Ibuprofen

Package leaflet (information for patients)

Tradename
Ibuprofen

Dosage form
Tablets 200 mg.

Description
Round, flat, beveled to the edge white tablets with an imprint in the form of the brand name "V" on one side.

Structure
Active ingredient: Ibuprofen 200 mg.
Excipients: microcrystalline cellulose 102, calcium stearate, aerosil® 200 (hydrophilic pyrogenic silicon dioxide).

Pharmacotherapeutic group
Non-steroidal anti-inflammatory and antirheumatic drugs. Derivatives of propionic acid.

Pharmacological properties
Pharmacodynamics
Ibuprofen is a propionic acid derivative and has an analgesic, anti-inflammatory, antipyretic effect. Inhibits cyclooxygenase I and II, blocking the synthesis of prostaglandins.
Experimental data show that ibuprofen can inhibit the effects of low-dose aspirin when taken simultaneously. In one study, when a single dose of 400 mg ibuprofen was taken within 8 hours before or within 30 minutes after taking aspirin (81 mg), there was a decrease in the effect of aspirin on thromboxane formation and platelet aggregation. However, the limitation of these data and the uncertainty about extrapolating ex vivo data implies that there are no firm conclusions for the regular use of ibuprofen and clinically significant effects are not likely to occur with casual ibuprofen use.
Pharmacokinetics
Ibuprofen is rapidly absorbed from the gastrointestinal tract, the maximum plasma concentration is observed 1-2 hours after ingestion. The half-life is about 2 hours. Ibuprofen is metabolized in the liver, excreted by the kidneys unchanged or as conjugates. Excretion by the kidneys is rapid and complete. Ibuprofen binds well to plasma proteins.

Indications for use
Ibuprofen is used as an analgesic and anti-inflammatory agent in the treatment of rheumatoid arthritis (including juvenile rheumatoid arthritis or Still's disease), ankylosing spondylitis, osteoarthritis, and other non- rheumatoid (seronegative) arthropathies. Ibuprofen is indicated: for the treatment of non-rheumatic inflammatory processes in the periarticular tissues, such as frozen shoulder (inflammation of the lining of the joint), bursitis, tendonitis, tendovaginitis and back pain. Ibuprofen can also be used to relieve pain from soft tissue injuries such as sprains. Ibuprofen is also indicated as a pain reliever for mild to moderate pain in conditions such as dysmenorrhea, toothache or postoperative pain, for symptomatic relief of headaches, including migraines.
Ibuprofen is used as an antipyretic agent.

Method of administration and dosage
For oral administration. It is advisable to use it during or after a meal with water. The tablets should be swallowed whole, not chewed, broken, or crushed to avoid discomfort and throat irritation.
Side effects can be minimized by using the lowest effective dose for a short time.
For the treatment of rheumatoid arthritis, ankylosing spondylitis, osteoarthritis, non- rheumatoid (seronegative) arthropathies, non-rheumatic inflammatory processes of the periarthricular tissues ("frozen" shoulder, bursitis, tendinitis, tendovaginitis and lower back pain):
Adults: The recommended dosage of ibuprofen is 1200-1800 mg daily in divided doses. Some patients can take 600-1200 mg of ibuprofen per day. In severe or acute conditions, the dosage can be increased, provided that the total daily dose does not exceed 2400 mg, in several doses.
Children: the daily dose of ibuprofen is 20 mg / kg body weight, in divided doses. In juvenile rheumatoid arthritis, the dose may be increased to 40 mg / kg body weight in several doses. Not recommended for children weighing less than 7 kg.
Elderly patients: at increased risk of side effects. If NSAIDs are required, ibuprofen should be used at the lowest effective dose for a short time. The patient should regularly check for gastrointestinal bleeding while taking NSAIDs.
In the presence of renal or hepatic impairment, the dosage should be determined individually.
For relief of mild to moderate pain syndrome in dysmenorrhea, postoperative pain, symptomatic treatment of headache:
Children, adolescents 12-18 years old and adults: 1-2 tablets, if necessary, up to 3 times a day. The period between doses of the drug should be at least 4 hours. Do not exceed 6 tablets per day.
As an antipyretic agent: 1 tablet, if necessary, up to 3 times a day.

