Active ingredients: Flurbiprofen
FROBEN 100 mg Coated tablets
FROBEN 5mg / ml Syrup
FROBEN 100 mg Suppositories
FROBEN 200 mg Prolonged-release capsules, hard
FROBEN 100 mg Effervescent granules
Froben package inserts are available for pack sizes: - FROBEN 100 mg Coated tablets, FROBEN 5mg / ml Syrup, FROBEN 100 mg Suppositories, FROBEN 200 mg Prolonged-release capsules, FROBEN 100 mg Effervescent granules
- FROBEN 0.25% Mouthwash, FROBEN 0.25% Solution to be sprayed
Why is Froben used? What is it for?
PHARMACOTHERAPEUTIC CATEGORY
Non-steroidal anti-inflammatory-antirheumatic.
THERAPEUTIC INDICATIONS
FROBEN is an anti-inflammatory drug belonging to the class of NSAIDs (Non-Steroidal Anti-Inflammatory Drugs) which exerts a strong anti-inflammatory, analgesic and antipyretic action.
As a function of the high antiprostaglandin activity, FROBEN is used in all those morbid conditions in which the inflammatory component is predominant and electively in: phlebology, gynecology, pulmonology, rheumatology, traumatology, orthopedics, etc.
Contraindications When Froben should not be used
Flurbiprofen is contraindicated in patients with known hypersensitivity (asthma, urticaria or allergic type) to flurbiprofen or to any of the excipients, and to aspirin or other NSAIDs.
Flurbiprofen is also contraindicated in patients with a history of gastrointestinal bleeding or perforation related to previous NSAID treatment.
Flurbiprofen should not be taken by patients with active or anamnestic ulcerative colitis, Crohn's disease, recurrent peptic ulcer or gastrointestinal bleeding (defined as two or more distinct episodes of proven ulceration or bleeding).
Flurbiprofen is contraindicated in patients with severe heart failure.
Third trimester of pregnancy
Precautions for use What you need to know before you take Froben
Flurbiprofen should be administered with caution to patients with a history of peptic ulcer and other gastrointestinal diseases as these conditions may be exacerbated.
The risk of gastrointestinal bleeding, ulcer or perforation is higher with increasing flurbiprofen dosage in patients with a history of ulcer, particularly if complicated with haemorrhage and perforation and in the elderly. These patients should start treatment at the lowest dose. available.
Gastrointestinal bleeding, ulcer or perforation have been reported with all NSAIDs at any time during treatment. These adverse events can be fatal and can occur with or without warning symptoms or with a previous history of serious gastrointestinal events.
Patients with a history of gastrointestinal disease, particularly if elderly, should report any unusual abdominal symptoms (especially gastrointestinal bleeding) in the initial stages of treatment.
Elderly patients have an increased frequency of adverse reactions to NSAIDs, especially gastrointestinal haemorrhage and perforation, which can be fatal.
Undesirable effects can be minimized with the use of the lowest effective dose for the shortest possible duration of treatment needed to control symptoms (see section 4.2 and below on gastrointestinal and cardiovascular risks). Concomitant use of protective agents (misoprostol or proton pump inhibitors) should be considered for these patients and also for patients taking low doses of aspirin or other drugs that may increase the risk of gastrointestinal events (see below and Interactions section).
When gastrointestinal bleeding or ulceration occurs in patients taking Froben the treatment should be discontinued.
Cardiovascular and cerebrovascular effects
Adequate monitoring and instruction are required in patients with a history of mild to moderate hypertension and / or congestive heart failure as fluid retention and edema have been reported in association with NSAID treatment.
Clinical studies and epidemiological data suggest that the use of some NSAIDs, especially at high doses and for long-term treatments, may be associated with a modest increased risk of arterial thrombotic events such as myocardial infarction or stroke. There are no data. sufficient to rule out a similar risk for flurbiprofen.
Patients with uncontrolled hypertension, congestive heart failure, established ischemic heart disease, peripheral arterial disease and / or cerebrovascular disease should only be treated with flurbiprofen after careful consideration. Similar considerations should be made before initiating long-term treatment in patients with risk factors for cardiovascular disease (eg, hypertension, hyperlipidaemia, diabetes mellitus, smoking).
Flurbiprofen, like other NSAIDs, can inhibit platelet aggregation and prolong bleeding time.
Skin reactions
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. In the early stages of therapy, patients appear to be at higher risk: l "Onset of the reaction occurs in most cases within the first month of treatment. Flurbiprofen should be discontinued at the first appearance of skin rash, mucosal lesions or any other signs of hypersensitivity.
Other Reactions
Caution should be used when initiating treatment with NSAIDs such as flurbiprofen in patients with considerable dehydration.
Particular caution must be adopted in the treatment of patients with severely reduced renal, cardiac or hepatic function, since the use of NSAIDs can lead to deterioration of renal function.
In such patients, the dosage should be kept as low as possible and renal function monitored.
Cases of bronchospasm have been reported with flurbiprofen in patients with a history of bronchial asthma.
