IBUPROFEN - GENERIC DRUG - PACKAGE LEAFLET - LEAFLETS

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Ibuprofen - Generic Drug - Package Leaflet

Indications Contraindications Precautions for use Interactions Warnings Dosage and method of use Overdose Unwanted Effects Shelf Life

Active ingredients: Ibuprofen

IBUPROFEN DOC 400 mg film-coated tablets
IBUPROFEN DOC 600 mg film-coated tablets

Why is Ibuprofen - Generic Drug used? What is it for?

PHARMACOTHERAPEUTIC CATEGORY

IBUPROFEN DOC (Ibuprofen) belongs to the category of non-steroidal anti-inflammatory drugs (NSAIDs).

THERAPEUTIC INDICATIONS

As an antirheumatic in:

osteoarthritis in all its localizations (cervical, dorsal, lumbar osteoarthritis; osteoarthritis of the shoulder, hip, knee, diffuse osteoarthritis, etc.), scapulo-humeral periarthritis, lumbago, sciatica, radiculo-neuritis; fibrositis, tenosynovitis, myositis , sports traumatology, rheumatoid arthritis, Still's disease. As an analgesic in painful forms of different etiology:
in accidental and sports traumatology;
in dental practice, in post-extraction pain and after odontostomatological interventions;
in obstetrics: in post-episiotomic and post-partum pain;
in gynecology: in the prevention and treatment of dysmenorrhea;
in surgery: in the treatment of post-operative pain;
in ophthalmology: in post-operative pain and painful forms of various etiology;
in general medicine: in the treatment of migraine and headache.

Contraindications When Ibuprofen - Generic Drug should not be used

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 (glomerular filtration less than 30ml / min).
Severe heart failure.
Severe or active peptic ulcer.
History of gastrointestinal bleeding or perforation related to previous active treatments or history of recurrent peptic ulcer / haemorrhage (two or more distinct episodes of proven ulceration or bleeding).
Ibuprofen should not be given to patients with medical conditions that lead to an increased bleeding tendency
Ibuprofen is contraindicated during the third trimester of pregnancy (see "Special warnings" section).
Severe dehydration (caused by vomiting, diarrhea or insufficient fluid intake). Use in children with a body weight of less than 40 kg or in children under 12 years of age.

Precautions for use What you need to know before taking Ibuprofen - Generic Drug

Caution is needed in patients with certain conditions, which may worsen:

congenital disorders of porphyrin metabolism (eg acute intermittent porphyria);
Systemic lupus erythematosus and mixed connective tissue disease - increased risk of aseptic meningitis;
directly after major surgery;
in patients who react allergically to other substances, as there is an increased risk of hypersensitivity reactions for them even with the use of IBUPROFEN DOC;
in patients suffering from hay fever, nasal polyps or chronic obstructive respiratory disease as there is an increased risk of allergic reactions for them. These can manifest as asthma attacks (so-called analgesic asthma), Quincke's edema or urticaria.

The concomitant use of ibuprofen with other NSAIDs, including selective cyclooxygenase-2 (COX-2) inhibitors, should be avoided due to an increased risk of ulceration or bleeding (see "Interactions").

Undesirable effects can be minimized by using the lowest effective dose for the shortest possible duration of treatment needed to control symptoms (see section "Dose, method and time of administration" and below on gastrointestinal and cardiovascular risks. Like other NSAIDs, ibuprofen can mask signs of infection.

Senior citizens

Elderly patients have an increased frequency of adverse reactions to NSAIDs, especially gastrointestinal bleeding and perforation, which can be fatal (see section "Dose, method and time of administration).

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 "Contraindications"), 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. Concomitant use of gastroprotective 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 "Interactions").

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 in patients taking concomitant medications that may 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 "Interactions") When gastrointestinal bleeding or ulceration occurs in patients taking IBUPROFEN 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 "Undesirable effects").

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.

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, Stevens-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. Treatment with ibuprofen should be discontinued at the first appearance of skin rash, mucosal lesions or any other signs of hypersensitivity as well as if visual disturbances or persistent signs of liver dysfunction occur.

In exceptional cases, chickenpox can be at the origin of serious skin and infectious complications of the soft tissues. Until now, the contribution of NSAIDs in the worsening of these infections cannot be excluded. Therefore, it is recommended to avoid the use of IBUPROFEN DOC in case of chickenpox.

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 kidney damage, with the risk of renal failure (analgesic nephropathy). This risk may increase in case of physical exertion associated with loss of salts and dehydration, therefore this condition must be avoided.

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 renal failure. Patients most at risk of these reactions are those with impaired renal function, heart failure, liver dysfunction, the elderly and all those patients taking diuretics and ACE inhibitors. Discontinuation of NSAID therapy, usually it is followed by the recovery of the pretreatment state.

In case of prolonged use, monitor renal function particularly in case of diffuse lupus erythematosus.

There is a risk of impaired renal function in dehydrated children and adolescents.

Respiratory disorders

IBUPROFEN DOC should be prescribed with caution in patients with bronchial asthma or current or previous allergic disease because 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 experienced such reactions after the use of other analgesics, antipyretics, non-steroidal anti-inflammatory drugs and in subjects with bronchial hyperreactivity (asthma), nasal polyposis or previous episodes of angioedema (see the sections "Contraindications" and "Undesirable effects").

Reduced cardiac, renal and hepatic function

Particular caution should be exercised when treating 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.

