Active ingredients: Ibuprofen
ANTALFEBAL CHILDREN 100 mg / 5 ml oral suspension
Why is Antalfebal used? What is it for?
ANTALFEBAL is an analgesic, anti-inflammatory and antipyretic (non-steroidal anti-inflammatory drug, NSAID).
Uses of ANTALFEBAL
- Mild to moderate pain
- Fever
Contraindications When Antalfebal should not be used
Do not give or take ANTALFEBAL if you have:
- Allergy (hypersensitivity) to ibuprofen, to another anti-inflammatory drug, to Allura Red AC dye or to any other ingredient in ANTALFEBAL.
- Previous manifestations of allergic reaction after taking acetylsalicylic acid or other non-steroidal anti-inflammatory drugs, such as: - asthma attacks - swelling of the mucous membrane of the nose - skin reactions (for example, redness, hives or similar)
- Active gastroduodenal bleeding or ulcers (peptic ulcers) or history of recurrent gastroduodenal bleeding or ulcers (at least two distinct episodes of known ulceration or bleeding)
- Previous episodes of perforation or bleeding of the gastrointestinal tract related to previous NSAID therapy
- Previous episodes of cerebral bleeding (cerebrovascular event) or other active bleeding
- Previous severe impairment of renal or hepatic function
- Previous severe heart failure
- Recent significant fluid loss (caused by vomiting, diarrhea or lack of fluid intake).
Do not take ANTALFEBAL in the last trimester of pregnancy.
Precautions for use What you need to know before taking Antalfebal
To minimize undesirable events it is advisable to use the lowest effective dose for the shortest possible time. Do not exceed the recommended dose or 4 days of treatment without the advice of a doctor / pharmacist. In the presence of serious illnesses and / or taking other drugs, for example antibiotics, anti-rejection drugs in case of organ transplant or anticoagulants, before using ANTALFEBAL consult your doctor.
Safety in the gastrointestinal tract
Avoid the concomitant use of ANTALFEBAL with NSAID drugs, including so-called COX-2 inhibitors (selective cyclooxygenase-2 inhibitors). In case of concomitant use of other NSAID drugs, ANTALFEBAL must be taken carefully following the doctor's prescription.
It is advisable to consult your doctor before using ANTALFEBAL for the treatment of abdominal pain. Gastrointestinal bleeding, ulceration or perforation, sometimes fatal, have been reported for all NSAIDs during treatment, with or without warning signs or a previous history of serious gastrointestinal events. The risk of gastrointestinal bleeding, ulceration or perforation is higher with high doses of NSAIDs, in patients with a history of ulcer, particularly if complicated with haemorrhage or perforation (see section 2 "What you need to know before taking ANTALFEBAL"). For these patients it is advisable to start treatment with the lowest recommended dose.
Combination therapy with protective agents (e.g., misoprostol or proton pump inhibitors) is indicated in this patient population, as well as in those requiring concomitant intake of small doses of acetylsalicylic acid (ASA) or other drugs that could increase gastrointestinal risk.
In case of patients with previous manifestations of gastrointestinal side effects, it is recommended to refer to the doctor any type of unusual abdominal symptoms (especially gastrointestinal bleeding), particularly in the initial stages of treatment.
Particular caution is advised in the case of patients using 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 acetylsalicylic acid (see section 2 "Concomitant use of other drugs") In the event of gastrointestinal bleeding or ulcers in the patient receiving ANTALFEBAL, treatment should be discontinued.
Particular attention is advised in the administration of NSAIDs in patients with a positive history of gastrointestinal diseases (ulcerative colitis, Crohn's disease), as the use of these drugs could aggravate these conditions (see section 4 "Possible side effects").
Effects on the cardiovascular system
Anti-inflammatory / pain-relieving drugs such as ibuprofen may be associated with a modest increased risk of heart attack or stroke, especially when given in high doses. Do not exceed the recommended dose or duration of treatment.
You should discuss your therapy with your doctor or pharmacist before taking ANTALFEBAL if you have:
- heart problems including heart attack, angina (chest pain) or if you have a history of heart attack, coronary artery bypass surgery, peripheral arterial disease (poor circulation in the legs or feet due to narrowing or blocked arteries) or any type of stroke ( including "mini-stroke" or "TIA", transient ischemic attack);
- high blood pressure, diabetes, high cholesterol, family history of heart disease or stroke, or if you are a smoker.
Skin reactions
Very rarely, severe skin reactions with redness and blistering, sometimes fatal (exfoliative dermatitis, Stevens-Johnson syndrome and toxic epidermal necrolysis / Lyell's syndrome) have been reported in association with the use of NSAID drugs (see section 4 "Possible side effects "). The greatest risk of developing these reactions occurs in the initial stages of treatment: in most patients, the onset of the reaction occurs in the first month of therapy. ANTALFEBAL should be discontinued immediately upon the appearance of skin rash, mucosal lesions or other signs of hypersensitivity.
Medical supervision is required in particular in the case of:
- Acute intermittent porphyria.
- In certain autoimmune diseases (systemic lupus erythematosus and mixed connective tissue diseases), ANTALFEBAL should only be used after a "careful evaluation of the benefit / risk ratio.
- Gastrointestinal disorders or a history of chronic inflammatory bowel disease (ulcerative colitis, Crohn's disease).
- Hypertension or heart failure.
- Impaired renal or hepatic function.
- Allergies (for example, reactions to other medicines, asthma, hay fever), chronic edema of the mucous membrane of the nose or chronic diseases of the airways that obstruct the same.
