Buscofenact 400mg 20 soft capsules

INDICATIONS

Short-term symptomatic treatment of: - mild to moderate pain such as headache, toothache and menstrual pain; - fever and pain associated with the common cold. BuscofenAct is indicated in adults and adolescents with a body weight greater than 40 kg (12 years of age and older).

ACTIVE INGREDIENTS

One soft capsule contains 400 mg of ibuprofen. Excipients with known effect: Sorbitol 95.94 mg/capsule (see section 4.4). For the full list of excipients, see section 6.1.

EXCIPIENTS

Capsule contents: Macrogol 600 Potassium hydroxide Purified water Capsule shell : Gelatin Liquid sorbitol Purified water Printing ink Ingredients of Opacode WB black NS-78-17821: Black iron oxide (E172) Propylene glycol (E1520) Hypromellose 6cP

CONTRAINDICATIONS AND SIDE EFFECTS

BuscofenAct soft capsules are contraindicated in case of: - hypersensitivity to ibuprofen or to any of the excipients listed in paragraph 6.1; - history of hypersensitivity (e.g. bronchospasm, asthma, rhinitis, angioedema or urticaria) associated with the intake of acetylsalicylic acid or other non-steroidal anti-inflammatory drugs (NSAIDs); - haematological disorders of unknown origin; - history of recurrent or ongoing peptic ulcer/haemorrhage (two or more distinct episodes of proven ulceration or bleeding); - history of gastrointestinal bleeding or perforation, related to previous NSAID therapy; - cerebrovascular haemorrhage or other bleeding episodes; - severe heart failure (NYHA class IV) (see also section 4.4); - severe hepatic insufficiency or severe renal insufficiency (see also section 4.4); - patients in the third trimester of pregnancy (see section 4.6); - adolescents with body weight below 40 kg and children under 12 years of age; - patients with severe dehydration (due to vomiting, diarrhea or insufficient fluid intake).

DOSAGE

Dosage Adults and adolescents with body weight > 40 kg (12 years of age and older): initial dose of 400 mg of ibuprofen. If necessary, an additional 400 mg dose of ibuprofen can be taken. The interval between one dose and another must be established based on the symptoms observed and the maximum recommended daily dose, and must not be less than 6 hours. Do not take more than 1200 mg of ibuprofen in 24 hours. For short term treatments only. Undesirable effects can be minimized by using the lowest effective dose for the shortest possible treatment duration needed to control symptoms (see section 4.4). If BuscofenAct soft capsules must be taken in adults for more than 3 days in case of fever or for more than 4 days for the treatment of pain or if symptoms worsen, the patient is advised to consult his doctor. It is recommended to take on a full stomach for people with gastric disorders. If taken shortly after eating, the onset of the effect of BuscofenAct may be delayed. If this happens, do not take BuscofenAct more than recommended in section 4.2 (dosage) or until the correct interval between one dose and another has elapsed. Particular patient populations Elderly No particular dosage changes are required. Due to possible side effects (see section 4.4), elderly subjects should be carefully monitored. Renal failure No particular dose modifications are required in patients with mild or moderate renal impairment (for patients with severe renal impairment, see section 4.3). Hepatic failure (see section 5.2) No special dose modifications are required in patients with mild or moderate hepatic impairment (for patients with severe hepatic dysfunction, see section 4.3). Pediatric population BuscofenAct is contraindicated in adolescents with body weight below 40 kg and in children under 12 years of age due to the high content of active ingredient (see section 4.3). 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. Method of administration For oral use. The soft capsules should not be chewed.

CONSERVATION

This medicine does not require any particular storage temperature.

