Brufen Pain Relief Orosoluble Medical Device 12 Sachets x40mg

Brufen Pain in buccal granules

PHARMACOTHERAPEUTIC CATEGORY:
Non-steroidal anti-inflammatory / antirheumatic drugs - derivatives of propionic acid.

ACTIVE PRINCIPLES:
One sachet contains: Active ingredient: ketoprofen 40 mg lysine salt (corresponding to 25 mg of ketoprofen).
Excipient with known effects: aspartame.
For the full list of excipients, see section 6.1.

EXCIPIENTS:
Mannitol, xylitol, lime flavor, lemon flavor, cool fragrance, aspar tame, talc, basic butylated methacrylate copolymer, magnesium stear ato, colloidal hydrated silica, hypromellose, stearic acid, povidone, sodium lauryl sulfate.

INDICATIONS:
Symptomatic treatment of acute mild and moderate pain.

CONTRAINDICATIONS / SECONDAR EFFECT:
It must not be administered in the following cases: - hypersensitivity to the active substance, to other non-steroidal anti-inflammatory drugs (NSAIDs) or to any of the excipients listed in section 6.1.
- patients with a history of hypersensitivity reactions, such as b ronchospasm, asthma attacks, acute rhinitis, nasal polyps, urticaria, angioneurotic edema or other allergic-type reactions to ketoprofen or substances with a similar mechanism of action [for example acetyl salicylic acid (ASA) or other non-steroidal anti-inflammatory drugs (NSAIDs)].
Severe anaphylactic reactions, rarely fatal, have been reported in these patients (see section 4.8).
- active peptic ulcer / haemorrhage, or a history of gastrointestinal haemorrhage, ulceration or perforation (two or more distinct, proven episodes of bleeding or ulceration) or chronic dyspepsia.
- gastr or intestinal bleeding or gastrointestinal perforation following previous NSAID therapy or other active bleeding or bleeding disorders.
- severe heart failure.
- severe hepatic insufficiency.
- severe renal insufficiency.
- haemorrhagic diathesis and other coagulation disorders, or patients subject to anticoagulant therapy.
- patients undergoing major surgery.
- third trimester of pregnancy and lactation (see section 4.6) - children and adolescents under the age of 15 years.

DOSAGE:
Dosage.
Adults and adolescents over 15 years: 1 sachet, in a single dose, or repeated 2-3 times a day, in the most painful and intense forms.
The duration of therapy should be limited to the completion of the painful episode (see section 4.4).
Special populations i.
Elderly: Elderly patients should adhere to the minimum dosages indicated above.
Patients with mild or moderate renal impairment: it is recommended to monitor the volume of diuresis and renal function (see section 4.4).
Patients with mild or moderate hepatic impairment: should be followed closely and treated with the lowest effective daily dose (see section 4.4).
BRUFEN PAIN should not be used in patients with severe hepatic and renal dysfunction (see section 4.3).
Pediatric population: BRUFEN PAIN is contraindicated in children and adolescents under the age of 15 years.
Method of administration: the contents of the sachet can be post or directly on the tongue.
It dissolves with saliva: this allows it to be used without water.
It is preferable to take the medicine with a full stomach.

STORAGE:
This medicinal product does not require any special storage conditions.

