Prescription doses of ibuprofen: Ibuprofen Dosage Guide + Max Dose, Adjustments
An Overview of Clinical Pharmacology of Ibuprofen
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Ibuprofen Dosing | Medication Dosing | Patient Resources | Framingham Pediatrics | Practices | Alliance
The following table gives ibuprofen dosing guidelines by weight. It can be used for both Children’s Motrin and Children’s Advil. Ibuprofen can be administered every six hours.
Ibuprofen is a very effective medicine for fever and for pain. Unlike acetaminophen, it is also a very effective anti-inflammatory medication. Like acetaminophen, it has no effect on other symptoms related to a cold. Please remember to never use ANY fever medicine for INFANTS UNDER FOUR MONTHS OF AGE without talking to our office first. In addition, please **DO NOT USE IBUPROFEN FOR FEVER IN INFANTS UNDER SIX MONTHS WITHOUT SPEAKING WITH OUR OFFICE FIRST**. If your child has a stiff neck, is unusually lethargic or unresponsive, or might be dehydrated please call our office immediately.
The most common side effects of ibuprofen are abdominal pain, nausea, and vomiting. Giving the medicine with a full stomach is the best way to help prevent these side effects. If your child already has these symptoms, it might be better to use acetaminophen instead.
Note that ibuprofen is now available in a variety of dosage forms and concentrations. Please be sure to use the dose appropriate for the type of medication you are using. In addition, use only the dropper provided with the oral drops to measure the dosage of ibuprofen. This dropper is a very different size than the dropper provided with acetaminophen drops and other droppers available, and improper use could result in over- or under-dosing.
(50 mg/1. 25 ml)
(100 mg/5 ml)
|12-17 lbs||50 mg||1.25 ml||2.5 ml|
|18-21 lbs||75 mg||1.875 ml||4 ml|
|22-32 lbs||100 mg||2.5 ml||5 ml|
|33-43 lbs||150 mg||3.75 ml||7.5 ml||3||1 ½|
|44-54 lbs||200 mg||5 ml||10 ml||4||2||2|
|55-65 lbs||250 mg||12. 5 ml||5||2 ½||2 ½|
|66-76 lbs||300 mg||15 ml||6||3||3|
|77-87 lbs||350 mg||17.5 ml||7||3 ½||3 ½|
|88-98 lbs||400 mg||20 ml||8||4||4|
Ibuprofen Dosing | Contact Us
Safety of ibuprofen in clinical practice | Balabanova R.M., Zapryagaeva M.E.
B ol is the body’s main reaction to any tissue damage, so its relief is a problem for doctors of any specialty.
According to modern concepts of the mechanisms of development and transmission of the pain signal, a reasonable treatment of pain is considered to be an integrated approach using various groups of pharmacological agents, the mechanism of action of which is primarily aimed at suppressing the synthesis of inflammatory mediators and limiting the flow of nociceptive information from the periphery to the central nervous system.
Analgesics are widely used throughout the world. In England, more than 20 million people receive prescriptions for non-steroidal anti-inflammatory drugs (NSAIDs), and in a year (1999-2000) more than 100 million prescriptions were written for COX-2 inhibitors .
NSAIDs are most in demand primarily in rheumatic diseases for relief of articular syndrome, in trauma, postoperative conditions, renal colic, migraine, dysmenorrhea, neurological diseases, and recently their preventive effect in colon cancer and Alzheimer’s disease has been discussed. According to a survey conducted in Western European countries, NSAIDs are prescribed by more than 80% of general practitioners [5,18].
Leading in sales are over-the-counter analgesics, which are used as antipyretics and relieve pain of various origins: headache, toothache, dysmenorrhea, etc.
In 1998, 16.1 billion OTC NSAIDs were sold in the United States compared to 2.9 billion prescriptions. Of particular concern is the violation of the dosing regimen of the drug (about 1/3 of patients take prescription NSAIDs in larger doses than recommended by the doctor).
Given the predicted aging of the planet, the number of people in need of NSAIDs will steadily increase. This poses the challenge for clinicians to ensure the safety of NSAID treatment. In the United States, more people die each year from medical errors than from street injuries, lung cancer, and AIDS . One of the reasons for this is ignorance of the mechanism of action of drugs, especially with combined use, and possible adverse reactions.
