Nurofen® for children

INSTRUCTIONS FOR MEDICAL USE OF THE MEDICINAL PRODUCT NUROFEN® FOR CHILDREN (NUROFEN® FOR CHILDREN)

Composition:

Active substance: ibuprofen;

5 ml of suspension contain ibuprofen 100 mg;

Excipients: liquid maltitol; citric acid, monohydrate; sodium citrate; sodium chloride; sodium saccharin; domiphen bromide; polysorbate 80; xanthan gum; orange flavor 2M16014; glycerin; purified water.

Pharmaceutical form. Orange-flavored oral suspension.

Main physicochemical characteristics: white or almost white suspension with an orange odor.

Pharmacotherapeutic group.

Non-steroidal anti-inflammatory and antirheumatic agents. Propionic acid derivatives.

ATC code M01AE01.

Pharmacological properties.

Pharmacodynamics.

Ibuprofen is a non-steroidal anti-inflammatory drug (NSAID), a propionic acid derivative, which has demonstrated efficacy by inhibiting the synthesis of prostaglandins. In humans, ibuprofen reduces pain associated with inflammation, swelling, and fever. Ibuprofen exerts analgesic, antipyretic, and anti-inflammatory effects. The onset of analgesic and antipyretic action of ibuprofen has been shown to occur within 30 minutes. In addition, ibuprofen reversibly inhibits platelet aggregation.

Experimental data indicate that ibuprofen may inhibit the effect of low-dose acetylsalicylic acid (aspirin) on platelet aggregation when these drugs are used concomitantly. In a study, when a single 400 mg dose of ibuprofen was administered within 8 hours before or within 30 minutes after immediate-release aspirin (81 mg), a reduced effect of acetylsalicylic acid on thromboxane formation or platelet aggregation was observed. However, the limited nature of these data and uncertainty regarding the extrapolation of ex vivo data to the clinical setting do not allow definitive conclusions to be drawn regarding the chronic use of ibuprofen. Therefore, clinically significant effects are considered unlikely with occasional use of ibuprofen.

Pharmacokinetics.

Ibuprofen is rapidly absorbed after administration and quickly distributed throughout the body. Elimination is rapid and complete, occurring via the kidneys.

Maximum plasma concentrations are reached within 45 minutes after oral administration on an empty stomach. When administered with food, peak levels are observed within 1–2 hours. This time may vary depending on different dosage forms.

The elimination half-life is approximately 2 hours.

In limited studies, ibuprofen has been detected in breast milk at very low concentrations.

Clinical characteristics.

Indications.

Symptomatic treatment of fever and pain of various origin in children aged from 3 months to 12 years with body weight of at least 5 kg (including fever after vaccination, acute respiratory viral infections, influenza, teething pain, pain after tooth extraction, toothache, headache, sore throat, ligament sprain pain, and other types of pain, including those of inflammatory origin).

Contraindications.

• Hypersensitivity to ibuprofen or to any of the excipients of the medicinal product.
• History of hypersensitivity reactions (e.g., bronchospasm, bronchial asthma, rhinitis, angioedema, or urticaria) following administration of acetylsalicylic acid (aspirin) or other nonsteroidal anti-inflammatory drugs (NSAIDs).
• Active peptic ulcer/gastrointestinal bleeding or history of recurrent episodes (two or more documented episodes of peptic ulcer or bleeding).
• History of gastrointestinal bleeding or perforation related to previous NSAID therapy.
• Severe hepatic insufficiency, severe renal insuff游戏副本

Special precautions for use.

Adverse effects associated with ibuprofen can be minimized by using the lowest effective dose needed to treat symptoms for the shortest duration necessary.

Elderly individuals have an increased frequency of adverse reactions to NSAIDs, particularly gastrointestinal bleeding and perforations, which may be fatal. Patients of advanced age are at increased risk of complications from adverse reactions. Long-term use of NSAIDs is not recommended in elderly individuals. If prolonged therapy is necessary, patients should be monitored regularly.

