IV Ibuprofen for Analgesia

Ibuprofen is a non-steroidal anti-inflammatory drug (NSAID). Although most familiar in its oral form, ibuprofen can also be administered as an intravenous (IV) medication for more rapid effects. IV ibuprofen is approved in the US as an analgesic (pain reliever) and antipyretic (fever reducer) (Southworth and Sellers, 2020).

Ibuprofen’s main action within the body is the inhibition of prostaglandin synthesis. Prostaglandins are pro-inflammatory chemical signals that increase blood vessel permeability, recruit immune cells and promote edema (fluid accumulation). They also make pain receptors more sensitive to stimulation (Mazaleuskaya et al, 2015). Additionally, a prostaglandin synthesized in the hypothalamus (a region of the brain that works to maintain body homeostasis), PGE2, is a mediator of fever (Mazaleuskaya et al, 2015). Ibuprofen blocks prostaglandin synthesis by inhibiting the cyclooxygenas enzymes COX1 and COX2; it thus has anti-inflammatory, analgesic and antipyretic action (Mazaleuskaya et al, 2015). Additional pathways through which ibuprofen may act are still being explored. One interesting theory is that ibuprofen may be able to activate the brain’s cannabinoid receptors, which would decrease the perception of pain (Mazaleuskaya et al, 2015).

IV ibuprofen is often used with opioid medication as a multi-modal treatment plan for pain after surgery. Opioids are very strong pain relievers; however, they have a high risk of dependence and misuse, as well as other adverse effects such as medication interactions (Southworth and Sellers, 2020). They also do not address any underlying cause of pain, whereas NSAIDs are able to decrease inflammation (Southworth and Sellers, 2020). IV NSAIDs ketorolac and diclofenac are also approved in the US for pain relief but ibuprofen is the only IV NSAID currently approved for both pain relief and fever reduction (Southworth and Sellers, 2020).

IV ibuprofen has been shown to reduce the quantity of opioids required by a patient when compared to a placebo and other drugs like acetaminophen. Its use decreases patients’ subjective levels of pain as well as measurable levels of stress hormones in the postoperative period (Southworth and Sellers, 2020). Studies report that ibuprofen is well tolerated by patients and that there is no statistically significant increase in severe adverse events when compared with a placebo. It is also well-tolerated as a rapid infusion, given over 5-10 minutes (Southworth and Sellers, 2020).

Although generally considered safe, NSAIDs, including ibuprofen, have some side effects related to the inhibition of COX1 and COX2, which contribute to other processes throughout the body besides prostaglandin synthesis. Inhibition of COX1 is related to gastrointestinal (GI) symptoms and long-term inhibition of COX2 may have cardiovascular risks (Southworth et al, 2015). Ibuprofen is not selective for either COX1 or COX2, as compared with ketorolac which is more selective for COX1 and diclofenac which is more selective for COX2. Ibuprofen thus may have a more favorable risk profile in terms of GI and cardiovascular complications (Southworth et al, 2015).

IV ibuprofen may also have impacts on the effectiveness of other medications that patients take concurrently. Low dose aspirin, used for antiplatelet therapy to prevent stroke and heart attack, may be less effective since ibuprofen can block platelet COX1. This can also increase bleeding risk if patients are being given other anticoagulants or selective serotonin reuptake inhibitors (SSRI’s) (Mazaleuskaya et al, 2015). Ibuprofen may also decrease effectiveness of antihypertensive drugs, since the inhibition of prostaglandins in the kidney tubules causes the blood vessels to constrict, a mechanism of hypertension (Mazaleuskaya et al, 2015). Finally, patients taking lithium need to have their serum lithium levels monitored, since NSAIDS reduce lithium clearance from the body and can lead to toxic levels in the blood (Mazaleuskaya et al, 2015).


Mazaleuskaya LL, Theken KN, Gong L, et al. PharmGKB summary: ibuprofen pathways. Pharmacogenet Genomics. 2015;25(2):96-106. doi:10.1097/FPC.0000000000000113 

Southworth SR, Sellers JA. Narrative Summary of Recently Published Literature on Intravenous Ibuprofen. Clin Ther. 2020;42(7):1210-1221. doi:10.1016/j.clinthera.2020.05.004 

Southworth SR, Woodward EJ, Peng A, Rock AD. An integrated safety analysis of intravenous ibuprofen (Caldolor(®)) in adults. J Pain Res. 2015;8:753-765. Published 2015 Oct 23. doi:10.2147/JPR.S93547