Buscofen 12 Soft Capsules 200mg

INDICATIONS

Pain of various origins and nature (menstrual pain, headache, toothache, neuralgia, osteoarticular and muscular pain).

ACTIVE INGREDIENTS

Coated tablets: 1 tablet contains: ibuprofen 200 mg Soft gelatin capsules: 1 soft capsule contains: ibuprofen 200 mg For the full list of excipients, see section 6.1.

EXCIPIENTS

Coated tablets - blister pack of 20 tablets Corn starch, sodium carboxymethyl starch, magnesium stearate, hydroxypropyl methylcellulose, polyethylene glycol 6000, talc, titanium dioxide, anti-foam emulsion. Soft capsules - blisters of 12 or 24 capsules Macrogol 600, potassium hydroxide, purified water, gelatin, partially dehydrated liquid sorbitol.

CONTRAINDICATIONS AND SIDE EFFECTS

- Hypersensitivity to the active substance or to any of the excipients. - Subjects with hypersensitivity to acetylsalicylic acid or other analgesics, antipyretics, non-steroidal anti-inflammatory drugs (NSAIDs), in particular when hypersensitivity is associated with nasal polyposis, angioedema and/or asthma. - Severe liver failure. - Severe renal insufficiency (glomerural filtration less than 30 ml/min). - Severe heart failure (NYHA class IV). - Subjects suffering from blood dyscrasias of unknown origin, porphyria, hypertension, severe uncontrolled coronary insufficiency. - Severe or active peptic ulcer. - History of gastrointestinal hemorrhage or perforation related to previous active treatments or history of recurrent peptic hemorrhage/ulcer (two or more distinct episodes of demonstrated ulceration or bleeding). - Subjects with clinical conditions that cause an increased tendency to bleeding. - In conjunction with surgical interventions (including dental operations). - Subjects who have suffered significant fluid losses (due to vomiting, diarrhea or poor fluid intake). - During the third trimester of pregnancy (see par. 4.6). - Children under 12 years old.

DOSAGE

Do not administer to children under 12 years of age. Side effects can be minimized by using the lowest effective dose for the shortest possible treatment duration needed to control symptoms (see section 4.4). Coated tablets Adults and adolescents over 12 years old 1-2 tablets, two - three times a day, preferably on a full stomach. However, do not exceed the dose of 1200 mg (6 tablets) per day. Do not exceed the recommended doses. If the use of the medicine is necessary for more than 3 days in adolescents, or in the case of worsening of symptoms, the doctor should be consulted. Elderly Elderly patients must adhere to the minimum doses indicated. Patients with renal failure In the presence of renal insufficiency, elimination may be reduced and the dosage should be adjusted accordingly. Soft capsules Adults and adolescents over 12 years old 1-2 soft capsules, two - three times a day, preferably on a full stomach. However, do not exceed the dose of 1200 mg (6 soft capsules) per day. Do not exceed the recommended doses. If the use of the medicine is necessary for more than 3 days in adolescents, or in the case of worsening of symptoms, the doctor should be consulted. Elderly Elderly patients must adhere to the minimum doses indicated. Patients with renal failure In the presence of renal insufficiency, elimination may be reduced and the dosage should be adjusted accordingly. Buscofen should not be used for more than 7 days. If higher doses are necessary or if longer treatment is required, then you should contact your doctor. The coated tablets and soft capsules should be swallowed without chewing, preferably with a little water. It is recommended to take it during or after meals, particularly for people with gastric disorders.

CONSERVATION

Coated tablets - blister pack of 20 tablets Store at room temperature. Soft capsules - blisters of 12 or 24 capsules No storage conditions.

