Strepsils Max Pro

Active Ingredient: Flurbiprofen 8.75 mg.
Lozenge: A round, pale yellow to brown lozenge with an icon intagliated on both sides of the lozenge.
Oromucosal Spray: Clear, colourless to slightly yellow solution.
Excipients/Inactive Ingredients: Lozenge: Macrogol 300, potassium hydroxide, lemon flavour, levomenthol, liquid sucrose, liquid glucose, honey.
Oromucosal Spray: Betadex, Disodium phosphate dodecahydrate, Citric acidmonohydrate, Methyl parahydroxybenzoate (E218), Propyl parahydroxybenzoate (E216),Sodium hydroxide, Mint flavour, Cherry flavour, N,2,3-Trimethyl-2-isopropylbutanamide,Saccharin sodium, Hydroxypropyl betadex and Purified water.

Pharmacotherapeutic Group: Other throat preparations, throat preparations. ATC Code: R02AX01.
Pharmacology: Pharmacodynamics: Lozenge: 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 2-3 hours.
Oromucosal Spray: 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 8.75 mg dose dissolved in artificial saliva has been shown to reduce prostaglandin synthesis in cultured human respiratory cells. According to studies using the whole blood assay, flurbiprofen is a mixed COX-1/COX-2 inhibitor with some selectivity towards COX-1. Pre-clinical studies suggest that the R (-) enantiomer of flurbiprofen and related NSAIDs may act on the central nervous system; the suggested mechanism is by inhibition of induced COX-2 at the level of the spinal cord.
A single dose of flurbiprofen 8.75 mg delivered locally to the throat as three sprays has been demonstrated to relieve sore throat, including swollen and inflamed sore throats through a significant change in the severity of throat soreness area under the change (AUC) from baseline curve (mean difference (standard deviation)) for active treatment versus placebo from 0 to 2 hours (-1.82 (1.35) vs -1.13 (1.14)), 0 to 3 hours (-2.01 (1.405) vs -1.31 (1.233)) and 0 to 6 hours (-2.14 (1.551) vs -1.50 (1.385)). Significant differences in the AUC from baseline curve from 0 - 6 hours compared to placebo were also seen for other qualities of sore throat including pain intensity (-22.50 (17.894) vs -15.64 (16.413)), difficulty swallowing (-22.50 (18.260) vs -16.01 (15.451)), swollen throat (-20.97 (18.897) vs -13.80 (15.565)) and sore throat pain relief (3.24 (1.456) vs 2.47 (1.248)). The change from baseline at individual time points across the different qualities of sore throat demonstrated significance starting from 5 minutes and lasting for up to 6 hours.
For those patients taking antibiotics for Strep infection, there was statistically significant greater relief of sore throat pain intensity for flurbiprofen 8.75 mg lozenge from 7 hours and onwards after antibiotics were taken. The analgesic effect of flurbiprofen 8.75 mg lozenge was not reduced by the administration of antibiotics to treat patients with streptococcal sore throat.
Multiple-dose efficacy over 3 days has also been demonstrated. The mint-flavoured spray is easy and convenient to use and reaches the sore area of the throat, improving the ability to talk and use the voice whilst providing a soothing and coating effect for the throat.
Paediatric Population: No specific studies in children have been undertaken with Strepsils Max Pro Direct Spray 8.75 mg per dose. Efficacy and safety studies on flurbiprofen 8.75 mg lozenges have included children aged 12 - 17 years, although small sample size means that no statistical conclusions can be drawn.
Pharmacokinetics: Lozenge: Flurbiprofen is rapidly absorbed following the use of Strepsils Max Pro Honey & Lemon 8.75 mg Lozenge with plasma concentrations peaking at 30-40 minutes. Peak concentrations are achieved more rapidly than, but are if similar magnitude to, those achieved after an equivalent swallowed dose.
Flurbiprofen is rapidly distributed throughout the body. It is mainly metabolized by hydroxylation and excreted via the kidneys.
It is extensively bound to plasma proteins and has an elimination half-life of 3-6 hours.
Flurbiprofen is excreted in very small amounts in human milk (less than 0.05 μg/mL).
Oromucosal Spray: Absorption: A single dose of flurbiprofen 8.75 mg is delivered directly to the throat as three sprays and the flurbiprofen is readily absorbed, with detection in the blood between 2 and 5 minutes and plasma concentrations peaking at 30 minutes after administration, but remaining at a mean low level of 1.6 μg/mL which is approximately 4 times lower than a 50 mg tablet dose. Strepsils Max Pro Direct Spray 8.75 mg per dose demonstrates bioequivalence to flurbiprofen 8.75 mg lozenge. Absorption of flurbiprofen can occur from the buccal cavity by passive diffusion. Rate of absorption is dependent on pharmaceutical form with peak concentrations achieved more rapidly than, but of similar magnitude to, those achieved after an equivalent swallowed dose.
Distribution: Flurbiprofen is rapidly distributed throughout the body and is extensively bound to plasma proteins.
Metabolism/Excretion: 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 (less than 0.05 μg/ml). Approximately 20-25% of a flurbiprofen oral dose is excreted unchanged.
Special Groups: No difference in pharmacokinetic parameters between elderly and young adult volunteers has been reported following oral administration of flurbiprofen tablets. No pharmacokinetic data have been generated in children below 12 years of age following administration of Flurbiprofen 8.75 mg however, administration of both flurbiprofen syrup and suppository formulations indicate no significant differences in pharmacokinetic parameters compared with adults.

