Instructions for Ibuprom Max PP film-coated tablets 400 mg No. 24
Composition
active ingredient: ibuprofen;
1 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;
shell: 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;
grey ink: shellac glaze approx. 45% (20% esterified) in ethyl alcohol, titanium dioxide (E 171), N-butyl alcohol, iron oxide (black) (E 172), propylene glycol (E 1520), isopropyl alcohol, ammonium hydroxide (28%) (E 527), simethicone.
Dosage form
Film-coated tablets.
Main physicochemical properties: white or almost white tablets, with a slight sheen, biconvex, oval-shaped, with a gray inscription "IBUPROM" on one side and "RR" on the other side.
Pharmacotherapeutic group
Nonsteroidal anti-inflammatory and antirheumatic drugs. Propionic acid derivatives.
ATX code M01A E01.
Pharmacological properties
Pharmacodynamics
Ibuprofen is a nonsteroidal anti-inflammatory drug (NSAID), a propionic acid derivative, which exerts a directed effect against pain, fever and inflammation by inhibiting the synthesis of prostaglandins - mediators of pain and inflammation. In addition, ibuprofen reversibly inhibits platelet aggregation.
Experimental data suggest 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 when single doses of ibuprofen 400 mg were administered within 8 hours before or within 30 minutes after immediate-release acetylsalicylic acid (81 mg), a reduction in the effect of aspirin acetylsalicylic acid on thromboxane formation or platelet aggregation was observed. Although there is uncertainty about the extrapolation of these data to the clinical situation, it cannot be excluded that regular long-term use of ibuprofen may reduce the cardioprotective effect of low-dose acetylsalicylic acid. With non-systematic 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. The maximum concentration in the blood serum is determined 45 minutes after administration (if taken on an empty stomach). When this drug is used with food, peak levels are observed 1-2 hours after administration. Ibuprofen is metabolized in the liver, excreted by the kidneys in unchanged form or in the form of metabolites. The half-life is almost 2 hours. In elderly patients, no significant differences in the pharmacokinetic profile are observed.
In a pharmacokinetic study conducted in 57 healthy volunteers comparing Ibuprom Max PP and the reference drug (ibuprofen, film-coated tablets, 400 mg), bioequivalence of both drugs was demonstrated in terms of maximum plasma concentration (Cmax), time to maximum plasma concentration (Tmax) and area under the concentration-time curve (AUC). The study demonstrated that measurable ibuprofen plasma levels (1.82 ± 0.76 μg/ml) were observed 5 minutes after administration of Ibuprom Max PP. The ibuprofen plasma concentration 10 and 15 minutes after administration of Ibuprom Max PP was 4.23 ± 3.61 μg/ml and 7.94 ± 6.67 μg/ml, respectively.
Indication
Symptomatic treatment of headaches, including migraines, toothaches, dysmenorrhea (menstrual pain), neuralgia, back pain, joints, muscles, as well as symptoms of colds and flu.
Contraindication
Hypersensitivity to ibuprofen or to any of the components of the drug. Hypersensitivity reactions (e.g. asthma, rhinitis, angioedema or urticaria) after taking ibuprofen, acetylsalicylic acid or other NSAIDs. Gastric and duodenal ulcer/bleeding in active form or history of recurrence (two or more severe episodes of confirmed ulcer or bleeding). History of gastrointestinal bleeding or perforation of the gastrointestinal wall associated with the use of NSAIDs. Severe hepatic impairment, renal impairment, heart failure (NYHA class IV). Last trimester of pregnancy. Cerebrovascular or other bleeding. Disorders of blood formation or blood clotting.
Interaction with other medicinal products and other types of interactions
- acetylsalicylic acid, as this may increase the risk of adverse reactions, except in cases where acetylsalicylic acid (dose not exceeding 75 mg per day) has been prescribed by a doctor. Experimental data indicate that, when used simultaneously, ibuprofen may inhibit the effect of low doses of acetylsalicylic acid on platelet aggregation. However, the uncertainty regarding the possibility of extrapolating these data to the clinical situation does not allow drawing definitive conclusions that regular long-term use of ibuprofen may reduce the cardioprotective effect of low doses of acetylsalicylic acid. Therefore, with non-systematic use of ibuprofen, such clinically significant effects are considered unlikely;
- other NSAIDs, including selective cyclooxygenase-2 inhibitors.
