What are the common side effects of ibuprofen. How can you manage headaches and dizziness caused by ibuprofen. What are the serious side effects that require immediate medical attention. How does long-term ibuprofen use affect your body.

Common Side Effects of Oral Ibuprofen

Ibuprofen, a widely used nonsteroidal anti-inflammatory drug (NSAID), can cause various side effects when taken orally. Understanding these effects is crucial for safe and effective use of the medication. Let’s explore the common side effects that occur in more than 1 in 100 people and how to manage them effectively.

Headaches: Causes and Management

Headaches are a common side effect of ibuprofen. To manage this:

• Rest and stay hydrated
• Limit alcohol consumption
• Avoid taking additional pain medications

If headaches persist for over a week or become severe, consult your doctor.

Dizziness: What to Do When It Occurs

Feeling dizzy after taking ibuprofen can be concerning. Here’s how to handle it:

• Stop your current activity and sit or lie down
• Avoid caffeine, nicotine, and alcohol
• Refrain from driving or cycling while dizzy

If dizziness persists for more than a few days, seek medical advice.

Nausea and Vomiting: Coping Strategies

Nausea and vomiting are unpleasant but manageable side effects. To alleviate these symptoms:

• Stick to simple, non-spicy meals
• Take ibuprofen with food or milk
• Stay hydrated with small, frequent sips of water

If vomiting leads to signs of dehydration, consult a healthcare professional immediately.

Gastrointestinal Side Effects: Wind and Indigestion

Ibuprofen can cause gastrointestinal discomfort, including wind and indigestion. These effects can be mitigated by:

• Avoiding trigger foods like beans, lentils, and onions
• Eating smaller, more frequent meals
• Incorporating regular exercise into your routine

Over-the-counter remedies like charcoal tablets or antacids may provide relief, but persistent indigestion warrants medical attention.

Topical Ibuprofen: Side Effects and Precautions

While topical ibuprofen generally causes fewer side effects than oral forms, it’s not without risks. The primary concern is increased skin sensitivity to sunlight. How can you protect yourself when using topical ibuprofen?

• Use sunscreen with a high SPF
• Limit sun exposure, especially during peak hours
• Wear protective clothing when outdoors

If you experience persistent skin issues, consult your healthcare provider.

Serious Side Effects Requiring Immediate Attention

While rare, some side effects of ibuprofen can be severe and require immediate medical intervention. What are the warning signs to watch for?

• Black stools or blood in vomit (indicating stomach bleeding)
• Swollen ankles, blood in urine, or cessation of urination (signs of kidney problems)
• Severe chest or stomach pain (possible stomach or gut perforation)
• Difficulty breathing or worsening asthma symptoms
• Severe headache with fever and stiff neck (potential meningitis)
• Blurred vision or hallucinations

If you experience any of these symptoms, seek emergency medical care immediately.

Allergic Reactions to Ibuprofen: Recognizing Anaphylaxis

Although rare, severe allergic reactions (anaphylaxis) to ibuprofen can occur. What are the signs of a serious allergic reaction?

• Skin rash, including itching, redness, swelling, or peeling
• Wheezing or difficulty breathing
• Chest tightness
• Trouble speaking
• Swelling of the mouth, face, lips, tongue, or throat

Anaphylaxis is a medical emergency requiring immediate hospitalization. If you suspect an allergic reaction, call emergency services without delay.

Long-Term Side Effects of Ibuprofen Use

Prolonged use of ibuprofen, especially in high doses, can lead to serious health complications. What are the potential long-term effects of ibuprofen use?

• Stomach or intestinal ulcers
• Increased risk of heart attack or stroke
• Kidney damage
• Liver problems
• High blood pressure

To mitigate these risks, doctors may prescribe protective medications for long-term ibuprofen users. Regular check-ups and monitoring are essential for those on extended ibuprofen regimens.

Alternatives to Ibuprofen: Exploring Safer Options

Given the potential side effects of ibuprofen, many people seek alternatives for pain and inflammation management. What are some safer options to consider?

• Acetaminophen (paracetamol) for pain relief
• Topical analgesics for localized pain
• Natural anti-inflammatories like turmeric or ginger
• Physical therapy and exercise for chronic pain
• Mindfulness and relaxation techniques for stress-related pain

Always consult with a healthcare provider before switching medications or starting new treatment regimens.

The Importance of Proper Dosage and Administration

Minimizing the risk of side effects starts with proper use of ibuprofen. How can you ensure you’re taking ibuprofen safely?

• Follow recommended dosages strictly
• Take with food to reduce stomach irritation
• Use the lowest effective dose for the shortest time possible
• Avoid combining with other NSAIDs
• Inform your doctor of all medications you’re taking

Remember, even over-the-counter medications can have significant impacts on your health when misused.

Special Considerations for At-Risk Groups

Certain populations may be at higher risk for ibuprofen side effects. Who should exercise extra caution when using ibuprofen?

• Elderly individuals
• People with a history of stomach ulcers
• Those with kidney or liver disease
• Individuals with heart conditions
• Pregnant women, especially in the third trimester

If you fall into any of these categories, consult your healthcare provider before using ibuprofen.

Monitoring and Reporting Side Effects

Vigilance is key in managing the risks associated with ibuprofen use. How can you play an active role in medication safety?

• Keep a symptom diary when starting ibuprofen
• Report any unusual symptoms to your healthcare provider promptly
• Participate in medication reviews with your doctor regularly
• Use the Yellow Card Scheme to report suspected side effects

By actively monitoring and reporting side effects, you contribute to the ongoing safety assessment of ibuprofen and other medications.

Understanding Drug Interactions with Ibuprofen

Ibuprofen can interact with various medications, potentially increasing the risk of side effects. What are some common drug interactions to be aware of?

• Anticoagulants (blood thinners)
• Certain antidepressants
• Other NSAIDs
• Some blood pressure medications
• Diuretics

Always inform your healthcare provider about all medications, supplements, and herbal products you’re taking to avoid potentially harmful interactions.

The Role of Genetic Factors in Ibuprofen Response

Emerging research suggests that genetic factors may influence an individual’s response to ibuprofen. How might genetics play a role in side effect risk?

• Variations in genes affecting drug metabolism
• Genetic predisposition to gastrointestinal sensitivity
• Inherited factors influencing kidney function

As personalized medicine advances, genetic testing may help predict and prevent adverse reactions to medications like ibuprofen.

In conclusion, while ibuprofen is an effective and widely used medication for pain and inflammation, it’s crucial to be aware of its potential side effects. By understanding the risks, taking appropriate precautions, and maintaining open communication with healthcare providers, patients can maximize the benefits of ibuprofen while minimizing potential harm. Remember, your health and safety are paramount – when in doubt, always seek professional medical advice.