Caution should be exercised in patients with the following conditions:

• Systemic lupus erythematosus and mixed connective tissue disease – due to an increased risk of aseptic meningitis;
• Inherited disorders of porphyrin metabolism, e.g., acute intermittent porphyria;
• Gastrointestinal disorders and chronic inflammatory bowel disease (ulcerative colitis, Crohn’s disease);
• History of hypertension and/or heart failure, as there are reports of fluid retention and edema associated with NSAID therapy;
• Renal impairment – due to the possibility of worsening kidney function;
• Hepatic dysfunction;
• Immediately after major surgical procedures;
• Hay fever, nasal polyps, or chronic obstructive respiratory diseases due to an increased risk of allergic reactions, including asthma attacks (so-called analgesic-induced asthma), Quincke’s edema, or urticaria;
• Patients with a history of allergic reactions to other substances, due to an increased risk of hypersensitivity reactions to ibuprofen.

Respiratory effects.

Bronchospasm may occur in patients suffering from bronchial asthma or allergic diseases, or with a history of such conditions.

Other NSAIDs.

Concomitant use of ibuprofen with other NSAIDs, including selective cyclooxygenase-2 inhibitors, should be avoided, as this increases the risk of adverse reactions.

Systemic lupus erythematosus and mixed connective tissue disease.

Ibuprofen should be used with caution in patients with systemic lupus erythematosus and mixed connective tissue disease due to an increased risk of aseptic meningitis.

Cardiovascular and cerebrovascular effects.

Patients with a history of hypertension and/or heart failure should begin treatment cautiously (medical consultation is required), as fluid retention, hypertension, and edema have been reported during ibuprofen therapy, as with other NSAIDs.

Clinical trial data and epidemiological evidence suggest that the use of ibuprofen, particularly at high doses (2400 mg per day) and during long-term treatment, may be associated with a small increased risk of arterial thrombotic events (e.g., myocardial infarction or stroke). Overall, epidemiological studies do not show that low doses of ibuprofen (e.g., ≤1200 mg per day) are associated with an increased risk of myocardial infarction.

Cases of Kounis syndrome have been reported in patients receiving ibuprofen. Kounis syndrome is defined as cardiovascular symptoms caused by an allergic or hypersensitivity reaction associated with coronary artery spasm, which may potentially lead to myocardial infarction.

Renal effects.

Generally, regular use of analgesics, especially combinations of different painkillers, may lead to chronic kidney damage with a risk of renal failure (analgesic nephropathy).

Caution should be exercised in patients with renal impairment due to the possibility of worsening kidney function.

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

Hepatic effects.

Hepatic dysfunction.

Gastrointestinal effects.

NSAIDs should be used with caution in patients with a history of gastrointestinal disorders (ulcerative colitis, Crohn’s disease), as their condition may worsen. Such patients should consult a physician.

There have been reports of gastrointestinal bleeding, perforation, and ulcers, which may be fatal, occurring at any stage of NSAID treatment, regardless of the presence of warning symptoms or a history of severe gastrointestinal disorders.

The risk of gastrointestinal bleeding, ulceration, or perforation increases with higher NSAID doses, a history of peptic ulcer disease (especially complicated by bleeding or perforation), and in elderly patients. These patients should start treatment with the lowest dose. For these patients, as well as for those requiring concomitant use of low-dose acetylsalicylic acid or other drugs that may increase gastrointestinal risk, combination therapy with protective agents (e.g., misoprostol or proton pump inhibitors) is recommended.

Patients with a history of gastrointestinal toxicity, especially elderly individuals, should be informed about any unusual gastrointestinal symptoms (particularly gastrointestinal bleeding), especially at the beginning of treatment.

Caution should be exercised when treating patients who are concurrently using medications that may increase the risk of ulceration or bleeding, such as oral corticosteroids, anticoagulants (e.g., warfarin), selective serotonin reuptake inhibitors, or antiplatelet agents (e.g., acetylsalicylic acid).

In case of gastrointestinal bleeding or ulceration in patients receiving ibuprofen, treatment should be discontinued immediately.

Female fertility impairment.

Limited data suggest that cyclooxygenase/prostaglandin synthesis inhibitors may impair female fertility by affecting ovulation. This effect is reversible upon discontinuation of therapy.

