IBUPROFEN EFFERVESCENT TABLETS 200 MG, IBUSOLVE 200 MG EFFERVESCENT TABLETS - summary of medicine characteristics

1 NAME OF THE MEDICINAL PRODUCT

Ibuprofen Effervescent Tablets 200mg

Ibusolve 200mg Effervescent Tablets

2 QUALITATIVE AND QUANTITATIVE COMPOSITION

Ibuprofen 200mg

Each tablet contains 661mg Sodium

For excipients, see 6.1.

3 PHARMACEUTICAL FORM

Effervescent tablets

4 CLINICAL PARTICULARS

4.1 Therapeutic indications

For the relief of rheumatic or muscular pain, pain of non-serious arthritic conditions, backache, neuralgia, migraine, headache, dental pain, dysmenorrhoea, feverishness, symptoms of colds and influenza.

4.2 Posology and method of administration

The lowest effective dose should be used for the shortest duration necessary to relieve symptoms (see section 4.4). For oral administration and short-term use only.

Adults and the elderly

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.

Initial dose – One or two tablets to be taken. The initial dose may be followed by further doses of one or two tablets every four hours. Leave at least four hours between doses and do not take more than 1200mg (6 tablets) in any 24 hour period. To be taken preferably after food.

Adolescents (age range: > 12 years to < 18 years)

If this medicinal product is required for more than 3 days, or if symptoms

worsen a doctor should be consulted.

Children

Not suitable for children under 12 years.

Directions

The tablets must be dissolved in half a glass of water (100ml). The tablets dissolve more quickly in warm water, or if stirred.

4.3 Contraindications

Hypersensitivity to active substance or to any of the excipients listed in section 6.1.

Patients who have previously shown hypersensitivity reactions (e.g. asthma, rhinitis, angioedema or urticaria) in response to ibuprofen, aspirin or other non-steroidal anti- inflammatory drugs.

History of gastrointestinal bleeding or perforation, related to previous NSAIDs therapy. Ibuprofen should not be used in patients with an active or previous peptic ulcer or gastrointestinal haemorrhage (two or more distinct episodes of proven ulceration or bleeding).

Ibuprofen should not be given to patients with conditions involving an increased tendency to bleeding.

Severe hepatic failure, renal failure or severe heart failure (NYHA Class IV) (See section 4.4, Special warnings and precautions for use).

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 section 4.2, and GI and cardiovascular risks below).

As with other NSAIDs, ibuprofen may mask the signs of infection.

The use of ibuprofen with concomitant NSAIDs, including cyclooxygenase-2 selective inhibitors, should be avoided due to the increased risk of ulceration or bleeding (see section 4.5).

The diagnosis of medication overuse headache (MOH) should be suspected in patients who have frequent or daily headaches despite (or because of) the regular use of analgesic medication. Patients with medication overuse headache should not be treated by increasing the dose of the analgesic. In such cases the use of analgesics should be discontinued.

The concomitant consumption of excessive alcohol with NSAIDs, including ibuprofen may increase the risk of adverse effects on the gastrointestinal tract, such as GI haemorrhage or the central nervous system, possibly due to an additive effect.

Elderly

The elderly have an increased frequency of adverse reactions due to NSAID, especially especially gastrointestinal bleeding and perforation, which may be fatal (see section 4.2).

Paediatric population

There is a risk of renal impairment in dehydrated adolescents

Gastrointestinal bleeding, ulceration and perforation

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. 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 section 4.5).

Patients with a history of gastrointestinal disease, particularly when elderly, should report any unusual abdominal symptoms (especially gastrointestinal 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 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.

NSAIDs should be given with care to patients with a history of ulcerative colitis or Crohn’s diseaseas these conditions may be exacerbated (See section 4.8).

Respiratory disorders and hypersensitivity reactions

Caution is required if ibuprofen is administered to patients suffering from, or with a previous history of, bronchial asthma, chronic rhinitis or allergic diseases since NSAIDs have been reported to precipitate bronchospasm, urticaria or angioedema in such patients.

Cardiac, renal and hepatic impairment

The administration of an NSAID may cause a dose dependent reduction in prostaglandin formation and precipitate renal failure. The habitual concomitant intake of various similar painkillers further increases this risk. Patients at greatest risk of this reaction are those with impaired renal function, cardiac impairment, liver dysfunction, those taking diuretics and the elderly. For these patients, use the lowest effective dose, for the shortest possible duration and monitor renal function especially in long-term treated patients (see also section 4.3).

