Nurofen^® Multisymptom (Tablets) Instructions for Use

Marketing Authorization Holder

Reckitt Benckiser Healthcare (UK), Ltd. (United Kingdom)

Manufactured By

Higlance Laboratories Pvt. 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

Nurofen® Multisymptom

Tablets 400 mg+325 mg: 5, 7, 10, 14, 20, 50, 70 or 100 pcs.

Dosage Form, Packaging, and Composition

Tablets white or almost white, oval, biconvex, with a score on one side.

Excipients: microcrystalline cellulose – 20 mg, corn starch – 136.44 mg, talc – 10 mg, magnesium stearate – 10 mg, colloidal silicon dioxide – 6.06 mg, sodium carboxymethyl starch – 10 mg.

5 pcs. – blisters (1) – cardboard packs.
7 pcs. – blisters (1) – cardboard packs.
7 pcs. – blisters (10) – cardboard packs.
10 pcs. – blisters (1) – cardboard packs.
10 pcs. – blisters (2) – cardboard packs.
10 pcs. – blisters (5) – cardboard packs.
10 pcs. – blisters (10) – cardboard packs.
5 pcs. – blisters (1) – perforated cardboard packs.
5 pcs. – blisters (2) – perforated cardboard packs.
7 pcs. – blisters (1) – perforated cardboard packs.
7 pcs. – blisters (2) – perforated cardboard packs.
10 pcs. – blisters (1) – perforated cardboard packs.
10 pcs. – blisters (2) – perforated cardboard packs.

Clinical-Pharmacological Group

Combination analgesic-antipyretic

Pharmacotherapeutic Group

Non-narcotic analgesic agent (NSAID + non-narcotic analgesic)

Pharmacological Action

Combined analgesic drug. The action of the drug is due to its constituent components.

Ibuprofen is a non-steroidal anti-inflammatory drug (NSAID) with analgesic, anti-inflammatory, and antipyretic effects. By inhibiting COX-1 and COX-2, it disrupts arachidonic acid metabolism, reducing the amount of prostaglandins (mediators of pain, inflammation, and hyperthermic response) both at the site of inflammation and in healthy tissues, and suppresses the exudative and proliferative phases of inflammation.

Paracetamol non-selectively blocks COX, mainly in the CNS, and has little effect on water-salt balance 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.

It reduces arthralgia at rest and during movement, reduces morning stiffness and joint swelling, and helps increase the range of motion.

Pharmacokinetics

Ibuprofen

Absorption and Distribution

Well absorbed from the gastrointestinal tract. Absorption is slightly reduced when the drug is taken after meals. T_max when taken on an empty stomach is 45 min, when taken after meals – 1.5-2.5 h, in synovial fluid – 2-3 h (the concentration of ibuprofen is higher than in blood plasma). Plasma protein binding is 90%.

Metabolism and Excretion

Undergoes presystemic and postsystemic metabolism in the liver. After absorption, about 60% of the pharmacologically inactive R-form of ibuprofen is slowly transformed into the active S-form. The isoenzyme CYP2C9 is involved in the metabolism of ibuprofen.

Has biphasic elimination kinetics with T_1/2 2-2.5 h. Excreted by the kidneys (unchanged not more than 1%) and to a lesser extent with bile.

Paracetamol

Absorption and Distribution

Absorption is high. T_max is reached in 0.5-2 h. C_max in blood plasma is 5-20 µg/ml. Plasma protein binding is 15%. Penetrates the BBB. Less than 1% of the paracetamol dose taken by a nursing mother passes into breast milk. Therapeutically effective concentration of paracetamol in plasma is achieved when administered at a dose of 10-15 mg/kg.

Metabolism and Excretion

Metabolized in the liver (90-95%): 80% undergoes conjugation reactions with glucuronic acid and sulfates to form inactive metabolites; 17% undergoes hydroxylation to form active metabolites, which conjugate with glutathione to form inactive metabolites. With a lack of glutathione, these metabolites can block the enzyme systems of hepatocytes and cause their necrosis. The isoenzyme CYP2E1 is also involved in the metabolism of paracetamol.