Severe cutaneous adverse reactions (SCARs).

Severe cutaneous adverse reactions (SCARs), including exfoliative dermatitis, erythema multiforme, Stevens–Johnson syndrome (SJS), toxic epidermal necrolysis (TEN), drug reaction with eosinophilia and systemic symptoms (DRESS syndrome), and acute generalized exanthematous pustulosis (AGEP), which may be life-threatening or fatal, have been reported with ibuprofen use (see section "Adverse reactions"). Most such reactions occurred within the first month of treatment.

If signs or symptoms suggestive of these reactions appear, ibuprofen should be discontinued immediately and alternative treatment considered (if necessary).

In rare cases, varicella may lead to severe skin and soft tissue infections. At present, the potential influence of NSAIDs on worsening these infections cannot be excluded; therefore, it is recommended to avoid the use of ibuprofen in cases of varicella.

Masking symptoms of underlying infections.

This medicinal product may mask symptoms of infectious disease, potentially delaying the initiation of appropriate treatment and thereby complicating the course of illness. This has been observed in community-acquired bacterial pneumonia and bacterial complications of varicella. When the medicinal product is used for fever or pain relief during infection, monitoring of the infectious condition is recommended. In outpatient settings, patients should consult a physician if symptoms persist or worsen.

Very rarely, severe acute hypersensitivity reactions (e.g., anaphylactic shock) have been observed. At the first sign of a hypersensitivity reaction following ibuprofen administration, treatment should be discontinued and immediate medical attention sought.

Ibuprofen may temporarily inhibit platelet aggregation. Therefore, careful monitoring of patients with coagulation disorders is recommended.

With prolonged use of ibuprofen, liver function tests, kidney function, and hematological parameters/blood counts should be monitored regularly.

Prolonged use of any analgesic for headache treatment may worsen this condition. In such cases, patients should consult a physician and discontinue treatment. Medication-overuse headache should be considered in patients suffering from frequent or daily headaches despite (or because of) regular use of analgesics.

Concomitant use of alcohol and NSAIDs may exacerbate undesirable effects related to the active substance, particularly those affecting the gastrointestinal tract or central nervous system.

NSAIDs may mask symptoms of infection and fever.

This medicinal product contains liquid maltitol. It should not be administered to patients with rare hereditary fructose intolerance. Due to the presence of liquid maltitol, this medicinal product may have a mild laxative effect.

This medicinal product contains 27.75 mg of sodium per 15 mL of suspension (equivalent to 1.85 mg of sodium per 1 mL of suspension). This should be taken into account by patients on a low-sodium diet.

If you are an adult, consult a physician or pharmacist before taking this medicinal product in the following cases: if you are pregnant, trying to become pregnant, elderly, or a smoker.

Use during pregnancy or breastfeeding.

The product is intended for use in children under 12 years of age.

Pregnancy.

Inhibition of prostaglandin synthesis may adversely affect pregnancy and/or embryonic/fetal development. Epidemiological data indicate an increased risk of miscarriage, congenital heart defects, and gastroschisis following the use of prostaglandin synthesis inhibitors in early pregnancy. The risk is believed to increase with higher doses and longer duration of treatment. The absolute risk of cardiovascular malformations increases from less than 1% to approximately 1.5%.

From the 20th week of pregnancy, ibuprofen use may cause oligohydramnios due to fetal renal dysfunction. This may occur soon after starting treatment and is usually reversible upon discontinuation. Additionally, there have been reports of arterial duct constriction following treatment in the second trimester, most of which resolved after stopping treatment. Therefore, ibuprofen should not be prescribed during the first and second trimesters unless clearly necessary. If ibuprofen is used by a woman trying to conceive or during the first and second trimesters of pregnancy, the dose should be as low as possible and the duration of treatment as short as possible. Fetal monitoring for oligohydramnios and arterial duct constriction should be considered after several days of ibuprofen exposure starting from the 20th gestational week. Ibuprofen use should be discontinued if oligohydramnios or arterial duct constriction is detected.