Ibuprofen should be used with caution in combination with the following drugs:
Anticoagulants: NSAIDs may enhance the effect of anticoagulants such as warfarin;
Antihypertensives (ACE inhibitors and angiotensin II antagonists) and diuretics: NSAIDs may reduce the effect of diuretics and other antihypertensive drugs. In some patients with impaired renal function (e.g. dehydrated patients or elderly patients with compromised renal function), the concomitant use of an ACE inhibitor or angiotensin II antagonist and drugs that inhibit cyclooxygenase may lead to further deterioration of renal function, including possible acute renal failure, which is usually reversible. Therefore, such combinations should be prescribed with caution, especially in elderly patients. If long-term treatment is necessary, the patient should be adequately hydrated and the need for monitoring renal function should be determined at the beginning of combined treatment and thereafter. Diuretics increase the risk of nephrotoxic effects of NSAIDs;
corticosteroids: increased risk of ulcers and bleeding in the gastrointestinal tract;
Lithium: there is evidence of a potential increase in plasma lithium levels;
Methotrexate: there is a possibility of increasing the level of methotrexate in the blood plasma;
Zidovudine: Increased risk of hematological toxicity with concomitant use of zidovudine and NSAIDs. There is evidence of an increased risk of hemarthrosis and hematoma in HIV-infected patients with hemophilia when treated concomitantly with zidovudine and ibuprofen.
cardiac glycosides: NSAIDs can exacerbate cardiac dysfunction, reduce glomerular filtration function of the kidneys, and increase the level of glycosides in blood plasma;
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 mifepristone administration, as they may reduce its effectiveness;
Quinolone antibiotics: Patients taking ibuprofen and quinolone antibiotics at the same time may have an increased risk of seizures.
Sulfonylurea drugs and phenytoin: possible enhancement of the effect.
Application features
Side effects associated with ibuprofen can be minimized by using the lowest effective dose necessary to treat symptoms for the shortest period of time.
Caution should be exercised when treating patients with:
• systemic lupus erythematosus and mixed connective tissue disease;
• diseases of the gastrointestinal tract and chronic inflammatory bowel diseases (ulcerative colitis, Crohn's disease);
• arterial hypertension and/or heart failure;
• impaired kidney function;
• liver dysfunction;
• blood clotting disorders (ibuprofen may prolong bleeding time).
Elderly patients have an increased incidence of adverse reactions to NSAIDs, especially gastrointestinal bleeding and perforation, which can be fatal.
Effects on the respiratory system.
Bronchospasm may occur in patients who suffer from bronchial asthma or allergic diseases, or have a history of these diseases.
Other NSAIDs.
The 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 diseases.
Ibuprofen should be used with caution in systemic lupus erythematosus and mixed connective tissue disease due to an increased risk of aseptic meningitis.
Effect on the gastrointestinal tract.
NSAIDs should be used with caution in patients with chronic inflammatory bowel disease and a history of gastrointestinal diseases (ulcerative colitis, Crohn's disease), as their condition may be exacerbated.
The risk of gastrointestinal bleeding, perforation or ulceration increases with increasing doses of NSAIDs, in patients with a history of peptic ulcer disease, especially complicated by bleeding or perforation, and in the elderly. These patients should be started on the lowest dose.
Caution should be exercised when treating patients receiving concomitant medications that increase the risk of gastrotoxicity or bleeding, such as oral corticosteroids, anticoagulants (e.g. warfarin) or antiplatelet agents (e.g. acetylsalicylic acid).
With long-term treatment for these patients, as well as for patients who require concomitant use of low doses of acetylsalicylic acid or other drugs that increase the risk for the gastrointestinal tract, the doctor may need to prescribe combination therapy with misoprostol or proton pump inhibitors.
Patients with a history of gastrointestinal toxicity, particularly elderly patients, should be informed of any unusual gastrointestinal symptoms (especially gastrointestinal bleeding), particularly at the beginning of treatment.
In the event of gastrointestinal bleeding or ulceration in patients receiving ibuprofen, treatment should be discontinued immediately.
Effects on the cardiovascular and cerebrovascular systems.
Patients with hypertension and/or a history of mild to moderate congestive heart failure should be treated with caution (consultation with a doctor is necessary), since fluid retention, hypertension and edema have been reported with ibuprofen, as with other NSAIDs.
Clinical trial and epidemiological data suggest that the use of ibuprofen, especially at high doses (2400 mg/day), and in long-term use may be associated with a small increased 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/day) may be associated with an increased risk of arterial thrombotic events.
Patients with uncontrolled 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 clinical assessment. High doses (2400 mg/day) should be avoided. The clinical assessment should also be carefully considered before initiating long-term treatment in patients with risk factors for cardiovascular complications (e.g. hypertension, hyperlipidemia, diabetes mellitus, smoking), especially if high doses of ibuprofen (2400 mg/day) are required.
Effect on the kidneys.
Risk of renal failure due to deterioration of renal function. Long-term use of NSAIDs may lead to a dose-dependent decrease in prostaglandin synthesis and provoke the development of renal failure.
Children and adolescents with dehydration are at risk of developing kidney failure.
