Bofen

Composition:

Active ingredient: ibuprofen;

5 ml of the medicinal product contains ibuprofen (calculated as 100% dry substance) – 100 mg;

Excipients: sodium benzoate (E 211), glycerol, liquid maltitol, sodium saccharin, sodium citrate, citric acid monohydrate, sodium chloride, polysorbate 80, xanthan gum, orange flavour, purified water.

Pharmaceutical form. Oral suspension.

Main physicochemical properties: white or almost white suspension with a characteristic orange odour.

Pharmacotherapeutic group. Drugs affecting the musculoskeletal system. Nonsteroidal anti-inflammatory and antirheumatic drugs. Propionic acid derivatives. Ibuprofen.
ATC code M01A E01.

Pharmacological properties.

Pharmacodynamics.

The medicinal product exerts antipyretic, anti-inflammatory and analgesic effects. The mechanism of action is based on inhibition of prostaglandin synthesis – mediators of temperature response, inflammation and pain.

Pharmacokinetics.

After oral administration, ibuprofen is absorbed in the gastrointestinal tract and begins to act within a short period of time. The effect of the medicinal product lasts up to 8 hours.

Clinical characteristics.

Indications.

• Symptomatic treatment of fever of various origins in children aged from 3 months (with body weight not less than 5 kg) to 12 years, including fever after immunization, acute respiratory viral infections, influenza;
• headache, toothache, sore throat, pain during teething, pain after tooth extraction, ligament sprains and other types of pain, including inflammatory origin.

Contraindications.

• Hypersensitivity to ibuprofen or to other components of the medicinal product;
• hypersensitivity to acetylsalicylic acid or to other nonsteroidal anti-inflammatory drugs (NSAIDs);
• concomitant use with other NSAIDs, including selective cyclooxygenase-2 inhibitors;
• hypersensitivity reactions (e.g., asthma, rhinitis, angioedema or urticaria) previously observed after administration of ibuprofen, acetylsalicylic acid (aspirin) or other NSAIDs;
• blood coagulation disorders or bleeding;
• cerebrovascular or other bleeding;
• peptic ulcer disease/bleeding in the active phase or their recurrences in medical history (two or more pronounced episodes of peptic ulcer or bleeding);
• gastrointestinal bleeding/perforation in medical history associated with previous NSAID therapy;
• severe impairment of liver or kidney function; heart failure (NYHA class IV);
• hearing loss;
• severe dehydration (caused by vomiting, diarrhoea or insufficient fluid intake);
• third trimester of pregnancy;
• hereditary fructose intolerance.

Interaction with other medicinal products and other types of interactions.

Ibuprofen, as well as other NSAIDs, should not be used in combination with:

aspirin: since this may increase the risk of adverse reactions, except when aspirin (dose not exceeding 75 mg per day) is prescribed by a physician;

other NSAIDs, including selective cyclooxygenase-2 inhibitors: simultaneous use of two or more NSAIDs should be avoided, as this may increase the risk of adverse effects.

Ibuprofen should be used with caution in combination with the following drugs

Anticoagulants: NSAIDs may enhance the therapeutic effect of anticoagulants such as warfarin.

Antihypertensive drugs (ACE inhibitors and angiotensin II antagonists) and diuretics: their effect may be weakened. In some patients with impaired kidney function (e.g., due to dehydration or in elderly patients with impaired kidney function), concomitant use of ACE inhibitors or angiotensin II antagonists and drugs that inhibit cyclooxygenase may lead to further deterioration of kidney function, including possible acute kidney injury, which is usually reversible. Therefore, such combinations should be prescribed with caution, especially in elderly patients. If long-term treatment is necessary, adequate hydration of the patient should be ensured and monitoring of kidney function should be considered at the beginning of combination therapy and periodically thereafter. Diuretics may increase the risk of nephrotoxic effects of NSAIDs.

Corticosteroids (including glucocorticoids): may increase the risk of adverse reactions, especially gastrointestinal ulcers and bleeding.

Antiplatelet agents and selective serotonin reuptake inhibitors: may increase the risk of gastrointestinal bleeding.

Cardiac glycosides (including digoxin): may exacerbate heart failure, reduce glomerular filtration rate and increase glycoside levels in blood plasma.

Lithium: possible increase in its plasma levels due to reduced renal excretion of these drugs.

Methotrexate: possible reduction in tubular secretion of methotrexate, thereby increasing its blood concentration and haematotoxicity.

Calcineurin inhibitors (cyclosporine, tacrolimus): NSAIDs enhance the nephrotoxicity of these drugs through effects on renal prostaglandins.