Ibuprofen should be given with care to patients with a history of heart failure or hypertension since oedema has been reported in association with ibuprofen administration.

Cardiovascular and cerebrovascular effects

Appropriate monitoring and advice are required for patients with a history of hypertension and/or mild to moderate congestive heart failure as fluid retention and oedema have been reported in association with NSAID therapy.

Clinical studies suggest that use of ibuprofen, particularly at high doses (2400mg/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.

<1200mg/day) is associated with an increased risk of arterial thrombotic events.

Patients with uncontrolled hypertension, congestive heart failure (NYHA IIIII), established ischaemic heart disease, peripheral arterial disease, and/or cerebrovascular disease should only be treated with Ibuprofen after careful consideration and high doses (2400mg/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.

Renal effects

Caution should be used when initiating treatment with ibuprofen in patients with considerable dehydration. There is a risk of renal impairment especially in dehydrated children, adolescents and the elderly.

As with other NSAIDs, long-term administration of ibuprofen has resulted in renal papillary necrosis and other renal pathologic changes. Renal toxicity has also been seen in patients in whom renal prostaglandins have a compensatory role in the maintenance of renal perfusion. In these patients, administration of an NSAID may cause a dose dependant reduction in prostaglandin formation and, secondarily, in renal blood flow, which may cause renal failure.

Patients at greatest risk of this reaction are those with impaired renal function, heart failure, liver dysfunction, those taking diuretics and ACE inhibitors and the elderly. Discontinuation of NSAID therapy is usually followed by recovery to the pre-treatment state.

SLE and mixed connective tissue disease

In patients with systemic lupus erythematosus (SLE) and mixed connective tissue disorders increased risk of aseptic meningitis (see below and section 4.8).

Severe skin reactions

Serious skin reactions, some of them fatal, including exfoliative dermatitis, Stevens-Johnson syndrome, and toxic epidermal necrolysis have been reported 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 within the first month of treatment in the majority of cases. Acute generalised exanthematous pustulosis (AGEP) has been reported in relation to ibuprofen-containing products. Ibuprofen should be discontinued, at the first appearance of skin rash, mucosal lesions, or any other sign of hypersensitivity.

In exceptional cases, varicella can be at the origin of serious cutaneous and soft tissues infectious complications. To date, the contributing role of NSAIDs in the worsening of these infections cannot be ruled out. Thus, it is advisable to avoid use of Ibuprofen in case of varicella.

Haematological effects

Ibuprofen, like other NSAIDs, can interfere with platelet aggregation and prolong bleeding time in normal subjects.

Aseptic meningitis

Aseptic meningitis has been observed on rare occasions in patients on ibuprofen therapy. Although it is probably more likely to occur in patients with systemic lupus erythematosus and related connective tissue diseases, it has been reported in patients who do not have an underlying chronic disease.

Impaired female fertility

The use of Ibuprofen may impair female fertility and is not recommended in women attempting to conceive. In women who have difficulties conceiving or who are undergoing investigation of infertility, withdrawal of ibuprofen should be considered.

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 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.

The label will include:

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 asthma, liver, heart, kidney or bowel problems.

are in the first 6 months of pregnancy.

If symptoms persist or worsen, consult your dentist or doctor.

This medicinal product contains 661 mg sodium per tablet, equivalent to 33% of the WHO recommended maximum daily intake of 2 g sodium for an adult.

The maximum daily dose of this product is equivalent to 198% of the WHO recommended maximum daily intake for sodium. Effervescent Tablets are considered high in sodium. This should be particularly taken into account for those on a low salt diet.

4.5 Interaction with other medicinal products and other forms of interaction

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

Antihypertensives, beta-blockers and diuretics: NSAIDs may diminish the effect of anti-hypertensives, such as ACE inhibitors, angiotensin-II receptor antagonists, beta-blockers and diuretics. Diuretics can also increase the risk of nephrotoxicity of NSAIDs.

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

Cholestyramine; The concomitant administration of ibuprofen and cholestyramine may reduce the absorption of ibuprofen in the gastrointestinal tract. However, the clinical significance is unknown.

