Administration of SoluMatrix indomethacin after bunionectomy surgery was shown to have opioid-sparing effects, according to a study published in the Clinical Journal of Pain.1
Although nonsteroidal anti-inflammatory drugs such as indomethacin have proven to be effective pain relievers, they are associated with an increased risk for serious dose-related gastrointestinal and cardiovascular adverse events.2,3
The researchers conducted a phase 3 study (Clinicaltrials.gov identifier: NCT01543685) to examine the opioid-sparing effects of SoluMatrix indomethacin, for which they randomly assigned 462 patients (ages 18-65 years) with moderate to severe pain after bunionectomy surgery to 1 of the following groups: 40 mg SoluMatrix 3 times daily, 40 mg SoluMatrix twice daily, 20 mg SoluMatrix 3 times daily, celecoxib 400 mg loading dose plus 200 mg twice daily, or placebo.
“SoluMatrix® indomethacin (TIVORBEX® [indomethacin]) capsules were developed using SoluMatrix Fine Particle Technology™ to provide effective pain relief at low doses,” wrote the researchers. “SoluMatrix indomethacin 40-mg and 20-mg capsules result in rapid indomethacin absorption providing an approximately 21% and 62% lower systemic exposure, respectively, compared with 50-mg immediate-release indomethacin capsules.”
Patients were allowed to use rescue opioid medication if needed, the amount and timing of which was assessed, both for the first and second day after the initial dose of study medication.
Before surgery, patients were anesthetized with a popliteal sciatic block (40 mL of 0.5% ropivacaine). A standard Mayo block of the first metatarsal (2% lidocaine) could be added if necessary. A continuous popliteal infusion (0.5% mepivacaine; initial rate, 8 mL/hour) ensured postsurgical pain management. “Mepivacaine was specifically chosen as the local anesthetic for the infusion due to its short half-life (2-3 hours), to minimize any potential carry-over effects during the treatment period,” the researchers noted.
After regional anesthesia was discontinued in the early morning hours the day after surgery (postoperative day 1), patients were asked to rate their pain intensity on a 0- to 100-mm visual analogue scale. Those who experienced pain intensity ≥40 mm within 9 hours after discontinuing regional anesthesia were eligible for inclusion in the study.
Patients who took SoluMatrix indomethacin 3 times daily after bunionectomy surgery used less opioid rescue medication on day 1 after surgery compared with those taking placebo (20 mg, P =.003 vs 40 mg, P =.034). On day 2, fewer patients in all active treatment groups used opioid rescue medication compared with placebo (P <.001). All the active treatment groups also used significantly fewer rescue medication tablets on days 1 and 2 compared with placebo (P <.001).
The most common adverse events were nausea, postprocedural edema, and headache.
Summary and Clinical Applicability
“Our data, combined with the demonstration of efficacy for postbunionectomy pain vs placebo, suggest that SoluMatrix indomethacin, which has been approved for the management of mild-to-moderate acute pain, is a potential treatment option for appropriate conditions associated with acute pain, including patients in emergency room settings,” the researchers concluded.
Limitations & Disclosures
Inpatient clinical data were limited to a 48-hour collection period. Therefore, no inferences could be made regarding long-term improvement in pain perceived.
This study was supported by funding from Iroko Pharmaceuticals, LLC. Several of the study authors received consulting fees from a number of pharmaceutical companies.
- Gharibo C, Argoff C, Markenson JA, et al. Opioid-sparing effects of SoluMatrix Indomethacin in a phase 3 study in patients with acute postoperative pain [published online June 6, 2017]. Clin J Pain. doi:10.1097/AJP.0000000000000525
- Castellsague J, Riera-Guardia N, Calingaert B, et al. Individual NSAIDs and upper gastrointestinal complications: a systematic review and meta-analysis of observational studies (the SOS project). Drug Saf. 2012;35:1127-1146.
- Varas-Lorenzo C, Castellsague J, Stang MR, et al. The use of selective cyclooxygenase-2 inhibitors and the risk of acute myocardial infarction in Saskatchewan, Canada. Pharmacoepidemiol Drug Saf. 2009;18:1016-1025.