Side effects of ibuprofen – NHS

Common side effects of tablets, capsules, granules and liquid

These common side effects of ibuprofen taken by mouth happen in more than 1 in 100 people. There are things you can do to help cope with them:

Headaches

Make sure you rest and drink plenty of fluids. Try not to drink too much alcohol. It’s important not to take any other medicines for pain to help with headaches. Talk to your doctor if the headaches last longer than a week or are severe.

Feeling dizzy

If ibuprofen makes you feel dizzy, stop what you’re doing and sit or lie down until you feel better. Avoid coffee, cigarettes and alcohol. If the dizziness does not get better within a couple of days, speak to your pharmacist or doctor. Do not drive or ride a bike while you’re feeling dizzy.

Feeling sick (nausea)

Stick to simple meals. Do not eat rich or spicy food. Always take ibuprofen tablets, capsules, granules or liquid with a meal or snack or with a drink of milk.

Being sick (vomiting)

Have small, frequent sips of water to avoid dehydration. Speak to a pharmacist if you have signs of dehydration, such as peeing less than usual or having dark, strong-smelling pee. Do not take any other medicines to treat vomiting without speaking to a pharmacist or doctor.

If you take contraceptive pills and you’re being sick, your contraception may not protect you from pregnancy. Check the pill packet for advice.

Wind

Try not to eat foods that cause wind (like lentils, beans and onions). Eat smaller meals, eat and drink slowly, and exercise regularly. There are pharmacy medicines that can also help, such as charcoal tablets or simeticone.

Indigestion

If you get repeated indigestion stop taking ibuprofen and see your doctor as soon as possible. If you need something to ease the discomfort, try taking an antacid, but do not put off going to the doctor.

Speak to a doctor or pharmacist if the advice on how to cope does not help and a side effect is still bothering you or does not go away.

Common side effects of gel, mousse and spray

You’re less likely to have side effects when you apply ibuprofen to your skin than with tablets, capsules, granules or liquid because less gets into your body. But you may still get the same side effects, especially if you use a lot on a large area of skin.

Applying ibuprofen to your skin can sometimes cause your skin to become more sensitive than normal to sunlight. Speak to your doctor if this is a problem.

Serious side effects

Call a doctor or contact 111 straight away and stop taking ibuprofen if you have:

• black poo or blood in your vomit – these can be signs of bleeding in your stomach
• swollen ankles, blood in your pee or not peeing at all – these can be signs of a kidney problem

Go to 111. nhs.uk or call 111.

Immediate action required: Call 999 or go to A&E now if:

• you have severe chest or stomach pain – these can be signs of a hole in your stomach or gut
• you have difficulty breathing, or asthma symptoms that become worse
• you get a severe headache, a high temperature or stiff neck, and a dislike of bright lights – these can be signs or inflammation of the protective membranes that surround the brain and spinal cord (meninges)
• you have blurred vision or you see or hear things that are not real (hallucinations)

Find your nearest A&E

Serious allergic reaction

In rare cases, it’s possible to have a serious allergic reaction (anaphylaxis) to ibuprofen.

Immediate action required: Call 999 or go to A&E now if:

• you get a skin rash that may include itchy, red, swollen, blistered or peeling skin
• you’re wheezing
• you get tightness in the chest or throat
• you have trouble breathing or talking
• your mouth, face, lips, tongue or throat start swelling

You could be having a serious allergic reaction and may need immediate treatment in hospital.

Long term side effects

Ibuprofen can cause ulcers in your stomach or gut, especially if you take it by mouth for a long time or in big doses. If you need to take it for a long time your doctor may also prescribe a medicine to help protect your stomach.

Other side effects

These are not all the side effects of ibuprofen tablets, capsules and syrup. For a full list see the leaflet inside your medicines packet.

Information:

You can report any suspected side effect using the Yellow Card safety scheme.

Visit Yellow Card for further information.

Page last reviewed: 18 November 2021

Next review due: 18 November 2024

Recognizing the Risks of Chronic Nonsteroidal Anti-Inflammatory Drug Use in Older Adults

Ann Longterm Care. Author manuscript; available in PMC 2011 Aug 19.

Published in final edited form as:

Ann Longterm Care. 2010; 18(9): 24–27.

PMCID: PMC3158445

NIHMSID: NIHMS315767

PMID: 21857795

Author information Copyright and License information Disclaimer

Older adults commonly take nonsteroidal anti-inflammatory drugs (NSAIDs) chronically. Studies of older adults show that chronic NSAID use increases the risk of peptic ulcer disease, acute renal failure, and stroke/myocardial infarction. Moreover, chronic NSAID use can exacerbate a number of chronic diseases including heart failure and hypertension, and can interact with a number of drugs (eg, warfarin, corticosteroids). Preferred analgesics in older adults that may have a lower risk of these adverse drug reactions include acetaminophen, a nonacetylated salicylate (eg, salsalate), a short half-life NSAID (eg, ibuprofen), or low-dose opioid/opioid-like agents in combination with acetaminophen (in appropriate patients).

Nonsteroidal anti-inflammatory drugs (NSAIDs) are a common class of analgesics used chronically for persistent pain due to osteoarthritis and other musculoskeletal disorders in older adults.^1-3 Specifically, an estimated 40% of people age 65 years and older fill one or more prescriptions for a NSAID each year.⁴ Considering that NSAIDs are also currently available over the counter, it is clear to see that even larger numbers of older adults are exposed to NSAIDs in the United States.

While these agents can be effective in treating inflammation and pain, older adults are at increased risk for adverse drug reactions (ADRs) due to age-related loss of physiological organ reserve, increased comorbidities, polypharmacy, and changes in pharmacokinetics.⁵ As a result, NSAID use causes an estimated 41,000 hospitalizations and 3300 deaths each year among older adults.² Some specific ADRs of concern with chronic use of NSAIDs include gastrointestinal (GI), renal, cardiovascular (CV), cerebrovascular, and central nervous system (CNS) adverse effects.⁶ This review will begin by describing key evidence for these organ-specific ADRs associated with the chronic use of NSAIDs in older adults and finish with general recommendations for healthcare providers to avoid/minimize these ADRs.

