Over-the-counter medicine ideal for the symptomatic treatment of mild to moderate pain, such as headache (cephalea), acute migraine, with or without aura and dental pain.
Active ingredients
Each tablet contains 200 mg ibuprofen (as lysine salt). Each tablet contains 400 mg ibuprofen (as lysine salt).
Excipients
Tablet core: microcrystalline cellulose (E460), colloidal anhydrous silica (E551), crospovidone (E1202), povidone (E1201), magnesium stearate (E572), talc (E553b).
Tablet coating: hydrolysed polyvinyl alcohol (E1203), titanium dioxide (E171), macrogol (E152 1), talc (E553b).
Printing ink: shellac (E904), black iron oxide (E172), ammonium hydroxide (E527).
Directions
(200 mg only) For the symptomatic treatment of mild to moderate pain, such as headache, dental pain, menstrual pain and fever and pain in the common cold.
(400 mg only) For the symptomatic treatment of mild to moderate pain, such as headache, acute migraine with or without aura, dental pain, menstrual pain and fever and pain in the common cold.
Dosage
Adults and adolescents >= 40 kg body weight (12 years of age and over). (200 mg only)
Starting dose: 200 mg or 400 mg.
If necessary, an additional dose of 1 or 2 tablets (200 mg to 400 mg) may be taken.
The corresponding interval between doses should be chosen based on the symptoms and the maximum recommended daily dose.
It must not be less than 6 hours for a 400 mg dose and not less than 4 hours for a 200 mg dose.
Do not exceed the dose of 1200 mg in any 24-hour period.
(400 mg only) Starting dose: 400 mg.
If necessary, an additional dose of 400 mg may be taken. The corresponding dose interval should be chosen based on symptoms and the maximum recommended daily dose.
It should not be less than 6 hours for a 400 mg dose.
Do not exceed the dose of 1200 mg in any 24-hour period.
For the treatment of migraine the dose should be one 400 mg tablet as a single dose, if necessary 400 mg with intervals of 4 to 6 hours.
Do not exceed 1200 mg in any 24-hour period. Paediatric population (200 mg only).
Children over 6 years (20 kg - 40 kg body weight).
Ibuprofen should only be used in children with a body weight of at least 20 kg.
The maximum daily dose of ibuprofen is 20 - 30 mg of ibuprofen per kg of body weight, divided into 3 or 4 individual doses with an interval between doses of 6 to 8 hours.
The maximum recommended daily dose should not be exceeded.
A maximum dosage of 30 mg/kg ibuprofen in any 24-hour period should not be exceeded.
The following dosage information applies. Body weight: 20 kg - 29 kg; single dose: 1 tablet (200 mg ibuprofen); maximum daily dose: 3 tablets (equivalent to 600 mg ibuprofen).
Body weight: 30 kg - 39 kg; single dose: 1 tablet (200 mg ibuprofen); maximum daily dose: 4 tablets (equivalent to 800 mg ibuprofen).
If this medicine is required for more than 3 days in children over 6 years of age and in adolescents or if the symptoms worsen, it is necessary to contact a doctor.
Children under 6 years of age. The medicine is contraindicated in children under 6 years of age.
(400 mg only) The drug is contraindicated in adolescents under 40 kg of body weight or in children under 12 years of age.
If this medicine is required for more than 3 days in children over 12 years of age and in adolescents or if the symptoms worsen, it is necessary to contact a doctor.
Undesirable effects may be minimised by using the lowest effective dose for the shortest duration necessary to control symptoms.
For short-term use only.
If the medicine is required for more than 3 days in case of migraine or fever or for more than 4 days for the treatment of pain or if the symptoms worsen, the patient should be advised to consult a doctor.
Elderly patients No dose adjustment is necessary.
Elderly patients should be monitored particularly carefully due to the possible adverse effect profile.
Patients with gastric sensitivity Patients with sensitive stomachs should take the medicine during a meal.
Taking ibuprofen after a meal may delay the onset of its action.
If this occurs, additional ibuprofen should not be taken until the corresponding dosing interval has elapsed.
Patients with renal impairment.
