What are the recommended prescription doses of ibuprofen. How should the dosage be adjusted for different conditions. What is the maximum safe dose of ibuprofen. How does ibuprofen work in the body. What are the potential side effects and precautions for ibuprofen use.

Understanding Ibuprofen: Mechanism of Action and Clinical Uses

Ibuprofen is a widely used nonsteroidal anti-inflammatory drug (NSAID) with analgesic, antipyretic, and anti-inflammatory properties. It works by inhibiting the enzyme cyclooxygenase (COX), which is responsible for the production of prostaglandins – mediators of pain, fever, and inflammation.

Clinical uses of ibuprofen include:

• Pain relief (headaches, toothaches, menstrual cramps, etc.)
• Reduction of fever
• Management of inflammatory conditions (e.g., arthritis)
• Treatment of minor injuries

How effective is ibuprofen compared to other pain relievers? Studies have shown that ibuprofen is generally as effective as acetaminophen for pain relief and fever reduction, but with the added benefit of anti-inflammatory action. However, the choice between the two often depends on the specific condition and individual patient factors.

Prescription Doses of Ibuprofen: Guidelines and Considerations

Prescription doses of ibuprofen are typically higher than over-the-counter doses and are tailored to the patient’s specific condition, age, and overall health status. The following are general guidelines for prescription ibuprofen dosages:

Adult Dosages:

• Mild to moderate pain: 400-600 mg every 4-6 hours
• Severe pain: 800 mg every 6-8 hours
• Rheumatoid arthritis, osteoarthritis, and ankylosing spondylitis: 1200-3200 mg daily, divided into 3-4 doses

Pediatric Dosages:

• Children 6 months to 12 years: 5-10 mg/kg every 6-8 hours
• Adolescents: 200-400 mg every 4-6 hours

How should ibuprofen dosages be adjusted for specific conditions? For chronic conditions like arthritis, higher doses may be prescribed initially and then reduced to the lowest effective dose. In patients with renal impairment, dosage reductions may be necessary to prevent further kidney damage.

Maximum Safe Dose of Ibuprofen: Avoiding Overdose and Toxicity

The maximum safe dose of ibuprofen varies depending on the indication and duration of use. Generally, the following limits are recommended:

• Adults: Maximum 3200 mg per day
• Children: Maximum 40 mg/kg per day

What are the risks of exceeding the maximum safe dose of ibuprofen? Exceeding these limits can increase the risk of serious side effects, including gastrointestinal bleeding, cardiovascular events, and kidney damage. It’s crucial to follow prescribed dosages and consult a healthcare provider before increasing the dose.

Pharmacokinetics of Ibuprofen: Absorption, Distribution, and Elimination

Understanding the pharmacokinetics of ibuprofen is essential for appropriate dosing and administration. Key aspects include:

• Absorption: Rapidly absorbed from the gastrointestinal tract
• Peak plasma concentration: Reached within 1-2 hours of oral administration
• Half-life: Approximately 2 hours
• Metabolism: Primarily hepatic
• Excretion: Mainly via urine (90%) and feces (10%)

How does the pharmacokinetics of ibuprofen affect its dosing schedule? Due to its short half-life, ibuprofen is typically administered every 4-6 hours for optimal pain relief and anti-inflammatory effects. Extended-release formulations may allow for less frequent dosing in some cases.

Special Populations: Dosage Adjustments and Precautions

Certain populations may require dosage adjustments or special precautions when using ibuprofen:

Elderly Patients:

Older adults may be more susceptible to side effects and may require lower doses. Start with the lowest effective dose and monitor closely for adverse reactions.

Patients with Renal Impairment:

Ibuprofen should be used with caution in patients with kidney disease. Dosage reductions may be necessary, and regular monitoring of renal function is recommended.

Patients with Hepatic Impairment:

While no specific dosage adjustments are required for mild to moderate liver disease, caution is advised in patients with severe hepatic impairment.

Pregnant and Breastfeeding Women:

Ibuprofen should be avoided during pregnancy, especially in the third trimester. It can be used with caution during breastfeeding, but alternative pain relievers may be preferred.

How should healthcare providers approach ibuprofen dosing in these special populations? A tailored approach, considering the individual’s medical history, concomitant medications, and specific health concerns, is essential for safe and effective use of ibuprofen in these groups.

Side Effects and Adverse Reactions: Recognizing and Managing Risks

While ibuprofen is generally well-tolerated, it can cause various side effects, especially with long-term use or high doses. Common side effects include:

• Gastrointestinal disturbances (nausea, dyspepsia, diarrhea)
• Headache
• Dizziness
• Fluid retention
• Hypertension

More serious adverse reactions can include:

• Gastrointestinal bleeding or ulceration
• Cardiovascular events (heart attack, stroke)
• Renal impairment
• Severe skin reactions
• Anaphylaxis (rare)

How can the risk of side effects be minimized when using prescription doses of ibuprofen? To reduce the risk of adverse reactions, healthcare providers should:

1. Use the lowest effective dose for the shortest duration possible
2. Consider gastroprotective agents in high-risk patients
3. Monitor patients regularly, especially those on long-term therapy
4. Educate patients about potential side effects and when to seek medical attention

Drug Interactions: Important Considerations for Ibuprofen Use

Ibuprofen can interact with various medications, potentially altering their effectiveness or increasing the risk of side effects. Significant interactions include:

• Anticoagulants (e.g., warfarin): Increased risk of bleeding
• Antihypertensives: Reduced blood pressure-lowering effect
• Diuretics: Increased risk of renal impairment
• Lithium: Increased lithium levels and toxicity risk
• Other NSAIDs: Increased risk of gastrointestinal side effects
• Methotrexate: Increased methotrexate levels and toxicity risk

How should healthcare providers manage potential drug interactions with ibuprofen? Careful medication review, dose adjustments, and close monitoring are essential when prescribing ibuprofen to patients taking other medications. In some cases, alternative pain management strategies may be necessary.