Mifepristone: NSAIDs should not be taken within 8-12 days after mifepristone administration, as this may lead to reduced efficacy of the latter.

Zidovudine: increased risk of haemarthrosis and haematomas in HIV-infected patients receiving concomitant treatment with zidovudine and ibuprofen.

Quinolone antibiotics: possible increased risk of seizures.

Sulfonylurea drugs and phenytoin: possible enhancement of effect.

Probenecid, sulfinpyrazone: concomitant use with ibuprofen may cause delayed elimination of the latter from the body.

Aliskiren, α-adrenergic blockers, β-adrenergic blockers, calcium channel blockers, clonidine, methyldopa, nitrates: NSAIDs counteract their antihypertensive effect.

Aminoglycosides: NSAIDs may reduce the excretion of aminoglycosides.

Cholestyramine: concomitant administration may reduce absorption of ibuprofen in the gastrointestinal tract. Clinical significance is unknown.

Antidepressants, clopidogrel, prasugrel, heparin, pentoxifylline, herbal extracts (e.g., Ginkgo biloba): possible increased risk of bleeding when used with NSAIDs, including ibuprofen.

CYP2C9 inhibitors: possible pharmacokinetic interaction: increased duration of effect (exposure) of ibuprofen (CYP2C9 substrate). Dose reduction of ibuprofen should be considered when used concomitantly with potent CYP2C9 inhibitors (such as voriconazole, fluconazole), especially at high doses of ibuprofen.

Special precautions.

Consult a physician before starting use of the medicinal product!

To reduce the risk of adverse reactions, the lowest effective dose should be used for the shortest duration necessary to relieve disease symptoms.

Ibuprofen may mask signs of infection.

Masking symptoms of underlying infections: ibuprofen may mask symptoms of infectious disease, which may lead to delayed initiation of appropriate treatment and thereby complicate the course of the disease. This has been observed in community-acquired bacterial pneumonia and bacterial complications of varicella. When ibuprofen is used for fever or pain relief in infection, monitoring of the infectious disease is recommended. In outpatient settings, patients should consult a physician if symptoms persist or worsen.

It is recommended to avoid using ibuprofen in cases of active varicella due to the possible risk of severe skin infections and soft tissue complications.

Use of NSAIDs, including ibuprofen, may provoke bronchospasm, asthma attacks, nasal mucosal swelling in patients suffering from bronchial asthma, chronic obstructive pulmonary diseases, allergic conditions or with previous history of these conditions. Severe acute hypersensitivity reactions, including anaphylactic shock, have been rarely observed. At the first signs of hypersensitivity reactions, use of the medicinal product Bofen should be discontinued.

Caution is required when using ibuprofen in patients:

• with systemic lupus erythematosus and other connective tissue diseases due to increased risk of aseptic meningitis as a manifestation of hypersensitivity reactions; aseptic meningitis has also been observed in patients without these chronic diseases;
• with congenital porphyrin metabolism disorders, e.g., acute porphyria;
• with gastrointestinal disorders and chronic inflammatory bowel disease (ulcerative colitis, Crohn's disease);
• with a history of severe allergies due to increased risk of hypersensitivity reactions;
• with hepatic dysfunction – arterial hypertension and/or heart failure in liver dysfunction may progress and/or fluid retention may occur.

Patients with arterial hypertension and/or mild to moderate congestive heart failure in medical history should start long-term treatment with caution (medical consultation required), as cases of fluid retention, arterial hypertension and oedema have been reported during ibuprofen therapy, as with other NSAIDs.

Ibuprofen should be prescribed only after careful benefit/risk assessment in patients with uncontrolled arterial hypertension, congestive heart failure, stable ischemic heart disease, peripheral artery disease and/or cerebrovascular pathology.

Coumadin syndrome cases have been reported in patients receiving ibuprofen therapy. Coumadin syndrome is defined as cardiovascular symptoms caused by an allergic or hypersensitivity reaction associated with coronary artery constriction, potentially leading to myocardial infarction.

Use of ibuprofen, especially at high doses (2400 mg per day), and long-term treatment may lead to a slight increase in the risk of arterial thrombotic complications (e.g., myocardial infarction or stroke). Low-dose ibuprofen (e.g., ≤ 1200 mg per day) may increase the risk of myocardial infarction. Long-term NSAID therapy should be prescribed to patients with significant cardiovascular risk factors (such as arterial hypertension, hyperlipidemia, diabetes mellitus, smoking) only after careful consideration.

