Nurofen Junior 125 mg 10 suppositories children

In ottemperanza all'articolo 118 “autorizzazione della pubblicità presso il pubblico” del decreto legislativo 24 aprile 2006, numero 219

INDICATIONS

Short-term symptomatic treatment of mild and moderate pain. Short-term symptomatic treatment of fever. Nurofenjunior suppositories are indicated when oral administration is not recommended, e.g. in case of vomiting. Nurofenjunior is indicated in children from 12.5 kg (2 years) to 20.5 kg (6 years) body weight

ACTIVE INGREDIENTS

Each suppository contains: ibuprofen 125 mg For the complete list of excipients, see section 6.1.

EXCIPIENTS

Solid semi-synthetic glycerides

CONTRAINDICATIONS AND SIDE EFFECTS

Hypersensitivity to the active substance or to any of the excipients listed in paragraph 6.1. Patients who have previously shown hypersensitivity reactions (e.g. bronchospasm, angioedema, asthma, rhinitis or urticaria) associated with acetylsalicylic acid, ibuprofen or other non-steroidal anti-inflammatory medicinal products. History of gastrointestinal bleeding or perforation associated with previous treatment with NSAIDs. In the presence or history of recurrent peptic ulcer/haemorrhage (two or more confirmed episodes of ulceration or bleeding). Patients with severe renal insufficiency, severe hepatic insufficiency or severe heart failure. Patients with a history of cerebrovascular bleeding or other active bleeding. Patients with unexplained disorders of blood formation. Patients with severe dehydration (caused by vomiting, diarrhea or insufficient fluid intake). In the last trimester of pregnancy (see section 4.6). Children weighing less than 12.5 kg (under 2 years of age).

DOSAGE

Dosage Only for a short period of treatment. The maximum daily dose of ibuprofen is 20-30 mg/kg of body weight, divided into 3 or 4 administrations. This means: Children with a body weight between 12.5 and 17 kg (between 2 and 4 years): 1 suppository at the beginning of treatment, to be repeated, if necessary, after at least 6-8 hours. No more than 3 suppositories should be administered in any 24 hour period. Children with a body weight between 17 and 20.5 kg (between 4 and 6 years): 1 suppository at the beginning of treatment, to be repeated if necessary, after at least 6 hours. No more than 4 suppositories should be administered in any 24 hour period. Nurofenjunior 125 mg suppositories are contraindicated in children weighing less than 12.5 kg (under 2 years of age), as lower dosage suppositories are required (see also section 4.3). Administration in patients with renal or hepatic insufficiency must take place after consulting the doctor. If this medicine is required for more than 3 days, or if symptoms worsen, a doctor should be consulted. Undesirable effects can be minimized by using the lowest effective dose for the shortest possible treatment duration needed to control symptoms (see section 4.4). Method of administration Rectal use

