Reckitt Benckiser Ireland Limited

Nurofen for Children 60 mg Suppositories Age 3 months to 2 years

1 suppository contains: Ibuprofen 60 mg

For excipients, see 6.1

Suppositories

White or yellowy-white cylindrical suppositories

Reduction of fever and relief of mild to moderate pain, such as teething pain, toothache, headache, sprains and strains and to ease the pain of sore throats and earache.

Relief of pain and fever associated with colds and influenza.

For rectal use only.

Do not use in children under 3 months of age without medical advice.

The maximum total daily dose of Nurofen for Children 60 mg Suppositories Age 3 months to 2 years is 20-30 mg/Kg of body weight, administered in three to four single doses. This can be achieved as follows:

Do not use this product in children weighing less than 6kg .

For short term use only.

Patients with severe hepatic failure, severe renal failure or severe heart failure.

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

Patients with a known hypersensitivity to ibuprofen or any other constituents of the medicinal product.

Patients with a history of bronchospasm, asthma, rhinitis, urticaria, associated with aspirin or other non-steroidal anti-inflammatory drugs.

During the last trimester of pregnancy (see section 4.6)

The use of Nurofen for Children 60mg Suppositories Age 3 months to 2 years with concomitant NSAIDs including cyclooxygenase-2 selective inhibitors should be avoided.

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

Elderly: The elderly have an increased frequency of adverse reactions to NSAIDs especially gastrointestinal bleeding and perforation which may be fatal.

Gastrointestinal bleeding, ulceration and perforation: GI bleeding, ulceration or perforation, which can be fatal, has been reported with all NSAIDs at any time during treatment, with or without any warning symptoms or a previous history of serious GI events.

The risk of GI bleeding, ulceration or perforation is higher with increasing NSAID doses, in patients with a history of ulcer, particularly if complicated with haemorrhage or perforation (see section 4.3), and in the elderly. These patients should commence treatment on the lowest dose available. Combination therapy with protective agents (e.g. misoprostol or proton pump inhibitors) should be considered for these patients, and also for patients requiring concomitant low dose aspirin, or other drugs likely to increase gastrointestinal risk (see below and 4.5).

Patients with a history of GI toxicity, particularly when elderly, should report any unusual abdominal symptoms (especially GI bleeding) particularly in the initial stages of treatment.

Caution should be advised in patients receiving concomitant medications which could increase the risk of ulceration or bleeding, such as oral corticosteroids, anticoagulants such as warfarin, selective serotonin reuptake inhibitors or anti-platelet agents such as aspirin (see section 4.5).

When GI bleeding or ulceration occurs in patients receiving Nurofen for Children 60mg Suppositories Age 3 months to 2 years, the treatment should be withdrawn.

NSAIDs should be given with care to patients with a history of gastrointestinal disease (ulcerative colitis, Crohn's Disease) as their condition may be exacerbated (see section 4.8 – undesirable effects).

Caution (discussion with doctor or pharmacist) is required prior to starting treatment in patients with a history of hypertension and/or heart failure as fluid retention and oedema have been reported in association with NSAID therapy.

Cardiovascular and cerebrovascular effects

Clinical trial and epidemiological data suggest that use of ibuprofen, particularly at high doses (2400mg daily) and in long term treatment may be associated with a small increased risk of arterial thrombotic events (for example myocardial infarction or stroke). Overall, epidemiological studies do not suggest that low dose ibuprofen (e.g. < 1200mg daily) is associated with an increased risk of myocardial infarction.

Caution is required in patients with renal impairment (see section 4.3) since renal function may deteriorate. In patients with renal impairment, renal function should be monitored as it may deteriorate following the use of NSAIDs.

Caution is required in patients with hepatic impairment (see section 4.3)

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

As NSAIDs can interfere with platelet function, they should be used with caution in patients with idiopathic thrombocytopenic purpura (ITP), intracranial haemorrhage and bleeding diathesis.

Serious skin reactions, some of them fatal, including exfoliative dermatitis, Stevens-Johnson syndrome, and toxic epidermal necrolysis, have been reported very rarely in association with the use of NSAIDs (see 4.8). Patients appear to be at highest risk of these reactions early in the course of therapy, the onset of the reaction occurring in the majority of cases within the first month of treatment. Nurofen for Children 60mg Suppositories Age 3 months to 2 years should be discontinued at the first appearance of skin rash, mucosal lesions, or any other sign of hypersensitivity.