Interactions Which drugs or foods can modify the effect of Froben
Tell your doctor or pharmacist if you have recently taken any other medicines, even those without a prescription. Attention should be paid in patients treated with any of the medicines listed below, as interactions have been reported in some patients.
Diuretics, ACE inhibitors and angiotensin II antagonists: NSAIDs may reduce the effect of diuretics and other antihypertensive drugs. In some patients with impaired renal function (e.g. dehydrated patients or elderly patients with impaired renal function) coadministration of an ACE inhibitor or angiotensin II antagonist and agents that inhibit the cyclo-oxygenase system may lead to further deterioration of renal function, including possible acute renal failure, usually reversible These interactions should be considered in patients taking Flurbiprofen concomitantly with ACE inhibitors or angiotensin II antagonists. Therefore, the combination should be administered with caution, especially in elderly patients.
Patients should be adequately hydrated and monitoring of renal function should be considered after initiation of concomitant therapy and on a periodic basis thereafter.
Cardiac glycosides: NSAIDs can exacerbate heart failure, reduce the degree of glomerular filtration and increase plasma levels of cardiac glycosides.
Anticoagulants, such as warfarin: increased anticoagulant effect.
Aspirin: As with other NSAID-containing medicinal products, concomitant administration of flurbiprofen and aspirin is generally not recommended due to the potential for increased side effects.
Anti-aggregating agents: increased risk of gastrointestinal bleeding.
Selective serotonin reuptake inhibitors (SSRIs): increased risk of gastrointestinal bleeding.
Lithium salts: lithium removal decrease.
Methotrexate: Caution is advised in case of concomitant administration of flurbiprofen and methotrexate as NSAIDs may increase methotrexate levels.
Ciclosporins: increased risk of nephrotoxicity with NSAIDs.
Corticosteroids: increased risk of gastrointestinal ulcer or haemorrhage with NSAIDs.
Cox-2 inhibitors and other NSAIDs: Concomitant use of other NSAIDs, including selective cyclooxygenase-2 inhibitors, should be avoided due to potential additive effects.
Quinolone Antibiotics: Results from animal studies suggest that NSAIDs may increase the risk of seizures associated with the use of quinolone antibiotics. Patients taking NSAIDs and quinolones may have an increased risk of developing seizures.
Mifepristone: NSAIDs should not be taken for 8-12 days after administration of mifepristone as NSAIDs may reduce the effects of mifepristone.
Tacrolimus: Possible increased risk of nephrotoxicity when co-administered with NSAIDs.
Zidovudine: increased risk of haematic toxicity when co-administered with NSAIDs. There is evidence of an increased risk of haemarthrosis and hematoma in HIV-infected haemophiliac patients concomitantly treated with Zidovudine and other NSAIDs.
Warnings It is important to know that:
Pregnancy
Inhibition of prostaglandin synthesis can adversely affect pregnancy and / or embryo / fetal development.
Results of epidemiological studies suggest an increased risk of miscarriage and cardiac malformation and gastroschisis after use of a prostaglandin synthesis inhibitor in early pregnancy. The absolute risk of cardiac malformations increased from less than 1% to approximately 1.5%. The risk has been considered to increase with dose and duration of therapy. In animals, administration of prostaglandin synthesis inhibitors has been shown to cause increased pre- and post-implantation loss and mortality. embryo-fetal.
In addition, an increased incidence of various malformations, including cardiovascular, has been reported in animals given prostaglandin synthesis inhibitors during the organogenetic period.
During the first and second trimester of pregnancy, flurbiprofen should not be administered except in strictly necessary cases.
If flurbiprofen is used by a woman attempting to conceive or during the first and second trimester of pregnancy, the dose and duration of treatment should be kept as low as possible.
During the third trimester of pregnancy, all prostaglandin synthesis inhibitors can expose the fetus to:
- Cardiopulmonary toxicity (with premature closure of the arterial duct and pulmonary hypertension);
- Renal dysfunction, which can progress to renal failure with oligo-hydroamnios;
the mother and the newborn, at the end of pregnancy, to:
- Possible prolongation of bleeding time, an antiplatelet effect that can occur even at very low doses;
- Inhibition of uterine contractions resulting in delayed or prolonged labor. Consequently flurbiprofen is contraindicated during the third trimester of pregnancy.
Feeding time
Flurbiprofen is excreted in breast milk; however the amount excreted is only a small fraction of the maternal dose. Administration of flurbiprofen is not recommended in nursing mothers.
Effects on ability to drive and use machines
It does not affect the ability to drive and use machines.
Important information about some of the ingredients
The tablets contain lactose and sucrose therefore patients with rare hereditary problems of galactose or fructose intolerance, the Lapp lactase deficiency, glucose-galactose malabsorption or sucrase isomaltase insufficiency should not take this medicine.
The syrup contains sucrose therefore patients with rare hereditary problems of fructose intolerance, glucose-galactose malabsorption or sucrase isomaltase insufficiency should not take this medicine.