Ibuprofen in Specific Clinical Scenarios: Optimizing Treatment Outcomes

The use of prescription ibuprofen doses can be particularly beneficial in certain clinical scenarios, but requires careful consideration of risks and benefits:

Acute Pain Management:

Higher doses of ibuprofen (e.g., 400-800 mg) can provide effective pain relief for acute conditions such as dental pain, post-operative pain, or migraine headaches. The duration of treatment should be limited to minimize the risk of side effects.

Chronic Inflammatory Conditions:

In rheumatoid arthritis or osteoarthritis, long-term use of prescription ibuprofen doses may be necessary. Regular monitoring for side effects and periodic reassessment of the need for continued therapy are crucial.

Dysmenorrhea:

Ibuprofen is often prescribed for menstrual pain due to its ability to reduce prostaglandin production. Doses of 400-600 mg every 6-8 hours are typically effective.

Fever Reduction in High-Risk Patients:

In some cases, such as in patients with cardiovascular disease, prescription doses of ibuprofen may be preferred over other antipyretics for fever reduction. However, the potential cardiovascular risks must be carefully weighed against the benefits.

How can healthcare providers determine the most appropriate use of prescription ibuprofen in these scenarios? A thorough assessment of the patient’s medical history, current medications, and individual risk factors is essential. In many cases, a multimodal approach combining ibuprofen with other pain management strategies may provide the best outcomes while minimizing risks.

In conclusion, prescription doses of ibuprofen can be a valuable tool in managing pain and inflammation across various clinical scenarios. However, careful consideration of dosing, potential side effects, and individual patient factors is crucial to ensure safe and effective use. Healthcare providers should stay informed about the latest guidelines and research to optimize ibuprofen therapy for their patients.

An Overview of Clinical Pharmacology of Ibuprofen

1. Tripathi KD. Non steroidal anti inflammatory drugs and anti pyretic analgesics. In: Essentials of medical pharmacology. 5^th edn., Jaypee Brothers, New Delhi, 2003. p. 176. [Google Scholar]

2. Abrahm P.
KI KD. Nitro-argenine methyl ester, a non selective inhibitor of nitric oxide synthase reduces ibuprofen-induced gastric mucosal injury in the rat.
Dig Dis
2005;50(9):1632-1640 . 10.1007/s10620-005-2908-y [PubMed] [CrossRef] [Google Scholar]

3. Bradbury F. How important is the role of the physician in the correct use of a drug? An observational cohort study in general practice. Int J Clin Prat 2004; (144):27-32. [PubMed]

4. Chavez ML, DeKorte CJ. Valdecoxib: a review.
Clin Ther
2003. Mar;25(3):817-851. 10.1016/S0149-2918(03)80110-8 [PubMed] [CrossRef] [Google Scholar]

5. Wahbi AA, Hassan E, Hamdy D, Khamis E, Barary M. Spectrophotometric methods for the determination of Ibuprofen in tablets.
Pak J Pharm Sci
2005. Oct;18(4):1-6. [PubMed] [Google Scholar]

6. Roberts LK, Morrow JD. Analgesic antipyretic and anti inflammatory agents and drugs wmplyed in treatment of gout. In: Hardman JG and Limbird LE editors. Goodman and Gillman’s the pharmacological basis of therapeutics. 10^th ed., McGraw hill, New York, Chicago, 2001. p. 711. [Google Scholar]

7. Ritter JM, Lewis L, Mant TG. Analgesics and the control of pain. In: A text book of clinical pharmacology. 4^th ed., Arnold London, 1999. p. 216. [Google Scholar]

8. Herzfeld CD, Kummel R.
Dissociation constant, solubilities and dissolution rate of some selective non steroidal anti inflammatory drugs.
Drug Dev Ind Pharm
1983;9(5):767-793. [Google Scholar]

9. Ross JM, DeHoratius J. Non narcotic analgesics. In: DiPalma JR and DiGregorio GJ editors. Basic pharmacology in medicine. 3^rd ed., McGraw hill publishing company New York, 1990. p. 311-316. [Google Scholar]

10. Antal EJ, Wright CE, III, Brown BL, Albert KS, Aman LC, Levin NW. The influence of hemodialysis on the pharmacokinetics of ibuprofen and its major metabolites.
J Clin Pharmacol
1986. Mar;26(3):184-190. [PubMed] [Google Scholar]

11. Katzung BG, Furst DE. Non steroidal anti inflammatory drugs, disease miodifying anti rheumatic drugs, non opioid analgesics, drugs used in gout. In: Katzung BG editor. Basic and clinical pharmacology, 7^th ed., Appliton and Lang Stamford, Connecticut, 1998. p.586, 1068. [Google Scholar]

12. Olive G. Analgesic/Antipyretic treatment: ibuprofen or acetaminophen? An update. Therapie
2006. Mar-Apr;61(2):151-160. 10.2515/therapie:2006034 [PubMed] [CrossRef] [Google Scholar]

13. Compreton EL, Glass RC, Hird ID. The pharmacokinetic of ibuprofen in elderly and young subjects. 1984 Boots research reports DT 84041.