T_1/2 is 1-4 h. Excreted by the kidneys as metabolites, only 3% unchanged. In elderly patients, the clearance of the drug decreases and increases.

Indications

• Headache (including migraine);
• Toothache;
• Algomenorrhea (painful menstruation);
• Neuralgia;
• Myalgia (muscle pain);
• Back pain;
• Joint pain; pain syndrome in inflammatory and degenerative diseases of the musculoskeletal system;
• Pain with bruises, sprains, dislocations, fractures;
• Post-traumatic and postoperative pain syndrome;
• Febrile conditions (elevated body temperature);
• For the symptomatic treatment of acute respiratory diseases (colds) and influenza: febrile conditions (elevated body temperature), headache, muscle pain.

The drug is intended for symptomatic therapy, reducing pain and inflammation at the time of use; it does not affect the progression of the disease.

ICD codes

Dosage Regimen

Orally, after meals, without chewing, with a sufficient amount of water.

For adults 1 tablet 3 times/day. The maximum daily dose is 3 tablets.

For children over 12 years old (body weight over 40 kg) 1 tablet 2 times/day.

The duration of treatment is no more than 3 days as an antipyretic and no more than 5 days as an analgesic. Continuation of treatment with the drug is possible only after consultation with a doctor.

Adverse Reactions

From the digestive system dyspeptic phenomena, diarrhea, erosive and ulcerative lesions of the gastrointestinal tract, gastrointestinal bleeding, impaired liver function, NSAID-gastropathy (nausea, vomiting, abdominal pain, heartburn, loss of appetite, flatulence, pain and discomfort in the epigastric region), irritation, dryness of the oral mucosa or mouth pain, ulceration of the gum mucosa, aphthous stomatitis, pancreatitis, constipation, hepatitis.

From the respiratory system: shortness of breath, bronchospasm.

From the sensory organs: hearing loss, ringing or noise in the ears, reversible toxic optic neuritis, blurred vision or diplopia, dryness and irritation of the eyes, swelling of the conjunctiva and eyelids (of allergic origin), scotoma.

From the nervous system dizziness, headache, insomnia, anxiety, nervousness and irritability, psychomotor agitation, drowsiness, depression, confusion, hallucinations, rarely – aseptic meningitis (more often in patients with autoimmune diseases).

From the cardiovascular system: development or worsening of heart failure, tachycardia, increased blood pressure.

From the urinary system: acute renal failure, allergic nephritis, nephrotic syndrome (edema), polyuria, cystitis.

Allergic reactions skin rash, itching, angioedema, anaphylactoid reactions, anaphylactic shock, bronchospasm, fever, multiforme exudative erythema (including Stevens-Johnson syndrome), toxic epidermal necrolysis (Lyell’s syndrome), eosinophilia, allergic rhinitis.

From the hematopoietic system: anemia (including hemolytic, aplastic), thrombocytopenia and thrombocytopenic purpura, agranulocytosis, leukopenia.

Other edema, increased sweating.

Contraindications

• Increased individual sensitivity to the components of the drug (including to other NSAIDs);
• Peptic ulcer of the stomach and duodenum in the acute phase;
• Gastrointestinal bleeding;
• Severe renal failure (CC less than 30 ml/min);
• 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);
• Genetic absence of glucose-6-phosphate dehydrogenase;
• Blood system diseases;
• Period after coronary artery bypass grafting;
• Progressive kidney diseases;
• Severe liver failure or active liver disease;
• Confirmed hyperkalemia;
• Inflammatory bowel diseases;
• III trimester of pregnancy;
• Lactation period;
• Children under 12 years of age.

With caution

Bronchial asthma, bronchospasm, chronic heart failure, viral hepatitis, alcoholic liver damage, hepatic and/or renal failure, benign hyperbilirubinemias (Gilbert’s syndrome, Dubin-Johnson and Rotor syndromes), liver cirrhosis with portal hypertension, nephrotic syndrome; diabetes mellitus, peripheral artery diseases, peptic ulcer of the stomach and duodenum (in history); gastritis, enteritis, colitis, old age.