CONSERVATION

Do not store above 25°C

WARNINGS

Side effects can be minimized by using the lowest effective dose for the shortest possible treatment duration needed to control symptoms (see gastrointestinal and cardiovascular effects below). Elderly people: Elderly patients have an increased frequency of adverse reactions to NSAIDs, especially gastrointestinal bleeding and perforation, which may be fatal. Elderly people have an increased risk of consequences from adverse reactions. Caution is required in patients with: • Systemic lupus erythematosus or mixed connective tissue disease, due to the increased risk of aseptic meningitis (see section 4.8). • Congenital disorders of porphyrin metabolism (e.g., acute intermittent porphyria). • Gastrointestinal disorders and chronic inflammatory bowel diseases (ulcerative colitis, Crohn's disease) (see section 4.8). • History of hypertension and/or heart failure since fluid retention and edema have been reported in association with NSAID therapy • Renal damage, as renal function may worsen (see sections 4.3 and 4.8). • Liver dysfunction (see sections 4.3 and 4.8) • Immediately after major surgery • Hay fever, nasal polyps or chronic obstructive respiratory disease, as there is an increased risk of allergic reactions in these patients. These may manifest as asthma attacks (so-called “analgesic asthma”), Quincke's edema or urticaria • In patients who have already experienced allergic reactions to other substances, as they are at higher risk of developing hypersensitivity reactions following the administration of Nurofenjunior Other NSAIDs: the use of Nurofenjunior in children should be avoided concomitantly with the administration of other NSAIDs including selective cyclooxygenase-2 inhibitors. Masking of symptoms of underlying infections Nurofenjunior may mask the symptoms of infection, which could delay starting appropriate treatment and therefore worsen the outcome of the infection. This has been observed in community-acquired bacterial pneumonia and bacterial complications of chickenpox. When Nurofenjunior is administered for the relief of fever or pain related to infection, monitoring of the infection is recommended. In non-hospital settings, the patient should seek medical attention if symptoms persist or worsen. Cardiovascular and cerebrovascular effects: caution is required (advice from a doctor or pharmacist) before administering Nurofenjunior to patients with a history of hypertension and/or heart failure, since fluid retention, hypertension and edema have been reported following NSAID therapy. Clinical studies and epidemiological data suggest that the use of ibuprofen, especially at high doses (2400 mg/day) and for long-term treatments, may be associated with a modest increase in the risk of events arterial thrombosis (e.g. myocardial infarction or stroke). In general, epidemiological studies do not indicate that low doses of ibuprofen (e.g. ≤ 1200 mg/day) are associated with an increased risk of myocardial infarction. Gastrointestinal (GI) effects: During treatment with all NSAIDs, gastrointestinal bleeding, ulceration or perforation, which may be fatal, have been reported at any time, with or without warning symptoms or previous history of serious gastrointestinal events, disorders of the rectum and anus. The risk of gastrointestinal haemorrhage, ulceration or perforation is higher with increased doses of NSAIDs, in patients with a history of ulcer, particularly if complicated by haemorrhage or perforation (see section 4.3) and in the elderly. These patients should start treatment with the lowest dose. For these patients and also for patients taking low doses of acetylsalicylic acid or other drugs that may increase the risk of gastrointestinal events, the concomitant use of gastroprotective agents (e.g. misoprostol or proton pump inhibitors) should be considered (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) 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 or antiplatelet agents such as acetylsalicylic acid (see section 4.5). When gastrointestinal bleeding or ulceration occurs in patients taking Nurofenjunior, 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). Respiratory: Bronchospasm may worsen in patients with or with a history of bronchial asthma, chronic rhinitis, sinusitis, nasal polyposis, or allergic disease. Other considerations: Severe acute hypersensitivity reactions (e.g. anaphylactic shock) are observed very rarely. At the first signs of hypersensitivity reaction after administration/taking of Nurofenjunior, therapy should be discontinued. Medical rescue measures, in line with the symptoms, must be undertaken by specialized personnel. Ibuprofen, the active ingredient in Nurofenjunior, can temporarily inhibit the function of platelets (thrombocyte aggregation). It is therefore recommended to carefully monitor patients with coagulation disorders. In case of prolonged administration of Nurofenjunior, regular monitoring of liver values, renal function as well as blood counts is required. Prolonged use of any type of pain reliever for headaches can worsen symptoms. If this situation occurs or is suspected, the doctor should be consulted and treatment should be suspended. The diagnosis of medication overuse headache (MOH) should be suspected in patients who experience frequent or daily headaches despite or because of regular use of headache medications. Side effects related to the active ingredient, in particular those relating to the gastrointestinal tract or central nervous system, may be increased by taking NSAIDs in combination with alcohol. In patients with heart failure, renal or hepatic failure, in those taking diuretics or who have undergone major surgery resulting in dehydration, monitoring of urine output and renal function should be considered. Renal disorders: in general, the habitual use of analgesics, especially the combination of different analgesic substances, can cause permanent kidney damage, with risk of renal failure (analgesic nephropathy). Pediatric population: There is a risk of kidney damage in dehydrated children. Compromised female fertility: see paragraph 4.6. Severe skin reactions: 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). Patients appear to be at higher risk in the early stages of therapy: the onset of the reaction occurs in most cases within the first month of treatment. Acute generalized exanthematous pustulosis (PEAG) has been reported in connection with ibuprofen-containing medicinal products. Nurofenjunior should be discontinued at the first appearance of signs and symptoms of severe skin reactions, such as rash, mucosal lesions or any other sign of hypersensitivity. Chickenpox can exceptionally cause serious infectious complications to the skin and soft tissues. It is advisable to avoid using Nurofenjunior in case of chickenpox.

