NUROFEN oral suspension (strawberry), 100mg/5ml 100ml bottle

Components and release form

The drug is produced in 2 forms: gel and tablets. The tablets are coated with a light film and have a round shape. Sold in packages.

Nurofen in gel form is intended for external use. It has a colorless and homogeneous consistency with an inherent odor of alcohol.

The main component is ibuprofen. The tablets contain auxiliary elements: croscarmellose sodium, colloidal silicon dioxide, stearic acid.

Additional components in the gel are: sodium hydroxide, isopropyl alcohol, water.

Instructions for use

It is better to use the medicine only after consultation with a specialist and as prescribed.

Tablets can be given to adults and children over 12 years of age, no more than 200 mg 3-4 times a day. The drug is taken after meals. For faster and more noticeable results, you can double the dose and take it 3 times a day.

The ointment is intended for external use. Can only be used by persons over 12 years of age. No more than 125 mg of the main active ingredient can be used at a time. The gel can be applied no more than 4 times a day, with an interval of at least 4 hours. If after 12-14 days the condition does not improve, then you should stop taking the drug.

Experience of using Nurofen-gel in clinical practice

Rheumatic diseases are one of the main causes of temporary disability, disability and decreased quality of life of patients, especially among middle-aged and elderly people, which determines the important socio-economic significance of this pathology and the need for further study and improvement of methods for diagnosing and treating this nosology.

The main clinical manifestations characteristic of this group of diseases are pain and inflammation. According to Harris, almost 90% of patients with various types of chronic pain have reduced ability to work, and 2/3 have reduced activity in everyday life. This, in turn, leads to the development of depressive or anxiety states in more than half of the patients, and the severity of these manifestations in such patients is 2 times higher than in the population [1].

The most widely used group of drugs in rheumatology is represented by nonsteroidal anti-inflammatory drugs (NSAIDs). They differ in the severity of anti-inflammatory, analgesic and antipyretic effects, as well as in terms of individual sensitivity and tolerability, which must be taken into account when selecting therapy for each individual patient. The main mechanism of action of NSAIDs is associated with the suppression of cyclooxygenase (COX), an enzyme involved in the production of prostaglandins, mediators of pain and inflammation.

One well-known and commonly used NSAID is ibuprofen. The drug was created in 1962 and has established itself as a drug with good efficacy and tolerability, which has been confirmed in a number of clinical studies [2]. According to data obtained by Professor Autret-Leca (France), in terms of tolerability, ibuprofen is one of the best drugs among NSAIDs. Ibuprofen can be used in both adult patients and children. Unlike aspirin, ibuprofen does not cause Reye's syndrome. In addition, the drug, unlike paracetamol, does not form toxic metabolites, and its toxicity in case of accidental or intentional overdose is lower, which determines a wider therapeutic range of ibuprofen use.

Currently, a sufficient amount of data has been accumulated indicating that the main therapeutic effects of NSAIDs (analgesia, anti-inflammatory and antipyretic effects) are the result of inhibition of the so-called induced COX isoform (COX-2), which is normally absent and produces prostaglandins when activated by inflammatory mediators . At the same time, the development of adverse reactions is associated with inhibition of the COX-1 isoform, which under physiological conditions produces prostaglandins with a protective function and has a cytoprotective effect on the gastric mucosa, prevents platelet aggregation when released by endothelial cells and participates in the normal functioning of the kidneys. Thus, the use of classical NSAIDs, which suppress the production of both pro-inflammatory and physiological prostaglandins, is associated with an increased risk of “NSAID gastropathy”, the development and increase of arterial hypertension and a number of other adverse reactions. In this regard, if it is necessary to use NSAIDs, local therapy is widely used, which helps to create a maximum concentration of an analgesic and anti-inflammatory drug at the site of the lesion and does not have such a pronounced negative effect on the body as with the systemic use of NSAIDs. In addition, the use of local therapy helps to reduce the dose of orally and parenterally administered NSAIDs.

There are certain requirements for locally applied products [3]. The drug must be effective and must not cause local toxic or allergic reactions; the concentration of the drug in the blood should not reach a level that leads to the development of adverse events, but it is necessary to create high concentrations of the drug in the target tissues.

In terms of evidence of the effect of NSAIDs when applied locally, the analysis of the results of controlled studies on the treatment of acute and chronic pain conducted by RA Moore and co-authors is of interest [4]. For acute pain, 37 placebo-controlled studies including 3556 patients and 24 actively controlled studies (4171 patients) were analyzed; for chronic pain, 13 (1161 patients) and 12 (1272 patients), respectively. The results of these studies indicate that topical use of NSAIDs is statistically more effective than placebo agents for pain relief. The authors give preference to ketoprofen, ibuprofen and piroxicam.

