Boots Cold & Flu Relief with Ibuprofen – Summary of Product Characteristics (SmPC) for healthcare professionals

1 NAME OF THE MEDICINAL PRODUCT

Boots Cold & Flu Relief with Ibuprofen

2 QUALITATIVE AND QUANTITATIVE COMPOSITION

Ibuprofen BP 200.0mg

Pseudoephedrine Hydrochloride BP 30.0mg

Excipient(s) with known effect

Sunset yellow FCF (E110)

For the full list of excipients, see section 6.1.

3 PHARMACEUTICAL FORM

Tablets

An orange, round, biconvex, film coated tablet, debossed with ‘CF’ on one face

4 CLINICAL PARTICULARS

4.1 Therapeutic indications

For the relief of the 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 short-term use only.

The lowest effective dose for the shortest duration necessary to relieve symptoms (see section 4.4). The patient should consult a doctor if symptoms persist or worsen, or if the product is required for more than 7 days.

Posology

Adults, the elderly and children over 12 years:

Take 1 or 2 tablets with water, up to three times a day. Leave at least four hours between doses. Do not take more than 6 tablets in any 24 hour period.

Children under 12 years:

Not suitable for children under 12 years.

Method of administration

For oral administration with water.

4.3 Contraindications

Hypersensitivity to ibuprofen, pseudoephedrine, or any of the ingredients in the product.

Patients who have previously shown hypersensitivity reactions (e.g. asthma, rhinitis, angioedema, urticaria), in response to ibuprofen, 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 NSAID therapy.

Severe acute or chronic kidney disease / renal failure.

Severe heart failure or hepatic failure (See section 4.4) (NYHA Class IV).

During pregnancy (See section 4.6).

Not to be used in children under 12 years.

Severe coronary heart disease and cardiovascular disease. Severe hypertension or uncontrolled hypertension

Patients with tachycardia, severe renal impairment, angina pectoris, hyperthyroidism, diabetes, phaeochromocytoma, closed angle glaucoma.

Monoamine oxidase inhibitors (MAOIs), or within 14 days of stopping treatment (see section 4.5).

Patients taking beta-blockers (see section 4.5).

Concomitant use of other sympathomimetic decongestants.

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 previous history of bronchial asthma or allergic disease.

Other NSAIDs:

The use of Boots Cold & Flu Relief with Ibuprofen with concomitant NSAIDs including cyclo-oxygenase-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.

The risk of renal impairment is increased in children, adolescents and elderly, particularly in volume depleted states (e.g. dehydration, which may be due to nausea and vomiting, hypotension, sepsis) and hypovolaemia related to other known effects (e.g. GI haemorrhage).

Renal tubular acidosis and hypokalaemia may occur following acute overdose and in patients taking ibuprofen products over long periods at high doses (typically greater than 4 weeks), including doses exceeding the recommended daily dose.

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 occlusive vascular disease, hypertension and/or heart failure as fluid retention, hypertension and oedema have been reported in associated 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.

Posterior reversible encephalopathy syndrome (PRES) and reversible cerebral vasoconstriction syndrome (RCVS)

Cases of PRES and RCVS have been reported with the use of pseudoephedrine-containing products (see section 4.8). The risk is increased in patients with severe or uncontrolled hypertension, or with severe acute or chronic kidney disease/renal failure (see section 4.3).

Pseudoephedrine should be discontinued and immediate medical assistance sought if the following symptoms occur: sudden severe headache or thunderclap headache, nausea, vomiting, confusion, seizures and/or visual disturbances. Most reported cases of PRES and RCVS resolved following discontinuation and appropriate treatment.

Cases of Kounis syndrome have been reported in patients treated with Ibuprofen. Kounis syndrome has been defined as cardiovascular symptoms secondary to an allergic or hypersensitivity reaction associated with constriction of coronary arteries and potentially leading to 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 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 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 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 ibuprofen, the treatment should be withdrawn.

