Opioid-induced Nausea And Vomiting Research Articles

Naldemedine for Opioid-Induced Constipation in Patients With Cancer: A Multicenter, Double-Blind, Randomized, Placebo-Controlled Trial.

Opioid-induced constipation is the most frequent and non-self-limiting adverse effect of opioid analgesia, reducing adherence and interfering with pain relief. This clinical trial aimed to clarify the preventive effect of naldemedine versus placebo for constipation in patients with cancer starting regularly dosed strong opioids therapy. This multicenter, double-blinded, randomized, placebo-controlled, confirmatory trial was conducted between July 2021 and May 2023 at four academic hospitals in Japan (ClinicalTrials.gov identifier: jRCTs031200397). Patients with cancer starting a first-time regularly dosed strong opioid for cancer pain and age 20+ years were included. Eligible patients were randomly assigned to the naldemedine (Symproic 0.2 mg) or placebo group in a 1:1 ratio for 14 days with protocol treatment. The primary end point was the proportion of patients with a Bowel Function Index (BFI) of <28.8 on day 14. The secondary end points included frequency of spontaneous bowel movements (SBM), quality of life (QOL), and frequency of opioid-induced nausea and vomiting (OINV). Of the 103 patients assessed for eligibility, 99 received either naldemedine (n = 49) or placebo (n = 50). A BFI of <28.8 on day 14 was significantly more likely to occur in the naldemedine group (64.6%; 95% CI, 51.1 to 78.1) versus placebo (17.0%; 95% CI, 6.3 to 27.8), and the difference between groups was 47.6% (95% CI, 30.3 to 64.8; P < .0001). The frequency of SBM, QOL, and the severity of OINV were nominally significant in the naldemedine group than in the control group. Naldemedine prevented constipation and improved constipation-related QOL, with possible preventive effect on OINV in patients with cancer starting regularly dosed opioids therapy.

Pharmacological treatment of cancer pain and opioid induced nausea and vomiting: online survey and comparison with current guidelines

PurposeWe assumed that in Palliative Care, even in common clinical situations, the choice of drugs differs substantially between physicians. Therefore, we assessed the practice of pharmaceutical treatment choices of physicians for cancer pain and opioid-induced nausea and vomiting (OINV) and the rationale for their choices.MethodsAn online survey was conducted with physicians covering the following domains: i) Cancer pain therapy: non-opioids in addition to opioids: choice of drug ii) prevention of OINV: choice of drug and mode of application. Current guidelines concerning cancer pain therapy and prevention of OINV were compared.ResultsTwo-hundred-forty European physicians responded to our survey. i) Use of non-opioids in addition to opioids for the treatment of cancer pain: Only 1.3% (n = 3) of respondents never used an additional non-opioid. Others mostly used: dipyrone/metamizole (49.2%, n = 118), paracetamol/acetaminophen (34.2%, n = 82), ibuprofen / other NSAIDs (11.3%, n = 27), specific Cox2-inhibitors (2.1%, n = 5), Aspirin (0.4%, n = 1), no answer (2.9%, n = 7). ii) Antiemetics to prevent OINV: The drugs of choice were metoclopramide (58.3%, n = 140), haloperidol (26.3%, n = 63), 5-HT3 antagonists (9.6%, n = 23), antihistamines (1.3%, n = 3) and other (2.9%, n = 7); no answer (1.7%, n = 4). Most respondents prescribed the substances on-demand (59.6%, n = 143) while others (36.3%, n = 87) provided them as around the clock medication. Over both domains, most physicians answered that their choices were not based on solid evidence from randomized controlled trials (RCTs). Guidelines were inconsistent regarding if and what non-opioid to use for cancer pain and recommend anti-dopaminergic drugs for prevention or treatment of OINV.ConclusionsPhysician’s practice in palliative care for the treatment of cancer pain and OINV differed substantially. Respondents expressed the lack of high-quality evidence- based information from RCTs. We call for evidence from methodologically high-quality RCTs to be available to inform physicians about the benefits and harms of pharmacological treatments for common symptoms in palliative care.

Investigating the efficacy and safety of olanzapine prophylaxis for opioid-induced nausea and vomiting (JORTC-PAL20): a study protocol for an open-label, single-arm exploratory study

IntroductionIn opioid therapy for cancer pain, opioid-induced nausea and vomiting (OINV) occur in 20%–40% of patients during initial opioid treatment or increasing opioid doses. OINV result in failure to achieve...

Exploratory study investigating the efficacy and safety of olanzapine prophylaxis for opioid-induced nausea and vomiting (JORTC-PAL20).