Hematological effects

Ibuprofen, like other NSAIDs, can inhibit platelet aggregation and has been shown to prolong bleeding time in healthy subjects. Therefore, careful monitoring of patients with bleeding disorders or on anticoagulant therapy is recommended.

Aseptic meningitis

On rare occasions, aseptic meningitis has been observed 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 seen in patients who did not have concomitant chronic diseases (see section "Undesirable effects").

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.

Prolonged use of any pain reliever for headache can make it worse. If this occurs or is suspected, medical advice should be sought and treatment discontinued. The diagnosis of drug abuse headache (MOH) should be suspected in patients who have frequent or daily headaches despite (or due to) regular use of headache medicines.

Following concomitant alcohol consumption, the undesirable effects related to the active substance, especially those affecting the gastrointestinal tract or the central nervous system, may increase during the use of NSAIDs.

Impaired fertility

The use of IBUPROFEN DOC, as with any prostaglandin synthesis and cyclooxygenase inhibitor drug, is not recommended in women who intend to become pregnant (see also the section "Special warnings").

The administration of ibuprofen should be discontinued in women who have fertility problems or who are undergoing fertility investigations.

Interactions Which drugs or foods can modify the effect of Ibuprofen - Generic Drug

Tell your doctor or pharmacist if you are taking or have recently taken any other medicines, even those without a prescription.

Ibuprofen (like other NSAIDs) should not be used in combination with:

Low-dose acetylsalicylic acid (aspirin):

Experimental data indicate an attenuation of the inhibitory effects of acetylsalicylic acid on platelet aggregation when administered concomitantly with ibuprofen. This interaction may reduce the desired cardiovascular protective effect of acetylsalicylic acid. Therefore ibuprofen should only be used with particular caution in patients treated with acetylsalicylic acid for the inhibition of platelet aggregation.

other NSAIDs including salicylates> 100 mg / day: these substances may increase the risk of adverse reactions affecting the gastrointestinal tract. However, it is advisable not to combine ibuprofen with other NSAIDs.

The following associations should be avoided with ibuprofen:

acetylsalicylic acid:

The combination of acetylsalicylic acid and other NSAIDs must be due to the increased risk of haemorrhage. Experimental data suggest that, when administered concomitantly, ibuprofen may inhibit the effect of low dose acetylsalicylic acid on 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.

anticoagulants (dicumarolics): NSAIDs can increase the effects of anticoagulants, such as warfarin. Patients receiving coumarins should be monitored. Experimental studies show that ibuprofen enhances the effects of warfarin on bleeding time. NSAIDs and dicumarols are metabolised by the same CYP2C9 enzyme.
antiplatelet agents: NSAIDs should not be combined with antiplatelet agents such as ticlopidine due to additive inhibition of platelet function (see below).
methotrexate: NSAIDs can inhibit the tubular secretion of methotrexate and reduce its clearance with a consequent increase in the risk of toxicity; consequently, in case of treatment with methotrexate in high doses, the prescribing of NSAIDs should always be avoided (see below).
cardiac glycosides: NSAIDs can exacerbate heart failure, reduce the rate of glomerular filtration and increase plasma levels of cardiac glycosides.
Cox-2 inhibitors: Concomitant use with other NSAIDs, including selective cyclooxygenase-2 inhibitors, should be avoided due to potential additive effect.
plant extracts: Ginkgo Biloba may increase the risk of bleeding in association with NSAIDs.
mifepristone: due to the anti-prostaglandin 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 cervical maturation or uterine contractility and does not reduce the clinical efficacy of the drug on pregnancy termination.
Sulfonylureas: NSAIDs may enhance the effect of sulfonylureas. Rare cases of hypoglycaemia have been reported in patients receiving sulfonylureas taking ibuprofen.
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.

The following combinations with ibuprofen may require dose adjustment:

aminoglycosides: NSAIDs can decrease the excretion of aminoglycosides. - lithium: the simultaneous administration of lithium and NSAIDs causes an increase in plasma levels of lithium due to reduced elimination, with the possibility of reaching the toxic threshold. If this combination is necessary, it is necessary to monitor the lithemia, in order to adapt the lithium dosage during concomitant treatment with ibuprofen.
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 renal function, which includes possible acute renal failure, usually reversible. These interactions should be considered in patients taking ibuprofen 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.
beta-blockers: NSAIDs counteract the antihypertensive effect of agents that block betaadrenoreceptors.
selective serotonin reuptake inhibitors (SSRIs): increased risk of gastrointestinal bleeding; the mechanism may be linked to a reduction in the uptake of serotonin in platelets.
cyclosporins: concomitant administration with NSAIDs is believed to increase the risk of nephrotoxicity due to reduced synthesis of prostacyclin in the kidney. Consequently, in case of combination treatment, renal function should be carefully monitored.
captopril: experimental studies indicate that ibuprofen counteracts the effect of captopril on sodium excretion.
cholestyramine: the concomitant administration of ibuprofen and cholestyramine can reduce the absorption of ibuprofen (25%) from the gastrointestinal tract. These medicines should be administered at an interval of at least 2 hours.
thiazides, thiazide-related preparations and loop diuretics: NSAIDs can counteract the diuretic effect of furosemide and bumetanide, probably by inhibiting prostaglandin synthesis. They can also counteract the antihypertensive effect of thiazides.
tacrolimus: concomitant administration of NSAIDs and tacrolimus is thought to increase the risk of nephrotoxicity due to reduced synthesis of prostacyclin in the kidney. Consequently, in case of combination treatment, renal function should be carefully monitored.
methotrexate: the risk of a potential interaction between an NSAID and methotrexate should also be considered in connection with low dose methotrexate treatment, particularly in patients with renal impairment. When the combination treatment is given, renal function should be monitored. Caution should be exercised when both NSAID and methotrexate are administered over 24 hours, as plasma levels of methotrexate may increase, causing increased toxicity (see above).
corticosteroids: increased risk of gastrointestinal ulceration or bleeding. - antiplatelet medicines: increased risk of gastrointestinal bleeding (see above).
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.
ritonavir: An increase in concentration of NSAIDs is possible. - probenecid: slows down the excretion of NSAIDs, with possible increase in their plasma concentrations.
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 or fluconazole.