Side effects
From the gastrointestinal tract: the most commonly observed adverse reactions are gastrointestinal. Peptic ulcer, perforation, or gastrointestinal bleeding, sometimes fatal, especially in old age. Nausea, vomiting, diarrhea, flatulence, constipation, dyspepsia, abdominal pain, melena, bloody vomiting, ulcerative stomatitis, exacerbation of colitis and Crohn's disease have been reported after ibuprofen use. Less commonly, gastritis developed. Rarely - perforation of the wall of the gastrointestinal tract. Very rare - pancreatitis.
From the immune system: hypersensitivity reactions have been reported after taking NSAIDs. In particular: nonspecific allergic reaction and anaphylaxis; impaired airway reactivity (asthma, bronchospasm, or shortness of breath); various manifestations on the skin (rash of various types, itching, urticaria, purpura, Quincke's edema and, less often, exfoliative and bullous dermatoses (including Stevens- Johnson syndrome, toxic epidermal necrolysis and erythema multiforme).
From the side of the cardiovascular system: edema, hypertension and manifestations of heart failure have been reported in the treatment of NSAIDs. Epidemiological data suggest that the use of ibuprofen, especially in high doses (2400 mg / day), with long-term treatment, may cause a slight increase in the risk of arterial thrombosis, causing myocardial infarction or stroke.
From the side of the blood and lymphatic system: leukopenia, thrombocytopenia, neutropenia, agranulocytosis, aplastic anemia and hemolytic anemia.
Mental disorders: insomnia, anxiety, depression, confusion, hallucinations.
Disorders of the nervous system: optic neuritis, headache, paresthesia, dizziness, drowsiness.
Infections and invasions: rhinitis and aseptic meningitis (especially in patients with existing autoimmune disorders such as systemic lupus erythematosus and mixed connective tissue diseases) with symptoms of stiff neck, headache, nausea, vomiting, fever, or disorientation.
From the side of the organ of vision: visual impairment and toxic neuropathy of the optic nerve.
From the ear and vestibular apparatus: hearing impairment, tinnitus and dizziness.
From the hepatobiliary system: impaired liver function, liver failure, hepatitis and jaundice
From the skin and subcutaneous tissue: Stevens- Johnson syndrome and toxic epidermal necrolysis (very rare), photosensitivity reactions.
From the side of the kidneys and urinary tract: impaired renal function and toxic nephropathy in various forms, including interstitial nephritis, nephrotic syndrome and renal failure.
General disorders: malaise, fatigue.

Contraindication
Ibuprofen is contraindicated in patients with hypersensitivity to the active or auxiliary substances of the drug.
Ibuprofen should not be used by patients who have previously been marked hypersensitivity reactions (e.g., asthma, urticaria, edema Quincke or rhinitis) after taking ibuprofen, aspirin or other NSAIDs.
Ibuprofen is also contraindicated in patients with a history of gastrointestinal bleeding or perforation associated with previous ibuprofen therapy. Ibuprofen should not be used in patients with recurrent peptic ulcer disease or gastrointestinal bleeding (two or more episodes of proven ulceration or bleeding). Ibuprofen should not be prescribed to patients with conditions accompanied by an increased tendency to bleeding.
Ibuprofen is contraindicated in patients with severe heart failure, hepatic and renal failure.
Ibuprofen is contraindicated during the last trimester of pregnancy.

Overdose
Toxicity: Signs and symptoms of toxicity are generally not seen at doses below 100 mg / kg in children and adults. However, supportive therapy may be necessary in some cases. In children, signs and symptoms of toxicity are observed when taking ibuprofen at a dose of 400 mg / kg and above.
Symptoms: Most patients taking significant amounts of ibuprofen have symptoms within 4-6 hours.
The most common symptoms of an overdose are nausea, vomiting, abdominal pain, lethargy, and drowsiness. Central nervous system symptoms: headache, tinnitus, dizziness, convulsions, loss of consciousness. Rarely: nystagmus, metabolic acidosis, hypothermia, renal effects, gastrointestinal bleeding, coma, apnea, diarrhea, central nervous system and respiratory depression. Confusion, agitation, loss of consciousness, and cardiovascular toxicity, including hypotension, bradycardia, and tachycardia, have also been noted. In cases of significant overdose, renal failure and liver damage are possible. Significant overdose is generally well tolerated if no other drugs have been taken.
Treatment: symptomatic. Within an hour after an overdose, you must take activated charcoal, as well as perform gastric lavage (for adults). Renal and liver function should be carefully monitored. Forced diuresis is shown. Patients should be followed up for 4 hours after taking potentially toxic doses of ibuprofen. Frequent or prolonged seizures can be treated with intravenous diazepam. Other treatments may be prescribed based on the patient's clinical symptoms.

