Active ingredients: Ibuprofen
BRUFEN 400 mg Coated tablets
Brufen package inserts are available for pack sizes:- BRUFEN 400 mg Coated tablets
- BRUFEN 600 mg Ibuprofen coated tablets
- BRUFEN 600 mg effervescent granules Ibuprofen
- BRUFEN 800 mg prolonged-release coated tablets
- 20 mg / ml Oral suspension
Why is Brufen used? What is it for?
PHARMACOTHERAPEUTIC CATEGORY
Brufen (Ibuprofen) belongs to the category of non-steroidal anti-inflammatory drugs (NSAIDs)
THERAPEUTIC INDICATIONS
As an antirheumatic in:
- osteoarthritis in all its localizations (cervical, dorsal, lumbar osteoarthritis; osteoarthritis of the shoulder, hip, knee, diffuse osteoarthritis, etc.), scapulo-humeral periarthritis, lumbago, sciatica, radiculo-neuritis; fibrositis, tenosynovitis, myositis , sports traumatology; rheumatoid arthritis, Still's disease.
As an analgesic in painful forms of different etiology:
- in accidental and sports traumatology;
- in dental practice, in post-extraction pain and after odontostomatological interventions;
- in obstetrics: in post-episiotomic and post-partum pain;
- in gynecology: in the prevention and treatment of dysmenorrhea;
- in surgery: in the treatment of post-operative pain;
- in ophthalmology: in post-operative pain and painful forms of various etiology;
- in general medicine: in the treatment of migraine and headache.
Contraindications When Brufen should not be used
- Hypersensitivity to the active substance or to any of the excipients.
- Subjects with hypersensitivity to acetylsalicylic acid or to other analgesics, antipyretics, non-steroidal anti-inflammatory drugs (NSAIDs), particularly when hypersensitivity is associated with nasal polyposis, angioedema and / or asthma.
- Severe hepatic insufficiency.
- Severe renal insufficiency (glomerular filtration less than 30ml / min).
- Severe heart failure.
- Severe or active peptic ulcer.
- History of gastrointestinal bleeding or perforation related to previous active treatments or history of recurrent peptic ulcer / haemorrhage (two or more distinct episodes of proven ulceration or bleeding).
- Ibuprofen should not be given to patients with medical conditions that lead to an increased bleeding tendency.
- Ibuprofen is contraindicated during the third trimester of pregnancy (see Special warnings).
Children under 12 years of age.
Precautions for use What you need to know before taking Brufen
The concomitant use of Brufen with other NSAIDs, including selective cyclooxygenase-2 (COX-2) inhibitors, should be avoided due to an increased risk of ulceration or bleeding (see Interactions).
Undesirable effects can be minimized by using the lowest effective dose for the shortest possible duration of treatment needed to control symptoms (see Dose, method and time of administration and the sections below on gastrointestinal and cardiovascular risks).
Like other NSAIDs, ibuprofen can mask signs of infection.
Senior citizens
Elderly patients have an increased frequency of adverse reactions to NSAIDs, especially gastrointestinal bleeding and perforation, which can be fatal (see Dose, method and time of administration).
Gastrointestinal bleeding, ulceration and perforation
Gastrointestinal bleeding, ulceration and perforation, which can be fatal, have been reported during treatment with all NSAIDs at any time, with or without warning symptoms or a previous history of serious gastrointestinal events.
In the elderly and in patients with a history of ulcer, particularly if complicated with haemorrhage or perforation (see Contraindications), the risk of gastrointestinal bleeding, ulceration or perforation is higher with increased doses of NSAIDs. These patients should start treatment with the lowest available dose. Concomitant use of gastroprotective 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). .
Patients with a history of gastrointestinal toxicity, particularly the elderly, should report any unusual gastrointestinal symptoms (especially gastrointestinal bleeding) particularly in the initial stages of treatment.
Caution should be exercised in patients taking concomitant medications that may increase the risk of ulceration or bleeding, such as oral corticosteroids, anticoagulants such as warfarin, selective serotonin reuptake inhibitors (SSRIs) or antiplatelet agents such as acetylsalicylic acid (see Interactions). .
When gastrointestinal bleeding or ulceration occurs in patients taking Brufen the treatment should be discontinued.
NSAIDs should be administered with caution to patients with a history of gastrointestinal disease (ulcerative colitis, Crohn's disease) as these conditions may be exacerbated (see Undesirable Effects ").
Use with caution even in patients with coagulation defects.
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.
Patients with uncontrolled hypertension, congestive heart failure, established ischemic heart disease, peripheral arterial disease and / or cerebrovascular disease should only be treated with ibuprofen after careful consideration. Similar considerations should be made before initiating long-term treatment in patients with risk factors for cardiovascular events (eg, hypertension, hyperlipidaemia, diabetes mellitus, smoking).
Dermatological effects
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 Undesirable effects).
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. Brufen treatment should be stopped at the first appearance of skin rash, mucosal lesions. or any other signs of hypersensitivity as well as if you have visual disturbances or persistent signs of liver dysfunction.
Kidney effects
When initiating treatment with ibuprofen, caution should be exercised in patients with considerable dehydration.
Long-term use of ibuprofen, as with other NSAIDs, has led to renal papillary necrosis and other renal pathological changes.
In general, the habitual use of analgesics, especially combinations of different analgesic active ingredients, can lead to permanent renal lesions, with the risk of renal failure (analgesic nephropathy).
Renal toxicity has been reported in patients in whom renal prostaglandins have a compensatory role in maintaining renal perfusion. Administration of NSAIDs in these patients may result in a dose-dependent reduction in prostaglandin formation and, as a secondary effect, in renal blood flow. This can quickly lead to kidney failure.