Ischaemic colitis

Some cases of ischaemic colitis have been reported with pseudoephedrine. Pseudoephedrine should be discontinued and medical advice sought if sudden abdominal pain, rectal bleeding or other symptoms of ischaemic colitis develop.

Severe cutaneous adverse reactions (SCARs):

Severe cutaneous adverse reactions (SCARs), including exfoliative dermatitis, erythema multiforme, Stevens-Johnson syndrome (SJS), Toxic Epidermal Necrolysis (TEN), Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS syndrome) and acute generalized exanthematous pustulosis (AEGP), which can be life-threatening or fatal have been reported in association with the use of ibuprofen (see section 4.8). Most of these reactions occurred within the first month of use. If signs and symptoms suggestive of these reactions appear this medicine should be withdrawn immediately, and an alternative treatment considered (as appropriate).

AGEP may occur with ibuprofen and pseudoephedrine-containing products. This acute pustular eruption may occur within the first 2 days of treatment, with fever, and numerous, small, mostly non-follicular pustules arising on a widespread oedematous erythema and mainly localized on the skin folds, trunk, and upper extremities. Patients should be carefully monitored. If signs and symptoms such as pyrexia, erythema, or many small pustules are observed, administration of Boots Cold & Flu Relief with Ibuprofen should be discontinued, and appropriate measures taken if needed.

Masking of symptoms of underlying infections

Ibuprofen can mask symptoms of infection, which may lead to delayed initiation of appropriate treatment and thereby worsening the outcome of the infection. This has been observed in bacterial community acquired pneumonia and bacterial complications to varicella. When Boots Cold & Flu Relief with Ibuprofen is administered for fever or pain relief in relation to infection, monitoring of infection is advised. In non-hospital settings, the patient should consult a doctor if symptoms persist or worsen.

To be used with caution in patients with elevated intraocular pressure, prostatic enlargement and hyperexcitability.

To be used with caution in combination with antihypertensives including adrenergic neuron blockers (see section 4.5). The effects of a single dose on the blood pressure of these patients should be observed before recommending repeated or unsupervised treatment.

To be used with caution with other sympathomimetic agents such as appetite suppressants and amphetamine-like psycho-stimulants (see section 4.5). If hallucinations, restlessness, or sleep disturbances are experienced whilst taking the product, use of the product should be discontinued.

Ischaemic optic neuropathy

Cases of ischaemic optic neuropathy have been reported with pseudoephedrine. Pseudoephedrine should be discontinued if sudden loss of vision or decreased visual acuity such as scotoma occurs.

Important information about some of the ingredients of this medicine (see section 2 and 6.1)

This medicine contains Sunset yellow FCF (E 110) which may cause allergic reactions.

This medicine contains less than 1 mmol sodium (23 mg) per tablet, that is to say essentially ‘sodium-free’.

The label will include:

Read all of the enclosed leaflet for full instructions.

Do not take this medicine:

• If you have a stomach ulcer, perforation or bleeding, or have had one twice or more in the past
• If you have had perforation or a bleeding stomach after taking a non-steroidal anti-inflammatory medicine (you may have been sick and it contained blood or dark particles that look like coffee grounds, passed blood in your stools or passed black tarry stools)
• If you are allergic to ibuprofen, pseudoephedrine or any other ingredient of this medicine, or to aspirin or other non-steroidal anti-inflammatory medicines
• If you have had a worsening of asthma, runny nose, itchy skin or facial swelling after taking aspirin or similar medicines
• If you are taking aspirin with a daily dose above 75mg, or other non-steroidal anti-inflammatory (NSAID) medicines
• If you have severe acute (sudden) or chronic (long-term) kidney disease or kidney failure

• If you have severe liver, heart or blood vessel disease, including fast heart rate

  (tachycardia), angina

• If you have very high blood pressure (hypertension) or hypertension not controlled by your medication
• If you have glaucoma, an overactive thyroid, diabetes, or a tumour near your kidney (phaeochromocytoma)

• If you are taking monoamine oxidase inhibitors (for depression and known as

  MAOIs), or have taken them within the last 14 days

• If you are taking beta-blockers
• If you are using other sympathomimetic decongestants (including nasal sprays)
• If you are pregnant or breast feeding
• If you are under 12 years of age.