Precautions
Like other NSAIDs, ibuprofen can mask the symptoms of infection. The use of ibuprofen in combination with other NSAIDs, including selective cyclooxygenase-2 inhibitors, should be avoided due to the increased risk of ulceration or bleeding.
Elderly patients: Elderly patients have an increased incidence of adverse reactions to NSAIDs, especially gastrointestinal bleeding and perforation, which can be fatal. Bleeding, ulceration, or perforation, which can be fatal, has been reported with all NSAIDs. The risk of gastrointestinal bleeding, ulceration, or perforation increases with increasing doses of NSAIDs, especially in patients with a history of peptic ulcer disease, as well as in elderly patients. These patients should start treatment with the lowest dose. Combination therapy with protective agents (eg, misoprostol, proton pump inhibitors) should be considered for these patients, as well as for patients requiring aspirin or other drugs that may increase the risk of gastrointestinal bleeding. Patients with a history of gastrointestinal illness, in particular the elderly, should report any unusual stomach pain (especially gastrointestinal bleeding), especially during the initial phase of treatment. Caution should be exercised when taking the drug in patients with concomitant medications that increase the risk of ulcers or bleeding (oral corticosteroids, anticoagulants such as warfarin, serotonin reuptake inhibitors, or antiplatelet drugs such as aspirin). If gastrointestinal bleeding or ulcers develop in patients taking ibuprofen, treatment should be discontinued. NSAIDs should be used with caution in patients with a history of ulcerative colitis or Crohn's disease. Patients suffering from or with a history of bronchial asthma should be careful when taking ibuprofen. In patients with cardiac disorders, impaired liver function, elderly patients, and those taking diuretics, it is necessary to monitor renal function. Ibuprofen should be used with caution in patients with a history of heart failure and hypertension. Appropriate monitoring and consultation is necessary for patients with hypertension and / or moderate heart failure, as fluid retention and edema are possible when taking NSAIDs. Epidemiological data indicate that the use of ibuprofen, especially at a high dose (2,400 mg per day) for a long time, may be associated with a slight increase in the risk of arterial thrombotic events such as myocardial infarction or stroke. In general, epidemiological studies do not suggest that taking low doses of ibuprofen (eg, <1200 mg per day) is associated with an increased risk of arterial thromboembolic complications, in particular myocardial infarction. Patients with uncontrolled hypertension, congestive heart failure, coronary artery disease, peripheral arterial disease, or cerebrovascular disease should take ibuprofen after careful counseling. Such counseling should be given before starting treatment for patients with risk factors for cardiovascular disease (eg, hypertension, hyperlipidemia, diabetes mellitus, smoking). Ibuprofen should be used with caution in patients with significant dehydration. As with other NSAIDs, prolonged use of ibuprofen can lead to papillary renal necrosis and other pathological renal changes. In connection with the use of NSAIDs, it is possible to develop serious skin reactions, some with fatal outcomes, including exfoliative dermatitis, Stevens- Johnson syndrome, and toxic epidermal necrolysis. In most cases, these reactions occurred during the first month of treatment. The drug should be discontinued at the first appearance of a skin rash, damage to the mucous membrane, or if signs of hypersensitivity appear. Ibuprofen, like other NSAIDs, affects platelet aggregation and increases bleeding time. Aseptic meningitis occurs in relatively rare cases in patients taking ibuprofen. The likelihood of aseptic meningitis is higher in patients with systemic lupus erythematosus and connective tissue diseases, but it was also reported in patients without chronic diseases. The drug can lead to impaired female fertility, which should be considered by women who have difficulty conceiving.