WARNINGS

Side effects can be minimized by using the lowest effective dose for the shortest possible duration of treatment necessary to achieve symptom control (see the paragraphs below dedicated to gastrointestinal and cardiovascular risks). Caution is required in patients with certain clinical conditions, which could worsen: - patients with systemic lupus erythematosus and various connective tissue diseases have a greater risk of developing aseptic meningitis (see section 4.8); - congenital pathology of porphyrin metabolism (for example acute intermittent porphyria); - gastrointestinal diseases and chronic inflammatory intestinal diseases (ulcerative colitis, Crohn's disease) (see section 4.8); - hypertension and/or cardiac impairment as renal function may worsen (see sections 4.3 and 4.8); - renal damage (see sections 4.3 and 4.8); - hepatic dysfunction (see sections 4.3 and 4.8); - immediately after major surgery; - in patients who have allergic reactions to other substances, since for such patients there is a greater risk of hypersensitivity reactions also following the use of BuscofenAct; - in patients suffering from hay fever, nasal polyps or chronic obstructive airway diseases since for such patients there is a greater risk of allergic reactions occurring. Such reactions may present as asthma attacks (so-called analgesic asthma), Quincke's edema or urticaria. Gastrointestinal effects The use of BuscofenAct soft capsules in combination with other NSAIDs, including selective cyclooxygenase-2 inhibitors, increases the risk of adverse reactions and should be avoided. Elderly Elderly subjects present a greater frequency of adverse reactions to NSAIDs, especially bleeding and gastrointestinal perforation, which can be fatal (see section 4.2). Gastrointestinal bleeding, ulceration or perforation Gastrointestinal haemorrhage, ulceration or perforation, sometimes fatal, have been reported, at any stage of treatment, with the use of all NSAIDs, with or without prodromal symptoms or a previous history of gastrointestinal events. If gastrointestinal bleeding or ulceration occurs in patients taking ibuprofen, treatment should be discontinued. The risk of gastrointestinal haemorrhage, ulceration or perforation increases with higher doses of NSAIDs, in patients with a history of ulcer, particularly if complicated by haemorrhage or perforation (see section 4.3), and in elderly patients. These patients should start treatment with the lowest available dose. Concomitant therapy with protective agents (e.g. misoprostol or proton pump inhibitors) should be considered for these patients and also for patients concomitantly taking low doses of acetylsalicylic acid or other drugs that may increase the risk of gastrointestinal events (see below and section 4.5). Patients with a history of gastrointestinal toxicity, especially the elderly, should report any unusual abdominal symptoms (especially gastrointestinal bleeding), especially in the initial stages of treatment. Caution should be used in patients receiving concomitant treatment with drugs that may increase the risk of ulceration or haemorrhage, such as oral corticosteroids, anticoagulants such as warfarin, selective serotonin reuptake inhibitors or antiplatelet agents such as acetylsalicylic acid (see section 4.5). NSAIDs should be administered with caution to patients with a history of gastrointestinal diseases (ulcerative colitis, Crohn's disease) as their conditions may worsen (see section 4.8). Severe skin reactions Very rarely, serious skin reactions, some of them fatal, have been reported in association with the use of NSAIDs (see section 4.8), including exfoliative dermatitis, Stevens-Johnson syndrome and toxic epidermal necrolysis. Patients appear to be at increased risk for these reactions in the early stages of therapy; in fact, in most cases, the reaction occurs in the first month of treatment. Acute generalized exanthematous pustulosis (PEAG) has been reported in connection with ibuprofen-containing medicinal products. The administration of BuscofenAct soft capsules must be suspended at the first appearance of skin rash, mucosal lesions or any other sign of hypersensitivity. Exceptionally, chickenpox can cause serious skin infections and soft tissue complications. It is recommended not to use BuscofenAct soft capsules during chickenpox. Masking of symptoms of underlying infections BuscofenAct soft capsules may mask the symptoms of infection, which could delay the initiation of 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 BuscofenAct soft capsules are 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. Cardiovascular and cerebrovascular effects Caution is required (discuss with your doctor or pharmacist) before starting treatment in patients with a history of hypertension and/or heart failure, since fluid retention, hypertension and edema have been reported in association with NSAID therapy. Clinical studies suggest that the use of ibuprofen, especially at high doses (2400 mg per day), may be associated with a modest increase in the risk of arterial thrombotic events (e.g. myocardial infarction or stroke). Overall, epidemiological studies do not suggest that low doses of ibuprofen (e.g. ≤ 1200 mg per 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 per 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 per day) of ibuprofen are necessary. Other warnings and precautions Very rarely, severe acute hypersensitivity reactions (e.g. anaphylactic shock) have been observed. At the first signs of a hypersensitivity reaction following the intake/administration of BuscofenAct soft capsules, therapy should be suspended. The required medical measures must be carried out by experienced personnel. Ibuprofen, the active ingredient in BuscofenAct soft capsules, can temporarily inhibit platelet function (platelet aggregation). Therefore, patients with platelet disorders should be carefully monitored. In case of prolonged treatment with ibuprofen, liver and kidney parameters, as well as the blood count, should be monitored regularly. Prolonged use of any headache pain reliever can make it worse. If this situation occurs or is suspected, you should consult your doctor and stop treatment. The diagnosis of medication overuse headache (MOH) should be suspected in patients with frequent or daily headaches despite (or because of) regular use of headache medications. In general, the habitual use of analgesics, in particular the combination of different analgesic active ingredients, can lead to permanent kidney damage with the risk of renal failure (analgesic nephropathy). This risk may be increased under physical exertion associated with salt loss and dehydration. Therefore this must be avoided. In case of concomitant consumption of alcohol during the use of NSAIDs, adverse events related to the active ingredient, especially those affecting the gastrointestinal tract or central nervous system, may increase. Pediatric population In dehydrated adolescents there is a risk of impaired renal function. Sorbitol BuscofenAct contains 95.94 mg of sorbitol in each capsule. Patients with hereditary fructose intolerance, a rare genetic disease, should not take this medicine.