Use in Pregnancy and Lactation

Contraindicated in the III trimester of pregnancy and during lactation (breastfeeding).

Use in Hepatic Impairment

Contraindication: severe liver failure or active liver disease.

Use in Renal Impairment

Contraindication: progressive kidney diseases.

Pediatric Use

Contraindication: children under 12 years of age.

Special Precautions

When used simultaneously with indirect anticoagulants, monitoring of the blood coagulation system is necessary.

When using the drug for more than 5-7 days, peripheral blood counts and the functional state of the liver should be monitored.

If symptoms of NSAID-gastropathy appear, careful monitoring is indicated, including esophagogastroduodenoscopy, blood test with determination of hemoglobin and hematocrit, stool test for occult blood. If it is necessary to determine 17-ketosteroids, the drug should be discontinued 48 hours before the study.

Paracetamol distorts the results of laboratory tests of glucose and uric acid content in blood plasma.

Simultaneous use of the drug with other medicines containing Paracetamol and/or NSAIDs should be avoided.

During treatment, it is not recommended to consume alcoholic beverages.

Effect on the ability to drive vehicles and mechanisms

Caution should be exercised and driving vehicles and engaging in potentially hazardous activities that require increased concentration and speed of psychomotor reactions should be avoided.

Overdose

Symptoms symptoms of impaired liver function under the influence of paracetamol may appear 12-48 hours after an overdose. In severe overdose – liver failure with progressive encephalopathy, coma, death; acute renal failure with tubular necrosis (including in the absence of severe liver damage); arrhythmia, pancreatitis.

Treatment: administration of SH-group donors and precursors of glutathione synthesis – methionine after 8-9 hours and acetylcysteine after 12 hours after overdose. The need for additional therapeutic measures (further administration of methionine, intravenous administration of acetylcysteine) is determined depending on the concentration of paracetamol in the blood, as well as on the time elapsed after its intake.

Drug Interactions

Combination with ethanol, glucocorticosteroids, corticotropin increases the risk of erosive and ulcerative lesions of the gastrointestinal tract.

Ibuprofen enhances the effect of direct (heparin) and indirect (coumarin and indandione derivatives) anticoagulants, thrombolytics (alteplase, anistreplase, streptokinase, urokinase), antiplatelet agents, colchicine – the risk of hemorrhagic complications increases.

Enhances the hypoglycemic effect of insulin and oral hypoglycemic drugs.

Weakens the effects of antihypertensive drugs and diuretics (by inhibiting the synthesis of renal prostaglandins).

Increases the concentration in the blood of digoxin, lithium preparations and methotrexate.

Caffeine enhances the analgesic effect of ibuprofen.

Cyclosporine and gold preparations increase nephrotoxicity.

Cefamandole, cefoperazone, cefotetan, valproic acid, plicamycin increase the incidence of hypoprothrombinemia.

Antacids and cholestyramine reduce the absorption of ibuprofen.

Diflunisal increases the plasma concentration of paracetamol by 50%, which increases the risk of hepatotoxicity.

Myelotoxic drugs enhance the manifestations of hematotoxicity of the drug.

When used simultaneously with acetylsalicylic acid, Ibuprofen reduces its anti-inflammatory and antiplatelet effect.

Inducers of microsomal oxidation in the liver (phenytoin, ethanol, barbiturates, flumecinol, rifampicin, phenylbutazone, tricyclic antidepressants) increase the production of hydroxylated active metabolites, which causes the possibility of severe intoxication in case of overdose.

Storage Conditions

The drug should be stored out of the reach of children, in a dry, dark place at a temperature not exceeding 25°C (77°F).

Shelf Life

Shelf life – 3 years. Do not use after the expiration date printed on the package.

Dispensing Status

The drug is approved for use as an over-the-counter product.

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.