The spectrum of potential NSAID-related GI adverse effects is wide, ranging from dyspepsia to life-threatening gastric bleeding.² A nested case control study from nearly two decades ago (before the introduction of cyclooxygenase-2 [COX-2] selective NSAIDs) showed that NSAIDs increase the risk of fatal peptic ulcers by nearly fivefold in older adults;⁷ other studies have shown that the risk of peptic ulcer complications is increased by three- to fivefold in older adults using NSAIDs. ² This risk is much more pronounced in those taking concomitant systemic corticosteroids and warfarin.^8,9 In addition, the risk is increased as early as within the first month of treatment and is sustained over time.^3,10 Often, these peptic ulcers are asymptomatic but can lead to significant morbidity and mortality. The evidence for which NSAIDs are less risky is limited. One retrospective cohort study found that celecoxib, as compared to nonselective NSAIDs (ibuprofen, diclofenac, naproxen) carried the least risk of hospitalization for GI bleeding among elderly persons.¹¹ Of note, all NSAIDs (ie, nonselective and COX-2 selective) carry a boxed warning for adverse GI events. Overall, the rate of hospitalizations for peptic ulcer disease (PUD) increases with age, from 1 per 1000 per year in populations younger than age 50 years to 2-6 per 1000 per year in older adults (> 65 yr), with an estimated 15-35% of all peptic ulcer complications being due to NSAID use. ^2,12

Similar to NSAID-related GI adverse effects, NSAID-induced renal dysfunction has a wide spectrum of negative effects, including decreased glomerular perfusion, decreased glomerular filtration rate, and acute renal failure (ARF). While it is important to recognize that ARF can develop at any point during long-term NSAID therapy, the risk may be highest among those who have recently initiated therapy. Specifically, in a nested case control study of older adults, the risk of ARF was increased nearly twofold for all NSAIDs (nonselective and COX-2 selective NSAIDs) within 30 days of initial use/prescribing.¹³ This is consistent with previous studies reporting that NSAIDs increase the risk of ARF in the elderly.^14,15 This risk is further increased in those older adults with preexisting chronic kidney disease (CKD) and in those who use long half-life NSAIDs.¹⁶ Thus, diligent monitoring of renal function (eg, blood urea nitrogen/serum creatinine to estimate creatinine clearance) is critical in older adults receiving NSAIDs, especially those who are at increased risk. ¹⁴ Of note, salsalate may be preferred among the NSAIDs as it is rarely associated with nephrotoxicity.⁵ Overall, it is estimated that 2.5 million individuals in the United States experience adverse renal effects from NSAID use annually,¹⁷ with older adults being in the highest-risk group in the population.

NSAIDs have been shown to worsen/increase the risk of various CV and cerebrovascular outcomes, with some studies suggesting a greater risk associated with COX-2 selective NSAIDs as compared to nonselective NSAIDs.^11,18-23 One retrospective cohort study of older adults showed that naproxen carried the least risk of hospitalization for acute myocardial infarction (MI) among users of aspirin as compared to other nonselective NSAIDs (ibuprofen, diclofenac) and COX-2 selective NSAIDs (celecoxib, rofecoxib) used with aspirin.¹¹ In contrast, a prospective, population-based cohort study found an increased risk of stroke with the use of nonselective NSAIDs (including naproxen), as well as with COX-2 selective NSAIDs (including celecoxib) in those not taking aspirin. On an individual NSAID analysis, naproxen users were found to have more than a twofold increased risk of stroke.²⁰ Of note, all NSAIDs (ie, nonselective and COX-2 selective) carry a boxed warning for adverse CV events, including MI and stroke. Further research is needed to confirm individual NSAID adverse CV risk profiles.

One clinical trial of patients with hypertension (HTN) showed that piroxicam and ibuprofen blunted the effects of antihypertensive drugs (lisinopril/hydrochlorothiazide), significantly increasing systolic blood pressure (SBP) by 7.7-9.9%. An acetaminophen (APAP) period (in place of the NSAID) led to a significant decrease in blood pressure toward baseline, and a second exposure to the NSAIDs led to another significant increase in SBP of 7.0-7.7%, adding strong support to the evidence of causality.²¹ In addition, a cohort study of community-dwelling elderly individuals

The NSAID should be used at the lowest effective dose for the shortest period of time.

found that those who were taking antihypertensive therapy and NSAIDs had SBPs approximately 5 mmHg higher than those not taking NSAIDs, and were more likely to have SBP higher than 140 mmHg.¹⁸

NSAIDs have also been shown to cause or exacerbate heart failure (HF) in older adults. Specifically, a cohort study of older adults found that rofecoxib and nonselective NSAIDS (naproxen, ibuprofen, and diclofenac), but not celecoxib, were significantly associated with an increased risk of admission for HF as compared to those not taking NSAIDs.¹⁹ In contrast, another cohort study found that among patients who had survived their first hospitalization because of HF, subsequent use of any NSAID (including celecoxib, as well as ibuprofen, diclofenac, naproxen, and other NSAIDs) led to a significantly increased risk of death.²²

Finally, an important point of clinical debate is the interaction between low-dose, cardioprotective aspirin and NSAIDs potentially interfering with the antiplatelet effect of aspirin. The American Geriatrics Society⁵ recommends avoiding the coadministration of aspirin and ibuprofen based on a 2006 Food and Drug Administration warning. However, it is important to recognize that evidence suggests that this warning should also apply to naproxen, but not celecoxib.^23,24

NSAID use has been shown to be associated with a number of CNS effects including aseptic meningitis, psychosis, and cognitive dysfunction.^1,2 This latter point may seem to be inaccurate, but the literature suggests otherwise. At the time of this writing, the studies to date have not consistently shown a benefit from chronic NSAID use in reducing the risk of dementia or cognitive impairment.²⁵ Interestingly, though, several studies have shown that high-dose NSAIDs (ie, anti-inflammatory doses) may actually increase the risk of cognitive impairment.^26,27 In particular, indomethacin appears to cause more CNS effects than other NSAIDs in the elderly. ²⁸

One approach to reducing ADRs associated with NSAIDs is to avoid the use of specific agents and use preferred alternative analgesics (). This is particularly important in those older adults with preexisting HTN, CKD, HF, and/or PUD, or those taking concomitant warfarin or corticosteroids. An alternative option would be to use APAP, which has been shown to be equally effective to NSAIDs in a number of studies of patients with mild-to-moderate osteoarthritis pain. Of note, patients who say that APAP does not work for them may not have used an optimal dose (3-4 g/day in divided doses for at least 2 wk), which would be required in order to show a lack of effectiveness. If APAP does not work and NSAID use is not contraindicated, a trial of analgesic dosing of a nonacetylated salicylate (eg, salsalate) or ibuprofen or celecoxib may be acceptable. For those with moderate-to-moderately severe osteoarthritis pain, a trial of a low-dose opioid or opioid-like agent (eg, codeine, tramadol) in combination with APAP is another option. The rationale for this approach is to combine two different mechanisms of analgesic action. In those elderly persons who require chronic NSAIDs, a proton pump inhibitor or misoprostol should be used to avoid the risk of PUD.^9,12 In general, long half-life NSAIDs (eg, naproxen, oxaprozin, piroxicam) and specific other NSAIDs (eg, indomethacin, ketorolac) should be avoided because their risk outweighs their potential benefits.²⁸

Table

Preferred Analgesic Agents for Treatment of Nociceptive Pain in Older Adults

Drug	Initial Dosing	Special Considerations in Older Adults
Mild-to-Moderate Pain
APAP	325-500 mg every 4 h or 500-1000 mg every 6 h; maximum daily dose of 4000 mg	Does not interfere with platelet function; reduce maximum dose 50% to 75% in patients with hepatic insufficiency or history of alcohol abuse
Celecoxib	100 mg daily	Higher doses associated with higher incidence of GI and CV side effects; patients with indications for cardioprotection require aspirin
Ibuprofen	200 mg 3-4 times/day; maximum daily dose of 3200 mg	Risk of GI bleeding increased in persons > 75 yr; misoprostol or PPI should be prescribed for long-term users
Salsalate	500-750 mg every 12 h; maximum daily dose of 3000 mg	Does not interfere with platelet function; GI bleeding and nephrotoxicity are rare
Moderate-to-Moderately Severe Pain
APAP/Codeine	325/30 mg every 6 h; maximum daily dose of 12 tablets	Monitor for constipation, confusion, and falls; same considerations for APAP as listed above
APAP/Tramadol	325/37. 5 mg every 6 h; maximum daily dose of 8 tablets	Renally adjusted dose when estimated creatinine clearance < 30 mL/min: maximum of 2 tablets every 12 h; treatment should not exceed 5 days; same considerations for APAP as listed above

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APAP = acetaminophen; GI = gastrointestinal; CV = cardiovascular; PPI = proton pump inhibitor.