Ibuprofen has been used for local therapy since the 1980s, both for analgesia for sports injuries and to relieve inflammation. Using 10% ibuprofen cream in 40 patients with various forms of post-traumatic damage, G. Baracchi et al [5] after 14 days obtained significant differences in the severity of pain, joint swelling and functional activity compared with placebo. The effectiveness of the drug, according to doctors, was very high and high in 17 patients treated with ibuprofen, and only 3 in the placebo group. Low effectiveness or complete absence of positive effects was observed in 3 cases in patients of the main group and in 17 cases in the placebo group.

The cream was also evaluated therapeutically by other researchers who used it in the treatment of pain resulting from acute ankle sprain in 51 patients. The placebo group included 49 patients. Patients were included in the study no later than 24 hours after injury. The differences in terms of pain relief were significant in the first two days of therapy, and by the 14th day the indicators leveled off [6].

Rapid relief of pain and restoration of joint function after 7 days of using a cream containing ibuprofen in the treatment of tendonitis was also noted by RL Dreiser [7].

Domestic rheumatologists used domestic 5% ibuprofen cream in adult patients with rheumatoid arthritis (RA) and osteoarthritis and in children with juvenile chronic arthritis (JCA) [3]. Improvement was noted in 75.6% of patients with RA and in 90% of patients with osteoarthritis, as assessed by the patients themselves, and in 80.9% and 87.2% of patients, respectively, as assessed by the doctor. In 1/3 of patients with osteoarthritis and 1/4 of patients with RA, it was possible to reduce the daily dose of NSAIDs by 30–50%.

In patients with JCA, by the end of the course of treatment, indicators of local inflammation such as pain at rest and on palpation, as well as swelling, significantly decreased. Thus, the authors conclude that the cream used is effective in the treatment of articular syndrome in patients with rheumatic diseases. The drug is well tolerated and in some patients can serve as an alternative to the systemic use of NSAIDs.

The good effect and tolerability of 5% ibuprofen cream is evidenced by the data of M. Guillaume, who treated patients with osteoarthritis of small joints of the hands [8]. When assessing the intensity of pain at rest, movement, pressure, and joint function at the end of treatment (day 14), the results were significantly better than in the placebo group. In addition, during the treatment period, patients' sleep improved.

Later, more convenient forms of ibuprofen were created for local therapy - gels that are quickly absorbed, do not leave marks on clothing, and are not inferior in effectiveness to their predecessors.

Nurofen-gel, containing ibuprofen 5% as an active substance (manufacturer: Boots Healthcare International), meets all these requirements. A study by M. Dominkus et al [9] demonstrated that after local application of 5% ibuprofen gel, the concentration of the drug in the fascia, muscles and subcutaneous fat was significantly higher than in the blood plasma (p < 0.05), which confirms the low risk of developing systemic adverse reactions when using this gel. The therapeutic level of drug concentration at the destination site is maintained for 15 hours after topical use of the drug, which determines the long-term effect of the gel. According to Peters, when administered percutaneously, the concentration of ibuprofen in muscles and fascia is 500 times higher than in plasma, and is only 5% of that when administered orally [10]. In addition, when applied topically, ibuprofen has a half-life of 8–12 hours (orally, 2 hours).

Similar data were obtained by PW Billigmann [11], who determined the concentration of the drug in various tissues after a 3-day application of 6 g of ibuprofen microgel (dose equivalent to 300 mg of ibuprofen) 3 times a day or 8 g of microgel (dose equivalent to 400 mg of ibuprofen) 3 times per day (table).

The effectiveness of 5% ibuprofen gel was assessed in a placebo-controlled study in patients with soft tissue diseases [12]. Patients received active gel (group 1) or placebo gel (group 2) for 7 days. The severity of pain and changes in physical activity were determined using a visual analogue scale.

By the 7th day of therapy, a statistically significant (p < 0.001) superiority of the therapeutic effect of ibuprofen gel compared to placebo control was revealed. When assessing pain in group 1, 75% of patients showed a clinically significant reduction in pain, while in group 2 this figure was only 39%. Clinically significant improvement in physical activity was noted by 79% of patients in group 1 and 44% of patients in group 2.

