Brudol^® for children (Suppositories) Instructions for Use

Marketing Authorization Holder

Belupo, Pharmaceuticals & Cosmetics d.d. (Croatia)

ATC Code

M01AE01 (Ibuprofen)

Active Substance

Ibuprofen (Rec.INN registered by WHO)

Dosage Forms

	Brudol® for children	Rectal suppositories (for children) 60 mg: 10 pcs.
		Rectal suppositories (for children) 125 mg: 10 pcs.

Dosage Form, Packaging, and Composition

Rectal suppositories (for children) white or almost white, torpedo-shaped.

Excipients: hard fat (Novata BCF PH) – 720 mg.

5 pcs. – strips (2) – cardboard packs.

Rectal suppositories (for children) white or almost white, torpedo-shaped.

Excipients: hard fat (Novata BCF PH) – 1075 mg.

5 pcs. – strips (2) – cardboard packs.

Clinical-Pharmacological Group

NSAID

Pharmacotherapeutic Group

NSAID

Pharmacological Action

NSAID, a derivative of phenylpropionic acid. It has anti-inflammatory, analgesic, and antipyretic effects.

The mechanism of action is associated with inhibition of COX activity, the main enzyme in the metabolism of arachidonic acid, which is a precursor of prostaglandins that play a major role in the pathogenesis of inflammation, pain, and fever. The analgesic effect is due to both peripheral (indirectly, through suppression of prostaglandin synthesis) and central mechanisms (inhibition of prostaglandin synthesis in the central and peripheral nervous system). It suppresses platelet aggregation.

Pharmacokinetics

Ibuprofen is metabolized in the liver (90%). 80% of the dose is excreted in the urine mainly as metabolites (70%), 10% unchanged; 20% is excreted through the intestine as metabolites.

Indications

Symptomatic treatment as an anti-inflammatory and antipyretic agent: inflammatory and degenerative diseases of the joints and spine (including rheumatic and rheumatoid arthritis, ankylosing spondylitis, osteoarthritis), joint syndrome in gout exacerbation, psoriatic arthritis, tendinitis, bursitis, radiculitis, traumatic inflammation of soft tissues and the musculoskeletal system. Neuralgia, myalgia, pain syndrome in infectious and inflammatory diseases of the ENT organs, adnexitis, algodysmenorrhea, headache and toothache. Fever in infectious and inflammatory diseases, in childhood infections, in post-vaccination reactions in children.

ICD codes

Dosage Regimen

Administer rectally.

Select the appropriate suppository strength based on the child’s age and body weight.

For children weighing 6 to 8 kg (typically approximately 3 to 9 months), use the 60 mg suppository.

For children weighing 8 to 12.5 kg (typically approximately 9 months to 2 years), use the 60 mg suppository.

For children weighing 12.5 to 25 kg (typically approximately 2 to 6 years), use the 125 mg suppository.

Administer a single suppository per dose.

Do not exceed three doses in 24 hours.

Maintain an interval of at least 6 to 8 hours between administrations.

The maximum daily dose must not exceed 30 mg per kg of the child’s body weight.

Calculate the total daily dose based on the child’s current weight for safety.

Use the lowest effective dose for the shortest duration necessary to control symptoms.

Do not use for more than 3 days for fever.

If pain persists for more than 3 days or fever for more than 2 days, discontinue use and consult a physician.

Ensure the child’s weight is known before administration to determine correct dosing.

This product is contraindicated for children with a body weight under 6 kg.

Adverse Reactions

From the hematopoietic system: very rarely – hematopoietic disorders (anemia, leukopenia, aplastic anemia, hemolytic anemia, thrombocytopenia, pancytopenia, agranulocytosis).

From the immune system infrequently – hypersensitivity reactions – nonspecific allergic reactions and anaphylactic reactions, respiratory tract reactions (bronchial asthma, including its exacerbation, bronchospasm, dyspnea, shortness of breath), skin reactions (itching, urticaria, purpura, angioedema, exfoliative and bullous dermatoses, including toxic epidermal necrolysis (Lyell’s syndrome), Stevens-Johnson syndrome, erythema multiforme), allergic rhinitis, eosinophilia; very rarely – severe hypersensitivity reactions, including facial, tongue and laryngeal edema, dyspnea, tachycardia, arterial hypotension (anaphylaxis, angioedema or severe anaphylactic shock).