14. Senekjian HO, Lee C, Kuo TH, Krothapalli R. An absorption and disposition of ibuprofen in hemodialysed uremic patients. Eur J Rheumatism and inflammation 1983; 6(2):155-162. [PubMed]

15. Physician’s desk reference. 51^st ed., Published by Medical Economic Company, Inc. at Montvale, 1997. p. 1389-1391. [Google Scholar]

16. Moore N. Forty years of ibuprofen use.
Int J Clin Pract Suppl
2003. Apr;(135):28-31. [PubMed] [Google Scholar]

17. Wood DM, Monaghal J, Streete P, Jones AL, Dargan PI. Fourty five years of ibuprofen use. 2006 Critical care, 10: R 44. [PMC free article] [PubMed]

18. Nozu K. Flurbiprofen: highly potent inhibitor of prostaglandin synthesis.
Biochim Biophys Acta
1978. Jun;529(3):493-496. [PubMed] [Google Scholar]

19. Adams SS, McCullough KF, Nicholson JS. The pharmacological properties of ibuprofen, an anti-inflammatory, analgesic and antipyretic agent.
Arch Int Pharmacodyn Ther
1969. Mar;178(1):115-129. [PubMed] [Google Scholar]

20. Pottast H, Dressman JB, Junginger HE, Midha KK, Oestr H, Shah VP, et al.
Biowaiver monographs for immediate release solid oral dosage forms: ibuprofen.
J Pharm Sci
2005;94(10):2122. [PubMed] [Google Scholar]

21. Bhattacharya SK, Sen P, Ray A. Central nervous system. In: Das PK editor. Pharmacology, 2^nd ed., Elsevier, New Delhi, 2003. p. 268. [Google Scholar]

22. Sharma PK, Garg SK, Narang A. Pharmacokinetics of oral ibuprofen in premature infants.
J Clin Pharmacol
2003. Sep;43(9):968-973. 10.1177/0091270003254635 [PubMed] [CrossRef] [Google Scholar]

23. Kravs DM, Pharm JT. Neonatal therapy. In: Koda-Kimble MA, Young LV, Kradjan WA, Guglielmo BJ, Alldredge BK and Corelli RL editors. Applied therapeutics: the clinical use of drugs, 8^th ed., Lipponcott William and Wilkins A Wolters Kluwer company Philadelphia New York, 2005. p. 94-23. [Google Scholar]

24. Tan SC, Patel BK, Jackson SH, Swift CG, Hutt AJ. Ibuprofen stereochemistry: double-the-trouble?
Enantiomer
1999;4(3-4):195-203. [PubMed] [Google Scholar]

25. Russell TM, Young LY. Arthritic disorders: gout and hyperurecemia. In: Koda-Kimble MA, Young LV, Kradjan WA, Guglielmo BJ, Alldredge BK and Corelli RL editors. Applied therapeutics: the clinical use of drugs. 8^th ed., Lipponcott William and Wilkins A Wolters Kluwer company Philadelphia New York, 2005. p. 42-45. [Google Scholar]

26. Frank WA, Brown MM.
Ibuprofen in acute poly articular gout.
Arthritis Rheum. Arthritis Rheum.
1976;19(2):269 . 10.1002/art.1780190225 [PubMed] [CrossRef] [Google Scholar]

27. Wagner W, Khanna P, Furst DE. Non-steroidal-anti inflammatory drugs, disease modifying anti rheumatic drugs, non opioid analgesics and drugs used in Gout. In: Katzung BG editor. Basic and clinical pharmacology 9^th ed., McGraw hill Booston, 2004. p. 585. [Google Scholar]

28. Gall EP, Caperton EM, McComb JE, Messner R, Multz CV, O’Hanlan M, et al.. Clinical comparison of ibuprofen, fenoprofen calcium, naproxen and tolmetin sodium in rheumatoid arthritis.
J Rheumatol
1982. May-Jun;9(3):402-407. [PubMed] [Google Scholar]

29. Winstanley P, Walley T. Drug for arthritis. In: Medical pharmacology: a clinical core text for integrated curriculum with self assessment. Churchill Livingstone, Adinburgh, 2002. p. 105-107. [Google Scholar]

30. Calrk WG, Brater DC, Jhonson AR. Non steroidal anti inflammatory, anti pyretic analgesics. In: Goth’s medical pharmacology. 13^th ed., Mosby year book. St: Louis Baltimore Booston. 1992. [Google Scholar]

31. Hollingworth P. The use of non-steroidal anti-inflammatory drugs in paediatric rheumatic diseases.
Br J Rheumatol
1993. Jan;32(1):73-77. 10.1093/rheumatology/32.1.73 [PubMed] [CrossRef] [Google Scholar]

32. Nuki G, Ralston SH, Luqmani R. Diseases of connective tissues, joints and bones. In: Haslett C, Chilvers ER, Hunter JAA and Boon NA editors. Davidson’s principles and practice of medicine, 18^th ed., Chirchil Livingstone UK, 1999. p. 842-843. [Google Scholar]

33. Coussement W. Gastrointestinal toxicology: toxicological pathology and sources of intestinal toxicity. In: Niesink RJM, DeVries J and Hollinger MA editors. Toxicology: principles and applications CRC Press, Boca Raton, New York, 1996. p. 655. [Google Scholar]

34. Burke A, Smyth E, FitzGerald GA. Analgesic-anti pyretic and anti inflammatory Agents; Pharmacotherapy of gout. In: Bruntom LL, Lazo JS and Parker KL (editors). Goodmans and Gilman’s the pharmacological basis of therapeutics. 11^th ed., McGraw Hill, New York, 2006. p. 676-700. [Google Scholar]

35. Konstan MW, Krenicky JE, Finney MR, Kirchner HL, Hilliard KA, Hilliard JB, et al.. Effect of ibuprofen on neutrophil migration in vivo in cystic fibrosis and healthy subjects.
J Pharmacol Exp Ther
2003. Sep;306(3):1086-1091. 10.1124/jpet.103.052449 [PubMed] [CrossRef] [Google Scholar]

36. Mackey JE, Anbar RD. High-dose ibuprofen therapy associated with esophageal ulceration after pneumonectomy in a patient with cystic fibrosis: a case report.
BMC Pediatr
2004. Sep;4:19. 10.1186/1471-2431-4-19 [PMC free article] [PubMed] [CrossRef] [Google Scholar]

37. Rifai N, Sakamoto M, Law T, Galpchian V, Harris N, Colin AA. Use of a rapid HPLC assay for determination of pharmacokinetic parameters of ibuprofen in patients with cystic fibrosis.
Clin Chem
1996. Nov;42(11):1812-1816. [PubMed] [Google Scholar]