The safety of NSAIDs is now the top priority. Possible side effects when using NSAIDs include damage to the gastrointestinal tract, impaired platelet aggregation, kidney function, and a negative effect on the cardiovascular system. Gastrointestinal disturbances are the most common side effects with NSAIDs. Among the frequently used NSAIDs, drugs that are particularly unfavorable in this regard can be distinguished – indomethacin, piroxicam, flurbiprofen; relatively safe drugs – ibuprofen, diclofenac, ketoprofen, as well as selective COX-2 inhibitors [4,9].
A number of researchers explain the clinical effect and the development of adverse reactions by the half-life of NSAIDs, while the more dangerous of them are long-lived (Table 1).
The development of side effects is often dose-dependent, as shown in Table 2, from which it follows that the analgesic dose of ibuprofen (1200 mg/day) is as safe as placebo.
The main mechanism that determines the safety of the drug is its ability to inhibit the activity of cyclooxygenase-2 (Table 3). However, no direct relationship between the anti-inflammatory and analgesic effect and the severity of COX-2 inhibition was found.
The most common side effects caused by inhibition of COX-1 and 5-lipoxygenase  are gastrointestinal damage, impaired renal function, platelet aggregation, etc. (Table 4).
Gastrointestinal side effects are believed to be one of the most common adverse events associated with the use of NSAIDs . However, there was a clear dose-dependence of the risk of developing NSAID-gastropathy [14,16] (Table 5).
The dose of ibuprofen 1200 mg/day is regarded as one of the safest in relation to gastrointestinal complications.
Especially often OTC NSAIDs are used not only as analgesics, but also as antipyretics, competing with acetaminophen. Comparison of the effect of ibuprofen 400 mg and acetaminophen 1000 mg in the treatment of 113 patients with sore throat caused by tonsillopharyngitis  showed that ibuprofen is significantly more effective, especially during the first 6 hours. With short-term use of these drugs, tolerability was equal.
In France and England, 1108 general practitioners participated in a randomized trial of 3 analgesics: acetylsalicylic acid (ASA), acetaminophen, ibuprofen. The study included 8677 adult patients with pain of musculoskeletal origin, throat, acute respiratory infections . The treatment was carried out for 1–7 days in doses: ASA and acetaminophen 3 g/day, ibuprofen up to 1. 2 g/day. The frequency of significant adverse events was when taking ASA – 18.7%, ibuprofen – 13.7%, acetaminophen – 14.5%. The total number of gastrointestinal complications was noted in 5.8% of those treated with ibuprofen, 7.3% with acetaminophen and 10.6% with ASA. Gastrointestinal bleeding was absent in patients treated with ibuprofen, but was diagnosed in 4 patients on acetaminophen (which does not inhibit COX-1) and in 2 on ASA.
According to the time of development of gastrointestinal complications, ASA treatment was the most unfavorable, because they appeared already on the first day after taking 1-2 tablets. Panel Conclusion: GPs should prefer ibuprofen over ASA and acetaminophen due to the poorer tolerability of ASA and the potential risk of acetaminophen overdose.
The high safety of ibuprofen is also evidenced by the fact that it has been an over-the-counter drug for more than 20 years in the country where it was created in 1962 by S. Adams et al. , who worked for Boots (Great Britain) (Fig. 1).
Fig. 1. Risk of upper GI bleeding associated with NSAIDs 
Among the undesirable include complications from the cardiovascular system, in particular, heart failure, the risk of which is higher in patients with arterial hypertension, heart disease and kidney disease (Table 6) . According to the ANA, the frequency of these events when using NSAIDs in patients with hypertension exceeds 25%. The likelihood of developing heart failure is higher when using NSAIDs with a long half-life (piroxicam) than with a short one (ibuprofen, diclofenac). There is a higher risk of developing heart failure in people over 55 years of age, especially those taking diuretics.
Randomized trial in 8059 patients with rheumatoid arthritis and osteoarthritis receiving celecoxib 400 mg/day, ibuprofen 800 mg/day, diclofenac 75 mg/day. showed an equal incidence of cardiovascular complications .
