Strefen Honey and Lemon

Active ingredient flurbiprofen 8.75mg

For excipients, see 6.1.

Lozenge

A round, pale yellow to brown lozenge with an icon intagliated on both sides of the lozenge.

Strefen Honey and Lemon are indicated for the symptomatic relief of sore throat.

Adults the elderly and children over the age of 12 years:

One lozenge sucked/dissolved slowly in the mouth every 3 - 6 hours as required. Maximum 5 lozenges in a 24 hour period.

The lowest effective dose should be used for the shortest duration necessary to relieve symptoms. The patient should consult a doctor if symptoms persist or worsen, or if the product is required for more than 3 days.

It is recommended that this product should be used for a maximum of three days

As with all lozenges, to avoid local irritation, Strefen Honey and Lemon should be moved around the mouth whilst sucking.

Hypersensitivity to flurbiprofen or any of the excipients in the product.

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

Severe heart failure, renal failure or hepatic failure (see section 4.4)

Last trimester of pregnancy.

Undesirable effects may be minimised by using the lowest effective dose for the shortest possible 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 history of, bronchial asthma or allergic disease.

Other NSAIDs: The use of Strefen Honey and Lemon 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)

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 trial and epidemiological data suggest that the use of NSAIDs particularly at high doses (2400 mg daily) and in long-term treatment may be associated with a small increased risk of arterial thrombotic events (for example myocardial infarction or stroke).

Impaired female 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.

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 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-platelet agents such as aspirin (see section 4.5).

When GI bleeding or ulceration occurs in patients receiving flurbiprofen, the treatment should be withdrawn.

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 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 in the majority of cases within the first month of treatment. Strefen Honey and Lemon should be discontinued at the first appearance of skin rash, mucosal lesions, or any other sign of hypersensitivity.

The label will include:

Read the enclosed leaflet before taking this product

Do not take if you:

• have (or have had two or more episodes of) a stomach ulcer, perforation or bleeding

• are allergic to flurbiprofen, to any of the ingredients, or to aspirin or other painkillers

• are taking other NSAID pain killers or aspirin with a daily dose above 75mg

• or the patient is under 12 years of age.

Speak to your doctor or pharmacist before use if you

• Have or have had asthma, diabetes, high cholesterol, high blood pressure, a stroke, heart, liver, kidney or bowel problems,

• Are a smoker

• Are pregnant

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

Flurbiprofen should be avoided in combination with:

Aspirin: 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).

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

Flurbiprofen 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 since NSAIDs may diminish the effects of these drugs. 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.

Lithium: There is evidence for potential increase in plasma levels of lithium.

Methotrexate: There is evidence for the potential increase in plasma levels of 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 hematological 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.

Whilst no teratogenic effects have been demonstrated in animal experiments, the use of Strefen Honey and Lemon should, if possible, be avoided during the first 6 months of pregnancy.

During the 3^rd trimester, flurbiprofen is contraindicated as there is a risk of premature closure of the foetal 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 Contraindications).

Flurbiprofen appears in the breast milk in very low concentration and is unlikely to affect the breast-fed infant adversely.

See section 4.4 regarding female fertility.

None expected at recommended doses and duration of therapy.

Strefen Honey and Lemon have the potential for inducing transient local irritation of the buccal mucosa. The most frequently reported adverse event in clinical trials was taste perversion.

Hypersensitivity reactions have been reported and these may consist of

(a) non-specific allergic reactions and anaphylaxis

(b) respiratory tract reactivity e.g. asthma, aggravated asthma, bronchospasm, dyspnoea

(c) various skin reactions e.g. pruritus, urticaria, 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 NSAIDS at doses available over the counter for short-term use. In the treatment of chronic conditions, under long-term treatment, additional adverse effects may occur.

Hypersensitivity reactions:

Uncommon: Hypersensitivity reactions with urticaria and pruritis

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

Exacerbation of asthma and bronchospasm.

Gastrointestinal:

The most commonly observed adverse events are gastrointestinal in nature.

Uncommon: abdominal pain, nausea, 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 colitis and Crohn's disease (section 4.4).

Nervous System:

Uncommon: Headache

Very rare: Aseptic meningitis – single cases have been reported very rarely.

Renal:

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

Hepatic:

Very rare: liver disorders.

Haematological:

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.

Dermatological:

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.

Immune System:

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).

Cardiovascular and Cerebrovascular

Oedema, hypertension and cardiac failure, have been reported in association with NSAID treatment.

Clinical trial and epidemiological data suggest that the use of NSAIDS (particularly at high doses 2400 mg 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).

Symptoms Most 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 the 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.

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. Give bronchodilators for asthma.

Pharmacotherapeutic Group: Propionic acid derivatives, anti-inflammatory and anti-rheumatic products.

ATC Code: R02AX01

Flurbiprofen is a non-steroidal anti-inflammatory drug which has potent analgesic, antipyretic and anti-inflammatory properties which are thought to result from the drug's ability to inhibit prostaglandins synthesis.

The onset of pain relief, reduction in throat soreness and reduction in throat swelling was observed 30 minutes after taking a lozenge and duration of action extended to 2-3 hours.

Flurbiprofen is rapidly absorbed following the use of STREFEN with plasma concentrations peaking at 30 - 40 minutes. Peak concentrations are achieved more rapidly than, but are of similar magnitude to, those achieved after an equivalent swallowed dose.

Flurbiprofen is rapidly distributed throughout the body. It is mainly metabolised by hydroxylation and excreted via the kidneys.

It is extensively bound to plasma proteins and has an elimination half-life of 3 to 6 hours.

Flurbiprofen is excreted in very small amounts in human milk (less than 0.05ug/ml).

In rats exposed to 0.4mg/kg/day and above during pregnancy an increased incidence of stillborn pregnancy has been observed. However, the relevance of this fact to humans is doubtful and not reflected in human experience with flurbiprofen so far.

Macrogol 300

Potassium hydroxide

Lemon flavour

Levomenthol

Liquid sucrose

Liquid glucose

Honey

Not applicable.

36 months.

Store in the original package

A push through strip consisting of 250 microns opaque PVC/PVdC (polyvinyl chloride/polyvinyl di-chloride) blister, heat sealed to hard tempered 20 micron aluminium foil. Blisters are enclosed in a cardboard carton in pack sizes of 2, 4, 6, 8, 10, 12, or 16 lozenges

None

Crookes Healthcare Limited

1 Thane Road West

Nottingham

NG2 3AA

United Kingdom

PL 00327/0135

19/09/2006

07/06/2011