Talk to your pharmacist or doctor before taking this medicine if you have any medical conditions or are taking any other medicines.

If symptoms persist, or pain or fever worsen, or if any new symptoms occur, consult your doctor or pharmacist.

Warning: Do not exceed the stated dose.

Keep all medicines out of the sight and reach of children.

4.5 Interaction with other medicinal products and other forms of interaction

Pseudoephedrine:

Linezolid: Pseudoephedrine may cause elevated blood pressure in patients taking linezolid.

Monoamine oxidase inhibitors (MAOIs) and Reversible inhibitors of monoamine oxidase (RIMAs): Should not be given to patients receiving MAOI therapy or within 14 days of ceasing such treatment. Increased risk of hypertensive crisis.

Moclobemide: Risk of hypertensive crisis.

Ergot alkaloids (ergotamine & methysergide): Increased risk of ergotism.

Beta-blockers: This medicine may block hypotensive effects.

Cardiac glycosides: Increased risk of dysrhythmias.

Other sympathomimetic agents, such as decongestants, amphetamine-like psychostimulants, and appetite suppressants: Pseudoephedrine may potentiate their effects. Risk of hypertension (see section 4.3).

Oxytocin: Risk of hypertension.

Anticholinergics: Pseudoephedrine enhances the effects of anticholinergic drugs (such as tricyclic antidepressants (TCAs)).

Methyldopa: The effect of pseudoephedrine may be diminished.

Ibuprofen:

Ibuprofen (like other NSAIDs) should be avoided in combination with: Acetylsalicylic acid: 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 4.4).

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 this 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 effects (See section 4.4).

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 and pseudoephedrine may diminish the effect 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.

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. Sympathomimetics such as pseudoephedrine may increase risk of dysrhythmias.

Lithium: There is evidence for potential increases 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 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.

4.6 Fertility, pregnancy and lactation

In summary: This medicine is contraindicated in pregnancy. If this medicine is used by a woman attempting to conceive, the dose should be kept as low and duration of treatment as short as possible.

Pregnancy

Pseudoephedrine:

There are limited amount of data on the use of pseudoephedrine in pregnant women. The use of pseudoephedrine during the first trimester of pregnancy has been associated with an increased frequency of gastroschisis (a developmental defect in the abdominal wall with intestinal herniation) and of small intestinal atresia (congenital obstruction of small intestine). Due to the vasoconstrictive properties of pseudoephedrine, it may induce a reduction in uteroplacental circulation.

Pseudoephedrine is not recommended in pregnancy.

Ibuprofen:

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 embryo-foetal lethality. In addition, increased incidences of various malformations, including cardiovascular, have been reported in animals given a prostaglandin synthesis inhibitor during the organogenetic period.

From the 20th week of pregnancy onward, ibuprofen use may cause oligohydramnios resulting from foetal renal dysfunction. This may occur shortly after treatment initiation and is usually reversible upon discontinuation. In addition, there have been reports of ductus arteriosus constriction following treatment in the second trimester, most of which resolved after treatment cessation. Therefore during the first and second trimester of pregnancy, ibuprofen should not be given unless clearly necessary.

Antenatal monitoring for oligohydramnios and ductus arteriosus constriction should be considered after exposure to ibuprofen for several days from gestational week 20 onward. Ibuprofen should be discontinued if oligohydramnios and ductus arteriosus constriction are found.