Lithium: Decreased elimination of lithium.

Methotrexate: NSAIDs may inhibit the tubular secretion of methotrexate and reduce clearance of methotrexate..

Ciclosporin: Increased risk of nephrotoxicity.

Mifepristone: A decrease in the efficacy of the medicinal product can theoretically occur due to the antiprostaglandin properties of NSAIDs. Limited evidence suggests that coadministration of NSAIDs on the day of prostaglandin administration does not adversely influence the effects of mifepristone or the prostaglandin on cervical ripening or uterine contractility and does not reduce the clinical efficacy of medicinal termination of pregnancy.

Other analgesics and cyclooxygenase-2 selective inhibitors: Avoid concomitant use of two or more NSAIDs, includingCox-2 inhibitors, as this may increase the risk of adverse effects (see section 4.4).

Aspirin (Acetylsalicylic acid)

As with other products containing NSAIDs, 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 aspirin 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 use (see section 5.1).

Corticosteroids: Increased risk of gastrointestinal ulceration or bleeding with NSAIDs (see section 4.4).

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

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.

Sulfonylureas: NSAIDs may potentiate the effects of sulfonylurea medications. There have been rare reports of hypoglycaemia in patients on sulfonylurea medications receiving ibuprofen.

Anti-platelet agents and selective serotonin reuptake inhibitors (SSRIs): Increased risk of gastrointestinal bleeding with NSAIDs (see section 4.4).

Tacrolimus: Possible increased risk of nephrotoxicity when NSAIDs are given with tacrolimus

Zidovudine: Increased risk of haematological toxicity when NSAIDs are given withzidovudine. There is evidence of an increased risk of haemarthroses and haematoma in HIV (+) haemophiliacs receiving concurrent treatment with zidovudine and ibuprofen.

Aminoglycosides: NSAIDs may decrease the excretion of aminoglycosides.

Herbal extracts: Ginkgo biloba may potentiate the risk of bleeding with NSAIDs.

CYP2C9 Inhibitors: Concomitant administration of ibuprofen with CYP2C9 inhibitors may increase the exposure to ibuprofen (CYP2C9 substrate). In a study with voriconazole and fluconazole (CYP2C9 inhibitors), an increased S(+)-,ibuprofen exposure by approximately 80 to 100% has been shown. Reduction of the ibuprofen dose should be considered when potent CYP2C9 inhibitors are administered concomitantly, particularly when high-dose ibuprofen is administered with either voriconazole or fluconazole.

4.6 Fertility, pregnancy and lactation

Pregnancy

Inhibition of prostaglandin synthesis may adversely affect the pregnancy and/or embryo/foetal development. Data from epidemiological studies suggest an increased risk of miscarriage and of cardiac malformation and gastroschisis after the use of a prostaglandin synthesis inhibitor in early pregnancy. The risk is believed to increase with dose and duration of therapy. In animals, the administration of a prostaglandin synthesis inhibitor has been shown to result in increased pre- and post-implantation losses 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. During the first and second trimester of pregnancy, ibuprofen should not be given unless clearly necessary. If ibuprofen is used by a woman attempting to conceive, or during the first or 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 the following:

Cardiopulmonary toxicity (with premature closure of the ductus arteriosus and pulmonary hypertension)

Renal dysfunction, which may progress to renal failure with oligohydramnios.

At the end of pregnancy, prostaglandin synthesis inhibitors may expose the mother and the neonate to the following:

Possible prolongation of bleeding time

Inhibition of uterine contractions, which may result in delayed or prolonged labour.

Consequently, Ibuprofen is contraindicated during the third trimester of pregnancy.

Breastfeeding

In the limited studies so far available, NSAIDs can appear in the breast milk in very low concentrations. NSAIDs should, if possible, be avoided when breastfeeding.

See section 4.4 regarding female fertility.

4.7 Effects on ability to drive and use machines

Undesirable effects such as dizziness, drowsiness, fatigue and visual disturbances are possible after taking NSAIDs. If affected, patients should not drive or operate machinery.

4.8 Undesirable effects

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, gastrointestinal haemorrhage and exacerbation of colitis and Crohn's disease (see section 4.4) have been reported following ibuprofen administration. Less frequently, gastritis, duodenal ulcer, gastric ulcer and gastrointestinal perforation have been observed.