Patients with renal impairment, cardiac impairment, hepatic impairment, patients taking diuretics, and the elderly are at high risk of this reaction. Renal function should be monitored in such patients.
Severe forms of skin reactions.
Very rarely, severe skin reactions, which can be fatal, including exfoliative dermatitis, Stevens-Johnson syndrome and toxic epidermal necrolysis, may occur with the use of NSAIDs.
The risk of such reactions is highest at the beginning of therapy, with the majority of these reactions occurring within the first month of treatment. A case of acute generalized exanthematous pustulosis has also been reported following the use of ibuprofen-containing medicinal products.
At the first signs of skin rash, pathological changes in the mucous membranes, or any other signs of hypersensitivity, ibuprofen should be discontinued.
Impact on fertility in women.
There is limited evidence that drugs that inhibit cyclooxygenase/prostaglandin synthesis may affect the ovulation process. This process is reversible after discontinuation of treatment.
Long-term use (applies to doses of 2400 mg per day and treatment duration of more than 10 days) of ibuprofen may impair female fertility and is not recommended in women trying to conceive. This medicine should not be used in women who have difficulty conceiving or are undergoing investigation for infertility.
Effect on the liver.
Caution should be exercised when treating patients with impaired liver function.
It is recommended to avoid the use of ibuprofen in case of chickenpox.
Use during pregnancy or breastfeeding
Inhibition of prostaglandin synthesis may adversely affect pregnancy and/or embryo/foetal development. Epidemiological data indicate an increased risk of miscarriage, congenital heart defects and gastroschisis after administration of prostaglandin synthesis inhibitors during early pregnancy. The absolute risk of cardiovascular malformations increased from less than 1% to approximately 1.5%. The risk is thought to increase with increasing dose and duration of therapy. In animals, the use of prostaglandin synthesis inhibitors has been associated with an increased incidence of pre- and post-implantation loss and embryo/foetal lethality. In addition, an increased incidence of various malformations, 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 unless, in the opinion of the physician, the expected benefit to the patient outweighs the potential risk to the fetus. In women attempting to conceive and during the first and second trimesters of pregnancy, the lowest possible dose should be used for the shortest possible period of time. Monitoring of amniotic fluid levels by ultrasound should be considered if ibuprofen treatment lasts longer than 48 hours.
Do not use NSAIDs from the 20th to the 28th week of pregnancy unless directed by a doctor. Use of NSAIDs from the 20th week of pregnancy and later may cause rare but serious kidney problems in the unborn baby. This can lead to low amniotic fluid levels and possible complications such as impaired lung maturation and loss of joint movement (limb contractures) in the newborn baby.
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); renal dysfunction, which may progress to renal failure, accompanied by oligohydramnios;
for the mother at the end of pregnancy and the newborn: increased bleeding time, antiplatelet effect, which may develop even at very low doses; suppression of uterine contractions, leading to delayed or prolonged labor.
Ibuprofen is contraindicated in the third trimester of pregnancy.
Many studies have shown that ibuprofen and its metabolites pass into breast milk in very small amounts (0.0008% of the dose received). Given the lack of reports of harmful effects of the drug on infants, there is no need to discontinue breastfeeding during short-term use of ibuprofen in recommended doses.
Ability to influence reaction speed when driving vehicles or other mechanisms
When used in accordance with the recommended doses and duration of treatment, the drug does not affect the reaction rate when driving or operating other mechanisms. Patients who experience dizziness, drowsiness, disorientation or visual disturbances while taking NSAIDs should refrain from driving or operating mechanisms.
Method of administration and doses
For oral administration for short-term use.
Adults and children over 12 years of age (over 40 kg): 1 tablet every 4 hours. The tablets should be taken with water. Do not take more than 3 tablets in 24 hours. The maximum daily dose is 1200 mg.
The lowest effective dose should be used for the shortest possible period necessary to relieve symptoms (see section "Special instructions for use"). If symptoms persist for more than 3 days after the start of treatment or worsen, you should consult a doctor.
Patients with gastrointestinal diseases are recommended to take the drug with food.
Patients with impaired renal and hepatic function should have their doses adjusted individually.
Elderly patients do not require special dosage.
Children.
Do not use in children under 12 years of age.
Overdose
The use of the drug in children in doses exceeding 400 mg/kg may cause symptoms of intoxication. In adults, the dose effect is less pronounced. The half-life in case of overdose is 1.5-3 hours.
Treatment. There is no specific antidote. Treatment should be symptomatic and supportive, including maintaining a patent airway and monitoring cardiac function and vital signs until the patient is stable. Oral administration of activated charcoal is recommended within 1 hour of ingestion of a potentially toxic dose. If ibuprofen has already been absorbed, alkaline agents may be administered to promote urinary excretion of the acidic ibuprofen.