WARNINGS:
Administer with caution in patients with allergic manifestations or previous allergy.
Treatment with ketoprofen lysine salt must be discontinued at the first appearance of skin rash, mucosal lesions or any other sign of hypersensitivity.
Undesirable effects can be minimized by using the lowest effective dose for the shortest possible duration of treatment needed to control symptoms.
Concomitant use with other NSAIDs, including selective cyclooxygenase-2 inhibitors, should be avoided.
Elderly patients have an increased frequency of adverse reactions to NSAIDs, especially gastrointestinal bleeding and perforation, which can be fatal.
In the presence of an infection, it should be taken into account that the anti-inflammatory, analgesic and antipyretic properties of ketoprofen can mask common symptoms of the progression of the infection such as fever.
Cardiovascular and cerebrovascular effects: adequate monitoring and appropriate instructions are necessary in patients with a history of hypertension and / or mild to moderate congestive heart failure since fluid retention, hypertension have been found in association with treatment with NSAIDs. and edema.
The use of some NSAIDs may be associated with a modest increased risk of arterial thrombotic events.
There are insufficient data to exclude a similar risk for ketoprofen lysine salt when it is administered at the daily dose of one sachet, as a single dose, or repeated 2-3 times a day.
Patients with uncontrolled hypertension, congestive heart failure, established ischemic heart disease, peripheral arterial disease and / or cerebrovascular disease should only be treated with toprofen lysine salt after careful consideration.
Similar considerations should be made before initiating long-term treatment in patients with risk factors for cardiovascular disease.
Trointestinal gas haemorrhage, ulceration and perforation, which can be fatal, have been reported during treatment.
Some epidemiological evidence suggests that ketoprofen lysine salt may be associated with a higher risk of severe gastrointestinal toxicity than other NSAIDs, especially at high doses.
In the elderly and in patients with a history of ulcer, particularly when combined with haemorrhage or perforation, the risk of gastrointestinal haemorrhage, ulceration or perforation is higher with increasing doses of NSAIDs.
These patients should start treatment with the lowest available dose.
Concomitant use of protective agents should be considered for these patients and also for patients taking low doses of aspirin or other drugs that may increase the risk or of gastrointestinal events.
Patients with a history of gastr or intestinal toxicity should report any unusual gastrointestinal symptoms.
Caution should be exercised in patients taking medications with comitants that may increase the risk of ulceration or bleeding, such as oral corticosteroids, anticoagulants such as warfarin, selective serotonin reuptake inhibitors or antiplatelet agents such as aspirin.
When gastrointestinal bleeding or ulceration occurs in patients taking ketoprofen lysine salt the treatment should be discontinued.
NSAIDs should be administered with caution to patients with a history of gastrointestinal disease as these conditions may be exacerbated.
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: the onset of the reaction occurs in most cases within the first month of treatment.
Ketoprofen lysine salt should be discontinued at the first appearance of skin rash, mucosal lesions or any other signs of hypersensitivity '.
It can increase plasma urea nitrogen and creatinine.
Ketoprofen lysine salt can be associated with adverse effects on the renal system which can lead to glomerular nephritis, renal papillary necrosis, nephrotic syndrome and acute renal insufficiency.
Carefully monitor renal function at the start of treatment in patients with heart failure, with cirrhosis and nephrosis, in patients on diuretic therapy, with chronic renal insufficiency particularly if the elderly.
In such patients the administration of ketoprofen lysine salt can cause a reduction in renal blood flow, caused by the inhibition of prostaglandins and lead to renal alterations.
It can cause transient small increases in some liver parameters and also significant increases in SGOT and SGP T.
In the event of a significant increase in these parameters, the therapy must be interrupted.
In patients with impaired liver function or previous liver disease, transaminases should be evaluated regularly, particularly during long-term therapy.
Cases of jaundice and hepatitis have been reported with ketopr ofene lysine salt.
Attention is required when administering ketoprofen lysine salt to patients with hepatic porphyria as it could trigger an attack.
Ketoprofen lysine salt should be administered with caution in patients with haematopoietic disorders, systemic lupus erythematosus or mixed connective tissue disorders.
The use of NSAIDs can compromise fertility and is not recommended in women intending to become pregnant.
The administration of ketoprofen should be discontinued in women who have difficulty conceiving or who are undergoing investigation of fertility.
Treatment should be discontinued if visual disturbances such as blurred vision occur.
Patients presenting with asthma associated with chronic rhinitis and allergy, chronic sinusitis and / or nasal polyposis have a higher risk of allergy to aspirin and / or NSAIDs than the rest of the population.
Administration of this medicine can cause asthma attacks or bronchospasm, especially in subjects allergic to acetyl salicylic acid (aspirin) or NSAIDs.
Therefore in these subjects, as well as in the case of chronic obstructive pulmonary disease or nephropathy, the drug should only be used under medical supervision.
To avoid any hypersensitivity or photosensitization phenomena, it is advisable not to expose yourself to the sun during use.
Contains 10.56 mg of aspam per dose equivalent to 31.78 mg per maximum recommended daily dose.
Aspartame is a source of phenylalanine.
It can be harmful in patients with phenylketonuria.

