Intravenous versus Oral Acetaminophen for Pain: Systematic Review of Current Evidence to Support Clinical Decision-Making

Abstract

Background: Intravenous (IV) acetaminophen is increasingly used around the world for pain control for a variety of indications. However, it is unclear whether IV administration offers advantages over oral administration. Objective: To identify, summarize, and critically evaluate the literature comparing analgesic efficacy, safety, and pharmacokinetics for IV and oral dosage forms of acetaminophen. Data Sources: A literature search of the PubMed, Embase, and International Pharmaceutical Abstracts databases was supplemented with keyword searches of Science Direct, Wiley Library Online, and Springer Link databases for the period 1948 to November 2014. The reference lists of identified studies were searched manually. Study Selection and Data Extraction: Randomized controlled trials comparing IV and oral dosage forms of acetaminophen were included if they assessed an efficacy, safety, or pharmacokinetic outcome. For each study, 2 investigators independently extracted data (study design, population, interventions, follow-up, efficacy outcomes, safety outcomes, pharmacokinetic outcomes, and any other pertinent information) and completed risk-of-bias assessments. Data Synthesis: Six randomized clinical trials were included. Three of the studies reported outcomes pertaining to efficacy, 4 to safety, and 4 to pharmacokinetics. No clinically significant differences in efficacy were found between the 2 dosage forms. Safety outcomes were not reported consistently enough to allow adequate assessment. No evidence was found to suggest that increased bioavailability of the IV formulation enhances efficacy outcomes. For studies reporting clinical outcomes, the results of risk-of-bias assessments were largely unclear. Conclusions: For patients who can take an oral dosage form, no clear indication exists for preferential prescribing of IV acetaminophen. Decision-making must take into account the known adverse effects of each dosage form and other considerations such as convenience and cost. Future studies should assess multiple-dose regimens over longer periods for patients with common pain indications such as cancer, trauma, and surgery.

Intravenous versus oral paracetamol for acute pain in adults in the emergency department setting: a prospective, double-blind, double-dummy, randomised controlled trial

“…Although the intravenous preparation is often anecdotally regarded as superior, our results demonstrating no difference are congruent with a recent systematic review comparing oral and intravenous paracetamol in a variety of settings 9. These authors included six randomised trials in the review, only three of which assessed efficacy outcomes and all were in the postoperative setting.…”

“…Analgesics such as oral paracetamol, oxycodone and non-steroidal anti-inflammatory drugs are used as adjuncts or for less severe pain presentations. An intravenous preparation of paracetamol has been available for 10–15 years, although availability in EDs is often restricted 9. In the ED setting, intravenous paracetamol has been compared with intravenous morphine and other active comparators, with conflicting results 10–13.…”

Comparison of Intravenous and Rectal Paracetamol for Pain Relief in Children Undergoing Tonsillectomy Surgery

“…Thus, even though intravenous paracetamol seems better in terms of pharmacokinetics profile studies have shown that differences in plasma exposure between routes of administration may not necessarily result in differences in clinical outcomes. 16 Limitation in our study was plasma levels of the drug were not measured at corresponding pain score level. We used only single dose of rectal paracetamol for post-operative pain, as tonsillectomy results only in mild-to-moderate pain relief and is unnecessary leading to physical discomfort.…”

Perioperative pain management strategies among women having reproductive surgeries

“…The addition of acetaminophen to opioid-based postoperative pain management results in a reduction in opioid consumption of 20–40% over the first 24 hours after various major and minor surgical procedures (20)(21,22) (12,23). Whether efficacy of acetaminophen differs by route of administration is controversial; although some studies suggest benefit to IV acetaminophen (24), the majority of studies have not shown any significant benefit to the administration of IV over oral acetaminophen in decreasing opioid use (25–27). There are also currently no high quality data specifically demonstrating the impact of postoperative acetaminophen on opioid consumption after reproductive/gynecologic surgery, but it is likely that the benefits observed for other surgeries will translate.…”