If ibuprofen is used by a woman attempting to conceive, 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 (premature constriction/closure of the ductus arteriosus and pulmonary hypertension);
• renal dysfunction (see above); which may progress to renal failure with oligohydramnios;

the mother and the neonate, at the end of 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, this medicine is contraindicated during pregnancy (see section 4.3).

Breastfeeding

In limited studies, ibuprofen appears in the breast milk in very low concentrations and is unlikely to affect the breast-fed infant adversely. Pseudoephedrine has been detected in human milk with a small percentage of the maternal dose potentially administered to the breastfed infant. Irritability and disturbed sleep have been reported in breastfed infants. Pseudoephedrine may suppress lactation. Avoid if lactation not well established or if milk production is insufficient.

Fertility

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

The most commonly observed adverse events are with ibuprofen are gastrointestinal in nature.

The following list of adverse effects relates to those experienced with ibuprofen at OTC doses (maximum 1200mg per day) and sympathomimetics including pseudoephedrine for short-term use. In the treatment of chronic conditions, under long-term treatment, additional adverse effects may occur.

Adverse events which have been associated with Ibuprofen and sympathomimetics including pseudoephedrine are given below, listed by system organ class and frequency. Frequencies are defined as: Very common (≥1/10), Common (≥1/100 and <1/10), Uncommon (≥1/1000 and <1/100), Rare (≥1/10,000 and <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.

Description of Selected Adverse Reactions:

¹ Examples include anaemia, leucopenia, thrombocytopenia, pancytopenia and agranulocytosis. First signs are fever, sore throat, superficial mouth ulcers, flu-like symptoms, severe exhaustion, unexplained bleeding and bruising.

² Hypersensitivity reactions: These may consist of (a) non-specific allergic reaction and anaphylaxis, (b) respiratory tract reactivity including asthma, aggravated asthma, bronchospasm and dyspnoea, or (c) various skin reactions, including pruritis, urticaria, purpura, angioedema and, more rarely, severe forms of skin reactions such as exfoliative and bullous dermatoses (including toxic epidermal necrolysis can occur, Stevens-Johnson Syndrome and erythema multiforme).

3 The pathogenic mechanism of drug-induced aseptic meningitis is not fully understood. However, the available data suggest that NSAID-related meningitis develops in individuals rendered susceptible by an underlying autoimmune disorder who were previously sensitized or had a natural immunity to the drug. 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 autoimmune disorders (such as systemic lupus erythematosus and mixed connective tissue disease).

⁴ 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).

⁵ The adverse events observed most often are gastrointestinal in nature.

⁶ Sometimes fatal, particularly in elderly.

⁷ See section 4.4.

⁸ Especially in long-term use, associated with increased serum urea and oedema. Also includes papillary necrosis.

* Renal tubular acidosis and hypokalaemia have been reported in the post-marketing setting typically following prolonged use of the ibuprofen component at higher than recommended doses

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 Website www.mhra.gov.uk/yellowcard or search for MHRA Yellow Card in the Google Play or Apple App Store.

4.9 Overdose

In children, ingestion of more than 400mg/kg ibuprofen may cause symptoms. In adults, the dose response is less clear cut. The half-life in overdose is 1.5 – 3 hours.

Symptoms

Symptoms include headache, nausea, vomiting, epigastric pain, gastrointestinal bleeding, rarely diarrhoea, disorientation, excitation, drowsiness, tinnitus. In cases of significant poisoning acute renal failure and liver damage are possible. In serious poisoning metabolic acidosis may occur and prothrombin time/INR may be prolonged, probably due to interference with the actions of circulatory clotting factors. Acute renal failure and liver damage may occur. Exacerbation of asthma is possible in asthmatics.

Prolonged use at higher than recommended doses may result in severe hypokalaemia and renal tubular acidosis. Symptoms may include reduced level of consciousness and generalised weakness (see section 4.4 and section 4.8).