INTERACTIONS:
Combinations not recommended - Other NSAIDs, (including selective inhibitors of cyclooxygenase-2), including high doses of salicylates (> = 3g / e): the simultaneous administration of several NSAIDs may increase the risk of gastrointestinal ulcers and bleeding, for a synergistic effect.
- Anticoagulants (eg heparin and warfarin) and antiplatelet agents (eg ticlopidine and clopidogrel): increased risk of bleeding due to inhibition of platelet function and damage to the gastrointestinal mucosa (see section 4.4).
If concomitant subadministration cannot be avoided, patients should be carefully monitored.
- Lithium: risk of increased plasma lithium levels, which can sometimes reach toxic levels due to reduced renal excretion of lithium.
Where necessary, plasma lithium levels should be carefully monitored with possible dosage adjustment during and after AF NS therapy.
- Methotrexate, used in high doses (greater than 15 mg / week): increased risk of methotrexate blood toxicity, particularly when given in high doses (> 15 mg / week), possibly due to displacement of methotrexate from binding protein and the reduction of its renal clearance.
- Hydantoins and sulfonamides: the toxic effects of these substances can be increased.
Combinations requiring precaution - Corticosteroids: increased risk of gastrointestinal ulceration or bleeding (see section 4.4).
Diuretics: Patients taking diuretics, particularly if dehydrated, are at high risk of developing renal failure secondary to a reduction in renal blood flow caused by inhibition of prostaglandins.
Patients should be adequately hydrated and monitoring of renal function should be considered after initiation of concomitant therapy (see section 4.
4).
NSAIDs can reduce the effect of diuretics.
The concomitant use of NSAIDs and potassium-sparing diuretics, in addition to a reduction of the diuretic effect and potential for nephrotoxicity, may also lead to hyperkalaemia.
- ACE inhibitors and angiotensin II antagonists: 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 an angiotensin II antagonist and Agents that inhibit the cyclooxyxynase system may lead to further deterioration of renal function, with possible onset of acute renal failure.
The combination should therefore 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.
- Methotrexate used in low doses, less than 15 mg / week: a complete blood count should be performed every week during the first weeks of combined therapy.
In the presence of even a slight worsening of renal function or in elderly patients, monitoring should be more frequent.
- Pentoxifylline: increased risk of bleeding.
Clinical monitoring should be increased and bleeding time monitored more frequently.
- Zidovudine: risk of increased toxicity on the red cell line by action on reticulocytes, with severe anemia occurring one week after the initiation or treatment with the NSAID.
Check the complete haemocytometric test and reticulocyte count one or two weeks after starting treatment with the NSAID.
- Tenofovir: concomitant administration of tenofovir disoproxil fumarate and NSAIDs may increase the risk of renal failure.
- Sulfonylureas: NSAIDs can increase the hypoglycemic effect of sulfonylureas by displacing them from the binding conditions with plasma proteins.
Associations that need to be considered: - Antihypertensives (beta-blockers, angiotensin converting enzyme inhibitors, diuretics): NSAIDs can reduce the effect of antihypertensive drugs by inhibiting prostaglandin synthesis.
- Thrombolytics: increased risk of bleeding.
- Probenecid: concomitant administration of probenecid can considerably reduce the plasma clearance of ketoprofen and consequently the plasma concentrations of ketoprofen may be increased; this interaction may be due to an inhibitory mechanism at the site of renal tubular secretion and glucuronoconjugation and requires an adaptation of the ketoprofen dose.
- Selective se rotonin reuptake inhibitors (SSRIs) and tricyclic antidepressants: increased risk of gastrointestinal and intracranial haemorrhage (see section 4.4).
- C iclosporin, tacrolimus: risk of additive nephrotoxic effects, particularly in the elderly.
Renal function should be measured during associated therapy.
- Quinolone antibiotics: Animal data indicate that NSAIDs may increase the risk of seizures associated with quinolone antibiotics.
Patients taking NSAIDs and quinolones may have an increased risk of developing vulsions.