- Episodes of acute severe hypersensitivity (eg, anaphylactic shock) have been observed very rarely. At the first signs of a severe hypersensitivity reaction following the use of ANTALFEBAL, discontinue therapy immediately and seek medical attention.
- Infections: Ibuprofen may mask the signs, especially in the case of chickenpox. If you have or worsen signs of infection (for example erythema, edema, hyperthermia, pain, fever) while using ANTALFEBAL, consult your doctor immediately. (see also section 4 "Possible side effects").
- Ibuprofen, the active ingredient in ANTALFEBAL, can temporarily inhibit platelet function (thrombocytic aggregation). Consequently, patients with coagulation disorders should be treated with particular care.
- In case of concomitant use of anticoagulant or hypoglycemic drugs, it is recommended to carry out checks on coagulation and blood sugar levels. In case of prolonged use of ANTALFEBAL, it is necessary to carry out checks on liver values, renal function and blood counts.
- In case of surgical procedures, inform the doctor or dentist if the patient is being treated with ANTALFEBAL.
- In case of prolonged use of painkillers, headaches may occur which should not be treated with an increase in the dose of the drug. In case of recurrent headache despite the use of ANTALFEBAL, consult your doctor.
- In general, the habitual intake of painkillers, in particular the combination of numerous analgesic active ingredients, can cause permanent damage to the kidneys with the risk of renal failure (analgesic nephropathy).
- There is a risk of impaired renal function in dehydrated children and adolescents.
In all these cases it is advisable to consult your doctor before taking this medicine.
Interactions Which drugs or foods can modify the effect of Antalfebal
If the patient has recently taken other medicinal products, including non-prescription drugs, please inform your doctor or pharmacist.
ANTALFEBAL can affect or be affected by other medicines. Eg:
- medicines that have an anticoagulant effect (i.e. substances that thin the blood by preventing the formation of clots, e.g. aspirin / acetylsalicylic acid, warfarin, ticlopidine)
- medicines that reduce high blood pressure (ACE inhibitors such as captopril, beta blockers such as atenolol, angiotensin II receptor antagonists such as losartan)
Also some other medicines can influence or be influenced by treatment with ANTALFEBAL. Therefore, always consult your doctor or pharmacist before using ANTALFEBAL with other medicines.
Increased effect and / or side effects
- If the following drugs are taken simultaneously with ibuprofen, their concentrations in the blood may increase: - digoxin (cardioactive agent) - phenytoin (anticonvulsant agent) - lithium (agent used in the treatment of psychiatric disorders)
In case of correct use (maximum 4 days), a control of serum levels referred to lithium, digoxin and phenytoin is not normally required.
- Agents that inhibit blood clotting
- Methotrexate (agent for the treatment of tumors or some rheumatic diseases): do not take ANTALFEBAL in the 24 hours before or after taking methotrexate. The concomitant use of the two drugs can lead to higher concentrations of methotrexate with an increase in its side effects .
- Acetylsalicylic acid and other anti-inflammatory pain relievers, including COX-2 inhibitors (non-steroidal anti-inflammatory drugs), selective serotonin reuptake inhibitors (drugs to treat depressive states) and cortisone preparations (glucocorticoids): increased risk of ulcers and bleeding of the gastrointestinal tract.
- Drugs that contain probenecid or sulfinpyrazone (agents for the treatment of gout): these agents can delay the elimination of ibuprofen. There may be a buildup of ibuprofen in the body, with an increase in its side effects.
Weakening of the effect
- Drugs that increase fluid elimination (diuretics) and drugs to treat hypertension (antihypertensives)
- ACE inhibitors (agents for the treatment of heart failure and hypertension): increased risk of impaired renal function.
- Low dose acetylsalicylic acid: the effect on platelet aggregation of low dose acetylsalicylic acid can be inhibited (see section 2 "Follow the instructions for use of ANTALFEBAL carefully").
Other possible interactions
- Zidovudine (drug for the treatment of AIDS): There is an increased risk of bleeding in the joints and following bruises in hemophiliacs with HIV infection.
- Ciclosporin (drug with immunosuppressive effect, for example in the case of organ transplantation, and for the treatment of rheumatism): risk of kidney damage.
- Tacrolimus: risk of kidney damage.
- Potassium-sparing diuretic agents (certain diuretics): with concomitant use, increased potassium levels may occur.
- Sulfonylureas (agents used to lower blood sugar levels): in case of concomitant use, check glycemic values even if, unlike other NSAIDs, interactions between ibuprofen and sulfonylureas have not yet been described.
- Anticoagulant agents: There have been isolated reports of interactions between ibuprofen and anticoagulant agents. In case of concomitant use, control of blood clotting is recommended.
Taking ANTALFEBAL with food and drink
During the use of ANTALFEBAL it is not recommended to drink alcoholic beverages.
Warnings It is important to know that:
Pregnancy and breastfeeding
Pregnancy
This medicinal product has been formulated specifically for short-term pediatric use, however, if pregnancy is ascertained while using ANTALFEBAL, your doctor should be informed. Unless otherwise directed by your doctor, avoid the use of this medicine in the first 6 months of pregnancy. In the last trimester of pregnancy ANTALFEBAL is contraindicated and therefore should not be taken due to the increased risk of complications for the mother and the child. The medicine belongs to a category of drugs (NSAIDs) that can impair the fertility of women. This effect is reversible on discontinuation of the drug.
Feeding time
Small amounts of the active ingredient ibuprofen and its catabolic products are secreted into breast milk. No risks to the infant are known to date and, consequently, breastfeeding should not be discontinued if the recommended dose is used for the maximum recommended duration of 4 days for mild to moderate fever or pain.