INTERACTIONS

Other NSAIDs, including salicylates - Possible effects: Concomitant administration of several NSAIDs may increase the risk of gastrointestinal bleeding and ulcers due to a synergistic effect. Therefore, the concomitant use of ibuprofen with other NSAIDs should be avoided (see section 4.4).

Digoxin - Possible effects: The concomitant use of BuscofenAct soft capsules with drugs containing digoxin may increase serum levels of digoxin. Usually, if digoxin is used correctly (for a maximum of 4 days) it is not necessary to check its serum levels.

Corticosteroids - Possible effects: Corticosteroids may increase the risk of adverse reactions, particularly of the gastrointestinal tract (gastrointestinal bleeding or ulceration) (see section 4.4).

Antiplatelet agents - Possible effects: Increased risk of gastrointestinal bleeding (see section 4.4).

Acetylsalicylic acid - Possible effects: Concomitant administration of ibuprofen and acetylsalicylic acid is generally not recommended due to the potential for increased side effects. Experimental data suggest that ibuprofen may competitively inhibit the effect of low-dose acetylsalicylic acid on platelet aggregation when the two medicinal products 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).

Anticoagulants - Possible effects: NSAIDs may increase the effects of anticoagulants, such as warfarin (see section 4.4).

Phenytoin - Possible effects: Concomitant use of BuscofenAct and phenytoin preparations may increase serum levels of phenytoin. Usually, when used correctly (for a maximum of 4 days) it is not necessary to control serum phenytoin levels.

Selective serotonin reuptake inhibitors (SSRIs) - Possible effects: Increased risk of gastrointestinal bleeding (see section 4.4).

Lithium - Possible effects: Concomitant use of BuscofenAct with lithium preparations may increase serum lithium levels. Usually, if used correctly (for a maximum of 4 days) it is not necessary to check serum lithium levels.

Probenecid and sulfinpyrazone - Possible effects: Drugs containing probenecid and sulfinpyrazone can delay the elimination of ibuprofen.

Diuretics, ACE inhibitors, beta-blockers and angiotensin II antagonists - Possible effects: NSAIDs can reduce the effect of diuretics and other antihypertensive medicines. In some patients with compromised renal function (especially dehydrated patients or elderly patients with compromised renal function) the co-administration of an ACE inhibitor, a beta-blocker or angiotensin II antagonists and agents that inhibit cyclo-oxygenase may result in further worsening of renal function, including possible acute renal failure, which is usually reversible. Therefore, these combinations should be administered with caution especially in elderly patients. Patients should be adequately hydrated and monitoring of renal function should be considered at the initiation of concomitant therapy and on a periodic basis thereafter.

Potassium-sparing diuretics - Possible effects: The concomitant intake of BuscofenAct and potassium-sparing diuretics can lead to hyperkalemia.

Methotrexate - Possible effects: BuscofenAct administered in the 24 hours before or after taking methotrexate can increase its concentrations and therefore its toxicity.

Ciclosporins - Possible effects: The risk of renal damage induced by cyclosporines may be increased by the concomitant use of some NSAIDs. This effect cannot be excluded in case of simultaneous intake of ciclosporin and ibuprofen.

Tacrolimus - Possible effects: The risk of nephrotoxicity increases in case of concomitant administration of ibuprofen and tacrolimus.

Zidovudine - Possible effects: In case of concomitant administration of ibuprofen and zidovudine, there is evidence of an increased risk of haemarthrosis and haematomas in HIV-positive haemophiliacs.

Sulfonylureas - Possible effects: Clinical research has shown that interactions exist between nonsteroidal anti-inflammatory drugs and antidiabetic drugs (sulfonylureas). Although no interactions between ibuprofen and sulfonylureas have been described so far, in case of concomitant use of these two drugs it is advisable to monitor blood sugar levels.

