INSTRUCTION FOR MEDICAL USE OF THE MEDICINAL PRODUCT Ibuprom (Ibuprom®)

Composition:

Active substance: ibuprofen;

1 tablet contains 200 mg of ibuprofen;

Excipients: microcrystalline cellulose, maize starch, pregelatinized starch, guar gum, talc, crospovidone (type A), colloidal anhydrous silicon dioxide, hydrogenated vegetable oil, hydroxypropylcellulose, polyethylene glycol (macrogol 400), gelatin, sucrose, kaolin, confectionery sugar, calcium carbonate, acacia (spray dried), titanium dioxide (E 171), Opalux White AS 7000 (titanium dioxide (E 171), sucrose, sodium benzoate (E 211)), carnauba wax.

Pharmaceutical form. Coated tablets.

Main physicochemical properties: round, biconvex, sugar-coated white tablets.

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

ATC code M01A E01.

Pharmacological Properties

Pharmacodynamics

Ibuprofen is a non-steroidal anti-inflammatory drug (NSAID), a derivative of propionic acid, which exerts analgesic, antipyretic, and anti-inflammatory effects by inhibiting the synthesis of prostaglandins—mediators of pain and inflammation. In addition, ibuprofen reversibly inhibits platelet aggregation.

Experimental data indicate that ibuprofen may competitively inhibit the effect of low-dose aspirin (acetylsalicylic acid) on platelet aggregation when both agents are administered concomitantly. Some pharmacodynamic studies have shown that administration of single doses of ibuprofen 400 mg within 8 hours before or within 30 minutes after immediate-release aspirin (81 mg) resulted in reduced effect of aspirin (acetylsalicylic acid) on thromboxane formation or platelet aggregation. Although uncertainty exists regarding extrapolation of these data to the clinical setting, it cannot be excluded that regular long-term use of ibuprofen may reduce the cardioprotective effect of low-dose acetylsalicylic acid. With occasional (non-regular) use of ibuprofen, such a clinically significant effect is considered unlikely.

Pharmacokinetics

Ibuprofen is well absorbed in the gastrointestinal tract and binds to plasma proteins. Maximum serum concentration is reached within 45 minutes after administration (when taken on an empty stomach). When the drug is taken with food, peak levels are observed within 1–2 hours after intake. Ibuprofen is metabolized in the liver and excreted by the kidneys either unchanged or as metabolites. The elimination half-life is approximately 2 hours. In elderly patients, no significant differences in pharmacokinetic profile have been observed.

Clinical characteristics.

Indications.

Symptomatic therapy of headache and toothache, dysmenorrhea (cyclic menstrual pain), neuralgia, back, joint, and muscle pain, rheumatic pain, as well as symptoms of cold and flu.

Contraindications.

Hypersensitivity to ibuprofen or to any of the excipients of the medicinal product.
Hypersensitivity reactions (e.g., asthma, rhinitis, angioedema, or urticaria) following the administration of ibuprofen, acetylsalicylic acid (aspirin), or other NSAIDs.
Active peptic ulcer or gastrointestinal bleeding, or history of recurrent episodes (two or more confirmed episodes of peptic ulcer or bleeding).
History of gastrointestinal bleeding or perforation related to previous NSAID therapy.
Severe heart failure (NYHA class IV), severe hepatic impairment, or severe renal impairment.
Third trimester of pregnancy.
Children with body weight less than 20 kg.
Patients with cerebrovascular or other active bleeding conditions.
Patients with dehydration due to vomiting, diarrhea, or insufficient fluid intake.

Interaction with other medicinal products and other forms of interaction.

