Ibuprom max rr

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

Composition:

Active substance: ibuprofen;

One film-coated tablet contains 400 mg of ibuprofen;

Excipients: microcrystalline cellulose, corn starch, pregelatinized starch, hydrogenated vegetable oil, crospovidone (type A), talc, colloidal anhydrous silicon dioxide;

Coating: Opadry White 65F280000 (polyvinyl alcohol (E 1203), macrogol 3350 (E 1521), titanium dioxide (E 171), talc (E 553b), aluminum potassium silicate and titanium dioxide (E 171)), carnauba wax.

Pharmaceutical form. Film-coated tablets.

Main physicochemical properties: white or almost white tablets with slight sheen, double-convex, oval-shaped.

Pharmacotherapeutic group. Non-steroidal anti-inflammatory and anti-rheumatic drugs. Propionic acid derivatives.

ATC code M01AE01.

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 400 mg doses of ibuprofen within 8 hours before or within 30 minutes after immediate-release acetylsalicylic acid (81 mg) was associated with reduced effects of aspirin (acetylsalicylic acid) on thromboxane formation or platelet aggregation. Although there is uncertainty regarding the 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 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. No significant differences in the pharmacokinetic profile have been observed in elderly patients.

In a pharmacokinetic study involving 57 healthy volunteers comparing Ibuprom Max PR with a reference product (ibuprofen, film-coated tablets, 400 mg), bioequivalence of both products was demonstrated for the parameters of maximum plasma concentration (Cmax), time to reach maximum plasma concentration (Tmax), and area under the plasma concentration-time curve (AUC). The study demonstrated that measurable plasma levels of ibuprofen (1.82 ± 0.76 μg/mL) were observed as early as 5 minutes after administration of Ibuprom Max PR. Plasma concentrations of ibuprofen at 10 and 15 minutes after administration of Ibuprom Max PR were 4.23 ± 3.61 μg/mL and 7.94 ± 6.67 μg/mL, respectively.

Clinical characteristics.

Indications.

Symptomatic treatment of headache, including migraine, dental pain, dysmenorrhea (menstrual pain), neuralgia, back pain, joint pain, muscle pain, as well as symptoms of cold and flu.

Contraindications.

• Hypersensitivity to ibuprofen or to any of the components of the drug.
• Hypersensitivity reactions (e.g., asthma, rhinitis, angioneurotic edema, or urticaria) following the administration of ibuprofen, acetylsalicylic acid, or other NSAIDs.
• Active peptic ulceration 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 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 coagulation or hemostasis.

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 (dose not exceeding 75 mg per day) has been prescribed by a physician. Experimental data indicate that ibuprofen may inhibit the effect of low-dose acetylsalicylic acid on platelet aggregation. However, uncertainty regarding the extrapolation of these data to clinical situations 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 produce clinically significant effects;
• 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 effect 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 ACE inhibitors or angiotensin II antagonists with cyclooxygenase-inhibiting agents may lead to further deterioration of renal function, including potentially acute renal failure, which is usually reversible. Therefore, such combinations should be used with caution, especially in elderly patients. If long-term treatment is necessary, adequate hydration of the patient should be ensured, and monitoring of renal function should be considered at the initiation of combination therapy and thereafter. Diuretics increase the risk of nephrotoxic effects of NSAIDs.

Corticosteroids: increased risk of gastrointestinal ulceration and bleeding.

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

Methotrexate: there is a possibility of increased 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 who are 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 used earlier than 8–12 days after administration of mifepristone, as they may reduce its efficacy.

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

Oral sulfonylurea agents 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 duration necessary.

Caution is advised 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).

Elderly patients have an increased frequency of adverse reactions to NSAIDs, particularly gastrointestinal bleeding and perforations, which may 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.

Gastrointestinal effects.

NSAIDs should be used cautiously in patients with chronic inflammatory bowel diseases and 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 prior warning symptoms or 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 complicated by bleeding or perforation, and in elderly patients. These patients should start treatment with the lowest doses.