Contains information from references ⁵and ⁶.

This review has summarized the potential risks associated with chronic NSAID use in older adults, including GI, renal, CV/cerebrovascular, and CNS adverse effects. Although only ADRs affecting these four organ systems were discussed in this review, it is important to recognize that NSAIDs can cause various other adverse effects (eg, hepatotoxicity, cutaneous toxicity).² Moreover, it is important to note that nonpharmacological approaches (weight reduction, increasing physical activity) may also help patients who are experiencing musculoskeletal pain. ²⁹ For patients already taking NSAIDS chronically, healthcare providers should assess whether the patient could switch to APAP or salsalate. If the patient still requires a NSAID, GI prophylaxis should be considered in all older patients, especially those with other risk factors; importantly, the NSAID should be used at the lowest effective dose for the shortest period of time.

As the aging population rapidly grows over the next few decades, the risks associated with chronic NSAID use will remain an important public health issue. Hopefully, health-care providers armed with the above information who carefully and consistently monitor chronic NSAID use in their older patients will avoid these preventable complications.

The writing of this paper was supported by National Institute on Aging grants (R01AG027017, P30AG024827, T32 AG021885, K07AG033174, R01AG034056), a National Institute of Mental Health grant (R34 MH082682), a National Institute of Nursing Research grant (R01 NR010135), and an Agency for Healthcare Research and Quality grant (R01 HS017695).

The authors report no relevant financial relationships.

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safety and efficacy in general clinical practice

ASA – acetylsalicylic acid

Gastrointestinal tract

IHD – ischemic heart disease

PM – medicines

NSAIDs – non-steroidal anti-inflammatory drugs

COX – cyclooxygenase

PG – prostaglandin

TxA2 – thromboxane

Modern clinical practice is difficult to imagine without the use of various non-steroidal anti-inflammatory drugs (NSAIDs). In ancient Greece, more than 3.5 thousand years ago, Hippocrates used willow bark extract as an antipyretic and analgesic. Much later, in the 17th century, a substance was isolated from it, which was called salicylic acid (from Latin salix – willow). At the end of the 19th century, the production of salicylic acid and acetylsalicylic acid (ASA) began in Germany. Currently, more than 20 different representatives of this group are known in clinical practice, with differences in chemical structure, features of the mechanism of action, indications for use and tolerability.

The mechanism of action of NSAIDs. NSAIDs inhibit the synthesis of prostaglandins (PG), which are important physiological and pathological mediators. PGs are involved in such processes as pain, inflammation, oncogenesis, osteoporosis, regulation of body temperature (hyperthermia) and kidney function, etc. From arachidonic acid, with the participation of the enzyme cyclooxygenase (COX), PGh3 is formed, which is the precursor of such PGs as thromboxane (TxA2), prostacyclin, or PGI ₂ , D ₂ , E ₂ and F ₂ (see illustration). Figure 1. The mechanism of action of NSAIDs [2, 3]. Two main isoforms of COX are known: COX-1 and COX-2. The issue of isolation under experimental conditions of the third isoform, COX-3, as a variant of COX-1 remains unresolved [1]. The first isoform (COX-1) is synthesized constantly and works according to a universal mechanism, i.e. regardless of the organ or tissue in which the synthesis takes place. Synthesis of the second isoform (COX-2) is stimulated by various inflammatory factors (lipopolysaccharides, interleukins, tumor necrosis factor α) in various cells of the human body, such as endothelium, osteoclasts, synoviocytes, monocytes, and macrophages [2].

The main pharmacodynamic properties of NSAIDs – anti-inflammatory, antipyretic and analgesic effects – are provided through the inhibition of COX-1 and COX-2. It is the inhibition of COX-1 and COX-2 that causes the main adverse reactions against the background of the use of NSAIDs. Prostaglandins PGE ₂ and PGI ₂ , which are synthesized with the participation of COX-1 in the gastrointestinal tract (GIT), are mucosal cytoprotectors by reducing the secretion of hydrochloric acid by parietal cells of the stomach, improving blood flow and stimulating mucus production. In addition, with the participation of COX-1, the synthesis of TxA ₂ in platelets with vasoconstrictive and proaggregant properties. NSAIDs, blocking the synthesis of COX-1, can lead to damage to the mucous membrane of the stomach and intestines and impaired platelet aggregation. Thus, NSAIDs increase the risk of developing severe gastrointestinal diseases such as inflammation, bleeding, and penetration of the stomach or intestines. The risk of developing such complications is higher in the elderly and does not depend on the duration of drug use [4].

The classification of NSAIDs is presented in Table . 1. Among the representatives of NSAIDs, there are differences in the chemical structure, features of action and in the degree of inhibition of COX-1 and COX-2. The selectivity of NSAIDs in relation to COX isoforms is usually assessed by the ratio of the degree of inhibition of COX-1 to COX-2 (selectivity coefficient). Selective inhibitors of COX-2 are those NSAIDs in which this coefficient is more than 5, highly selective inhibitors – if this coefficient is more than 50 (see table 1) . NSAIDs with high selectivity for COX-2 are called coxibs (from English – cyclo-oxygenase, abbreviated version of COX).

Clinical pharmacology of ibuprofen. One of the NSAIDs widely used in clinical practice is ibuprofen, which was synthesized by S. Adams and D. Nicholson in the UK in 1962. In the Russian Federation, it is registered under the trade name Nurofen (original drug). It has pronounced anti-inflammatory, analgesic and antipyretic effects, which, combined with good tolerability, predictability of side effects and a low risk of complications, has led to its widespread use in clinical practice.

According to the chemical structure, ibuprofen is a derivative of propionic acid, according to the mechanism of action, it is a non-selective inhibitor of COX-1 and COX-2, lipoxygenase involved in the synthesis of pro-inflammatory leukotrienes [6].

Ibuprofen is a racemic mixture of two optical left- and right-handed isomers, the S (+) and R (-) enantiomers. The clinical efficacy of ibuprofen is mainly due to the action of the S (+) form, however, the presence of the R (–) isomer explains some of the anti-inflammatory properties of ibuprofen [7].

