Ibuclin Junior^® (Tablets) Instructions for Use

Marketing Authorization Holder

Dr. Reddy’s Laboratories Ltd. (India)

Contact Information

Dr. Reddy’s Laboratories Ltd. (India)

ATC Code

M01AE51 (Ibuprofen in combination with other drugs)

Active Substances

Ibuprofen (Rec.INN registered by WHO)

Paracetamol (Rec.INN registered by WHO)

Dosage Form

Ibuclin Junior®

Dispersible tablets [for children] 100 mg+125 mg: 10, 20, or 200 pcs.

Dosage Form, Packaging, and Composition

Dispersible tablets [for children] pink in color with specks, round, flat-cylindrical, with a bevel and a score on one side, with a characteristic odor.

Excipients: microcrystalline cellulose, corn starch, lactose, sodium carboxymethyl starch (type A), Ponceau 4R dye (E124), glycerol, colloidal silicon dioxide, orange flavor DC 100 PH, pineapple flavor DC 106 PH, peppermint leaf oil, aspartame, magnesium stearate, talc.

10 pcs. – blisters (1) – cardboard packs.
10 pcs. – blisters (2) – cardboard packs.
10 pcs. – blisters (20) – cardboard packs.

Clinical-Pharmacological Group

Combination analgesic-antipyretic

Pharmacotherapeutic Group

Analgesics; other analgesics and antipyretics; anilides

Pharmacological Action

A combined drug, the action of which is due to its constituent components.

Ibuprofen – an NSAID, has analgesic, anti-inflammatory, and antipyretic effects. By inhibiting COX-1 and COX-2, it disrupts the metabolism of arachidonic acid, reduces the amount of prostaglandins (mediators of pain, inflammation, and hyperthermic reaction), both in the focus of inflammation and in healthy tissues, and suppresses the exudative and proliferative phases of inflammation.

Paracetamol – non-selectively blocks COX, mainly in the CNS, has a weak effect on water-salt metabolism and the gastrointestinal mucosa. It has analgesic and antipyretic effects. In inflamed tissues, peroxidases neutralize the effect of paracetamol on COX-1 and COX-2, which explains the low anti-inflammatory effect.

The effectiveness of the combination is higher than that of the individual components.

Pharmacokinetics

Absorption

Ibuprofen

Absorption – high, rapidly and almost completely absorbed from the gastrointestinal tract. Time to reach maximum concentration (T_Cmax) after oral administration is about 1-2 hours.

Paracetamol

Absorption – high. C_max value is 5-20 µg/ml, T_max is 0.5-2 hours.

Distribution

Ibuprofen

Binding to plasma proteins – more than 90%. It slowly penetrates into the joint cavity, accumulates in the synovial fluid, creating higher concentrations in it than in the blood plasma.

Paracetamol

Binding to plasma proteins – less than 10% and increases slightly in case of overdose. Sulfate and glucuronide metabolites do not bind to plasma proteins even at relatively high concentrations. It is distributed fairly evenly in body fluids. Penetrates the blood-brain barrier. Less than 1% of the taken dose of paracetamol passes into breast milk.

Metabolism

Ibuprofen

After absorption, about 60% of the pharmacologically inactive R-form is slowly transformed into the active S-form. It undergoes metabolism.

Paracetamol

About 90-95% of paracetamol is metabolized in the liver to form inactive conjugates with glucuronic acid (60%), taurine (35%), and cysteine (3%), as well as a small amount of hydroxylated and deacetylated metabolites. A small part of the drug is hydroxylated by microsomal enzymes to form a highly active N-acetyl-p-benzoquinone imine, which binds to the sulfhydryl groups of glutathione. When liver glutathione stores are depleted (in case of overdose), hepatocyte enzyme systems can be blocked, leading to the development of their necrosis. In children, the ability to form conjugates with glucuronic acid is lower than in adults.

Excretion

Ibuprofen

T_1/2 – about 2 hours. More than 90% is excreted by the kidneys (unchanged no more than 1%) and, to a lesser extent, with bile in the form of metabolites and their conjugates.

