg Tablets Sudafed Congestion & Headache Relief Dual Action 200mg/6.1mg Tablets Sudafed Sinus Pain Relief 200mg/6.1mg Tablets

2    QUALITATIVE AND QUANTITATIVE COMPOSITION

Ibuprofen 200 mg

Phenylephrine hydrochloride 6.1 mg

Sucrose 31.66 mg per tablet Tartrazine 0.274 mg per tablet

For full list of excipients, see Section 6.1.

3    PHARMACEUTICAL FORM

Film-coated tablets (Tablets)

Green, round bi-convex sugar coated tablet.

4    CLINICAL PARTICULARS

4.1    Therapeutic indications

For the relief of symptoms of cold and 'flu with associated congestion, including aches and pains, headache, fever, sore throat, blocked nose and sinuses.

4.2 Posology and method of administration

For oral administration and short-term use only.

Adults, the elderly and children 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 between 12 and 18 years this medicinal product is required for more than 3 days, or if symptoms worsen a doctor should be consulted.

If in adults the product is required for more than 10 days, or if the symptoms worsen the patient should consult a doctor.

Two tablets every 8 hours, preferably with or after food. Leave at least 4 hours between doses and do not exceed six tablets in any 24 hour period.

Not to be given to children under 12 years.

4.3 Contraindications

Hypersensitivity to ibuprofen, phenylephrine hydrochloride or any of the excipients in the product.

Hypertension and severe coronary heart disease.

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).

Active or history of recurrent peptic ulcer/haemorrhage (two or more distinct episodes or 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 Section 4.4).

Pregnancy (see section 4.6).

Use with concomitant NSAIDs including cyclo-oxygenase-2 specific inhibitors (see Section 4.5).

Patients being treated with monoamine oxidase inhibitors or within 14 days of ceasing such treatment (see section 4.5).

Patients with diabetes mellitus.

Patients with closed angle glaucoma.

Patients with hyperthyroidism.

Patients suffering from prostatic enlargement.

Patients suffering with phaeochromocytoma.

4.4 Special warnings and precautions for use Ibuprofen

Undesirable effects may be minimised by using the lowest effective dose for the shortest duration necessary to control symptoms (see gastrointestinal and cardiovascular risks below).

The elderly are at increased risk of consequence 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 this product 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 aged between 12 and 18 years.

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) 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 limited evidence that drugs which inhibit cyclooxygenase/ 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 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.

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-platelets 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 exfoliating 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 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. This product should be discontinued at the first appearance of skin rash, mucosal lesions or any other sign of hypersensitivity.

Phenylephrine Hydrochloride

Vascular disorders: Phenylephrine hydrochloride should be used with caution in patients with occlusive vascular disease including Raynaud's Phenomenon.

Phenylephrine should be used with care in patients with hyperthyroidism, cardiovascular disease, diabetes mellitus, closed angle glaucoma, prostatic enlargement and hypertension.

General

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

4.5 Interaction with other medicinal products and other forms of interaction Ibuprofen

Ibuprofen should not be used in combination with:

Acetylsalicylic acid

Concomitant administration of ibuprofen and acetylsalicylic acid is not generally recommended because of the potential of increased adverse effects.

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 cyclo-oxygenase-2 selective inhibitors: Avoid concomitant use of two or more NSAIDs as this may increase the risk of adverse reactions (see Section 4.4).

Ibuprofen should be used with caution in combination with:

Anti-coagulants: NSAIDs may enhance the effects of anticoagulants 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.

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 increase in plasma levels of lithium. Methotrexate: There is 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 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.

Phenylephrine Hydrochloride

Phenylephrine Hydrochloride should not be used in combination with:

Monoamine Oxidase Inhibitors (MAOIs): Phenylephrine hydrochloride is not recommended for patients currently receiving or within two weeks of stopping therapy with monoamine oxidase inhibitors (MAOIs) (See section 4.3).

Phenylephrine Hydrochloride should be used with caution in combination with:

Sympathomimetic Amines: Phenylephrine hydrochloride may enhance the cardiovascular effects of other sympathomimetic amines (e.g. decongestants).

Beta-blockers and other Vasodilators: Phenylephrine hydrochloride may adversely interact with other vasodilators and beta-blockers.

Anticholinergic Drugs: Phenylephrine hydrochloride may enhance the effects of anticholinergic drugs such as tricyclic antidepressants.

Cardiac Glycosides: Phenylephrine hydrochloride may increase the possibility of arrhythmias in digitalised patients.

4.6 Fertility, pregnancy and lactation

Whilst no teratogenic effects have been demonstrated to ibuprofen in animal experiments, the use of ibuprofen should, if possible, be avoided during the first six months of pregnancy.

During the third trimester, ibuprofen is contraindicated 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 4.3).

In limited studies, ibuprofen appears in the breast milk in very low concentrations and is unlikely to affect the breast-fed infant adversely.

See Section 4.4 regarding female fertility.

Phenylephrine Hydrochloride

The safety of phenylephrine hydrochloride during pregnancy and lactation has not been established but in view of a possible association of foetal abnormalities with first trimester exposure to phenylephrine hydrochloride, use during pregnancy should be avoided.

Due to the vasoconstrictive properties of phenylephrine hydrochloride, it should be used in caution in patients with a history of pre-eclampsia.

Phenylephrine hydrochloride may reduce placental perfusion and so should be used in pregnancy only if the benefits outweigh this risk.

There is no data available on the use of phenylephrine in lactation.

Ibuprofen and Phenylephrine Hydrochloride Combination

The safety of the combination during pregnancy has not been established.