Patients most at risk of these reactions are those with reduced kidney function, heart failure, liver dysfunction, the elderly and all those patients taking diuretics and ACE inhibitors. Discontinuation of NSAID therapy is usually followed by recovery of the pretreatment state.
In case of prolonged use, monitor renal function particularly in case of diffuse lupus erythematosus.
There is a risk of impaired renal function in dehydrated children and adolescents.
Respiratory disorders
Brufen should be prescribed with caution in patients with bronchial asthma, chronic rhinitis or current or previous allergic disease as bronchospasm, urticaria or angioedema may occur. The same applies to those subjects who have experienced bronchospasm after the use of aspirin or other NSAIDs.
Hypersensitivity reactions
Analgesics, antipyretics, non-steroidal anti-inflammatory drugs can cause hypersensitivity reactions, potentially serious (anaphylactoid reactions), even in subjects not previously exposed to this type of drug. The risk of hypersensitivity reactions after taking ibuprofen is greater in subjects who have presented these reactions after the use of other analgesics, antipyretics, non-steroidal anti-inflammatory drugs and in subjects with bronchial hyperreactivity (asthma), nasal polyposis or previous episodes of angioedema (see Contraindications and Undesirable Effects).
Reduced cardiac, renal and hepatic function
Particular caution should be taken in the treatment of patients with impaired cardiac, hepatic or renal function since the use of NSAIDs may lead to a deterioration of renal function. The usual concomitant use of several painkillers may further increase this risk. In patients with impaired cardiac, hepatic or renal function, the lowest effective dose should be used for the shortest treatment period and periodic monitoring of clinical and laboratory parameters, especially in case of prolonged treatment (see Contraindications).
Hematological effects
Ibuprofen, like other NSAIDs, can inhibit platelet aggregation and has been shown to prolong bleeding time in healthy subjects.
Aseptic meningitis
On rare occasions, aseptic meningitis has been observed in patients receiving ibuprofen. Although this is more likely to occur in patients with systemic lupus erythematosus and related connective tissue disorders, it has also been seen in patients who did not have concomitant chronic diseases (see Undesirable effects).
Since ocular changes have been detected in animal studies with non-steroidal anti-inflammatory drugs, it is recommended, in case of prolonged treatments, to carry out periodic ophthalmological checks.
The use of Brufen, as with any prostaglandin synthesis and cyclooxygenase inhibitor drug, is not recommended in women planning to become pregnant (see Special warnings).
Brufen should be discontinued in women who have fertility problems or who are undergoing fertility investigations.
Interactions Which drugs or foods can change the effect of Brufen
Tell your doctor or pharmacist if you have recently taken any other medicines, even those without a prescription.
Ibuprofen (like other NSAIDs) should be used with caution in combination with:
corticosteroids: increased risk of gastrointestinal ulceration or bleeding (see Precautions for use);
anticoagulants: NSAIDs may increase the effects of anticoagulants, such as warfarin (see Precautions for use). Patients on coumarins should be monitored;
acetylsalicylic acid and other NSAIDs: these substances may increase the risk of adverse reactions affecting the gastrointestinal tract (see Precautions for use). Experimental data indicate that ibuprofen may inhibit the effects of low-dose acetylsalicylic acid on platelet aggregation when drugs are administered concurrently. However, the limited data and the uncertainties relating to their application to the clinical situation do not allow definitive conclusions to be drawn for the continued use of ibuprofen; there appears to be no clinically relevant effect from the occasional use of ibuprofen. However, it is advisable not to combine ibuprofen with aspirin or other NSAIDs;
antiplatelet agents and selective serotonin reuptake inhibitors (SSRIs): increased risk of gastrointestinal bleeding (see Precautions for use);
diuretics, ACE inhibitors and angiotensin II antagonists: NSAIDs may reduce the effect of diuretics and other antihypertensive drugs. Diuretics may also increase the risk of NSAID-associated nephrotoxicity.
In some patients with impaired renal function (e.g. dehydrated or elderly patients) 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 function. renal failure, which includes possible acute renal failure, usually reversible. These interactions should be considered in patients taking Brufen concomitantly with ACE inhibitors or angiotensin II antagonists. Therefore, this 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 periodically thereafter;
lithium: the simultaneous administration of lithium and NSAIDs causes an increase in plasma lithium levels due to reduced elimination, with the possibility of reaching the toxic threshold. If this combination is necessary, lithemia should be monitored in order to adapt the lithium dosage during concomitant treatment with ibuprofen;
methotrexate: NSAIDs can inhibit the tubular secretion of methotrexate and reduce its clearance with a consequent increase in the risk of toxicity;
aminoglycosides: NSAIDs can decrease the excretion of aminoglycosides;
cardiac glycosides: NSAIDs can exacerbate heart failure, reduce glomerular filtration rate and increase plasma levels of cardiac glycosides;
cholestyramine: the concomitant administration of ibuprofen and cholestyramine may reduce the absorption of ibuprofen from the gastrointestinal tract. However, the clinical relevance of this interaction is unknown;
cyclosporine: increase the risk of nephrotoxicity with NSAIDs;
Cox-2 inhibitors and other NSAIDs: concomitant use with other NSAIDs, including selective cyclooxygenase-2 inhibitors, should be avoided due to potential additive effect (see Precautions for use);
plant extracts: Ginkgo Biloba may increase the risk of bleeding in combination with NSAIDs;
mifepristone: Due to the anti-prostaglandin properties of NSAIDs, a decrease in drug efficacy may theoretically occur. Limited evidence suggests that co-administration of NSAIDs on the day of prostaglandin administration does not adversely affect the effects of mifepristone or prostaglandin on cervical ripening or uterine contractility and does not reduce the clinical efficacy of the drug on pregnancy termination;
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 seizures;
sulfonylureas: NSAIDs may increase the effect of sulfonylureas. Rare cases of hypoglycaemia have been reported in patients receiving sulfonylureas taking ibuprofen;
tacrolimus: Possible increased risk of nephrotoxicity when NSAIDs are administered with tacrolimus;
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;
ritonavir: an increase in the concentration of NSAIDs is possible;
probenecid: slows down the excretion of NSAIDs, with possible increase in their plasma concentrations;
CYP2C9 inhibitors: concomitant administration of ibuprofen and CYP2C9 inhibitors may increase exposure to ibuprofen (CYP2C9 substrate). In a study with voriconazole and fluconazole (CYP2C9 inhibitors), increased exposure to S (+) - ibuprofen from approximately 80% to 100% was observed. Reduction of the dose of ibuprofen should be considered when administering them. concomitantly strong inhibitors of CYP2C9, particularly when high doses of ibuprofen are administered with voriconazole or fluconazole.