During the third trimester of pregnancy, all prostaglandin synthesis inhibitors may pose risks:

Risks to the fetus:

• Cardio-pulmonary toxicity (premature constriction/closure of the arterial duct and pulmonary hypertension);
• Renal dysfunction (see above);

Risks to the mother at the end of pregnancy and to the newborn:

• Possible prolongation of bleeding time, anti-aggregatory effect, which may occur even at very low doses;
• Inhibition of uterine contractions, leading to delayed or prolonged labor.

Therefore, ibuprofen is contraindicated during the third trimester of pregnancy (see section "Contraindications").

Breastfeeding. Ibuprofen and its metabolites are excreted into breast milk in low concentrations. To date, no adverse effects on the infant have been reported; therefore, interruption of breastfeeding is usually not required during short-term treatment of pain and fever at recommended doses.

Fertility.

There is some evidence that drugs inhibiting cyclooxygenase/prostaglandin synthesis may impair female fertility by affecting ovulation. This effect is reversible upon discontinuation of treatment.

Therefore, the use of ibuprofen is not recommended in women experiencing difficulty conceiving.

Ability to affect reaction speed when driving or operating machinery.

The product is intended for use in children under 12 years of age. When used according to recommended doses and treatment duration, no effect on the ability to drive or operate machinery is expected.

Dosage and Administration.

The lowest effective dose should be used for the shortest duration necessary to relieve symptoms (see section "Special Instructions").

Side effects can be minimized by using the lowest effective dose required to control symptoms for the shortest possible duration.

For oral use. The recommended daily dose is 20 – 30 mg per kg of body weight, divided into equal doses according to age and body weight, administered at intervals of 6 – 8 hours. To ensure accurate dosing, the package contains a dosing syringe. The recommended dose should not be exceeded. For short-term use only.

Age	Body weight (kg)	Recommended dose
3-6 months	5-7.6	2.5 ml of suspension (50 mg) up to 3 times a day.
6-12 months	7.7-9	2.5 ml of suspension (50 mg) up to 3-4 times a day.
1-3 years	10-16	5 ml of suspension (100 mg) up to 3 times a day.
4-6 years	17-20	7.5 ml of suspension (150 mg) up to 3 times a day.
7-9 years	21-30	10 ml of suspension (200 mg) up to 3 times a day.
10-12 years	31-40	15 ml of suspension (300 mg) up to 3 times a day.

Do not use in children under 3 months of age unless directed by a physician.

Do not use this medicinal product in children with body weight less than 5 kg.

For children aged 3 to 6 months: if symptoms persist for longer than 24 hours after initiation of treatment or worsen (after 3 doses), medical advice should be sought immediately.

For children aged 6 months to 12 years: if symptoms persist for more than 3 days after initiation of treatment or worsen, medical advice should be sought.

For fever following vaccination (children aged 3–6 months), the recommended daily dose is 2.5 mL of suspension (50 mg), with an additional 2.5 mL of suspension (50 mg) if needed after 6 hours, but not exceeding 5 mL of suspension (100 mg) within 24 hours. If symptoms persist, medical advice should be sought.

In patients with sensitive stomach, the medication should be taken during meals.

Shake well before use.

Special patient groups:

Renal impairment: dose reduction is not required in patients with mild to moderate renal function impairment (for patients with severe renal impairment, see section "Contraindications").

Hepatic impairment: dose reduction is not required in patients with mild to moderate hepatic function impairment (for patients with severe hepatic impairment, see section "Contraindications").

In case of overdose, seek immediate medical advice.

Children.

The medication is indicated for children aged 3 months to 12 years with body weight of at least 5 kg.

Overdose.

In pediatric patients, symptoms of overdose may occur with ibuprofen doses exceeding 400 mg/kg. Adults are generally less sensitive to overdose effects. The elimination half-life in overdose is 1.5–3 hours.