Quinolone antibiotics - Possible effects: Animal studies indicate that NSAIDs may increase the risk of convulsions associated with the use of quinolone antibiotics. Patients taking NSAIDs and quinolones may have an increased risk of developing seizures.

CYP2C9 inhibitors - Possible effects: 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 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.

Mifepristone - Possible effects: NSAIDs should not be used for 8-12 days after administration of mifepristone as NSAIDs may reduce the effect of mifepristone.

SIDE EFFECTS

The list of side effects below refers to all side effects that have been experienced during treatment with ibuprofen, including those observed during long-term and high-dose treatment in patients suffering from rheumatic diseases. The declared frequencies, which occur with an incidence higher than very rare cases, refer to the short-term use of daily doses up to a maximum of 1200 mg of ibuprofen for the oral dosage form and a maximum of 1800 mg for the suppositories. It should be taken into account that the following side effects are fundamentally dose-dependent and vary from individual to individual. The most commonly observed side events are gastrointestinal in nature. Peptic ulcer, perforation or gastrointestinal haemorrhage, even with fatal outcome, may occur, especially in the elderly (see section 4.4). Following administration, nausea, vomiting, diarrhoea, flatulence, constipation, dyspepsia, abdominal pain, melena, haematemesis, ulcerative stomatitis, worsening of colitis and Crohn's disease have been reported (see section 4.4). Gastritis was observed less frequently. The risk of gastrointestinal bleeding depends on the dose and duration of treatment. Edema, hypertension and heart failure have been reported in association with treatment with NSAIDs. Clinical studies suggest that the use of ibuprofen, especially at high doses (2400 mg per 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). Patients should be informed to immediately stop taking BuscofenAct and to consult their doctor if a serious adverse reaction occurs. Adverse reactions are listed below by system organ class, and by frequency, according to the following categories: 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 (cannot be estimated on the basis of available data)

Infections and infestations: Very rare In conjunction with the use of non-steroidal anti-inflammatory drugs, a worsening of infectious inflammations has been observed (e.g. development of necrotizing fasciitis). This is probably associated with the mechanism of action of nonsteroidal anti-inflammatory drugs. Symptoms of aseptic meningitis with stiff neck, headache, nausea, vomiting, fever or blurred consciousness have been observed during treatment with ibuprofen. Patients with autoimmune diseases (SLE, mixed connective tissue disease) appear to be predisposed.

Blood and lymphatic system disorders: Very rare Hematopoietic disorders (anaemia, leukopenia, thrombocytopenia, pancytopenia, agranulocytosis). The first signs may be: fever, sore throat, superficial sores in the mouth, flu-like symptoms, severe tiredness, nosebleeds and skin bleeding. In long-term therapy, blood counts should be monitored regularly.

Immune system disorders: Uncommon Hypersensitivity reactions with skin rashes, and itching, asthma attacks (with possible drop in blood pressure).

Immune system disorders: Very rare Severe generalized hypersensitivity reactions, the signs of which may be facial edema, swelling of the tongue, swelling of the larynx with constriction of the airways, respiratory distress, tachycardia, drop in blood pressure, up to life-threatening fatal shock. If any of these symptoms occur, and this can happen even on the first use, immediate medical attention is required.

Psychiatric disorders: Very rare Psychotic reactions, depression.

Nervous system disorders: Uncommon Central nervous system disorders, such as headache, dizziness, insomnia, agitation, irritability or tiredness.

Eye disorders: Uncommon Visual disturbances.

Ear and labyrinth disorders: Rare Tinnitus.

Cardiac disorders: Very rare Palpitations, heart failure, myocardial infarction.

Vascular disorders: Very rare Arterial hypertension, vasculitis.

Gastrointestinal disorders: Common Gastrointestinal disorders, such as heartburn, abdominal pain, nausea, dyspepsia, vomiting, flatulence, diarrhea, constipation, slight gastrointestinal blood loss which in exceptional cases leads to anemia.

Gastrointestinal disorders: Uncommon Gastrointestinal ulcer with potential for haemorrhage and perforation. Ulcerative stomatitis, worsening of colitis and Crohn's disease (see section 4.4), gastritis.

Gastrointestinal disorders: Very rare Esophagitis, pancreatitis, formation of diaphragmatic intestinal strictures. If you feel severe pain in the upper abdomen or if you experience melena or hematemesis, you are advised to inform your doctor immediately and stop taking the medicine.

Hepatobiliary disorders: Very rare Liver dysfunction, liver damage, especially in case of prolonged therapy, liver failure, acute hepatitis.