The syrup contains para-hydroxybenzoates which can cause allergic reactions (including delayed)
Dosage and method of use How to use Froben: Dosage
Undesirable effects can be minimized by using the lowest effective dose for the shortest possible duration of treatment needed to control symptoms (see precautions for use section)
ORAL PHARMACEUTICAL FORMS:
Adults
The recommended dose is 150 to 200 mg per day in two, three or four divided doses or in one administration for prolonged-release capsules. In patients with severe symptoms or with recent illness or during exacerbations, the total daily dose can be increased up to 300 mg in divided doses. The prolonged-release capsules should be swallowed whole with some water, preferably in the evening after eating.
In case of dysmenorrhea, a dosage of 100 mg can be taken at the onset of symptoms followed by 50 or 100 mg every 4-6 hours. The maximum total dose should not exceed 300 mg.
Senior citizens
The elderly are at greater risk of serious consequences from adverse reactions. Although flurbiprofen is generally well tolerated in the elderly, some patients, especially those with impaired renal function, may eliminate NSAIDs more slowly than normal. In these cases, flurbiprofen should be taken with caution and the dosage should be determined individually.
If the intake of an NSAID is considered necessary, the lowest dose should be taken and patients closely monitored.
Children (6-12 years)
The pharmaceutical form recommended for children is syrup. The recommended dose is 3 to 4 mg / kg / day in divided doses.
SUPPOSITORIES
Adults and children over 12 years
For rectal administration. A suppository can be administered twice daily or can substitute an equivalent dose of oral therapy to provide a daily dosage of 100 mg to 200 mg. In severe or acute cases, the total daily dose can be increased up to 300 mg in separate administrations. The maximum daily dose should not exceed 300 mg.
Senior citizens
The elderly are at greater risk of serious consequences from adverse reactions. Although flurbiprofen is generally well tolerated in the elderly, some patients, especially those with impaired renal function, may eliminate NSAIDs more slowly than normal. In these cases, flurbiprofen should be taken with caution and the dosage should be determined individually.
Children
The administration of suppositories based on flurbiprofen is not indicated in children under the age of 12 years.
Overdose What to do if you have taken too much Froben
Symptoms
Symptoms of overdose may include nausea, vomiting and gastrointestinal irritation.
Treatment
Treatment should include gastric lavage and, if necessary, correction of the serum electrolyte picture. There is no specific antidote for flurbiprofen. In case of accidental ingestion / intake of an excessive dose of FROBEN, notify your doctor immediately or go to the nearest hospital.
IF YOU HAVE ANY DOUBTS ABOUT USING FROBEN, CONTACT YOUR DOCTOR OR PHARMACIST.
Side Effects What are the side effects of Froben
Like all medicines, FROBEN can cause side effects, although not everybody gets them.
Disorders of the blood and lymphatic system
Thrombocytopenia, aplastic anemia and agranulocytosis
Disorders of the immune system
Anaphylaxis, angioedema, allergic reaction.
Psychiatric disorders
Depression
Disorders of the nervous system
Dizziness, cerebrovascular accidents, visual disturbances, optic neuritis, migraine, paraesthesia, depression, confusion, hallucination, vertigo, malaise, fatigue and somnolence.
Acoustic and labyrinth disturbances
Tinnitus
Cardiovascular Disorders
Edema, hypertension and heart failure
Clinical studies and epidemiological data suggest that the intake of some NSAIDs (especially at high doses and in the case of long-term treatment) may be associated with an increased risk of arterial thrombotic events (eg myocardial infarction or stroke).
Respiratory, thoracic and mediastinal disorders
Respiratory tract reactivity (asthma, bronchospasm and dyspnoea)
Gastrointestinal Disorders
The most commonly observed adverse events are gastrointestinal in nature.
Nausea, vomiting, diarrhea, flatulence, constipation, dyspepsia, abdominal pain, melaena, haematemesis, ulcerative stomatitis, gastrointestinal haemorrhage and exacerbation of colitis and Crohn's disease have been reported following administration of flurbiprofen (see Contraindications section). Gastritis, peptic ulcer, perforation and ulcer haemorrhage were observed less frequently. Local irritation can occur with suppositories. Cases of pancreatitis have been reported very rarely.
Skin and subcutaneous tissue disorders
Skin disorders including rash, pruritus, urticaria, purpura, angioedema and very rarely bullous dermatosis (including Stevens-Johnson Syndrome, Toxic Epidermal Necrolysis and Erythema multiforme).
During clinical trials with flurbiprofen patches, the most commonly reported adverse reactions were local skin reactions (including redness, rash, itching, rash, numbness and tingling); however the incidence was low (4.6%).
Kidney and urinary system disorders
Nephrotoxicity in various forms, including interstitial nephritis and nephrotic syndrome.
As with other NSAIDs, rare cases of renal failure have been reported.
Compliance with the instructions contained in the package leaflet reduces the risk of undesirable effects.
If any of the side effects gets serious or if you notice any undesirable effects not listed in this leaflet, please inform your doctor or pharmacist.
Expiry and Retention
Expiry: see the expiry date indicated on the package. Warning: do not use the product after the expiry date indicated on the package. The expiry date refers to the product in intact packaging, correctly stored.
Froben 5mg / ml Syrup is valid for 6 months after first opening.
Coated tablets, syrup: Store at a temperature not exceeding 25 ° C.