INTERACTIONS

Ibuprofen should not be used in combination with: Acetylsalicylic acid (aspirin): unless low-dose acetylsalicylic acid, as per common clinical practice, has been advised by the doctor, as it may increase the risk of adverse reactions (see section 4.4). Other NSAIDs including selective cyclooxygenase 2 inhibitors: avoid concomitant use of two or more NSAIDs as it may increase the risk of adverse reactions (see section 4.4) Experimental data suggest that ibuprofen may inhibit the effects of low-dose acetylsalicylic acid on platelet aggregation when the drugs are administered concomitantly. However, the paucity of data and the uncertainties relating to the application of data extrapolated ex vivo to the clinical situation do not allow definitive conclusions to be drawn for the regular use of ibuprofen and no relevant clinical effect is considered probable in case of occasional use of ibuprofen (see section 5.1). Ibuprofen (like other NSAIDs) should be used with caution in association with: - Corticosteroids: increased risk of gastrointestinal ulceration or haemorrhage (see section 4.4) - Anticoagulants: NSAIDs may increase the effects of anticoagulants, such as warfarin (see section 4.4) - Phenytoin: concomitant use of Nurofenjunior with phenytoin may increase the serum levels of these medicines. Correct use of the drugs (administered for a maximum period of 3 days) does not normally require monitoring of serum phenytoin levels. - Antiplatelet agents and selective serotonin reuptake inhibitors (SSRIs): may increase the risk of gastrointestinal bleeding (see section 4.4). - Anti-hypertensives (ACE inhibitors, beta-blockers and angiotensin II antagonists) and diuretics: NSAIDs can decrease the effectiveness of these medicines. 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, a beta-blocker or an angiotensin II antagonist and agents that inhibit cyclooxygenases may lead to a further deterioration of renal function, including possible 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 at regular intervals thereafter. Diuretics may increase the risk of NSAID nephrotoxicity. - Lithium: there is evidence to support a potential increase in plasma lithium levels. Correct use of the drugs (administered for a maximum period of 3 days) does not normally require monitoring of serum lithium levels. - Probenecid and sulfinpyrazone: Medicines containing probenecid or sulfinpyrazone may delay the excretion of ibuprofen. - Potassium-sparing diuretics: concomitant administration of Nurofenjunior and potassium-sparing diuretics may lead to hyperkalemia (monitoring of serum potassium is recommended). - Cardiac glucosides (Digoxin): NSAIDs can worsen heart failure, reduce GFR and plasma levels of glucosides. Concomitant use of Nurofenjunior with digoxin preparations may increase serum levels of these medicines. Correct use of the drugs (administered for a maximum period of 3 days) does not normally require monitoring of serum digoxin levels. - Methotrexate: there is evidence to support a potential increase in plasma levels of methotrexate. Administration of Nurofenjunior in the 24 hours before and after the administration of methotrexate may lead to high concentrations of methotrexate and an increase in its toxic effects. - Tacrolimus: the risk of nephrotoxicity increases if the two medicines are administered simultaneously. - Ciclosporin: there is limited evidence to support a possible interaction between the two medicines with consequent increased risk of nephrotoxicity. - Zidovudine: there is evidence of an increased risk of haemarthrosis and haematoma in HIV-positive haemophilia patients treated concomitantly with zidovudine and ibuprofen. - Sulfonylureas: clinical studies have shown interactions between nonsteroidal anti-inflammatory drugs and antidiabetics (sulfonylureas). Although no interactions between ibuprofen and sulphonylureas have been described so far, monitoring of blood glucose values ​​is recommended as a precautionary measure during concomitant intake. - Quinolone antibiotics: data from animal studies 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. - 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), an increased exposure to S(+)-ibuprofen by approximately 80% to 100% was demonstrated. Reduction of the ibuprofen dose should be considered when strong CYP2C9 inhibitors are coadministered, particularly when high doses of ibuprofen are administered with voriconazole or fluconazole.

SIDE EFFECTS

The list of the following side effects includes all side effects that have been recognized during treatment with ibuprofen, even those observed during prolonged high-dose therapy in patients with rheumatism. The frequencies reported, which extend beyond reports of very rare side effects, refer to short periods of treatment for daily doses up to a maximum of 1,200 mg of ibuprofen for oral pharmaceutical forms and up to a maximum of 1,800 mg for suppositories. It should be taken into account that the following adverse reactions are predominantly dose-dependent and vary from individual to individual. Adverse reactions associated with the administration of ibuprofen are listed below according to system organ class and frequency. Frequencies are defined as: very common (≥1/10), common (≥1/100, <1/10), uncommon (≥1/1,000, <1/100), rare (≥1/10,000, <1/1,000), very rare (<1/10,000), not known (cannot be estimated from the available data). Within each frequency grouping, adverse events are presented in order of decreasing seriousness. The most often observed adverse reactions are gastrointestinal in nature. Adverse reactions are in most cases dose-dependent. In particular, the risk of gastrointestinal bleeding depends on the dosage and duration of treatment. Peptic ulcers, perforation or gastrointestinal haemorrhage, sometimes fatal, may occur, particularly in the elderly (see section 4.4). Nausea, vomiting, diarrhoea, flatulence, constipation, dyspepsia, abdominal pain, melena, haematemesis, ulcerative stomatitis, exacerbation of colitis and Crohn's disease have been reported following administration of ibuprofen (see section 4.4). Less frequently, gastritis was observed. Edema, hypertension and heart failure have been reported in association with NSAID treatment. Clinical studies and epidemiological data suggest that the use of ibuprofen, particularly at high doses (2,400 mg per day) and for long-term treatment, may be associated with a slightly increased risk of arterial thrombotic events (e.g. myocardial infarction or stroke) (see section 4.4). Worsening of infection-related inflammation (e.g. development of necrotizing fasciitis) associated with the use of non-steroidal anti-inflammatory drugs has been described. This is probably due to the mechanism of action of non-steroidal anti-inflammatory drugs. If signs of an infection occur or worsen while using Nurofenjunior, the patient is recommended to contact a doctor immediately to assess whether anti-infective/antibiotic therapy is necessary. For prolonged treatments blood counts should be checked regularly. If any symptoms of hypersensitivity reactions occur, the patient should be instructed to immediately inform the doctor and stop taking Nurofenjunior; this can also happen upon first use, in which case immediate medical assistance is required. The patient should be instructed to stop taking the medicine and consult a doctor immediately if severe pain in the upper abdomen or melena or haematemesis occurs.