WARNINGS

The use of Buscofen concomitantly 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). Side effects can be minimized by using the lowest effective dose for the shortest duration of treatment needed to control symptoms (see paragraphs below on gastrointestinal and cardiovascular risks). Pediatric population In dehydrated adolescents there is a risk of impaired renal function. Elderly Elderly patients have an increased frequency of adverse reactions to NSAIDs, especially gastrointestinal bleeding and perforation, which may be fatal (see section 4.2). Gastrointestinal haemorrhage, ulceration and perforation Gastrointestinal haemorrhage, ulceration and perforation which may be fatal have been reported during treatment with all NSAIDs, at any time, with or without warning symptoms or previous history of serious gastrointestinal events. In the elderly and in patients with a history of ulcer, especially if complicated by haemorrhage or perforation (see section 4.3), the risk of gastrointestinal haemorrhage, ulceration or perforation is higher with increased doses of NSAIDs. These patients should start treatment with the lowest available dose. For these patients and also for patients taking low doses of acetylsalicylic acid or other drugs that may increase the risk of gastrointestinal events, the concomitant use of protective agents (misoprostol or proton pump inhibitors) should be considered (see below and section 4.5). 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 by patients taking concomitant medications that may increase the risk of ulceration or bleeding, such as oral corticosteroids, anticoagulants such as warfarin, selective reuptake serotonin (SSRI) or antiplatelet agents such as acetylsalicylic acid (see section 4.5). When gastrointestinal bleeding or ulceration occurs in patients taking Buscofen, 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 in patients with coagulation defects. 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 and edema have been found in association with treatment with NSAIDs. Clinical studies suggest that the use of ibuprofen, especially at high doses (2400 mg/day), may be associated with a modest increase in the risk of arterial thrombotic events (e.g. 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 arterial thrombotic events. Patients with uncontrolled hypertension, congestive heart failure (NYHA class II-III), established ischemic heart disease, peripheral arterial disease and/or cerebrovascular disease should be treated with ibuprofen only after careful consideration and high doses (2400 mg/day) should be avoided. Careful consideration must also be exercised before starting patients with risk factors for cardiovascular events (e.g. hypertension, hyperlipidemia, diabetes mellitus, cigarette smoking habit) on long-term treatment, especially if high doses (2400 mg/day) of ibuprofen are necessary. Severe 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 (see section 4.8). In the early stages of therapy, patients appear to be exposed to higher risk; the onset of the reaction occurs in most cases within the first month of treatment. Acute generalized exanthematous pustulosis (PEAG) has been reported in connection with ibuprofen-containing medicinal products. Treatment with Buscofen should be discontinued at the first appearance of skin rash, mucosal lesions or any other sign of hypersensitivity. Masking of symptoms of underlying infections Buscofen may mask the symptoms of infection, which could delay starting appropriate treatment and therefore worsen the outcome of the infection. This has been observed in community-acquired bacterial pneumonia and bacterial complications of chickenpox. When Buscofen is administered for the relief of fever or pain related to infection, monitoring of the infection is recommended. In non-hospital settings, the patient should seek medical attention if symptoms persist or worsen. Renal 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 kidney damage with the risk of onset of renal failure (analgesic nephropathy). Renal toxicity has been reported in patients in whom renal prostaglandins have a compensatory role in maintaining renal perfusion. The administration of NSAIDs in these patients may result in a dose-dependent reduction in prostaglandin formation and, as a secondary effect, renal blood flow. This can quickly lead to renal failure. The patients most at risk of these reactions are those with reduced renal 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 to the pretreatment state. In case of prolonged use, monitor renal function, particularly in cases of diffuse lupus erythematosus. Respiratory disorders Buscofen should be prescribed with caution in patients with bronchial asthma or current or previous allergic diseases because bronchospasm could occur. The same applies to those subjects who have experienced bronchospasm after using aspirin or other NSAIDs. Hypersensitivity reactions Analgesics, antipyretics, non-steroidal anti-inflammatories can cause potentially serious hypersensitivity reactions (anaphylactoid reactions), even in subjects not previously exposed to this type of drugs. The risk of hypersensitivity reactions after taking ibuprofen is greater in subjects who have experienced such 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 4.2 and 4.8). Reduced cardiac, renal and hepatic function Particular caution should be taken when treating patients with severely reduced cardiac, hepatic or renal function. In such patients it is advisable to resort to periodic monitoring of clinical and laboratory parameters, especially in case of prolonged treatment. Ibuprofen may cause an increase in serum concentrations of aminotransferases, and other markers of liver function, in patients without previous evidence of liver function disorders. These usually include relatively modest and transient increases over the normal range. If these abnormalities are clinically significant or if they are persistent then treatment with ibuprofen should be discontinued and the response following discontinuation of treatment monitored. Ibuprofen may cause sodium, potassium and water retention in patients who have not previously shown signs of kidney disease, due to the effect on renal perfusion. This may cause edema or cause acute decompensation of cardiac function or hypertension in predisposed individuals. Patients at greatest risk of overt renal failure are elderly people, dehydrated or hypovolemic patients, patients with congestive heart failure, cirrhosis, nephrotic syndrome, renal failure, those on diuretics and patients who have recently undergone surgery. Discontinuation of treatment is usually followed by a rapid return to pre-treatment renal function. Ibuprofen may also interfere with the natriuretic effects of diuretics. Hematological effects Ibuprofen, like other NSAIDs, can inhibit platelet aggregation and has shown evidence of prolonging bleeding time in healthy subjects. Aseptic meningitis On rare occasions, aseptic meningitis has been observed in patients receiving ibuprofen. Although it is more likely to occur in patients with systemic lupus erythematosus and related connective tissue diseases, it has also been observed in patients who did not have concomitant chronic diseases (see section 4.8). Since ocular alterations have been detected during 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 Buscofen, like any other drug that inhibits prostaglandin synthesis and cyclooxygenase, is not recommended in women intending to become pregnant (see also section 4.6). The administration of Buscofen should be suspended in women who have fertility problems or who are undergoing fertility investigations.