TPS12151 Background: In opioid therapy for cancer pain, it is essential to manage opioid-related adverse effects. Opioid-induced nausea and vomiting (OINV) is common, occurring in 20–40% of patients during initial opioid treatment or after opioid doses are increased. Tolerance to OINV develops within a few days to a week. In patients with cancer, OINV results in decreased quality of life as well as failure to relieve pain due to poor opioid adherence, thus increasing the psychological barriers to opioid use. Therefore, antiemetics are used for OINV prophylaxis, but their efficacy and safety in this context have not yet been fully elucidated. Olanzapine is a promising antiemetic for prophylaxis against nausea and vomiting induced by highly emetogenic chemotherapy, and it is less likely to cause extrapyramidal symptoms than haloperidol and prochlorperazine. We are conducting this exploratory study to evaluate the efficacy and safety of olanzapine prophylaxis against OINV. Methods: This single-arm, single-center exploratory study will evaluate the prophylactic antiemetic efficacy and safety of olanzapine (5 mg PO once a day for 5 days) in patients with cancer pain reserving initial regular opioid therapy. Thirty-five patients will be enrolled. This study was designed to provide preliminary efficacy data, with a primary objective of assessing the proportion of patients who achieved complete control (CC) of OINV during 120 hours of opioid treatment. CC was defined as the absence of emetic episodes, the lack of a need for rescue medication to treat nausea, and minimal or no nausea (3 or less on an 11-point categorical scale). Secondary endpoints include the following: the complete response (CR) rate, defined as the percentage of patients with no emetic episodes and no rescue medication use; the total control (TC) rate, defined as the percentage of patients with no emetic episodes, no rescue medication use, and no nausea during the 120 hours of opioid treatment; the time from opioid initiation to the first emetic episode; the time from opioid initiation to the first administration of a rescue antiemetic; the time to treatment failure, defined as the time from opioid initiation to the first emetic episode or to the administration of a rescue antiemetic; the number of emetic episodes; the levels of nausea, anorexia, sleepiness, pain, and fatigue, all determined using a numerical rating scale (0–10); the impact of antiemetic therapy on daily life severity and patient satisfaction, determined using a 7-grade categorical scale; and adverse events graded by PRO-CTCAE ver.1.0 and CTCAE ver. 5.0. The study is currently open, and 25 patients have been enrolled at time of abstract submission. Clinical trial information: jRCTs031220008 .

Postoperative Nausea and Vomiting in Pediatric Patients.

Postoperative nausea and vomiting (PONV), postoperative vomiting (POV), post-discharge nausea and vomiting (PDNV), and opioid-induced nausea and vomiting (OINV) continue to be causes of pediatric morbidity, delay in discharge, and unplanned hospital admission. Research on the pathophysiology, risk assessment, and therapy for PDNV, OINV and pain therapy options in children has received increased attention. Multimodal pain management with the use of perioperative regional and opioid-sparing analgesia has helped decrease nausea and vomiting. Two common emetogenic surgical procedures in children are adenotonsillectomy and strabismus repair. Although PONV risk factors differ between adults and children, the approach to decrease baseline risk is similar. As PONV and POV are frequent in children, antiemetic prophylaxis should be considered for those at risk. A multimodal approach for antiemetic and pain therapy involves preoperative risk evaluation and stratification, antiemetic prophylaxis, and pain management with opioid-sparing medications and regional anesthesia. Useful antiemetics include dexamethasone and serotonin 5-hydroxytryptamine-3 (5-HT3) receptor antagonists such as ondansetron. Multimodal combination prophylactic therapy using two or three antiemetics from different drug classes and propofol total intravenous anesthesia should be considered for children at high PONV risk. "Enhanced recovery after surgery" protocols include a multimodal approach with preoperative preparation, adequate intravenous fluid hydration, opioid-sparing analgesia, and prophylactic antiemetics. PONV guidelines and management algorithms help provide effective postoperative care for pediatric patients.

Preventive effects of naldemedine, peripherally acting μ-opioid receptor antagonist, on morphine-induced nausea and vomiting in ferrets

AimsNaldemedine is a peripherally acting μ-opioid receptor antagonists (PAMORAs) indicated for the treatment of opioid-induced constipation (OIC). We investigated the preventive effect of naldemedine on morphine-induced nausea and vomiting in ferrets and conducted a pharmacokinetic/pharmacodynamic (PK/PD) analysis. Main methodsThe antiemetic effect of naldemedine was evaluated as the frequency and time of retching (rhythmic abdominal contractile motion) and vomiting (throwing up vomit or similar reactions) caused by morphine in ferrets. After a single oral administration of naldemedine to ferrets, the plasma concentrations of naldemedine and morphine were measured by liquid chromatography–tandem mass spectrometry. Key findingsNaldemedine showed a potent and dose-dependent anti-emetic effects against morphine-induced emetic responses, for up to 6 h. The dose of naldemedine that produced half the maximal effect (ED50) value for anti-emetic effect of naldemedine in the morphine-treated ferrets was 0.033 mg/kg. The PK/PD analysis revealed that the antiemetic effect was related to the plasma naldemedine concentration, with a half maximal effective concentration that produces half the maximal effect (EC50) of 3.51 ng/mL. The plasma concentration producing an antiemetic effect was almost 200-fold lower than that inducing an anti-analgesic effect in rats. SignificanceNaldemedine showed potent inhibition of morphine-induced vomiting for up to 6 h after dosing. These data suggest that naldemedine possesses antiemetic properties and could be effective against opioid-induced nausea and vomiting (OINV).

A preliminary study of the effect of naldemedine tosylate on opioid-induced nausea and vomiting.