Another double-blind, placebo-controlled study compared the effectiveness of topical application of 5% ibuprofen gel and orally administered ibuprofen (1200 mg/day) in patients with pathology of periarticular soft tissues [13]. Patients of the 1st group received active gel and placebo tablets (50 people), in the 2nd group - active tablets and placebo gel (50 people). Therapy was carried out for at least 7 days. According to the results of the study, both groups revealed similar effectiveness of the therapy in terms of such indicators as the time required to achieve complete clinical improvement (p = 0.59), as well as to eliminate individual symptoms, namely pain at rest, with movement and swelling in the affected joints.

High efficiency and good tolerability of 5% ibuprofen gel have been demonstrated in osteoarthritis, RA, JCA [8, 14], and various lesions of the tendon-muscular system, both traumatic and inflammatory [15].

When prescribing the drug, patients should be explained that to achieve the effect, it is necessary to apply the gel 3-4 times in the optimal dosage, taking into account the area of ​​the affected joint (for small strips - 1-2 cm, for large strips - 5-10 cm) and the condition of the skin cover. The gel should not be applied to open wounds or mucous membranes.

Thus, Nurofen-gel is an effective remedy for local therapy of patients with soft tissue damage, is well tolerated and can be recommended for use in the practice of a rheumatologist, traumatologist and therapist.

Literature

1. Lesnovskaya E. E., Konopleva E. F. Finalgon in the fight against pain // Russian Medical Journal. 2001. T. 9. No. 7–8. pp. 277–278.
2. Geppe N. A. To the 40th anniversary of the creation of ibuprofen. First international conference on the use of ibuprofen in pediatrics//Russian Medical Journal. 2002. T. 10. No. 18.
3. Nasonova V. A., Muravyov Yu. V., Kuzmina N. N. Is local therapy of articular syndrome with the drug “Dolgit” for rheumatic diseases an alternative to the systemic prescription of non-steroidal anti-inflammatory drugs // Therapeutic archive. 1998. No. 11. P. 64–66.
4. Moore RA, Tramer MR, Carroll D. et al. Quantitive systematic review of topically applied non-steroidal anti-inflammatory drugs//Br. Med. J. 1998; 316:333–338.
5. Baracchi G., Messina Denaro S., Piscini S. Study of the topical application of isobutylphenyl-propionic acid (Ibuprofen) in traumatic inflammation. Double-blind comparison with a placebo//Gaz Med It. 1982; 141:691–694.
6. Campbell J., Dunn T. Evaluation of topical ibuprofen cream in the treatment of acute ankle sprains//J. Accident and Emergency Medicine. 1994; 11: 178–182.
7. Dreiser RL Clinical study of the efficacy and tolerance of percutaneous ibuprofen in the treatment of tendonitis//J. Intern. Med. 1988; 119: 70–73.
8. Guillaume M. Clinical study on the efficacy and tolerance of percutaneous ibuprofen in the symptomatic treatment of arthrosis of small joints//Le Journal International de Medicine. 1989; 1–4.
9. Dominkus M., Nicolakis M., Kotz R. et al. Comparison of tissue and plasma levels of ibuprofen after oral and topical administration //Arzneimittelforschung. 1996; 46(12): 1138–1143.
10. Peters H., Chlud K., Berner G. et al. Zur perkutanen kinetic von ibuprofen//Aktuelle Rheumatologie.1987; 12: 208–211.
11. Billigman PW Treatment of ankle-joint sprains with ibuprofen microgel. Rapidly effective percutaneous therapy without systemic stress//Therapiewoche. 1996; 21:1187–1192.
12. Machen J., Whitefield M. Efficacy of a proprietary ibuprofen gel in soft tissue injuries: a randomized, double-blind placebo-controlled study//Int. J. Clin. Pract. 2002; 56(2): 102–106.
13. Whitefield M., O, Kane CJ, Anderson S. Comparative efficacy of a proprietary topical ibuprofen gel and oral ibuprofen in acute soft tissue injuries: a randomized, double-blind study//J. Clin. Pharm. Ther. 2002; 27(6): 409–417.
14. Schimek J., Hilken K., Vogtle-Junkert U. Percutaneous medication used on its own in rheumatological therapy: an alternative to oral treatment?//Therapiewoche. 1991; 41: 1170–1176.
15. Castiaux JP Openstudy of the tolerance if ibuprofen 5% gel in the treatment of mild lesions of the musculoskeletal and connective tissues in 30 pstients //Study Report. 192; 533.

