Active ingredients: Ibuprofen
BUSCOFEN 200 mg soft capsules
Why is Buscofen used? What is it for?
WHAT IS IT
Buscofen belongs to the class of analgesics, anti-inflammatories, ie medicines that fight pain and inflammation.
WHY IT IS USED
Buscofen is used for pain of various origins and nature (menstrual pain, headache, toothache, neuralgia, osteoarticular and muscle pain).
Contraindications When Buscofen should not be used
- Hypersensitivity to the active substance or to any of the excipients.
- Children under 12 years of age.
- Patients with clinical conditions that lead to an increased tendency to bleed.
- History of asthma, nasal polyposis or angioedema after taking acetylsalicylic acid or other non-steroidal anti-inflammatory drugs.
- History of gastrointestinal bleeding or perforation following non-steroidal anti-inflammatory treatments.
- History of recurrent peptic haemorrhage / ulcer or gastric haemorrhage (two or more distinct episodes of proven ulceration or bleeding).
- Severe hepatic insufficiency.
- Severe renal insufficiency.
- Severe heart failure.
- During the third trimester of pregnancy (see section "What to do during pregnancy and breastfeeding").
Precautions for use What you need to know before taking Buscofen
- Ibuprofen should be taken with caution by asthmatics and, more particularly, by those subjects who have experienced bronchospasm after the use of acetylsalicylic acid or other NSAIDs (non-steroidal anti-inflammatory drugs), as well as by those who have a previous clinical history of gastrointestinal bleeding or ulcer.
- The use of Buscofen should be avoided concomitantly with NSAIDs, including selective COX-2 inhibitors.
- In the elderly and in patients with a history of ulcer, particularly if complicated with haemorrhage or perforation (see section "When it should not be used"), 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. The concomitant use of protective agents (misoprostol or proton pump inhibitors) should be considered for these patients and also for patients taking low doses of aspirin or other drugs that may increase the risk of gastrointestinal events (see below and section "Which Medicines or foods may change the "effect of the medicine").
- 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.
- 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 "Undesirable effects").
- When gastrointestinal bleeding or ulceration occurs in patients taking Buscofen the treatment should be discontinued.
- Caution should be exercised in patients taking concomitant medications that could increase the risk of ulceration or bleeding, such as oral corticosteroids, anticoagulants such as warfarin, selective serotonin reuptake inhibitors or antiplatelet agents such as aspirin (see section "What medicines or foods can change the "effect of the medicine").
- Medicines such as Buscofen 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 (3 days).
- If you have heart problems or 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 discuss your therapy with your doctor. or with the pharmacist.
Interactions Which drugs or foods may change the effect of Buscofen
Tell your doctor or pharmacist if you have recently taken any other medicines, even those without a prescription.
Particularly:
- corticosteroids (medicinal products containing cortisone or cortisone-like substances), acetylsalicylic acid or other NSAIDs (anti-inflammatory or analgesic): this may increase the risk of gastrointestinal ulcers or bleeding;
- anticoagulants (medicines to thin the blood such as warfarin) as NSAIDs can increase the effects of these medicines. Antiplatelet drugs (medicines that delay blood clotting) and selective serotonin reuptake inhibitors (medicines used for depression) as these can increase the risk of gastrointestinal adverse reactions; ACE inhibitors, angiotensin II antagonists and diuretics (used to treat high blood pressure) as NSAIDs may decrease the effects of these medicines and in some cases there may be further deterioration of renal function with possible acute renal failure, 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 monitoring of renal function should be considered after initiation of concomitant therapy and periodically thereafter;
- lithium (a medicine for manic-depressive disorders and depression) as the effect of lithium can be increased;
- methotrexate (a medicine for cancer or rheumatoid arthritis) as the effect of methotrexate may be increased;
- aminoglycosides: NSAIDs can decrease the excretion of aminoglycosides;
- cardiac glycosides: NSAIDs can exacerbate heart failure, reduce the rate of glomerural filtration and increase the levels of cardiac glycosides;
- phenytoin: NSAIDs may lead to increased plasma concentrations of phenytoin;
- cholestyramine: the concomitant administration of ibuprofen and cholestyramine may reduce the absorption of ibuprofen from the gastrointestinal tract. However, the clinical relevance is unknown;
- cyclosporins: 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 the potential additive effect;
- plant extracts: Ginkgo Biloba can increase the risk of bleeding in association with NSAIDs;
- mifepristone: due to the antiprostaglandin properties of NSAIDs, there may theoretically be a decrease in drug efficacy. 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 maturation cervical 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 enhance 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 given with tacrolimus;
- zidovudine: increased risk of blood 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 elimination of NSAIDs, with possible increase in their plasma concentrations;
- sulfinpyrazone: can delay the excretion of ibuprofen;
- 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 and fluconazole.