Before taking any medicine, consult your doctor or pharmacist.
Effects on ability to drive and use machines
Short-term intake of ANTALFEBAL does not affect the ability to drive or use machines.
Important information about some of the ingredients of ANTALFEBAL
The medicine contains sucrose (5 ml of syrup contains approximately 1.5 g of sucrose). This data is important in the case of a diabetic patient. In case of patient with intolerance to some sugars, contact your doctor before administering the medicine. The medicine contains Allura Red AC dye (5 ml of syrup contains 0.035 mg) which can cause allergic reactions.
Dosage and method of use How to use Antalfebal: Dosage
When administering ANTALFEBAL always strictly follow the instructions contained in this package leaflet. If in doubt or uncertainty, consult your doctor or pharmacist. Unless otherwise instructed by your doctor, adhere to the following standard doses:
If the use of the medicine is necessary for more than 3 days in children over 6 months of age and adolescents, or in the case of worsening of symptoms, the doctor must be consulted. In case of administration of the maximum single dose wait at least 4 hours before giving the next dose.
Shake the bottle vigorously before use. For an accurate dose, the package comes with a graduated measuring cup, 5 ml of syrup is equivalent to 100 mg of ibuprofen. ANTALFEBAL can be taken either concomitantly or between meals. In patients with gastric sensitivity it is recommended to take ANTALFEBAL with meals.
Duration of use
Do not administer ANTALFEBAL for more than 4 days without first consulting your doctor or pharmacist. If symptoms persist or worsen during this time, see your doctor.
It is advisable to inform your doctor or pharmacist if you have the impression that the effects of ANTALFEBAL are too strong or too weak. Do not increase the medicinal dose on your own.
Special patient groups
Kidney failure
No dose reduction is required in patients with mild to moderate renal impairment (in the case of patients with severe renal impairment, see section 2 "Do not give or take ANTALFEBAL if you have").
Hepatic insufficiency
No dose reduction is required in patients with mild to moderate hepatic impairment (in case of patients with severe hepatic impairment, see section 2 "Do not give or take ANTALFEBAL if you have").
Children
ANTALFEBAL should not be administered to infants under 6 months of age or body weight below 5 kg, as there is no adequate documentary experience in this age group.
Overdose What to do if you have taken too much Antalfebal
If you take more ANTALFEBAL than you should
Possible symptoms of an overdose of the drug are as follows:
- central nervous system disorders such as headache, dizziness and light-headedness, numbness and unconsciousness (including seizures in children);
- gastrointestinal disorders, such as stomach pain, nausea and vomiting, bleeding from the gastrointestinal tract;
- impaired kidney and liver function;
- drop in blood pressure;
- decreased respiratory activity (respiratory depression);
- bluish-purplish discoloration of the skin and mucous membranes (cyanosis).
Tell your doctor immediately if you suspect an overdose of ANTALFEBAL. The doctor will decide what measures to take depending on the severity of the poisoning.
If you forget to take ANTALFEBAL
Do not give / take a double dose to replace the missed dose.
Contact your doctor or pharmacist if you have any further questions regarding the use of this medicine.
Side Effects What are the side effects of Antalfebal
Like all medicinal products, ANTALFEBAL can have side effects, although not everyone treated gets them. If the following side effects are observed, inform your doctor who will decide how to proceed.
In the evaluation of undesirable effects, the following incidence rates are used as a reference:
The list of side effects below includes all side effects that have been reported for patients taking ibuprofen, including those occurring in patients with rheumatism on long-term therapy with high doses of the drug. The reported incidence rates include very rare cases, concern the short-term use of daily doses up to a maximum of 1,200 mg of ibuprofen in the case of pharmaceutical forms intended for oral administration, corresponding to 60 ml of ANTALFEBAL. It should be noted that the following adverse reactions are mostly dose-dependent and vary from patient to patient. The most commonly observed side effects are gastrointestinal in nature. Gastroduodenal ulcers (peptic ulcers), gastrointestinal perforation or bleeding may occur, sometimes with fatal outcome, particularly in the elderly ( see section 2 "Strictly follow the instructions for using ANTALFEBAL"). Nausea, vomiting, diarrhea, flatulence, constipation, digestive disturbances, abdominal pain, picee stools, haematemesis, ulcerative stomatitis (inflammation of the mucous membrane of the mouth with ulceration), exacerbation of intestinal diseases, such as colitis, have been reported after use of the drug ulcerative disease and Crohn's disease (see section 2 "Strictly follow the instructions for use of ANTALFEBAL"). Inflammation of the gastric mucosa has been observed less frequently. In particular, the risk of gastrointestinal bleeding depends on the dose and duration of treatment. Edema, hypertension and heart failure have been reported in association with NSAID treatment. Drugs such as ANTALFEBAL may be reported. be associated with a slightly increased risk of heart attack (myocardial infarction) or stroke.
Heart ailments
Very rare: heart beat (palpitations), heart failure, heart attack (myocardial infarction)
Disorders of the lymphatic and blood system:
Very rare: haematopoiesis disorders (anemia, leukopenia, thrombocytopenia, pancytopenia, agranulocytosis). The first symptoms may be fever, sore throat, superficial oral lesions, flu-like disorders, marked fatigue, epistaxis and skin bleeding. In cases, discontinue therapy immediately and seek medical attention Never administer analgesic or antipyretic drugs without medical advice.