Consult your doctor before using ibuprofen with other medicines.

Warnings It is important to know that:

In case of prolonged use, monitor renal function particularly in case of diffuse lupus erythematosus.

Medicines such as IBUPROFEN DOC may be associated with a small 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.

If you have heart problems, 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 consult your doctor or pharmacist.

Pregnancy

Ask your doctor or pharmacist for advice before taking any medicine.

The use of IBUPROFENE DOC, like any drug that inhibits prostaglandin synthesis and cyclooxygenase, is not recommended in women who intend to become pregnant. In fact, inhibition of prostaglandin synthesis can negatively affect pregnancy and / or embryo development. fetal.

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 was considered 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.

First and second trimester: during the first and second trimester of pregnancy, IBUPROFENE DOC must not be administered except in strictly necessary cases and under direct medical supervision.

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.

Third quarter: 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 may occur even at very low doses;
Inhibition of uterine contractions resulting in delayed or prolonged labor.

Consequently, IBUPROFENE DOC is contraindicated during the third trimester of pregnancy.

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 through effects on ovulation and is not recommended in women attempting to conceive. The administration of ibuprofen should be discontinued in women who have fertility problems or who are undergoing fertility investigations.

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.

Dosage and method of use How to use Ibuprofen - Generic Drug: Dosage

Adults and adolescents weighing 40 kg and over (aged 12 years and over):

400 mg tablets: 2 - 4 per day in the opinion of the doctor.
600 mg tablets: 1 - 3 tablets per day in the opinion of the doctor.

The maximum daily dose of ibuprofen should not exceed 1800 mg. In rheumatology, to improve morning stiffness, the first oral dose is administered when the patient awakens; subsequent doses can be taken with meals.

In the presence of renal insufficiency, elimination can be reduced and the dosage should be adjusted accordingly.

Undesirable effects can be minimized by using the lowest effective dose for the shortest possible duration of treatment needed to control symptoms (see section "Precautions for use").

If the use of the drug is necessary for more than 3 days in adolescents, or in the case of worsening of symptoms, the doctor should be consulted.

If the use of the medicinal product is necessary for more than 4 days in adults, the doctor should be consulted.

Children and adolescents weighing less than 40 kg (less than 12 years of age)

IBUPROFEN DOC is not recommended in adolescents weighing less than 40 kg or in children under 12 years of age.

Senior citizens

Elderly patients are at increased risk of serious consequences of adverse reactions. If administration of an NSAID is deemed necessary, the lowest effective dose should be used for the shortest duration possible. Patients should be monitored regularly for gastrointestinal bleeding during NSAID therapy. If renal or hepatic function is impaired, the dosage should be evaluated on an individual basis.

In the treatment of elderly patients, the dosage must be carefully established by the physician who will have to evaluate a possible reduction of the dosages indicated above.

Renal impairment

Caution is required when administering to patients with renal impairment. Dosage should be evaluated on an individual basis. The dose should be kept as low as possible and renal function monitored.

Hepatic impairment

Caution is required when administering to patients with hepatic impairment. Dosage should be assessed on an individual basis and the dose should be kept as low as possible.

Method of administration

The tablets should be swallowed whole with water.

In patients with gastric sensitivity it is recommended to take ibuprofen with meals.

Overdose What to do if you have taken an overdose of Ibuprofen - Generic Drug

Symptoms

Most patients 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, and very rarely diarrhea. Gastrointestinal bleeding is also possible.

Effects on the central nervous system (CNS) include headache, tinnitus, dizziness, seizures, and loss of consciousness. In the case of more severe poisoning, toxicity is observed in the central nervous system, manifesting as drowsiness, and occasionally arousal and disorientation or coma. Occasionally patients develop seizures

Nystagmus, metabolic acidosis, hypothermia, renal effects, gastrointestinal bleeding, coma, apnea, diarrhea and CNS and respiratory depression have also been reported rarely.

Disorientation, arousal state, fainting and cardiovascular toxicity including hypotension, bradycardia and tachycardia have been reported. In cases of significant overdose, renal failure and liver damage are possible. Metabolic acidosis may occur in severe poisoning and prothrombin time / INR may be prolonged, possibly due to interference with the actions of circulatory clotting factors. Asthma exacerbation is possible in asthmatic patients.

Treatment

There is no specific antidote to ibuprofen overdose. In the event of an overdose, symptomatic and supportive treatment is therefore indicated.

In case of accidental intake of an excessive dose of the medicine, notify your doctor immediately or go to the nearest hospital.

