INSTRUCTIONS FOR MEDICAL USE OF THE MEDICINAL PRODUCT IBUPROM MAX (IBUPROM® MAX)

Composition:

Active substance: ibuprofen;

1 coated tablet contains 400 mg of ibuprofen;

Excipients: core: lactose monohydrate; povidone; corn starch; talc; sodium croscarmellose; magnesium stearate; colloidal anhydrous silicon dioxide;

coating: sucrose, talc, corn starch, titanium dioxide (E 171), carnauba wax, white wax.

Pharmaceutical form. Coated tablets.

Main physicochemical properties: white-colored, oval-shaped, biconvex tablets with a sugar coating.

Pharmacotherapeutic group.

Non-steroidal anti-inflammatory and antirheumatic agents. Propionic acid derivatives. Ibuprofen. ATC code M01A E01.

Pharmacological Properties

Pharmacodynamics

Ibuprofen is a nonsteroidal 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 acetylsalicylic acid on platelet aggregation when these drugs are used concomitantly. Some pharmacodynamic studies have shown that administration of single doses of 400 mg ibuprofen within 8 hours before or within 30 minutes after immediate-release acetylsalicylic acid (81 mg) reduces the effect of acetylsalicylic acid on thromboxane formation or platelet aggregation. Although uncertainty remains 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 (intermittent) use of ibuprofen, such a clinically significant effect is considered unlikely.

Pharmacokinetics

Ibuprofen is well absorbed from 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 occur within 1–2 hours after ingestion. Ibuprofen is metabolized in the liver and excreted by the kidneys either unchanged or as metabolites. The elimination half-life is approximately 2 hours. No significant differences in the pharmacokinetic profile have been observed in elderly patients.

Clinical characteristics.

Indications.

Symptomatic treatment of headache, including migraine, toothache, dysmenorrhea (menstrual pain), neuralgia, back, joint, and muscle 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, or other NSAIDs.
Active peptic ulcer or gastrointestinal bleeding, or history of recurrent episodes (two or more episodes of confirmed peptic ulcer or bleeding).
History of gastrointestinal bleeding or perforation related to previous NSAID therapy.
Severe impairment of liver function, renal function impairment, or heart failure (NYHA class IV).
Third trimester of pregnancy.
Cerebrovascular or other bleeding disorders.
Disorders of blood formation or blood coagulation.

Interaction with other medicinal products and other forms of interaction.

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

Acetylsalicylic acid, as this may increase the risk of adverse reactions, except when acetylsalicylic acid (at a dose not exceeding 75 mg per day) has been prescribed by a physician. Experimental data indicate that ibuprofen may interfere with the antiplatelet effect of low-dose acetylsalicylic acid. However, uncertainty regarding the extrapolation of these data to clinical practice does not allow definitive conclusions about whether regular long-term use of ibuprofen may reduce the cardioprotective effect of low-dose acetylsalicylic acid. Therefore, occasional use of ibuprofen is considered unlikely to cause clinically significant interactions;
Other NSAIDs, including selective cyclooxygenase-2 inhibitors.

Ibuprofen should be used with caution in combination with the following medicinal products:

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

Antihypertensive agents (ACE inhibitors and angiotensin II antagonists) and diuretics: NSAIDs may attenuate the effects of diuretics and other antihypertensive drugs. In some patients with impaired renal function (e.g., dehydrated patients or elderly patients with compromised renal function), concomitant use of an ACE inhibitor or angiotensin II antagonist with cyclooxygenase-inhibiting agents may lead to further deterioration of renal function, including potentially reversible acute renal failure. Therefore, such combinations should be used with caution, especially in elderly patients. In cases of prolonged treatment, adequate hydration should be ensured, and monitoring of renal function should be considered at the start of combined therapy and periodically thereafter. Diuretics increase the risk of nephrotoxic effects of NSAIDs.

Corticosteroids: increased risk of gastrointestinal ulcers and bleeding.

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

MTX (methotrexate): possible increase in methotrexate plasma levels.