Strepsils Max Pro Honey & Lemon 8.75 mg Lozenge are indicated for the symptomatic relief of sore throat.
Strepsils Max Pro Direct Spray 8.75 mg per dose is indicated for the short-term symptomatic relief of acute sore throat in adults.

Lozenge: 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 physician 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, Strepsils Max Pro Honey & Lemon 8.75 mg Lozenges should be moved around the mouth whilst sucking.
Oromucosal Spray: Recommended Dosage: Adults aged 18 years and over: One dose (3 sprays) administered to the back of the throat every 3-6 hours as required, up to a maximum of 5 doses in a 24 hour period.
Do not inhale whilst spraying.
It is recommended that this product should be used for a maximum of three days.
Before first use, activate the pump by pointing the nozzle away from you and spraying a minimum of four times until a fine, consistent mist is produced. The pump is then primed and ready for use.
Between each dose, point the nozzle away from you and spray a minimum of once ensuring a fine, consistent mist is produced. Always ensure a fine consistent mist is produced before dosing the product.
Paediatric population: The safety and efficacy of Strepsils Max Pro Direct Spray 8.75 mg per dose in children or adolescents under 18 years has not been established.
Elderly patients: 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.
The lowest effective dose should be administered for the shortest duration necessary to control symptoms (see Precautions).
Route of Administration: For oromucosal administration and short-term use only.

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, blurred vision 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 or gastric lavage and if necessary correction of serum electrolytes if the patient presents within one 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.

Hypersensitivity to flurbiprofen, aspirin, other NSAIDs, other lozenge ingredients or any of the excipients in the product.
Patients who have previously shown hypersensitivity reactions (e.g. bronchospasm, asthma, rhinitis, angioedema, or urticaria) in response to aspirin or other non-steroidal anti-inflammatory drugs.
Active, existing or history of peptic ulcerations/haemorrhage (two or more distinct episodes of proven ulceration or bleeding) and intestinal ulceration.
History of gastrointestinal bleeding or perforation, severe colitis, haemorrhagic or haematopoietic disorders related to previous NSAIDs therapy.
Severe heart failure, renal failure or hepatic failure (see Precautions).
Last trimester of pregnancy (see Use in Pregnancy & Lactation).
Oromucosal Spray: Children and adolescents below 18 years.