Disorders of the nervous system
Uncommon: central nervous system disorders such as headache, dizziness and lightheadedness, numbness, agitation, irritability or tiredness
Eye disorders
Uncommon: vision disturbances
Ear and labyrinth disorders
Rare: ringing in the ears (tinnitus)
Gastrointestinal disorders
Common: gastrointestinal disturbances, such as heartburn, stomach pain, nausea, vomiting, flatulence, diarrhea, constipation and mild gastrointestinal blood loss which in exceptional cases can cause a loss of red blood cells (anemia)
Uncommon: gastroduodenal ulcers (peptic ulcers), with the possibility of bleeding and ulceration, inflammation of the mucous membrane of the mouth with ulceration (ulcerative stomatitis), exacerbation of ulcerative colitis or Crohn's disease, inflammation of the lining of the stomach (gastritis)
Very rare: inflammation of the esophagus (oesophagitis) and pancreas (pancreatitis), formation of narrowing in the large and small intestine which occurs in the form of a membrane (intestinal diaphragm atresia).
In case of severe pain in the upper abdomen, haematemesis, blood in the stools and / or black discolouration of the stools, immediately discontinue administration of ANTALFEBAL and seek medical attention.
Renal and urinary disorders
Very rare: increased water retention in the tissues (edema), particularly in patients with hypertension or renal insufficiency, nephrotic syndrome (accumulation of water in the body [edema] and marked excretion of proteins in the urine), inflammatory kidney disease (interstitial nephritis ), which may accompany acute renal failure.
Damage to kidney tissue (papillary necrosis) and higher concentrations of uric acid in the blood can also occur.
Reduced urinary excretion, accumulation of water in the body (edema) and a general feeling of malaise can be an expression of kidney disease or can lead to kidney failure.
In the event of the presence or worsening of these symptoms, immediately stop administering ANTALFEBAL and contact your doctor.
Alterations of skin and subcutaneous tissue
Very rare: severe skin reactions, such as rash with erythema and blistering (for example, Stevens-Johnson syndrome, toxic epidermal necrolysis / Lyell's syndrome), hair loss (alopecia) In exceptional cases, during a "chickenpox infection or facial erysipelas / St. Anthony's fire severe skin infections and soft tissue complications can occur (see also "Infections and Infestations").
Infections and infestations
Very rare: Worsening of infection-related inflammations (for example, development of necrotizing fasciitis) has been described very rarely coinciding with the use of certain anti-inflammatory drugs (non-steroidal anti-inflammatory drugs to which ANTALFEBAL also belongs).
Symptoms of inflammation of the cerebral cortex (aseptic meningitis), such as severe headache, nausea, vomiting, fever, neck stiffness or drowsiness have been observed. Patients who have already suffered from autoimmune diseases (systemic lupus erythematosus and mixed connective tissue diseases) appear to be at increased risk.
In case of presence or worsening of signs of infection (for example erythema, edema, hyperthermia, pain, fever) while using ANTALFEBAL, consult your doctor immediately (see also section 2 "Medical supervision is required especially in case of ").
Vascular disorders
Very rare: high blood pressure (arterial hypertension)
Immune system disorders (hypersensitivity reactions)
Uncommon: hypersensitivity reactions with rash and itching, as well as asthma attacks (with possible drop in blood pressure). Stop taking ANTALFEBAL and consult your doctor.
Very rare: severe generalized hypersensitivity reactions. Symptoms can be: swelling of the face, tongue and larynx with narrowing of the airways, dyspnoea, palpitations, hypotension or even fatal shock.
Allura Red AC dye can cause allergic reactions. In the event of the appearance of one of these symptoms - which may occur from the first administration - seek immediate medical assistance.
Hepatobiliary disorders
Very rare: liver function abnormalities, liver damage, particularly in long-term therapy, liver failure, acute inflammation of the liver (hepatitis). In case of prolonged use, regular monitoring of liver values is recommended.
Psychiatric disorders
Very rare: psychotic reactions, depression.
In case of worsening of an undesirable effect or in the presence of an undesirable effect not mentioned in this leaflet, inform your doctor or pharmacist.
Expiry and Retention
Keep out of the reach and sight of children.
Do not use this medicine after the expiry date stated on the bottle and carton. The expiry date refers to the last day of the month indicated.This medicinal product does not require any special thermal storage conditions.
The shelf life after opening the package is 6 months. After this period the residual medicine must be discarded.
Medicines should not be disposed of via wastewater or household waste. Ask your pharmacist how to throw away medicines you no longer use. This will help protect the environment.
Composition and pharmaceutical form
What ANTALFEBAL contains
The active ingredient is ibuprofen: 5 ml of oral suspension contain 100 mg of ibuprofen.
The other ingredients are: acesulfame potassium, glycerol, sodium benzoate (E211), polysorbate 80, sucrose, pregelatinised maize starch, purified water, xanthan gum, anhydrous citric acid, Allura Red AC dye (E129), bubblegum flavor consisting of aroma artificial watermelon, natural and artificial watermelon flavor and sweet blend flavor.
Pharmaceutical form of ANTALFEBAL and contents of the pack
Oral suspension.
ANTALFEBAL is a pink colored suspension available in packs of one bottle containing 100, 150, 200 ml of oral suspension.
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
ANTALFEBAL CHILDREN 100 MG / 5 ML ORAL SUSPENSION
02.0 QUALITATIVE AND QUANTITATIVE COMPOSITION
5 ml of oral suspension contain
100 mg of ibuprofen (equivalent to 2%).
5 ml of oral suspension contains 1.5 g of sucrose and 0.035 mg of Allura Red dye.
For the complete list of excipients, see section 6.1.
03.0 PHARMACEUTICAL FORM
Pink suspension.