No dose reduction is required in patients with mild to moderate renal impairment.
Patients with hepatic impairment.
No dose reduction is required in patients with mild to moderate hepatic impairment.
Method of administration For oral administration and short-term use only.
Ibuprofen tablets should be swallowed whole with plenty of water.
Do not chew the tablets.
Conservation
This medicinal product does not require any special storage conditions.
Contraindications/Side Effects
Ibuprofen is contraindicated in patients: with hypersensitivity to the active substance or to any of the excipients, with previous hypersensitivity reactions (e.g. bronchospasm, angioedema, rhinitis, urticaria or asthma) in response to acetylsalicylic acid (ASA) or other nonsteroidal anti-inflammatory drugs (NSAIDs), with presence or history of recurrent peptic ulcer/haemorrhage (two or more distinct episodes of proven ulceration or bleeding), with history of gastrointestinal bleeding or perforation related to previous NSAID treatment, with severe hepatic insufficiency, severe renal insufficiency or severe cardiac insufficiency (NYHA Class IV), (200 mg only) children under 20 kg in weight (approximately 6 years of age); (Only 400 mg) adolescents weighing less than 40 kg or children under 12 years of age; with cerebrovascular haemorrhage or other types of active bleeding, with unexplained blood formation disorders, with severe dehydration (caused by vomiting, diarrhoea or insufficient fluid intake), during the last trimester of pregnancy.
Warnings
Undesirable effects may be minimised by using the lowest effective dose for the shortest duration necessary to achieve symptom control (see effects on the gastrointestinal and cardiovascular systems).
Caution should be exercised when administering ibuprofen to patients suffering from the following conditions, which may be aggravated: inborn errors of porphyrin metabolism (e.g. acute intermittent porphyria), coagulation disorders (ibuprofen may prolong the duration of coagulation), directly after major surgery, systemic lupus erythematosus and mixed connective tissue diseases (e.g. increased risk of aseptic meningitis), hypertension and/or heart failure, since renal function may deteriorate, in patients suffering from hay fever, nasal polyps or chronic obstructive respiratory disorders, since there is an increased risk of allergic reactions for them. These may present an asthma attack (so-called analgesic asthma), Quincke's edema or urticaria, in patients who react with allergies to other substances, since there is also an increased risk of the appearance of hypersensitivity reactions during the use of ibuprofen.
Elderly. The elderly have an increased frequency of adverse reactions to NSAIDs, especially gastrointestinal bleeding and perforation, which may be fatal.
Respiratory reactions Bronchospasm may be precipitated in patients suffering from bronchial asthma or allergic diseases or with a history of such pathologies.
Other NSAIDs. The use of ibuprofen with other NSAIDs, including selective cyclooxygenase-2 inhibitors, increases the risk of adverse reactions and should be avoided.
Renal effects. Renal impairment, as renal function may deteriorate further.
In general terms, the habitual intake of analgesics, particularly the combination of different analgesic substances, can lead to permanent kidney damage with risk of kidney failure (analgesic nephropathy).
This risk may increase with physical exertion associated with salt loss and dehydration.
Therefore it should be avoided.
There is a risk of renal impairment in dehydrated children and adolescents.
Hepatic effects. Hepatic dysfunction. It is appropriate to discontinue ibuprofen therapy when deterioration of liver function occurs concomitantly with its administration.
After discontinuation of treatment, the health condition usually returns to normal.
Occasional blood glucose monitoring is also appropriate.
Cardiovascular and cerebrovascular effects. Particular caution is required (discuss with your doctor or pharmacist) before starting treatment in patients with a history of hypertension and/or heart failure, because fluid retention, hypertension and edema have been reported in association with NSAID therapy.
Patients with uncontrolled hypertension (NYHA class II-III), congestive heart failure, established ischemic heart disease, peripheral arterial disease, and/or cerebrovascular disease should be treated with ibuprofen only after careful consideration and high doses (2400 mg/day) should be avoided.
Careful consideration should also be exercised before initiating long-term treatment in patients with risk factors for cardiovascular events (e.g. hypertension, hyperlipidaemia, diabetes mellitus or smoking), particularly if high doses of ibuprofen (2400 mg/day) are required.