R. M. Balabanova, Doctor of Medical Sciences, Professor T. P. Grishaeva , Candidate of Medical Sciences Institute of Rheumatology, Moscow

Contraindications

The drug has an extensive list of contraindications. Before taking it, you should familiarize yourself with it in detail:

• erosive and ulcerative lesions of the gastrointestinal tract;
• heart failure;
• allergy to acetylsalicylic acid, which is accompanied by asthma, urticaria;
• serious kidney and liver diseases;
• problems with vision and hearing;
• bleeding in the gastrointestinal tract;
• 3rd trimester of pregnancy;
• lactation period;
• intracranial hemorrhages;
• children under 6 years old;
• increased susceptibility to the constituent components of the drug.

The medicine in the form of tablets should be taken with extreme caution in patients with diabetes mellitus, serious somatic diseases, bronchial asthma, and coronary heart disease.

Patients with bronchial asthma and urticaria should avoid using the drug in gel form. Also, children under 12 years of age and people with excessive sensitivity to the main and auxiliary components should not be used.

NUROFEN oral suspension (strawberry), 100mg/5ml 100ml bottle

The simultaneous use of ibuprofen with the following drugs should be avoided: · Acetylsalicylic acid: with the exception of low doses of acetylsalicylic acid (not more than 75 m by a doctor, since combined use may increase the risk of side effects. With simultaneous use, ibuprofen reduces the anti-inflammatory and antiplatelet effect of acetylsalicylic acid (possibly increased incidence of acute coronary insufficiency in patients receiving small doses of acetylsalicylic acid as an antiplatelet agent after starting ibuprofen).Other NSAIDs, including selective COX-2 inhibitors: the simultaneous use of two or more drugs from the group of NSAIDs should be avoided -due to a possible increase in the risk of side effects.Use with caution simultaneously with the following drugs: · Anticoagulants and thrombolytic drugs: NSAIDs may enhance the effect of anticoagulants, in particular warfarin and thrombolytic drugs. · Antihypertensives (ACE inhibitors and angiotensin II antagonists) and diuretics: NSAIDs may reduce the effectiveness of drugs in these groups. Diuretics and ACE inhibitors may increase the nephrotoxicity of NSAIDs. · Glucocorticosteroids: increased risk of gastrointestinal ulceration and gastrointestinal bleeding. · Antiplatelet agents and selective serotonin reuptake inhibitors: increased risk of gastrointestinal bleeding. · Cardiac glycosides: simultaneous administration of NSAIDs and cardiac glycosides can lead to worsening heart failure, a decrease in glomerular filtration rate and an increase in the concentration of cardiac glycosides in the blood plasma. · Lithium preparations: there is evidence of the likelihood of an increase in the concentration of lithium in the blood plasma during the use of NSAIDs. · Methotrexate: there is evidence of the likelihood of an increase in the concentration of methotrexate in the blood plasma during the use of NSAIDs. · Cyclosporine: increased risk of nephrotoxicity with simultaneous administration of NSAIDs and cyclosporine. · Mifepristone: NSAIDs should be started no earlier than 8-12 days after taking mifepristone, as NSAIDs may reduce the effectiveness of mifepristone. · Tacrolimus: When NSAIDs and tacrolimus are co-administered, the risk of nephrotoxicity may increase. · Zidovudine: Concomitant use of NSAIDs and zidovudine may lead to increased hematotoxicity. There is evidence of an increased risk of hemarthrosis and hematomas in HIV-positive patients with hemophilia who received concomitant treatment with zidovudine and ibuprofen. · Quinolone antibiotics: In patients receiving concomitant treatment with NSAIDs and quinolone antibiotics, the risk of seizures may be increased.

Adverse reactions and overdose

If Nurofen is used for painful periods, toothache or fever for several days, then no adverse reactions should occur. With prolonged use, adverse reactions may occur:

• from the digestive system: stomach ulcer, constipation, anorexia, indigestion, pain in the mouth, hepatitis;
• from the central nervous system: headache, lethargy, drowsiness, stress, emotionality, insomnia;
• from the cardiovascular system: increased blood pressure, heart failure;
• from the senses: the appearance of tinnitus, deterioration of vision and hearing, swelling of the eyelids;
• from the hematopoietic system: leukopenia, anemia;
• from the respiratory system: bronchospasm, shortness of breath.

Other effects include allergies such as urticaria, angioedema, itching and excessive sweating.

If Nurofen is taken continuously for a long time, ulceration of the gastric mucosa may occur and bleeding may begin.

In case of overdose, a delayed reaction, drowsiness, stress, headache, and high blood pressure appear.

If the permissible dose is exceeded, you need to rinse your stomach, drink activated charcoal and engage in symptomatic therapy.