Consult your doctor before using ibuprofen with other medicines.
Warnings It is important to know that:
In case of prolonged use, monitor renal function particularly in case of diffuse lupus erythematosus.
Medicines such as BRUFEN may be associated with a modest increased risk of heart attack ("myocardial infarction") or stroke. Any risk is more likely with high doses and prolonged treatments. Do not exceed the recommended dose or duration of treatment.
If you have heart problems, a history of stroke or if you think you may be at risk for these conditions (for example if you have high blood pressure, diabetes or high cholesterol or if you are a smoker) you should consult your doctor or pharmacist.
Fertility, pregnancy and breastfeeding
Ask your doctor or pharmacist for advice before taking any medicine.
Pregnancy
The use of Brufen, like any drug that inhibits prostaglandin synthesis and cyclooxygenase, is not recommended in women intending to become pregnant. In fact, inhibition of prostaglandin synthesis can negatively 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 loss of pre- and post-implantation and embryo-fetal mortality.
In addition, an increased incidence of various malformations, including cardiovascular, has been reported in animals given prostaglandin synthesis inhibitors during the organogenetic period.
First and second trimester: during the first and second trimester of pregnancy, Brufen should not be administered except in strictly necessary cases and under direct medical supervision. If Brufen 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.
Third quarter: During the third trimester of pregnancy, all prostaglandin synthesis inhibitors can expose
the fetus a:
- 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, and antiplatelet effect which may occur even at very low doses;
- Inhibition of uterine contractions resulting in delayed or prolonged labor. Consequently, Brufen is contraindicated during the third trimester of pregnancy.
Feeding time
NSAIDs can be found in breast milk in very low concentrations. If possible, NSAIDs should be avoided during breastfeeding.
Fertility
The use of ibuprofen may impair female fertility and is not recommended in women attempting to conceive. Brufen should be discontinued in women who have fertility problems or who are undergoing fertility investigations
Effects on ability to drive and use machines
Undesirable effects such as dizziness, sleepiness, fatigue and visual disturbances may occur after taking ibuprofen. This should be taken into consideration when greater vigilance is required such as when driving a car or operating machinery.
Important information about some of the ingredients
Brufen tablets contain lactose. If you have been told by your doctor that you have "intolerance to some sugars, contact your doctor before taking this medicinal product.
Dosage and method of use How to use Brufen: Dosage
- 400 mg tablets: 2 - 4 per day in the opinion of the doctor.
The maximum daily dose of Brufen should not exceed 1800 mg. In rheumatology, to improve morning stiffness, the first oral dose is administered when the patient awakens; subsequent doses can be taken with meals.
Pediatric population:
The safety and efficacy of Brufen in children under the age of 12 has not yet been established. In the presence of renal insufficiency the elimination may be reduced and the dosage adjusted accordingly.
In the treatment of elderly patients, the posology must be carefully established by the doctor who will have to evaluate a possible reduction of the dosages indicated above.
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).
Method of administration
Take Brufen tablets with plenty of water. To avoid oral discomfort and throat irritation the tablets must be swallowed whole and must not be chewed, broken, broken or sucked.
Overdose What to do if you have taken too much Brufen
Symptoms
Most patients who have ingested significant amounts of ibuprofen will experience symptoms within 4-6 hours.
The most commonly reported symptoms of overdose include: nausea, vomiting, abdominal pain, lethargy and somnolence.
Effects on the central nervous system (CNS) include headache, tinnitus, dizziness, seizures, and loss of consciousness.
Nystagmus, metabolic acidosis, hypothermia, renal effects, gastrointestinal bleeding, coma, apnea, diarrhea and CNS and respiratory depression have also been reported rarely. Disorientation, arousal state, fainting and cardiovascular toxicity including hypotension, bradycardia have been reported. and tachycardia.Renal failure and liver damage are possible in cases of significant overdose.
Treatment
There is no specific antidote to ibuprofen overdose. In the event of an overdose, symptomatic and supportive treatment is therefore indicated.
In case of accidental intake of an excessive dose of Brufen, notify your doctor immediately or go to the nearest hospital. If you have any questions about the use of Brufen, ask your doctor or pharmacist.
Side Effects What are the side effects of Brufen
Like all medicines, Brufen can cause side effects, although not everybody gets them.
The side effects seen with ibuprofen are generally common to other analgesics, antipyretics, non-steroidal anti-inflammatory drugs.