Undesirable effects may be minimised by using the lowest effective dose for the shortest possible duration necessary to control symptoms.
Respiratory: Bronchospasm may be precipitated in patients suffering from, or with a previous history of bronchial asthma or allergic disease. Flurbiprofen lozenges and spray should be used with caution in these patients.
Other NSAIDs: The use of flurbiprofen lozenges and spray with concomitant NSAIDs including cyclooxygenase-2 selective inhibitors should be avoided (see Interactions).
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 (see Adverse Reactions), however this effect is not usually seen with short term limited use products such as flurbiprofen lozenges and spray.
Cardiovascular, Renal and 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 products such as flurbiprofen lozenges and spray.
Cardiovascular and cerebrovascular effects: Caution (discussion with physician 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 and in long-term treatment) may be associated with a small increased risk of arterial thrombotic events (for example myocardial infarction or stroke). There are insufficient data to exclude such a risk for flurbiprofen when given at a daily dose of no more than 5 lozenges or 5 doses (3 sprays per dose). All NSAIDs should not be used perioperatively in patients who have recently undergone coronary artery bypass graft (CABG) surgery and revascularisation procedures.
Hepatic: Mild to moderate hepatic dysfunction (see Contraindications and Adverse Reactions).
Nervous System effects: 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.
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 Adverse Reactions).
Gastrointestinal bleeding, ulceration or perforation, which can be fatal has been reported with all NSAIDs at any time 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 Contraindications), and in the elderly, however this effect is not usually seen with short term limited use products such as flurbiprofen lozenges or spray.
Patients with a history of GI toxicity, particularly the elderly, should report any unusual abdominal symptoms (especially GI bleeding) to their healthcare professional.
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 acetylsalicylic acid (see Interactions). If 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 NSAIDs (see Adverse Reactions).
Flurbiprofen lozenges and spray should be discontinued at the first appearance of skin rash, mucosal lesions, or any other sign of hypersensitivity.
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 lozenges and spray therapy. It should be considered whether initiation of an anti-infective antibiotic therapy is indicated.
In cases of purulent bacterial pharyngitis/tonsillitis, the patient is advised to consult a physician as the treatment needs to be re-evaluated.
Treatment should be administered for three days maximum.
If the symptoms get worse or if new symptoms occur, the treatment should be re-evaluated.
If mouth irritation occurs, flurbiprofen treatment should be withdrawn.
Effects on ability to drive and use machines: No studies on the effects on the ability to drive and use of machines have been performed.
Use in the Elderly: The elderly have an increased frequency of adverse reactions to NSAIDs, especially gastrointestinal bleeding and perforation, which may be fatal.
Lozenge: Sugar intolerance: Patients with rare hereditary problems of fructose intolerance, glucose-galactose malabsorption or sucrose-isomaltase insufficiency should not take this medicine.
Oromucosal Spray: This product contains methyl parahydroxybenzoate and propyl parahydroxybenzoate which may cause allergic reactions (possibly delayed).
Haematological effects: Flurbiprofen, like other NSAIDs, may inhibit platelet aggregation and prolong bleeding time. Flurbiprofen spray should be used with caution in patients with a potential for abnormal bleeding.
Risk of GI Ulceration, Bleeding and Perforation with NSAID: Serious GI toxicity such as bleeding, ulceration and perforation can occur at any time, with or without warning symptoms, in patients treated with NSAID therapy. Although minor upper GI problems (e.g. dyspepsia) are common, usually developing early in therapy, prescribers should remain alert for ulceration and bleeding in patients treated with NSAIDs even in the absence of previous GI tract symptoms.
Studies to date have not identified any subset of patients not at risk of developing peptic ulceration and bleeding.
Patients with prior history of serious GI events and other risk factors associated with peptic ulcer disease (e.g. alcoholism, smoking, and corticosteroid therapy) are at increased risk. Elderly or debilitated patients seem to tolerate ulceration or bleeding less than other individuals and account for most spontaneous reports for fatal GI events.