Paracetamol

T_1/2 – 2-3 hours. It is excreted by the kidneys, mainly in the form of glucuronide and sulfate conjugates (less than 5% is excreted unchanged).

Indications

For children aged 3 to 18 years

• Febrile syndrome;
• Pain syndrome of mild or moderate intensity of various etiologies: toothache, pain with sprains, dislocations, fractures;
• As an auxiliary drug for the treatment of pain and febrile syndrome in sinusitis, tonsillitis, acute infectious and inflammatory diseases of the upper respiratory tract (pharyngitis, tracheitis, laryngitis).

ICD codes

Dosage Regimen

The drug is taken orally. Before use, the Ibuclin Junior^® tablet should be dissolved in 5 ml (1 teaspoon) of water.

The minimum time interval between doses of the drug is 6 hours.

Single and daily doses, as well as the frequency of administration, depend on the age and body weight of the child.

In case of impaired renal or liver function, the interval between doses of the drug should be at least 8 hours.

The drug should not be taken for more than 5 days as an analgesic and for more than 3 days as an antipyretic without medical supervision.

Adverse Reactions

In therapeutic doses, the drug is usually well tolerated.

Adverse reactions are listed below and grouped by system-organ class with an indication of their frequency: very common (≥ 1/10); common (≥ 1/100, < 1/10); uncommon (≥ 1/1000, < 1/100); rare (≥ 1/10000, < 1/1000); very rare (< 1/10000); unknown (cannot be estimated from the available data). Adverse reactions within each system-organ class are listed in descending order of their severity with an indication of their frequency (within the same frequency category).

From the immune system rare – skin rash, itching, urticaria; very rare – Kounis syndrome and severe skin reactions such as erythema multiforme, exfoliative dermatitis, Stevens-Johnson syndrome, toxic epidermal necrolysis; unknown – DRESS syndrome and acute generalized exanthematous pustulosis.

From the blood and lymphatic system rare – thrombocytopenia, leukopenia, pancytopenia, neutropenia, agranulocytosis.

From the gastrointestinal tract: rare – dyspeptic phenomena, with long-term use in high doses – hepatotoxic effect.

Reporting of Suspected Adverse Reactions

It is important to report suspected adverse reactions after registration of the drug in order to ensure continuous monitoring of the benefit-risk ratio of the drug. Healthcare professionals are recommended to report any suspected adverse drug reactions through the national adverse reaction reporting systems of the member states of the Eurasian Economic Union.

Contraindications

• Hypersensitivity to ibuprofen, paracetamol, and other NSAIDs or to any of the excipients included in the drug;
• Gastric and duodenal ulcer in the acute phase;
• Complete or incomplete combination of bronchial asthma, recurrent polyposis of the nose and paranasal sinuses and intolerance to acetylsalicylic acid or other NSAIDs (including in history);
• Severe renal failure (creatinine clearance less than 30 ml/min);
• Optic nerve lesions;
• Genetic absence of glucose-6-phosphate dehydrogenase;
• Blood system diseases;
• Period after coronary artery bypass surgery;
• Progressive kidney diseases;
• Severe hepatic failure or active liver disease;
• Confirmed hyperkalemia;
• Active gastrointestinal bleeding;
• Inflammatory bowel diseases;
• Hereditary galactose intolerance, Lapp lactase deficiency or glucose-galactose malabsorption;
• Pregnancy of more than 20 weeks;
• Children under 3 years of age.

With caution chronic heart failure, cerebrovascular diseases, dyslipidemia/hyperlipidemia, diabetes mellitus, peripheral arterial diseases, smoking, creatinine clearance less than 60 ml/min, history of ulcerative lesions of the gastrointestinal tract, presence of Helicobacter pylori infection, long-term use of NSAIDs, alcoholism, severe somatic diseases, simultaneous use of oral corticosteroids (including prednisolone), anticoagulants (including warfarin), antiplatelet agents (including acetylsalicylic acid, clopidogrel), selective serotonin reuptake inhibitors (including citalopram, fluoxetine, paroxetine, sertraline); pregnancy up to 20 weeks.