Clinical trials suggest that use of ibuprofen, particularly at a high dose (2400 mg/day) and in long term treatment, may be associated with a small increased risk of arterial thrombotic events (for example myocardial infarction or stroke).
Overall, epidemiological studies do not indicate that low doses of ibuprofen (e.g. <=1200 mg/day) are associated with an increased risk of arterial thrombotic events.
Alteration of female fertility.
There is some evidence that drugs which inhibit cyclooxygenase/prostaglandin synthesis may cause alterations in female fertility by an effect on ovulation.
This is reversible upon discontinuation of treatment.
Gastrointestinal safety. 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.
Gastrointestinal bleeding, ulceration or perforation, which can be fatal, has been reported with all NSAIDs at any time during treatment, with or without warning symptoms or a previous history of serious GI events.
In patients with a history of ulcer, particularly if complicated by haemorrhage or perforation, and in the elderly, the risk of gastrointestinal bleeding, ulceration or perforation is higher with increasing doses of NSAIDs.
These patients should start treatment on the lowest available dose.
Concomitant use of protective agents (e.g. misoprostol or proton pump inhibitors) should be considered for these patients as well as for patients taking concomitant low-dose acetylsalicylic acid or other drugs likely to increase the risk of gastrointestinal events.
Patients with a history of gastrointestinal toxicity, particularly when elderly, should report any unusual gastrointestinal symptoms (especially gastrointestinal bleeding) promptly, particularly in the initial stages of treatment.
Caution should be exercised in treating patients receiving concomitant medications which could increase the risk of ulceration or bleeding, such as oral corticosteroids, anticoagulants such as warfarin, selective serotonin reuptake inhibitors or anti-platelet agents such as acetylsalicylic acid.
If gastrointestinal bleeding or ulceration occurs in patients receiving ibuprofen, the treatment should be withdrawn.
Skin reactions Serious skin reactions, some of them fatal, such as exfoliative dermatitis, Stevens-Johnson syndrome, and toxic epidermal necrolysis, have been reported very rarely in association with the use of NSAIDs.
In the early stages of therapy, patients appear to be at higher risk of these reactions: in fact, the onset of the reaction occurs in most cases within the first month of treatment.
The use of ibuprofen should be discontinued at the first appearance of skin rash, mucosal lesions, or any other sign of hypersensitivity.
In rare cases, chickenpox can cause severe skin reactions and infectious complications of soft tissues.
Interactions
The use of ibuprofen should be avoided in association with acetylsalicylic acid.
Concomitant administration of ibuprofen and cetylsalicylic acid is generally not recommended due to the potential for increased adverse effects.
Experimental data suggest that ibuprofen may competitively inhibit the effect of low-dose aspirin on platelet aggregation when the two drugs are administered concomitantly.
Although there are uncertainties regarding the extrapolation of these data to the clinical situation, the possibility that regular, long-term use of ibuprofen may reduce the cardioprotective effect of low-dose aspirin cannot be excluded. No clinically relevant effect is considered likely following occasional use of ibuprofen.
Other NSAIDs including salicylates and selective cyclooxygenase-2 inhibitors: Avoid concomitant use of two or more NSAIDs, as this may increase the risk of gastrointestinal ulcers and bleeding due to a synergistic effect.
Anticoagulants: NSAIDs may increase the effects of anticoagulants, such as warfarin.
Diuretics, ACE inhibitors and angiotensin II antagonists: NSAIDs may reduce the effect of diuretics and other antihypertensive drugs.
In some patients with compromised renal function (e.g. dehydrated patients or elderly patients with compromised renal function) the co-administration of an ACE inhibitor or an angiotensin II antagonist and agents that inhibit the cyclooxygenase system may result in further deterioration of renal function, including acute renal failure, which is usually reversible.
Therefore, the combination should be administered with caution, especially in elderly patients.
Patients should be adequately hydrated and consideration should be given to monitoring renal function after initiation of concomitant therapy and regularly thereafter.