Gastrointestinal disorders: the most commonly observed adverse events are gastrointestinal in nature. Peptic ulcers, gastrointestinal perforation or haemorrhage, sometimes fatal, may occur, particularly in the elderly (see Precautions for use). Gastrointestinal perforation with the use of ibuprofen has been rarely observed.
Nausea, vomiting, diarrhea, flatulence, constipation, dyspepsia, epigastric pain, heartburn, abdominal pain, melaena, haematemesis, ulcerative stomatitis, exacerbation of colitis and Crohn's disease have been reported following administration of Brufen (see Precautions for use) .
Gastritis has been observed less frequently.
Pancreatitis has also been observed very rarely.
Disorders of the immune systemHypersensitivity reactions have been reported following treatment with NSAIDs. These may consist of a) non-specific allergic reaction and anaphylaxis, b) respiratory tract reactions including asthma, even severe, bronchospasm or dyspnoea or c) various skin disorders, including various types of rash, itching, urticaria, purpura, angioedema and, more rarely, exfoliative and bullous dermatitis (including Stevens-Johnson syndrome, toxic epidermal necrolysis and erythema multiforme).
Cardiac and vascular diseasesEdema, fatigue, hypertension and heart failure have been reported in association with NSAID treatment.
Medicines such as Brufen may be associated with a modest increased risk of heart attack ("myocardial infarction") or stroke.
Other less frequently reported adverse events for which causality has not necessarily been established include:
Disorders of the blood and lymphatic system: leukopenia, thrombocytopenia, neutropenia, agranulocytosis, aplastic anemia and haemolytic anemia.
Psychiatric disorders: insomnia, anxiety, depression, confusion, hallucinations. Nervous system disorders: headache, paraesthesia, dizziness, somnolence, optic neuritis.
Infections and infestations: rhinitis and aseptic meningitis (especially in patients with pre-existing autoimmune disorders, such as systemic lupus erythematosus and mixed connective tissue disease) with symptoms of neck stiffness, headache, nausea, vomiting, fever or disorientation (see Precautions for use). l "exacerbation of infection-related inflammations (eg development of necrotizing fasciitis). If signs of an infection appear or worsen while using Brufen you should see your doctor immediately.
Diseases of the respiratory system: bronchospasm, dyspnea, apnea.
Eye disorders: rare cases of ocular alteration with consequent visual disturbances, toxic optic neuropathy. Ear and labyrinth disorders: impaired hearing, tinnitus, vertigo.
Hepatobiliary disorders: impaired liver function, liver failure, hepatitis and jaundice.
Skin and subcutaneous tissue disorders: bullous reactions, including Stevens-Johnson syndrome and toxic epidermal necrolysis (very rare), and photosensitivity reactions. In exceptional cases, severe skin infections and soft tissue complications can occur during chickenpox infection (see Infections and Infestations).
Renal and urinary disorders: impairment of renal function and toxic nephropathy in various forms, including interstitial nephritis, nephrotic syndrome and renal failure. General disorders and administration site conditions: malaise, fatigue.
Compliance with the instructions contained in the package leaflet reduces the risk of undesirable effects.
Reporting of side effects
If you get any side effects, talk to your doctor or pharmacist. This includes any possible side effects not listed in this leaflet. You can also report side effects directly via the national reporting system at https://www.aifa.gov.it/content/segnalazioni-reazioni-avverse.
By reporting side effects you can help provide more information on the safety of this medicine.
Expiry and Retention
Expiry: see the expiry date indicated on the package
The expiry date refers to the product in intact packaging, correctly stored
Warning: do not use the medicine after the expiry date indicated on the package.
Medicines should not be disposed of via wastewater or household waste. Ask your pharmacist how to dispose of medicines you no longer use. This will help protect the environment.
Keep this medicine out of the sight and reach of children.
COMPOSITION
One 400 mg coated tablet contains: 400.0 mg ibuprofen. Excipients: microcrystalline cellulose, croscarmellose sodium, hydroxypropylmethylcellulose, lactose, sodium lauryl sulfate, magnesium stearate, Opaspray M-1-7111B White, colloidal anhydrous silica, talc.
PHARMACEUTICAL FORM AND CONTENT
400 mg coated tablets - 30 tablets
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
BRUFEN
02.0 QUALITATIVE AND QUANTITATIVE COMPOSITION
• BRUFEN 400 mg Coated tablets
One tablet contains:
Active principle:
Ibuprofen 400 mg
Excipients: lactose 26.7 mg
• BRUFEN 600 mg Coated tablets
One tablet contains:
Active principle:
Ibuprofen 600 mg
Excipients: lactose 40 mg
• BRUFEN 600 mg Effervescent granules
One sachet contains:
Active principle:
Ibuprofen 600 mg
Excipients: sucrose 1000 mg
For the full list of excipients, see section 6.1
03.0 PHARMACEUTICAL FORM
Coated tablets, effervescent granules.
04.0 CLINICAL INFORMATION
04.1 Therapeutic indications
As an antirheumatic in:
- osteoarthritis in all its localizations (cervical, dorsal, lumbar osteoarthritis; osteoarthritis of the shoulder, hip, knee, diffuse osteoarthritis, etc.), scapulo-humeral periarthritis, lumbago, sciatica, radiculo-neuritis; fibrositis, tenosynovitis, myositis, sports traumatology, rheumatoid arthritis, Still's disease.
As an analgesic in painful forms of different etiology:
- in accidental and sports traumatology;
- in dental practice, in post-extraction pain and after odontostomatological interventions;
- in obstetrics: in post-episiotomic and post-partum pain;
- in gynecology: in the prevention and treatment of dysmenorrhea;
- in surgery: in the treatment of post-operative pain;
- in ophthalmology: in post-operative pain and painful forms of various etiology;
- in general medicine: in the treatment of migraine and headache.