Infections and infestations - Frequency: Very rare. Adverse reaction: Worsening of infection-related inflammation (e.g. development of necrotizing fasciitis), in exceptional cases severe skin infections and soft tissue complications have been reported during a chickenpox infection.

Blood and lymphatic system disorders - Frequency: Very rare. Adverse reaction: Hematopoietic disorders (anaemia, leukopenia, thrombocytopenia, pancytopenia, agranulocytosis). The first signs are: fever, sore throat, superficial mouth ulcers, flu-like symptoms, severe fatigue, nasal and skin bleeding and bruising. In these cases the patient should be advised to stop taking the medicine immediately, to avoid any self-medication medicine containing analgesics or antipyretics and to consult his doctor.

Psychiatric disorders - Frequency: Very rare. Adverse reaction: Psychotic reactions, depression.

Immune system disorders - Adverse reaction: Hypersensitivity reactions consisting of:¹

Immune system disorders - Frequency: Uncommon. Adverse reaction: Urticaria and itching.

Immune system disorders - Frequency: Very rare. Adverse reaction: Severe hypersensitivity reactions. Symptoms may be: swelling of the face, tongue and larynx, dyspnea, tachycardia, hypotension (anaphylaxis, angioedema or severe shock). Asthma exacerbation.

Immune system disorders - Frequency: Not known. Adverse reaction: Respiratory tract reactivity including asthma, bronchospasm, or dyspnea.

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

Nervous system disorders - Frequency: Very rare. Adverse reaction: Aseptic meningitis²

Eye disorders - Frequency: Uncommon. Adverse reaction: Visual disturbances.

Ear and labyrinth disorders - Frequency: Rare. Adverse reaction: Tinnitus.

Cardiac disorders - Frequency: Very rare. Adverse reaction: Heart failure, palpitations and edema, myocardial infarction.

Vascular disorders - Frequency: Very rare. Adverse reaction: Hypertension, vasculitis.

Gastrointestinal disorders - Frequency: Common. Adverse reaction: Gastrointestinal problems, such as abdominal pain, nausea and dyspepsia. Diarrhea, flatulence, constipation, heartburn, vomiting and slight blood loss in the stomach and/or intestines which in exceptional cases can cause anemia.

Gastrointestinal disorders - Frequency: Uncommon. Adverse reaction: Gastrointestinal ulcers, perforation or gastrointestinal bleeding. Ulcerative stomatitis, worsening of colitis or Crohn's disease (see section 4.4), gastritis, localized rectal irritation.

Gastrointestinal disorders - Frequency: Very rare. Adverse reaction: Esophagitis and formation of diaphragmatic-like intestinal structures, pancreatitis.

Hepatobiliary disorders - Frequency: Very rare. Adverse reaction: Liver dysfunction, liver damage, particularly in long-term therapy, liver failure, acute hepatitis.

Skin and subcutaneous tissue disorders - Frequency: Uncommon. Adverse reaction: Various skin rashes.

Skin and subcutaneous tissue disorders - Frequency: Very rare. Adverse reaction: Severe forms of skin reactions such as bullous reactions including Stevens-Johnson syndrome, erythema multiforme and toxic epidermal necrolysis, alopecia.

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

Renal and urinary disorders - Frequency: Rare. Adverse reaction: Rarely, kidney tissue damage (papillary necrosis) may occur.

Renal and urinary disorders - Frequency: Rare. Adverse reaction: and high concentrations of urea in the blood.