From the digestive system infrequently – abdominal pain, nausea, dyspepsia (including heartburn, bloating); rarely – diarrhea, flatulence, constipation, vomiting; very rarely – peptic ulcer, perforation or gastrointestinal bleeding, melena, hematemesis, in some cases fatal, especially in elderly patients, ulcerative stomatitis, gastritis; frequency unknown – exacerbation of colitis and Crohn’s disease.

From the liver and biliary tract: very rarely – liver function disorders, increased activity of liver transaminases, hepatitis and jaundice.

From the urinary system: very rarely – acute renal failure (compensated and decompensated), especially with prolonged use, in combination with an increase in plasma urea concentration and the appearance of edema, hematuria and proteinuria; nephritic syndrome, nephrotic syndrome, papillary necrosis, interstitial nephritis, cystitis.

From the nervous system infrequently – headache; very rarely – aseptic meningitis.

From the cardiovascular system: frequency unknown – heart failure, peripheral edema; with prolonged use, increased risk of thrombotic complications (e.g., myocardial infarction, stroke), increased blood pressure.

From the respiratory system: frequency unknown – bronchial asthma; bronchospasm; dyspnea.

From laboratory parameters: possible – decrease in hematocrit or hemoglobin, increased bleeding time, decrease in plasma glucose concentration, decrease in creatinine clearance, increase in plasma creatinine concentration, increase in liver transaminase activity.

Contraindications

Hypersensitivity to ibuprofen; erosive and ulcerative lesions of the gastrointestinal tract in the acute phase or ulcer bleeding in the active phase or in history (2 or more confirmed episodes of peptic ulcer or ulcer bleeding); bleeding or perforation of gastrointestinal ulcer in history, provoked by the use of NSAIDs; severe heart failure (functional class IV according to NYHA classification); severe impairment of renal and/or liver function; optic nerve diseases, “aspirin triad”, hematopoietic disorders; period after coronary artery bypass surgery; intracranial or other bleeding; hemophilia and other blood clotting disorders (including hypocoagulation), hemorrhagic diatheses; proctitis; III trimester of pregnancy; child’s body weight under 6 kg.

With caution simultaneous use of other NSAIDs; history of a single episode of gastric and duodenal ulcer or gastrointestinal ulcer bleeding; gastritis, enteritis, colitis, presence of Helicobacter pylori infection, ulcerative colitis; bronchial asthma or allergic diseases in the acute stage or in history; systemic lupus erythematosus or mixed connective tissue disease (Sharp’s syndrome) – increased risk of aseptic meningitis; chickenpox; renal failure, including with dehydration (creatinine clearance less than 30-60 ml/min), nephrotic syndrome, hepatic failure, liver cirrhosis with portal hypertension; hyperbilirubinemia; arterial hypertension and/or heart failure; cerebrovascular diseases; blood diseases of unclear etiology (leukopenia and anemia); severe somatic diseases; dyslipidemia/hyperlipidemia; diabetes mellitus; peripheral artery diseases; smoking; frequent alcohol consumption; simultaneous use of drugs that may increase the risk of ulcers or bleeding, in particular, oral corticosteroids (including prednisolone), anticoagulants (including warfarin), selective serotonin reuptake inhibitors (including citalopram, fluoxetine, paroxetine, sertraline) or antiplatelet agents (including acetylsalicylic acid, clopidogrel); I-II trimester of pregnancy; breastfeeding period; elderly age.

Use in Pregnancy and Lactation

Use during pregnancy and breastfeeding is contraindicated.

Use in Hepatic Impairment

Contraindicated in severe liver function impairment. Use with caution in concomitant liver diseases.

Use in Renal Impairment

Contraindicated in severe renal function impairment. Use with caution in concomitant kidney diseases.

Pediatric Use

Ibuprofen is contraindicated for rectal use in children with a body weight under 6 kg.

Geriatric Use

Should be prescribed with caution to elderly patients to avoid worsening of concomitant diseases.