Potassium-sparing diuretics: Concomitant administration of ibuprofen and potassium-sparing diuretics may lead to hyperkalaemia (monitoring of serum potassium is recommended).
Corticosteroids: increased risk of adverse reactions, especially of the gastrointestinal tract (gastrointestinal ulceration or bleeding).
Antiplatelet agents and selective serotonin reuptake inhibitors (SSRIs): increased risk of gastrointestinal bleeding.
Digoxin: NSAIDs may exacerbate heart failure, reduce glomerular filtration rate, and increase plasma digoxin levels.
A serum digoxin check is not required, as a rule, in correct use (maximum 4 days).
Phenytoin: Concomitant use of ibuprofen with phenytoin preparations may increase serum phenytoin levels.
A monitoring of serum phenytoin is not required, as a rule, in correct use (maximum 4 days).
Lithium: There is evidence of potential increases in plasma lithium levels.
A serum lithium check is not required, as a rule, in correct use (maximum 4 days).
Methotrexate: Administration of ibuprofen within 24 hours before administration of methotrexate may lead to an increase in methotrexate concentration and an increase in toxic effects.
Ciclosporin: The risk of a damaging effect on the kidneys due to ciclosporin is increased by co-administration of some NSAIDs.
This effect cannot be excluded even when ciclosporin is combined with ibuprofen.
Mifepristone. NSAIDs should not be used for 8-12 days after mifepristone administration, because NSAIDs may reduce the effect of mifepristone.
Sulfinpyrazone: Medicines containing sulfinpyrazone may delay the excretion of ibuprofen.
Probenecid: Medicines containing probenecid may reduce the excretion of NSAIDs and may increase their serum concentrations.
Tacrolimus: possible increased risk of nephrotoxicity if NSAIDs are co-administered with tacrolimus.
Zidovudine: Increased risk of haematological toxicity when NSAIDs are co-administered with zidovudine.
A blood count is recommended 1-2 weeks after initiation of co-administration.
There are indications of an increased risk of haemarthrosis and haematoma in HIV-positive patients with haemophilia receiving concomitant treatment with zidovudine and ibuprofen.
Sulfonylureas: NSAIDs may either increase or decrease the hypoglycaemic effect of sulfonylureas.
Caution is advised in case of simultaneous treatment.
Quinolone antibiotics: Animal data suggest that NSAIDs may increase the risk of convulsions associated with quinolone antibiotics.
Patients taking NSAIDs and quinolones may be at increased risk of developing seizures.
Alcohol, bisphosphonates, oxpentifylline (pentoxifylline), and sulfinpyrazone: may potentiate the gastrointestinal effects and the risk of bleeding or ulceration.
Baclofen: increased baclofen toxicity.
Side effects
Possible side effects are those observed with ibuprofen and acid.
Adverse effects are mostly dose-dependent and vary individually.
In particular, the risk of gastrointestinal bleeding is dependent on the dose and duration of treatment.
The following side effects are related to short-term use of low-dose ibuprofen (up to 1200 mg daily for mild to moderate pain and fever).
Other adverse effects may occur with treatments for other indications or prolonged use.
Adverse reactions associated with ibuprofen are listed in the table below by system organ class and frequency.
Frequencies are defined as very common (>= 1/10), common (>= 1/100 and < 1/10), uncommon (>= 1/1000 and < 1/100), rare (>= 1/10,000 and < 1/1000), very rare (< 1/10,000) and not known (cannot be estimated from the available data).
For each frequency, undesirable effects are listed in descending order of frequency.
Pathologies of the haemolymphopoietic system.
Very rare: haematopoietic disorders.
Immune system disorders.
Uncommon: hypersensitivity reactions with urticaria and pruritus; very rare: severe hypersensitivity reactions.
Symptoms may include: swelling of the face, tongue and larynx, edema, dyspnea, tachycardia, hypotension (anaphylaxis, angioedema or severe shock).
Psychiatric disorders: Rare: confusion, hallucinations; not known: psychotic disorders, depression.
Nervous system disorders: Common: headache, drowsiness, vertigo, fatigue, agitation, dizziness, insomnia, irritability; very rare: aseptic meningitis.