SIDE EFFECTS:
The most commonly observed adverse events are gastrointestinal in nature.
Peptic ulcers, gastrointestinal perforation or haemorrhages, sometimes fatal, may occur, particularly in the elderly (see section 4.4).
The frequency and extent of these effects are reduced by taking the drug on a full stomach.
The manifestations of hypersensitivity 'can take the character of severe systemic reactions (edema of the larynx, edema of the glottis, dyspnoea, palpitations) up to anaphylactic shock.
In these cases, immediate medical assistance is required.
The following adverse reactions have been observed following administration of ketoprofen lysine salt in adults.
The frequency of adverse events is classified as follows: very common (> = 1/10); common (> = 1/100, <1/10); uncommon (> = 1/1000, <1/100); rare (> = 1 / 10,000, <1/1000); very rare (<1 / 10,000); not known (frequency cannot be estimated from the available data).
Infections and infestations.
Not known: aseptic meningitis, lymphangitis.
Disorders of the blood and lymphatic system.
Rare: haemorrhagic anemia.
Not known: agranulocytosis, thrombocytopenia, bone marrow aplasia, haemolytic anemia, leukopenia, neutropenia, aplastic anemia, leukocyte yes, thrombocytopenic purpura.
Disorders of the immune system.
Not known: anaphylactic reactions (including shock), hypersensitivity '.
Psychiatric disorders.
Not known: depression, hallucinations, mood swings, excitability, insomnia.
Nervous system disorders.
Not common: headache, dizziness, sleepiness.
Rare: paraesthesia.
Not known: syncope, convulsions, dysgeusia, tremor, hyperkinesia, dyskinesia, dizziness.
Eye disorders.
Rare: blurred vision (see section 4.4).
Not known: periorbital edema.
Ear and labyrinth disorders o.
Rare: tinnitus.
Cardiac pathologies.
Not known: heart failure, palpitations, tachycardia.
Vascular pathologies.
Not known: hypotension, hypertension, vasodilation, vasculitis.
Respiratory, thoracic and mediastinal disorders.
Rare: asthma.
Not known: edema of the larynx, bronchospasm (especially in patients with known hypersensitivity to acetylsalicylic acid and other NSAIDs), rhinitis, dyspnoea, laryngospasm, acute respiratory failure.
Gastrointestinal disorders.
Common: nausea, vomiting, dyspepsia, abdominal pain.
Uncommon: constipation, diarrhea, flatulence, gastritis.
Rare: ulcerative stomatitis, peptic ulcer.
Not known: exacerbation of colitis and Crohn's disease, gastrointestinal haemorrhages and perforation (see section 4.4), gastric ulcer, duodenal ulcer, pancreatitis, melaena, haematemesis, gastric pain, erosive gastritis, tongue edema.
Hepatobiliary disorders.
Rare: hepatitis, increased serum transaminase levels, elevated serum bilirubin levels due to liver disorders, jaundice.
Pathology of the skin and subcutaneous tissue.
Uncommon: rash, pruritus.
Not known: photosensitization, alopecia, urticaria, angioedema, bullous eruptions, including Stevens-Johnson syndrome, Lyell's syndrome and toxic epidermal necrolysis, erythema, exanthema, exant but maculo-papular, purpura, dermatitis.
Renal and urinary disorders.
Not known: water retention, haematuria, acute renal failure, tubulointerstitial nephritis, nephritic syndrome, glomerular nephritis, acute tubular necrosis, renal papillary necrosis, nephrotic syndrome, oliguria, renal function test abnormality, dysuria.
General disorders and administration site conditions.
Uncommon: edema, fatigue.
Not known: chills, asthenia, vault edema, peripheral edema.
Diagnostic tests.
Rare: weight gain.
Reporting of suspected adverse reactions The reporting of suspected adverse reactions occurring after the authorization of the drug is important, as it allows continuous monitoring of the benefit / risk ratio of the drug.
Healthcare professionals are asked to report any suspected adverse reactions via the national reporting system at http: //www.agenziafarmaco.g ov.it/content/come-segnalare-una-sospetta-reazione-avversa.

PREGNANCY AND BREASTFEEDING:
Pregnancy: inhibition of prostaglandin synthesis can negatively affect pregnancy and / or embryo / fetal development.
Results from epidemiological studies suggest an increased risk of miscarriage and cardiac malformation and gastroschisis after the 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 was believed to increase with dose and duration of therapy.
In animals, administration of prostaglandin synthesis inhibitors has been shown to cause an increase in pre- and post-implantation loss, embryo-fetal mortality and an increase in the incidence of various malformations, including cardiovascular ( see paragraph 5.3).
Therefore ketoprofe ne should not be administered during the first and second trimesters of pregnancy unless strictly necessary.
If ketoprofen is used in women wishing to become pregnant 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 closing of the arterial duct and pulmonary hypertension); - renal dysfunction, which can 'progress to renal failure with os oligo-hydroamni; the mother and the newborn, at the end of pregnancy, to: - possible prolongation of the bleeding time, and antiplatelet effect which can occur even at very low doses; - inhibition of uterine contractions resulting in delayed or prolonged labor.
BRUFEN PAIN is therefore contraindicated during the third trimester of pregnancy.
Lactation: Since no data are available on the secretion of ketoprofen lysine salt in breast milk, ketoprofen should not be administered during lactation.
Fertility: the use of ketoprofen lysine salt, as well as any drug inhibitor of prostaglandin synthesis and cyclooxygenase is not recommended in women who intend to become pregnant.
The administration of ketoprofen lysine salt should be discontinued in women who have fertility problems 'or who are undergoing investigation of fertility'.