Lozenge: Whilst no teratogenic effects have been demonstrated in animal experiments, the use of Strepsils Max Pro Honey & Lemon 8.75 mg Lozenge should, if possible, be avoided during the first 6 months of pregnancy.
During the 3rd 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 Contraindications).
Flurbiprofen appears in the breast milk in very low concentration and is unlikely to affect the breastfed infant adversely.
Oromucosal Spray: 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 has been shown to result in increased pre- and post-implantation loss 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, 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 oligo-hydroamniosis; the mother and the neonate, at the end of pregnancy, to: possible prolongation of bleeding time, an anti-aggregating effect which may occur even at very low doses; inhibition of uterine contractions resulting in delayed or prolonged labour.
Consequently, flurbiprofen is contraindicated during the third trimester of pregnancy (see Contraindications).
Breast-feeding: In limited studies, flurbiprofen appears in the breast milk in 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 spray is not recommended for use in nursing mothers.
Fertility: There is some evidence that drugs which inhibit cyclooxygenase/prostaglandin synthesis may cause impairment of female fertility by an effect on ovulation. This is reversible on withdrawal of treatment.

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, dyspnoea; 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), (see Precautions). There is insufficient data to exclude such a risk for flurbiprofen 8.75 mg lozenges and oromucosal spray, solution.
The following list of adverse effects relates to those experienced with flurbiprofen at OTC doses for short term use: (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).
Blood and lymphatic system disorders: Not known: anaemia, thrombocytopenia.
Immune system disorders: Rare: anaphylactic reaction.
Psychiatric disorders: Uncommon: insomnia.
Cardiovascular and cerebrovascular disorders: Not known: Oedema, hypertension and cardiac failure.
Nervous system disorders: Common: dizziness, headache, paraesthesia.
Uncommon: somnolence.
Respiratory, thoracic and mediastinal disorders: Common: throat irritation.
Uncommon: exacerbation of asthma and bronchospasm, dyspnoea, wheezing, oropharyngeal blistering, pharyngeal hypoaesthesia.
Gastrointestinal disorders: Common: diarrhoea, mouth ulceration, nausea, oral pain, paraesthesia oral, oropharyngeal pain, oral discomfort (warm or burning feeling or tingling of the mouth).
Uncommon: abdominal distension, abdominal pain, constipation, dry mouth, dyspepsia, flatulence, glossodynia, dysgeusia, oral dysaesthesia, vomiting.
Hepatobiliary disorders: Not known: hepatitis.
Skin and subcutaneous tissue disorders: Uncommon: various skin rashes, pruritus.
Not known: severe forms of skin reaction such as bullous reactions, including Stevens-Johnson syndrome and toxic epidermal necrolysis.
General disorders and administration site conditions: Uncommon: pyrexia, pain.

Flurbiprofen should be avoided in combination with: Other NSAIDs including cyclooxygenase-2 selective inhibitors: Avoid concomitant use of two or more NSAIDs as this may increase the risk of adverse effects (esp. gastrointestinal adverse events such as ulcers and bleeding) (see Precautions).
Acetylsalicylic acid (low dose): Unless low-dose aspirin (not above 75 mg daily) has been advised by a doctor, as this may increase the risk of adverse reactions (see Precautions).
Flurbiprofen should be used with caution in combination with: Anticoagulants: NSAIDs may enhance the effects of anti-coagulants, such as warfarin (see Precautions).
Anti-platelet Agents: Increased risk of gastrointestinal ulceration or bleeding (see Precautions).
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 (see Contraindications).
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 (SSRIs): Increased risk of gastrointestinal ulceration or bleeding (see Precautions).
Tacrolimus: Possible increased risk of nephrotoxicity when NSAIDs are given with tacrolimus.
Zidovudine: Increased risk of hematological toxicity when NSAIDs are given with zidovudine.
No studies so far have revealed any interactions between flurbiprofen and tolbutamide or antacids.
Paediatric population: No additional information available.

Incompatibilities: Not applicable.

Lozenge: Store in a dry place below 30°C, in the original package.
Shelf life: 24 months.
Oromucosal Spray: Do not store above 30°C. Do not refrigerate or freeze. Do not use this medicine for more than 6 months after the first use.

Preparations for Oral Ulceration & Inflammation

R02AX01 - flurbiprofen ; Belongs to the class of other throat preparations.

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