Prolonged-release hard capsules: no special storage precautions.
KEEP THE MEDICINAL PRODUCT OUT OF THE REACH AND SIGHT OF CHILDREN
Medicines should not be disposed of via wastewater or household waste. Ask your pharmacist how to throw away medicines you no longer use. This will help protect the environment.
COMPOSITION
FROBEN 100 mg Coated tablets
One tablet contains: active ingredient: flurbiprofen 100.0 mg. Excipients: stearic acid, corn starch, carnauba wax, glucose, sandracca, lactose, magnesium stearate, povidone, sucrose, anhydrous colloidal silica, talc, titanium dioxide.
FROBEN 5mg / ml Syrup
100 ml of syrup contain: active ingredient flurbiprofen 0.5 g. Excipients: purified water, propylene glycol, natural banana flavor, carmellose sodium, glycerin, levomenthol, methyl parahydroxybenzoate, sodium citrate, propyl parahydroxybenzoate, sucrose, sodium saccharinate.
FROBEN 100 mg Suppositories
One suppository contains: active ingredient: flurbiprofen 100.0 mg. Excipients: solid semisynthetic glycerides.
FROBEN 200 mg Prolonged-release capsules, hard
One 200 mg capsule contains: active ingredient: microencapsulated flurbiprofen 200.0 mg. Excipients: anhydrous colloidal sillice, microcrystalline cellulose, Eudragit RS 100, macrogol 6000, magnesium stearate.
Composition of the capsule: titanium dioxide, gelatin, quinoline yellow, glycerin, Black Opacode, red iron oxide.
FROBEN 100 mg Effervescent granules
One sachet contains: active ingredient: flurbiprofen 100 mg. Excipients: citric acid, orange flavor, macrogol 6000, sodium saccharin, sucrose, sodium bicarbonate, sodium carbonate.
PHARMACEUTICAL FORM AND CONTENT
- Coated tablets in packs of 10 tablets of 100 mg *
- Coated tablets in packs of 30 tablets of 100 mg
- 5mg / ml Syrup in 160ml bottle
- Suppositories in packs of 10 suppositories of 100 mg *
- Prolonged-release hard capsules in packs of 20 capsules of 200 mg
- Effervescent granules in packs of 10 sachets of 100 mg *
- Effervescent granules in packs of 30 sachets of 100 mg *
* not on the market
Source Package Leaflet: AIFA (Italian Medicines Agency). Content published in January 2016. The information present may not be up-to-date.
To have access to the most up-to-date version, it is advisable to access the AIFA (Italian Medicines Agency) website. Disclaimer and useful information.
01.0 NAME OF THE MEDICINAL PRODUCT
FROBEN
02.0 QUALITATIVE AND QUANTITATIVE COMPOSITION
• FROBEN 100 mg Coated tablets
One coated tablet contains:
Active principle:
Flurbiprofen 100.0 mg
• FROBEN 5mg / ml Syrup
100 ml of syrup contain:
Active principle:
Flurbiprofen 0.5 g
• FROBEN 100 mg Suppositories
One suppository contains:
Active principle:
Flurbiprofen 100.0 mg
• FROBEN 0.25% Mouthwash
100 ml of solution contain:
Active principle:
Flurbiprofen 0.25 g
• FROBEN 0.25% Solution to be nebulised
100 ml of solution contain:
Active principle:
Flurbiprofen 0.25 g
• FROBEN 200 mg Prolonged-release hard capsules
One capsule contains:
Active principle:
Microencapsulated flurbiprofen 200.0 mg
• FROBEN 100 mg Effervescent granules
One sachet contains:
Active principle:
Flurbiprofen 100.0 mg
For the full list of excipients, see section 6.1
03.0 PHARMACEUTICAL FORM
Coated tablets, syrup, suppositories, mouthwash, nebuliser solution, prolonged-release hard capsules, effervescent granules.
04.0 CLINICAL INFORMATION
04.1 Therapeutic indications
FROBEN is an anti-inflammatory drug belonging to the class of NSAIDs which exerts a marked anti-inflammatory, analgesic and antipyretic action.
As a function of its high antiprostaglandin activity, FROBEN is used in all those morbid conditions in which the inflammatory component is a predominant characteristic and electively in: phlebology, gynecology, pulmonology, rheumatology, traumatology, orthopedics, etc.
FROBEN 0.25% Mouthwash and FROBEN 0.25% Solution to be nebulized are used in the symptomatic treatment of irritative-inflammatory states also associated with oropharyngeal pain (e.g. gingivitis, stomatitis, pharyngitis), also as a consequence of conservative dental therapy or extractive.
04.2 Posology and method of administration
Undesirable effects can be minimized by using the lowest effective dose for the shortest possible duration of treatment needed to control symptoms (see section 4.4).
ORAL PHARMACEUTICAL FORMS:
Adults
The recommended dose is 150 to 200 mg per day in two, three or four divided doses or in one administration for prolonged-release capsules. In patients with severe symptoms or with recent illness or during exacerbations, the total daily dose can be increased up to 300 mg in divided doses. The prolonged-release capsules should be swallowed whole with some water, preferably in the evening after eating.