Interaction with other medicinal products
Caution should be exercised in patients taking any of the following medicines.
Antihypertensives, beta-blockers, and diuretics: NSAIDs can reduce the effects of antihypertensive drugs such as angiotensin - converting enzyme (ACE) inhibitors, beta-blockers, and diuretics. Diuretics can also increase the risk of NSAID nephrotoxicity.
Cardiac glycosides: NSAIDs can worsen heart failure, decrease the glomerular filtration rate (GFR), and increase the plasma concentration of cardiac glycosides.
Cholestyramine : when administered concomitantly with ibuprofen, it may reduce the absorption of ibuprofen in the gastrointestinal tract.
Lithium: simultaneous administration with lithium salts leads to a decrease in the excretion of lithium.
Methotrexate : NSAIDs can inhibit the tubular secretion of methotrexate and decrease the clearance of methotrexate.
Cyclosporine : increased risk of nephrotoxicity.
Mifepristone : a decrease in the effectiveness of the drug can theoretically occur due to the antiprostaglandin effect of NSAIDs. Limited evidence suggests that coadministration of NSAIDs on the day of prostaglandin administration does not adversely affect the effect of mifepristone or prostaglandins on cervical maturation and does not reduce the clinical efficacy of drug abortion.
Other analgesics and selective inhibitors of cyclooxygenase-2 (COX-2): It is recommended to avoid the simultaneous use of two or more NSAIDs, including COX-2 inhibitors, as this may increase the risk of side effects.
Aspirin: The concomitant use of ibuprofen and aspirin is not recommended because of the possible increased side effects, including an increased risk of gastrointestinal ulcers or bleeding. Experimental evidence suggests that ibuprofen can suppress the effect of low-dose aspirin on platelet aggregation when dosed together.
Corticosteroids: There is an increased risk of gastrointestinal ulcers and bleeding when taking corticosteroids with NSAIDs.
Anticoagulants: NSAIDs can enhance the effects of anticoagulants such as warfarin. Quinolone antibiotics: Patients taking NSAIDs and quinolones at the same time may have an increased risk of seizures.
Sulfonylurea derivatives : NSAIDs can enhance the hypoglycemic effect of sulfonylureas.
Antiplatelet agents and selective serotonin reuptake inhibitors (SSRIs): increased risk of gastrointestinal bleeding when co-administered with NSAIDs.
Cyclosporine : a possible increase in the risk of nephrotoxicity with the simultaneous use of NSAIDs with cyclosporine.
Zidovudine : increased risk of hematological toxicity with concomitant use of NSAIDs with zidovudine. There is an increased risk of hematomas in HIV (+) patients receiving concomitant treatment with zidovudine and ibuprofen.
Aminoglycosides : NSAIDs can reduce the excretion of aminoglycosides.
Herbal extracts: Ginkgo biloba may increase the risk of bleeding when used with NSAIDs.
CYP2C9 inhibitors: Concomitant use of ibuprofen with CYP2C9 inhibitors may increase the duration of action of ibuprofen (a CYP2C9 substrate). It has been shown that the simultaneous administration of ibuprofen with voriconazole and fluconazole (CYP2C9 inhibitors) leads to an increase in the duration of ibuprofen action by about 80-100%. It is necessary to reduce the dosage of ibuprofen while prescribing with strong inhibitors of CYP2C9, especially when using high doses of ibuprofen in conjunction with voriconazole or fluconazole.

Special instructions
Treatment with the drug should be carried out in the minimum effective dose, the minimum possible short course. During long-term treatment, it is necessary to monitor the picture of peripheral blood and the functional state of the liver and kidneys. When symptoms of gastropathy appear, careful monitoring is shown, including esophagogastroduodenoscopy, a general blood test (determination of hemoglobin), and fecal occult blood test.
If it is necessary to determine 17-ketosteroids, the drug should be changed 48 hours before the study.
Patients should refrain from all types of activities that require increased attention, quick mental and motor reactions. It is not recommended to take ethanol during the treatment period.

Pregnancy and elbowing
Pregnancy
Suppression of prostaglandin synthesis can adversely affect pregnancy and intrauterine development of the fetus. Epidemiological data show an increased risk of miscarriage and malformations of the heart and gastrointestinal tract after the use of inhibitors of prostaglandin synthesis in early pregnancy. It has been shown in animals that the administration of inhibitors of prostaglandin synthesis leads to an increase in pre- and post-implantation mortality of the embryo and fetus. In addition, in animals treated with inhibitors of prostaglandin synthesis during organogenesis, the incidence of various malformations, including the cardiovascular system, increases. During the first and second trimester of pregnancy, ibuprofen should be avoided unless absolutely necessary. When planning pregnancy, in the first or second trimesters of pregnancy, the dose of ibuprofen prescribed should be as low as possible, and the duration of treatment as short as possible. During the third trimester of pregnancy, the use of any inhibitors of prostaglandin synthesis can lead to the following:
- cardiopulmonary toxicity (with premature closure of the ductus arteriosus and pulmonary hypertension);
- impaired renal function, which can progress to renal failure with oligohydramnios.
In late pregnancy, prostaglandin synthesis inhibitors can put the mother and newborn at risk for:
- the possibility of lengthening the bleeding time;
- suppression of uterine contractions, which can lead to delay or prolonged labor. Therefore, ibuprofen is contraindicated during the third trimester of pregnancy.
Lactation
In limited studies, it has been found that NSAIDs can be observed in breast milk at very low concentrations. Breastfeeding should be avoided if possible while taking NSAIDs.

Influence on the ability to drive vehicles and work with mechanisms
Does not affect.

Storage conditions
Store in a dry, dark place at a temperature not exceeding 25 ° C, out of the reach of children.

Shelf life
3 years. Do not use after the expiration date printed on the package.

Vacation conditions
Without recipe.

Packaging
Ibuprofen 200 mg Tablets. There are 25 tablets in a blister. 2 blisters are packed in a cardboard box together with an enclosed leaflet.