Symptoms. In most patients, ingestion of a clinically significant amount of NSAIDs causes only nausea, vomiting, epigastric pain, or less commonly, diarrhea. Tinnitus, headache, and gastrointestinal bleeding may also occur. In more severe poisoning, toxic effects on the central nervous system may develop, such as vertigo, dizziness, drowsiness, occasionally excitement, disorientation, or coma. Seizures may occasionally occur. Prolonged use at doses exceeding the recommended levels or overdose may lead to renal tubular acidosis and hypokalemia. In severe poisoning, prolongation of prothrombin time/INR may occur (likely due to interaction with circulating blood coagulation factors). Acute renal failure, liver injury, hypotension, respiratory depression, and cyanosis may develop. In patients with bronchial asthma, exacerbation of asthma may occur. Nystagmus, visual disturbances, and loss of consciousness are also possible.

Treatment. There is no specific antidote. Treatment should be symptomatic and supportive, including maintenance of airway patency and continuous monitoring of cardiac function and vital signs until the patient stabilizes. Consider administration of activated charcoal orally or gastric lavage if less than 1 hour has passed since ingestion of a potentially toxic dose. If ibuprofen has already been absorbed, alkalizing agents may be used to enhance urinary excretion of acidic ibuprofen. For frequent or prolonged seizures, intravenous diazepam or lorazepam should be administered. In case of bronchial asthma exacerbation, bronchodilators should be administered. Seek immediate medical assistance.

Side effects.

The following list of adverse reactions includes all undesirable effects reported during treatment with ibuprofen, including those observed with high doses and long-term therapy in patients with rheumatic diseases. The specified frequencies beyond very rare reports refer to short-term use of doses (maximum 1200 mg ibuprofen per day) for oral dosage forms.

It should be noted that the adverse reactions listed are predominantly dose-dependent and may vary individually for each patient.

Adverse reactions reported during ibuprofen use are listed below by organ systems and frequency of occurrence. Frequency of adverse reactions is defined as follows: very common (≥1/10), common (≥1/100 to <1/10), uncommon (≥1/1000 to <1/100), rare (≥1/10000 to <1/1000), very rare (<1/10000), and frequency not known (cannot be estimated based on available data). Within each frequency group, adverse reactions are listed in descending order of severity.

The most frequently observed adverse reactions are gastrointestinal. Adverse reactions are mostly dose-dependent; in particular, the risk of gastrointestinal bleeding depends on dose and duration of treatment. Gastrointestinal ulcers, perforation, or gastrointestinal hemorrhage, sometimes fatal, may occur, especially in elderly patients. Nausea, vomiting, diarrhea, abdominal distension, constipation, dyspepsia, abdominal pain, melena, hematemesis, ulcerative stomatitis, and exacerbations of colitis and Crohn’s disease have been reported after ibuprofen use. Gastritis has been observed less frequently.

Edema, arterial hypertension, and heart failure have been reported in association with NSAID therapy.

Clinical trial data and epidemiological evidence suggest that the use of ibuprofen, particularly at high doses of 2400 mg per day and during long-term treatment, may be associated with a slightly increased risk of arterial thrombotic events (e.g., myocardial infarction or stroke).

There are case reports of worsening infections, such as necrotizing fasciitis, temporally associated with NSAID use. This may be related to the mechanism of action of NSAIDs.

If signs of infection develop or worsen during ibuprofen use, patients are advised to seek immediate medical attention. The need for antimicrobial/antibiotic therapy should be assessed.

Regular blood tests are recommended during long-term therapy.

Patients should immediately consult a physician and discontinue ibuprofen if any symptoms of hypersensitivity reactions occur, which may develop even after the first dose. Immediate medical assistance is required in such cases.

If severe epigastric pain, melena, or hematemesis occur, the medication should be discontinued immediately and medical advice sought.

Infections and infestations.

Very rare: exacerbation of infection-related inflammation (e.g., development of necrotizing fasciitis). In exceptional cases, chickenpox may lead to severe skin and soft tissue infections.

Blood and lymphatic system disorders.

Very rare: blood dyscrasias (anemia, leukopenia, thrombocytopenia, pancytopenia, agranulocytosis). Initial symptoms include sore throat, oral ulceration, influenza-like symptoms, severe exhaustion, epistaxis, skin bleeding, and bruising.

Immune system disorders.

Hypersensitivity reactions¹; uncommon: urticaria and pruritus.