04.0 CLINICAL INFORMATION
04.1 Therapeutic indications
Mild to moderate pain. Fever.
04.2 Posology and method of administration
The dose of ANTALFEBAL depends on age or body weight.
Generally, the total daily dose is 20-30 mg of ibuprofen per kg of body weight, divided into 3-4 single doses. The total recommended daily dose should not be exceeded.
If the use of the medicine is necessary for more than 3 days in children over 6 months of age and adolescents, or in the case of worsening of symptoms, the doctor should be consulted.
If the maximum single dose is taken, the interval between one dose and the next should be 4 hours.
The bottle should be shaken vigorously before use. To ensure an accurate dose, the package includes a measuring cup.
ANTALFEBAL can be taken both concomitantly and between meals. In patients with gastric sensitivity it is recommended to take ANTALFEBAL with meals.
ANTALFEBAL should not be taken for more than 4 days without first consulting a doctor or dentist. If symptoms persist or worsen during this time, see your doctor.
To minimize undesirable effects it is advisable to use the lowest effective dose for the shortest possible time (see section 4.4).
Special patient groups
Kidney failure
In patients with mild to moderate renal impairment no dose reduction is required (in case of patients with severe renal impairment, see section 4.3).
Hepatic insufficiency
In patients with mild to moderate hepatic impairment no dose reduction is required (in case of patients with severe hepatic impairment, see section 4.3).
Children
ANTALFEBAL should not be administered to infants under 6 months of age or body weight below 5 kg, as there is no adequate experience to support its use in this age group.
04.3 Contraindications
§ Hypersensitivity to the active ingredient ibuprofen, to other non-steroidal anti-inflammatory drugs (NSAIDs), to the Allura Red AC dye, or to any excipient;
§ history of asthma attacks, edema of the nasal mucosa or skin reactions following the use of acetylsalicylic acid or other non-steroidal anti-inflammatory drugs;
§ peptic ulcer / active haemorrhage, or a history of peptic ulcer / recurrent haemorrhage (two or more distinct episodes of ascertained ulceration or bleeding);
§ positive history of gastrointestinal bleeding or perforation related to previous treatment with NSAIDs;
§ cerebrovascular event or other active haemorrhage;
§ severe liver or kidney dysfunction;
§ severe heart failure;
§ last three months of pregnancy (see par.4.6)
§ in case of substantial fluid loss (caused by vomiting, diarrhea or lack of fluid intake).
04.4 Special warnings and appropriate precautions for use
Gastrointestinal safety
The use of ANTALFEBAL in combination with other NSAIDs, including selective cyclooxygenase-2 inhibitors, is not recommended.
To minimize undesirable events it is advisable to use the minimum effective dose for the shortest possible time (see section 4.2 and gastrointestinal and cardiovascular risks below).
Senior citizens
The elderly population has a higher incidence of adverse reactions to NSAIDs, in particular gastrointestinal bleeding and perforation, sometimes fatal (see section 4.2).
Gastrointestinal bleeding, ulceration and perforation
Gastrointestinal bleeding, ulceration or perforation, sometimes fatal, have been reported for all NSAIDs during treatment, with or without warning signs or a previous history of serious gastrointestinal events.
The risk of GI bleeding, ulceration or perforation is greater at high doses of NSAIDs, in patients with a history of ulcer, particularly if complicated with haemorrhage or perforation (see section 4.3) and in the elderly. For these patients it is advisable to start treatment with the lowest recommended dose.
The combination with protective agents (for example, misoprostol or proton pump inhibitors) is indicated in this patient population, as well as in the case of subjects requiring concomitant intake of small doses of acetylsalicylic acid or other drugs that could increase gastrointestinal risk (see below and section 4.5).
Patients with a history of gastrointestinal toxicity, particularly if elderly, should report any unusual abdominal symptoms (especially gastrointestinal bleeding) to their physician, particularly in the initial stages of treatment.
Particular caution is advised in patients who concomitantly use drugs that may increase the risk of ulceration or bleeding, such as oral corticosteroids, anticoagulants such as warfarin, selective serotonin reuptake inhibitors or antiplatelet agents such as acetylsalicylic acid (see par. 4.5).
In case of gastrointestinal bleeding or perforation in patients receiving ANTALFEBAL, the treatment should be discontinued.
Pay particular attention in the administration of NSAIDs in patients with a positive history of gastrointestinal diseases (ulcerative colitis, Crohn's disease), as the use of these drugs could aggravate these conditions (see section 4.8).
Cardiovascular and cerebrovascular effects
Particular caution (interview with doctor or pharmacist) before starting treatment is recommended in patients with a history of hypertension and / or heart failure, as fluid retention, hypertension and edema have been reported in association with NSAID therapy.
Clinical and epidemiological data suggest that the use of ibuprofen, particularly at high doses (2400 mg / day) and in long-term treatment, may be associated with a slightly increased risk of arterial thrombotic events (for example, myocardial infarction or stroke) In general, epidemiological studies have not shown that low-dose ibuprofen (e.g. 1200 mg / day) is associated with an increased risk of myocardial infarction.
Skin reactions
Serious skin reactions, some of them with a fatal outcome, including exfoliating dermatitis, Stevens-Johnson syndrome and toxic epidermal necrolysis, have been reported very rarely in association with the use of NSAIDs (see section 4.8). Patients appear to be at most high risk for these reactions in the early stages of therapy: the onset of the reaction occurs in most cases within the first month of treatment. ANTALFEBAL should be discontinued immediately upon the appearance of skin rash, mucosal lesions or other signs of hypersensitivity.