Some medicines such as anticoagulants and antiplatelet agents (eg acetylsalicylic acid, warfarin, ticlopidine), antihypertensives (ACE inhibitors, eg captopril, beta-blockers, angiotensin II antagonists) and other medicines may interact with treatment with ibuprofen. Consult your doctor before using ibuprofen with other medicines.
Warnings It is important to know that:
- The use of Buscofen, as well as any drug that inhibits prostaglandin synthesis and cyclo-oxygenase, is not recommended in women who intend to become pregnant.
- Buscofen should be discontinued in women who have fertility problems or who are undergoing fertility investigations.
- Adolescents: There is a risk of impaired renal function in dehydrated adolescents.
- Elderly: Elderly patients have an increased frequency of adverse reactions to NSAIDs, especially gastrointestinal bleeding and perforation, which can be fatal (see section "How to use this medicine").
- 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, 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. For these patients, and also for patients taking low doses of acetylsalicylic acid or other drugs that may increase the risk of gastrointestinal events, concomitant use of protective agents (misoprostol or proton pump inhibitors) should be considered. 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 could 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 section "What medicines or foods can change the" effect of the medicine "). When gastrointestinal bleeding or ulceration occurs estinale 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 can be exacerbated. Use with caution even in patients with coagulation defects.
- Caution is required (consult your doctor or pharmacist) before starting treatment in patients with a history of hypertension and / or heart failure as fluid retention, hypertension and edema have been reported in association with treatment with NSAIDs. 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).
- Serious skin reactions, some of them fatal, including exfoliative dermatitis, Steven-Johnson syndrome and toxic epidermal necrolysis, have been reported very rarely in association with the use of NSAIDs (see section "Undesirable effects"). Patients in the early stages of therapy they appear to be at higher risk: the onset of the reaction occurs in most cases within the first month of treatment. Buscofen should be discontinued at the first appearance of skin rash, mucosal lesions or any other signs of hypersensitivity.
- 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 kidney lesions permanent, with risk of renal failure (analgesic nephropathy).Renal toxicity has been reported in patients in whom renal prostaglandins play 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: Buscofen should be used with caution by 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 greater in subjects who have presented 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 angioedema (see sections "When it should not be used" and "Undesirable effects").
- Reduced cardiac, renal and hepatic function: Particular caution should be exercised in the treatment of 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.
- Haematological Effects: Ibuprofen, like other NSAIDs, can inhibit platelet aggregation and has been shown to prolong bleeding time in healthy subjects.
- Aseptic meningitis: Aseptic meningitis has been observed on rare occasions 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 "Which medicines or foods can change the" effect of the medicine "). .
- 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.
- Like other NSAIDs, ibuprofen can mask signs of infection.
When it can be used only after consulting your doctor
- If you have hypertension (high blood pressure) and / or heart failure.
- If you have reduced kidney function.
- If you suffer from liver dysfunction.
- If you have bleeding defects.
- If you have or have suffered from gastrointestinal tract disorders (ulcerative colitis or Crohn's disease).