Ibuprofen belongs to the group of non-steroidal anti-inflammatory drugs (NSAIDs), which represent a large and chemically diverse group of drugs that are widely used in clinical practice.

Despite the fact that in recent years the number of NSAIDs has increased significantly and this group includes a lot of drugs that differ in chemical structure, features of action and application, ibuprofen remains the drug of choice for the treatment of pain and fever, especially in pediatric practice.

History of development

The history of the discovery of the drug began in 1957, when Stuart Adams, together with chemist John Nicholson, began to study the group of phenylpropionic acids. In 1962, the molecule BTS 13621 was created, now commonly known as ibuprofen. During preclinical and clinical studies, the drug showed good efficacy, good tolerability and caused less pronounced side effects from the gastrointestinal tract (GIT) than acetylsalicylic acid (ASA). For clinical use, the drug was registered on January 12, 1962 by the British Patent Office under the name Brufen. It was intended to be prescribed to patients with rheumatoid arthritis by prescription.

In the USA, the drug was registered in 1974 under the trade name Motrin.

Taking into account the accumulated clinical experience and the results of clinical studies, the indications for prescribing ibuprofen have expanded. In the UK, the drug has been marketed as an over-the-counter medicine since 1983 under the name Nurofen. In 1984, the drug acquired over-the-counter status in the USA. And by the end of 1985, more than 100 million people were using Nurofen in more than 120 countries. In 1985, Boots was awarded a Queen's Award in recognition of scientific and technical achievements in the development of the drug ibuprofen.

In 2006, based on data on the safety and effectiveness of ibuprofen obtained in clinical studies, a new indication for the drug was added - use in children over 6 years of age.

A drug with the trade name “Nurofen” (200 mg tablets) appeared on the Russian market in 1997; in subsequent years the following forms of ibuprofen were registered in Russia:

1998 – “Nurofen for children” (ibuprofen, 100 mg/5 ml);

2001 – “Nurofen Plus” (ibuprofen, 200 mg + codeine phosphate, 12.8 mg);

2002 – “Nurofen” effervescent tablets – the first soluble ibuprofen in Russia;

2003 – “Nurofen UltraCap” – capsules with ibuprofen solution inside;

2005 – “Nurofen forte” (ibuprofen, 400 mg);

2005 – “Nurofen” gel;

2006 – “Nurofen for children” with strawberry flavor;

2008 – “Nurofen for children” rectal suppositories, registered in Russia.

Currently, the drug has many names and is used among both adults and children to relieve pain and fever. For children, an ibuprofen suspension (20 mg/ml) is used – “Nurofen for Children”, which does not contain sugar and is approved for over-the-counter use in children aged 6 months and older, as well as suppositories indicated for children aged 3 months and older [1].

Pharmacokinetics of ibuprofen

When taken orally, ibuprofen is partially absorbed in the stomach and then completely in the small intestine. The time to maximum plasma concentration (Tmax) is approximately 1–2 hours after oral administration of ibuprofen tablets or pediatric suspension, although a higher Tmax (3 hours) has been reported in infants 6–18 months of age. In human plasma, ibuprofen is 99% protein bound. The high degree of protein binding results in a relatively low volume of distribution (0.1 l/kg).

Ibuprofen is metabolized in the liver and is rapidly cleared from plasma with a relatively short half-life (about 2 hours). Less than 10% is excreted unchanged in the urine. The two main metabolites, 2-hydroxyibuprofen and 2-carboxyibuprofen, which are formed as a result of hydroxylation and subsequent oxidation, do not have pharmacological activity. Urinary excretion of metabolites is usually complete within 24 hours of the last dose. The total urinary excretion of ibuprofen and its metabolites is linearly dependent on dosage [2].

Mechanism of action of NSAIDs

The mechanism of action of NSAIDs is the ability to inhibit cyclooxygenase (COX), an enzyme that catalyzes the conversion of free polyunsaturated fatty acids (arachidonic acid) into prostaglandins (PGs), as well as other biologically active substances, in particular thromboxanes (TPA2) [3].