Variety of dosage forms of ibuprofen. Modern opportunities for the use of ibuprofen are associated with advances in the field of pathophysiology of diseases and the development of new dosage forms of this drug. Currently, ibuprofen is represented on the drug market in a variety of dosage forms.

In addition to oral ibuprofen, it can also be used topically in the form of a gel, rectal (as suppositories) and parenteral (as solutions for intravenous administration) (Table 2). Modern technologies have made it possible to develop new dosage forms – capsules containing ibuprofen solution (nurofen ultracap) and ibuprofen derivatives – sodium dihydrate and lysinate. The advantages of the lysine salt of ibuprofen are the rate of dissolution of this compound, the increase in bioavailability and the rate of onset of the maximum concentration in blood plasma (nurofen express) [8-10].

In clinical practice, new dosage forms with modified release are also presented, i.e. with a mechanism and nature of the release of the medicinal substance changed in relation to the usual form. Such forms of ibuprofen are known as the form of quick release (immediate release – IR) and the form of slow release (sustained release – SR).

Pharmacokinetics of ibuprofen. The main pharmacokinetic parameters of ibuprofen, in particular the concentration of enantiomers in plasma or the area under the pharmacokinetic curve, depend on the dosage form and dose of ibuprofen (see table. 2) .

When taken orally, ibuprofen is rapidly absorbed from the upper small intestine. The bioavailability of ibuprofen as a weak acid when taken orally is on average 80%. Eating, as a rule, reduces the rate of absorption of ibuprofen, however, it has been shown that some foods and drinks (for example, Coca-Cola) can cause an increase in the degree of absorption. The time to reach the maximum concentration of ibuprofen isomers in plasma or serum is on average 1-2 hours and depends on the dosage form of ibuprofen (see table 2) . According to the rate of absorption, dosage forms of ibuprofen can be distributed in ascending order: ibuprofen tablets → ibuprofen suspension → ibuprofen solution. The rapid absorption of ibuprofen from liquid forms (suspension, solution) provides a faster analgesic and antipyretic effect.

After oral administration, 40-60% of the R (-) form of ibuprofen is metabolized in the intestine and liver to the S (+) form. Further biotransformation of ibuprofen takes place in 2 phases. I – phase of oxidative reactions is associated with a system of microsomal cytochrome P-450 enzymes (2C9, 2C8 and 2C19), providing the formation of inactive carboxyl and phenolic compounds. Differences in the genotypes of the P-450 2C9 system lead to differences in ibuprofen metabolism, an increase in the area under the pharmacokinetic curve, and a change in hepatic clearance [7]. Phase II of ibuprofen metabolism includes the formation of inactive glucuronic and taurine compounds, which are subsequently excreted mainly through the kidneys. Impaired liver function due to cirrhosis of the liver leads to a slower inversion of the R form (-) of ibuprofen to the S form (+), as well as an increase in the half-life to 3.4 hours. Impaired renal function also reduces the rate of excretion of ibuprofen metabolites.

Ibuprofen is highly bound to plasma albumin (90-99%). In adults, ibuprofen, when taken orally and intravenously, has a short half-life of about 2 hours. Ibuprofen penetrates well into the synovial fluid of inflamed joints, which provides analgesic and anti-inflammatory effects. The antipyretic effect of ibuprofen is due to the inhibition of PGE2 synthesis in the central nervous system. Ibuprofen is a lipophilic substance, however, only its free (non-albumin-bound) fraction penetrates the blood-brain barrier.

With topical application of ibuprofen, there is a slight decrease in the systemic bioavailability of the drug to 14-30% of that when taken orally [12], while after topical application, higher concentrations are observed in subcutaneous and soft tissues, including muscle [13]. A number of studies in patients of different categories have shown that the effectiveness of topical application of ibuprofen (5% gel) and ibuprofen (1200 mg/day) orally in both acute traumatic injuries of soft tissues and chronic pain syndrome is the same, and the tolerability of topical forms is better. [12, 14, 15].

The pharmacokinetic curve for rectal use is comparable to the pharmacokinetic data for oral administration. Absorption with rectal administration of ibuprofen is characterized by a high degree of bioavailability and the rapidity of the onset of the maximum plasma concentration. In addition, the peculiarities of the blood supply to the rectal region lead to the fact that only part of the drug is metabolized in the liver, which leads to an increase in the half-life.

Pharmacokinetic parameters do not differ significantly in both men and women, and in different age groups. Pharmacokinetic parameters in children older than 2 years and adolescents do not differ from those in adults. The only exceptions are children under 2 years of age, in which the metabolism of ibuprofen is significantly lower than in adults, which requires the correct dosing regimen of the drug depending on the child’s body weight. With increasing age, there is a slight increase in elimination half-lives, which reflects age-related changes in metabolism and clearance, but in older people, ibuprofen excretion does not undergo significant changes.

Safety of ibuprofen. The development of selective COX-2 inhibitors was aimed at overcoming the limitations of the use of NSAIDs due to the risk of adverse gastrointestinal reactions. However, during the introduction of coxibs into clinical practice, another safety problem arose during long-term use – an increase in the risk of developing cardiovascular thrombotic complications, myocardial infarction and stroke [16]. At the heart of the increased risk of developing thrombotic complications against the background of selective COX-2 inhibitors is an imbalance between thromboxane and prostacyclin, which regulate endothelial function and platelet aggregation. Selective coxibs, due to the selective blockade of COX-2, disrupt the balance between the level of thromboxane and prostacyclin, which is the basis for the development of thrombotic complications [2]. However, the results of subsequent clinical observations have shown that the use of non-selective NSAIDs also increases the risk of developing cardiovascular complications [17, 18]. Current international recommendations based on the results of long-term clinical trials limit the use of both coxibs and non-selective NSAIDs in patients with coronary heart disease (CHD), stroke, or at high risk of developing CAD [3, 5].

Another adverse reaction associated with long-term use of NSAIDs is impaired renal function, since both COX isoforms play a significant role in the regulation of kidney function. PG regulate vascular tone, maintain normal blood flow, which is necessary to maintain normal kidney function. It is now known that inhibition of COX-1 leads to a decrease in glomerular filtration rate, and inhibition of COX-2 slows sodium reabsorption in healthy volunteers and the elderly. According to a meta-analysis, selective COX-2 inhibitors increase the risk of developing renal failure and arrhythmia [2, 19].

Ibuprofen has a strong evidence base for safety, making it available over the counter in many parts of the world (at dosages less than 1200 mg).

The safety of ibuprofen has been demonstrated in many large clinical trials. Of greatest interest is a multicenter randomized study conducted in 1999 in France with the participation of 8677 patients (PAIN study), the purpose of which was to compare the efficacy and tolerability of over-the-counter analgesics: ASA, paracetamol and ibuprofen. It has been shown that ibuprofen (at a dose of less than 1200 mg) is tolerated as well as paracetamol, which was previously considered the standard of safety, and, compared with ASA, causes a significantly lower frequency of adverse reactions [20].