A study of the effect of NSAIDs on blood pressure in 1213 hypertensive patients showed that when taking ibuprofen, mean blood pressure was reduced by 0.3 mmHg. and rises by 6.1 mm Hg. when taking naproxen .
Neither classical NSAIDs nor selective COX-2 inhibitors provide cardioprotection, with the exception of low-dose ASA, which irreversibly inhibits COX-1 activity in platelets. In , it was shown that taking ibuprofen before ASA can block the inhibition of platelet COX-1 and reduce platelet aggregation caused by ASA, without affecting the level of serum thromboxane B2. This fact should be taken into account in the treatment of patients receiving ASA for the prevention of vascular complications, and it should be recommended to take it before ibuprofen, because. this sequence does not cancel the effect of acetylsalicylic acid.
With the advent of a new class of NSAIDs – selective COX-2 inhibitors – the question of their analgesic efficacy in comparison with classical NSAIDs is being actively discussed . The authors of this review point out that in the literature, clinical studies on the effectiveness of selective COX-2 inhibitors in the treatment of non-arthritic diseases are either mixed or absent. Analgesia for postoperative toothache with rofecoxib 50 mg was equal to 400 mg ibuprofen, and 200 mg celecoxib was weaker. With regard to acute tonic pain, there is no evidence of equality between these two groups of NSAIDs. The authors believe that inhibition of both COX isoforms is necessary to achieve the maximum analgesic effect, since there are data on the temporal and dynamic relationship of COX-1 and COX-2 and their participation in the formation of Pg E2 and subsequent clinical manifestations of pain .
The relative risk of edema in clinical practice among US hypertensive patients is presented in Figure 2 . As you can see, ibuprofen has a clear advantage over the compared drugs.
Fig. 2. Relative risk of edema development in clinical practice 
In the study CLASS , which compared the effect and tolerability of celecoxib and ibuprofen, it was shown that ibuprofen is inferior to celecoxib in the incidence of edema and increased blood pressure, but safer than rofecoxib (Fig. 3).
Fig. 3. Hypertension and edema 
In rheumatology, NSAIDs are prescribed for almost all diseases, given their triple mechanism of action. In foreign literature, an algorithm for the treatment of osteoarthritis is widely discussed, in which acetaminophen is put in the first place. A double-blind, randomized study conducted  showed that in patients with gonarthrosis, the anti-inflammatory dose of ibuprofen was 2.4 g/day. was more effective than analgesic – 1.2 g / day. and 4.0 g/day. acetaminophen, which was confirmed by a decrease in joint pain and improvement in motor function.
Analysis of Medline data on the effect of various analgesics (meloxicam, naproxen, diclofenac, ibuprofen, celecoxib, rofecoxib, codeine, morphine ) on the severity of pain in osteoarthritis (OA) showed that the best clinical effect was achieved when using ibuprofen, diclofenac and naproxen.
A review  on the treatment of OA presents the results of a double-blind study of ibuprofen and benoxyprofen in a 4-week study, indicating a 21% reduction in pain in both groups. Similar results were obtained when comparing fenoprofen calcium and ibuprofen.
The data [15,26] indicate that ibuprofen at a dose of 1.2–2.4 g/day is equally effective in gonarthrosis. and tramadol 200–400 mg/day, which once again confirms the high analgesic effect of ibuprofen.
A common reason for seeking medical attention and an equally common disability is low back pain (LBP), in which the acute phase of pain is usually limited to 7-8 days. NSAIDs are the drugs of choice for the relief of these pains . A comparative randomized study in which 48.3% of patients suffered from BNS showed that 1200 mg / day. ibuprofen are equivalent to 3 g of acetaminophen, more effective than 3 g of ASA, and safer than ASA and acetaminophen .
The analgesic effect of 1200 mg ibuprofen in LBP was confirmed in one of the studies , where it was shown that the average pain intensity according to VAS more than halved on the second day, and by the sixth day it completely or significantly decreased in 73% of patients.
In the US, up to 30% of visits to a doctor are associated with a feverish condition in children . As an antipyretic, ibuprofen is allowed at a dose of 5–20 mg/kg, which is comparable to the effect of acetaminophen.