- If you have or have suffered from asthma or allergic reactions, as bronchospasm (which causes difficulty in breathing) may occur.
- If you have systemic lupus erythematosus (chronic autoimmune disease that causes disorders in various parts of the body, especially the skin) or mixed connective tissue disease.
- Pregnancy and breastfeeding: see section "What to do during pregnancy and" breastfeeding ".
It is also advisable to consult your doctor in cases where these disorders have occurred in the past.
What to do during pregnancy and breastfeeding
If you are pregnant or breast-feeding, think you may be pregnant or are planning to have a baby, ask your doctor or pharmacist for advice before taking any medicine.
Do not take this medicine during the last 3 months of pregnancy. Also, avoid using this medicine during the first 6 months of pregnancy unless prescribed by your doctor.
Avoid taking this medicine if you are trying to get pregnant.
Pregnancy
Inhibition of prostaglandin synthesis can adversely affect pregnancy and / or embryo / fetal development.
Results of epidemiological studies suggest an increased risk of miscarriage and cardiac malformation and gastroschisis after use of a prostaglandin synthesis inhibitor in early pregnancy. The absolute risk of cardiac malformations increased from less than 1% to approximately 1.5%. The risk has been considered to increase with dose and duration of therapy. In animals, administration of prostaglandin synthesis inhibitors has been shown to cause increased loss of pre- and post-implantation and of 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.
During the third trimester of pregnancy, all prostaglandin synthesis inhibitors can exhibit:
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.
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. Buscofen should be discontinued in women who have fertility problems or who are undergoing fertility investigations.
Driving and using 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.
Health Education Notes
There are different types of pain, of various origins and nature, which we all face in the course of our everyday life with greater or lesser frequency: menstrual pain, headache, toothache, muscle and joint pain.
Menstrual pains (dysmenorrhea) are a very common ailment; in addition to pain, there are changes in mood (sadness, easy irritability) breast tension, generalized feeling of tiredness.
The elimination or reduction in the diet of substances such as coffee, salt or chocolate in favor of foods rich in vitamins, such as fruit, as well as the intake of hot herbal teas and chamomile, can help reduce these latter manifestations. Menstrual pain, sometimes of considerable intensity, can instead be fought with painkillers that act by reducing the amount of prostaglandins, substances produced by the uterus and considered to be the main causes of the disorder.
One of the most frequent pains is certainly headache (or cephalalgia). There are three main types of primary headaches (ie not due to other diseases): migraine, so called because the very intense pain is localized only on one side of the head; tension headache, the most common type, which occurs manifests with a circle in the head; cluster headache, characterized by attacks of excruciating pain affecting one eye or cheekbone.
Sometimes the headache can be a symptom of other diseases (allergies, anemia, myopia, intoxication, stomach upset, cervical arthrosis, sinusitis, constipation, head trauma). If you suffer from headaches it is important to try to identify the factors that can trigger it and prevent them (unregulated eating habits, particular foods, smoking, alcohol, stress, too intense physical exertion, excessive exposure to the sun, too loud noises, too much perfumes intense, etc.). If headache attacks are recurring, it is still advisable to contact your doctor.
Dosage and method of use How to use Buscofen: Dosage
How many
Adults and adolescents over 12 years: 1-2 soft capsules, two - three times a day. However, do not exceed the dose of 6 soft capsules per day without medical advice. Elderly patients should adhere to the minimum dosages indicated above.
When and for how long
Take the drug on a full stomach (preferably after breakfast, lunch or dinner). After three days of treatment without appreciable results, consult your doctor. Consult your doctor if the disorder occurs repeatedly or if you have noticed any recent changes in its characteristics. 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.
Like
The soft capsules should be swallowed without chewing, preferably with a little water. It is recommended to take it during or after meals for people with gastric disorders.
Overdose What to do if you have taken too much Buscofen
In case of accidental ingestion / intake of an excessive dose of Buscofen, notify your doctor immediately or go to the nearest hospital. Take this leaflet with you.