Frequent or prolonged muscle spasms should be treated with intravenous diazepam or lorazepam. Bronchodilators should be used in the case of bronchial asthma.
Adverse reactions
The most common adverse reactions are gastrointestinal in nature and are mostly dose-related. Adverse reactions are least common when the maximum daily dose is 1200 mg.
Clinical trial data suggest that the use of ibuprofen, especially at high doses (2400 mg per day), slightly increases the risk of arterial thrombotic complications (e.g. myocardial infarction or stroke).
Adverse reactions associated with the use of ibuprofen are classified by system organ class and frequency. The frequency is defined as follows: very common: ≥1/10; common: ≥1/100 and
From the blood and lymphatic system.
Very rare: anemia, leukopenia, thrombocytopenia, pancytopenia, agranulocytosis, which may occur with prolonged treatment, the first signs of which are fever, sore throat, ulcerative stomatitis in the oral cavity, flu-like symptoms, severe exhaustion, bleeding of unknown origin and bruising.
From the psychological side.
Rare: mental disorders, depression, insomnia, agitation, hallucinations, confusion.
From the organs of vision.
Frequency unknown: with prolonged treatment, visual disturbances and optic neuritis may occur.
From the side of the hearing organs.
Rare: with prolonged treatment, ringing in the ears and dizziness are possible.
From the immune system.
Uncommon: hypersensitivity reactions accompanied by urticaria and pruritus1. Very rare: severe hypersensitivity reactions, symptoms of which may include swelling of the face, tongue and larynx, dyspnoea, tachycardia, hypotension (anaphylaxis, angioedema or severe shock). Frequency not known: airway reactivity including asthma, bronchospasm or dyspnoea.
From the nervous system.
Uncommon: headache. Rare: dizziness. Very rare: aseptic meningitis2, some symptoms of which (rigidity of the neck muscles, headache, nausea, vomiting, fever or disorientation) may occur in patients with autoimmune diseases such as systemic lupus erythematosus, mixed connective tissue disease. Frequency not known: paraesthesia, somnolence.
From the side of the cardiac system.
Very rare: heart failure, edema.
From the vascular system.
Very rare: arterial hypertension. Frequency not known: arterial thrombosis (myocardial infarction or stroke).
From the digestive system.
Uncommon: abdominal pain, nausea, dyspepsia. Rare: diarrhoea, flatulence, constipation, vomiting. Very rare: gastric and duodenal ulcers, gastrointestinal perforation or gastrointestinal bleeding, melena, haematemesis, sometimes fatal (especially in elderly patients); ulcerative stomatitis, gastritis, pancreatitis, exacerbation of colitis and Crohn's disease.
From the liver.
Very rare: liver function disorders. Frequency unknown: hepatitis and jaundice may occur with prolonged treatment.
On the skin and subcutaneous tissue.
Rare: various types of skin rashes. Very rare: bullous reactions including Stevens-Johnson syndrome, erythema multiforme and toxic epidermal necrolysis. Frequency unknown: acute generalized exanthematous pustulosis, photosensitivity reactions.
On the part of the kidneys and urinary system.
Very rare: acute renal failure, papillary necrosis, especially with prolonged use, associated with increased blood urea levels and edema, hypernatremia (sodium retention), scanty urination. Frequency unknown: renal failure, nephrotoxicity, including interstitial nephritis and nephrotic syndrome.
General violations.
Rare: malaise, fatigue, irritability.
Laboratory studies.
Very rare: decreased hemoglobin level.
Description of selected adverse reactions
2 The pathogenic mechanism of drug-induced aseptic meningitis is not clear. Available data on aseptic meningitis associated with NSAIDs suggest a hypersensitivity reaction (due to temporal association with drug use and resolution of symptoms after drug withdrawal). In patients with autoimmune diseases (systemic lupus erythematosus and mixed connective tissue disease), isolated cases of symptoms of aseptic meningitis (neck stiffness, headache, nausea, vomiting, fever or disorientation) have been observed.
Expiration date
3 years.
Storage conditions
Does not require special storage conditions.
Keep out of reach of children.
Packaging
12 tablets in a blister; 1 or 2 or 4 blisters in a cardboard box.
Vacation category
Without a prescription.
Producer
US Pharmacia Sp. z oo, Poland.
Address
Ul. Ziebicka 40, 50-507 Wroclaw, Poland/Ul. Ziebicka 40, 50-507 Wroclaw, Poland.
Applicant
Unilab, LP, USA.
Location of the applicant and/or the applicant's representative.
966 Hungerford Drive, Office 3B, Rockville, MD 20850, USA/
966 Hungerford Drive, Suite 3B, Rockville, MD 20850, USA.
