STREPSILS INTENSIVE Lozenge Ref.[50291] Active ingredients: Flurbiprofen

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).

If the symptoms get worse or if new symptoms occur, the treatment should be re-evaluated by a healthcare professional. If mouth irritation occurs, treatment should be withdrawn.

Other NSAIDs: The use of Strepsils Intensive Lozenges with concomitant NSAIDs including cyclooxygenase-2 selective inhibitors should be avoided (see section 4.5).

Elderly: The elderly have an increased frequency of adverse reactions to NSAIDs especially gastrointestinal bleeding and perforation which may be fatal (see section 4.2)

Gastrointestinal effects

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When GI bleeding or ulceration occurs in patients receiving Strepsils Intensive Lozenges, the treatment should be withdrawn.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).

Cardiovascular and cerebrovascular effects

Clinical trial and epidemiological data suggest that use of some NSAIDs (particularly at high doses and in long term treatment) may be associated with a small increased risk of arterial thrombotic events (for example myocardial infarction or stroke). There is insufficient data to exclude such a risk for flurbiprofen when given at a daily dose of 8.75mg to 43.75mg per day.

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.

Nervous System Effects

Analgesic induced headache. In the eventof prolonged use of analgesics or usebeyond the product posology, headachemay occur, which must not be treated with increased doses of the medicinal product.

Renal and Hepatic Impairment

Caution is required in patients with renal or hepatic impairment. NSAIDs have been reported to cause nephrotoxicity in various forms including interstitial nephritis, nephrotic syndrome and renal failure. The administration of an NSAID may cause a dose dependent reduction in prostaglandin formation and precipitate renal failure. Patients at greatest risk of this reaction are those with impaired renal function, cardiac impairment, liver dysfunction, those taking diuretics and the elderly, however, this effect is not usually seen with short term, limited use flurbiprofen products.

Dermatological

Serious skin reactions, some of them fatal, including exfoliative dermatitis, Stevens-Johnson syndrome, and toxic epidermal necrolysis, have been reported very rarely in association with the use of NSAIDs (see 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. Strepsils Intensive Lozenges should be discontinued at the first appearance of skin rash, mucosal lesions, or any other sign of hypersensitivity.

Systemic lupus erythematosus and mixed connective tissue disease

Patients with systemic lupus erythematosus and mixed connective tissue disease may have an increased risk of aseptic meningitis, however this effect is not usually seen with short term and limited use products such as flurbiprofen.

Respiratory

Bronchospasm maybe precipitated in patients suffering from, or with a previous history of, bronchial asthma or allergic reactions. Flurbiprofen should be used with caution in these patients.

Infections

Since in isolated cases an exacerbation of infective inflammations (e.g. development of necrotising fasciitis) has been described in temporal association with the use of systemic NSAIDs as a class, the patient is advised to consult a physician immediately if signs of a bacterial infection occur or worsen during the flurbiprofen therapy.

Flurbiprofen can prolong bleeding time and caution is required in patients with potential for abnormal bleeding.

The use of flurbiprofen 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 flurbiprofen should be considered.

Excipients

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

This product contains only very low levels of gluten (from wheat starch). It is regarded as ‘gluten-free’ and is very unlikely to cause problems if you have coeliac disease. One lozenge contains no more than 21.38 micrograms of gluten. If you have wheat allergy (different from coeliac disease) you should not take this medicine.

This medicine also contains fragrances with Citral, Citronellol, d-Limonene, Farnesol, Geraniol and Linalool which may cause allergic reactions and Sulphur Dioxide (E220) which may rarely cause severe hypersensitivity reactions and bronchospasm.

This medicine contains butylated hydroxyanisole (E320) which may cause local skin reactions) e.g. contact dermatitis) or irritation to the eyes and mucous membranes.

No studies so far have revealed any interactions between flurbiprofen and tolbutamide or antacids.

Paediatric population: No additional information available.

Pregnancy

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 had been shown to result in increased pre- and post-implantation loss and embryo-foetal lethality. In addition, increase 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, flurbiprofen should not be given.

During the third trimester of pregnancy, all prostaglandin synthesis inhibitors may expose the foetus to:

• Cardiopulmonary toxicity (with premature closure of the ductus arteriosus and pulmonary hypertension)
• Renal dysfunction, which may progress to renal failure with olgio-hydroamniosis;

The mother and the neonate, at the end of pregnancy, to:

• Possible prolongation of bleeding time, an anti-aggregation effect which may occur even at very low doses.
• Inhibitions of uterine contractions resulting in delayed or prolonged labour.

Consequently, flurbiprofen is contraindicated during the third trimester of pregnancy (see section 4.3).

Breast-feeding

In limited studies, flurbiprofen appears in the breast milk in a very low concentration and is unlikely to affect the breast-fed infant adversely. However, because of possible adverse effects of NSAIDs on breast-fed infants, flurbiprofen is not recommended for use in nursing mothers.

Fertility

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.

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

Dizziness, drowsiness and visual disturbances are possible undesirable side effects after taking NSAIDs. If affected, the patient should not drive or operate machinery.

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

1. Non-specific allergic reactions and anaphylaxis,
2. Respiratory tract reactivity comprising asthma, aggravated asthma, bronchospasm or dyspnoea,
3. Assorted skin disorders, including rashes of various types, pruritus, urticaria, purpura, angioedema and more rarely exfoliative and bullous dermatoses (including epidermal necrolysis and erythema multiforme).

The list of the following adverse effects relates to those experienced with flurbiprofen at OTC doses, in short-term use.

The frequencies of the adverse drug reactions (ADRs) reported below are based on the reporting of adverse events in all patients receiving flurbiprofen 8.75 mg in placebo-controlled, open-label, and active comparator clinical trials.

They are tabulated by system organ class and frequency. Frequencies are defined as Very common (≥1/10); Common (≥1/100 and <1/10); Uncommon (≥1/1,000 to <1/100); Rare (≥1/10,000 to <1/1,000); Very rare (< 1/10,000); Not known (cannot be estimated from the available data).

Reporting of Suspected Adverse Events

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 Pharmacovigilance Section, Health Products Regulatory Authority, Kevin O’Malley House, Earlsfort Centre, Earlsfort Terrace, IRL – Dublin 2; Tel: +353 1 6764971; Fax: +353 1 6762517; Website: www.hpra.ie; E-mail: medsafety@hpra.ie.

Not applicable.