There is some evidence that drugs which inhibit cyclo-oxygenase/prostaglandin synthesis may cause impairment of female fertility by an effect on ovulation. This is reversible on withdrawal of treatment.

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

Caution is advised in patients with systemic lupus erythematosus as well as those with connective tissue disease (see section 4.8)

Caution is also required in patients with disorders of the anus or rectum.

Corticosteroids: increased risk of gastrointestinal ulceration or bleeding (see section 4.4).

Anti-coagulants: NSAIDs may enhance the effects of anticoagulants, such as warfarin (see section 4.4).

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

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

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

ACE inhibitors and Angiotensin II Antagonists: NSAIDs may reduce the effect of diuretics and other antihypertensive 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 ibuprofen 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.

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

Lithium: decreased elimination of lithium.

Methotrexate: decreased elimination of methotrexate.

Cyclosporin: increased risk of nephrotoxicity with NSAIDs.

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

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

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

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

Zidovudine: there is evidence of an increased risk of haemarthroses and haematoma in HIV (+) haemophiliacs receiving concurrent treatment with zidovudine and ibuprofen.

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

There is insufficient experience about the safety of use of ibuprofen in humans during pregnancy. As the influence of prostaglandin synthesis inhibition is unclear, it is recommended not to use ibuprofen during the first six months of pregnancy.

In the last trimester of pregnancy use of ibuprofen is contraindicated. Due to the mechanism of action, inhibition of uterine contractions, premature closure of ductus arteriosus and pulmonary hypertension of the neonate, an increased bleeding tendency in mother and child and increased formation of oedema in the mother could occur.

Ibuprofen and its metabolites can pass in very small concentrations (0.0008% of the maternal dose) into the breast milk. No harmful effects to infants are known, so it is not necessary to interrupt breast-feeding for short-term treatment with the recommended dose for mild to moderate pain and fever.

See section 4.4 on Special Warnings and Precautions for use regarding female fertility

Nurofen for Children 60mg Suppositories Age 3 months to 2 years has no or negligible influence on the ability to drive and use machines.

The list of the following 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 adverse effects may occur.

The frequencies are defined as follows:

Very common (1/10)

Common (1/100 to <1/10)

Uncommon (1/1000 to <1/100

Rare (1/10000 to <1/1000)

Very Rare (<1/10000)

Not known (cannot be estimated from the available data)

.

Symptoms of Overdosing

The symptoms of overdose can include nausea, vomiting, abdominal pain, headache, dizziness, drowsiness, nystagmus, blurred vision, tinnitus and, rarely, hypotension, metabolic acidosis, renal failure and loss of consciousness.

A dose in excess of 200mg/kg carries a risk of causing toxicity.

Therapeutic Measure in Overdosing

No specific antidote is available.

Patients should be treated symptomatically as required. Use supportive care where appropriate.

ATC Code:M01AE01

Ibuprofen is an NSAID that has demonstrated its efficacy in the common animal experimental inflammation models by inhibition of prostaglandin synthesis. In humans, ibuprofen reduces inflammatory pain, swelling and fever. Furthermore, ibuprofen reversibly inhibits platelet aggregation.

The clinical efficacy of ibuprofen has been demonstrated in fever and in pain associated with headache, toothache and dysmenorrhoea. Furthermore it has been demonstrated in patients with pain and fever associated with cold and flu and in pain models such as sore throat, muscular pain, soft tissue injury, backache.

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

After rectal administration, ibuprofen is absorbed quickly and almost completely with median peak plasma concentrations, which are seen 0.75 hours after use of a 60 mg suppository.

Ibuprofen is extensively bound to plasma proteins.

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

The toxicity of ibuprofen in animal experiments was observed as lesions and ulcerations in the gastrointestinal tract. Ibuprofen did not show a mutagenic potential in vitro and was not carcinogenic in rats and mice. Experimental studies have demonstrated that ibuprofen crosses the placenta, but there is not evidence of any teratogenic action.

Hard Fat

Not applicable.

2 years

Do not store above 25°C.

PE 40g/m²/aluminium foil 45μm/lacquer 1.0 g/m²

Pack size: 10 or 20 Suppositories. Not all pack sizes may be marketed.

None.

Reckitt Benckiser Ireland Ltd.,

7 Riverwalk,

Citywest Business Campus, dublin 24

PA 979/32/7

Date of first authorisation: 12^th September 2008

April 2009