The risk of gastrointestinal bleeding, perforation, ulcers increases with higher NSAID doses in patients with a history of ulcers, especially if complicated by bleeding or perforation, and in elderly patients. These patients should start treatment with minimal doses. Caution should be exercised when treating patients receiving concomitant drugs that may increase the risk of gastropathy or bleeding, such as oral corticosteroids or anticoagulants (e.g., warfarin) or antiplatelet agents (e.g., aspirin). For long-term treatment of these patients, as well as for patients requiring concomitant use of low-dose acetylsalicylic acid (aspirin) or other drugs that may increase gastrointestinal risk, combined therapy with misoprostol or proton pump inhibitors should be considered by a physician. Patients with gastrointestinal disorders in medical history, especially elderly patients, should be informed about any unusual gastrointestinal symptoms (mainly bleeding), particularly gastrointestinal bleeding at the beginning of treatment. In case of gastrointestinal bleeding or ulcers in patients receiving ibuprofen, treatment should be immediately discontinued.

Ibuprofen, like other NSAIDs, may affect platelet aggregation and prolong bleeding time in healthy individuals.

Ibuprofen should be used with caution in patients with significant dehydration.

NSAID use may lead to nephrotoxicity, dose-dependent reduction in prostaglandin synthesis and provoke kidney failure due to impaired renal circulation. Kidney function should be monitored in such patients. After discontinuation of NSAID therapy, kidney function usually returns to normal.

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

Upon appearance of signs and symptoms indicating these reactions, ibuprofen should be immediately discontinued and alternative treatment considered (if necessary).

There is limited evidence that cyclooxygenase/prostaglandin synthesis inhibitors (such as NSAIDs) may impair fertility in women by affecting ovulation. This effect is reversible upon discontinuation of therapy.

Long-term use of any analgesics for headache treatment may worsen headache. In such cases, consult a physician and discontinue treatment. Consider the possibility of medication-overuse headache in patients suffering from frequent or daily headaches despite (or due to) regular use of headache medications.

Concomitant use of alcohol and NSAIDs may exacerbate adverse reactions related to the active ingredient, especially those affecting the gastrointestinal tract or central nervous system.

NSAIDs may mask symptoms of infection and fever.

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

The medicinal product contains 4.17 mg of sodium in 5 ml of suspension. This should be taken into account for patients on a sodium-controlled diet.

Do not exceed recommended doses.

Use during pregnancy or breastfeeding.

The medicinal product is intended for use only in children with body weight not less than 5 kg, aged from 3 months to 12 years.

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 after use of prostaglandin synthesis inhibitors in early pregnancy. The risk is believed to increase with higher doses and longer duration of therapy. The absolute risk of cardiovascular defects increased from less than 1% to approximately 1.5%.

Use of ibuprofen from the 20th week of pregnancy may cause oligohydramnios due to fetal kidney dysfunction. This may occur shortly after initiation of treatment and is usually reversible after discontinuation of the medicinal product. Additionally, cases of fetal arterial duct constriction have been reported after treatment in the second trimester, most of which resolved after discontinuation of therapy. Therefore, ibuprofen should not be taken during the first two trimesters of pregnancy unless, in the physician's opinion, the potential benefit to the patient outweighs the potential risk to the fetus. If ibuprofen is used by a woman trying to conceive or during the first or second trimester of pregnancy, the lowest possible dose should be used for the shortest possible duration. Fetal monitoring for oligohydramnios and arterial duct constriction should be considered if exposure to ibuprofen occurs for several days starting from the 20th gestational week. Use of the medicinal product Bofen should be discontinued if oligohydramnios or arterial duct constriction in the fetus is detected.

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

• for the fetus: cardiopulmonary toxicity characterized by premature constriction/closure of the arterial duct and pulmonary hypertension; kidney dysfunction, which may progress to kidney failure accompanied by oligohydramnios (see above);
• for the mother at the end of pregnancy and the newborn: possible prolongation of bleeding time, antiplatelet effect, which may develop even at very low doses; inhibition of uterine contractions leading to delayed or prolonged labour. Possible increased risk of oedema in the mother. Therefore, ibuprofen is contraindicated during the third trimester of pregnancy.

Breastfeeding.

Ibuprofen and its metabolites pass into breast milk in low concentrations. Currently, there is no evidence of negative effects on the infant; therefore, breastfeeding usually does not need to be interrupted during short-term treatment of pain and fever with 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, use of ibuprofen is not recommended for women with difficulty conceiving.

Ability to influence reaction speed when driving or operating machinery.

The medicinal product is intended for use only in children up to 12 years of age.

When used according to recommended doses and treatment duration, no influence of the medicinal product on the ability to drive or operate machinery is expected.