When comparing the frequency of adverse reactions of the gastrointestinal tract, it was noted that ibuprofen is characterized by high safety due to the presence of a low-active enantiomer R, which is a competitor for the active form S for the active center of COX-1, which is responsible for the synthesis of PG, which protect the gastrointestinal mucosa. In addition, the short half-life of ibuprofen may also provide a safety advantage for the use of this drug.

Ibuprofen does not form toxic metabolites, its toxicity after accidental or intentional overdose is lower and it has a relatively higher therapeutic index (about 4 times higher than that of paracetamol). For ibuprofen, the development of Reye’s syndrome (acute hepatic encephalopathy in children while taking ASA) is also uncharacteristic [14, 21].

Clinical efficacy of ibuprofen. Ibuprofen is an effective analgesic for acute pain syndrome of various origins. At a dose of 400 mg, it has repeatedly proved its advantage over placebo in postoperative, toothache, sore throat, dysmenorrhea, tension headache and migraine, soft tissue injury, neuralgia and myalgia, as well as a number of other conditions accompanied by severe pain syndrome.

For headaches, ibuprofen as a first-line drug is included in the list of analgesics recommended by WHO, as well as by the European Federation of Neurological Societies (EFNS) for the treatment of mild to moderate migraine attacks (class A) [22, 23]. The effectiveness of ibuprofen in the treatment of cephalgia has been proven in many placebo-controlled clinical trials, as well as several meta-analyses, including in children and adolescents [24-28].

At a dose of 200–400 mg, ibuprofen is the “gold standard” for the treatment of moderate pain in patients with postoperative toothache [29]. A meta-analysis demonstrated high efficacy of ibuprofen compared to placebo in 72 studies. Ibuprofen significantly reduced pain in all patients by at least 50% at an average of 4.7 hours. Repeat analgesia was required in only 48% of patients who took ibuprofen at a dose of 200 mg, and in 42% at a dose of 400 mg [30] . Another meta-analysis based on 33 studies revealed the advantage of ibuprofen (400 mg) in relieving pain after tooth extraction compared with paracetamol (1000 mg), as well as a combination of paracetamol (600-650 mg) and codeine (60 mg) [31].

Particularly acute is the issue of choosing an effective and safe NSAID in pediatric practice, in view of the fact that fever and pain are leading in a number of diseases, including respiratory infections, most common in young children. Large multicenter randomized trials have shown that among all antipyretic analgesics, ibuprofen and paracetamol are the safest drugs. Thus, a meta-analysis combining 24 randomized and 12 observational studies in the period from 1950 to 2008, did not show statistically significant differences in the incidence of adverse reactions of the gastrointestinal tract and kidneys, as well as in the effect on the course of bronchial asthma when taking ibuprofen, paracetamol and placebo [32]. The largest systematic review of data on the efficacy and safety of ibuprofen compared with paracetamol in the treatment of fever and pain in children and adults was conducted in 2010. It included 85, including large randomized trials in the period 2008-2009. The authors made conclusion that ibuprofen is more effective than paracetamol in the treatment of fever and pain in all age groups with equal safety [33].

According to the WHO recommendation, ibuprofen at a dose of 5-10 mg/kg, along with paracetamol, is the drug of choice as an antipyretic and analgesic (for mild to moderate pain) in children from 3 months of age. No other NSAIDs can be recommended for use in pediatric practice due to the lack of the necessary evidence base for their efficacy and safety [34, 35].

Ibuprofen is also currently the only drug on the WHO formulary for the treatment of patent ductus arteriosus in newborns [36]. New, potentially possible, indications for the use of ibuprofen are being studied.

Cystic fibrosis. Several clinical studies have demonstrated the effect of ibuprofen on slowing down the progression of the pulmonary process (slowing the decrease in forced expiratory volume in 1 second) in patients with cystic fibrosis with long-term use in various age groups [37-39]. The results obtained are probably associated with a decrease in the influx of polymorphonuclear cells into the lungs and, consequently, the inflammatory process [40]. Despite the fact that large doses of ibuprofen were used, the risk of developing adverse reactions of the gastrointestinal tract remained low [37, 38].

Parkinson’s disease. It is believed that one of the key links in the pathogenesis of Parkinson’s disease is neuroinflammation. Based on this assumption, several studies have been conducted, the purpose of which was to determine the role of NSAIDs in the development of the disease. A 2010 meta-analysis of 7 large epidemiological studies demonstrated a 15% reduction in the risk of developing Parkinson’s disease in the general group of patients taking NSAIDs, as well as 29% and 21%, respectively, with regular and long-term use of NSAIDs. The strongest neuroprotective effect was noted for ibuprofen, which was also confirmed by a number of other studies [41–43].

Breast cancer. Currently, there is great interest in the positive effects of NSAIDs, primarily ASA and ibuprofen, on the risk of developing various types of cancer [44-46]. According to the results of a meta-analysis (38 studies, n = 2 788715), conclusions were drawn about the possible oncoprotective effect of NSAIDs, primarily ibuprofen (relative risk 0. 79 with a 95% confidence interval from 0.64 to 0.97) in relation to the development of breast cancer [ 47]. Another meta-analysis (26 studies, n=528,705) showed similar results [48]. Perhaps, after conducting large placebo-controlled studies, the use of ibuprofen will be recommended as a cancer prevention.

Thus, when prescribing therapy, it is important to make a choice in favor of a time-tested remedy. More than 40 years of experience with the use of ibuprofen in wide clinical practice in almost 80 countries as an over-the-counter drug is a good example of its effectiveness and safety [49].

On the occasion of the 40th anniversary of the creation of ibuprofen. The first international conference on the use of ibuprofen in pediatrics | Geppe N.A.

P The first International Conference on the Use of Ibuprofen in Pediatrics took place on March 2, 2002 in Prague. The creator of ibuprofen, Boots Healthcare International, invited pediatricians from 18 countries to discuss the role of ibuprofen in treating fever and pain in children. The guest of honor at the conference was Dr. Stuart Adams, who was the first to receive ibuprofen 40 years ago while working for Boots Pure Drug (Figure 1). The purpose of the conference was to discuss at the international level all the pros and cons regarding the use of ibuprofen in pediatrics.

Fig. 1. Stuart Adams with colleagues in the early 60s (on the right in the picture)

Development of ibuprofen

In 1957, Stuart Adams, together with chemist John Nicholson, began to investigate the group of phenylpropionic acids. In 1962, BTS 13621 was created, commonly known today as ibuprofen. The drug showed good efficacy, good tolerability and caused less pronounced gastrointestinal side effects than acetylsalicylic acid. Many clinical studies followed that confirmed these properties of ibuprofen. The drug was registered on January 12, 1962 by the British Patent Office under the name Brufen. It began to be used as a prescription drug for the treatment of rheumatoid arthritis. In the US, since 1974, ibuprofen has been used under the trade name Motrin. Since 1983, the drug has been marketed in the UK as an over-the-counter drug called Nurofen. Significant in the history of ibuprofen was 1985, when Boots was awarded the Queen’s Award in recognition of the scientific and technological achievements in the development of this drug. Currently, the drug has many names and is used in both adults and children for the relief of pain and fever. For children, ibuprofen suspension (20 mg / ml) is used – “Nurofen for Children”, which does not contain sugar, is approved for over-the-counter use in children aged 6 months and over.