04.2 Posology and method of administration
400 mg tablets: 2 - 4 tablets per day in the opinion of the doctor.
600 mg tablets and granules: 1 - 3 tablets per day in the opinion of the doctor.
The maximum daily dose of Brufen should not exceed 1800 mg. In rheumatology, to improve morning stiffness, the first oral dose is administered when the patient awakens; subsequent doses can be taken with meals.
In the presence of renal insufficiency, elimination can be reduced and the dosage should be adjusted accordingly.
In the treatment of elderly patients, the dosage must be carefully established by the physician who will have to evaluate a possible reduction of the dosages indicated above.
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).
04.3 Contraindications
Hypersensitivity to the active substance or to any of the excipients.
Subjects with hypersensitivity to acetylsalicylic acid or to other analgesics, antipyretics, non-steroidal anti-inflammatory drugs (NSAIDs), particularly when hypersensitivity is associated with nasal polyposis, angioedema and / or asthma.
Severe hepatic insufficiency.
Severe renal insufficiency (glomerular filtration less than 30ml / min).
Severe heart failure.
Severe or active peptic ulcer.
History of gastrointestinal bleeding or perforation related to previous active treatments or history of recurrent peptic ulcer / haemorrhage (two or more distinct episodes of proven ulceration or bleeding).
Ibuprofen should not be given to patients with medical conditions that lead to an increased bleeding tendency
Ibuprofen is contraindicated during the third trimester of pregnancy (see section 4.6).
04.4 Special warnings and appropriate precautions for use
The concomitant use of Brufen with other NSAIDs, including selective cyclooxygenase-2 (COX-2) inhibitors, should be avoided due to an increased risk of ulceration or bleeding (see section 4.5).
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).
Like other NSAIDs, ibuprofen can mask signs of infection.
Senior citizens
Elderly patients have an increased frequency of adverse reactions to NSAIDs, especially gastrointestinal bleeding and perforation, which can be fatal (see section 4.2).
Gastrointestinal bleeding, ulceration and perforation
Gastrointestinal bleeding, ulceration and perforation, which can be fatal, have been reported during treatment with all NSAIDs at any time, with or without warning symptoms or a previous history of serious gastrointestinal events.
In the elderly and in patients with a history of ulcer, particularly if complicated with haemorrhage or perforation (see section 4.3), the risk of gastrointestinal bleeding, ulceration or perforation is higher with increasing doses of NSAIDs. These patients should start treatment with the lowest available dose. Concomitant use of gastroprotective 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 section "Interactions").
Patients with a history of gastrointestinal toxicity, particularly the elderly, should report any unusual gastrointestinal symptoms (especially gastrointestinal bleeding) particularly in the initial stages of treatment.
Caution should be exercised in patients taking concomitant medications that may increase the risk of ulceration or bleeding, such as oral corticosteroids, anticoagulants such as warfarin, selective reuptake serotonin (SSRIs) or antiplatelet agents such as acetylsalicylic acid (see section 4.5).
When gastrointestinal bleeding or ulceration occurs in patients taking Brufen the treatment should be discontinued.
NSAIDs should be administered with caution to patients with a history of gastrointestinal disease (ulcerative colitis, Crohn's disease) as these conditions may be exacerbated (see section 4.8).
Use with caution even in patients with coagulation defects.
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 ibuprofen, especially at high doses (2400 mg / day) and for long-term treatment, may be associated with a modest increased risk of arterial thrombotic events (eg myocardial infarction or stroke) In general, epidemiological studies do not suggest that low doses of ibuprofen (e.g. ≤ 1200 mg / day) are associated with an increased risk of myocardial infarction.
Patients with uncontrolled hypertension, congestive heart failure, established ischemic heart disease, peripheral arterial disease and / or cerebrovascular disease should only be treated with ibuprofen after careful consideration. Similar considerations should be made before initiating long-term treatment in patients with risk factors for cardiovascular events (eg, hypertension, hyperlipidaemia, diabetes mellitus, smoking).
Dermatological effects
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 section 4.8). 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. Treatment with Brufen should be discontinued at the first appearance of skin rash, mucosal lesions or any other signs of hypersensitivity, as well as if visual disturbances or persistent signs of liver dysfunction occur.
Kidney effects
When initiating treatment with ibuprofen, caution should be exercised in patients with considerable dehydration.
Long-term use of ibuprofen, as with other NSAIDs, has led to renal papillary necrosis and other renal pathological changes.
In general, the habitual use of analgesics, especially combinations of different analgesic active ingredients, can lead to permanent renal lesions, with the risk of renal failure (analgesic nephropathy).
Renal toxicity has been reported in patients in whom renal prostaglandins have a compensatory role in maintaining renal perfusion. Administration of NSAIDs in these patients may result in a dose-dependent reduction in prostaglandin formation and, as a secondary effect, in renal blood flow. This can quickly lead to kidney failure.
Patients most at risk of these reactions are those with reduced kidney function, heart failure, liver dysfunction, the elderly and all those patients taking diuretics and ACE inhibitors. Discontinuation of NSAID therapy is usually followed by recovery from the pretreatment state.
In case of prolonged use, monitor renal function, particularly in the case of diffuse lupus erythematosus.
Respiratory disorders
Brufen should be prescribed with caution in patients with bronchial asthma or current or previous allergic disease as bronchospasm may develop. The same applies to those subjects who have experienced bronchospasm after the use of aspirin or other NSAIDs.