The effectiveness and safety of ibuprofen in pediatric practice are covered in a review by prof. Geppe H.A. . Pediatricians consider ibuprofen the best tolerated NSAID in children . Prof. Antret-Leca  concluded: “Compared to acetaminophen and ASA, ibuprofen has less overdose toxicity and therefore a wider therapeutic window.”
Ibuprofen is safe because it is approved for use in children under 2 years of age. An analysis of the treatment (double-blind study) of 84,000 children under 2 years of age for fever with ibuprofen at a dose of 5-10 mg/kg and acetaminophen 12 mg/kg showed that ibuprofen does not increase the risk of hospitalization of children .
The presented data indicate that ibuprofen has a high analgesic effect at a dose of up to 1200 mg / day, is well tolerated by adults and children, is used in infants and premature babies, is not inferior in tolerance to selective COX-2 inhibitors.
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Evidence base for the efficacy and safety of ibuprofen in pediatrics
Summary. The article provides an analysis of recent research data on the evaluation of the efficacy and safety of ibuprofen as a first-line antipyretic in pediatric practice. Particular attention is paid to studies on the pharmacokinetics, efficacy and safety of ibuprofen in children with fever in children of different ages, including various formulations of the drug (suspension, suppositories).
According to the American Academy of Pediatrics (AAP), about a third of visits to pediatricians are due to the development of fever in children. Fever in children, as a rule, is the cause of unscheduled visits to the doctor, telephone consultations of parents with doctors, and self-treatment with over-the-counter forms of drugs.
In case of fever, doctors need to focus on improving the child’s comfort level, tolerance of hyperthermia, as well as assessing the severity of the child’s condition and identifying the underlying disease, which helps to minimize the risk of complications. The pediatrician should alert parents to signs of fever tolerance in the child, such as activity levels, as well as look for signs of serious illness and monitor adequate fluid intake. According to AAP experts, improving the level of comfort of the child should be the primary goal of therapy with the use of antipyretics.
According to domestic recommendations, when prescribing antipyretics, a pediatrician should be guided, first of all, by clinical indications – hyperthermia> 38.5 ° C, for children at risk -> 38.0 ° C (Marushko Yu.V., Chief G. G., 2011), and also take into account the age of the child, since not all drugs used in adults are approved for use in pediatric practice. Some drugs (acetylsalicylic acid, metamizole sodium, etc.) can be used in children only for special indications or only from a certain age.
Taking into account the data on the association between the development of Reye’s syndrome and the use of acetylsalicylic acid, the negative effect of metamizole sodium on the hematopoietic system with the development of agranulocytosis, as well as the likelihood of developing anaphylactic shock against the background of its use, in the last 20 years, the main interest of researchers and practitioners has been directed to study of the antipyretic effect of ibuprofen and paracetamol in pediatric practice.
Ibuprofen is one of the most widely prescribed and used over-the-counter antipyretic drugs worldwide. The history of the use of ibuprofen dates back to 1970s, when it began to be used as a first-line anti-inflammatory drug in adults. It should be noted that ibuprofen was one of the first and most effective drugs removed from the list of prescription drugs (Kyllönen M. et al., 2005). During the free dispensing of ibuprofen in UK pharmacies, it has become the most popular analgesic and antipyretic both in children (it is currently allowed to be used in children from 3 months of age) and in adults (Kyllönen M. et al., 2005).
Pharmacological properties of ibuprofen
According to the pharmacological classification, ibuprofen belongs to the class of non-steroidal anti-inflammatory drugs (NSAIDs), is a derivative of propionic acid. Its main effects – antipyretic and anti-inflammatory – are mediated by inhibition of cyclooxygenase activity and, accordingly, the synthesis of prostaglandins – mediators of pain, inflammation and temperature response.
Ibuprofen also has an analgesic effect, which is widely used to relieve headache, toothache and other types of pain, including in pediatric surgical practice. Ibuprofen has a wide range of applications: in pediatrics – as an antipyretic, in rheumatology – in juvenile arthritis, and recently its anti-inflammatory activity has been used in the complex treatment of patients with cystic fibrosis (Beaver W.T., 2003; Han E.E. et al., 2004; Kyllönen M. et al., 2005; Lands L.C. et al., 2007).