38. Zawada ET, Jr. Renal consequences of nonsteroidal antiinflammatory drugs.
Postgrad Med
1982. May;71(5):223-230. [PubMed] [Google Scholar]

39. Volans G, Hartley V, McCrea S, Monagham J.
Non opioid analgesic poisoning. Clinical medicine.
Clin Med (Northfield IL)
2003;3(2):119-123. [PMC free article] [PubMed] [Google Scholar]

40. Seifert SA, Bronstein AC, McGuire T. Massive ibuprofen ingestion with survival.
J Toxicol Clin Toxicol
2000;38(1):55-57. 10.1081/CLT-100100917 [PubMed] [CrossRef] [Google Scholar]

41. Bhushan R, Martens J. Resolution of enantiomers of ibuprofen by liquid chromatography: a review.
Biomed Chromatogr
1998. Nov-Dec;12(6):309-316. 10.1002/(SICI)1099-0801(199811/12)12:6<309::AID-BMC763>3.0.CO;2-K [PubMed] [CrossRef] [Google Scholar]

42. Moore TA, Hersh EV.
Celecoxib and refecoxib. The role of Cox-II inhibitors in dental practice.
J Am Dent Assoc
2011;132(4):451-456. [PubMed] [Google Scholar]

43. Jones K, Seymour RA, Hawkesford JE. Synergistic interactions between the dual serotonergic, noradrenergic reuptake inhibitor duloxetine and the non-steroidal anti-inflammatory drug ibuprofen in inflammatory pain in rodents. British Journal of Oral and Maxilofacial surgey 1997; 35(3):173-176. [PubMed]

44. Grimes DA, Hubacher D, Lopez LM, Schulz KF.
Non steroidal anti inflammatory drugs for heavy bleeding or apin associated with intra uterine- device use.
Cochrane Database Syst Rev
2006;18(4) . 10.1002/14651858.CD006034.pub2 [PMC free article] [PubMed] [CrossRef] [Google Scholar]

45. Pouresmail Z, Ibrahimzadeh R. Effects of acupressure and ibuprofen on the severity of primary dysmenorrhea.
J Tradit Chin Med
2002. Sep;22(3):205-210. [PubMed] [Google Scholar]

46. Aycock DG. Ibuprofen: a monograph. Am. Pharm., NS 1991; 31(1):46-49. [PubMed]

47. Milsom I, Minic M, Dawood MY, Akin MD, Spann J, Niland NF, et al.. Comparison of the efficacy and safety of nonprescription doses of naproxen and naproxen sodium with ibuprofen, acetaminophen, and placebo in the treatment of primary dysmenorrhea: a pooled analysis of five studies.
Clin Ther
2002. Sep;24(9):1384-1400. 10.1016/S0149-2918(02)80043-1 [PubMed] [CrossRef] [Google Scholar]

48. Dawood MY, Khan-Dawood FS. Clinical efficacy and differential inhibition of menstrual fluid prostaglandin F2alpha in a randomized, double-blind, crossover treatment with placebo, acetaminophen, and ibuprofen in primary dysmenorrhea.
Am J Obstet Gynecol
2007. Jan;196(1):35–, e1-e5.. 10.1016/j.ajog.2006.06.091 [PubMed] [CrossRef] [Google Scholar]

49. Dawood MY. Primary dysmenorrhea: advances in pathogenesis and management.
Obstet Gynecol
2006. Aug;108(2):428-441. 10.1097/01.AOG.0000230214.26638.0c [PubMed] [CrossRef] [Google Scholar]

50. Karttunen P, Saano V, Paronen P, Peura P, Vidgren M. Pharmacokinetics of ibuprofen in man: a single-dose comparison of two over-the-counter, 200 mg preparations.
Int J Clin Pharmacol Ther Toxicol
1990. Jun;28(6):251-255. [PubMed] [Google Scholar]

51. Diamond S, Freitag FG. The use of ibuprofen plus caffeine to treat tension-type headache.
Curr Pain Headache Rep
2001. Oct;5(5):472-478. 10.1007/s11916-001-0060-8 [PubMed] [CrossRef] [Google Scholar]

52. Schoenen J. Treatment of tension headache. Rev Neurol (Paris)
2000;156(4)(Suppl 4):S87-S92. [PubMed] [Google Scholar]

53. Erlewyn-Lajeunesse MD, Coppens K, Hunt LP, Chinnick PJ, Davies P, Higginson IM, et al.. Randomised controlled trial of combined paracetamol and ibuprofen for fever.
Arch Dis Child
2006. May;91(5):414-416. 10.1136/adc.2005.087874 [PMC free article] [PubMed] [CrossRef] [Google Scholar]

54. Krishna S, Pukrittayakamee S, Supanaranond W, ter Kuile F, Ruprah M, Sura T, et al.. Fever in uncomplicated Plasmodium falciparum malaria: randomized double-‘blind’ comparison of ibuprofen and paracetamol treatment.
Trans R Soc Trop Med Hyg
1995. Sep-Oct;89(5):507-509. 10.1016/0035-9203(95)90087-X [PubMed] [CrossRef] [Google Scholar]

55. Evers S, Rahmann A, Kraemer C, Kurlemann G, Debus O, Husstedt IW, et al.. Treatment of childhood migraine attacks with oral zolmitriptan and ibuprofen.
Neurology
2006. Aug;67(3):497-499. 10.1212/01.wnl.0000231138.18629.d5 [PubMed] [CrossRef] [Google Scholar]

56. Melton LM, Keith AB, Davis S, Oakley AE, Edwardson JA, Morris CM. Chronic glial activation, neurodegeneration, and APP immunoreactive deposits following acute administration of double-stranded RNA.
Glia
2003. Oct;44(1):1-12. 10.1002/glia.10276 [PubMed] [CrossRef] [Google Scholar]