If you have any questions about the use of ibuprofen, ask your doctor or pharmacist.

Side Effects What are the side effects of Ibuprofen - Generic Drug

Like all medicines, Ibuprofen DOC can cause side effects, although not everybody gets them.

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 "Precautions for use"). 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 ibuprofen. d "employment").

Gastritis has been observed less frequently.

Pancreatitis, esophagitis and intestinal narrowing have also been observed very rarely. The patient should be instructed to stop the medicine and to see the doctor immediately if severe upper abdominal pain or melaena or haematemesis occurs.

Immune system disorders: Hypersensitivity reactions have been reported following treatment with NSAIDs. These may consist of a) non-specific allergic reaction and anaphylaxis, b) respiratory tract reactions including asthma, even severe, bronchospasm or dyspnoea or c) various skin disorders, including various types of rash, itching, urticaria, purpura, angioedema and, more rarely, exfoliative and bullous dermatitis (including Stevens-Johnson syndrome, toxic epidermal necrolysis and erythema multiforme).

Very rarely: severe general hypersensitivity reactions. Symptoms could be: swelling of the face, tongue and larynx, dyspnoea, tachycardia, hypotension (angioedema or severe shock). If any of these symptoms occur, which can happen even on first use, immediate medical attention is required.

Cardiac and vascular disorders: edema, fatigue, hypertension and heart failure, vasculitis have been reported in association with NSAID treatment. Medicines such as ibuprofen may be associated with a small increased risk of heart attack ("myocardial infarction") or stroke.

Blood and lymphatic system disorders: leukopenia, thrombocytopenia, neutropenia, agranulocytosis, aplastic anemia and haemolytic anemia. The first signs are: fever, sore throat, superficial mouth ulcers, flu-like symptoms, severe exhaustion, bleeding and unexplained bruising. In these cases the patient should be advised to discontinue the medicinal product immediately, to avoid any self-medication containing analgesics or antipyretics and to consult the doctor. In long-term therapy, blood counts should be performed regularly.

Very rarely: pancytopenia.

Psychiatric disorders: insomnia, anxiety, depression, confusion, hallucinations, psychotic reactions.

Nervous system disorders: headache, paraesthesia, dizziness, somnolence, optic neuritis, insomnia, agitation, irritability or fatigue. Infections and infestations: aseptic rhinitis and meningitis (especially in patients with pre-existing autoimmune disorders, such as systemic lupus erythematosus and mixed connective tissue disease) with symptoms of neck stiffness, headache, nausea, vomiting, fever or disorientation (see section "Precautions d" use "). If signs of an" infection occur or worsen during the use of ibuprofen, tests should be performed to see if this is an "indication for anti-infective / antibiotic therapy.

Respiratory system disorders: bronchospasm, dyspnoea, apnea, asthma. Eye disorders: rare cases of ocular alteration with consequent visual disturbances, toxic optic neuropathy.

Ear and labyrinth disorders: impaired hearing, tinnitus, vertigo.

Hepatobiliary disorders: impaired liver function, liver failure, hepatitis and jaundice, liver damage, liver injury.

Skin and subcutaneous tissue disorders: rash (rash), pruritus, purpura, angioedema, bullous reactions, including Stevens-Johnson syndrome and toxic epidermal necrolysis (very rare), erythema multiforme, photosensitivity reactions and alopecia. In exceptional cases, severe skin infections and soft tissue complications can occur during a "chickenpox infection" (see also "Infections and Infestations").

Renal and urinary disorders: impairment of renal function and toxic nephropathy in various forms, including interstitial nephritis, nephrotic syndrome and renal failure.

Renal tissue damage (papillary necrosis) and elevated blood uric acid concentrations may also occur rarely.

Very rarely: edema formation, particularly in patients with arterial hypertension or renal insufficiency, nephrotic syndrome, interstitial nephritis which may be accompanied by acute renal insufficiency. Renal function should therefore be monitored regularly.

General disorders and administration site conditions: malaise, fatigue and edema.

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 the address 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

Keep this medicine out of the sight and reach of children.

Expiry: see the expiry date printed on the package.

Warning: do not use the medicine after the expiry date indicated on the package

The expiry date refers to the product in intact packaging, correctly stored

Medicines should not be disposed of via wastewater or household waste. Ask your pharmacist how to dispose of medicines you no longer use. This will help protect the environment.

COMPOSITION

IBUPROFENE DOC 400 mg

One tablet contains:

Active ingredient: ibuprofen 400 mg.

Excipients:

- tablet core: corn starch, pregelatinised starch, microcrystalline cellulose, colloidal anhydrous silica, magnesium stearate.

- tablet coating: cellulose derivative / polyoxyl 40 stearate, hypromellose, titanium dioxide, propylene glycol, macrogol 8000.

IBUPROFENE DOC 600 mg

One tablet contains:

Active ingredient: ibuprofen 600 mg.

Excipients:

- tablet core: corn starch, pregelatinised starch, microcrystalline cellulose, colloidal anhydrous silica, magnesium stearate.

- tablet coating: cellulose derivative / polyoxyl 40 stearate, hypromellose, titanium dioxide, propylene glycol, macrogol 8000.

PHARMACEUTICAL FORM AND CONTENT

IBUPROFEN DOC 400 mg film-coated tablets - box of 10 tablets.

IBUPROFEN DOC 400 mg film-coated tablets - carton of 30 tablets.