If you take too much of the medicine, the following symptoms may occur: nausea, vomiting, stomach pain, headache, dizziness, lethargy, drowsiness, blurred vision, ringing in the ears, seizures and loss of consciousness. Rarely: nystagmus, metabolic acidosis, hypothermia, renal effects, gastrointestinal bleeding, coma, apnea, CNS and respiratory system depression.
Disorientation, arousal state and cardiovascular toxicity including hypotension (low blood pressure), bradycardia and tachycardia have been reported.
In cases of significant overdose, liver failure and liver damage are possible.
Note to healthcare professional: Gastric lavage and correction of blood electrolytes are indicated in the event of overdose. There is no specific antidote to ibuprofen.
If you have any questions about the use of Buscofen, ask your doctor or pharmacist.
Side Effects What are the side effects of Buscofen
Like all medicines, Buscofen can cause side effects, although not everybody gets them. Adverse reactions that can occur are:
Cardiac and vascular diseases
Edema (swelling due to the accumulation of fluid in the tissues) and fatigue, hypertension (high blood pressure) and heart failure.
Medicines such as Buscofen may be associated with a small increased risk of heart attack ("myocardial infarction") or stroke.
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.
Disorders of the blood and lymphatic system
Reduction in the number of blood cells (leukopenia, haemolytic anemia, neutropenia, thrombocytopenia, agranulocytosis, aplastic anemia). In such cases, the first symptoms are fever, sore throat, superficial ulceration of the oral mucosa, a sense of fatigue, nosebleeds and skin bleeding.
Psychiatric disorders: insomnia, anxiety, depression, confusional state, hallucinations.
Nervous system disorders
Headache, paraesthesia, dizziness, somnolence, optic neuritis.
Eye disorders
Ocular alterations with consequent visual disturbances, toxic optic neuropathy.
Gastrointestinal disorders
They are the most frequently reported adverse reactions.
Nausea, vomiting, diarrhea, flatulence, constipation, dyspepsia, epigastric pain, heartburn, abdominal pain, melaena (black stools), haematemesis (vomiting of blood), ulcerative stomatitis, worsening of existing intestinal problems (ulcerative colitis or Crohn's disease) .
Gastritis has been reported less frequently.
Very rarely: peptic ulcers, gastrointestinal perforation and bleeding, sometimes fatal, particularly in the elderly.
Pancreatitis has also been observed very rarely.
Gastrointestinal perforation has rarely been observed with the use of ibuprofen.
Renal and urinary disorders
Impairment of renal function and toxic nephropathy in various forms, including interstitial nephritis, nephrotic syndrome and renal failure.
Skin and subcutaneous tissue disorders
Severe forms of skin reactions characterized by rash with redness and blistering or blisters in the skin and / or mucous membranes (erythema multiforme, Steven-Johnson syndrome and toxic epidermal necrolysis). Photosensitivity reactions are possible.
Hepatobiliary disorders
Abnormal liver function, abnormal liver function, hepatic failure, hepatitis and jaundice (yellowing of the skin) have been reported very rarely, especially following long-term treatment.
Ear and labyrinth disorders
Impaired hearing, tinnitus, vertigo.
General disorders and administration site conditions
Malaise, fatigue.
Respiratory, thoracic and mediastinal disorders
Bronchospasm, dyspnea, apnea.
Disorders of the immune system
Hypersensitivity reactions have been reported following NSAID treatment. These can consist of: a) non-specific allergic reaction and anaphylaxis; b) respiratory tract reactions including asthma, even severe, bronchospasm or dyspnoea; c) various skin disorders, including various types of rash, pruritus, urticaria, purpura, angioedema and, more rarely, exfoliative and bullous dermatitis (including Stevens-Johnson syndrome, toxic epidermal necrolysis and erythema multiforme).
Undesirable effects can be minimized by using the lowest effective dose for the shortest duration of treatment needed to control symptoms.