In case of dysmenorrhea, a dosage of 100 mg can be taken at the onset of symptoms followed by 50 or 100 mg every 4-6 hours. The maximum total dose should not exceed 300 mg.
Senior citizens
The elderly are at greater risk of serious consequences from adverse reactions. Although flurbiprofen is generally well tolerated in the elderly, some patients, especially those with impaired renal function, may eliminate NSAIDs more slowly than normal. In these cases, flurbiprofen should be taken with caution and the dosage should be determined individually.
If the intake of an NSAID is considered necessary, the lowest dose should be taken and patients closely monitored.
Children (6-12 years)
The pharmaceutical form recommended for children is syrup. The recommended dose is 3 to 4 mg / kg / day in divided doses.
SUPPOSITORIES
Adults and children over 12 years
For rectal administration. A suppository can be administered twice daily or can substitute an equivalent dose of oral therapy to provide a daily dosage of 100 mg to 200 mg. In severe or acute cases, the total daily dose can be increased up to 300 mg in separate administrations. The maximum daily dose should not exceed 300 mg.
Senior citizens
The elderly are at greater risk of serious consequences from adverse reactions. Although flurbiprofen is generally well tolerated in the elderly, some patients, especially those with impaired renal function, may eliminate NSAIDs more slowly than normal. In these cases, flurbiprofen should be taken with caution and the dosage should be determined individually.
Children
The administration of suppositories based on flurbiprofen is not indicated in children under the age of 12 years.
MOUTHWASH
The recommended dose is two or three rinses or gargles a day with 10ml of mouthwash. It can be diluted in water.
SOLUTION TO NEBULIZE
The recommended dose is 2 sprays 3 times a day addressed directly to the affected area.
04.3 Contraindications
Flurbiprofen is contraindicated in patients with known hypersensitivity (asthma, urticaria or allergic type) to flurbiprofen or to any of the excipients, and to aspirin or other NSAIDs. Flurbiprofen is also contraindicated in patients with a history of gastrointestinal bleeding or perforation related to previous NSAID treatment.
Flurbiprofen should not be taken by patients with active or anamnestic ulcerative colitis, Crohn's disease, recurrent peptic ulcer or gastrointestinal bleeding (defined as two or more distinct episodes of proven ulceration or bleeding).
Flurbiprofen is contraindicated in patients with severe heart failure.
Third trimester of pregnancy
04.4 Special warnings and appropriate precautions for use
Gastrointestinal Effects
Flurbiprofen should be administered with caution to patients with a history of peptic ulcer and other gastrointestinal diseases as these conditions may be exacerbated.
The risk of gastrointestinal bleeding, ulcer or perforation is higher with increasing flurbiprofen dosage in patients with a history of ulcer, particularly if complicated with haemorrhage and perforation and in the elderly. These patients should start treatment at the lowest dose. available.
Gastrointestinal bleeding, ulcer or perforation have been reported with all NSAIDs at any time during treatment. These adverse events can be fatal and can occur with or without warning symptoms or with a previous history of serious gastrointestinal events.
Patients with a history of gastrointestinal disease, particularly if elderly, should report any unusual abdominal symptoms (especially gastrointestinal bleeding) in the initial stages of treatment.
Elderly patients have an increased frequency of adverse reactions to NSAIDs, especially gastrointestinal haemorrhage and perforation, which can be fatal.
Undesirable effects can be minimized with the use of the lowest effective dose for the shortest possible duration of treatment needed to control symptoms (see section 4.2 and the paragraphs below on gastrointestinal and cardiovascular risks).
Concomitant use of protective agents (misoprostol or proton pump inhibitors) should be considered for these patients and also for patients taking low dose aspirin or other drugs that may increase the risk of gastrointestinal events (see below and section 4.5).
When gastrointestinal bleeding or ulceration occurs in patients taking Froben the treatment should be discontinued.
Cardiovascular and cerebrovascular effects
Adequate monitoring and instruction are required in patients with a history of mild to moderate hypertension and / or congestive heart failure as fluid retention and edema have been reported in association with NSAID treatment.
Clinical studies and epidemiological data suggest that the use of some NSAIDs, especially at high doses and for long-term treatments, may be associated with a modest increased risk of arterial thrombotic events such as myocardial infarction or stroke. There are no data. sufficient to rule out a similar risk for flurbiprofen.
Patients with uncontrolled hypertension, congestive heart failure, established ischemic heart disease, peripheral arterial disease and / or cerebrovascular disease should only be treated with flurbiprofen after careful consideration. Similar considerations should be made before initiating long-term treatment in patients with risk factors for cardiovascular disease (eg, hypertension, hyperlipidaemia, diabetes mellitus, smoking).
Flurbiprofen, like other NSAIDs, can inhibit platelet aggregation and prolong bleeding time.
Skin reactions
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. Patients appear to be at higher risk in the early stages of therapy. : The onset of the reaction occurs in most cases within the first month of treatment. Flurbiprofen should be discontinued at the first appearance of skin rash, mucosal lesions or any other signs of hypersensitivity.