Method of administration and dosage.

For short-term use.

Shake the suspension well before each use.

Dosage depends on the child's age and body weight. The daily dose is 20-30 mg/kg of body weight. The lowest effective dose should be used for the shortest time necessary to relieve symptoms (see section "Special precautions").

The single dose should be 5-10 mg/kg of body weight.

The maximum daily dose should not exceed 30 mg/kg of body weight.

For fever and pain:

children aged 3 to 6 months – 2.5 ml of suspension (50 mg) every 8 hours, but not more than 3 times a day, daily dose is 7.5 ml (150 mg);

from 6 to 12 months – 2.5 ml of suspension (50 mg) every 6-8 hours, but not more than 4 times a day, daily dose is 10 ml (200 mg);

from 1 to 3 years – 5 ml of suspension (100 mg) every 8 hours, but not more than 3 times a day, daily dose is 15 ml (300 mg);

from 4 to 6 years – 7.5 ml of suspension (150 mg) every 8 hours, but not more than 3 times a day, daily dose – not more than 22.5 ml (450 mg);

from 7 to 9 years – 10 ml of suspension (200 mg) 3 times a day (600 mg per day);

from 10 to 12 years – 15 ml of suspension (300 mg) 3 times a day (900 mg per day).

For fever after immunization:

children aged 3-6 months – 2.5 ml (50 mg), if necessary – another 2.5 ml (50 mg) after 6 hours, but not more than 5 ml (100 mg) within 24 hours.

Duration of use depends on the course of the disease and usually lasts 3 days; if fever does not subside within 3 days, consult a physician.

If symptoms persist for more than 24 hours from onset of illness in children aged 3-6 months, consult a physician immediately.

Special patient categories.

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

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

In case of overdose, consult a physician immediately.

Children.

The medicinal product is intended for use in children aged from 3 months (with body weight not less than 5 kg) to 12 years at doses specified in the section "Method of administration and dosage". Children under 7 years of age should use the medicinal product only under medical supervision.

Overdose.

Administration to children exceeding 400 mg/kg body weight may cause symptoms of intoxication. The half-life in overdose is 1.5-3 hours.

Symptoms: depend on the amount of medicinal product taken and time elapsed since intake, but individual reactions cannot be excluded. In most cases – abdominal pain, nausea, vomiting, diarrhoea. Tinnitus, lethargy, drowsiness, headache and gastrointestinal bleeding are also possible.

In more severe poisonings, neurological toxicity symptoms such as dizziness, stupor, respiratory depression/apnoea, cyanosis, dyspnoea, nystagmus, visual disturbances, sometimes excitement, seizures, disorientation, loss of consciousness, coma may occur.

In severe poisonings – significant arterial hypotension, bradycardia/tachycardia, atrial fibrillation, hyperkalemia, metabolic acidosis, possible prolongation of prothrombin time, acute kidney failure, liver damage. In patients with bronchial asthma, worsening of asthma symptoms is possible.

Treatment: should be symptomatic and supportive, including ensuring airway patency. Gastric lavage is recommended (only within 1 hour after intake), activated charcoal, alkaline drinks, forced diuresis. In case of frequent or prolonged muscle spasms, treatment should include intravenous administration of diazepam or lorazepam. In case of bronchial asthma, bronchodilators should be used. Monitoring of cardiac parameters and vital signs is necessary to stabilize the patient's condition. Hemodialysis is ineffective.

Adverse reactions.

The following list of adverse reactions includes all adverse events reported during ibuprofen treatment, including those observed with high doses and long-term therapy in patients with rheumatism. It should be noted that the listed adverse reactions are mainly dose-dependent and vary individually for each patient.

Immune system: hypersensitivity reactions¹, including skin rashes¹, urticaria and pruritus; non-specific allergic reactions; anaphylactoid/anaphylactic reactions, including facial, tongue, laryngeal swelling, Quincke's edema with dyspnoea, tachycardia, arterial hypotension, anaphylactic shock; bronchial asthma, worsening of bronchial asthma symptoms, bronchospasm¹; aseptic meningitis² with nuchal rigidity, headache, nausea, vomiting, fever, disorientation – usually in patients with existing autoimmune diseases (such as systemic lupus erythematosus, connective tissue diseases).

Blood and lymphatic system: blood disorders (anaemia, including haemolytic, aplastic anaemia, decreased haematocrit and haemoglobin levels, leucopenia, thrombocytopenia with/without purpura, pancytopenia, neutropenia, agranulocytosis, eosinophilia), bruising, reversible platelet aggregation, pulmonary eosinophilia. Initial signs: fever, sore throat, oral mucosal erosions, flu-like symptoms, feeling of increased fatigue, bleeding, including from the nose, ecchymoses, menorrhagia. Blood count should be monitored during long-term ibuprofen therapy.