INTERACTIONS

Ibuprofen (like other NSAIDs) should be used with caution in association with: - corticosteroids: increased risk of gastrointestinal ulceration or haemorrhage (see section 4.4); - anticoagulants: NSAIDs may increase the effects of anticoagulants such as warfarin (see section 4.4). It is advisable to monitor patients being treated with coumarins; - acetylsalicylic acid and other NSAIDs: these substances may increase the risk of adverse reactions affecting the gastrointestinal tract (see section 4.4). Concomitant administration of ibuprofen and acetylsalicylic acid is generally not recommended due to the potential for increased side effects. Experimental data suggest that ibuprofen can competitively inhibit the effect of low-dose acetylsalicylic acid on platelet aggregation when the two drugs are administered simultaneously. Although there are uncertainties regarding the extrapolation of these data to the clinical situation, the possibility cannot be excluded that regular, long-term use of ibuprofen may reduce the cardioprotective effect of acetylsalicylic acid at low doses. No relevant clinical effects are considered likely following 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 can reduce the effect of diuretics and other antihypertensive drugs. Diuretics may also increase the risk of NSAID-associated nephrotoxicity. In some patients with compromised renal function (e.g. dehydrated or elderly patients) co-administration of an ACE inhibitor or an angiotensin II antagonist and agents that inhibit the cyclo-oxygenase system may lead to further deterioration of renal function, including possible acute renal failure, which is usually reversible. These interactions should be considered in patients taking Buscofen 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 consideration should be given to monitoring renal function after initiation of concomitant therapy and periodically thereafter; - lithium: the simultaneous administration of lithium and NSAIDs causes an increase in lithium levels in the blood due to reduced elimination, with the possibility of reaching the toxic threshold. If this association is necessary, monitor lithium levels in order to adapt the lithium dosage during simultaneous 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 the glomerular filtration rate and increase plasma levels of cardiac glycosides; - phenytoin: NSAIDs may lead to an increase in plasma concentrations of phenytoin; - cholestyramine: the concomitant administration of ibuprofen and cholestyramine can reduce the absorption of ibuprofen from the gastrointestinal tract. However, the clinical relevance of this interaction is unknown; - ciclosporins: increase the risk of nephrotoxicity with NSAIDs. - COX-2 inhibitors and other NSAIDs: concomitant use with other NSAIDs, including selective cyclooxygenase-2 inhibitors, must be avoided due to potential additive effect (see section 4.4); - plant extracts: Ginkgo Biloba may increase the risk of bleeding in association with NSAIDs; - mifepristone: Due to the antiprostaglandin properties of NSAIDs, a decrease in the effectiveness of the medicine may theoretically occur. Limited evidence suggests that co-administration of NSAIDs on the day of prostaglandin administration does not negatively influence the effects of mifepristone or prostaglandin on cervical maturation or uterine contractility and does not reduce the clinical efficacy of the medicinal product 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 can increase the effect of sulfonylureas. Rare cases of hypoglycemia have been reported in patients treated with sulfonylureas while taking ibuprofen; - tacrolimus: possible increased risk of nephrotoxicity when NSAIDs are administered with tacrolimus; - zidovudine: increased risk of blood toxicity in case of co-administration with NSAIDs. There is evidence of an increased risk of haemarthrosis and hematoma in haemophiliac patients affected by HIV in simultaneous treatment 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; - sulfinpyrazone : may delay the excretion of ibuprofen; - CYP2C9 inhibitors: Coadministration 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 by approximately 80% to 100% was observed. Reduction of the ibuprofen dose should be considered when strong CYP2C9 inhibitors are co-administered, particularly when high doses of ibuprofen are administered with voriconazole and fluconazole.