Ibuprofen has demonstrated positive effects on various body tissues in acute inflammatory processes. In addition, other effects of ibuprofen have been proven: for example, it inhibits platelet aggregation, restores the reduced activity of polysegmentonuclear leukocytes (in particular, the ability to phagocytosis), which, of course, is a beneficial effect in the treatment of children with acute respiratory diseases accompanied by fever (Skubitz K.M., Hammerschmidt D.E., 1986). The results of numerous studies have also demonstrated the positive effect of the use of ibuprofen in inflammatory processes in the lungs, improvement in the nervous system in injuries, positive changes in the myocardium in heart attack (Rockwell W. B., Ehrlich H.P., 1990).
Currently, ibuprofen in dosage forms intended for use in children is presented as a mixture of distereoisomers, including S (+) – and R (-) – enantiomers in a ratio of 1: 1, while it was considered for a long time that it is the first type that is associated with the main pharmacological properties of ibuprofen, and that it is the S (+) enantiomer that is its only active form. However, in recent years it has been proven that the R(-)-enantiomer is able to enhance the synthesis of endogenous cannabinoids and thus affect signal processing in the brain. It is believed that this effect causes a pronounced analgesic effect of ibuprofen.
The pharmacokinetics of ibuprofen in children when taken orally is due to good oral absorption, reaching a maximum plasma concentration after 45 minutes (Autret-Leca E., 2003). After oral administration, ibuprofen is almost completely and rapidly absorbed (if taken on an empty stomach) or after 1-2 hours (if taken after a meal). Ibuprofen is 90–99% bound to plasma proteins and penetrates into the synovial fluid, is metabolized in the liver to two inactive metabolites, and is quickly and almost completely excreted by the kidneys. Ibuprofen is metabolized in the liver with the help of cytochromes P450 and 2C9, 2C8, a certain amount (10%) is displayed unchanged. The half-life (T ½ ) is 2 hours.
It is the rapid metabolism and the absence of the formation of active metabolites that explain the low toxicity of ibuprofen and a wide therapeutic window, which distinguishes it favorably from, for example, paracetamol.
Observe some age-related features of the pharmacokinetics of ibuprofen. At the same time, it was convincingly demonstrated that changes in the values of T ½ , the volume of distribution and the concentration of the ibuprofen racemic mixture increase progressively from the neonatal period to 1–3 years, reaching at this age values corresponding to those in adults. It should be noted that with the rectal route of administration, ibuprofen is rapidly and almost completely absorbed, reaching the maximum concentration in the blood plasma after 45 minutes, which practically does not differ from similar indicators of the bioavailability of the oral dosage form – suspension. Good bioavailability of the rectal form of the drug is important in practical medicine, since vomiting, refusal to take per os and other reasons may make it difficult to use ibuprofen suspension. The rectal route of administration is an alternative and effective way to solve these problems, which is confirmed by the evidence base.
M. Kyllönen et al (2005), studying the pharmacokinetics of ibuprofen in suppositories in children and adults, included in the study three groups of children aged 1–7 weeks, 8–25 weeks, 26–52 weeks and adults aged 20– 40 years. 20 minutes after the administration of ibuprofen and for up to 10 hours, blood was taken to determine the enantiomers of ibuprofen. Already at the 20th minute, both enantiomers were determined in blood samples. A higher maximum concentration of ibuprofen was determined in adults compared to children, T ½ was greater in children aged 1–7 weeks, indicating greater absorption of the drug in adults, but more accelerated metabolism in children, especially at the age of 1–7 weeks (Kyllönen M. et al., 2005).
In addition, there is evidence that the time of distribution in the blood plasma and clearance (clearance factor) of NSAIDs, including ibuprofen, in children aged 3 months-2.5 years are increased compared with similar indicators in adults. At the same time, the indicator T ½ does not differ from that in adults, which reflects the features of the pharmacokinetics of NSAIDs and indicates their rapid absorption in young children (Litalien C., Jacqz-Aigrain E., 2001).