Particular caution is advised in the case of patients with:
§ acute intermittent porphyria,
§ systemic lupus erythematosus and mixed connective tissue diseases,
§ gastrointestinal disorders, ulcerative colitis or Crohn's disease,
§ hypertension, edema,
§ heart failure,
§ impaired renal function,
§ liver disorders,
§ allergies (for example, skin reactions to other agents, asthma, hay fever), chronic edema of the mucous membranes or obstruction of the airways,
§ infections, as ibuprofen could mask the signs, especially in the case of chickenpox.
In case of taking ibuprofen there may be a risk of a worsening or a delayed diagnosis of bacterial infections of the soft tissues. (In the package leaflet the patient is informed that in case of infection the medicine should only be taken if advised by the doctor as the risk for certain infections may increase).
Episodes of acute severe hypersensitivity (eg, anaphylactic shock) have been observed very rarely.
When the first symptoms of a hypersensitivity reaction appear after taking / administering ANTALFEBAL, stop treatment immediately. The necessary medical measures must be taken by specialist medical personnel, in line with the symptoms manifested. Ibuprofen may temporarily inhibit platelet function (thrombocytic aggregation). Consequently, patients with coagulation disorders should be carefully monitored.
In case of prolonged use of ANTALFEBAL, it is recommended to carry out regular checks of liver values, renal function and blood count.
Prolonged use of high-dose analgesics can lead to headaches which therefore should not be treated with further doses of the drug.
The habitual intake of analgesics in general, but especially the combination of several pain relievers, can cause permanent kidney damage and expose you to the risk of kidney failure (analgesic nephropathy).
There is a risk of impaired renal function in dehydrated children and adolescents.
Information about some of the ingredients of ANTALFEBAL
The medicinal product contains sucrose (5 ml of oral suspension contains approximately 1.5 g). Administration of this medicinal product should be avoided in patients with rare hereditary problems of fructose intolerance, glucose-galactose malabsorption or sucrose-isomaltase insufficiency. Furthermore, this must be taken into account in patients with diabetes mellitus.
The medicine contains Allura Red AC dye (0.035 mg) which may cause allergic reactions.
04.5 Interactions with other medicinal products and other forms of interaction
Ibuprofen (like other NSAIDs) should be taken with caution when administered concomitantly with the following drugs:
Other NSAIDs, including salicylates
Concomitant use of several NSAIDs may increase the risk of gastrointestinal bleeding and ulcers due to a synergistic effect. Concomitant use of ibuprofen and other NSAIDs should therefore be avoided (see section 4.4).
Digoxin, phenytoin, lithium
Concomitant use of ANTALFEBAL and preparations of digoxin, phenytoin or lithium may increase the serum levels of these medicinal products. With correct use (maximum 4 days), a control of serum levels of lithium, digoxin and phenytoin is normally not necessary.
Diuretics, ACE inhibitors and angiotensin II receptor antagonists
NSAIDs may impair the action of diuretics and other hypertensives. In some patients with impaired renal function (for example, dehydrated or elderly subjects with impaired renal function) concomitant use of an ACE inhibitor or angiotensin receptor antagonists II which inhibit cyclooxygenase may lead to further worsening of kidney function, including acute renal failure, which is usually reversible. Consequently, co-administration requires special caution, especially in the elderly. After initiation of concomitant therapy, and on a periodic basis thereafter, patients should be adequately hydrated and their renal function monitored.
Concomitant administration of ANTALFEBAL and potassium-sparing diuretics may cause hyperkalaemia.
Corticosteroids
Increased risk of gastrointestinal bleeding or ulceration (see section 4.4).
Antiplatelet agents and serotonin reuptake inhibitors (SSRIs)
Increased risk of gastrointestinal bleeding (see section 4.4).
Acetylsalicylic acid
Experimental data show that ibuprofen can inhibit the effect on platelet aggregation of low-dose acetylsalicylic acid when drugs are administered concomitantly. However, the paucity of the data and the uncertainties regarding their application to the clinical situation mean that no firm conclusions can be drawn about the regular use of ibuprofen, and no clinically relevant effect is considered likely for the occasional use of ibuprofen ( see par. 5.1).
Methotrexate
The administration of ANTALFEBAL in the 24 hours preceding or following the assumption of methotrexate, can lead to high concentrations of the same and to an enhancement of its toxicological effect.
Cyclosporine
The risk of a kidney-damaging effect from cyclosporine is increased by concomitant administration of certain non-steroidal anti-inflammatory drugs. This effect cannot be excluded in case of concomitant use of cyclosporine and ibuprofen.
Anticoagulants
NSAIDs may potentiate the effect of anticoagulants, such as warfarin (see section 4.4).
Sulfonylureas
Clinical studies have shown interactions between non-steroidal anti-inflammatory drugs and oral antidiabetic drugs (sulfonylureas). Although interactions between ibuprofen and sulfonylureas have not been described so far, a check of blood glucose values is recommended in case of concomitant intake.
Tacrolimus
The risk of nephrotoxicity is greater in case of concomitant administration of the two drugs.
Zidovudine
During concomitant treatment, there was an increased risk of haemarthrosis and hematoma for HIV-positive patients prone to bleeding.
Probenecid and sulfinpyrazone:
Medicinal products containing probenecid or sulfinpyrazone may delay the elimination of ibuprofen.
04.6 Pregnancy and lactation
Pregnancy
Inhibition of prostaglandin synthesis may have adverse effects on pregnancy and / or embryo-fetal development.