PGs have versatile biological activity:

• are mediators of the inflammatory response: they accumulate in the focus of inflammation and cause local vasodilation, edema, exudation, migration of leukocytes and other effects (mainly PGE2 and PGI2);
• sensitize receptors to pain mediators (histamine, bradykinin) and mechanical influences, lowering the sensitivity threshold;
• increase the sensitivity of the hypothalamic thermoregulation centers to the action of endogenous pyrogens formed in the body under the influence of microbes, viruses, toxins (mainly PGE2);
• perform the function of protecting the mucous membrane of the gastrointestinal tract (increasing the secretion of mucus and alkali; maintaining the integrity of endothelial cells inside the microvessels of the mucous membrane, helping to maintain blood flow in it; maintaining the integrity of granulocytes and, thus, maintaining the structural integrity of the mucous membrane);
• affect kidney function: cause vasodilation, maintain renal blood flow and glomerular filtration rate, increase renin release, sodium and water excretion, participate in potassium homeostasis.

In recent years, it has been recognized that there are two major cyclooxygenase isoenzymes that are inhibited by NSAIDs. The first isoenzyme, COX-1, controls the production of PGs, which regulate the integrity of the gastrointestinal mucosa, platelet function and renal blood flow; and the second, COX-2, is involved in the synthesis of PG during inflammation. Moreover, COX-2 is absent under normal conditions, but is formed under the influence of certain tissue factors that initiate the inflammatory response (for example, cytokines) [4]. In this regard, it is assumed that the anti-inflammatory effect of NSAIDs is due to inhibition of COX-2, and their adverse reactions are due to inhibition of COX-1 [5].

Studies modeling the interaction of ibuprofen stereoisomers with the corresponding COXs have shown the high affinity of this drug for the active center of COX-2, which explains its low ulcerogenic activity and high degree of safety in over-the-counter doses [6].

The severity of the anti-inflammatory properties of NSAIDs correlates with the degree of COX inhibition. Among them, the following order of activity is noted: meclofenamic acid, suprofen, indomethacin, diclofenac, mefenamic acid, flufenamic acid, naproxen, phenylbutazone, acetylsalicylic acid, ibuprofen.

Ibuprofen, when used in low (“over-the-counter”) doses, 800–1200 mg/day, has an analgesic and anti-inflammatory effect, with a safety profile comparable to paracetamol. When used in high doses, 1800–2400 mg/day, especially for a long time in patients suffering from severe diseases of the musculoskeletal system (osteoarthritis), ibuprofen exhibits a therapeutic effect similar to that of coxibs. This property of ibuprofen is explained by its moderate activity in inhibiting COX-1 and COX-2, as well as the short half-life of the drug [7].

There are several mechanisms of analgesic action of NSAIDs: central and peripheral [8]. The peripheral mechanism is mediated by the effect on PGs, which increase the sensitivity of pain receptors to physical and chemical stimulants, such as bradykinin, which in turn promotes the release of PGs from tissues [9].

The central mechanism is determined by the ability of NSAIDs to influence the thalamic centers of pain sensitivity (local blocking of PGE2, PGF2α in the central nervous system), resulting in inhibition of the transmission of pain impulses to the cortex [10].

The analgesic effect of NSAIDs is more pronounced for pain of mild and moderate intensity, which is localized in the muscles, joints, tendons, nerve trunks, as well as for headaches or toothaches. For severe visceral pain associated with injury, surgery, or a tumor, most NSAIDs are less effective and are inferior in pain relief to narcotic analgesics. At the same time, a number of controlled studies have shown a fairly high analgesic activity of ibuprofen, ketorolac, ketoprofen, metamizole for colic and postoperative pain. Based on the results of one of these studies, a comparative characteristic of the analgesic effect of the most commonly used NSAIDs in clinical practice was derived [11]: ketorolac 30 mg < (ketoprofen 25 mg = ibuprofen 400 mg, flurbiprofen 50 mg) > (ASA 650 mg = paracetamol 650 mg = fenoprofen 200 mg = naproxen 250 mg = etodolac 200 mg = diclofenac 50 mg = mefenamic acid 500 mg) > nabumetone 1000 mg. Based on the data presented, it can be noted that propionic acid derivatives have a higher analgesic activity: ketoprofen, ibuprofen, flubiprofen.

The effectiveness of NSAIDs for back pain of both vertebrogenic and non-vertebrogenic nature has been well studied and proven by numerous studies. Ibuprofen is one of the most preferred NSAIDs for the relief of back pain of various origins due to its more favorable spectrum of side effects compared to other representatives of this group. The large-scale randomized comparative clinical trial PAIN [12], which included more than 1400 patients, showed that ibuprofen at a dose of up to 1200 mg/day is characterized by similar tolerability as paracetamol and is superior to ASA in this regard.

Clinical experience of use for tension-type headaches shows [13] that the choice of ibuprofen in this situation is justified not only from the point of view of relieving painful episodes, but also in course prescription.