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

acetylsalicylic acid (aspirin), as this may increase the risk of adverse reactions, except when aspirin (dose not exceeding 75 mg per day) has been prescribed by a physician. Experimental data indicate that concomitant use of ibuprofen may inhibit the antiplatelet effect of low-dose aspirin. However, the limited nature of these data and uncertainty regarding extrapolation of ex vivo data to the clinical setting do not allow definitive conclusions regarding the regular use of ibuprofen. Therefore, with occasional use of ibuprofen, such clinically significant effects are considered unlikely;
other NSAIDs, including selective cyclooxygenase-2 inhibitors. Concomitant 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 medicinal products:

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

Antihypertensive agents (ACE inhibitors and angiotensin II antagonists) and diuretics: NSAIDs may reduce the effectiveness of these drugs. In some patients with impaired renal function (e.g., dehydrated patients or elderly patients with compromised renal function), concomitant use of ACE inhibitors or angiotensin II antagonists with cyclooxygenase-inhibiting agents may lead to further deterioration of renal function, including possible acute renal failure, which is usually reversible. These interactions should be considered in patients receiving coxibs concomitantly with ACE inhibitors or angiotensin II antagonists. Therefore, such combinations should be used with caution, particularly in elderly patients. If treatment is necessary, ensure adequate hydration of the patient and consider monitoring renal function at the start of combination therapy and periodically thereafter. Diuretics may increase the risk of nephrotoxic effects of NSAIDs.

Corticosteroids: increased risk of gastrointestinal ulcers and bleeding.

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

Cardiac glycosides: NSAIDs may exacerbate cardiac dysfunction, reduce glomerular filtration rate, and increase plasma levels of glycosides.

Lithium: evidence suggests a potential increase in plasma lithium levels.

Metotrexate: possible increase in plasma methotrexate levels.

Cyclosporine: increased risk of nephrotoxicity.

Mifepristone: NSAIDs should not be administered earlier than 8–12 days after mifepristone administration, as they may reduce its efficacy.

Tacrolimus: possible increased risk of nephrotoxicity when used concomitantly with NSAIDs.

Zidovudine: increased risk of hematologic toxicity when zidovudine is used concomitantly with NSAIDs. Evidence suggests an increased risk of hemarthrosis and hematoma in HIV-infected patients with hemophilia receiving concomitant treatment with zidovudine and ibuprofen.

Quinolone antibiotics: patients receiving ibuprofen and quinolone antibiotics concomitantly may have an increased risk of seizures.

Sulfonylurea derivatives and phenytoin: possible potentiation of effect.

Special precautions for use.

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

Elderly patients have an increased frequency of adverse reactions to NSAIDs, particularly gastrointestinal bleeding and perforation, which can be fatal.

Respiratory effects.

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

Cases of aseptic meningitis have been reported during ibuprofen therapy. Although this effect is more likely in patients with systemic lupus erythematosus and other connective tissue diseases, cases have also been reported in some patients without chronic conditions. Therefore, this should be considered when using Ibuprom.

Effects on the cardiovascular and cerebrovascular systems.

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

Clinical trial data and epidemiological evidence indicate that the use of ibuprofen, especially at high doses (2400 mg per day) and with prolonged treatment, may lead to a small increase in the risk of arterial thrombotic complications (e.g., myocardial infarction or stroke). Overall, epidemiological data do not suggest that low-dose ibuprofen (e.g., ≤ 1200 mg per day) increases the risk of arterial thrombotic complications.

Ibuprofen should be prescribed to patients with uncontrolled hypertension, congestive heart failure (NYHA classes II–III), diagnosed ischemic heart disease, peripheral arterial disease, and/or cerebrovascular disease only after careful assessment of the clinical picture. High doses (2400 mg per day) should be avoided.

Careful clinical evaluation should also be performed before initiating long-term treatment in patients with risk factors for cardiovascular complications (such as hypertension, hyperlipidemia, diabetes, smoking), especially if high doses of ibuprofen (2400 mg per day) are required.

Cases of Kounis syndrome have been reported in patients receiving treatment with Ibuprom. 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.

Effects on kidneys/liver.

Caution should be exercised in patients with renal impairment due to the possibility of worsening kidney function. Ibuprofen should be used with caution in patients with kidney or liver disease, particularly during concomitant diuretic therapy, as inhibition of prostaglandin synthesis may lead to fluid retention and further deterioration of renal function. These patients should receive the lowest possible dose of ibuprofen and require regular monitoring of kidney function. In cases of dehydration, adequate fluid intake should be ensured. There is a risk of renal failure in children aged 6 years and older and adolescents who are dehydrated.