Data from epidemiological studies show an increased risk of miscarriage and cardiac malformations and gastroschisis after use of prostaglandin synthesis inhibitors in early pregnancy. The risk has been estimated to increase with dose and duration of therapy. In animals, administration of a prostaglandin synthesis inhibitor has been shown to cause increased pre- and post-implantation loss and embryo-fetal mortality.Furthermore, an increased incidence of various malformations, including cardiovascular, has been reported in animals given prostaglandin synthesis inhibitors during the organogenic period.
During the first and second trimester of pregnancy, ibuprofen should not be given unless clearly needed. If ibuprofen is used by a woman trying to conceive, or during the first and second trimester of pregnancy , the treatment should be as short as possible and the dose as low as possible.
During the third trimester of pregnancy, all prostaglandin synthesis inhibitors can expose the fetus to:
• cardiopulmonary toxicity (with premature closure of the arterial duct and pulmonary hypertension);
• renal dysfunction, which can progress to renal failure with oligohydramnios;
the mother and the unborn child, at the end of pregnancy, to:
• possible prolongation of bleeding time, an 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
Small amounts of the active ingredient ibuprofen and its catabolic products are secreted into breast milk. As no adverse effects are known to the infant so far, breastfeeding may not be stopped if the recommended dose is taken for the short-term treatment of mild to moderate pain or fever.
Fertility
There is some evidence that substances that inhibit cyclooxygenase / prostaglandin synthesis can cause a woman's fertility to be impaired through their effect on ovulation. This effect is reversible on discontinuation of the drug.
04.7 Effects on ability to drive and use machines
Short-term intake of ANTALFEBAL does not affect the ability to drive or use machines.
04.8 Undesirable effects
In each incidence group, undesirable effects are reported in order of decreasing severity.
The list of the following undesirable effects includes all undesirable effects reported in case of treatment with ibuprofen, including those in patients with rheumatism undergoing long-term therapy at high doses. The incidence rates, which also include very rare cases, concern the short-term use of daily doses up to a maximum of 1200 mg of ibuprofen administered orally and 1800 mg of ibuprofen in suppositories.
For the following undesirable effects it must be taken into account that they are, in general, dose dependent and subjective.
The most commonly observed undesirable effects are gastrointestinal in nature. Peptic ulcers, perforation or gastrointestinal bleeding, sometimes with fatal outcome, may occur, particularly in the elderly population (see section 4.4). After administration, nausea, vomiting, diarrhea, flatulence, constipation, dyspepsia, abdominal pain, melaena, haematemesis, ulcerative stomatitis, exacerbation of colitis and Crohn's disease have been reported (see section 4.4). Gastritis was observed less frequently. In particular, the risk of gastrointestinal bleeding is dependent on both the dose and the duration of treatment.
Edema, hypertension and heart failure have been reported in association with NSAID treatment.
Data from clinical studies and epidemiological examinations show that the use of ibuprofen, particularly at high doses (2,400 mg / day), and in long-term therapies may be associated with a slightly increased risk of arterial thrombotic events (for example , myocardial infarction or stroke) (see section 4.4).
Cardiac pathologies
Very rare: palpitations, heart failure, myocardial infarction.
Disorders of the blood and lymphatic system
Very rare: haematopoiesis disorders (anemia, leukopenia, thrombocytopenia, pancytopenia, agranulocytosis).
The first symptoms can be fever, sore throat, superficial lesions of the oral cavity, flu-like disorders, marked fatigue, epistaxis and skin bleeding.
In long-term therapy, regular monitoring of blood counts is advisable.
Nervous system disorders
Uncommon: Central nervous system disorders, such as headache, dizziness and wobbling, sleepiness, agitation, irritability or tiredness.
Eye disorders
Uncommon: vision disturbances.
Ear and labyrinth disorders
Rare: tinnitus.
Gastrointestinal disorders
Common: gastrointestinal pain, such as heartburn, abdominal pain, nausea, vomiting, flatulence, diarrhea, constipation and gastrointestinal blood loss which in exceptional cases can cause anemia.
Uncommon: gastrointestinal ulcers, with the possibility of bleeding and perforation. Ulcerative stomatitis, exacerbation of colitis and Crohn's disease (see section 4.4), gastritis.
Very rare: esophagitis, pancreatitis, intestinal diaphragm atresia formation.
In case of severe epigastric pain, haematemesis, or melaena the patient should immediately discontinue treatment and seek medical attention.
Renal and urinary disorders
Very rare: edema formation, particularly in patients with arterial hypertension or renal insufficiency, nephrotic syndrome, interstitial nephritis which may be accompanied by acute renal insufficiency.
Renal tissue changes (papillary necrosis) and elevated blood uric acid concentrations may also occur rarely. Consequently, renal function must be monitored regularly.
Skin and subcutaneous tissue disorders
Very rare: Bullous reactions including Stevens-Johnson syndrome and toxic epidermal necrolysis.
In exceptional cases, severe skin infections and soft tissue complications may occur during a "chickenpox infection" (see also "Infections and Infestations").
Infections and infestations
Exacerbation of infection-related inflammation (eg, development of necrotizing fasciitis) has been reported very rarely in conjunction with the use of non-steroidal anti-inflammatory drugs. This event may be associated with the mechanism of action of non-steroidal anti-inflammatory drugs.
In the event of the onset or worsening of an "infection during the use of ANTALFEBAL" the patient should immediately seek medical attention. It is necessary to ascertain whether there are indications for initiating anti-infective / antibiotic therapy.
Very rarely, symptoms of aseptic meningitis with neck stiffness, headache, nausea, vomiting, fever or drowsiness have been observed during treatment with ibuprofen. Patients with autoimmune diseases (SLE, mixed connective tissue diseases) appear to be predisposed.