A clinical experimental study of the effectiveness of ibuprofen at a dose of 800 mg/day for 12 days shows a decrease under its influence in both the intensity of the pain syndrome (by 4.4 points on a visual analogue scale) and the degree of the negative impact of pain on the life activity of patients, an increase in the threshold of perception pain, as well as a decrease in the severity of accompanying pain manifestations. The pathogenetic justification for the use of NSAIDs in an acute attack of migraine cephalgia has clinical confirmation. The antimigraine effectiveness of ibuprofen in doses of 200 and 400 mg was studied in a double-blind, placebo-controlled study [14], which showed that the drug affects not only painful manifestations, but also the accompanying symptoms of nausea, photo- and phonophobia. Two hours after taking ibuprofen, these effects were observed in almost half of the cases (compared to 28% of controls). In this case, to relieve severe headaches, the use of 400 mg of ibuprofen was required. The effectiveness of a small dose of ibuprofen (200 mg) in relieving a mild to moderate migraine attack, assessed 2.5 hours after dosing, was equivalent to the effectiveness of 500 mg ASA, but the reduction in headache intensity occurred more quickly [15]. A study of the clinical effectiveness of ibuprofen (800 mg/day) in the preventive (course) treatment of migraine (for 14 days) demonstrated some features of its action [13]. Along with a decrease in the intensity of painful attacks, a slight decrease in their frequency was noted; The greatest changes were observed in the duration of a cephalalgia attack.

The trigger for the hyperthermic reaction is exogenous pyrogens (bacteria, viruses, toxins, allergens, medications), which, when entering the body, affect the thermal center of the hypothalamus through fever mediators. The first and most important of them is endogenous pyrogen - a low molecular weight protein produced by leukocytes (monocytes, macrophages) after activation by lymphokines. Endogenous pyrogen is specific for fever and acts on thermosensitive neurons of the preoptic region of the hypothalamus, where the synthesis of PGE1 and PGE2 is induced with the participation of serotonin. The essence of the antipyretic effect of NSAIDs comes down to inhibition of the transmission of excitation in the nuclei of the hypothalamus. Since PGs are not involved in maintaining normal body temperature, NSAIDs do not affect the normal temperature. The inhibitory effect of NSAIDs on thermoregulation is also expressed in a decrease in the release of serotonin, adrenaline and acetylcholine by the cells of the hypothalamus.

Ibuprofen at a dose of 400 mg is effective in reducing fever. Of the 2626 patients who took part in the randomized trial, 94% confirmed the high effectiveness, 91% confirmed the rapidity of action and 81% confirmed the duration of action of the drug [16].

Clinical studies have found that ibuprofen is more effective than paracetamol in reducing very high body temperature in children [17]. This effect was demonstrated in a double-blind, parallel-group study in children treated with single doses of ibuprofen 5 and 10 mg/kg, paracetamol 10 mg/kg, and placebo for fever. Ibuprofen at a dose of 10 mg/kg was more effective in reducing body temperature than paracetamol at a dose of 10 mg/kg, both in the subgroup of children with very high fever (39.2 °C; p < 0.05) and in the entire group in overall (p < 0.05).

The rapid metabolism and excretion of ibuprofen goes some way to explaining the relatively low toxicity of this drug compared to some other NSAIDs. A study that included more than 84 thousand children aged 6 months to 12 years showed that the risk of serious side effects with ibuprofen was no higher than with paracetamol [18].

Undesirable effects

The meta-analysis by D. Henry et al. focused primarily on serious upper gastrointestinal complications associated with NSAID use, which are the most common adverse effects of treatment with these drugs. Based on the data obtained, the authors arranged widely used NSAIDs in a certain sequence and concluded that long-term use of all these drugs leads to the development of gastrointestinal complications. At the same time, taking ibuprofen in a dose of up to 2400 mg/day is associated with the lowest risk of developing severe gastrointestinal complications and according to this indicator, NSAIDs are ranked as follows: ibuprofen < ASA < diclofenac < naproxen < indomethacin < piroxicam [19].

A number of studies have analyzed the risk of myocardial infarction in patients taking NSAIDs [21, 22]. In the group of patients using a therapeutic dose of ibuprofen in treatment, the risk of developing a heart attack was minimal compared with diclofenac and rofecoxib: 1.07 (95% confidence interval [CI] - 1.02–1.12) versus 1.44 (95% CI – 1.32–1.56) and 1.26 (95% CI – 1.17–1.36), respectively [21].