SIDE EFFECTS

The side effects observed 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, perforation or gastrointestinal haemorrhage, sometimes fatal, may occur, particularly in the elderly (see section 4.4). Gastrointestinal perforation with ibuprofen use has been observed rarely. After administration of Buscofen the following have been reported: nausea, vomiting, diarrhea, flatulence, constipation, dyspepsia, epigastric pain, heartburn, abdominal pain, melena, hematemesis, ulcerative stomatitis, exacerbation of colitis and Crohn's disease (see section 4.4). Less frequently, gastritis has been observed. Pancreatitis has also been observed very rarely. Immune system disorders: Hypersensitivity reactions have been reported following treatment with NSAIDs. These may consist of a) non-specific allergic reaction and anaphylaxis, b) reactions affecting the respiratory tract including asthma, even severe, bronchospasm or dyspnea or c) skin disorders, including rashes of various types, pruritus, urticaria, purpura, angioedema and, more rarely, exfoliative and bullous dermatitis (including Stevens - Johnson syndrome, toxic epidermal necrolysis and erythema multiforme). Cardiac and vascular pathologies: Edema and fatigue, hypertension and heart failure have been reported in association with NSAID treatment. Clinical studies suggest that the use of ibuprofen, especially at high doses (2400 mg/day), may be associated with a modest increase in the risk of arterial thrombotic events (e.g. myocardial infarction or stroke) (see section 4.4). Other adverse events reported less frequently and for which causality has not necessarily been established include: Pathologies of the blood and lymphatic system: leukopenia, thrombocytopenia, neutropenia, agranulocytosis, aplastic anemia and hemolytic anemia. Psychiatric disorders: insomnia, anxiety, depression, confusional state, hallucinations. Nervous system disorders: headache, paraesthesia, dizziness, drowsiness, 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). Respiratory, thoracic and mediastinal disorders: bronchospasm, dyspnea, apnea. Eye pathologies: rare cases of ocular alteration resulting in visual disturbances, toxic optic neuropathy.Ear and labyrinth disorders: impaired hearing, tinnitus, dizziness. Hepatobiliary disorders: impaired liver function, liver failure, hepatitis and jaundice. Pathologies of the skin and subcutaneous tissue: bullous reactions including Stevens-Johnson syndrome and toxic epidermal necrolysis (very rare), photosensitivity reactions and drug reaction with eosinophilia and systemic symptoms (DRESS syndrome) (frequency not known), acute generalized exanthematous pustulosis (PEAG) (frequency not known). Renal and urinary disorders: impairment of renal function and toxic nephropathy in various forms, including interstitial nephritis, nephrotic syndrome and renal failure. Systemic pathologies and conditions relating to the administration site: malaise, fatigue. Reporting of suspected adverse reactions Reporting suspected adverse reactions that occur after authorization of the medicine is important, as it allows continuous monitoring of the benefit/risk balance of the medicine. Healthcare professionals are asked to report any suspected adverse reactions via the national reporting system at https://www.aifa.gov.it/content/segnalazioni-reazioni-avverse.