In general, chronic use of analgesics, especially combinations of different painkillers, may lead to persistent kidney damage with a risk of renal failure (analgesic nephropathy). The highest risk of this reaction exists in elderly patients, patients with renal, cardiac, or hepatic impairment, and those receiving diuretic or ACE inhibitor therapy. After discontinuation of NSAID therapy, renal function usually returns to the pre-treatment state.

Like other NSAIDs, ibuprofen may cause mild, temporary increases in certain liver function parameters, as well as significant increases in AST and ALT levels. If these parameters increase substantially, treatment should be discontinued.

During prolonged ibuprofen use, regular monitoring of liver function, kidney function, and hematological parameters/blood counts is necessary.

Effects on female fertility.

Limited data suggest that medicinal products that inhibit cyclooxygenase/prostaglandin synthesis may affect ovulation. This effect is reversible after discontinuation of treatment.

Effects on the gastrointestinal tract.

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

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

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

Patients with a history of gastrointestinal toxicity, particularly elderly patients, should be informed about any unusual gastrointestinal symptoms (especially gastrointestinal bleeding), particularly 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., aspirin).

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

Prolonged use of any analgesic for headache treatment may worsen this condition. In such cases, medical advice should be sought and treatment discontinued. Medication-overuse headache should be considered in patients with frequent or daily headaches that persist despite (or because of) regular use of headache medications.

Serious skin adverse reactions (SSARs)

Serious skin adverse reactions (SSARs), 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 during ibuprofen use (see section "Adverse reactions"). Most of these reactions occurred within the first month of treatment.

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

In rare cases, chickenpox may lead to severe skin and soft tissue infections. Currently, the influence of NSAIDs on the worsening of these infections cannot be excluded; therefore, the use of the medicinal product Ibuprom is not recommended in patients with chickenpox.

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

Since the medicinal product contains sucrose, it should not be administered to patients with rare hereditary fructose intolerance, glucose-galactose malabsorption syndrome, or sucrase-isomaltase deficiency.

One tablet contains 121.1 mg (0.35 mmol) of sucrose. The product should be used with caution in patients with diabetes mellitus.

Use during pregnancy or breastfeeding.

During the first and second trimesters of pregnancy, the use of this product should be avoided. The product is contraindicated during the third trimester of pregnancy.

According to limited data, ibuprofen passes into breast milk in very low concentrations; therefore, the likelihood of harmful effects on breastfed infants is very low.

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 absolute risk of cardiovascular malformations increased from less than 1% to approximately 1.5%. The risk is considered to increase with higher doses and longer duration of treatment.

In animal studies, prostaglandin synthesis inhibitors have been associated with increased pre- and post-implantation loss and embryonic/fetal mortality. In addition, increased incidence of various developmental abnormalities, including cardiovascular malformations, has been reported in animals treated with prostaglandin synthesis inhibitors during organogenesis.

NSAIDs should not be taken during the first two trimesters of pregnancy, except when, in the physician's opinion, the expected benefit to the patient outweighs the potential risk to the fetus. If ibuprofen is used by women attempting to conceive or during the first and second trimesters of pregnancy, the lowest possible dose should be used for the shortest possible duration. In such cases, monitoring of amniotic fluid levels by ultrasound should be considered if ibuprofen treatment exceeds 48 hours.

NSAIDs should not be used between the 20th and 28th weeks of pregnancy without medical prescription. The use of NSAIDs from the 20th week of pregnancy onwards may cause rare but serious kidney problems in the unborn child, which can lead to low amniotic fluid levels and potential complications.

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

to the fetus: cardiopulmonary toxicity (characterized by premature closure of the ductus arteriosus and pulmonary hypertension); renal dysfunction, which may progress to renal failure associated with oligohydramnios;
to the mother and newborn at the end of pregnancy: possible prolonged bleeding time, antiplatelet effect (which may develop even at very low doses); inhibition of uterine contractions, leading to delayed or prolonged labor.