The pharmacokinetics of ibuprofen, as well as other drugs in children of various age groups, is an interesting aspect for further research. Since significant changes in the expression of enzymes that metabolize drugs are described at different periods of child development, a number of authors, despite the study of the drug, present different data on the pharmacokinetics of ibuprofen. Thus, when studying age-related differences in the pharmacokinetics and dynamics of ibuprofen in children aged 3 months–10.4 years, R.E. Kauffman and M.V. Nelson (19)92) determined a delay of 1-3 hours between the peak plasma concentration of the drug and the peak decrease in body temperature. According to the authors, the onset of a decrease in body temperature occurred earlier in young children. Also, young children had a higher maximum antipyretic response and the degree of change in body temperature from baseline over time, which is presumably due to the relatively larger body surface and greater heat transfer in young children (Kauffman R.E., Nelson M.V., 1992).
R.D. Brown et al (1992), studying the pharmacodynamics of ibuprofen in children, measured ibuprofen concentration in blood plasma after taking a dose of the active substance at a rate of 5–10 mg/kg body weight in 153 children with fever. The maximum concentration of ibuprofen was observed 2.5 hours before the maximum decrease in body temperature, by this time the concentration of the drug was already 50% of the maximum. The area under the curve (Area Under the Curve – AUC) of ibuprofen was higher in children aged >2.5 years, the volume of distribution and clearance were lower in older children (Brown R.D. et al., 1992).
Clinical efficacy of ibuprofen
Simultaneously with the study of the pharmacokinetics of ibuprofen, the indicators of its clinical efficacy are constantly being studied, including in comparison with other widely used drugs (acetylsalicylic acid, paracetamol).
A study of the comparative clinical efficacy of ibuprofen, acetylsalicylic acid and paracetamol, conducted by a group of French scientists led by E. Autret (1997), included children aged 6–24 months. To evaluate the effectiveness of these substances, which were used in age dosages, the following effectiveness criteria were chosen: the area under the curve of the plasma concentration of the active substance (AUC), the percentage decrease in body temperature, as well as the comfort and well-being of the patient, determined by special scales. The greatest efficiency and improvement in the patient’s well-being in the first 6 hours was observed against the background of the use of ibuprofen, which proves its pronounced anti-inflammatory and antipyretic effect, which was also confirmed by the AUC of ibuprofen.
At the same time M.C. Nahata et al (1991), studying the pharmacokinetics of ibuprofen in 17 febrile children aged 3–17 years, used the drug at a single dose of 5 or 10 mg/kg. The authors did not establish a direct relationship between the dose of the active substance and the antipyretic effect – a comparable effect was noted when ibuprofen was used both at a dose of 5 mg/kg and 10 mg/kg. Also, age-related features of the pharmacokinetics of the drug in these groups of children were not recorded (Nahata M.C. et al., 1991).
N. Moore et al (2002) conducted a double placebo-controlled study to investigate the tolerance of ibuprofen, acetylsalicylic acid and paracetamol in 2815 patients (adolescents and adults) with symptoms of a cold and sore throat. The drug tolerance was assessed by the presence of significant side effects. The frequency of registration of side effects when taking ibuprofen, acetylsalicylic acid and paracetamol was 12.0; 15.7 and 12.3% respectively. Ibuprofen was better tolerated than paracetamol and acetylsalicylic acid. Side effects that were recorded for all drugs were mainly gastrointestinal in nature: abdominal pain and dyspepsia (Moore N. et al., 2002).
The data obtained slightly change the generally accepted opinion about the better tolerance of paracetamol and the absence of its effect on the gastrointestinal tract, and are also an important factor for practitioners when choosing antipyretic drugs.
When comparing the antipyretic activity of paracetamol and ibuprofen, no significant differences were found between the degree of decrease in body temperature (by 1–2 °C on average), the onset of action of the drugs (after 15 minutes) and the time of development of the peak effect (3–4 hours). However, ibuprofen demonstrated a longer duration of antipyretic effect (>6-8-10 hours) compared to paracetamol (4-6 hours), which, in turn, is reflected in the frequency of drug administration (every 4 hours for paracetamol and 6-8 hours for ibuprofen). The use of ibuprofen, like other NSAIDs, is associated with a risk of developing NSAID-induced gastropathy, but there is no data confirming its development when using ibuprofen for 3 days to relieve fever (Lesko S.M., Mitchell A.A., 1999).
