Efficacy, safety, and pharmacokinetics of intravenous ibuprofen for fever in hospitalized pediatric patients

Clinical Research 8 min 172

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Created On: 14/02/2020

Efficacy, safety, and pharmacokinetics of intravenous ibuprofen for fever in hospitalized pediatric patients

Fever is one of the common symptom in medical evaluation in infants and children accounting for about 65% ambulatory pediatric visits.

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Key take away

A single dose of Intravenous Ibuprofen, 10 mg/kg provided a significant reduction of temperature in febrile pediatric patients compared to those who received 10 mg/kg acetaminophen at 2 h and 4 h post-treatment.

Background

Fever is one of the common symptom in medical evaluation in infants and children accounting for about 65% ambulatory pediatric visits. At a temperature higher than 38.3 °C [101Fahrenheit (F), antipyretic medication is indicated. Ibuprofen, an antipyretic and analgesic, is recommended worldwide as a first-line agent for the treatment of pain and fever in adults and children. It is available in both oral solid and liquid formulations. Oral antipyretics are commonly used in hospitals to treat pediatric patients with fever. However, patients who undergo surgery or admitted to hospitals possess difficulties in ingestion, digestion, and absorption of oral antipyretics. Therefore, rectal formulations are also available for some medications, such as acetaminophen; but this route of administration provides peak levels that may vary by as much as nine-fold and often therapeutic levels are not achieved. During the study design and upon study initiation, intravenous (IV) antipyretics, including IV acetaminophen were not approved by FDA; therefore, to design a comparator study, an oral acetaminophen comparator arm was included. Ibuprofen in IV form was approved by the FDA in 2009 for the treatment of pain and fever and it has shown to be effective in the treatment of pain and fever in adults.

Rationale behind the research:

There is lack of data in support of efficacy and safety of IV Ibuprofen in the treatment of hospi-talized paediatric patients with fever. Therefore, this study was conducted to assess the effec-tiveness and safety of single or multiple doses of IV Ibuprofen to Acetaminophen (oral or sup-pository) in pediatric patients with fever.

Objective:

To assess the effectiveness and safety of single or multiple doses of IV Ibuprofen to Acetaminophen (oral or suppository) in pediatric patients with fever and to evaluate plasma Ibuprofen concentrations.

Method

Study outcomes

Primary outcomes: The primary outcome of the study was to estimate the impact of a single dose of IV Ibuprofen compared to acetaminophen in reducing the temperature in the first 2 h after administration
Secondary outcomes: Assessment of the change in temperature after the first 30, 60, and 240 min of treatment, evaluation of the change in temperature versus time after 4 and 24 h of treatment, evaluation of the time to afebrile (temperature less than 100.4 °F [38 °C]) status, and to determine the percentage of patients becoming afebrile after 4 h

Time Points: Baseline and every 4 h until 120 h

Result

Study Outcomes

Baseline: No significant baseline differences were observed between the groups.
Primary outcomes: Treatment with IV Ibuprofen compared to acetaminophen resulted in a significantly higher reduction in temperature after 2 h and 4 h of treatment as measured by the area under the change from baseline versus time curve (AUC0–2)
Secondary outcomes: Treatment with IV ibuprofen resulted in a greater reduction in change from baseline temperature compared to treatment with acetaminophen. The difference between treatment groups was significant at 30 min after treatment and remained throughout the four-hour period following dosing (Fig.1 and 2).

There were no clinically significant differences in adverse events, including renal function, bleeding, or gastrointestinal events between the treatment groups throughout the study

Conclusion

Fever is the earliest and most visible sign of a disease process that can lead to an increased metabolic rate and other harmful effects. The treatment of fever is often done by oral antipyretics including acetaminophen and ibuprofen. But the oral route of administration often accompanies some typical problems in some cases of surgeries and hospitalized patients. Therefore, the IV route of antipyretics was studied in the research.

This open-label study evaluated the safety and efficacy levels of IV ibuprofen as compared to acetaminophen in pediatric hospitalized patients. The study demonstrated that IV ibuprofen was more effective than acetaminophen in reducing temperature after a single dose of either medication. No significant adverse effects were seen on treatment for 120 h after dosing or 1 week, thereby, confirming the safety levels of IV ibuprofen. The pharmacokinetic profile of ibuprofen was also evaluated which shows that clearance (C) and volume of distribution (Vd) of the drug increases with age. These findings were also consistent with another meta-analysis that concluded that ibuprofen was a more effective antipyretic in fifteen studies and no significant difference in an additional fifteen studies. Safety findings in these meta-analyses also remained consistent with the safety profiles established in previous studies in the literature.

Limitations

Selection and use of oral or rectal acetaminophen as the comparator drug was not optimal as it is not FDA approved
The strength of children under the age of 6 months was small, and the duration of exposure was also short

Clinical take-away

A single 10 mg/kg dose of IV ibuprofen shows a significant reduction of temperature in febrile pediatric patients as compared to those that receiving 10 mg/kg acetaminophen.

Source:

Samia N. Khalil et al. BMC Pediatrics. 2017; 17:42

Link:

https://bmcpediatr.biomedcentral.com/articles/10.1186/s12887-017-0795-y

Article:

A multicenter, randomized, open-label, active-comparator trial to determine the efficacy, safety, and pharmacokinetics of intravenous ibuprofen for treatment of fever in hospitalized pediatric patients

Authors:

Samia L Khalil et al.

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