57. Casper D, Yaparpalvi U, Rempel N, Werner P. Ibuprofen protects dopaminergic neurons against glutamate toxicity in vitro.
Neurosci Lett
2000. Aug;289(3):201-204. 10.1016/S0304-3940(00)01294-5 [PubMed] [CrossRef] [Google Scholar]

58. Townsend KP, Praticò D. Novel therapeutic opportunities for Alzheimer’s disease: focus on nonsteroidal anti-inflammatory drugs.
FASEB J
2005. Oct;19(12):1592-1601. 10.1096/fj.04-3620rev [PubMed] [CrossRef] [Google Scholar]

59. Ton TG, Heckbert SR, Longstreth WT, Jr, Rossing MA, Kukull WA, Franklin GM, et al.. Nonsteroidal anti-inflammatory drugs and risk of Parkinson’s disease.
Mov Disord
2006. Jul;21(7):964-969. 10.1002/mds.20856 [PubMed] [CrossRef] [Google Scholar]

60. Chen H, Jacobs E, Schwarzschild MA, McCullough ML, Calle EE, Thun MJ, et al.. Nonsteroidal antiinflammatory drug use and the risk for Parkinson’s disease.
Ann Neurol
2005. Dec;58(6):963-967. 10.1002/ana.20682 [PubMed] [CrossRef] [Google Scholar]

61. Carrasco E, Casper D, Werner P. Dopaminergic neurotoxicity by 6-OHDA and MPP+: differential requirement for neuronal cyclooxygenase activity.
J Neurosci Res
2005. Jul;81(1):121-131. 10.1002/jnr.20541 [PubMed] [CrossRef] [Google Scholar]

62. Elsisi NS, Darling-Reed S, Lee EY, Oriaku ET, Soliman KF. Ibuprofen and apigenin induce apoptosis and cell cycle arrest in activated microglia.
Neurosci Lett
2005. Feb;375(2):91-96. 10.1016/j.neulet.2004.10.087 [PubMed] [CrossRef] [Google Scholar]

63. Harris RE, Kasbari S, Farrar WB. Prospective study of nonsteroidal anti-inflammatory drugs and breast cancer.
Oncol Rep
1999. Jan-Feb;6(1):71-73. [PubMed] [Google Scholar]

64. Wilcox CM, Cryer B, Triadafilopoulos G. Patterns of use and public perception of over-the-counter pain relievers: focus on nonsteroidal antiinflammatory drugs.
J Rheumatol
2005. Nov;32(11):2218-2224. [PubMed] [Google Scholar]

65. Bateman DN. NSAIDs: time to re-evaluate gut toxicity.
Lancet
1994. Apr;343(8905):1051-1052. 10.1016/S0140-6736(94)90175-9 [PubMed] [CrossRef] [Google Scholar]

66. Rocca GD, Chiarandini P, Pietropaoli P. Analgesia in PACU: nonsteroidal anti-inflammatory drugs.
Curr Drug Targets
2005. Nov;6(7):781-787. 10.2174/138945005774574470 [PubMed] [CrossRef] [Google Scholar]

67. Tsokos M and Schmoldt A. Contribution of non steroidal anti inflammatory drugs to death associated with peptic ulcer disease:a prospective toxicological analysis of autopsy blood samples. Arch Pathol gLab Med 2001; 125 (12):1572-1574. [PubMed]

68. Dollery C. Therapeutic drugs 2^nd ed., vol. 1, Churchill Livingstone Edinbugh London, 1999. p. 12. [Google Scholar]

69. Wolfe MM, Lichenstein DR, Signh G. Gastrointestinal toxicity of non steroidal anti inflammatory drugs. M. Engl.J.Med 1999; 340:1888(24)-1899. [PubMed]

70. Oermann CM, Sockrider MM, Konstan MW. The use of anti-inflammatory medications in cystic fibrosis: trends and physician attitudes.
Chest
1999. Apr;115(4):1053-1058. 10.1378/chest.115.4.1053 [PubMed] [CrossRef] [Google Scholar]

71. Gambero A, Becker TL, Zago AS, de Oliveira AF, Pedrazzoli J, Jr. Comparative study of anti-inflammatory and ulcerogenic activities of different cyclo-oxygenase inhibitors.
Inflammopharmacology
2005;13(5-6):441-454. 10.1163/156856005774649377 [PubMed] [CrossRef] [Google Scholar]

72. Fulcher EM, Soto CD, Fulcher RM. Medications for disorders of the musculoskeletal system. In: Principles and applications. A work text for allied health professionals. Saunders, an imprint of Elsevier Science Philadelphia, 2003. p. 510. [Google Scholar]

73. Kennedy MJ. Inflammation and cystic fibrosis pulmonary disease.
Pharmacotherapy
2001. May;21(5):593-603. 10.1592/phco.21.6.593.34546 [PubMed] [CrossRef] [Google Scholar]

74. Kovesi TA, Swartz R, MacDonald N. Transient renal failure due to simultaneous ibuprofen and aminoglycoside therapy in children with cystic fibrosis.
N Engl J Med
1998. Jan;338(1):65-66. 10.1056/NEJM199801013380115 [PubMed] [CrossRef] [Google Scholar]

75. Durkin E, Moran AP, Hanson PJ. Apoptosis induction in gastric mucous cells in vitro: lesser potency of Helicobacter pylori than Escherichia coli lipopolysaccharide, but positive interaction with ibuprofen.
J Endotoxin Res
2006;12(1):47-56. [PubMed] [Google Scholar]

76. Vale JA, Meredith TJ. Acute poisoning due to non-steroidal anti-inflammatory drugs. Clinical features and management.
Med Toxicol
1986. Jan-Feb;1(1):12-31. [PubMed] [Google Scholar]

77. Rossi S. (2004). Australian medicine hand book ISBN 0-9578521-4-2. [Google Scholar]

78. Rang HP, Dale MM, Ritter JM. Anti-inflammatory and immunosuppressant drugs. In: Pharmacology. 5^th ed., Churchil Livingstone Edinburgh London, 1999. p. 248. [Google Scholar]