Other Reactions
Caution should be used when initiating treatment with NSAIDs such as flurbiprofen in patients with considerable dehydration.
Particular caution should be taken in the treatment of patients with severely reduced renal, cardiac or hepatic function, as the use of NSAIDs may lead to deterioration of renal function. In such patients the dosage should be kept as low as possible and renal function must be monitored.
Cases of bronchospasm have been reported with flurbiprofen in patients with a history of bronchial asthma.
At the recommended doses, the possible swallowing of FROBEN 0.25% Mouthwash and FROBEN 0.25% Solution to be nebulised does not cause any harm to the patient as these doses are much lower than those of the single systemic dosage of the product.
The use of FROBEN 0.25% Mouthwash and FROBEN 0.25% Solution to be nebulized, especially if prolonged, can give rise to sensitization phenomena or local irritation; in such cases it is necessary to stop the treatment and consult the doctor to establish, if necessary, appropriate therapy.
Do not use for prolonged treatments. After short periods of treatment without appreciable results, consult your doctor.
Important information about some of the ingredients
The tablets contain lactose and sucrose therefore patients with rare hereditary problems of galactose or fructose intolerance, the Lapp lactase deficiency, glucose-galactose malabsorption or sucrase isomaltase insufficiency should not take this medicine.
The syrup contains sucrose therefore patients with rare hereditary problems of fructose intolerance, glucose-galactose malabsorption or sucrase isomaltase insufficiency should not take this medicine.
The syrup, mouthwash and nebulizer solution contain para-hydroxybenzoates which can cause allergic reactions (including delayed ones).
04.5 Interactions with other medicinal products and other forms of interaction
Attention should be paid in patients treated with any of the medicines listed below, as interactions have been reported in some patients.
Diuretics, ACE inhibitors and angiotensin II antagonists: NSAIDs may reduce the effect of diuretics and other antihypertensive drugs. In some patients with impaired renal function (e.g. dehydrated patients or elderly patients with impaired renal function) the co-administration of an ACE inhibitor or angiotensin II antagonist and agents that inhibit the cyclo-oxygenase system may lead to further deterioration of renal function, including possible acute renal failure, usually reversible. These interactions should be considered in patients taking Flurbiprofen concomitantly with ACE inhibitors or angiotensin II antagonists. Therefore, the combination should be administered with caution, especially in elderly patients.
Patients should be adequately hydrated and monitoring of renal function should be considered after initiation of concomitant therapy and on a periodic basis thereafter.
Cardiac glycosides: NSAIDs can exacerbate heart failure, reduce the degree of glomerular filtration and increase plasma levels of cardiac glycosides.
Anticoagulants, such as warfarin: increased anticoagulant effect.
Aspirin: As with other NSAID-containing medicinal products, concomitant administration of flurbiprofen and aspirin is generally not recommended due to the potential for increased side effects.
Anti-aggregating agents: increased risk of gastrointestinal bleeding.
Selective serotonin reuptake inhibitors (SSRIs): increased risk of gastrointestinal bleeding.
Lithium salts: lithium removal decrease.
Methotrexate: Caution is advised in case of concomitant administration of flurbiprofen and methotrexate as NSAIDs may increase methotrexate levels.
Ciclosporins: increased risk of nephrotoxicity with NSAIDs.
Corticosteroids: increased risk of gastrointestinal ulcer or haemorrhage with NSAIDs.
Cox-2 inhibitors and other NSAIDs: Concomitant use of other NSAIDs, including selective cyclooxygenase-2 inhibitors, should be avoided due to potential additive effects.
Quinolone Antibiotics: Results from animal studies suggest that NSAIDs may increase the risk of seizures associated with the use of quinolone antibiotics. Patients taking NSAIDs and quinolones may have an increased risk of developing seizures.
Mifepristone: NSAIDs should not be taken for 8-12 days after administration of mifepristone as NSAIDs may reduce the effects of mifepristone.
Tacrolimus: Possible increased risk of nephrotoxicity when co-administered with NSAIDs.
Zidovudine: increased risk of haematic toxicity when co-administered with NSAIDs. There is evidence of an increased risk of haemarthrosis and hematoma in HIV-infected haemophiliac patients concomitantly treated with Zidovudine and other NSAIDs.
FROBEN 0.25% MOUTHWASH AND 0.25% SOLUTION TO NEBULIZE
At the recommended doses, no interactions with other medicinal or other drugs have been reported. However, inform your doctor if you are taking other medications.
04.6 Pregnancy and lactation
Pregnancy
Inhibition of prostaglandin synthesis can adversely affect pregnancy and / or embryo / fetal development.
Results of epidemiological studies suggest an increased risk of miscarriage and cardiac malformation and gastroschisis after use of a prostaglandin synthesis inhibitor in early pregnancy. The absolute risk of cardiac malformations increased from less than 1% to approximately 1.5%. The risk has been considered to increase with dose and duration of therapy. In animals, administration of prostaglandin synthesis inhibitors has been shown to cause increased pre- and post-implantation loss and mortality. embryo-fetal.
In addition, an increased incidence of various malformations, including cardiovascular, has been reported in animals given prostaglandin synthesis inhibitors during the organogenetic period.