In 1957, Stuart Adams, together with chemist John Nicholson, began to study the group of phenylpropionic acids. In 1962, BTS 13621 was created, commonly known today as ibuprofen. The drug showed good efficacy, good tolerability and caused less pronounced gastrointestinal side effects than acetylsalicylic acid. Many clinical studies followed that confirmed these properties of ibuprofen. The drug was registered on January 12, 1962 by the British Patent Office under the name Brufen. It began to be used as a prescription drug for the treatment of rheumatoid arthritis. In the USA since 19In 1974, ibuprofen began to be used under the trade name Motrin. Since 1983, the drug has been marketed in the UK as an over-the-counter drug called Nurofen. Significant in the history of ibuprofen was 1985, when Boots was awarded the Queen’s Award in recognition of the scientific and technological achievements in the development of this drug. Currently, the drug has many names and is used in both adults and children for the relief of pain and fever. For children, ibuprofen suspension (20 mg / ml) is used – “Nurofen for Children”, which does not contain sugar, is approved for over-the-counter use in children aged 6 months and over.

Ibuprofen safety

Tolerability and safety of a drug are one of the most important parameters when deciding whether it is appropriate to prescribe it to children. Antipyretic drugs are prescribed to children to reduce discomfort, dehydration, and eliminate febrile convulsions. At the same time, both antipyretics and non-drug measures are used, such as sufficient drinking, loose light clothing, temperature control in the room (no more than 20 ° C), a therapeutic bath with a water temperature 2 ° C below the body temperature of the child. The ongoing symptomatic therapy should have a quick and pronounced effect. In children, acetaminophen (paracetamol) and non-steroidal anti-inflammatory drugs (NSAIDs) are mainly used. In Russia, on the recommendation of the National Pharmacological Committee, acetylsalicylic acid is not indicated for the treatment of fever in children under 15 years of age, and the use of metamizole sodium (analgin) is also limited due to the high incidence of side effects.

All experts at the conference agreed that ibuprofen was comparable in tolerability to paracetamol and was shown to be safe. According to the data obtained by Professor Autret-Leca (France), ibuprofen is one of the best tolerated NSAIDs in adults, and in children the tolerance of the drug is even higher. She emphasized that treatment with ibuprofen was never accompanied by the occurrence of Reye’s syndrome. The professor summarized the literature data as follows: “Compared to paracetamol and acetylsalicylic acid, ibuprofen has less toxicity in overdose and therefore a wider therapeutic range.”

Professor Ioana Alina Anca (Romania) has seen from personal experience that ibuprofen is less toxic than paracetamol and other NSAIDs. Among other NSAIDs, ibuprofen causes the fewest gastrointestinal side effects. Professor Anka analyzed the use of ibuprofen in young children. For the period 1999–2001 at the Institute of Mother and Child in Bucharest, ibuprofen was prescribed to 576 children for the first 6 months. life according to the main indication – ARVI. Fever was reduced more quickly and for a longer time compared to acetaminophen. Out of 304 children in 1999, 9 had mild side effects. The use of ibuprofen in adjunctive therapy for bronchiolitis did not have a bronchospastic effect. The rapid onset and duration of antipyretic action, anti-inflammatory and analgesic effect explain the effectiveness of ibuprofen in children up to six months [10].

Clinical data presented by Professor Samuel Lesco (USA) showed that short-term use of ibuprofen is not associated with an increased risk of side effects in children. A large double-blind clinical trial compared ibuprofen (5 or 10 mg/kg) and paracetamol (12 mg/kg) in more than 84,000 children (aged 6 months to 2 years) treated for febrile conditions [12,13] . The results of the study demonstrated that ibuprofen did not increase the risk of hospitalization in children under 2 years of age compared with paracetamol.

Lesko and colleagues also studied the outcome of febrile illness in 1879 children with bronchial asthma (BA). Children were randomized into two groups – ibuprofen and acetaminophen. Since none of the children had a history of acetylsalicylic acid intolerance, the authors suggested that sensitivity to NSAIDs may not be recognized in young children with asthma. Among children treated with ibuprofen, the frequency of visits to the doctor was reduced and there was less likelihood of hospitalization for asthma than in the acetaminophen group. The results obtained debunk the hypothesis that ibuprofen, to a greater extent than acetaminophen, increases the risk of bronchospasm in children with bronchial asthma who do not have indications of intolerance to acetylsalicylic acid, and indicate the relative safety of ibuprofen treatment in children with asthma.

Professor John van den Ancker (USA) conducted a study on the safety of ibuprofen and paracetamol in children with overdose based on 10-year observations of the Center for Poison Control of the American Association. John van den Anker stressed that ibuprofen and paracetamol are relatively safe drugs when used correctly. Commonly used doses of ibuprofen in children are 4–10 mg/kg/dose, with a maximum of 40 mg/kg/day. When using ibuprofen at a dose of 100-200 mg / kg, most patients do not develop side effects or mild signs of an overdose appear (abdominal pain, nausea, vomiting, headache, drowsiness, ringing in the ears). When taking ibuprofen more than 400 mg / kg, severe overdose symptoms occur: apnea, metabolic acidosis, coma. When prescribing paracetamol, there is a risk of chronic overdose even when using the maximum daily dose in children (90 mg/kg). Chronic toxicity of paracetamol is difficult to detect and is therefore potentially harmful to children. John van den Anker concluded that the safety margin of ibuprofen is higher than that of paracetamol in both acute intoxication and chronic overdose.

Comparative analysis of the effectiveness of ibuprofen in relation to paracetamol and acetylsalicylic acid

Autret-Leca noted that a clinical study of ibuprofen and paracetamol (6 clinical studies) showed that the antipyretic activity of ibuprofen at doses of 7.5 and 10 mg/kg is equal to that of 10 mg/kg of paracetamol and that the effect of ibuprofen is longer ( Table 1). In 3 clinical studies, ibuprofen at doses of 6–10 mg/kg was shown to be equally effective as acetylsalicylic acid (10–15 mg/kg) in lowering fever, onset and duration of action. In a randomized, open, parallel, multicentre study of children aged 6 to 24 months with rectal temperature >39°C, ibuprofen (7.5 mg/kg, n=116), paracetamol (10 mg/kg, n=116) or acetylsalicylic acid (10 mg/kg, n=116) was prescribed. Dosing continued after 6 hours if necessary. Rectal temperature was measured before taking the first dose and after 1, 4, 6 hours. Ibuprofen has been shown to be more effective than paracetamol and acetylsalicylic acid. This was confirmed by a larger area under the curve, a large decrease in temperature after 4 hours, and a large number of children with rectal temperatures <38°C already after 4 hours (Fig. 2). The general condition was better in children who took ibuprofen rather than paracetamol. Significantly more parents reported good sleep on the second day in the ibuprofen group.

