Efficacy and Safety of NSAIDs in Infants: A Comprehensive Review of the Literature of the Past 20 Years

Abstract

Non-steroidal anti-inflammatory drugs (NSAIDs) are commonly used in infants, children, and adolescents worldwide; however, despite sufficient evidence of the beneficial effects of NSAIDs in children and adolescents, there is a lack of comprehensive data in infants. The present review summarizes the current knowledge on the safety and efficacy of various NSAIDs used in infants for which data are available, and includes ibuprofen, dexibuprofen, ketoprofen, flurbiprofen, naproxen, diclofenac, ketorolac, indomethacin, niflumic acid, meloxicam, celecoxib, parecoxib, rofecoxib, acetylsalicylic acid, and nimesulide. The efficacy of NSAIDs has been documented for a variety of conditions, such as fever and pain. NSAIDs are also the main pillars of anti-inflammatory treatment, such as in pediatric inflammatory rheumatic diseases. Limited data are available on the safety of most NSAIDs in infants. Adverse drug reactions may be renal, gastrointestinal, hematological, or immunologic. Since NSAIDs are among the most frequently used drugs in the pediatric population, safety and efficacy studies can be performed as part of normal clinical routine, even in young infants. Available data sources, such as (electronic) medical records, should be used for safety and efficacy analyses. On a larger scale, existing data sources, e.g. adverse drug reaction programs/networks, spontaneous national reporting systems, and electronic medical records should be assessed with childspecific methods in order to detect safety signals pertinent to certain pediatric age groups or disease entities. To improve the safety of NSAIDs in infants, treatment needs to be initiated with the lowest age-appropriate or weight-based dose. Duration of treatment and amount of drug used should be regularly evaluated and maximum dose limits and other recommendations by the manufacturer or expert committees should be followed. Treatment for non-chronic conditions such as fever and acute (postoperative) pain should be kept as short as possible. Patients with chronic conditions should be regularly monitored for possible adverse effects of NSAIDs.

Outcomes for 41 260 pediatric surgical patients with opioid‐free anesthesia: One center's experience

“…Shortly after its release to the market, ketorolac was linked to renal injury, 58 leading some to more conservative dosing. More recent studies show that conservative dosing regimens of 0.5 mg/kg every 6 hours result in therapeutic serum levels with a low risk for toxicity 59–61 . Two systematic reviews on adenotonsillectomy with ketorolac and postoperative bleeding yielded mixed results.…”

“…More recent studies show that conservative dosing regimens of 0.5 mg/kg every 6 hours result in therapeutic serum levels with a low risk for toxicity. [59][60][61] Two systematic reviews on adenotonsillectomy with ketorolac and postoperative bleeding yielded mixed results. Lewis et al were unable to exclude a higher risk of perioperative bleeding requiring surgical intervention with non-steroidal medication (OR 1.69, 95% CI: 0.71-4.01, p = .24) and therefore could not draw any conclusions about the effect of non-steroidal medications and bleeding.…”

Pain Management in Children Admitted to the Emergency Room: A Narrative Review

“…Despite this, several studies regarding the use of naproxen, ketoprofen, ketorolac, and diclofenac, mainly in a perioperative setting, have been carried out. The results were generally good, showing a potential opioid-sparing effect with no severe adverse events [ 96 , 97 ]. Interestingly, in one study, adult patients undergoing laparoscopic cholecystectomy were randomly allocated to one of three groups on admission, depending on a prescribed post-operative analgesic regimen [ 98 ].…”

Effect of Molecular Weight on the Dissolution Profiles of PEG Solid Dispersions Containing Ketoprofen

“…Ketoprofen, also known as 2-(3-benzoylphenyl)-propionic acid, belongs to the propionic acid group of a non-steroidal anti-inflammatory drugs (NSAID) [ 1 ]. Marketed since 1973, multiple clinical uses of ketoprofen can be listed, such as osteoarthritis, rheumatoid arthritis, gout, traumatic soft tissue injuries, low back pain, post-operative pain, headache, toothache, and fever [ 2 , 3 , 4 ]. However, the S-isomer is the more potent one compared to the R-isomer, and multiple reviews state that the racemic mixture, which is cheaper to manufacture, is still more potent than several other NSAIDs [ 5 , 6 ].…”