Very rare: severe hypersensitivity reactions, symptoms of which may include facial, tongue, and laryngeal edema, dyspnea, tachycardia, hypotension (anaphylactic reaction, angioedema, or severe shock). Asthma exacerbation.

Nervous system disorders.

Uncommon: headache, dizziness, insomnia, restlessness, irritability, or fatigue. Very rare: aseptic meningitis².

Cardiac disorders.

Very rare: heart failure, tachycardia, edema, myocardial infarction.

Frequency not known: Kounis syndrome.

Vascular disorders.

Very rare: arterial hypertension, vasculitis.

Gastrointestinal disorders.

Common: abdominal pain, nausea, dyspepsia, diarrhea, flatulence, constipation, heartburn, vomiting, and minor gastrointestinal blood loss, which in exceptional cases may lead to anemia.

Uncommon: gastric and duodenal ulcers, perforation, or gastrointestinal hemorrhage, melena, hematemesis, sometimes fatal (especially in elderly patients), ulcerative stomatitis, gastritis, exacerbation of colitis and Crohn’s disease.

Very rare: esophagitis, formation of diaphragm-like intestinal strictures, pancreatitis.

Hepatobiliary disorders.

Very rare: liver function abnormalities, hepatic injury, particularly during long-term therapy, liver failure, acute hepatitis.

Skin and subcutaneous tissue disorders.

Uncommon: various skin rashes¹.

Very rare: severe skin adverse reactions, including Stevens-Johnson syndrome, erythema multiforme, and toxic epidermal necrolysis¹, alopecia.

Frequency not known: drug reaction with eosinophilia and systemic symptoms (DRESS syndrome); acute generalized exanthematous pustulosis; photosensitivity reactions.

Respiratory, thoracic and mediastinal disorders.

Frequency not known: respiratory tract reactivity, including asthma, bronchospasm, or dyspnea¹.

Renal and urinary disorders.

Rare: acute renal impairment, particularly with long-term NSAID use, associated with increased serum urea levels. Also includes papillary necrosis.

Very rare: edema formation, especially in patients with arterial hypertension or renal insufficiency, nephrotic syndrome, interstitial nephritis, which may be accompanied by acute renal failure.

Laboratory investigations.

Rare: decreased hemoglobin levels.

Psychiatric disorders.

Very rare: psychotic reactions, depression; with prolonged use: hallucinations, confusion.

Eye disorders.

Frequency not known: visual disturbances, optic neuritis may occur with long-term treatment.

Ear and labyrinth disorders.

Frequency not known: dizziness may occur with long-term treatment.

Rare: tinnitus.

General disorders.

Frequency not known: malaise and fatigue.

Description of selected adverse reactions

¹ Reports exist of hypersensitivity reactions following ibuprofen treatment. These include (a) non-specific allergic reactions and anaphylaxis, (b) respiratory tract reactions, including bronchial asthma, asthma exacerbation, bronchospasm, or dyspnea, or (c) various skin disorders, including rashes of different types, pruritus, urticaria, purpura, angioedema, and less frequently exfoliative and bullous dermatoses (including epidermal necrolysis, Stevens-Johnson syndrome, and erythema multiforme).

² The pathogenic mechanism of drug-induced aseptic meningitis is not fully understood. However, available data on aseptic meningitis associated with NSAID use suggest a hypersensitivity reaction (based on temporal association with drug intake and symptom resolution after discontinuation). In particular, isolated cases of aseptic meningitis symptoms (such as neck stiffness, headache, nausea, vomiting, fever, or disorientation) have been observed during ibuprofen treatment in patients with pre-existing autoimmune disorders (such as systemic lupus erythematosus, mixed connective tissue disease).

Shelf life.

3 years.

Storage conditions.

Store out of reach of children at a temperature not exceeding 25 °C.

Packaging.

100 ml or 200 ml of suspension in a bottle. The bottle is placed in a cardboard box with a dosing syringe.

Prescription status.

Over-the-counter (without prescription).

Manufacturer.

Reckitt Benckiser Healthcare (UK) Limited.

Manufacturer's address and place of business.

Dansom Lane, Hull, HU8 7DS, United Kingdom.