The safety of ibuprofen in children was demonstrated in a large, randomized, double-blind study [23]. We assessed the increased risk of hospitalization in children receiving ibuprofen 5 or 10 mg/kg for fever (n = 55,765) compared with children receiving paracetamol 12 mg/kg (n = 28,130). Of the 83,915 children whose data were analyzed, 795 (1%) were admitted to hospital within 4 weeks of study entry. Ibuprofen, compared with paracetamol, did not increase the risk of hospitalization associated with any of the 4 serious treatment outcomes of gastrointestinal bleeding, development of renal failure, anaphylaxis or Reye's syndrome. To date, not a single case of the development of Reye's syndrome has been reported in children with viral diseases treated with ibuprofen [2].

Data from a meta-analysis (2009), which included 24 randomized clinical trials, showed that the tolerability and safety of ibuprofen in children under 18 years of age is similar to that of placebo and higher than that of paracetamol [24].

It has been established that after the age of 2 months, the kidneys in children are well enough developed to cope with the elimination of ibuprofen through glomerular filtration. A study including 49 children aged 3 months to 12 years showed no age-related differences in the rate of absorption and elimination of ibuprofen [20].

In 2010, data were published on the use of intravenous ibuprofen for the treatment of postoperative pain, acute pain and fever as a safe and well-tolerated NSAID, in particular in children, patients with cystic fibrosis, and elderly patients [25]. This makes it possible to use ibuprofen in a hospital, providing higher bioavailability, speed of onset of effect and effectiveness.

A study was conducted on the tolerability and safety of the use of ibuprofen in rectal suppositories in children. Children who were in 11 children's departments and clinics in Israel and needed antipyretic medications were prescribed ibuprofen suppositories (5–10 mg/kg). Treatment was carried out for 3 to 7 days. During the study, a physical examination of children was performed, body temperature was monitored, and parents were interviewed to identify adverse reactions during therapy and assess the child’s condition. A total of 490 children completed the study. The study noted high parental satisfaction with the therapy (4.5 ± 0.47 points on a scale of 1–5), with 92.2% of respondents saying they would use the medicine in the future. Adverse reactions were reported in 8 patients (1.63%), the most common of which was diarrhea, which did not require discontinuation of the drug [26].

A Russian multicenter open study was also conducted [27], the purpose of which was to evaluate the clinical effectiveness, tolerability and safety of the drug Nurofen for children (ibuprofen) rectal suppositories in the treatment of hyperthermic conditions in children with acute respiratory diseases. When assessing the effectiveness of ibuprofen compared to paracetamol during the first 30 minutes and 1 hour, no significant differences were noted between the groups: the average decrease in temperature in the observation group was 0.6 ± 0.2 and 1.3 ± 0.6 °C , in the control group – 0.7 ± 0.3 and 1.2 ± 0.5 °C, respectively. However, within 1 hour after using the antipyretic drug in the observation group (children receiving ibuprofen), temperature normalization occurred in 10% (3) of patients, while in the control group all children remained hyperthermia. During the first three hours, temperature normalization occurred in a third (10 children) of the group receiving ibuprofen, which was significantly higher than in the control group (3.3% - 1 child). During the first 6 hours, this trend persisted and normalization of temperature was achieved in 63.3% (19) of children in the observation group versus 36.7% (11) of patients in the control group. 72 hours after the use of antipyretic drugs, the number of children who did not have hyperthermia was equal in both groups and amounted to 86.7%.

According to the study results, the intensity of the intoxication syndrome decreased faster (within 3–6 hours) in the observation group (children receiving ibuprofen) compared to the control group.

Ibuprofen (Nurofen) meets all the requirements for an “ideal” over-the-counter analgesic: availability in various dosage forms (tablets, capsules, suspensions) that are quickly absorbed in the stomach and intestines; rapid creation of peak plasma concentrations; relatively short half-life and at the same time long-lasting effect; minimal spectrum of side effects with occasional and short-term doses, good range of safety and tolerability in children. The benefits of this drug have been demonstrated in international multicenter and randomized clinical trials. These facts are very important from the point of view of choosing the most optimal NSAID for the treatment of pain and fever. It is necessary to take into account the fact that the main side effects of NSAIDs, including gastrointestinal ones, are dose-dependent. And relief of pain and fever involves the use of ibuprofen (Nurofen) in analgesic and antipyretic doses, which are lower than anti-inflammatory doses and, accordingly, less dangerous for the patient.

Information about the author: Erofeeva Svetlana Borisovna – Candidate of Medical Sciences, doctor, clinical pharmacologist, City Clinical Hospital No. 61. E-mail