In view of the possible association of foetal abnormalities with first trimester exposure to phenylephrine hydrochloride and the contraindication of ibuprofen in the last trimester of pregnancy due to the risks of premature closure of the fetal ductus arteriosus with possible persistent pulmonary hypertension the combination product should not be used in pregnancy.

There is no data available on the use of the product during breastfeeding.

4.7 Effects on ability to drive and use machines

No studies on the effects on the ability to drive and use machines have been performed.

4.8 Undesirable effects

Hypersensitivity reactions have been reported following treatment with ibuprofen and these may consist of:

(a)    Non-specific allergic reaction and anaphylaxis.

(b)    Respiratory tract reactivity, e.g. asthma, aggravated asthma, bronchospasm or

dyspnoea.

(c)    Various skin reactions, e.g. pruritis, urticaria, angioedema and, 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 longterm treatment, additional adverse effects may occur.

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:

Non-specific allergic reactions.

Respiratory tract reactivity (e.g. asthma, aggravated asthma and bronchospasm). Various skin reactions including exfoliative and bullous dermatoses (including epidermal necrolysis and erythema multiforme).

Uncommon: Hypersensitivity reactions with urticaria and pruritus.

Very rare: Severe hypersensitivity reactions. Symptoms could include: facial, tongue and laryngeal swelling, dyspnoea, tachycardia, hypotension (anaphylaxis, angioedema or severe shock).

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 Special Warnings and Precautions for Use).

Nervous System Disorders:

Uncommon: Headache.

Vary rare: Aseptic Meningitis - single cases have been reported very rarely.

Cardiac Disorders and Vascular Disorders:

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 (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).

Gastrointestinal Disorders:

The most commonly observed side effects of ibuprofen 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 Special Warnings and Precautions for Use).

Hepatobiliary Disorders:

Very rare: Liver disorders.

Skin and Subcutaneous Tissue Disorders:

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.

Renal and Urinary Disorders:

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

Phenylephrine Hydrochloride

Immune System Disorders:

Rare: Non-specific allergic reactions.

Nervous System Disorders:

Uncommon: Headache.

Cardiac Disorders and Vascular Disorders:

Tachycardia, cardiac arrhythmias, palpitations, hypertension,

Gastrointestinal Disorders:

Rare: Nausea and vomiting.

Renal and Urinary Disorders:

Very rare: urinary retention in males.

Reporting of suspected adverse reactions

Reporting suspected adverse reactions after authorization 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 ibuprofen may cause symptoms. In adults, the dose response rate effect is less clear cut. The half-life in overdose is 1.5-3 hours.

Symptoms:

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 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.

Features of severe overdosage of phenylephrine include haemodynamic changes and cardiovascular collapse with respiratory depression.

Management:

Management of overdose should be symptomatic and supportive and include the maintenance of a clear airway and monitoring of cardiac and vital signs until stable. Consider gastric lavage or 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. The hypertensive effects of phenylephrine hydrochloride may be treated with an intravenous alpha-receptor blocking agent.

5    PHARMACOLOGICAL PROPERTIES

5.1    Pharmacodynamic properties

M01AE51 - Ibuprofen, combinations.

Ibuprofen

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. The therapeutic effect of ibuprofen in symptoms relating to the common cold and influenza has a duration of up to 8 hours.

Experimental data suggest that ibuprofen may competitively inhibit the effect of low dose acetylsalicylic acid on platelet aggregation when they are dosed concomitantly. Some pharmacodynamic 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).

Phenylephrine Hydrochloride is a post-synaptic alpha-receptor agonist with low cardioselective beta-receptor affinity and minimal central stimulant activity. It is a recognised decongestant and acts by vasoconstriction to reduce oedema and nasal swelling.

5.2 Pharmacokinetic properties

Ibuprofen

Ibuprofen is rapidly absorbed following administration and is rapidly distributed throughout the whole body. The excretion is rapid and complete via the kidneys. Maximum plasma concentrations are reached 45 minutes after ingestion if taken on an empty stomach. When taken with food, peak levels are observed after 1-2 hours. These times may vary with different dosage forms.

The half-life of ibuprofen is about 2 hours.

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

Phenylephrine Hydrochloride

Phenylephrine Hydrochloride is absorbed from the gastrointestinal tract, but has reduced bioavailability by the oral route due to first-pass metabolism.

It retains activity as a nasal decongestant when given orally, the drug distributing through the systemic circulation to the vascular bed of the nasal mucosa.

When taken by mouth as a nasal decongestant, phenylephrine is usually given at intervals of 4-6 hours.

Ibuprofen and Phenylephrine Hydrochloride Combination:

The ibuprofen component of this fixed combination (ibuprofen 200 mg plus phenylephrine hydrochloride 6.1 mg) is absorbed faster than standard ibuprofen 200 mg tablets, with therapeutic levels being reached in 26.4 minutes (from the fixed combination) as opposed to 55.2 minutes (for standard ibuprofen).

5.3 Preclinical safety data

There are no findings of relevance to the prescriber other than those already mentioned elsewhere in the SPC.

6.1    List of excipients

Core Excipients:

Calcium Hydrogen Phosphate Dihydrate Croscarmellose Sodium Cellulose, Powdered Talc

Simeticone

Silica, Colloidal Anhydrous

Coating Excipients:

Talc Sucrose Povidone K90 Calcium Carbonate Macrogol 6000 Macrogol 4000

Green Spruce Food Colourant* 630004 [Containing Sodium Sulphate (E514), Tartrazine (E102), Brilliant Blue (E133)]

Titanium Dioxide Shellac Theobroma Oil

6.2    Incompatibilities

Not applicable.

6.3 Shelf life

24 Months

6.4 Special precautions for storage

Do not store above 25°C.

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

Nature and contents of container