Domina

Composition: Each tablet contains 8,75mg Flurbiprofen

Mechanism of action:

Flurbiprofen is a propionic acid derivative NSAID which acts through inhibition of prostaglandin synthesis. In humans flurbiprofen has potent analgesic, antipyretic and anti-inflammatory properties and the 8.75mg dose dissolved in artificial saliva has been shown to reduce prostaglandin synthesis in cultured human respiratory cells, flurbiprofen is a mixed COX-1/COX-2 inhibitor with some selectivity towards COX-1.

The lozenge format dissolves in the mouth over 5 - 12 minutes and provides a measurable soothing and coating effect at 2 minutes. A single dose of flurbiprofen delivered locally to the throat in a lozenge has been demonstrated to relieve sore throat, including swollen and inflamed sore throats through a significant reduction in sore throat pain intensity from 22 minutes. At 2 hours post first dose, flurbiprofen 8.75mg lozenges provided significant resolution of some of the associated symptoms of sore throat present at baseline including coughing, loss of appetite and feverishness.

The analgesic effect of flurbiprofen was not reduced by the administration of antibiotics to treat patients with streptococcal sore throat.

Pharmacokinetic properties:

Flurbiprofen lozenges dissolve over 5 – 12 minutes and the flurbiprofen is readily absorbed, absorption of flurbiprofen can occur from the buccal cavity by passive diffusion.
Flurbiprofen is rapidly distributed throughout the body and is extensively bound to plasma proteins.
Flurbiprofen is mainly metabolised by hydroxylation and excreted via the kidneys. It has an elimination half-life of 3 to 6 hours. Flurbiprofen is excreted in very small amounts in human milk. Approximately 20-25% of a flurbiprofen oral dose is excreted unchanged.

Indications

Strep-Sore lozenges tablets are indicated for the short-term symptomatic relief of sore throat in adults and children over the age of 12 years.

Contraindications

Hypersensitivity to flurbiprofen or any of the excipients in the product.
Patients who have previously shown hypersensitivity reactions (e.g. asthma, bronchospasm, rhinitis, angioedema, or urticaria) in response to acetylsalicylic acid or other NSAIDs.
Active or history of recurrent peptic ulcer/haemorrhage (two or more distinct episodes of proven ulceration)
History of gastrointestinal bleeding or perforation, severe colitis, haemorrhagic or haematopoietic disorders related to previous NSAID therapy.
Last trimester of pregnancy.
Severe heart failure, severe renal failure or severe hepatic failure

Special warnings

Undesirable effects may be minimised by using the lowest effective dose for the shortest duration necessary to control symptoms.

The elderly have an increased frequency of adverse reactions to NSAIDs, especially gastrointestinal bleeding and perforation, which may be fatal.
Bronchospasm may be precipitated in patients suffering from, or with a previous history of bronchial asthma or allergic disease. Flurbiprofen lozenges should be used with caution in these patients.
The use of flurbiprofen lozenges with concomitant NSAIDs including cyclooxygenase-2 selective inhibitors should be avoided.
Patients with systemic lupus erythematosus and mixed connective tissue disease may have an increased risk of aseptic meningitis.
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 products such as flurbiprofen lozenges.

Caution 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 and in long term treatment) may be associated with a small increased risk of arterial thrombotic events (for example myocardial infarction or stroke)

Caution is required when using Strip-Sore tablets in patients with mild and moderate liver failure.
Analgesic induced headache- In the event of prolonged use of analgesics or use beyond the regulations headache may occur, which must not be treated with increased doses of the medicinal product.
If GI bleeding or ulceration occurs in patients receiving flurbiprofen, the treatment should be withdrawn.
Epidemiological studies suggest that systemic non-steroidal anti-inflammatory drugs (NSAIDs) can mask symptoms of infection, which may lead to delayed initiation of appropriate treatment and thereby worsening the outcome of the infection, the patient is advised to consult a physician immediately if signs of a bacterial infection occur or worsen during the Strip-Sore lozenges therapy.
This medicine contains sulphites, which may rarely cause severe hypersensitivity reactions and bronchospasm.

Side Effects:

Hypersensitivity reactions to NSAIDs have been reported and these may consist of:

Non-specific allergic reactions and anaphylaxis
Respiratory tract reactivity e.g. asthma, aggravated asthma, bronchospasm, dyspnea
Various skin reactions e.g. pruritus, urticaria, angioedema and more rarely exfoliative and bullous dermatoses (including epidermal necrolysis and erythema multiforme)
Oedema, hypertension and cardiac failure have been reported in association with NSAID treatment. 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),

Other side effects resulting from the use of flurbiprofen:

Common: dizziness, headache, paresthesia, throat irritation, Common: diarrhoea, mouth ulceration, nausea, oral pain, paraesthesia oral, oropharyngeal pain, oral discomfort.
Uncommon: insomnia, somnolence, exacerbation of asthma and bronchospasm, dyspnoea, wheezing, oropharyngeal blistering, pharyngeal hypoaesthesia, abdominal distension abdominal pain, constipation, dry mouth, dyspepsia, flatulence, glossodynia, dysgeusia, oral dysaesthesia, vomiting, various skin rashes, pruritus, pyrexia, pain.