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

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

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

Cyclosporine, tacrolimus: increased risk of nephrotoxicity.

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

Quinolone antibiotics: in patients receiving concomitant ibuprofen and quinolone antibiotics, an increased risk of seizures may occur.

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.

Caution is necessary when treating patients with:

systemic lupus erythematosus and mixed connective tissue disease;
gastrointestinal disorders and chronic inflammatory bowel diseases (ulcerative colitis, Crohn's disease);
arterial hypertension and/or heart failure;
impaired kidney function;
impaired liver function;
coagulation disorders (ibuprofen may prolong bleeding time).

Effects on the cardiovascular and cerebrovascular systems.

Patients with a history of arterial hypertension and/or moderate to severe congestive heart failure should be treated cautiously (medical consultation is required), as fluid retention, arterial hypertension, and edema have been reported during therapy with ibuprofen and other NSAIDs.

Clinical trial data and epidemiological evidence suggest that the use of ibuprofen, particularly at high doses (2400 mg per day), and prolonged treatment may lead to a small increase in the risk of arterial thrombotic events (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.

Patients with uncontrolled arterial hypertension, congestive heart failure (NYHA class II–III), ischemic heart disease, peripheral arterial disease, and/or cerebrovascular disease should only be treated with ibuprofen after careful assessment of their clinical condition. High doses (2400 mg per day) should be avoided. A careful clinical evaluation should also be performed before initiating long-term treatment in patients with risk factors for cardiovascular complications (e.g., arterial hypertension, hyperlipidemia, diabetes mellitus, 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 Max. 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 the respiratory system.

Bronchospasm may occur in patients with bronchial asthma or allergic diseases, or those with a history of such 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.

Effects on the kidneys.

Prolonged use of NSAIDs may lead to dose-dependent reduction in prostaglandin synthesis and may provoke the development of renal failure. Patients at high risk of this reaction include those with impaired kidney function, cardiac disorders, impaired liver function, patients taking diuretics, and elderly patients. Renal function should be monitored in such patients.

In dehydrated children and adolescents, there is a risk of developing renal failure.

Effects on the liver.

Caution is required when treating patients with impaired liver function.

Effects on female fertility.

Limited data suggest that medicinal products that inhibit cyclooxygenase/prostaglandin synthesis may affect the process of ovulation. This effect is reversible upon discontinuation of treatment. Long-term use (referring to a dose of 2400 mg per day and treatment duration exceeding 10 days) of ibuprofen may impair female fertility and is not recommended for women attempting to conceive. This medicinal product should not be used in women experiencing difficulty conceiving or undergoing infertility investigations.

Effects on the gastrointestinal tract.

NSAIDs should be used cautiously in patients with chronic inflammatory bowel diseases (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 disease, especially if complicated by bleeding or perforation, and in elderly patients. These patients should start treatment with the lowest doses. Caution should be exercised when treating patients receiving concomitant medications that increase the risk of gastotoxicity or bleeding, such as oral corticosteroids, anticoagulants (e.g., warfarin), or antiplatelet agents (e.g., acetylsalicylic acid). For long-term treatment, and in patients requiring concomitant low-dose acetylsalicylic acid or other drugs increasing gastrointestinal risk, combined therapy with misoprostol or proton pump inhibitors may be required.

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.

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

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 such reactions occurred within the first month of treatment.

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

Masking symptoms of underlying infections: Ibuprom Max 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 varicella. When Ibuprom Max is used for fever or pain relief during infection, monitoring for infection is recommended. In outpatient settings, patients should consult a physician if symptoms persist or worsen.

The use of ibuprofen is recommended to be avoided in cases of varicella.

Since the medicinal product contains lactose, patients with rare hereditary conditions such as galactose intolerance, Lapp lactase deficiency, or glucose-galactose malabsorption should not take this product.

Since the medicinal product contains sucrose, patients with rare hereditary fructose intolerance, glucose-galactose malabsorption, or sucrase-isomaltase deficiency should not use this product.