Ability to affect reaction speed when driving or operating machinery.

When used according to the recommended doses and treatment duration, the product does not affect reaction speed when driving vehicles or operating machinery.

Dosage and Administration

For oral use, intended for short-term use only.

The lowest effective dose required to treat symptoms should be used for the shortest possible duration (see section "Special Warnings and Precautions for Use"). If symptoms persist for more than 5 days from the start of treatment or worsen, medical advice should be sought.

The drug is indicated for adults and children with body weight above 20 kg (approximately 6 years of age). The usual dosage is 20 to 30 mg/kg body weight per day. The daily dose should not exceed 30 mg/kg body weight.

For children with body weight between 20 and 30 kg (aged 6 to 11 years), the recommended dose is 200 mg (1 tablet), with repeat doses administered as needed every 6 hours, but not exceeding a total of 600 mg (3 tablets) per day.

For adults and children with body weight above 30 kg, the recommended dose is 200–400 mg (1–2 tablets) every 4–6 hours as needed. Do not exceed 1200 mg (6 tablets) within 24 hours.

Elderly patients do not require a specific dose adjustment, except in cases of severe renal or hepatic impairment.

Ibuprom should be taken during or after food, without chewing. Tablets should be swallowed with water. Patients with increased gastric sensitivity are advised to take the drug with food.

Children

Do not use in children with body weight below 20 kg or under 6 years of age.

Overdose

Administration of doses exceeding 400 mg/kg in children may lead to symptoms of intoxication. In adults, the dose-effect relationship is less pronounced. The elimination half-life in overdose is 1.5–3 hours.

Symptoms. In most patients, ingestion of clinically significant amounts of NSAIDs causes only nausea, vomiting, epigastric pain, or less commonly, diarrhea. Other possible symptoms include tinnitus, headache, and gastrointestinal bleeding. In severe poisoning, toxic effects on the central nervous system may occur, manifesting as drowsiness, occasionally agitation, disorientation, or coma. Seizures may develop in some patients. In more severe cases, metabolic acidosis and prolonged prothrombin time/INR (likely due to interaction with circulating blood coagulation factors) may occur. Acute renal failure and liver damage may also develop. In patients with bronchial asthma, an exacerbation of asthma symptoms may occur.

Treatment. Management should be symptomatic and supportive, including maintenance of airway patency and continuous monitoring of cardiac function and vital signs until the patient's condition stabilizes. Oral administration of activated charcoal is recommended within 1 hour after ingestion of a potentially toxic dose. In cases of frequent or prolonged muscle spasms, treatment should include intravenous administration of diazepam or lorazepam. Bronchodilators should be used in patients with bronchial asthma.

Adverse Reactions

The following adverse reactions have been observed with short-term use of ibuprofen at doses not exceeding 1200 mg/day. Other adverse reactions may occur during treatment of chronic conditions or with prolonged use.

Adverse reactions associated with ibuprofen use are classified by system organ class and frequency. Frequency is defined as follows: very common: ≥1/10; common: ≥1/100 to <1/10; uncommon: ≥1/1000 to <1/100; rare: ≥1/10,000 to <1/1000; very rare: <1/10,000; frequency not known (cannot be estimated from available data).

Blood and lymphatic system disorders.

Very rare: blood dyscrasias^1.

Immune system disorders.

Uncommon: hypersensitivity reactions accompanied by urticaria and pruritus^2. Very rare: severe hypersensitivity reactions, symptoms of which may include facial, tongue and laryngeal swelling, dyspnea, tachycardia, hypotension (anaphylaxis, angioedema or severe shock)^2. Frequency not known: respiratory tract reactivity, including bronchial asthma, asthma exacerbation, bronchospasm or dyspnea.

Nervous system disorders.

Uncommon: headache. Very rare: aseptic meningitis^3.

Cardiac disorders.

Frequency not known: heart failure, edema^4, Couinaud's syndrome.