The conclusions of I. Bjarnason (2007) based on the analysis of scientific medical sources confirm that of all NSAIDs, ibuprofen has the most favorable gastrointestinal tolerance (Bjarnason I., 2007).
In addition, side effects from the digestive system, liver, kidneys when using paracetamol are more severe and have a worse curability compared to side reactions associated with the use of ibuprofen. This is due to the formation of active metabolites of paracetamol and their irreversible damaging effect on organ tissues (van den Anker J. N., 2013). Liver damage in children with the use of paracetamol, according to studies, is more often noted with prolonged use, which is associated with the accumulation of toxic metabolites, as well as when used in high doses or with frequent uncontrolled intake against the background of a narrow therapeutic window in both children and adults ( Ushkalova E., 2012).
G.M. Allan et al (2010) analyzed 10 studies with a total of 1078 participants, attempting to establish the benefits of clinical use of ibuprofen and paracetamol in lowering body temperature in children with fever, presenting it in the form of recommendations. According to the data obtained, ibuprofen demonstrates greater antipyretic activity. The incidence of adverse reactions in both drugs is comparable. When used as antipyretic agents, the risk of developing systemic reactions, association with the development of Reye’s syndrome, nephrological or gastrointestinal complications have not been identified (Allan G.M. et al. , 2010).
Data support the inclusion of ibuprofen as a first-line antipyretic in the 2011 updated World Health Organization guidelines.
Safety of ibuprofen
Data on the safety and greater clinical efficacy of ibuprofen in children with fever are supported by a meta-analysis by D. A. Perrott et al. (2004): analyzed 17 blind randomized trials according to electronic databases from their inception to 2002 inclusive, for a total of 1820 patients. A general trend was revealed – the antipyretic activity of ibuprofen, used in a single dose of 5-10 mg/kg, was higher at the 2nd, 4th and 6th hour after taking the drug compared to paracetamol. Single doses of ibuprofen and paracetamol (5–10 and 7–15 mg/kg, respectively) used in children demonstrated a comparable analgesic effect and a high safety profile (Perrott D.A. et al., 2004). At the same time, the drug load when using ibuprofen in terms of the child’s body weight is somewhat less than when using paracetamol.
The relative safety of ibuprofen use has been demonstrated in children with bronchial asthma (Lesko S. M., Mitchell A.A., 1995). Ibuprofen has not been shown to increase the risk of developing bronchospasm in children with asthma. V.A. Revyakina (2009) pointed out the high efficacy and relative safety of the use of the antipyretic drug Nurofen ® for children in patients with allergic diseases. Data have been obtained on the relationship between the use of paracetamol as an antipyretic in children under the age of 1 year and an increased risk of developing symptoms of bronchial asthma when they reach the age of 6–7 years, as well as an increased risk of developing allergic rhinoconjunctivitis and eczema against the background of the use of paracetamol in children in under the age of 1 year and 6–7 years (Beasley R. et al., 2008).
Combination regimens: pros and cons
In practice, physicians use ibuprofen and paracetamol simultaneously in various regimens. Such schemes have been studied in a number of studies, however, there are no final conclusions about their clinical effectiveness, especially about the safety of using a combination of two active substances in children.
Hay A.D. et al (2008) studied the advantages and disadvantages of combined paracetamol and ibuprofen in 156 febrile children aged 6 months to 6 years in a randomized controlled clinical trial. It was found that ibuprofen in combination with paracetamol reduced fever somewhat faster compared to monotherapy, however, during the observation period, there was no increase in the time without fever against the background of combined administration of drugs compared to ibuprofen monotherapy. At the same time, cases of drug overdose with combined use were registered in 21% of patients, which casts doubt on the advisability of using a combination of antipyretic drugs. The authors recommend the use of monotherapy with ibuprofen rather than combination therapy, since in the latter case the likelihood of overdose and the development of adverse reactions increases, and the effectiveness is not much higher than that when using ibuprofen alone (Hay A.D. et al., 2008).