Use during pregnancy or breastfeeding.

Inhibition of prostaglandin synthesis may negatively affect pregnancy and/or embryonic/fetal development. Epidemiological data indicate an increased risk of miscarriage, congenital heart defects, and gastroschisis following the 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 therapy. In animal studies, prostaglandin synthesis inhibitors have led to increased pre- and post-implantation loss and embryonic/fetal mortality. Additionally, increased frequency of various developmental abnormalities, including cardiovascular malformations, has been reported in animals treated with prostaglandin synthesis inhibitors during organogenesis.

NSAIDs should not be used from the 20th to the 28th week 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, leading to low amniotic fluid levels and potential complications.

Ibuprofen should not be used 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. Women attempting to conceive, as well as during the first and second trimesters of pregnancy, should use the lowest possible dose for the shortest duration. In cases where ibuprofen treatment exceeds 48 hours, monitoring of amniotic fluid levels by ultrasound should be considered.

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

for the fetus: cardiopulmonary toxicity (characterized by premature closure of the ductus arteriosus and pulmonary hypertension); impaired kidney function, which may progress to renal failure associated with oligohydramnios;

for the mother near term and the newborn: prolonged bleeding time, antiplatelet effect (which may develop even at very low doses); inhibition of uterine contractions, leading to delayed or prolonged labor.

Ibuprofen is contraindicated during the third trimester of pregnancy.

In some studies, ibuprofen has been detected in breast milk at very low concentrations; therefore, it is unlikely to have a negative effect on a breastfed infant.

Ability to influence reaction speed when driving or operating machinery.

When used according to recommended doses and treatment duration, the product does not affect reaction speed when driving vehicles or operating machinery. Patients who experience dizziness, drowsiness, disorientation, or visual disturbances while taking NSAIDs should refrain from driving or operating machinery.

Dosage and Administration

For oral use, for short-term use only, regardless of food intake.

Adults and children aged 12 years and older: 1 tablet every 4 hours. Tablets should be taken with water. Do not exceed 3 tablets within 24 hours. The maximum daily dose is 1200 mg.

The lowest effective dose should be used for the shortest duration necessary to relieve symptoms (see section "Special precautions for use"). If symptoms persist for more than 3 days after starting treatment or worsen, medical advice should be sought.

Elderly patients do not require special dosage adjustment.

Patients with mild to moderate renal or hepatic impairment do not require dose adjustment.

Children

Do not use in children under 12 years of age.

Overdose

Administration of doses exceeding 400 mg/kg in children may cause symptoms of intoxication. The effect of overdose is less pronounced in adults. 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, and less frequently diarrhea. Tinnitus, headache, and gastrointestinal bleeding may also occur. Severe poisoning may lead to toxic central nervous system effects, such as drowsiness, nystagmus, visual disturbances, and occasionally agitation, disorientation, or coma. Seizures may develop in some patients. More severe intoxication may result in hyperkalemia and metabolic acidosis, acute renal failure, liver damage, arterial hypotension, respiratory depression, and cyanosis. In patients with bronchial asthma, an exacerbation of asthma may occur.

Prolonged use at doses exceeding the recommended levels or overdose may lead to renal tubular acidosis and hypokalemia.

Treatment. Management should be symptomatic and supportive, including ensuring airway patency, monitoring cardiac function and vital signs until the patient's condition stabilizes. Oral administration of activated charcoal or gastric lavage is recommended within 1 hour after ingestion of a potentially toxic dose. If ibuprofen has already been absorbed, administration of alkaline agents may be used to accelerate urinary excretion of the acidic ibuprofen.

In cases of frequent or prolonged muscle spasms, treatment should include intravenous administration of diazepam or lorazepam. In cases of bronchial asthma, bronchodilators should be used.

Adverse reactions.

The most common adverse reactions are gastrointestinal in nature and mostly dose-dependent. Adverse reactions are least common when the maximum daily dose is 1200 mg.

