The International Association for the Study of Pain (IASP) defines pain as: “an unpleasant sensory and emotional experience associated with actual or potential tissue damage, or described in terms of such damage.”¹ Adequate postoperative pain control is not only of utmost importance to patients but also to physicians as well, because of the correlation to worse outcomes impacting patients’ health and quality of life, and in severe cases of poorly treated postoperative pain, degradation to severe chronic pain syndromes. Some adverse effects (AEs) that have been associated with inadequate pain control include delirium, chronic pain, and impairments in social and physical function.²,³

The current management of postoperative pain and recovery from painful procedures is considered unsatisfactory by many and continues to be an important clinical problem and an opportunity for improvement. Opioids have been a staple in the management of postoperative care and recovery; however, they are frequently associated with AEs such as nausea, vomiting, constipation, ileus, pruritus, and respiratory depression along with dependence, misuse, and over-reliance.⁴ These constraints have driven the search for an adequate method of pain control with an emphasis on nonopioid analgesics. A valuable method is intravenous lidocaine; a Cochrane retrospective review reported low to moderate evidence that this intervention impacted pain scores when compared to placebo.⁵ Another intervention is a multimodal technique for pain management. This approach involves the administration of two or more analgesics with different mechanisms of action via the same or different routes to optimize effectiveness while minimizing AEs. The American Society of Anesthesiologists Task Force recommends a regimen that includes acetaminophen, nonselective non-steroidal anti-inflammatory drug (NSAID), or cyclooxygenase-2 (COX-2) selective NSAIDs unless contraindicated.⁶

Meloxicam is an example of a long-acting preferential COX-2 inhibitor nonsteroidal NSAID with analgesic, antipyretic, and anti-inflammatory activities through reduction of prostaglandin biosynthesis. The use of oral meloxicam is limited by its slow onset of action due to its poor aqueous solubility. The peak plasma concentration is not reached until 9-11 hours after oral administration of a 30-mg dose and is thus not an ideal treatment for acute pain; however, intravenous meloxicam in its nanocrystal formulation is currently available due to its shorter time to peak plasma concentration.⁴

Related to the role of COX-1 constitutive enzyme activity facilitating platelet aggregation, vasoconstriction, and gastrointestinal and renal homeostasis, the safety concerns associated with intravenous meloxicam are similar to those of any NSAID or Coxib, including oral
meloxicam and incorporating concerns of bleeding, cardiovascular, and renal events.⁷,⁸ In one study, pooled data from a phase II/phase III clinical program exhibited low incidence of treatment-emergent adverse events (TEAEs). The intravenous meloxicam was reportedly tolerated well in subjects with moderate-to-severe postoperative pain, with most commonly reported TEAEs being nausea, vomiting, and headache. In this study, intravenous meloxicam also reduced need for postoperative opioid use when monitored, suggesting that IV meloxicam may represent a beneficial and suitable replacement of current postoperative pain management.⁸ This review, therefore, aims to delineate the medical research surrounding pain management and describe the safety and tolerability of intravenous meloxicam in the treatment of acute pain.

The safety of meloxicam IV has been evaluated across a wide range of both postoperative and perioperative pain management strategies. The full range of the pain spectrum is explored through numerous major surgeries, including, but not limited to, elective abdominal hysterectomy, bunionectomy, total knee arthroplasty (TKA), and spinal surgery. Meloxicam IV is a more selective COX-2 inhibitor, but like all NSAIDs, it carries the same black box warnings analogous to other NSAIDs, such as gastrointestinal bleeding, hepatorenal events, and thrombotic injury.⁷ These side effects were specifically explored in addition to others through various safety measures like vital signs, physical examination, laboratory values (hemoglobin and hematocrit), 12-lead EKGs, accessory medications (ie, multimodal analgesic protocol or standard of care), and supplemental medications (rescue opioid consumption) in both Phase II and Phase III trials.⁸ In a Phase II blinded, single-dose study exploring meloxicam IV at doses 5-60 mg after elective abdominal hysterectomy, only mild to moderate adverse events were reports and no serious adverse events were related to the study medication. Adverse events of special interest, specifically hepatic and anemic events, did not increase in incidence with increasing dosage.¹⁹ In a pooled analysis comparing 1426 adult subjects from seven postoperative studies, there was a higher association of side effects reported from the placebo groups vs meloxicam IV groups.⁸ Overall safety evaluations for meloxicam IV shows a lower incidence of adverse events compared with placebo and known adverse events with opioid use.²⁰

With the formulation of meloxicam for IV use, utilization in the acute pain setting is now possible due to its’ faster onset of action than its’ oral counterpart.⁹ IV meloxicam shows a rapid onset of analgesia, which is evident as early as 15-30 minutes after administration of a single dose of meloxicam IV 30 mg.⁴ The analgesic effect is also sustained over its 24-hour dosing interval.⁴ IV meloxicam has demonstrated analgesic efficacy in a variety of surgical settings, including orthopedic, abdominal, and colorectal surgeries.⁷ In comparison to placebo, all meloxicam IV doses showed statistically significant postoperative pain intensity relative to a placebo.¹⁹ Meloxicam was then compared to one of the common opioid analgesics, morphine, and was showed to produce statistically significant reductions in pain intensity at doses of meloxicam IV 60, 30, and 15 mg.¹⁹ In trials where opioid use was monitored, meloxicam reduced postoperative rescue opioid, which suggest that IV meloxicam may represent a useful alternative to current postoperative management options.⁸ With IV meloxicam, overall opioid consumption was significantly decreased postoperatively and was associated with quicker time for first dose to first ambulation and a first dose to discharge when compared to placebo.²⁰ Additionally, recent evidence suggests that IV meloxicam has also shown the ability to reduce postoperative pain if it is administered preoperatively in patients.⁷