Hypersensitivity reactions
Analgesics, antipyretics, non-steroidal anti-inflammatory drugs can cause hypersensitivity reactions, potentially serious (anaphylactoid reactions), even in subjects not previously exposed to this type of drug.The risk of hypersensitivity reactions after taking ibuprofen is higher in subjects who have presented these reactions after the use of other analgesics, antipyretics, non-steroidal anti-inflammatory drugs and in subjects with bronchial hyperreactivity (asthma), nasal polyposis or previous episodes of angioedema (see sections 4.3 and 4.8).
Reduced cardiac, renal and hepatic function
Particular caution should be exercised when treating patients with impaired cardiac, hepatic or renal function. In such patients, periodic monitoring of clinical and laboratory parameters should be used, especially in case of prolonged treatment.
Hematological effects
Ibuprofen, like other NSAIDs, can inhibit platelet aggregation and has been shown to prolong bleeding time in healthy subjects.
Aseptic meningitis
On rare occasions, aseptic meningitis has been observed in patients receiving ibuprofen.
Although this is more likely to occur in patients with systemic lupus erythematosus and related connective tissue disorders, it has also been observed in patients who did not have concomitant chronic diseases (see section 4.8).
Since ocular changes have been detected in animal studies with non-steroidal anti-inflammatory drugs, it is recommended, in case of prolonged treatments, to carry out periodic ophthalmological checks.
The use of Brufen, as with any prostaglandin synthesis and cyclooxygenase inhibitor drug, is not recommended in women intending to become pregnant (see also section 4.6).
Brufen should be discontinued in women who have fertility problems or who are undergoing fertility investigations.
Brufen tablets contain lactose: Patients with rare hereditary problems of galactose intolerance, lactase deficiency or glucose-galactose malabsorption should not take this medicine.
Brufen granules contain sucrose: Patients with rare hereditary problems of fructose intolerance, sucrase-isomaltase deficiency or glucose-galactose malabsorption should not take this medicine.
04.5 Interactions with other medicinal products and other forms of interaction
Ibuprofen (like other NSAIDs) should be used with caution in combination with:
corticosteroids : increased risk of gastrointestinal ulceration or bleeding (see section 4.4);
anticoagulants : NSAIDs may increase the effects of anticoagulants, such as warfarin (see section 4.4). Patients being treated with coumarins should be monitored;
acetylsalicylic acid and other NSAIDs : these substances may increase the risk of adverse reactions affecting the gastrointestinal tract (see section 4.4). Experimental data indicate that ibuprofen may inhibit the effects of low-dose acetylsalicylic acid on platelet aggregation when drugs are administered concomitantly. However, the limited data and uncertainties relating to their application to the clinical situation do not allow to draw firm conclusions for continued use of ibuprofen; there appears to be no clinically relevant effect from occasional use of ibuprofen (see section 5.1). However, it is advisable not to combine ibuprofen with aspirin or other NSAIDs;
antiplatelet agents and selective serotonin reuptake inhibitors (SSRIs) : increased risk of gastrointestinal bleeding (see section 4.4);
diuretics, ACE inhibitors and angiotensin II antagonists : NSAIDs may reduce the effect of diuretics and other antihypertensive drugs. Diuretics may also increase the risk of NSAID-associated nephrotoxicity.
In some patients with impaired renal function (e.g. dehydrated or elderly patients) 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 function. renal failure, which includes possible acute renal failure, usually reversible. These interactions should be considered in patients taking Brufen concomitantly with ACE inhibitors or angiotensin II antagonists. Therefore, this 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 periodically thereafter;
lithium : the simultaneous administration of lithium and NSAIDs causes an increase in plasma lithium levels due to reduced elimination, with the possibility of reaching the toxic threshold. If this combination is necessary, lithemia should be monitored in order to adapt the lithium dosage during concomitant treatment with ibuprofen;
methotrexate : NSAIDs can inhibit the tubular secretion of methotrexate and reduce its clearance with a consequent increase in the risk of toxicity;
aminoglycosides : NSAIDs can decrease the excretion of aminoglycosides;
cardiac glycosides : NSAIDs can exacerbate heart failure, reduce glomerular filtration rate and increase plasma levels of cardiac glycosides;
cholestyramine : the concomitant administration of ibuprofen and cholestyramine may reduce the absorption of ibuprofen from the gastrointestinal tract. However, the clinical relevance of this interaction is unknown;
cyclosporine : increase the risk of nephrotoxicity with NSAIDs;
Cox-2 inhibitors and other NSAIDs : concomitant use with other NSAIDs, including selective cyclooxygenase-2 inhibitors, should be avoided due to potential additive effect (see section 4.4);
plant extracts : Ginkgo Biloba may increase the risk of bleeding in combination with NSAIDs;
mifepristone : Due to the anti-prostaglandin properties of NSAIDs, a decrease in drug efficacy may theoretically occur. Limited evidence suggests that co-administration of NSAIDs on the day of prostaglandin administration does not adversely affect the effects of mifepristone or prostaglandin on cervical ripening or uterine contractility and does not reduce the clinical efficacy of the drug on pregnancy termination;
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 seizures;
sulfonylureas : NSAIDs may increase the effect of sulfonylureas. Rare cases of hypoglycaemia have been reported in patients receiving sulfonylureas taking ibuprofen;
tacrolimus : Possible increased risk of nephrotoxicity when NSAIDs are administered with tacrolimus;
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;
ritonavir : an increase in the concentration of NSAIDs is possible;
probenecid : slows down the excretion of NSAIDs, with possible increase in their plasma concentrations;
CYP2C9 inhibitors : Concomitant administration of ibuprofen and CYP2C9 inhibitors may increase exposure to ibuprofen (CYP2C9 substrate). In a study with voriconazole and fluconazole (CYP2C9 inhibitors), increased exposure to S (+) - ibuprofen from approximately 80% to 100% was observed. Reduction of the dose of ibuprofen should be considered when administering them. concomitantly strong inhibitors of CYP2C9, particularly when high doses of ibuprofen are administered with voriconazole or fluconazole.