Use in Pregnancy and Lactation

Pregnancy

If it is necessary to use the drug Ibuclin Junior^® during pregnancy, the expected benefit of therapy for the mother and the potential risk to the fetus or child should be carefully weighed.

If it is necessary to use in the first trimester of pregnancy, long-term use of the drug Ibuclin Junior^® should be avoided.

NSAIDs should not be used by women from the 20th week of pregnancy due to the possible development of oligohydramnios and/or kidney pathology in newborns (neonatal renal dysfunction).

Experimental studies have not established embryotoxic, teratogenic, or mutagenic effects of the components of the drug Ibuclin Junior^®.

Breastfeeding

If it is necessary to use the drug Ibuclin Junior^® during lactation (breastfeeding), the expected benefit of therapy for the mother and the potential risk to the child should be carefully weighed. If short-term use of the drug Ibuclin Junior^® is necessary during lactation, discontinuation of breastfeeding is usually not required.

Use in Hepatic Impairment

Contraindicated in severe hepatic failure or active liver disease.

Use in Renal Impairment

Contraindicated in severe renal failure (creatinine clearance less than 30 ml/min), progressive kidney diseases. With caution: creatinine clearance less than 60 ml/min.

Pediatric Use

Contraindicated in children under 3 years of age.

Special Precautions

The advisability of using the drug as an antipyretic is decided in each specific case, depending on the severity, nature, and tolerability of the febrile syndrome.

Ibuprofen may mask the objective signs of infectious diseases, therefore therapy with ibuprofen in patients with infectious diseases should be prescribed with caution.

To reduce the risk of adverse events from the gastrointestinal tract, the minimum effective dose should be used for the shortest possible course.

When used simultaneously with indirect anticoagulants, it is necessary to monitor the indicators of the blood coagulation system.

Concomitant use of the drug Ibuclin Junior^® with other NSAIDs should be avoided.

With long-term (more than 5 days) use of the drug, monitoring of peripheral blood and the functional state of the liver is necessary.

The drug may distort the results of laboratory tests in the quantitative determination of glucose, uric acid in blood serum, 17-ketosteroids (it is necessary to discontinue the drug 48 hours before the study).

Excipients

The drug Ibuclin Junior^® contains lactose. Patients with rare hereditary galactose intolerance, Lapp lactase deficiency, or glucose-galactose malabsorption should not take this drug.

The drug Ibuclin Junior^® contains Ponceau 4R dye, which can cause allergic reactions.

The drug Ibuclin Junior^® contains aspartame, a source of phenylalanine. It may be harmful to people with phenylketonuria.

Effect on the ability to drive vehicles and mechanisms

During the treatment period, the patient should refrain from engaging in potentially hazardous activities that require increased attention and speed of psychomotor reactions.

Overdose

Symptoms: gastrointestinal disorders (abdominal pain, diarrhea, nausea, vomiting, anorexia, epigastric pain), increased prothrombin time, bleeding after 12-48 hours, lethargy, drowsiness, depression, headache, tinnitus, impaired consciousness, heart rhythm disturbances, decreased blood pressure, manifestations of hepato- and nephrotoxicity, convulsions, possible development of hepatonecrosis.

Treatment: gastric lavage within the first 4 hours; alkaline drinking, forced diuresis; activated charcoal orally, administration of SH-group donors and glutathione synthesis precursors – methionine 8-9 hours after overdose and N-acetylcysteine orally or intravenously – after 12 hours, antacid drugs; hemodialysis; symptomatic therapy. The need for additional therapeutic measures (further administration of methionine, intravenous administration of N-acetylcysteine) is determined depending on the concentration of paracetamol in the blood, as well as the time elapsed after its intake.

Drug Interactions

Concomitant use of ibuprofen with the following drugs should be avoided

Acetylsalicylic acid: except for low doses of acetylsalicylic acid (not more than 75 mg/day) prescribed by a doctor, since concomitant use may increase the risk of side effects. With simultaneous use, Ibuprofen reduces the anti-inflammatory and antiplatelet effect of acetylsalicylic acid (an increase in the frequency of acute coronary insufficiency is possible in patients receiving low doses of acetylsalicylic acid as an antiplatelet agent after starting ibuprofen).