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. Undesirable effects can also be reported directly through 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
Warning: do not use the medicine after the expiry date indicated on the package.
Keep this medicine out of the reach and sight of children.
It is important to always have the information about the medicine available, so keep both the box and the package leaflet.
Composition and pharmaceutical form
COMPOSITION
One soft capsule contains: Active ingredient: ibuprofen 200 mg Excipients: macrogol 600, potassium hydroxide, purified water, gelatin, partially dehydrated liquid sorbitol.
HOW IT LOOKS
Buscofen comes in the form of soft gelatin capsules. The contents of the pack are 12 soft gelatin capsules of 200 mg.
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
BUSCOFEN
02.0 QUALITATIVE AND QUANTITATIVE COMPOSITION
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.
03.0 PHARMACEUTICAL FORM
Coated tablets.
Soft capsules.
04.0 CLINICAL INFORMATION
04.1 Therapeutic indications
Pain of various origins and nature (menstrual pain, headache, toothache, neuralgia, osteoarticular and muscle pain).
04.2 Posology and method of administration
Do not give to children under the age of 12.
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).
Tablets:
Adults and adolescents over 12 years
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 dose.
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.
Senior citizens
Elderly patients should adhere to the minimum doses indicated.
Patients with renal insufficiency
In the presence of renal insufficiency, elimination can be reduced and the dosage should be adjusted accordingly.
Soft capsules
Adults and adolescents over 12 years
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 dose.
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.
Senior citizens
Elderly patients should adhere to the minimum doses indicated.
Patients with renal insufficiency
In the presence of renal insufficiency, elimination can be reduced and the dosage should be adjusted accordingly.
Buscofen should not be used for more than 7 days. If higher doses are needed or if more prolonged treatment is required, then you should contact your doctor. The 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.
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 (glomerural filtration less than 30 ml / min).
- Severe heart failure.
- Subjects suffering from blood dyscrasias of unknown origin, from porphyria, from hypertension, from severe uncontrolled coronary insufficiency.
- Severe or active peptic ulcer.
- History of gastrointestinal haemorrhage or perforation related to previous active treatments or history of recurrent peptic haemorrhage / ulcer (two or more distinct episodes of proven ulceration or bleeding).
- Subjects with clinical conditions that cause an increased tendency to bleed.
- In conjunction with surgical interventions (including dental operations).
- Subjects who have suffered significant fluid losses (due to vomiting, diarrhea or poor ingestion of fluids).
- During the third trimester of pregnancy (see section 4.6).
- Children under 12 years old.
04.4 Special warnings and appropriate precautions for use
The concomitant use of Buscofen 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 by using the lowest effective dose for the shortest duration of treatment needed to control symptoms (see paragraphs below on gastrointestinal and cardiovascular risks).
Like other NSAIDs, ibuprofen can mask signs of infection.
Pediatric population
There is a risk of impaired renal function in dehydrated adolescents.
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 protective agents (misoprostol or proton pump inhibitors) should be considered for these patients and also for patients 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, 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 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 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, particularly at high doses (2400 mg per 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, Steven-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 be at higher risk; the onset of the reaction occurs in most cases within the first month of treatment. Treatment with Buscofen should be discontinued at the first appearance of skin rash, mucosal lesions or any other signs of hypersensitivity.
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 case of diffuse lupus erythematosus.
Respiratory disorders
Buscofen 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 par. 4.2 and 4.8).
Reduced cardiac, renal and hepatic function
Particular caution should be exercised when treating patients with severely reduced cardiac, hepatic or renal function. In such patients, periodic monitoring of clinical and laboratory parameters should be used, especially in case of prolonged treatment.
Ibuprofen may cause an increase in serum concentrations of aminotransferases, and other markers of liver function, in patients with no previous evidence of liver function disorders. These usually include relatively modest and transient increases from the normal range. If these abnormalities are clinically significant or persistent then treatment with ibuprofen should be discontinued and the response following treatment discontinuation monitored.