Clinical trial data indicate that the use of ibuprofen, particularly at high doses (2400 mg per day), is associated with a slightly increased risk of arterial thrombotic complications (e.g., myocardial infarction or stroke).

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

Cardiac system.

Frequency not known: heart failure, edema, Coumadin syndrome.

Gastrointestinal system.

Uncommon: abdominal pain, nausea, dyspepsia. Rare: diarrhea, flatulence, constipation, vomiting. Very rare: peptic ulcer, gastrointestinal perforations or gastrointestinal hemorrhage, melena, hematemesis, sometimes fatal (especially in elderly patients); ulcerative stomatitis, gastritis, pancreatitis, exacerbation of colitis and Crohn's disease.

Nervous system.

Uncommon: headache. Rare: vertigo. Very rare: aseptic meningitis (see below), individual symptoms of which (nuchal rigidity, headache, nausea, vomiting, fever, or disorientation) may occur in patients with autoimmune disorders such as systemic lupus erythematosus or mixed connective tissue disease. Frequency not known: paresthesia, somnolence.

Renal and urinary system.

Very rare: acute renal impairment, papillary necrosis, particularly with prolonged use, associated with increased plasma urea levels, edema, hypernatremia (sodium retention), oliguria. Frequency not known: renal failure, nephrotoxicity, including interstitial nephritis and nephrotic syndrome.

Hepatic system.

Very rare: hepatic function abnormalities. Frequency not known: hepatitis and jaundice may occur with prolonged treatment.

Vascular system.

Very rare: arterial hypertension. Frequency not known: arterial thrombosis (myocardial infarction or stroke).

Skin and subcutaneous tissue.

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

Blood and lymphatic system.

Very rare: anemia, leukopenia, thrombocytopenia, pancytopenia, agranulocytosis, which may occur with prolonged treatment, with initial signs including fever, sore throat, superficial oral ulcers, influenza-like symptoms, severe fatigue, unexplained bleeding, and bruising.

Psychiatric disorders.

Rare: psychiatric disorders, depression, insomnia, restlessness, hallucinations, confusion.

Eye disorders.

Frequency not known: visual disturbances, optic neuritis may occur with prolonged treatment.

Ear and labyrinth disorders.

Rare: tinnitus and dizziness may occur with prolonged treatment.

Immune system.

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

General disorders.

Malaise and fatigue, irritability.

Laboratory tests.

Very rare: decreased hemoglobin levels.

Description of selected adverse reactions

There have been reports of hypersensitivity reactions following treatment with ibuprofen. Such reactions include non-specific allergic reactions and anaphylaxis, respiratory tract reactions such as bronchial asthma, asthma exacerbation, bronchospasm, or dyspnea, and various skin disorders including rashes of different types, pruritus, urticaria, purpura, angioedema, and less commonly exfoliative and bullous dermatoses (including epidermal necrolysis and erythema multiforme).

The pathogenic mechanism of drug-induced aseptic meningitis is not fully understood. However, available data on aseptic meningitis associated with NSAID use suggest a hypersensitivity reaction (based on temporal association with drug intake and resolution of symptoms after drug discontinuation). In particular, isolated cases of aseptic meningitis symptoms (such as nuchal rigidity, headache, nausea, vomiting, fever, or disorientation) have been reported during ibuprofen treatment in patients with autoimmune disorders (such as systemic lupus erythematosus or mixed connective tissue disease).

Shelf life. 3 years.

Storage conditions.

Store in the original packaging at a temperature not exceeding 30 °C.

Keep out of reach of children.

Packaging.

Film-coated tablets, pack sizes of 6, 12, 24 (12 × 2) in blisters, 24 in bottles, in a cardboard box.

Prescription status. Over-the-counter.

Manufacturer.

TOV US Farmatsiya / US Pharmacia Sp. z o.o.

Manufacturer's address and place of business.

Ul. Ziebicka 40, 50-507 Wroclaw, Poland.

Marketing authorization holder.

Unilab, LP.

Address of the marketing authorization holder and/or its representative.

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

Ibuprom max