Skin and subcutaneous tissue disorders: Uncommon Various skin rashes.

Skin and subcutaneous tissue disorders: Very rare Bullous reactions such as Stevens-Johnson syndrome and toxic epidermal necrolysis (Lyell's syndrome), alopecia. In exceptional cases, serious skin and soft tissue infections may occur during chickenpox infection (see also "Infections and infestations").

Skin and subcutaneous tissue disorders: Not known Acute generalized exanthematous pustulosis (PEAG). Drug reaction with eosinophilia and systemic symptoms (DRESS syndrome). Photosensitivity reactions

Renal and urinary disorders: Rare Rarely, damage to the renal tissue (papillary necrosis) and high concentrations of uric acid in the blood may also be observed.

Renal and urinary disorders: Very rare Formation of edema, especially in patients with arterial hypertension or renal failure, nephrotic syndrome, interstitial nephritis, which may be accompanied by acute renal failure. Kidney function should be checked regularly.

If necessary, patients should be adequately informed to stop treatment with BuscofenAct and immediately consult a doctor if one of the following conditions occurs: - severe gastro-intestinal disorders, heartburn or abdominal pain; - haematemesis; - melena or blood in the urine; - skin reactions, such as itchy rashes; - respiratory distress and/or edema of the face or larynx; - fatigue associated with loss of appetite; - sore throat, associated with aphthous ulcers, fatigue and fever; - severe nosebleeds and skin bleeding; - abnormal tiredness associated with reduced urinary excretion; - edema of the feet or legs; - chest pain; - visual disturbances. 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

Symptoms in case of overdose Symptoms of overdose may manifest as central nervous system symptoms such as headache, dizziness, light-headedness and loss of consciousness (myoclonic convulsions also in children), abdominal pain, nausea, vomiting, gastrointestinal bleeding and liver and kidney dysfunction, hypotension, respiratory depression and cyanosis. In cases of severe poisoning, metabolic acidosis may occur. Therapeutic measures in case of overdose There is no specific antidote. If one hour after ingestion the patient has potentially toxic levels of the drug, resort to oral administration of activated charcoal.

PREGNANCY AND BREASTFEEDING

Pregnancy Inhibition of prostaglandin synthesis can negatively affect pregnancy and/or embryo/foetal development. Results of epidemiological studies suggest an increased risk of spontaneous abortion, cardiac malformations and gastroschisis after the use of a prostaglandin synthesis inhibitor in early pregnancy. The absolute risk of cardiovascular malformations increased from less than 1% to approximately 1.5%. The risk is thought to increase with increasing dose and duration of therapy. In animals, the administration of a prostaglandin synthesis inhibitor resulted in an increase in pre- and post-implantation loss and embryo-foetal mortality. Furthermore, an increased incidence of malformations, including cardiovascular ones, has been reported in animals treated with a prostaglandin synthesis inhibitor during the period of organogenesis. During the first and second trimester of pregnancy, ibuprofen should only be administered if absolutely necessary. If ibuprofen is used in women intending to conceive or during the first and second trimester of pregnancy, the dose should be kept as low as possible and the duration of treatment should be as short as possible. During the third trimester of pregnancy, all inhibitors of prostaglandin synthesis can expose the fetus to the risk of: - cardiopulmonary toxicity (with premature closure of the ductus arteriosus and pulmonary hypertension); - renal dysfunction, which can worsen to renal failure with oligo-hydramniosis. At the end of pregnancy, the mother and newborn to: - possible prolongation of bleeding time, an anti-aggregating effect that can occur even at very low doses; - inhibition of uterine contractions which can lead to a delay or prolongation of labor at the time of birth. Consequently, the administration of ibuprofen is contraindicated during the third trimester of pregnancy. Breastfeeding Ibuprofen and its metabolites can pass in low concentrations into breast milk. To date, no deleterious effects on infants are known. Therefore, for short-term treatment of pain and fever at the recommended dose, it should generally not be necessary to interrupt breastfeeding. Fertility There is some evidence that drugs that inhibit cyclooxygenase/prostaglandin synthesis may impair female fertility by affecting ovulation. Once treatment with ibuprofen is finished, the effect is reversible.

EFFECTS ON DRIVING ABILITY

Since taking BuscofenAct at the highest dosage may cause side effects on the central nervous system, such as tiredness and dizziness, in isolated cases the ability to react promptly, the ability to drive and use machinery may be impaired. This is especially true if the use of BuscofenAct is associated with alcohol consumption.