Ibuprofen can 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 can cause edema or cause acute decompensation of heart function or hypertension in predisposed individuals. Patients at increased risk for overt renal failure are elderly people, dehydrated or hypovolaemic patients, patients with congestive heart failure, cirrhosis, nephrotic syndrome, renal failure, those being treated with diuretics and patients who have recently undergone surgery.
Discontinuation of treatment is usually followed by a rapid return to pre-treatment renal function status. Ibuprofen may also interfere with the natriuretic effects of diuretics. Ibuprofen may mask symptoms (fever, pain, swelling) of an infection.
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 it 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 Buscofen, like any other drug that inhibits prostaglandin synthesis and cyclooxygenase, is not recommended in women who intend to become pregnant (see also section 4.6).
Buscofen should be discontinued in women who have fertility problems or who are undergoing fertility investigations.
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 enhance 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 the drugs are administered concomitantly. However, the limited data and uncertainties relating to their application to the clinical situation do not allow to to draw definitive conclusions for the continued use of ibuprofen; it seems that there are no clinically relevant effects from the 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, including possible acute renal failure, 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 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 the levels of lithium in the blood due to reduced elimination, with the possibility of reaching the toxic threshold. If this combination is necessary, monitor lithemia in order to adjust 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;
- phenytoin: NSAIDs may lead to increased plasma concentrations of phenytoin;
- 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 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 antiprostaglandin properties of NSAIDs, there may theoretically be a decrease in drug efficacy. 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 maturation cervical 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;
- sulfinpyrazone: can delay the excretion of ibuprofen;
- 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 and fluconazole.
04.6 Pregnancy and lactation
Pregnancy
Inhibition of prostaglandin synthesis may adversely affect pregnancy and / or embryo / fetal development. Data obtained from epidemiological studies suggest an increased risk of abortion, cardiac malformation and gastroschisis after the use of a prostaglandin synthesis inhibitor. during the early period of 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 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.
During the first and second trimester of pregnancy, ibuprofen should not be administered except in strictly necessary cases. If used by women about to conceive or during the first and second trimester of pregnancy, the dose and duration of treatment should be the lowest and shortest possible respectively.
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 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.
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 fertility, 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 Buscofen (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 can consist of to) non-specific allergic reaction and anaphylaxis, b) respiratory tract reactions including asthma, even severe, bronchospasm or dyspnoea or c) skin disorders including rash 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 diseases: Edema and fatigue, hypertension and heart failure have been reported in association with NSAID treatment. Clinical studies and epidemiological data suggest that the use of ibuprofen, particularly at high doses (2400 mg per day) and for long-term treatment, may be associated with a modest increased risk of arterial thrombotic events (eg myocardial infarction 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, confusional state, 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 nuchal rigidity, headache, nausea, vomiting, fever or disorientation (see section 4.4).
Respiratory, thoracic and mediastinal disorders: bronchospasm, dyspnea, apnea.
Eye disorders: rare cases of ocular alteration with consequent visual disturbances, toxic optic neuropathy.
Ear and labyrinth disorders: impaired hearing, tinnitus, dizziness.
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.
Reporting of suspected adverse reactions
Reporting of suspected adverse reactions occurring after authorization of the medicinal product is important as it allows continuous monitoring of the benefit / risk balance of the medicinal product. Healthcare professionals are asked to report any suspected adverse reactions via the national reporting system. "address https://www.aifa.gov.it/content/segnalazioni-reazioni-avverse.
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 people 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, convulsions, 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 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 for ibuprofen overdose. In the event of an overdose, symptomatic and supportive treatment is therefore indicated. Particular attention is paid to the control of blood pressure, acid-base balance and any gastrointestinal bleeding. Within 1 hour of ingestion of a potentially toxic quantity, the administration of activated charcoal should be considered. Alternatively, gastric lavage should be considered within 1 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 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
Pharmacotherapeutic group: anti-inflammatory and antirheumatic, non-steroidal product. Propionic acid and derivatives.