Renal and urinary disorders - Frequency: Very rare. Adverse reaction: Formation of edema particularly in patients with arterial hypertension or renal failure, nephrotic syndrome, interstitial nephritis which may be accompanied by acute renal failure.

Diagnostic tests - Frequency: Rare. Adverse reaction: Decreased hemoglobin level in the blood.

Description of some selected adverse reactions ¹ Hypersensitivity reactions have been reported following treatment with ibuprofen. These reactions may include a) non-specific allergic reactions and anaphylaxis, b) respiratory tract reactivity including asthma, worsening of asthma, bronchospasm or dyspnea, or c) various skin conditions including various skin rashes, pruritus, urticaria, purpura, angioedema and very rarely bullous and exfoliative dermatitis (including toxic epidermal necrolysis, Stevens-Johnson syndrome and erythema multiforme)² The pathogenetic mechanism of drug-induced aseptic meningitis is not completely known. However, the data available on aseptic meningitis related to NSAIDs leads us to think of an immune reaction (due to a temporary relationship with the intake of the medicine and the disappearance of symptoms after discontinuation of treatment). Of note, individual cases of symptoms of aseptic meningitis (such as numb neck, headache, nausea, vomiting, fever and disorientation) have been observed during treatment with ibuprofen in patients with pre-existing autoimmune disorders (such as systemic lupus erythematosus, mixed connective tissue disease). Reporting of suspected adverse reactions Reporting suspected adverse reactions that occur after authorization of the medicine is important, as it allows continuous monitoring of the benefit/risk balance of the medicine. Healthcare professionals are asked to report any suspected adverse reactions via the national reporting system at https://www.aifa.gov.it/content/segnalazioni-reazioni-avverse

OVERDOSE

The risk of toxicity may occur for doses higher than 200 mg/kg. a) Symptoms of overdose: Symptoms of overdose may include nausea, vomiting, abdominal pain or more rarely diarrhoea. Nystagmus, blurred vision, tinnitus, headache, and gastrointestinal bleeding are also possible. In more serious cases of poisoning, central nervous system toxicity is observed, manifested by vertigo, dizziness, drowsiness, occasionally excitation and disorientation, loss of consciousness or coma. Occasionally patients develop seizures. In cases of severe poisoning, metabolic acidosis may occur. Hypothermia and hyperkalemia may occur, and prothrombin time/INR may be prolonged, possibly due to interference with the action of circulating coagulation factors. Acute renal failure, liver damage, hypotension, respiratory depression and cyanosis may also occur. In asthmatic subjects, asthma exacerbation may occur. b) Treatment of overdose: There is no specific antidote. Treatment should be symptomatic and supportive and should include maintaining a patent airway and monitoring cardiac function and vital signs until the patient is stabilized. If frequent or prolonged, seizures should be treated with intravenous diazepam or lorazepam. Administer bronchodilators in case of asthma. The local poison center should be contacted for medical advice.

PREGNANCY AND BREASTFEEDING

Pregnancy Inhibition of prostaglandin synthesis can negatively influence pregnancy and/or embryo/foetal development. Results of epidemiological studies suggest an increased risk of miscarriage and cardiac malformations and gastroschisis after the use of a prostaglandin synthesis inhibitor in the early stages of pregnancy. The absolute risk of cardiac malformations was increased from less than 1% to approximately 1.5%. The risk is thought to increase with the dose and duration of therapy. In animals, the administration of prostaglandin synthesis inhibitors has been shown to cause an increase in pre- and post-implantation loss and embryo-fetal mortality. Furthermore, an increased incidence of various malformations, including cardiovascular ones, has been reported in animals to which prostaglandin synthesis inhibitors were administered during the organogenetic period. During the first and second trimester of pregnancy, ibuprofen should not be administered unless strictly necessary. If ibuprofen is used by a woman trying 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 inhibitors of prostaglandin synthesis can 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 oligo-hydramnios; the mother and the newborn, at the end of pregnancy, to: - possible prolongation of bleeding time, an anti-aggregating 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.Breastfeeding Ibuprofen and metabolites pass into breast milk only in small quantities. Since to date there are no known side effects in infants, interruption of breastfeeding is usually not required if the medicine is taken at the recommended doses for fever and pain for short-term treatments. Fertility There is evidence that medicinal products that inhibit cyclooxygenase/prostaglandin synthesis may cause impairment of female fertility by affecting ovulation. This effect is reversible after discontinuation of treatment.

EFFECTS ON DRIVING ABILITY

For short-term treatments, Nurofenjunior has negligible or no effect on the ability to drive or use machines.