During the first and second trimester of pregnancy, flurbiprofen should not be administered except in strictly necessary cases.
If flurbiprofen is used by a woman attempting to conceive or during the first and second trimester of pregnancy, the dose and duration of treatment should be kept as low as possible.
During the third trimester of pregnancy, all prostaglandin synthesis inhibitors can expose
the fetus to:
• Cardiopulmonary toxicity (with premature closure of the arterial duct and pulmonary hypertension);
• Renal dysfunction, which can progress to renal failure with oligo-hydroamnios;
the mother and the newborn, at the end of pregnancy, to:
• Possible prolongation of bleeding time, an antiplatelet effect that can occur even at very low doses;
• Inhibition of uterine contractions resulting in delayed or prolonged labor.
Consequently flurbiprofen is contraindicated during the third trimester of pregnancy.
Feeding time
Flurbiprofen is excreted in breast milk; however the amount excreted is only a small fraction of the maternal dose. Administration of flurbiprofen is not recommended in nursing mothers.
04.7 Effects on ability to drive and use machines
It does not affect the ability to drive and use machines.
04.8 Undesirable effects
Disorders of the blood and lymphatic system
Thrombocytopenia, aplastic anemia and agranulocytosis
Disorders of the immune system
Anaphylaxis, angioedema, allergic reaction.
Psychiatric disorders
Depression
Disorders of the nervous system
Dizziness, cerebrovascular accidents, visual disturbances, optic neuritis, migraine, paraesthesia, depression, confusion, hallucination, vertigo, malaise, fatigue and somnolence.
Acoustic and labyrinth disturbances
Tinnitus
Cardiovascular Disorders
Edema, hypertension and heart failure
Clinical studies and epidemiological data suggest that the intake of some NSAIDs (especially at high doses and in the case of long-term treatment) may be associated with an increased risk of arterial thrombotic events (eg myocardial infarction or stroke).
Respiratory, thoracic and mediastinal disorders
Respiratory tract reactivity (asthma, bronchospasm and dyspnoea)
Gastrointestinal Disorders
The most commonly observed adverse events are gastrointestinal in nature.
Nausea, vomiting, diarrhea, flatulence, constipation, dyspepsia, abdominal pain, melaena, haematemesis, ulcerative stomatitis, gastrointestinal haemorrhage and exacerbation of colitis and Crohn's disease have been reported following administration of flurbiprofen (see Contraindications section). Gastritis, peptic ulcer, perforation and ulcer haemorrhage were observed less frequently. Local irritation can occur with suppositories.
Cases of pancreatitis have been reported very rarely.
Skin and subcutaneous tissue disorders
Skin disorders including rash, pruritus, urticaria, purpura, angioedema and very rarely bullous dermatosis (including Stevens-Johnson Syndrome, Toxic Epidermal Necrolysis and Erythema multiforme).
During clinical trials with flurbiprofen patches, the most commonly reported adverse reactions were local skin reactions (including redness, rash, itching, rash, numbness and tingling); however the incidence was low (4.6%).
Kidney and urinary system disorders
Nephrotoxicity in various forms, including interstitial nephritis and nephrotic syndrome.
As with other NSAIDs, rare cases of renal failure have been reported.
04.9 Overdose
Symptoms
Symptoms of overdose may include nausea, vomiting and gastrointestinal irritation.
Treatment
Treatment should include gastric lavage and, if necessary, correction of the serum electrolyte picture.
There is no specific antidote for flurbiprofen.
05.0 PHARMACOLOGICAL PROPERTIES
05.1 Pharmacodynamic properties
Pharmacotherapeutic group: Anti-inflammatory and antirheumatic drugs, stomatological
ATC CODE: M01AE09, A01AD11
Flurbiprofen possesses analgesic, anti-inflammatory and antipyretic properties. This is thought to be related to the drug's ability to inhibit prostaglandin synthesis.
05.2 Pharmacokinetic properties
Following oral administration, flurbiprofen is readily absorbed from the gastrointestinal tract, with peak plasma concentrations occurring approximately 90 minutes after ingestion. Compared to tablets, absorption from suppositories may be more rapid but peak concentration serum is lower.
Flurbiprofen is about 99% protein bound and has an elimination half-life of about 3-4 hours. The urinary excretion rate of flurbiprofen and its two major metabolites, both in the free and conjugated state, is similar in both free and conjugated states. the oral and rectal routes of administration The metabolic patterns are also similar from a quantitative point of view for both routes of administration.
05.3 Preclinical safety data
Toxicological tests on animals have shown that flurbiprofen is well tolerated. Acute toxicity tests on various animal species, for oral administration, have shown that the LD50 of flurbiprofen is between 228-344 mg / kg. The administration of NSAIDs to pregnant rats can result in restriction of the fetal arterial duct.
Long-term clinical studies have shown no significant effects on hepatic or renal function or on the haematopoietic system.
There is no further information on preclinical data other than that already reported elsewhere in this Summary of Product Characteristics (see section 4.6).