ATC code: M01AE01.
Ibuprofen is a non-steroidal anti-inflammatory analgesic active ingredient, which has been shown to be effective as an inhibitor of prostaglandin synthesis in conventional preclinical studies on inflammation and pain models. In men, ibuprofen reduces pain, swelling and fever. which may result from or be associated with inflammatory stages. In addition, ibuprofen inhibits ADP-induced (adenosine diphosphate) and collagen-induced platelet aggregation.
Ibuprofen inhibits the synthesis of prostaglandins therefore decreases the intrauterine resting pressure, the active pressure and the frequency of the cyclic activity of the uterus as well as the release of prostaglandins into the systemic circulation.
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 for the continued use of ibuprofen; there appears to be no clinically relevant effect from the occasional use of ibuprofen.
05.2 Pharmacokinetic properties
Ibuprofen is absorbed almost completely from the gastrointestinal tract following oral administration.
Maximum plasma concentrations of 8.3 μg / mL (32.4% CV) for R-ibuprofen and 8.0 μg / mL (26.1% CV) for S-ibuprofen were observed within 1.1 hour of administration. oral ibuprofen.
The pharmacokinetics of ibuprofen are not affected by concomitant administration of antacids.
Ibuprofen binds massively to human plasma proteins (> 98%) and purified albumin at therapeutic concentrations.
The volume of distribution following a single oral administration is 0.1-0.2 L / kg.
Ibuprofen is subject to a significant one-way enantiomeric inversion from R-ibuprofen to S-ibuprofen in humans.
This reaction proceeds through the formation of the acyl-CoA-thioester of 2-arylpropionate.
Ibuprofen is extensively metabolised in the liver. In vitro tests suggest that cytochrome CYP2C9 is the major P450 isoenzyme mediating the oxidative metabolism of ibuprofen. Four different phase I metabolites (1-hydroxy-ibuprofen, 2-hydroxy-ibuprofen, 3-hydroxy-ibuprofen and carboxy- ibuprofen) have been identified in the urine.
An "additional metabolic pathway of ibuprofen is conjugation with glucuronic acid.
All identified metabolites are pharmacodynamically inactive.
Following oral administration of ibuprofen, 70-90% of the dose is recovered in the urine as a mixture of conjugated and non-conjugated forms of the metabolites of ibuprofen, only a minimal amount of the drug is excreted unchanged.
The mean elimination half-life is approximately 2 hours, plasma clearance approximately 0.05 L / h / kg.
Ibuprofen demonstrates a non-linear relationship between dose and total pharmacokinetics due to protein binding saturation in the dose range of 250-1200 mg.
However, the AUC of unbound plasma ibuprofen increases in direct proportion to the administered dose.
In chronic renal failure patients on hemodialysis, serum ibuprofen concentrations are lower, the volume of distribution as well as oral clearance are higher than in healthy subjects. Protein binding is reduced.
Patients with liver cirrhosis show longer half-lives and a significantly higher AUC than healthy people.
Children with cystic fibrosis show a decrease in maximum plasma concentrations and AUC.
Total clearance and volume of distribution are greater than in healthy individuals, while the elimination half-life as well as the time to peak plasma concentrations are not significantly different.
Elderly people (> 60 years) demonstrated significantly lower clearance than younger people. In women, there are no differences in pharmacokinetics between young and old.
Another study showed no difference in pharmacokinetic parameters between young and elderly males.
The pharmacokinetics of ibuprofen are not affected in children who received doses between 5 and 10 mg / kg or in children aged 3 to 10 years.
No age-related differences were generally observed in the absorption or terminal half-life of ibuprofen. However, children younger than 2.5 years showed higher clearance compared to older children, this is primarily related to the increased volume of distribution.