OVERDOSE

Toxicity Signs and symptoms of toxicity were generally not observed at doses below 100 mg/kg in children or adults. However, in some cases supportive treatment may be necessary. Children have been observed to exhibit signs and symptoms of toxicity after ingesting ibuprofen at doses of 400 mg/kg or greater. Symptoms Most patients who have ingested significant amounts of ibuprofen will experience symptoms within 4 to 6 hours. The most commonly reported overdose symptoms include nausea, vomiting, abdominal pain, lethargy, and drowsiness. Central nervous system (CNS) effects 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, fainting and cardiovascular toxicity including hypotension, bradycardia and tachycardia have been reported. In cases of significant overdose, renal failure and liver damage are possible. In cases of severe poisoning, metabolic acidosis may occur. Treatment There is no specific antidote for ibuprofen overdose. In case of 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. Administration of activated charcoal should be considered within 1 hour of ingestion of a potentially toxic quantity. Alternatively, in adults, gastric lavage should be considered within 1 hour of ingestion of a potentially life-threatening overdose. Adequate diuresis must be ensured and renal and hepatic functions must be closely monitored. The patient must remain under observation for at least four hours following ingestion of a potentially toxic amount of drug. Any occurrence of frequent or prolonged convulsions should be treated with intravenous diazepam. Depending on the patient's clinical condition, other support measures may be necessary. For more information, contact your local poison control center.

PREGNANCY AND BREASTFEEDING

Pregnancy Inhibition of prostaglandin synthesis can negatively affect pregnancy and/or embryo/foetal development. Data obtained from epidemiological studies suggest an increased risk of miscarriage, cardiac malformation and gastroschisis after the use of a prostaglandin synthesis inhibitor during early pregnancy. The absolute risk of cardiac malformations increased from less than 1% to approximately 1.5%. The risk is thought to increase with the dose and duration of therapy. In animals, the administration of prostaglandin synthesis inhibitors has been shown to cause an increase in pre- and post-implantation loss and embryo-foetal mortality. Furthermore, an increased incidence of various malformations, including cardiovascular malformations, has been reported in animals administered prostaglandin synthesis inhibitors during the organogenetic period. During the first and second trimester of pregnancy, ibuprofen should not be administered unless strictly necessary. When used by women in the process of conceiving or during the first and second trimester of pregnancy, the dose and duration of treatment should be as low and as short as possible, respectively. During the third trimester of pregnancy, all inhibitors of prostaglandin synthesis can expose the fetus to: - cardiopulmonary toxicity (with premature closure of the ductus arteriosus and pulmonary hypertension); - renal dysfunction, which can progress to renal failure with oligo-hydramnios; the mother and the newborn, at the end of pregnancy, to: - possible prolongation of bleeding time and anti-aggregating effect which can occur even at very low doses; - inhibition of uterine contractions resulting in delayed or prolonged labor. Consequently, ibuprofen is contraindicated during the third trimester of pregnancy. Breastfeeding In the few studies available to date, NSAIDs can be found in breast milk in very low concentrations. NSAIDs, if possible, should be avoided during breastfeeding. Fertility The use of ibuprofen may compromise female fertility and is not recommended in women trying to conceive. In women who have difficulty conceiving or who are undergoing fertility investigations, discontinuation of ibuprofen treatment should be considered.

EFFECTS ON DRIVING ABILITY

Following the intake of ibuprofen it is possible to experience side effects such as dizziness, drowsiness, fatigue and vision problems. This should be taken into consideration when increased vigilance is required such as when driving a car or operating machinery.