Caution is required 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 patients undergoing long-term treatment, as well as those requiring concomitant use of low-dose acetylsalicylic acid or other drugs increasing gastrointestinal risk, a physician may consider prescribing combination therapy with misoprostol or proton pump inhibitors.

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.

If gastrointestinal bleeding or ulcers occur in patients receiving ibuprofen, treatment should be discontinued immediately.

Cardiovascular and cerebrovascular effects.

Caution is advised when initiating treatment in patients with a history of arterial hypertension and/or moderate to severe congestive heart failure (medical consultation required), as fluid retention, arterial hypertension, and edema have been reported during ibuprofen therapy, as with other NSAIDs.

Clinical trial data and epidemiological evidence suggest that the use of ibuprofen, particularly at high doses (2400 mg per day) and with prolonged treatment, may lead to a slight 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.

Patients with uncontrolled arterial hypertension, congestive heart failure (NYHA class II–III), ischemic heart disease, peripheral arterial disease, and/or cerebrovascular disease should be treated with ibuprofen only after careful assessment of the clinical condition. High doses (2400 mg per day) should be avoided. Careful clinical evaluation is also required before initiating long-term treatment in patients with cardiovascular risk factors (e.g., arterial hypertension, hyperlipidemia, diabetes, smoking), especially if high ibuprofen doses (2400 mg per day) are needed.

Cases of Kounis syndrome have been reported in patients treated with Ibuprom Max RR. 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.

Renal effects.

There is a risk of renal impairment due to worsening kidney function. Prolonged use of NSAIDs may lead to dose-dependent reduction in prostaglandin synthesis and provoke the development of renal failure.

In dehydrated children and adolescents, there is a risk of developing 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. Kidney function should be monitored in these patients.

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 with 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 options should be considered (if necessary).

Effect on female fertility.

Limited data suggest that drugs inhibiting cyclooxygenase/prostaglandin synthesis may affect the process of ovulation. This effect is reversible upon discontinuation of treatment.

Long-term use of ibuprofen (referring to a dose of 2400 mg per day and treatment duration exceeding 10 days) may impair female fertility and is not recommended for women attempting to conceive. This medicinal product should not be used in women experiencing difficulties conceiving or undergoing infertility investigations.

Hepatic effects.

Caution is required when treating patients with impaired liver function.

Masking symptoms of underlying infections: Ibuprom Max RR may mask symptoms of infectious disease, potentially delaying the initiation of appropriate treatment and thereby complicating the course of the illness. This has been observed in bacterial community-acquired pneumonia and bacterial complications of varicella. If Ibuprom Max RR is used for fever or pain relief during infection, monitoring of the 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.

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, an increased frequency of various developmental abnormalities, including cardiovascular defects, 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. 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. Ultrasound monitoring of amniotic fluid levels should be considered if ibuprofen treatment exceeds 48 hours.

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. This may lead to low amniotic fluid levels and possible complications such as impaired lung maturation and reduced joint movement (joint contractures) in the newborn.

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 accompanied by 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.

Numerous studies have demonstrated that ibuprofen and its metabolites pass into breast milk in very small amounts (0.0008% of the administered dose). Given the lack of reports on harmful effects of the drug on infants, discontinuation of breastfeeding is not necessary during short-term use of ibuprofen at recommended doses.

Ability to influence reaction speed when driving or operating machinery.

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

Method of Administration and Dosage

For oral use for short-term use only.

Adults and children aged 12 years and older (with body weight over 40 kg): 1 tablet every 4 hours. Tablets should be taken with water. Do not take more than 3 tablets within 24 hours. The maximum daily dose is 1200 mg.

The lowest effective dose should be used for the shortest possible duration necessary to relieve symptoms (see section "Special Warnings and Precautions for Use"). If symptoms persist for more than 3 days from the start of treatment or worsen, consult a physician.

Patients with gastrointestinal disorders are recommended to take the medication with food.

Dosage should be individually adjusted in patients with renal or hepatic impairment.

Elderly patients do not require special dosage adjustment.

Children

Do not use in children under 12 years of age.