Interaction with other products:

Flurbiprofen should be avoided in combination with:

Other NSAIDS includingcyclooxygenase-2 selective inhibitors: Avoid concomitant use of two or more NSAIDs as this may increase the risk of adverse effects.
Acetylsalicylic acid (low dose): Unless low-dose aspirin (not above 75mg daily) has been advised by a doctor, as this may increase the risk of adverse reactions.

Flurbiprofen should be used with caution in combination with:

Anticoagulants: NSAIDs may enhance the effects of anti-coagulants, such as warfarin.
Anti-platelet Agents: Increased risk of gastrointestinal ulceration or bleeding.
Antihypertensive drugs (Diuretics, ACE inhibitors, angiotensin-II-antagonists): NSAIDs may reduce the effect of diuretics and other antihypertensive drugs may enhance nephrotoxicity caused by inhibition of cyclooxygenase, especially in patients with compromised renal function (Patients should be adequately hydrated).
Alcohol: May increase the risk of adverse reactions, especially of bleeding in the gastrointestinal tract.
Cardiac glycosides: NSAIDs may exacerbate cardiac failure, reduce GFR and increase plasma glycoside levels - adequate control and, if necessary, dose adjustment is recommended.
Ciclosporin: Increased risk of nephrotoxicity.
Corticosteroids: May increase the risk of adverse reactions, especially of the gastrointestinal tract.
Lithium: May increase serum levels of lithium – adequate control and, if necessary, dose adjustment is recommended.
Methotrexate: The administration of NSAIDs within 24 hours before or after administration of methotrexate may lead to elevated concentrations of methotrexate and an increase in its toxic effect.
Mifepristone: NSAIDs should not be used for 8 – 12 days after mifepristone administration as NSAIDs can reduce the effect of mifepristone.
Oral antidiabetics: Alteration of blood glucose levels reported (increased check rate recommended).
Phenytoin: May increase serum levels of phenytoin – adequate control and, if necessary, dose adjustment is recommended.
Potassium sparing diuretics: Concomitant use may cause hyperkalaemia.
Probenecid Sulfinpyrazone: Medicinal products that contain probenecid or sulfinpyrazone may delay the excretion of flurbiprofen.
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.
Selective serotonin reuptake inhibitors (SSRI's): Increased risk of gastrointestinal ulceration or bleeding.
Tacrolimus: Possible increased risk of nephrotoxicity when NSAIDs are given with tacrolimus.
Zidovudine: Increased risk of haematological toxicity when NSAIDs are given with zidovudine.

Pregnancy

Inhibition of prostaglandin synthesis may adversely affect the pregnancy and/or the embryo/foetal development. During the first and second trimester of pregnancy, flurbiprofen should not be given unless clearly necessary.

Flurbiprofen is contraindicated during the third trimester of pregnancy.

Lactation

In limited studies, flurbiprofen appears in the breast milk in very low concentration and is unlikely to affect the breastfed infant adversely. Strep- Sore lozenges are not recommended for use in nursing mothers.

Dosage and administration:

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.

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

Children under 12 years:

Not indicated.

Elderly: A general dose recommendation cannot be given, since to date clinical experience is limited. The elderly are at increased risk of the serious consequences of adverse reactions.

Impaired hepatic: In patients with mild to moderate impairment of hepatic function no dose reduction is required. In patients with severe hepatic insufficiency flurbiprofen is contraindicated.

Impaired renal: In patients with mild to moderate impairment of renal function no dose reduction is required. In patients with severe renal insufficiency flurbiprofen is contraindicated.

Method of administration

For Oromucosal administration and short-term use only.

As with all lozenges, to avoid local irritation, Strep- Sore should be moved around the mouth whilst sucking. The lowest effective dose should be used for the shortest duration necessary to relieve symptoms

Overdose

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 with NSAIDs, toxicity is seen in the central nervous system, manifesting as drowsiness, occasionally excitation, blurred vision and disorientation or coma. Occasionally patients develop convulsions. In serious poisoning with NSAIDs 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 or gastric lavage and if necessary, correction of serum electrolytes and if the patient presents within 1 hour of ingestion or a potentially toxic amount. If frequent or prolonged, convulsions should be treated with intravenous diazepam or lorazepam. Give bronchodilators for asthma. There is no specific antidote to flurbiprofen.