Eye disorders. Not known: amblyopia, blurred vision, reduced vision. Ear and labyrinth disorders. Rare: tinnitus.
Cardiac disorders: Very rare: palpitations, myocardial infarction, acute pulmonary oedema; not known: cardiac failure, oedema.
Vascular disorders: Not known: arterial hypertension.
Respiratory, thoracic and mediastinal disorders: Uncommon: rhinitis; very rare: exacerbation of asthma; not known: respiratory tract reactions such as bronchospasm, asthma or dyspnoea.
Gastrointestinal disorders. Very common: heartburn, abdominal pain, nausea, dyspepsia, diarrhoea, flatulence, constipation and vomiting; common: peptic ulcer, gastrointestinal perforation or bleeding, melaena, haematemesis, ulcerative stomatitis, colitis; uncommon: gastritis; very rare: esophagitis, pancreatitis, intestinal stricture; not known: exacerbation of colitis and Crohn's disease.
Hepatobiliary disorders: Very rare: liver dysfunction, liver damage, especially in long-term use, liver failure, acute hepatitis and jaundice.
Skin and subcutaneous tissue disorders. Uncommon: photosensitivity, rash; very rare: severe forms of skin and soft tissue reactions may occur during varicella infections, necrotising fasciitis, exfoliative dermatitis, bullous reactions, including Stevens-Johnson syndrome, erythema multiforme and toxic epidermal necrolysis; not known: alopecia, adverse reaction with eosinophilia and systemic symptoms (Dress syndrome); renal and urinary disorders. Uncommon: development of oedema, especially in patients with arterial hypertension or renal insufficiency, nephrotic syndrome, interstitial nephritis which may be associated with renal insufficiency; rare: renal papillary necrosis; very rare: acute renal failure, dysuria.
Reproductive system and breast disorders: Not known: menstrual disorders. Diagnostic tests: Rare: increased blood urea nitrogen, transaminases and alkaline phosphatase, decreased haemoglobin and haematocrit, inhibition of platelet aggregation, decreased serum calcium, increased serum uric acid; not known: prolonged bleeding time.
Reporting of suspected adverse reactions . Reporting suspected adverse reactions that occur after authorisation of the medicinal product is important. It allows continued 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 at http://www.agenziafarmaco.gov.it/content/com e-segnalare-una-sosp etta-reazione-avversa.
Pregnancy and breastfeeding
Pregnancy. Inhibition of prostaglandin synthesis may adversely affect pregnancy and/or embryo/fetal development.
Data from epidemiological studies show an increased risk of miscarriage and of cardiac malformation and gastroschisis after use of a prostaglandin synthesis inhibitor in early pregnancy.
The risk is believed to increase with dose and duration of therapy.
In animals, administration of prostaglandin synthesis inhibitors induced an increase in 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 period of organogenesis.
During the first and second trimester of pregnancy, ibuprofen should not be administered unless clearly necessary.
If ibuprofen is used by a woman attempting to conceive, or during the first and second trimester of pregnancy, the dose and duration of treatment should be kept as low as possible.
During the third trimester of pregnancy, all prostaglandin synthesis inhibitors may expose the fetus to: cardiopulmonary toxicity (with premature closure of the ductus arteriosus and pulmonary hypertension); renal dysfunction, which may progress to renal failure with oligohydramnios; the mother and the neonate, at the end of pregnancy, to: possible prolongation of bleeding time and antiaggregant effect which may occur even at very low doses; inhibition of uterine contractions with consequent delay or prolongation of labor.
Consequently, the use of ibuprofen is contraindicated during the third trimester of pregnancy.
Breastfeeding. Only small amounts of ibuprofen and its metabolites are excreted in breast milk.
To date, no harmful effects on infants are known.
Consequently, ibuprofen can be used during breastfeeding for the treatment of pain and fever in the short term and at the recommended doses.
Safety for long-term use has not been established.
Fertility. There is evidence that drugs which inhibit cyclooxygenase/prostaglandin synthesis may cause impairment of female fertility by an effect on ovulation.
This event is however reversible with suspension of treatment.