79. Pepper GA.
Non steroidal anti inflammatory drugs; New perspectives on a familiar drug class.
Rheumatology
2000;35(1):223-244. [PubMed] [Google Scholar]

80. Garnett WR. Clinical implications of drug interactions with coxibs.
Pharmacotherapy
2001. Oct;21(10):1223-1232. 10.1592/phco.21.15.1223.33891 [PubMed] [CrossRef] [Google Scholar]

81. Hansen KE, Elliott ME. (2005). Osteoarthritis. In:Dipiro JT, Talbert RL, Yee GC, Matzke GR, Wells BG and Posey LM editors. Pharmacotherapy; A pathophysiologic approach, 6^th ed., McGraw Hill New York, pp1696-1698. [Google Scholar]

82. Gladding PA, Webster MW, Farrell HB, Zeng IS, Park R, Ruijne N. The antiplatelet effect of six non-steroidal anti-inflammatory drugs and their pharmacodynamic interaction with aspirin in healthy volunteers.
Am J Cardiol
2008. Apr;101(7):1060-1063. 10.1016/j.amjcard.2007.11.054 [PubMed] [CrossRef] [Google Scholar]

83. Gaziano JM, Gibson CM. Potential for drug-drug interactions in patients taking analgesics for mild-to-moderate pain and low-dose aspirin for cardioprotection.
Am J Cardiol
2006. May;97(9A):23-29. 10.1016/j.amjcard.2006.02.020 [PubMed] [CrossRef] [Google Scholar]

84. FitzGerald GA. Parsing an enigma: the pharmacodynamics of aspirin resistance.
Lancet
2003. Feb;361(9357):542-544. 10.1016/S0140-6736(03)12560-3 [PubMed] [CrossRef] [Google Scholar]

85. MacDonald TM, Wei L. Effect of ibuprofen on cardioprotective effect of aspirin.
Lancet
2003. Feb;361(9357):573-574. 10.1016/S0140-6736(03)12509-3 [PubMed] [CrossRef] [Google Scholar]

86. Curtis JP, Wang Y, Portnay EL, Masoudi FA, Havranek EP, Krumholz HM. Aspirin, ibuprofen, and mortality after myocardial infarction: retrospective cohort study.
BMJ
2003. Dec;327(7427):1322-1323. 10.1136/bmj.327.7427.1322 [PMC free article] [PubMed] [CrossRef] [Google Scholar]

87. Palmer R, Weiss R, Zusman RM, Haig A, Flavin S, MacDonald B. Effects of nabumetone, celecoxib, and ibuprofen on blood pressure control in hypertensive patients on angiotensin converting enzyme inhibitors.
Am J Hypertens
2003. Feb;16(2):135-139. 10.1016/S0895-7061(02)03203-X [PubMed] [CrossRef] [Google Scholar]

88. Lee TH, Salomon DR, Rayment CM, Antman EM. Hypotension and sinus arrest with exercise-induced hyperkalemia and combined verapamil/propranolol therapy.
Am J Med
1986. Jun;80(6):1203-1204. 10.1016/0002-9343(86)90688-1 [PubMed] [CrossRef] [Google Scholar]

89. Ackerman Z, Cominelli S and Rynolds TB (2002). Effects of mesoprostol on ibuprofen- induced renal dysfunction in patients with decompunsated cirrhosis: results of double-blind placebo-controlled parallel group studies The American Journal of Gastrointenterology, 97(8):2033-2039. [PubMed]

90. McElwee NE, Veltri JC, Bradford DC, Rollins DE. A prospective, population-based study of acute ibuprofen overdose: complications are rare and routine serum levels not warranted.
Ann Emerg Med
1990. Jun;19(6):657-662. 10.1016/S0196-0644(05)82471-0 [PubMed] [CrossRef] [Google Scholar]

91. Hall AH; Smolinske SC; Conrad FL; Wruk KM; Kulig KW; Dwelle TL; Rumack BH. Ibuprofen overdose. Ann Emerg Med. 1986; 15(11):1308-13 (ISSN: 0196-0644). [PubMed]

92. Marciniak KE; Thomas IH; Brogan TV; Roberts JS; Czaja A; Mazor SS
Massive ibuprofen overdose requiring extracorporeal membrane oxygenation for cardiovascular support. Pediatr Crit Care Med. 2007; 8(2):180-182 (ISSN: 1529-7535). [PubMed]

93. Vale JA, Meredith TJ. Acute poisoning due to non-steroidal anti-inflammatory drugs. Clinical features and management.
Med Toxicol
1986. Jan-Feb;1(1):12-31. [PubMed] [Google Scholar]

94. Hippisley-Cox J, Coupland C. Risk of myocardial infarction in patients taking cyclo-oxygenase-2 inhibitors or conventional non-steroidal anti-inflammatory drugs: population based nested case-control analysis.
BMJ
2005. Jun;330(7504):1366. 10.1136/bmj.330.7504.1366 [PMC free article] [PubMed] [CrossRef] [Google Scholar]

95. Bhatt DL. NSAIDS and the risk of myocardial infarction: do they help or harm?
Eur Heart J
2006. Jul;27(14):1635-1636. 10.1093/eurheartj/ehl090 [PubMed] [CrossRef] [Google Scholar]

96. Ibuprofen Oral: AHFS detailed Monograph.

97. Solomon DH, Glynn RJ, Levin R, Avorn J. Nonsteroidal anti-inflammatory drug use and acute myocardial infarction.
Arch Intern Med
2002. May;162(10):1099-1104. 10.1001/archinte.162.10.1099 [PubMed] [CrossRef] [Google Scholar]

98. Almond C. Nonsteroidal anti-inflammatory agents. In: Emergency Medicine: A Comprehensive Study Guide 4^th ed. New York, NY: McGraw-Hill; 1995:792-795. [Google Scholar]