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 is believed 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. embryofetal.
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, Brufen should not be administered unless strictly necessary.
If Brufen 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, and antiplatelet effect which may occur even at very low doses;
Inhibition of uterine contractions resulting in delayed or prolonged labor.
Consequently, Brufen is contraindicated during the third trimester of pregnancy.
Feeding time
In the few studies available to date, NSAIDs can be found in breast milk in very low concentrations. If possible, NSAIDs should be avoided during breastfeeding.
Fertility
The use of Ibuprofen may impair female fertility and is not recommended in women attempting to conceive. In women who have difficulty conceiving or who are being investigated for infertility, discontinuation of ibuprofen treatment should be considered.
04.7 Effects on ability to drive and use machines
Undesirable effects such as dizziness, sleepiness, fatigue and visual disturbances may occur after taking ibuprofen. This should be taken into consideration when greater vigilance is required such as when driving a car or operating machinery.
04.8 Undesirable effects
The side effects seen with ibuprofen are generally common to other analgesics, antipyretics, non-steroidal anti-inflammatory drugs.
Gastrointestinal disorders: the most commonly observed adverse events are gastrointestinal in nature. Peptic ulcers, gastrointestinal perforation or haemorrhage, sometimes fatal, may occur, particularly in the elderly (see section 4.4). Gastrointestinal perforation with the use of ibuprofen has been rarely observed.
Nausea, vomiting, diarrhea, flatulence, constipation, dyspepsia, epigastric pain, heartburn, abdominal pain, melaena, haematemesis, ulcerative stomatitis, exacerbation of colitis and Crohn's disease have been reported following administration of Brufen (see section 4.4).
Gastritis has been observed less frequently.
Pancreatitis has also been observed very rarely.
Disorders of the immune systemHypersensitivity reactions have been reported following treatment with NSAIDs. These may consist of a) non-specific allergic reaction and anaphylaxis, b) respiratory tract reactions including asthma, even severe, bronchospasm or dyspnoea or c) various skin disorders, including various types of rash, itching, urticaria, purpura, angioedema and, more rarely, exfoliative and bullous dermatitis (including Stevens-Johnson syndrome, toxic epidermal necrolysis and erythema multiforme).
Cardiac and vascular diseasesEdema, fatigue, hypertension and heart failure have been reported in association with NSAID treatment. Clinical studies and epidemiological data suggest that the use of ibuprofen, especially at high doses (2400 mg / day) and for long-term treatment, may be associated with a modest increased risk of arterial thrombotic events (eg. myocardium or stroke) (see section 4.4).
Other less frequently reported adverse events for which causality has not necessarily been established include:
Disorders of the blood and lymphatic system: leukopenia, thrombocytopenia, neutropenia, agranulocytosis, aplastic anemia and haemolytic anemia.
Psychiatric disorders: insomnia, anxiety, depression, confusion, hallucinations.
Nervous system disorders: headache, paraesthesia, dizziness, somnolence, optic neuritis.
Infections and infestations: rhinitis and aseptic meningitis (especially in patients with pre-existing autoimmune disorders, such as systemic lupus erythematosus and mixed connective tissue disease) with symptoms of neck stiffness, headache, nausea, vomiting, fever or disorientation (see section 4.4).
Diseases of the respiratory system: bronchospasm, dyspnea, apnea.
Eye disorders: rare cases of ocular alteration with consequent visual disturbances, toxic optic neuropathy.
Ear and labyrinth disorders: impaired hearing, tinnitus, vertigo.
Hepatobiliary disorders: impaired liver function, liver failure, hepatitis and jaundice.
Skin and subcutaneous tissue disorders: bullous reactions, including Stevens-Johnson syndrome and toxic epidermal necrolysis (very rare), and photosensitivity reactions.
Renal and urinary disorders: impairment of renal function and toxic nephropathy in various forms, including interstitial nephritis, nephrotic syndrome and renal failure.
General disorders and administration site conditions: malaise, fatigue.
04.9 Overdose
Toxicity
Signs and symptoms of toxicity were generally not observed at doses below 100 mg / kg in children or adults. However, supportive treatment may be required in some cases. Children have been observed to exhibit signs and symptoms of toxicity after ingestion of ibuprofen at doses of 400 mg / kg or greater.
Symptoms
Most patients who have ingested significant amounts of ibuprofen will experience symptoms within 4-6 hours.
The most commonly reported symptoms of overdose include: nausea, vomiting, abdominal pain, lethargy and somnolence.
Effects on the central nervous system (CNS) include headache, tinnitus, dizziness, seizures, and loss of consciousness.
Nystagmus, metabolic acidosis, hypothermia, renal effects, gastrointestinal bleeding, coma, apnea, diarrhea and CNS and respiratory depression have also been reported rarely.
Disorientation, arousal state, fainting and cardiovascular toxicity including hypotension, bradycardia and tachycardia have been reported. In cases of significant overdose, renal failure and liver damage are possible.
Treatment
There is no specific antidote to ibuprofen overdose.
In the event of an overdose, symptomatic and supportive treatment is therefore indicated. Particular attention is due to the control of blood pressure, acid-base balance and any gastrointestinal bleeding.
Within one "hour" of ingestion of a potentially toxic amount, administration of activated charcoal should be considered. Alternatively, gastric lavage should be considered within one hour of ingestion of a potentially life-threatening overdose in adults.