IBUPROFEN DOC 600 mg film-coated tablets - carton of 30 tablets.

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.

More information on Ibuprofen - Generic Drug can be found in the "Summary of Characteristics" tab. 01.0 NAME OF THE MEDICINAL PRODUCT 02.0 QUALITATIVE AND QUANTITATIVE COMPOSITION 03.0 PHARMACEUTICAL FORM 04.0 CLINICAL PARTICULARS 04.1 Therapeutic indications 04.2 Posology and method of administration 04.3 Contraindications 04.4 Special warnings and appropriate precautions for use 04.5 Interactions with other medicinal products and other forms of interaction04.6 Pregnancy and lactation04.7 Effects on the ability to drive and use machines04.8 Undesirable effects04.9 Overdose05.0 PHARMACOLOGICAL PROPERTIES05.1 Pharmacodynamic properties05.2 Pharmacokinetic properties05.3 Preclinical data of 06.0 PHARMACEUTICAL PARTICULARS 06.1 Excipients 06.2 Incompatibilities 06.3 Shelf life 06.4 Special precautions for storage 06.5 Nature of the immediate packaging and contents of the package 06.6 Instructions for use and handling 07.0 HOLDER OF THE ALL AUTHORIZATION "PLACING ON MARKETING 08.0 AUTHORIZATION NUMBER" PLACING ON MARKET09.0 DATE OF PR IMA AUTHORIZATION OR RENEWAL OF THE AUTHORIZATION 10.0 DATE OF REVISION OF THE TEXT 11.0 FOR RADIOPharmaceuticals, FULL DATA ON INTERNAL RADIATION DOSIMETRY 12.0 FOR RADIOPharmaceuticals, ADDITIONAL DETAILED INSTRUCTIONS ON ESTEMPORAN PREPARATION AND QUALITY CONTROL

01.0 NAME OF THE MEDICINAL PRODUCT

IBUPROFENE DOC TABLETS COATED WITH FILM

02.0 QUALITATIVE AND QUANTITATIVE COMPOSITION

IBUPROFEN DOC 400 mg film-coated tablets

Each film-coated tablet contains 400 mg of ibuprofen.

IBUPROFEN DOC 600 mg film-coated tablets

Each film-coated tablet contains 600 mg of ibuprofen.

For the full list of excipients, see section 6.1.

03.0 PHARMACEUTICAL FORM

Film-coated tablets.

04.0 CLINICAL INFORMATION

04.1 Therapeutic indications

As an antirheumatic in:

• osteoarthritis in all its localizations (cervical, dorsal, lumbar osteoarthritis; osteoarthritis of the shoulder, hip, knee, diffuse osteoarthritis, etc.), scapulohumeral periarthritis, lumbago, sciatica, radiculo-neuritis; fibrositis, tenosynovitis, myositis, sports traumatology, rheumatoid arthritis, Still's disease.

As an analgesic in painful forms of different etiology:

• in accidental and sports traumatology;

• in dental practice, in post-extraction pain and after odontostomatological interventions;

• in obstetrics: in post-episiotomic and post-partum pain;

• in gynecology: in the prevention and treatment of dysmenorrhea;

• in surgery: in the treatment of post-operative pain;

• in ophthalmology: in post-operative pain and painful forms of various etiology;

• in general medicine: in the treatment of migraine and headache.

04.2 Posology and method of administration

Dosage

Adults and adolescents ≥ 40 kg (aged 12 years and over) :

400 mg tablets: 2 - 4 tablets per day in the opinion of the doctor.

600 mg tablets: 1 - 3 tablets per day in the opinion of the doctor.

In the presence of renal insufficiency, elimination can be reduced and the dosage should be adjusted accordingly.

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).

If the use of the drug is necessary for more than 3 days in adolescents, or in the case of worsening of symptoms, the doctor should be consulted.

If the use of the medicinal product is necessary for more than 4 days in adults, the doctor should be consulted.

Pediatric population :

IBUPROFEN DOC is not recommended in adolescents weighing less than 40 kg or in children under 12 years of age.

Elderly patients :

In the treatment of elderly patients, the dosage must be carefully established by the physician who will have to evaluate a possible reduction of the dosages indicated above.

Renal impairment :

Caution is required when administering to patients with renal impairment. Dosage should be evaluated on an individual basis. The dose should be kept as low as possible and renal function monitored (see sections 4.3 and 4.4).

Hepatic impairment :

Caution is required when administering to patients with hepatic impairment. Dosage should be assessed on an individual basis and the dose should be kept as low as possible (see section 4.3).

Method of administration

The film-coated tablets should be swallowed whole with water.

In patients with gastric sensitivity it is recommended to take ibuprofen with meals.

04.3 Contraindications

• Hypersensitivity to the active substance or to any of the excipients listed in section 6.1.

• 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 (glomerular filtration less than 30ml / min).

• Severe heart failure (NYHA class IV).

• Severe or active peptic ulcer.

• History of gastrointestinal bleeding or perforation related to previous active treatments or history of recurrent peptic ulcer / haemorrhage (two or more distinct episodes of proven ulceration or bleeding).

• Ibuprofen must not be given to patients with medical conditions that lead to an increased tendency to bleed.

• Ibuprofen is contraindicated during the third trimester of pregnancy (see section 4.6).

• Severe dehydration (caused by vomiting, diarrhea or insufficient fluid intake).