As with other sympathomimetics, pseudoephedrine overdose may cause symptoms of central nervous system and cardiovascular stimulation, including: anxiety, irritability, restlessness, palpitations, convulsions, urinary retention, fever, sinus tachycardia, cardiac arrhythmias, sweating, insomnia, dilated pupils, blurred vision, delusions, hallucinations, muscular weakness, difficulty in micturition, nausea, vomiting, tremors, respiratory depression, hypertension (symptoms of overdose associated with pseudoephedrine).

Symptoms associated with severe poisoning from either ibuprofen or

pseudoephedrine overdose include convulsions and coma.

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.

Bronchodilators should be given for asthma.

A rapidly acting alpha blocker, such as phentolamine, may be given to reserve alpha1-mediated effects such as hypertension, while a beta blocker may be given for beta1-mediated effects such as cardiac arrhythmias. In severe hypertension, rapidly acting vasodilators such as glyceryl trinitrate have also been used.

Good urine output should be ensured.

Renal and liver function should be closely monitored.

Patients should be observed for at least four hours after ingestion of potentially toxic amounts.

Other measures may be indicated by the patient's clinical condition.

5 PHARMACOLOGICAL PROPERTIES

5.1 Pharmacodynamic properties

Pharmacotherapeutic Group: Anti-inflammatory and antirheumatic products, propionic acid derivatives. Ibuprofen combinations. ATC Code: M01AE51

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.

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 400mg were taken within 8 h before or within 30 min after immediate release 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 this 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).

Pseudoephedrine hydrochloride is used as a nasal and bronchial decongestant which acts by vasoconstriction to reduce oedema and nasal swelling. It is a stereoisomer of ephedrine and has a similar action. It is a sympathomimetic agent with direct and indirect effects on adrenergic receptors. It has alpha- and beta-adrenergic activities and has stimulating effects on the central nervous system. It has a more longed, though less potent action than adrenaline. However, pseudoephedrine has been stated to have less pressor activity and central nervous system effects than ephedrine. The sympathomimetic effect of pseudoephedrine produced vasoconstriction which in turn relieves nasal congestion.

5.2 Pharmacokinetic properties

Ibuprofen is rapidly absorbed from the gastrointestinal tract.

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. Excretion by the kidneys is both rapid and complete. Ibuprofen is extensively bound to plasma proteins.

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 to 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. Pseudoephedrine is readily and completely 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 about 5-8 hours, which may be reduced by acidifying the urine. Its urinary elimination and hence half-life is pH dependent. Pseudoephedrine is rapidly distributed throughout the body, its volume of distribution being 2 to 3 l/kg.

5.3 Preclinical safety data

There are no preclinical data of relevance to the prescriber which are additional to that already included in other sections of the SPC.

6 PHARMACEUTICAL PARTICULARS

6.1 List of excipients

Tricalcium phosphate 118

Microcrystalline cellulose

Povidone K29-32

Croscarmellose sodium

Magnesium stearate

Purified water Ph Eur

Isopropyl alcohol

Hydroxypropylmethylcellulose

Talc

Mastercote orange FA1202A (solids) (including Sunset yellow FCF (E110))

6.2. Incompatibilities

None known.

6.3. Shelf Life

36 months

6.4. Special Precautions for Storage

Do not store above 25°C.

Store in original package.

6.5. Nature and Contents of Container

Blister trays of white pigmented 250µm PVC/40G GSM PVDC laminate heat-sealed to lacquered 20µm hard-temper aluminium foil, containing 12 tablets. One or two trays contained in a cardboard carton.

6.6. Instruction for Use/Handling

None.

7. MARKETING AUTHORISATION HOLDER

The Boots Company Plc

1 Thane Road West

Nottingham

NG2 3AA

8. MARKETING AUTHORISATION NUMBER(S)

PL 00014/0600

9 DATE OF FIRST AUTHORISATION/RENEWAL OF THE

AUTHORISATION

06/03/2009

10 DATE OF REVISION OF THE TEXT

27/06/2025