99. Garcia EB, Ruitenberg A, Madrestsma GS and Hintzen RQ (2003). Hyponatremic coma induced by desmopressin and ibuprofen in awomen with von willebrand’s disease Hemophilia, 9(2):232-234. [PubMed]

100. Oselin K, Anier K. Inhibition of human thiopurine S-methyltransferase by various nonsteroidal anti-inflammatory drugs in vitro: a mechanism for possible drug interactions.
Drug Metab Dispos
2007. Sep;35(9):1452-1454. 10.1124/dmd.107.016287 [PubMed] [CrossRef] [Google Scholar]

101. López JR, Domínguez-Ramírez AM, Cook HJ, Bravo G, Díaz-Reval MI, Déciga-Campos M, et al.. Enhancement of antinociception by co-administration of ibuprofen and caffeine in arthritic rats.
Eur J Pharmacol
2006. Aug;544(1-3):31-38. 10.1016/j.ejphar.2006.06.041 [PubMed] [CrossRef] [Google Scholar]

102. Dooley JM, Gordon KE, Wood EP, Brna PM, MacSween J, Fraser A. Caffeine as an adjuvant to ibuprofen in treating childhood headaches.
Pediatr Neurol
2007. Jul;37(1):42-46. 10.1016/j.pediatrneurol.2007.02.016 [PubMed] [CrossRef] [Google Scholar]

103. Tornio A, Niemi M, Neuvonen PJ, Backman JT. Stereoselective interaction between the CYP2C8 inhibitor gemfibrozil and racemic ibuprofen.
Eur J Clin Pharmacol
2007. May;63(5):463-469. 10.1007/s00228-007-0273-9 [PubMed] [CrossRef] [Google Scholar]

104. Bell EC, Ravis WR, Lloyd KB, Stokes TJ. Effects of St. John’s wort supplementation on ibuprofen pharmacokinetics.
Ann Pharmacother
2007. Feb;41(2):229-234. 10.1345/aph.1H602 [PubMed] [CrossRef] [Google Scholar]

105. Hynninen VV, Olkkola KT, Leino K, Lundgren S, Neuvonen PJ, Rane A, et al.. Effects of the antifungals voriconazole and fluconazole on the pharmacokinetics of s-(+)- and R-(-)-Ibuprofen.
Antimicrob Agents Chemother
2006. Jun;50(6):1967-1972. 10.1128/AAC.01483-05 [PMC free article] [PubMed] [CrossRef] [Google Scholar]

106. Rahman MM, Rahman MH, Rahman NN. Competitive binding of ibuprofen and naproxen to bovine serum albumin : modified form of drug-drug displacement interaction at the binding site.
Pak J Pharm Sci
2005. Jan;18(1):43-47. [PubMed] [Google Scholar]

107. Guindon J, De Léan A, Beaulieu P. Local interactions between anandamide, an endocannabinoid, and ibuprofen, a nonsteroidal anti-inflammatory drug, in acute and inflammatory pain.
Pain
2006. Mar;121(1-2):85-93. 10.1016/j.pain.2005.12.007 [PubMed] [CrossRef] [Google Scholar]

108. Kaminski R, Kozicka M, Parada-turska J, Dziki M, Kleinrok Z, Turski WA, et al. . Effect of non-steroidal anti-inflammatory drugs on the anticonvulsive activity of valproate and diphenylhydantoin against maximal electroshock-induced seizures in mice.
Pharmacol Res
1998. May;37(5):375-381. 10.1006/phrs.1998.0309 [PubMed] [CrossRef] [Google Scholar]

109. Kapil R, Nolting A, Roy P, Fiske W, Benedek I, Abramowitz W. Pharmacokinetic properties of combination oxycodone plus racemic ibuprofen: two randomized, open-label, crossover studies in healthy adult volunteers.
Clin Ther
2004. Dec;26(12):2015-2025. 10.1016/j.clinthera.2004.12.013 [PubMed] [CrossRef] [Google Scholar]

110. Pargal A, Kelkar MG, Nayak PJ. The effect of food on the bioavailability of ibuprofen and flurbiprofen from sustained release formulations.
Biopharm Drug Dispos
1996. Aug;17(6):511-519. 10.1002/(SICI)1099-081X(199608)17:6<511::AID-BDD969>3.0.CO;2-Y [PubMed] [CrossRef] [Google Scholar]

111. Kondal A, Garg SK. Influence of acidic beverage (Coca-Cola) on pharmacokinetics of ibuprofen in healthy rabbits.
Indian J Exp Biol
2003. Nov;41(11):1322-1324. [PubMed] [Google Scholar]

112. Garba M, Yakasai IA, Bakare MT, Munir HY. Effect of Tamarindus indica. L on the bioavailability of ibuprofen in healthy human volunteers.
Eur J Drug Metab Pharmacokinet
2003. Jul-Sep;28(3):179-184. 10.1007/BF03190483 [PubMed] [CrossRef] [Google Scholar]

113. Corelli R. (2004). Therapeutic and toxicity potential of over- the-counter agents. In: Katzung BG editor. Basic and clinical pharmacology 9^th ed. McGraw Hill Boston, pp.1068. [Google Scholar]

114. Tamburini J, Grimaldi D, Bricaire F, Bossi P. Acute bacterial meningitis in a patient receiving ibuprofen.
J Infect
2005. Nov;51(4):336-337. 10.1016/j.jinf.2004.06.017 [PubMed] [CrossRef] [Google Scholar]

115. Palmer GM. A teenager with severe asthma exacerbation following ibuprofen.
Anaesth Intensive Care
2005. Apr;33(2):261-265. [PubMed] [Google Scholar]

116. Gabardi S, Luu L. Nonprescription analgesics and their use in solid-organ transplantation: a review.
Prog Transplant
2004. Sep;14(3):182-190. [PubMed] [Google Scholar]

117. Macesková B. Use of over-the-counter drugs containing ibuprofen in self-medication. Ceska Slov Farm
2001. May;50(3):131-134. [PubMed] [Google Scholar]

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.