Elderly patients have an increased frequency of adverse reactions against the background of NSAID use, especially gastrointestinal bleeding and perforations, in some cases fatal.

Special Precautions

It is recommended to prescribe Ibuprofen for the shortest possible course and at the minimum effective dose necessary to relieve symptoms.

During long-term treatment, monitoring of the peripheral blood picture and functional state of the liver and kidneys is necessary. If symptoms of gastropathy appear, careful monitoring is indicated, including esophagogastroduodenoscopy, complete blood count (hemoglobin determination), stool test for occult blood.

The use of NSAIDs in patients with chickenpox may be associated with an increased risk of severe purulent complications of infectious and inflammatory diseases of the skin and subcutaneous fat (e.g., necrotizing fasciitis). In this regard, it is recommended to avoid the use of ibuprofen in chickenpox.

Ibuprofen suppresses COX and prostaglandin synthesis, affects ovulation, disrupting female reproductive function (reversible after discontinuation of treatment).

Effect on ability to drive vehicles and mechanisms

Patients who experience dizziness, drowsiness, lethargy, or visual disturbances when using ibuprofen should avoid driving vehicles and other activities requiring high concentration and speed of psychomotor reactions.

Drug Interactions

With simultaneous use, Ibuprofen reduces the effect of antihypertensive agents (ACE inhibitors, beta-blockers), diuretics (furosemide, hydrochlorothiazide).

With simultaneous use with anticoagulants, their effect may be enhanced.

With simultaneous use with corticosteroids, the risk of adverse effects from the gastrointestinal tract increases.

With simultaneous use, Ibuprofen may displace from plasma protein binding indirect anticoagulants (acenocoumarol), hydantoin derivatives (phenytoin), oral hypoglycemic drugs sulfonylurea derivatives.

With simultaneous use with amlodipine, a slight decrease in the antihypertensive effect of amlodipine is possible; with acetylsalicylic acid – the concentration of ibuprofen in plasma decreases; with baclofen – a case of increased toxic effect of baclofen has been described.

With simultaneous use with warfarin, an increase in bleeding time is possible, microhematuria and hematomas have also been observed; with captopril – a decrease in the antihypertensive effect of captopril is possible; with cholestyramine – a moderately pronounced decrease in the absorption of ibuprofen.

With simultaneous use with lithium carbonate, the concentration of lithium in plasma increases.

With simultaneous use with magnesium hydroxide, the initial absorption of ibuprofen increases; with methotrexate – the toxicity of methotrexate increases.

Simultaneous use of NSAIDs and cardiac glycosides may lead to worsening of heart failure, decreased glomerular filtration rate, and increased concentration of cardiac glycosides in plasma.

There is evidence of the likelihood of an increase in methotrexate concentration in plasma against the background of NSAID use.

With simultaneous use of NSAIDs and cyclosporine, the risk of nephrotoxicity increases.

NSAIDs may reduce the effectiveness of mifepristone, so NSAIDs should be started no earlier than 8-12 days after the end of mifepristone use.

With simultaneous use of NSAIDs and tacrolimus, an increased risk of nephrotoxicity is possible.

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

In patients receiving combined treatment with NSAIDs and quinolone antibiotics, the risk of seizures may increase.

In patients receiving NSAIDs and myelotoxic drugs simultaneously, hematotoxicity is enhanced.

With simultaneous use of ibuprofen and cefamandole, cefoperazone, cefotetan, valproic acid, plicamycin, the frequency of hypoprothrombinemia development increases.

With simultaneous use of ibuprofen and drugs that block tubular secretion, a decrease in excretion and an increase in plasma concentration of ibuprofen are noted.

With simultaneous use of ibuprofen and inducers of microsomal oxidation (phenytoin, ethanol, barbiturates, rifampicin, phenylbutazone, tricyclic antidepressants), an increase in the production of hydroxylated active metabolites occurs, increasing the risk of severe intoxications.

Storage Conditions

Store at 2°C (36°F) to 25°C (77°F). Keep in original packaging, protected from light. Keep out of reach of children.

Dispensing Status

Over-the-Counter

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.