Skin and subcutaneous tissue: rashes (including maculopapular), severe skin adverse reactions (SSARs), exfoliative and bullous dermatitis, including Stevens-Johnson syndrome, erythema multiforme and toxic epidermal necrolysis¹ (very rare), purpura; drug-induced eosinophilia with systemic symptoms (DRESS syndrome) (frequency unknown), acute generalized exanthematous pustulosis (AGEP) (frequency unknown) ; skin peeling, alopecia, photosensitization, increased sweating. In exceptional cases, severe skin infections and soft tissue complications during varicella may occur.

Digestive system: nausea, vomiting, appetite changes (including anorexia), discomfort or epigastric pain, dyspepsia, diarrhoea, dry mouth, flatulence, constipation; heartburn, glossitis, oesophagitis, gastritis, duodenitis, erosive-ulcerative gastrointestinal tract lesions (including erosive stomatitis, gastric ulcer), perforations or gastrointestinal bleeding (including rectal bleeding), melena, haematemesis, sometimes fatal, exacerbation of ulcerative colitis and Crohn's disease, pancreatitis.

Hepatobiliary system: liver function disorders, especially with long-term use, in the form of hepatitis, jaundice, hepatorenal syndrome, hepatic necrosis, liver failure.

Nervous system: headache, seizures, dizziness, confusion, malaise, fatigue, emotional lability, irritability, nervousness, depression, drowsiness, paraesthesia, insomnia, anxiety, psychomotor agitation, cerebrovascular complications, hallucinations, coma.

Urinary system: cystitis, dysuria, possible kidney function disorders leading to hyperkalemia, hyperuricemia, azotemia, decreased creatinine clearance, oliguria/polyuria, oedema, acute kidney failure (especially in patients with pre-existing significant kidney function disorders), tubular necrosis, papillary necrosis (especially with long-term use, associated with increased serum urea levels), toxic nephropathy in various forms, including interstitial nephritis, glomerulonephritis, nephritic syndrome, nephrotic syndrome, haematuria, proteinuria.

Cardiovascular system: fluid retention, oedema, arterial hypotension/hypertension, palpitations, arrhythmias (including sinus tachycardia/bradycardia), heart failure, usually in patients with cardiac dysfunction, arterial thrombosis (myocardial infarction or stroke), Coumadin syndrome (frequency unknown).

Sensory organs: tinnitus, hearing disturbances, hearing loss, vertigo, toxic optic neuritis, blurred vision, vision loss, scotoma, toxic amblyopia, diplopia, colour vision changes, conjunctivitis, dryness of eye mucous membranes.

Others: endocrine system and metabolism changes, respiratory depression, apnoea, non-cardiogenic pulmonary oedema, pneumonia, alveolitis, rhinitis.

Use of Bofen should be discontinued upon occurrence of any adverse reaction and a physician should be consulted immediately.

Description of individual adverse reactions

1 There are reports of hypersensitivity reactions after ibuprofen treatment. Such reactions include non-specific allergic reactions and anaphylaxis, respiratory tract reactions, including bronchial asthma, asthma exacerbation, bronchospasm or dyspnoea, or 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 pathogenesis mechanism of drug-induced aseptic meningitis is not fully understood. However, available data on aseptic meningitis associated with NSAID use indicate a hypersensitivity reaction (based on temporal relation to drug intake and symptom resolution after discontinuation of the drug). In particular, isolated cases of aseptic meningitis symptoms (such as nuchal rigidity, headache, nausea, vomiting, fever or disorientation) have been observed during ibuprofen treatment in patients with existing autoimmune disorders (such as systemic lupus erythematosus, mixed connective tissue disease).

Shelf life. 2 years.

After opening the bottle, the shelf life of the medicinal product is 30 days at a temperature not exceeding 25 ºC.

Do not use the medicinal product after the expiry date stated on the packaging.

Storage conditions.

In original packaging at a temperature not exceeding 25 ºC.

Keep out of reach of children.

Packaging.

100 ml in bottles and jars, 1 bottle or 1 jar in a carton with a dosing spoon.

Prescription status.

Over-the-counter.

Manufacturer.

Public Joint-Stock Company "Scientific and Production Center "Boryspil Chemical-Pharmaceutical Plant".

Manufacturer's address and place of business.

Ukraine, 03134, Kyiv, Miru St., 17.