Weight	Dose	Oral Drops (50 mg/1. 25 ml)	Suspension (100 mg/5 ml)	Chewables 50 mg	Chewables 100 mg	Caplets 100 mg
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 [18].

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 [22]. 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 [19] 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 [27]. 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 [10] 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 [23]. 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 [17]

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) [24]. 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 [1].

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 [25].

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 [13], 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 [21]. 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 [23].

The relative risk of edema in clinical practice among US hypertensive patients is presented in Figure 2 [28]. As you can see, ibuprofen has a clear advantage over the compared drugs.

Fig. 2. Relative risk of edema development in clinical practice [31]

In the study CLASS [14], 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 [14]

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 [11] 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 [8]) on the severity of pain in osteoarthritis (OA) showed that the best clinical effect was achieved when using ibuprofen, diclofenac and naproxen.

A review [12] 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 [6]. 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 [6].

The analgesic effect of 1200 mg ibuprofen in LBP was confirmed in one of the studies [2], 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 [7]. 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. [3]. Pediatricians consider ibuprofen the best tolerated NSAID in children . Prof. Antret-Leca [3] 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 [20].

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.

1. Belousov Yu.B., Gurevich K.G. The effect of NSAIDs and paracetamol on the cardiovascular system. Wedge. pharmacological therapy, 2002, 5, 5–7

2. Wayne A.M., Danilov A.B. The effectiveness of Solpofex in the treatment of pain in the lower back. Wedge. pharmacol. therapy, 1999, 8, 2, 47–78

3. Geppe H.A. First international conference on the use of ibuprofen in pediatric breast cancer, 2002, v10, no. 18, 831–835

4. Nasonov E.L. NSAIDs in rheumatic diseases: standard of care. RMJ, 2001, v9, no. 7–8, 265–270

5. Nasonov E.L. The use of NSAIDs: therapeutic aspects. RMJ, 2002, v10, no. 4, 206–212

6. Nasonova V.A. NSAIDs for acute pain in the lower back. Consilium medicum, 2002, vol. 4, no. 2, 102–106

7. Tabolin V.A., Osmanov I.M., Dlin V.V. The use of antipyretics in childhood. Wedge. farmak. therapy, 2002, v11, no. 5, 12–14

8. Babul N., Peloso P.M. Comparative Pharmacologic Response of analgesic agents on key outcome variables in osteoartritis. X World Congress on Pain, USA, 2002 P 211

9. Biarnason I.T. The effects on NSAIDs on the small intestine: clinical implications. New Standards in Arthritis Care, 1997, v6, N2, p2

10. Bourean F., Pelen F., e a Evaluation of Ibuprofen is Paracetamol Analgesic Activity using a Sore Throat Pain Model. Clin. Drug Invest., 1999, 17(1), 1–8

11. Brodley I.D., Brandt K.D., Kats B.P. e a Comparison of anti-inflammatory dose of ibuprofen, an analgesic dose of ibuprofen and acetomenofen in the treatment of patients with osteoartritis. N. Eugl. J. med., 1991, 325, 87–91

12. Brandt K.D. The role of Analgesics in the Management of OA Pain Amer. J. Therapeutics, 2000, v7 N2, 75–90

13. Catella–Lawson F. E a Cyclooxygenase inhibitors and the Antiplatelet effects of Aspirin. The New Eugle. J. Med., 2001, v345, 25, 1809–17

14. CLASS Advisory Committee Briefing Document FDA Arthritis Advisory Committee Meeting 2001, Maryland, Gaithersburg

15. Dalgin P. Comparison of tramadol HCL and ibuprofen for the chronic pain of OA. Arthr. Rheum., 1997, 40, 586

16. Gabriel S.E., Iaakkimainen L. e a Risk for serious gasthrointestinal complications related to use of NSAID. A meta-analysis. Am. Yntern. Med., 1991, 115: 787–796

17. Guthann S., Rodrigues G., Raiford F.S. Individual NSAIDs and other risk factors for Upper gastrointestinal bleeding and perforation. Epidemiology, 1997, 8, 18–24

18. Hillis W.S. Areas of Emerging interest in analgesics: cardiovascular complications. Am. J. Therapeutics, 2002, 9, 259–69

19. Laufer S., Tries S. Pharmacological profile of a new pyrrolizine derivative inhibiting the Enzymes COX and 5– lipoxygenase. Arzneim–Forsch Drug Res., 1994, 44: 629–636

20. Lesco S.M. The safety of acetaminophen and ibuprofen children less than two years old/ Pediatrics, 1999, 104, 4, 1–5

21. McCormack K., Twycross R. Are COX–2 selective inhibitors effective analgesics? Pain Reviews, 2001, 8, 13–26

22. Medical errors in the USA WHO pharmaceuticals Newsletter, 2000, N2, 13–14

23. Moore N. e a The pain study: paracetamol, aspirin, ibuprofen: New tolerability. Clinical Drug Invest., 1999, 18(2), 89–98

24. Page J., Henry D. Development of congestive heart failure in elderly patients: an under recognized public health problem. Arch. Int. Med., 2000, 160, 777–84

25. Pope J.E., Anderson I.I., Felson D.T.A meta-analysis of the effects of NSAIDs on blood pressure. Arch. Int. Med., 1993, 153, 477–84

26. Reid E. Tramadol in Musculoskeletal Pain–a Survey. Clin. Rheumat., 2002, v21(suppl. 1), 9–12

27. Singh G. Gasthrointestinal complications of prescription and over the counter NSAID; A view from the ARAMIS Database. Am. J. of Therapeutics, 2000, 7, 115–121

28. Zhao S. ea Comparison of edema clines associated with rofecoxib, celecoxib, and traditional NSAIDs among stable hypertensive patients in US insured population. Am. Rheum. Dis. , 2002, v 61, suppl 1, p 346

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).

Introduction

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.

Nurofen

^® 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).

Conclusions

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.