Overdose

Administration of the drug to children at doses exceeding 400 mg/kg may cause symptoms of intoxication. In adults, the effect of overdose is less pronounced. The half-life during 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 frequently, diarrhea. Tinnitus, headache, and gastrointestinal bleeding may also occur. In severe poisoning, toxic central nervous system effects may develop, manifesting as drowsiness, occasionally excitement, disorientation, or coma. Seizures may occasionally develop in patients. In more severe poisoning, hyperkalemia and metabolic acidosis, acute renal failure, liver damage, arterial hypotension, respiratory insufficiency, and cyanosis may occur. Prothrombin time may be prolonged. In patients with bronchial asthma, exacerbation of asthma may occur.

Prolonged use at doses higher than recommended or overdose may lead to renal tubular acidosis and hypokalemia.

Treatment
There is no specific antidote. Treatment should be symptomatic and supportive, including maintenance of airway patency and monitoring of cardiac function and vital signs until the patient's condition normalizes. Oral administration of activated charcoal is recommended within 1 hour after ingestion of a potentially toxic dose of the drug. If ibuprofen has already been absorbed, alkaline agents may be administered to enhance 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.

Side effects

The most common adverse reactions are gastrointestinal in nature and mostly dose-dependent. Adverse reactions are least frequently observed 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 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: anemia, leukopenia, thrombocytopenia, pancytopenia, agranulocytosis, which may occur during long-term treatment, with initial symptoms including fever, sore throat, oral ulcerative stomatitis, influenza-like symptoms, severe fatigue, unexplained bleeding, and bruising.

Psychiatric disorders

Rare: psychiatric disturbances, depression, insomnia, agitation, hallucinations, confusion.

Eye disorders

Frequency not known: visual disturbances, optic neuritis may occur during long-term treatment.

Ear and labyrinth disorders

Rare: tinnitus and vertigo may occur during long-term treatment.

Immune system disorders

Uncommon: hypersensitivity reactions presenting with urticaria and pruritus^1. Very rare: severe hypersensitivity reactions, symptoms of which may include facial, tongue, and laryngeal edema, dyspnea, tachycardia, hypotension (anaphylaxis, angioneurotic edema, or severe shock). Frequency not known: respiratory tract reactivity, including asthma, bronchospasm, or dyspnea.

Nervous system disorders

Uncommon: headache. Rare: dizziness. Very rare: aseptic meningitis^2, individual symptoms of which (nuchal rigidity, headache, nausea, vomiting, fever, or disorientation) may occur in patients with autoimmune diseases such as systemic lupus erythematosus or mixed connective tissue disease. Frequency not known: paresthesia, somnolence.

Cardiac disorders

Very rare: heart failure, edema. Frequency not known: Kounis syndrome.

Vascular disorders

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

Gastrointestinal disorders

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

Hepatobiliary disorders

Very rare: hepatic function abnormalities. Frequency not known: hepatitis and jaundice may occur during long-term treatment.

Skin and subcutaneous tissue disorders

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 reaction with eosinophilia and systemic symptoms (DRESS syndrome), acute generalized exanthematous pustulosis (AGEP), photosensitivity reactions.

Renal and urinary disorders

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.

General disorders

Rare: malaise, fatigue, irritability.

Laboratory investigations

Very rare: decreased hemoglobin levels.

Description of selected adverse reactions

^1 There have been reports of hypersensitivity reactions with ibuprofen use. 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.

^2 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 drug discontinuation). Isolated cases of aseptic meningitis symptoms (nuchal rigidity, headache, nausea, vomiting, fever, or disorientation) have been observed in patients with autoimmune diseases (systemic lupus erythematosus and mixed connective tissue disease).

Shelf life. 3 years.

Storage conditions.

No special storage conditions required.

Keep out of reach of children.

Packaging.

12 tablets per blister; 1, 2, or 4 blisters per cardboard box.

Prescription status. Over-the-counter.

Manufacturer.

US Pharma Sp. z o.o., Poland.

Manufacturer's address.

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

Marketing authorization holder.

Unilab, LP, USA.

Address of marketing authorization holder and/or its representative.

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