Other NSAIDs, including selective COX-2 inhibitors: simultaneous use of two or more drugs from the NSAID group should be avoided due to a possible increase in the risk of side effects.

Use with caution simultaneously with the following drugs

Anticoagulants and thrombolytic drugs: NSAIDs may enhance the effect of anticoagulants, in particular, warfarin and thrombolytic drugs.

Antihypertensive agents (ACE inhibitors and angiotensin II antagonists) and diuretics: NSAIDs may reduce the effectiveness of drugs in these groups. Diuretics and ACE inhibitors may increase the nephrotoxicity of NSAIDs.

Corticosteroids: increased risk of gastrointestinal ulcers and gastrointestinal bleeding.

Antiplatelet agents and selective serotonin reuptake inhibitors: increased risk of gastrointestinal bleeding.

Cardiac glycosides: simultaneous administration of NSAIDs and cardiac glycosides may lead to worsening of heart failure, decreased glomerular filtration rate, and increased concentration of cardiac glycosides in blood plasma.

Lithium preparations: there are data on the likelihood of an increase in the concentration of lithium in blood plasma while using NSAIDs.

Methotrexate: there are data on the likelihood of an increase in the concentration of methotrexate in blood plasma while using NSAIDs.

Cyclosporine: increased risk of nephrotoxicity with simultaneous administration of NSAIDs and cyclosporine.

Mifepristone: NSAIDs should be started no earlier than 8-12 days after taking mifepristone, since NSAIDs may reduce the effectiveness of mifepristone.

Tacrolimus: with simultaneous administration of NSAIDs and tacrolimus, an increase in the risk of nephrotoxicity is possible.

Zidovudine: simultaneous use of NSAIDs and zidovudine may lead to increased hematotoxicity. There are data on an increased risk of hemarthrosis and hematoma in HIV-positive patients with hemophilia receiving combined treatment with zidovudine and ibuprofen.

Quinolone antibiotics: in patients receiving combined treatment with NSAIDs and quinolone antibiotics, an increased risk of seizures is possible.

It is not recommended to take the drug Ibuclin Junior^® simultaneously with other paracetamol-containing drugs, as this may lead to an overdose of paracetamol.

Barbiturates, carbamazepine, phenytoin, diphenylhydantoin, primidone and other anticonvulsants, ethanol, rifampicin, zidovudine, flumecinol, phenylbutazone, butadione, St. John’s wort preparations and other inducers of microsomal oxidation increase the production of hydroxylated active metabolites, creating the possibility of severe liver damage with small overdoses of paracetamol (5 g and more).

Inhibitors of liver microsomal enzymes reduce the risk of hepatotoxic effects.

Under the influence of paracetamol, the elimination time of chloramphenicol increases by 5 times, thereby increasing the risk of chloramphenicol poisoning.

With regular long-term use, the drug enhances the effect of indirect anticoagulants (warfarin and other coumarins), which increases the risk of bleeding. Occasional single-dose use does not significantly affect the action of indirect anticoagulants.

Metoclopramide and domperidone increase, while cholestyramine decreases the absorption rate of paracetamol. The drug may reduce the effectiveness of uricosuric drugs.

Long-term concomitant use of paracetamol and other NSAIDs increases the risk of developing “analgesic” nephropathy and renal papillary necrosis, and the onset of end-stage renal failure.

Storage Conditions

The drug should be stored out of the reach of children, in the original packaging (blister in a carton), at a temperature not exceeding 25°C (77°F).

Shelf Life

Shelf life is 5 years. Do not use after the expiration date printed on the package.

Dispensing Status

The drug is dispensed by prescription.

Important Safety Information

This information is for educational purposes only and does not replace professional medical advice. Always consult your doctor before use. Dosage and side effects may vary. Use only as prescribed.