06.0 PHARMACEUTICAL INFORMATION
06.1 Excipients
• FROBEN 100 mg Coated tablets
Stearic acid, corn starch, carnauba wax, glucose, sandracca, lactose, magnesium stearate, povidone, sucrose, anhydrous colloidal silica, talc, titanium dioxide.
• FROBEN 5mg / ml Syrup
Purified water, propylene glycol, natural banana flavor, carmellose sodium, glycerin, levomentol, methyl para-hydroxybenzoate, sodium citrate, propyl para-hydroxybenzoate, sucrose, sodium saccharinate.
• FROBEN 100 mg Suppositories
Solid semisynthetic glycerides.
• FROBEN 0.25% Mouthwash and FROBEN 0.25% Solution to be sprayed
Purified water, alcohol, patent blue VE 131, glycerol, mint essence, methyl para-hydroxybenzoate, hydrogenated castor oil 40-polyoxyethylenate, potassium bicarbonate, propyl para-hydroxybenzoate, sodium saccharinate, sorbitol.
• FROBEN 200 mg Prolonged-release hard capsules
anhydrous colloidal silica, microcrystalline cellulose, Eudragit RS 100, macrogol 6000, magnesium stearate.
Composition of the capsule: titanium dioxide, gelatin, quinoline yellow, glycerin, Black Opacode, red iron oxide.
• FROBEN 100 mg Effervescent granules
Citric acid, orange flavor, macrogol 6000, sodium saccharin, sucrose, sodium bicarbonate, sodium carbonate.
06.2 Incompatibility
There are no known chemical-physical incompatibilities of flurbiprofen with other compounds.
06.3 Period of validity
• Prolonged-release hard capsules, effervescent granules, syrup, mouthwash: 3 years
• Coated tablets, suppositories: 5 years
• Solution to be sprayed: 2 years
• Froben 5mg / ml Syrup is valid for 6 months after first opening.
06.4 Special precautions for storage
100 mg coated tablets, syrup and mouthwash: Do not store above 25 ° C.
Prolonged-release 200 mg capsules, hard: No special storage precautions.
06.5 Nature of the immediate packaging and contents of the package
Coated tablets
• Carton containing 10 coated tablets of 100 mg in blister packs (PVC / PVDC and aluminum)
• Carton containing 30 coated tablets of 100 mg in blister packs (PVC / PVDC and aluminum)
Syrup
• Carton containing a 200 ml PET bottle with a 160 ml syrup polypropylene cap
Suppositories
• Box containing 10 suppositories of 100 mg in white strips (PVC)
Mouthwash
• Carton containing a dark glass bottle with a metal screw cap of 160 ml of solution
Solution to be sprayed
• Carton containing a white glass bottle with microdosing pump and dispenser of 15 ml of solution
Prolonged-release hard capsules
• Carton containing 20 x 200 mg prolonged-release hard capsules in blisters (PVC / PVDC and aluminum)
Effervescent granules
• Box containing 10 sachets of 100 mg effervescent granules in triple layer paper / aluminum / polythene material
• Box containing 30 sachets of 100 mg effervescent granules in triple layer paper / aluminum / polythene material
06.6 Instructions for use and handling
FROBEN 0.25% Solution to be nebulised:
Turn the spout to the right or left, without tampering with the dispenser.
Press the dispenser
07.0 MARKETING AUTHORIZATION HOLDER
BGP Products S.r.l. - Viale Giorgio Ribotta 11, 00144 Rome (RM)
08.0 MARKETING AUTHORIZATION NUMBER
• 10 coated tablets of 100 mg - A.I.C .: n. 024284162 *
• 30 coated tablets of 100 mg - A.I.C .: n. 024284034
• 5 mg / ml syrup - 1 bottle of 160 ml - A.I.C .: n. 024284073
• 10 suppositories of 100 mg - A.I.C .: n. 024284097 *
• 0.25% mouthwash - 160 ml bottle - A.I.C .: n. 024284109
• 0.25% solution to be nebulized - Bottle 15 ml - A.I.C .: n. 024284135
• 20 prolonged-release hard capsules of 200 mg - A.I.C .: n. 024284123
• 10 sachets of 100 mg effervescent granules - A.I.C .: n. 024284150 *
• 30 sachets of 100 mg effervescent granules - A.I.C .: n. 024284147 *
* not on the market
09.0 DATE OF FIRST AUTHORIZATION OR RENEWAL OF THE AUTHORIZATION
• 10 coated tablets of 100 mg: 27.01.2000
• 30 coated tablets of 100 mg: 22.11.1980
• 5mg / ml syrup - 1 bottle of 160 ml: 22.11.1980
• 10 suppositories of 100 mg: 07.07.1982
• 0.25% mouthwash - 160 ml bottle: 27.04.1991
• 0.25% nebuliser solution - 15 ml bottle: 11.11.1996
• 20 hard prolonged-release capsules of 200 mg: 02.08.1991
• 10 sachets of 100 mg effervescent granules: 28.01.2000
• 30 sachets of 100 mg effervescent granules: 28.01.2000
Renewal of the authorization: 01.06.2010
10.0 DATE OF REVISION OF THE TEXT
May 2015