Immune system disorders: Hypersensitivity reactions have been reported following treatment with NSAIDs. These may consist of (a) non-specific allergic reaction and anaphylaxis, (b) respiratory tract reactivity comprising asthma, aggravated asthma, bronchospasm or dyspnoea, or © assorted skin disorders, including rashes of various types, pruritus, urticaria, purpura, angioedema and, very rarely, erythema multiforme, bullous dermatoses (including Stevens- Johnson syndrome and toxic epidermal necrolysis).

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 high dose (2400 mg/day) may be associated with a small increased risk of arterial thrombotic events such as myocardial infarction or stroke (see section 4.4).

Infections and infestations: Rhinitis and aseptic meningitis (especially in patients with existing autoimmune disorders, such as systemic lupus erythematosus and mixed connective tissue disease) with symptoms of stiff neck, headache, nausea, vomiting, fever or disorientation (see section 4.4). Exacerbation of infection-related inflammations coinciding with the use of NSAIDs has been described. If signs of an infection occur or get worse during use of Ibuprofen the patient is therefore recommended to go to a doctor without delay.

Skin and subcutaneous tissue disorders: In exceptional cases, severe skin infections and soft-tissue complications may occur during a varicella infection (see also „Infections and infestations“)

The following adverse reactions possibly related to ibuprofen and displayed by MedDRA frequency convention and system organ classification. Frequency groupings are classified according to the subsequent conventions: very common (>1/10), Common (>1/100 to <1/10), Uncommon (>1/1,000 to <1/100), Rare (>1/10,000 to <1/1,000),

Very rare (<1/10,000) and Not known (cannot be estimated from the available data).

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 or search for MHRA Yellow Card in the Google Play or Apple App Store.

4.9. Overdose

Toxicity

Signs and symptoms of toxicity have generally not been observed at doses below 100 mg/kg in children or adults. However, supportive care may be needed in some cases.

Children have been observed to manifest signs and symptoms of toxicity after ingestion of 400 mg/kg or greater.

Symptoms

Most patients who have ingested clinically significant amounts of ibuprofen will manifest symptoms within 4 to 6 hours.

The most frequently reported symptoms of overdose include nausea, vomiting, abdominal pain, lethargy and drowsiness. Central nervous system (CNS) effects include tinnitus, headache, dizziness, convulsion, and loss of consciousness. Nystagmus, metabolic acidosis, hypothermia, renal effects, gastrointestinal bleeding, coma, apnoea, diarrhea and depression of the CNS and respiratory system have also been rarely reported. In serious poisoning, metabolic acidosis may occur Disorientation, excitation, fainting and cardiovascular toxicity, including hypotension, bradycardia and tachycardia have been reportedIn cases of significant overdose acute renal failure and liver damage are possible. Large overdoses are generally well tolerated when no other drugs are being taken.

Therapeutic measures

Patients should be treated symptomatically as required.

Within 1 hour of ingestion of a potentially toxic amount activated charcoal should be

considered. Alternatively, in adults, gastric lavage should be considered within one hour of ingestion of a potentially life-threatening overdose.

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

Frequent or prolonged convulsions should be treated with intravenous diazepam Other measures may be indicated by the patient's clinical condition.

5.1 Pharmacodynamic properties

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 pharmacodynamics 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 cannot be excluded. No clinically relevant effect is considered to be likely for occasional ibuprofen use (see section 4.5)

5.2 Pharmacokinetic properties

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 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.

5.3 Preclinical safety data

None stated.

6.1

Sodium bicarbonate

Sodium carbonate (anhydrous)

Sodium cyclamate

Sodium saccharin

Citric acid anhydrous

Docusate sodium

Polyethylene glycol powder 6000 Povidone

Orange mint flavour 611160E

Mango flav-o-lok 610575E

IMS

6.2 Incompatibilities

None stated.

6.3 Shelf life

24 months unopened.

6.4 Special precautions for storage

Store in a cool dry place.

6.5 Nature and contents of container

Strip pack using PPFM laminate, constructed of: 40gsm MGBK paper / 12gsm LDPE / 8p. aluminium foil / 23gsm LDPE. Strips are packed into a carton containing either 10, 12, 16, 24, 30, 36, 50, 56, 100 or 112 tablets

6.6 Special precautions for disposal None.