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

Vascular disorders.

Frequency not known: arterial hypertension^4.

Respiratory, thoracic and mediastinal disorders.

Frequency not known: respiratory tract reactivity, including asthma, bronchospasm or dyspnea^2.

Gastrointestinal disorders.

Uncommon: abdominal pain, nausea, dyspepsia^5. Rare: diarrhea, flatulence, constipation, vomiting. Very rare: peptic ulcer of the stomach and duodenum, gastrointestinal perforation or gastrointestinal hemorrhage, melena, hematemesis^6; ulcerative stomatitis, gastritis. Frequency not known: exacerbation of colitis and Crohn's disease^7.

Hepatobiliary disorders.

Very rare: liver function abnormalities.

Skin and subcutaneous tissue disorders.

Uncommon: various types of skin rashes^2. Very rare: serious skin adverse reactions (SSARs) (including erythema multiforme, exfoliative dermatitis, Stevens-Johnson syndrome and toxic epidermal necrolysis)^2. Frequency not known: drug-induced eosinophilia with systemic symptoms (DRESS syndrome), acute generalized exanthematous pustulosis (AGEP), photosensitivity reactions.

Renal and urinary disorders.

Very rare: acute renal function impairment^8. Frequency not known: renal failure.

Investigations.

Very rare: decreased hemoglobin levels.

Description of selected adverse reactions

^1 Includes anemia, leukopenia, thrombocytopenia, pancytopenia and agranulocytosis. Initial signs of these disorders include malaise, sore throat, superficial oral ulcers, influenza-like symptoms, severe fatigue, bleeding and unexplained bruising.

^2 Hypersensitivity reactions may include: (a) non-specific allergic reactions and anaphylaxis, (b) respiratory tract reactivity, including asthma, asthma exacerbation, bronchospasm and dyspnea, or (c) various forms of skin reactions, including pruritus, urticaria, purpura, angioedema, and less frequently, exfoliative and bullous dermatoses, including toxic epidermal necrolysis, Stevens-Johnson syndrome and erythema multiforme.

^3 The pathogenic mechanism of drug-induced aseptic meningitis is not fully understood. Available data on aseptic meningitis associated with NSAID use suggest a hypersensitivity reaction (based on temporal association with drug administration and resolution of symptoms after discontinuation). Cases of aseptic meningitis symptoms (nuchal rigidity, headache, nausea, vomiting, malaise or disorientation) have been reported in patients with autoimmune disorders (systemic lupus erythematosus and mixed connective tissue disease).

^4 Clinical trial and epidemiological data suggest that the use of ibuprofen (particularly at high doses of 2400 mg daily) and during long-term treatment may be associated with a slightly increased risk of arterial thrombotic complications (e.g., myocardial infarction or stroke).

^5 Gastrointestinal adverse reactions are the most commonly observed.

^6 Sometimes fatal.

^7 See section "Special precautions for use".

^8 Particularly with long-term use of NSAIDs, associated with increased serum urea levels and development of edema. Also includes papillary necrosis.

Shelf life. 3 years.

Storage conditions.

For blister packs of tablets: store at a temperature not exceeding 30 °C.

For bottles and sachets of tablets: no special storage conditions required.

Keep out of reach of children.

Packaging.

2 tablets per sachet; 10 tablets per blister in a cardboard box; 50 tablets per bottle in a cardboard box.

Availability. Over-the-counter (without prescription).

Manufacturer.

TOV US Farmacja, Poland / US Pharmacia Sp. z o.o., Poland.

Manufacturer's address.

Ul. Ziebicka 40, 50-507 Wrocław, Poland / Ul. Ziebicka 40, 50-507 Wrocław, Poland.

Marketing Authorization Holder.

Unilab, LP, USA / Unilab, LP, USA.

Address of Marketing Authorization Holder and/or its representative.

966 Hungerford Drive, Suite 3B, Rockville, MD 20850, USA / 966 Hungerford Drive, Suite 3B, Rockville, MD 20850, USA.