Vascular pathologies
Very rare: arterial hypertension.
Disorders of the immune system
Uncommon: hypersensitivity reactions with skin rash and itching, as well as asthma attacks (sometimes with hypotension). In the event of such events, the patient should inform the doctor immediately and discontinue use of ANTALFEBAL.
Very rare: severe general hypersensitivity reactions. Symptoms can be: swelling of the face, tongue and larynx with narrowing of the airways, dyspnoea, palpitations, hypotension or even fatal shock. Allura Red AC dye can cause allergic reactions.
In the event of the appearance of one of these symptoms - which may occur from the first administration - seek immediate medical assistance.
Hepatobiliary disorders
Very rare: impaired liver function, liver damage, particularly in long-term therapy, hepatic failure, acute hepatitis.
Psychiatric disorders
Very rare: psychotic reactions, depression.
04.9 Overdose
a) Symptoms of overdose:
Central nervous effects such as headache, dizziness, lightheadedness and loss of consciousness, as well as abdominal pain, nausea and vomiting, can be observed as symptoms of overdose. Hypotension, respiratory depression and cyanosis may also occur.
b) Treatment of overdose:
There is no specific antidote.
05.0 PHARMACOLOGICAL PROPERTIES
05.1 Pharmacodynamic properties
Pharmacotherapeutic group: Anti-inflammatory and anti-rheumatic products, non-steroids, derivatives of propionic acid. ATC code: M01AE01
Ibuprofen is a non-steroidal anti-inflammatory drug that has been shown to be effective in classical models of inflammation by inhibiting prostaglandin synthesis. In humans, ibuprofen reduces inflammation-related fever, swelling and pain. Furthermore, ibuprofen inhibits platelet aggregation induced by ADP (adenosine di-phosphate) and collagen.
Experimental data show that ibuprofen can inhibit the effect on platelet aggregation of low-dose acetylsalicylic acid when drugs are administered concomitantly. In one study, when a single dose of ibuprofen 400 mg was taken within 8 hours or 30 minutes after an immediate-release dose of acetylsalicylic acid (81 mg), a lesser effect of ASA on thromboxane formation was observed. or platelet aggregation. However, the lack of 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 and it seems that there are no clinically relevant effects from the "occasional use of" ibuprofen.
05.2 "Pharmacokinetic properties
No pharmacokinetic studies in children have been conducted with this medicine to date. However, literature data confirm that the absorption, distribution, metabolism and elimination of ibuprofen in children is similar to that observed in adults.
After oral administration, some of the ibuprofen is already absorbed in the stomach and the remainder by the small intestine. After hepatic metabolism (hydroxylation, carboxylation), all pharmacologically inactive metabolites are mainly excreted via the kidneys (90%), but also via bile. The elimination half-life in healthy subjects and in patients with liver or kidney disease is 1.8-3.5 hours, with plasma protein binding of approximately 99%.
Peak plasma levels occur 1-2 hours after oral administration.
05.3 Preclinical safety data
Chronic toxicity
The subchronic and chronic toxicity of ibuprofen evaluated in animal studies manifests itself in the form of lesions and ulcers of the gastrointestinal tract.
Mutagenic and carcinogenic potential.
In-vitro and in-vivo mutagenicity studies did not provide any clinically relevant indication of a mutagenic effect of ibuprofen.
Studies conducted in rats and mice on the carcinogenic potential of this substance did not report any indications of carcinogenic effects.
Reproductive toxicity
Ibuprofen led to the inhibition of ovulation in rabbits and hindered implantation in various animal species (rabbit, rat, mouse). Experimental studies in two animal species have shown that ibuprofen crosses the placenta. After administration of maternally toxic doses, a higher rate of malformations (ventricular septal defects) was observed in the offspring of rats.
06.0 PHARMACEUTICAL INFORMATION
06.1 Excipients
Acesulfame Potassium, Glycerol, Sodium Benzoate (E211), Polysorbate 80, Sucrose, Corn Starch, Purified Water, Xanthan Gum, Citric Acid, Allura Red AC Color (E129), Bubblegum flavor consisting of artificial watermelon flavor, natural flavor and artificial watermelon and sweet blend flavor.
06.2 Incompatibility
Not applicable
06.3 Period of validity
3 years.
Shelf life after opening the container: 6 months.
06.4 Special precautions for storage
No particular storage conditions.
06.5 Nature of the immediate packaging and contents of the package
Polypropylene bottle of 100 ml, 150 ml and 200 ml with cap with child resistant polypropylene and polyethylene safety closure.
For the dose, each package is equipped with a polypropylene measuring cap (certified medical device) to dose the suspension as needed (2.5 ml, 5 ml and 10 ml).
06.6 Instructions for use and handling
Unused medicine and waste derived from this medicine must be disposed of in accordance with local regulations.
07.0 MARKETING AUTHORIZATION HOLDER
Rottapharm S.p.A. - Galleria Unione, 5 - 20122 Milan
08.0 MARKETING AUTHORIZATION NUMBER
ANTALFEBAL CHILDREN 100 mg / 5 ml oral suspension - 1 bottle 100 ml AIC 041630017
ANTALFEBAL CHILDREN 100 mg / 5 ml oral suspension - 1 bottle 150 ml AIC 041630029
ANTALFEBAL CHILDREN 100 mg / 5 ml oral suspension - 1 bottle 200 ml AIC 041630031
09.0 DATE OF FIRST AUTHORIZATION OR RENEWAL OF THE AUTHORIZATION
17 September 2012