Adequate diuresis must be ensured and renal and hepatic functions closely monitored.
The patient must remain under observation for at least four hours following the ingestion of a potentially toxic quantity of drug.
Any occurrence of frequent or prolonged seizures should be treated with intravenous diazepam. Other supportive measures may be necessary depending on the patient's clinical condition.
For more information, contact your local poison control center.
05.0 PHARMACOLOGICAL PROPERTIES
05.1 Pharmacodynamic properties
Pharmaco-therapeutic category: non-steroidal anti-inflammatory and antirheumatic drugs - derivatives of propionic acid. ATC code: M01AE01
Ibuprofen is a synthetic analgesic-anti-inflammatory, also endowed with a marked antipyretic activity. Chemically it is the progenitor of phenylpropionic derivatives. The analgesic activity is non-narcotic and is 8-30 times higher than that of acetylsalicylic acid.
Ibuprofen is a potent inhibitor of prostaglandin synthesis and exerts its activity by inhibiting its synthesis at the peripheral level.
Experimental data indicate that ibuprofen may inhibit the effects of low-dose acetylsalicylic acid on platelet aggregation when the drugs are administered concomitantly. In one study, following administration of a single 400 mg dose of ibuprofen, taken within 8 hours before or 30 minutes after the administration of acetylsalicylic acid (81 mg), there was a decrease in the effect of acetylsalicylic acid on thromboxane formation and platelet aggregation. However, the limited data and the uncertainties relating to their application to the clinical situation do not allow definitive conclusions to be drawn in relation to the continued use of ibuprofen; there appears to be no clinically relevant effect with the occasional use of ibuprofen.
05.2 Pharmacokinetic properties
Ibuprofen is well absorbed after oral and rectal administration; taken on an empty stomach produces maximum serum levels in humans after about 45 minutes.The administration of equal doses preceded by ingestion of food revealed a slower absorption and the achievement of maximum levels in a period of time ranging from a minimum of one and a half hours to a maximum of three hours. The plasma half-life of the molecule is about two hours. Ibuprofen is metabolised in the liver to two inactive metabolites and these, together with unchanged ibuprofen, are excreted by the kidney both as such and conjugated. Excretion is rapid and serum levels show no signs of accumulation. 44% of a dose of ibuprofen is recovered in the urine as two pharmacologically inert metabolites and 20% as drug as such.
05.3 Preclinical safety data
The LD50 in albino mice is 800 mg / kg per os; while in the rat, again per os, it is 1600 mg / kg. However, it should be noted that the administration of NSAIDs to pregnant rats can lead to restriction of the fetal ductus arteriosus.
In animal experiments the chronic and subchronic toxicity of ibuprofen mainly manifested itself in the form of lesions and ulcerations of the gastrointestinal tract. in vitro and in vivo have not given clinical relevance of the mutagenic potential of ibuprofen. In studies in rats and mice there was no evidence of the carcinogenic effects of ibuprofen.
Ibuprofen leads to ovulation inhibition in rabbits, as well as implantation disturbance in various animal species (rabbits, rats, mice). Experimental research has shown that ibuprofen passes through the placenta; with maternally toxic doses, an increased incidence of malformations (eg ventricular septal defects) has been observed.
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
• BRUFEN 400 mg and 600 mg Tablets
Microcrystalline cellulose, croscarmellose sodium, hydroxypropylmethylcellulose, lactose, sodium lauryl sulfate, magnesium stearate, Opaspray M-1-7111B White, colloidal anhydrous silica, talc.
• BRUFEN 600 mg Granules
Malic acid, orange flavor, povidone, sucrose, sodium bicarbonate, anhydrous sodium carbonate, sodium lauryl sulfate, sodium saccharinate.
06.2 Incompatibility
There are no known physical-chemical incompatibilities of ibuprofen with other compounds.
06.3 Period of validity
Tablets: 3 years
Granulate: 2 years
06.4 Special precautions for storage
BRUFEN 600 mg Granules must be stored at a temperature not exceeding 25 ° C.
06.5 Nature of the immediate packaging and contents of the package
Tablets
Carton containing 30 tablets of 400 mg in blister (PVC / Alu)
Carton containing 30 tablets of 600 mg in blister (PVC / Alu)
Granulated
Box containing 10 sachets (paper / polythene / aluminum / polythene) of 600 mg granules
Carton containing 30 sachets (paper / polythene / aluminum / polythene) of 600 mg granules
06.6 Instructions for use and handling
None.
07.0 MARKETING AUTHORIZATION HOLDER
ABBOTT S.r.l. - S.R. 148 Pontina km 52 snc - 04011 CAMPOVERDE di APRILIA (LT)
08.0 MARKETING AUTHORIZATION NUMBER
30 tablets of 400 mg in PVC / Alu blister - A.I.C .: n. 022593204
30 tablets of 600 mg in PVC / Alu blister - A.I.C .: n. 022593216
10 sachets of 600 mg granules - A.I.C .: n. 022593178
30 sachets of 600 mg granules - A.I.C .: n. 022593103
09.0 DATE OF FIRST AUTHORIZATION OR RENEWAL OF THE AUTHORIZATION
30 tablets of 400 mg in PVC / Alu blisters: 09.06.2006
30 tablets of 600 mg in PVC / Alu blisters: 09.06.2006
10 sachets of 600 mg granules: 20.12.1999
30 sachets of 600 mg granules: 01.06.1990
Authorization renewal: 01.06.2010
10.0 DATE OF REVISION OF THE TEXT
AIFA determination of 03/04/2012
