CL-108, a new combination of a low-dose antiemetic with hydrocodone and acetaminophen, may be a safe and effective prophylactic medication for the treatment of opioid-induced nausea and vomiting (OINV) in individuals treated for moderate to severe acute pain, according to a study published in Pain Medicine.

CL-108, which consists of rapid-release 12.5 mg promethazine combined with 7.5 mg hydrocodone (HC) and 325 mg acetaminophen (APAP), was developed to reduce moderate to severe acute pain without opioid treatment-associated nausea. A total of 466 patients with moderate to severe pain associated with surgical removal of ≥2 affected third molar teeth (with ≥1 mandibular affected) were enrolled in this multicenter study. Pain was evaluated using a categorical pain intensity scale (PI-CAT). Participants were randomly assigned to receive CL-108 (n=211), HC/APAP (n=205), or placebo (n=50). Medications were taken on an as-needed basis every 4 to 6 hours. Participants were asked to self-assess their pain using the PI-CAT at regular intervals during a 24-hour period. Prospective assessments of nausea, vomiting, and other opioid-related adverse events were also performed. Co-primary end points included incidence of OINV and changes in pain intensity during the assessment period.

An average dose of 3.6, 3.5, and 3.3 of CL-108, HC/APAP were taken, respectively.. Greater reductions in pain intensity were observed with CL-108 vs placebo during the 24-hour assessment period (P <.001). In the 6 hours after the first dose, patients receiving CL-108 vs placebo reported 21.6% greater pain reduction and a ≥30% reduction in pain intensity was reported by 51% of participants taking CL-108 vs 20% of participants administered placebo (P <.001 for both). A higher percentage of patients taking HC/APAP vs CL-108 experienced OINV (31.7% vs 11.4%, respectively; P <.001), representing a 64% relative reduction in OINV risk associated with CL-108. Participants taking CL-108 vs HC/APAP reported milder nausea during the 24-hour treatment period (P <.001).

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The sole recruitment of patients at risk for developing nausea and the fact that pain intensity was self-reported represent study limitations.

“Experts suggest that a more practical risk assessment and use of a more liberal antiemetic-based preventive strategy in clinical practice could potentially lower the incidence of nausea and vomiting,” the researchers noted.

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Zuniga JR, Papas AS, Daniels SE, et al. Prevention of opioid-induced nausea and vomiting during treatment of moderate to severe acute pain: A randomized placebo-controlled trial comparing CL-108 (hydrocodone 7.5 mg/acetaminophen 325 mg/rapid-release, low-dose promethazine 12.5 mg) with conventional hydrocodone 7.5 mg/acetaminophen 325 mg [published online January 17, 2019]. Pain Med. doi:10.1093/pm/pny294