• IBUPROFEN DOC is contraindicated in children with a body weight of less than 40 kg or in children under 12 years of age.

04.4 Special warnings and appropriate precautions for use

Caution is needed in patients with certain conditions, which may worsen:

• congenital disorders of porphyrin metabolism (eg acute intermittent porphyria);

• Systemic Lupus Erythematosus and Mixed Connective Tissue Disease - increased risk of aseptic meningitis (see section 4.8);

• directly after major surgery;

• in patients who react allergically to other substances, as there is an increased risk of hypersensitivity reactions for them even with the use of IBUPROFEN DOC;

• in patients suffering from hay fever, nasal polyps or chronic obstructive respiratory disease as there is an increased risk of allergic reactions for them. These can manifest as asthma attacks (so-called analgesic asthma), Quincke's edema or urticaria.

The concomitant use of ibuprofen 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 with the use of the lowest effective dose for the shortest possible duration of treatment needed to control symptoms (see section 4.2 and the paragraphs below on gastrointestinal and cardiovascular risks).

Like other NSAIDs, ibuprofen can mask signs of infection.

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

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 gastroprotective 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 "Interactions").

When gastrointestinal bleeding or ulceration occurs in patients taking ibuprofen 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).

Cardiovascular and cerebrovascular effects

Clinical studies suggest that the use of ibuprofen, especially at high doses (2400 mg / day) 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 arterial thrombotic events.

Patients with uncontrolled hypertension, congestive heart failure (NYHA class II-III), established ischemic heart disease, peripheral arterial disease and / or cerebrovascular disease should only be treated with ibuprofen 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, hyperlipidemia, diabetes mellitus, cigarette smoking), especially if high doses are required (2400 mg / day) of ibuprofen.

Dermatological effects

Serious skin reactions, some of them fatal, including exfoliative dermatitis, Stevens-Johnson syndrome and toxic epidermal necrolysis, have been reported very rarely in association with the use of NSAIDs (see section 4.8). In the early stages of therapy patients appear to be at higher risk: the onset of the reaction occurs in most cases within the first month of treatment. Treatment with ibuprofen should be discontinued at the first appearance of skin rash, mucosal lesions or any other signs of hypersensitivity, as well as if visual disturbances or persistent signs of liver dysfunction occur.

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.

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 the case of diffuse lupus erythematosus.

There is a risk of impaired renal function in dehydrated children and adolescents.

Respiratory disorders

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 sections 4.3 and 4.8).

Reduced cardiac, renal and hepatic function

Hematological effects

Aseptic meningitis

On rare occasions, aseptic meningitis has been observed 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 4.8).

Impaired fertility

The use of IBUPROFEN DOC, as of any drug inhibitor of prostaglandin synthesis and cyclooxygenase, is not recommended in women who intend to become pregnant (see also section 4.6).

The administration of ibuprofen 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 not be used in combination with :

• acetylsalicylic acid: concomitant administration of ibuprofen and acetylsalicylic acid is generally not recommended due to the potential for increased side effects.

Experimental data suggest that ibuprofen can competitively inhibit the effect of low-dose acetylsalicylic acid on platelet aggregation when the two drugs are administered simultaneously. Although there is uncertainty regarding extrapolation of these data to the clinical situation, the possibility cannot be excluded that regular, long-term use of ibuprofen may reduce the cardioprotective effect of low-dose acetylsalicylic acid. No relevant clinical effects are considered likely following occasional use of ibuprofen (see section 5.1). This interaction may reduce the desired cardiovascular protective effect of acetylsalicylic acid. Therefore ibuprofen should only be used with particular caution in patients treated with acetylsalicylic acid for the inhibition of platelet aggregation.

- other NSAIDs including salicylates> 100 mg / day: these substances may increase the risk of adverse reactions affecting the gastrointestinal tract (see section 4.4). However, it is advisable not to combine ibuprofen with other NSAIDs (see section 4.4).

The following associations should be avoided with ibuprofen :

- anticoagulants (dicumarolics): NSAIDs may increase the effects of anticoagulants, such as warfarin (see section 4.4). Patients receiving coumarins should be monitored. Experimental studies show that ibuprofen enhances the effects of warfarin on bleeding time. NSAIDs and dicumarols are metabolised by the same CYP2C9 enzyme.

- antiplatelet agents: NSAIDs should not be combined with antiplatelet agents such as ticlopidine due to additive inhibition of platelet function (see below).

- methotrexate: NSAIDs can inhibit the tubular secretion of methotrexate and reduce its clearance with a consequent increase in the risk of toxicity; consequently, in case of treatment with methotrexate in high doses, the prescribing of NSAIDs should always be avoided (see below).

- cardiac glycosides: NSAIDs can exacerbate heart failure, reduce the rate of glomerular filtration and increase plasma levels of cardiac glycosides.

- Cox-2 inhibitors: 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 can increase the risk of bleeding in association with NSAIDs.

- mifepristone: due to the anti-prostaglandin properties of NSAIDs, there may theoretically be a decrease in the efficacy of the drug. 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 cervical ripening or uterine contractility and does not reduce the clinical efficacy of the drug on pregnancy termination.

- Sulfonylureas: NSAIDs may enhance the effect of sulfonylureas. Rare cases of hypoglycaemia have been reported in patients receiving sulfonylureas taking ibuprofen.

- zidovudine: increased risk of haematic toxicity in case of co-administration 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.