A positive correlation between ibuprofen serum concentrations and the analgesic effect can be demonstrated 1 to 3 hours after administration, suggesting that higher plasma levels lead to increased analgesia.
The bioavailability of the tablets and soft capsules is approximately equivalent to that of an aqueous solution.
05.3 Preclinical safety data
Single dose toxicity studies in animals revealed no evidence of significant sensitivity to oral ibuprofen.
The single dose toxicity data (LD50-values) of ibuprofen are:
- in mice: 320 mg / kg intraperitoneum 740 mg / kg oral
- in the rat: 636 mg / kg oral 626 mg / kg intraperitoneum
Chronic and subchronic toxicity of ibuprofen occurred in animals with lesions and ulcers in the gastrointestinal tract.
The threshold dose for ibuprofen for ulcers was 300 mg / kg / day in mice (13-week study) and 180 mg / kg / day in rat (26-week study).
Oral administration of high doses of 540 mg / kg / day induced moderate kidney injury and intestinal ulcers with peritonitis.
The threshold dose for ulcers in dogs is 8 mg / kg / day.
Erosion and ulcers of the pylorus and antrum were observed post-mortem in dogs at oral doses of 8 mg / kg and 16 mg / kg daily for 30 days in the absence of clinical symptoms of toxicity. These reactions are attributed to action. systemic ibuprofen.
The increased sensitivity of the dog can be explained by the higher and more prolonged plasma concentration in this species.
In the Ames test and the sister-chromatid exchange test, ibuprofen showed no mutagenic activity.
No carcinogenic potential was found in mice treated orally with ibuprofen 300 mg / kg / day for 42 weeks, followed by dose reduction to 100 mg / kg / day from week 42 to 80. Furthermore, no potential was found. carcinogenic in rats treated with 180 mg / kg / day for 56 weeks, followed by the administration of 60 mg / kg / day for the remaining 2 years of observation.
Administration of ulcerogenic doses of ibuprofen to rats and rabbits did not induce embryo-fetal toxicity and did not show teratogenic activity. Ibuprofen has been shown to cross the placental barrier in both species. Pregnant rats were more sensitive to the ulcerogenic effects of ibuprofen with a threshold dose of 20 mg / kg.
There is no further information on preclinical data other than that already reported elsewhere in this SPC (see section 4.6).
06.0 PHARMACEUTICAL INFORMATION
06.1 Excipients
Tablets
Corn starch, sodium carboxymethyl starch, magnesium stearate, hydroxypropylmethylcellulose, polyethylene glycol 6000, talc, titanium dioxide, antifoam emulsion.
Soft capsules
Polyethylene glycol 600, potassium hydroxide, purified water, gelatin, sorbitol special solution.
06.2 Incompatibility
Incompatibilities with other medicines are unknown.
06.3 Period of validity
Tablets: 2 years.
Soft capsules: 3 years.
06.4 Special precautions for storage
Tablets: Store at room temperature.
Soft capsules: Store at a temperature not exceeding 30 ° C.
06.5 Nature of the immediate packaging and contents of the package
Tablets
Carton containing 2 AL / PVC blisters of 10 tablets.
Soft capsules
Carton containing 1 AL / PVC / PVDC blister of 12 soft capsules.
Carton containing 1 AL / PVC / PVDC blister of 10 soft capsules.
06.6 Instructions for use and handling
Not relevant.
07.0 MARKETING AUTHORIZATION HOLDER
Boehringer Ingelheim Italia S.p.A.
Via Lorenzini, 8
20139 Milan
08.0 MARKETING AUTHORIZATION NUMBER
20 tablets: A.I.C. n. 029396013
12 soft capsules: A.I.C. n. 029396037
10 soft capsules: A.I.C. n. 029396025
09.0 DATE OF FIRST AUTHORIZATION OR RENEWAL OF THE AUTHORIZATION
10.12.1996 / 10.12.2006
10.0 DATE OF REVISION OF THE TEXT
October 15, 2014