Fig. 2. Efficacy of ibuprofen versus paracetamol and aspirin

During the discussions, other experts also reported on their experience of treating fever with ibuprofen. They believe that the popularity of ibuprofen among pediatricians is growing. Lesco noted that in his practice, parents once given ibuprofen to their children did not go back to using paracetamol.

Diseases such as otitis media and pharyngitis/tonsillitis are painful in children and require the use of painkillers. Pons reported data from three clinical trials on the efficacy of ibuprofen as an analgesic in the treatment of otitis media and tonsillopharyngitis in infants. Bertin and others (1991) conducted a randomized, double-blind, controlled, multicentre study [4]. 231 children (6 to 12 years of age, outpatients) with tonsillitis or pharyngitis received one of three treatments: ibuprofen (n=77, 10 mg/kg 3 times a day), paracetamol (n=77, 10 mg/kg 3 times a day) or placebo (n=77). All children received phenoxymethylpenicillin. Ibuprofen was more effective than paracetamol or acetylsalicylic acid. Tolerance was also good, no one dropped out of the study (Table 2).

In another randomized, double-blind, multicenter study by Bertin et al. (1996), 219 children (1 to 6 years of age) with otoscope-proven otitis media received one of three drugs: ibuprofen (n=71, 10 mg/kg 3 times a day), paracetamol (n=73, 10 mg/kg 3 times a day) or placebo (n=75) [5]. All study participants additionally received cefaclor. After 48 hours, 25.3% of children in the placebo group were still in pain compared to 9.6% in the paracetamol group and 7% in the ibuprofen group.

Professor Gerhard Gaedicke (Germany) reported on the growing popularity of ibuprofen in the treatment of mild to moderate postoperative pain, eg after tooth extractions, tonsillectomy, myringotomy with tympanostomy. Compared to ibuprofen, paracetamol is less effective as an analgesic. In addition, there is a danger of overdose: doses of 120–150 mg/kg of paracetamol are hepatotoxic and should be avoided.

In the experience of Gaedicke and colleagues, ibuprofen is as effective as paracetamol when combined with codeine. This was confirmed by a randomized controlled trial conducted in 1997. In this study, treatment with ibuprofen and paracetamol/codeine was equally effective in relieving pain after tonsillectomy. But the tolerability of ibuprofen was better (no opioid side effects – constipation, vomiting).

Two other studies reported by Gaedicke suggest that ibuprofen has a sparing effect on opioid receptors. Maunuksela and others (1982) showed that after all operations in children receiving ibuprofen, the need for additional morphine intake is reduced in recovery rooms on the day of operation and during the three days of the study period. Kokki et al. (1994) found similar results. In their randomized, double-blind study, 81 children (1–6 years) with postoperative pain were given spinal anesthesia and given either ibuprofen (40 mg/kg, rectally) or placebo. 42.5% of children in the treatment group did not require morphine compared to only 19.5% of children receiving placebo.

Dr. Daniel Annequin, Head of Pediatric Pain at the Armand Trouseau Children’s Hospital in Paris, reported on the importance of identifying headaches in children, classifying them and choosing a treatment for acute and chronic headaches. According to Daniel Annequin, if migraine therapy is started as early as possible, then relief comes faster. Ibuprofen (10 mg/kg) is now believed to have advantages in attack treatment, being twice as effective as acetaminophen in relieving migraine within 2 hours [8] (Table 3).

Long-term use of ibuprofen for juvenile idiopathic arthritis

The experience of using ibuprofen in juvenile idiopathic rheumatoid arthritis (JRA) was presented by Dr. Richard Mouy (France). This is a disease in which patients receive NSAIDs for a long time. Ibuprofen has been used in children with JRA for more than 30 years [15], and its effectiveness has been confirmed in numerous studies. With long-term use of NSAIDs, the literature describes numerous side effects in almost 40% of patients (piroxicam, indomethacin), requiring discontinuation of treatment in 35-50% of patients. Among patients taking ibuprofen, side effects are described in 30% of cases, while treatment was interrupted in only 10%, and better results were achieved compared with other NSAIDs. Numerous studies have shown that ibuprofen is an effective drug for JRA and should be used as the first line of NSAID therapy.

The experience of using ibuprofen in juvenile idiopathic rheumatoid arthritis (JRA) was presented by Dr. Richard Mouy (France). This is a disease in which patients receive NSAIDs for a long time. Ibuprofen has been used in children with JRA for more than 30 years [15], and its effectiveness has been confirmed in numerous studies. With long-term use of NSAIDs, the literature describes numerous side effects in almost 40% of patients (piroxicam, indomethacin), requiring discontinuation of treatment in 35-50% of patients. Among patients taking ibuprofen, side effects are described in 30% of cases, while treatment was interrupted in only 10%, and better results were achieved compared with other NSAIDs. Numerous studies have shown that ibuprofen is an effective drug for JRA and should be used as the first line of NSAID therapy.

Intravenous ibuprofen in the treatment of patent ductus arteriosus in preterm infants

Indomethacin is a drug that is now often used to close the ductus arteriosus. But it disrupts cerebral, renal and mesenteric blood flow. The conference presented data on the use of ibuprofen in newborns (Bart van Overmeire, Belgium). Ibuprofen has been shown to be a novel drug for the treatment of newborns with patent ductus arteriosus, causing fewer side effects than indomethacin. This is due to the fact that although both drugs inhibit cyclooxygenase-1 and cyclooxygenase-2, ibuprofen has less effect on cyclooxygenase-1 and therefore has fewer side effects on cerebral, mesenteric and renal blood flow. In extensive clinical comparative studies of the prophylactic and therapeutic use of ibuprofen and indomethacin for closure of the ductus arteriosus in newborns, ibuprofen has been shown to have equal efficacy and fewer renal side effects [18,19]. Recent pharmacokinetic studies of ibuprofen in very low birth weight newborns have shown that clearance in this group of children is significantly slowed down and the half-life of the drug is increased.

Characteristics of ibuprofen

Compared to other NSAIDs or paracetamol, ibuprofen has the following advantages:

• Unlike paracetamol, ibuprofen does not form toxic metabolites. Its toxicity after accidental or intentional overdose is lower.
• Ibuprofen has a relatively large therapeutic index (about 4 times higher than that of paracetamol).
• Among the NSAIDs, ibuprofen is best tolerated by adults and even better tolerated by children.
• The use of ibuprofen does not lead to the development of Reye’s syndrome.
• Unlike paracetamol, ibuprofen has an anti-inflammatory effect.
• Ibuprofen is increasingly being used in infants and even premature babies.

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