At the same time I. M. Paul et al (2010) allow the use of a combination of paracetamol and ibuprofen in medical practice. The randomized clinical trial conducted by the authors included children aged 6–84 months with episodes of fever to febrile values, who were divided into three groups depending on the treatment received. The children of the 1st group were prescribed ibuprofen, the 2nd – both ibuprofen and paracetamol in single doses, the 3rd – drugs according to an alternating scheme: first ibuprofen and after 3 hours – paracetamol. Ibuprofen was prescribed at a dose of 10 mg/kg of body weight, paracetamol — 15 mg/kg of body weight. At the 4th and 6th hours of the study, the combined and alternating regimens demonstrated better antipyretic activity compared to ibuprofen monotherapy. The authors do not report side effects of antipyretic therapy (Paul I.M. et al., 2010). In addition, this study and others like it were conducted with an insufficient number of participants, which once again forces the practitioner to think about the safety of alternating or combined use of ibuprofen and paracetamol and increased risk of side effects.
Thus, the question of the combined use of antipyretics requires further study in order to assess the effectiveness and safety of this approach.
® for children – original ibuprofen
Timchenko V.N. and co-authors (2011) studied the comparative efficacy and tolerability of the use of rectal suppositories containing 60 mg ibuprofen at a single dose of 5–10 mg/kg of body weight (Nurofen ® for children) and rectal suppositories containing paracetamol in a single dose of 10– 15 mg/kg. The study included 76 children with infectious fever aged from 3 months to 2 years. The effectiveness of the treatment was assessed by the rate of fever reduction, the duration of the antipyretic effect, the frequency of taking the drug, the duration of the fever in general, and the presence of undesirable effects in children. In the first 2.5 hours after the use of antipyretics, body temperature indicators decreased without significant differences in both groups. In the period of 3–5 hours of observation, the body temperature in children who received suppositories with ibuprofen was on average 0.4–0.9°C is lower, and the effect is longer than in the group of children who used suppositories with paracetamol, which indicates a more pronounced antipyretic effect of the first.
Israeli scientists conducted a pre-marketing study on the clinical efficacy of ibuprofen rectal formulation in 490 children requiring antipyretic therapy. All children received ibuprofen in the form of rectal suppositories at a single dose of 5–10 mg/kg of body weight. After 3–7 days of treatment, parameters such as parental feedback on the use of ibuprofen suppositories, possible adverse reactions, and the need for concomitant use of other drugs were evaluated. The degree of parental satisfaction was quite high — 4.5±0.47 points (on a scale of 1–5 points), 92.2% of parents reported their intention to use this form of ibuprofen in the future. Adverse reactions (most often diarrhea) were registered only in 1. 63% of cases (Hadas D. et al., 2011).
In Ukraine, ibuprofen as an antipyretic for use in children has become widespread relatively recently. In the last decade, the original ibuprofen drug Nurofen ® for children (Reckitt Benckiser Healthcare International, UK), presented in the form of a suspension for oral administration (100 mg ibuprofen / 5 ml in 100 ml bottles with strawberry and orange flavor) has been widely used. in children over the age of 3 months (with a body weight ≥5 kg) and rectal suppositories (60 mg ibuprofen) for use in children over the age of 3 months (with a body weight ≥6 kg). Indications for its use are symptomatic treatment of fever and pain of various origins (including fever after immunization, acute respiratory viral infection, influenza; pain during teething, after tooth extraction and other types of pain, including inflammatory genesis). The dose is selected depending on the age and body weight of the child – a single dose is 5-10 mg / kg, the maximum daily dose is up to 30 mg / kg. Nurofen ® tablets contain an intermediate therapeutic dose of ibuprofen (200 mg) which can be used in children ≥6 years of age. The presence of several dosage forms of the drug allows you to approach treatment for fever in a child individually – taking into account the age and clinical features of the disease (for example, the use of a rectal form in children with ongoing vomiting).
The given data indicate that the pediatrician, when prescribing antipyretics, should be guided primarily by clinical indications (body temperature> 38.5 ° C, for children at risk > 38.0 ° C) for prescribing antipyretics, a criterion for improving well-being child, and not a decrease in body temperature as such. High antipyretic efficacy, prolonged antipyretic effect and anti-inflammatory effect, good safety profile, infrequent adverse reactions allow considering the original drug ibuprofen Nurofen ® for children as a first line drug in children with fever.