The following combinations with ibuprofen may require dose adjustment :

- aminoglycosides: NSAIDs can decrease the excretion of aminoglycosides.

- lithium: the simultaneous administration of lithium and NSAIDs causes an increase in plasma lithium levels due to reduced elimination, with the possibility of reaching the toxic threshold. If this combination is necessary, lithemia should be monitored in order to adapt the lithium dosage during concomitant treatment with ibuprofen.

- 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 (eg 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 renal function , which includes possible acute renal failure, usually reversible. These interactions should be considered in patients taking ibuprofen 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.

- beta-blockers: NSAIDs counteract the antihypertensive effect of agents that block beta-adrenoceptors.

- selective serotonin reuptake inhibitors (SSRIs): increased risk of gastrointestinal bleeding (see section 4.4); The mechanism may be related to a reduction in serotonin uptake into platelets (see section 4.4).

- cyclosporins: concomitant administration with NSAIDs is believed to increase the risk of nephrotoxicity due to reduced synthesis of prostacyclin in the kidney. Consequently, in case of combination treatment, renal function should be closely monitored.

- captopril: experimental studies indicate that ibuprofen counteracts the effect of captopril on sodium excretion.

- cholestyramine: the concomitant administration of ibuprofen and cholestyramine can reduce the absorption of ibuprofen (25%) from the gastrointestinal tract. These medicines should be administered to

an interval of at least 2 hours.

- thiazides, thiazide-related preparations and loop diuretics: NSAIDs can counteract the diuretic effect of furosemide and bumetanide, probably by inhibiting prostaglandin synthesis. They can also counteract the antihypertensive effect of thiazides.

- tacrolimus: concomitant administration with NSAIDs and tacrolimus is believed to increase the risk of nephrotoxicity due to reduced synthesis of prostacyclin in the kidney. Consequently, in case of combination treatment, renal function should be closely monitored.

- methotrexate: the risk of a potential interaction between an NSAID and methotrexate should also be considered in relation to a treatment with low dose methotrexate, particularly in patients with renal impairment. When the combination treatment is given, renal function should be monitored. Caution should be exercised when both NSAID and methotrexate are administered over 24 hours, as plasma levels of methotrexate may increase, causing increased toxicity (see above).

- corticosteroids: increased risk of gastrointestinal ulceration or bleeding (see section 4.4).

- antiplatelet medicines: increased risk of gastrointestinal bleeding (see above).

- 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.

- ritonavir: an increase in the concentration of NSAIDs is possible.

- probenecid: slows down the excretion of NSAIDs, with possible increase in their plasma concentrations.

- 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 or fluconazole.

Interaction studies have only been performed in adults.

04.6 Pregnancy and lactation

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 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 mortality. embryofetal.

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 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 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 may occur even at very low doses;

- Inhibition of uterine contractions resulting in delayed or prolonged labor.

Consequently, IBUPROFENE DOC 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 through effects on ovulation and is not recommended in women attempting to conceive. In women who have difficulty conceiving or who are being investigated for infertility, discontinuation of ibuprofen treatment should be considered.

04.7 Effects on ability to drive and use machines

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.

Gastritis has been observed less frequently.

Esophagitic pancreatitis and intestinal narrowing have also been observed very rarely.

The patient should be instructed to stop the medicine and to see the doctor immediately if severe upper abdominal pain or melaena or haematemesis occurs.

Disorders of the immune systemHypersensitivity reactions have been reported following treatment with NSAIDs. These may consist of a) non-specific allergic reaction and anaphylaxis, b) respiratory tract reactions including asthma, even severe, bronchospasm or dyspnoea or c) various skin disorders, including various types of rash, itching, 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, fatigue, hypertension and heart failure, vasculitis have been reported in association with treatment with NSAIDs.

Clinical studies suggest that the use of ibuprofen, especially at high doses (2400 mg / day), may be associated with a modest increased risk of arterial thrombotic events (eg, myocardial infarction or stroke) (see section 4.4). .

Disorders of the blood and lymphatic system: leukopenia, thrombocytopenia, neutropenia, agranulocytosis, aplastic anemia and haemolytic anemia. The first signs are: fever, sore throat, superficial mouth ulcers, flu-like symptoms, severe exhaustion, bleeding and unexplained bruising. In these cases the patient should be advised to discontinue the medicinal product immediately, to avoid any self-medication containing analgesics or antipyretics and to consult the doctor. In long-term therapy, blood counts should be performed regularly.

Very rarely: pancytopenia.

Psychiatric disorders: insomnia, anxiety, depression, confusional state, hallucinations, psychotic reactions.

Nervous system disorders: headache, paraesthesia, dizziness, somnolence, optic neuritis, insomnia, agitation, irritability or fatigue.

Infections and infestations: rhinitis and aseptic meningitis (especially in patients with pre-existing autoimmune disorders, such as systemic lupus erythematosus and mixed connective tissue disease) with symptoms of neck stiffness, headache, nausea, vomiting, fever or disorientation (see section 4.4).

If signs of an infection develop or become worse while using ibuprofen, the patient is advised to go to the doctor without delay. Tests should be done to see if this is an "indication of anti-infective / antibiotic therapy.

Pathologies of the respiratory system: bronchospasm, dyspnea, apnea, asthma.

Eye disorders: rare cases of ocular alteration with consequent visual disturbances, toxic optic neuropathy.

Ear and labyrinth disorders: impaired hearing, tinnitus, vertigo.

Hepatobiliary disorders: impaired liver function, liver failure, hepatitis and jaundice, liver damage, liver injury.

Skin and subcutaneous tissue disorders: skin rash (rash), pruritus, purpura, angioedema, bullous reactions including Stevens-Johnson syndrome and toxic epidermal necrolysis (very rare), erythema multiforme, photosensitivity reactions and alopecia. In exceptional cases, severe skin infections and soft tissue complications can occur during a "chickenpox infection" (see also "Infections and Infestations").

Renal and urinary disorders: impairment of renal function and toxic nephropathy in various forms, including interstitial nephritis, nephrotic syndrome and renal failure.

Renal tissue damage (papillary necrosis) and elevated blood uric acid concentrations may also occur rarely.

General disorders and administration site conditions: malaise, fatigue and edema.

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

In adolescents and adults the dose response effect is not clearly defined in overdose.

The half-life in overdose is 1.5 - 3 hours.

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 patients 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 and very rarely diarrhea. Gastrointestinal bleeding is also possible.

Nystagmus, metabolic acidosis, hypothermia, renal effects, gastrointestinal bleeding, coma, apnea, diarrhea and CNS and respiratory depression have also been reported rarely.

Disorientation, arousal state, fainting and cardiovascular toxicity including hypotension, bradycardia and tachycardia have been reported. In cases of significant overdose, renal failure and hepatic injury are possible. In severe poisoning, metabolic acidosis may occur and the prothrombin time / INR may be prolonged, possibly due to interference with the actions of circulatory clotting factors. In patients asthmatics exacerbation of asthma is possible.

Treatment

There is no specific antidote to ibuprofen overdose.

In the event of an overdose, symptomatic and supportive treatment is therefore indicated, including maintenance of a patent airway. Particular attention is due to the control of blood pressure, vital signs, acid-base balance and any gastrointestinal bleeding.

Within one "hour" of ingestion of a potentially toxic amount, administration of activated charcoal should be considered. Alternatively, gastric lavage should be considered within one 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 the ingestion of a potentially toxic quantity of drug.

Any occurrence of frequent or prolonged seizures should be treated with intravenous diazepam or lorazepam. Depending on the patient's clinical condition, other supportive measures may be necessary. Administer bronchodilators for asthma.

For more information, contact your local poison control center.

05.0 PHARMACOLOGICAL PROPERTIES

05.1 Pharmacodynamic properties

Pharmaco-therapeutic category: non-steroidal anti-inflammatory and antirheumatic drugs - derivatives of propionic acid. ATC code: M01AE01.

Ibuprofen is a synthetic analgesic-anti-inflammatory, also endowed with a marked antipyretic activity. Chemically it is the progenitor of phenylpropionic derivatives.The analgesic activity is non-narcotic and is 8-30 times higher than that of acetylsalicylic acid.

Ibuprofen is a potent inhibitor of prostaglandin synthesis and exerts its activity by inhibiting its synthesis at the peripheral level.

Experimental data suggest that ibuprofen can competitively inhibit the effect of low-dose acetylsalicylic acid on platelet aggregation when the two drugs are administered simultaneously. In some pharmacodynamic studies, after administration of single doses of 400 mg of ibuprofen taken within 8 hours before or within 30 minutes after administration of immediate-release acetylsalicylic acid (81 mg), there was a decrease in the effect of " acetylsalicylic acid on thromboxane formation and platelet aggregation. Although there are uncertainties regarding the extrapolation of these data from the clinical situation, the possibility that regular, long-term use of ibuprofen may reduce the cardioprotective effect cannot be excluded. low dose acetylsalicylic acid. No relevant clinical effects are considered likely following occasional use of ibuprofen (see section 4.5).

05.2 "Pharmacokinetic properties

Ibuprofen is well absorbed after oral and rectal administration; taken on an empty stomach produces "maximum serum levels in humans after about 45 minutes. The administration of equal doses preceded by ingestion of food revealed slower absorption and reaching maximum levels over a period of time within a minimum of one" hour and a half and a maximum of three hours. The plasma half-life of the molecule is approximately two hours.

Ibuprofen is metabolised in the liver to two inactive metabolites and these, together with unchanged ibuprofen, are excreted by the kidney both as such and conjugated.

Excretion is rapid and serum levels show no signs of accumulation. 44% of a dose of ibuprofen is recovered in the urine as two pharmacologically inert metabolites and 20% as drug as such.

05.3 Preclinical safety data

The LD50 in albino mice is 800 mg / kg per os; while in the rat, again per os, it is 1600 mg / kg. However, it should be noted that the administration of NSAIDs to pregnant rats can lead to restriction of the fetal ductus arteriosus.

In animal experiments the chronic and subchronic toxicity of ibuprofen mainly manifested itself in the form of lesions and ulcerations of the gastrointestinal tract. in vitro and in vivo have not given clinical relevance of the mutagenic potential of ibuprofen. In studies in rats and mice there was no evidence of the carcinogenic effects of ibuprofen.

Ibuprofen leads to ovulation inhibition in rabbits, as well as implantation disturbance in various animal species (rabbits, rats, mice). Experimental research has shown that ibuprofen passes through the placenta; with maternally toxic doses, an increased incidence of malformations (eg ventricular septal defects) has been observed.

There is no further information on preclinical data other than that already reported elsewhere in this Summary of Product Characteristics (see section 4.6).