Opioid-induced nausea and vomiting (OINV) is induced by opioid receptor stimulation of chemoreceptor trigger zones and vestibular apparatus by opioids. Naldemedine tosylate (NALD) is a peripherally acting non-selective opioid receptor antagonist, used for opioid-induced constipation (OIC). However, the effect of NALD on OINV had not yet been investigated. In this retrospective study, we investigated the secondary effects of NALD on OINV. Patients who received sustained-release oral morphine or oxycodone preparation were enrolled in the study. Patients who used NALD (0.2mg) within 2days of opioid initiation were included in the analysis. The use of rescue antiemetics within 7days from opioid initiation was defined as OINV expression. Patients who received antiemetics before opioid initiation or those who received chemotherapy around 4days from opioid initiation were excluded from the analysis. The incidence of OINV was compared between patients who used and did not use NALD. In total, 982 patients were included in the study. Among them, 89 patients who received NALD and 614 patients who did not receive NALD were analyzed. The incidence of OINV in patients who used NALD was significantly lower than that of patients who did not use NALD (36.0% vs. 47.2%, p = 0.046). For patients with constipation, using NALD at an early stage of opioid initiation might have secondary benefits, such as relief from OINV, besides improvement of OIC. To confirm the effectiveness of NALD for OINV, the symptom grade and intensity during concomitant use of NALD should be observed in a future study.

(405) What is the Effect on Acute Pain when a Patient's Sleep is Disturbed by Opioid-Induced Nausea and Vomiting (OINV)?

Sleep is an important factor in postoperative recovery, especially for patients experiencing moderate-to-severe acute pain. In contrast, sleep disturbance may have deleterious effects on patient recovery, including increased pain and length-of-stay.1 However, it is unclear if nausea and vomiting interfere with sleep and with what analgesic consequence. Is there evidence of OINV-related sleep disturbance and its effect on acute pain in a randomized controlled trial (RCT)? In a previous RCT,2 it was noted that some patients using hydrocodone 7.5mg/acetaminophen 325mg (HC/APAP) awoke with nausea, retching and/or vomiting, requesting antiemetic therapy. In the current RCT,3 therefore, patients were observed while asleep so that emetic symptoms and pain could be documented if they awoke. Following first metatarsal bunionectomy, patients with moderate or severe pain on a categorical pain intensity scale and a 0-to-10 pain intensity scale (PI-NRS) were randomly assigned to take HC/APAP or placebo under double-blind conditions every 4-6 hours. Patients were monitored regularly as in-patients over 48 hours, including, in particular, during periods of sleeping between 9 pm and 7 am: if patients awoke from sleep, episodes of retching, vomiting and other adverse events were documented if present and patients rated nausea intensity on a 0-to-10 Likert scale and pain intensity on the PI-NRS. Of 113 HC/APAP-treated patients who developed OINV over the 48-hour treatment period, 29 patients (26%) awoke from sleep complaining of moderate-to-severe nausea, retching or vomiting, requesting an antiemetic. Compared to the summed pain intensity differences (SPID48) of these patients with OINV-related sleep disturbance (63.2), SPID48 values were 108% higher for the 137 HC/APAP-treated patients without OINV-related sleep disturbance (131.1, p<0.001). We conclude that OINV causes sleep disturbance, interfering with pain reduction and contributing to less effective pain relief. Future research should examine the effect of sleep disturbance of any etiology on pain control. Sleep is an important factor in postoperative recovery, especially for patients experiencing moderate-to-severe acute pain. In contrast, sleep disturbance may have deleterious effects on patient recovery, including increased pain and length-of-stay.1 However, it is unclear if nausea and vomiting interfere with sleep and with what analgesic consequence. Is there evidence of OINV-related sleep disturbance and its effect on acute pain in a randomized controlled trial (RCT)? In a previous RCT,2 it was noted that some patients using hydrocodone 7.5mg/acetaminophen 325mg (HC/APAP) awoke with nausea, retching and/or vomiting, requesting antiemetic therapy. In the current RCT,3 therefore, patients were observed while asleep so that emetic symptoms and pain could be documented if they awoke. Following first metatarsal bunionectomy, patients with moderate or severe pain on a categorical pain intensity scale and a 0-to-10 pain intensity scale (PI-NRS) were randomly assigned to take HC/APAP or placebo under double-blind conditions every 4-6 hours. Patients were monitored regularly as in-patients over 48 hours, including, in particular, during periods of sleeping between 9 pm and 7 am: if patients awoke from sleep, episodes of retching, vomiting and other adverse events were documented if present and patients rated nausea intensity on a 0-to-10 Likert scale and pain intensity on the PI-NRS. Of 113 HC/APAP-treated patients who developed OINV over the 48-hour treatment period, 29 patients (26%) awoke from sleep complaining of moderate-to-severe nausea, retching or vomiting, requesting an antiemetic. Compared to the summed pain intensity differences (SPID48) of these patients with OINV-related sleep disturbance (63.2), SPID48 values were 108% higher for the 137 HC/APAP-treated patients without OINV-related sleep disturbance (131.1, p<0.001). We conclude that OINV causes sleep disturbance, interfering with pain reduction and contributing to less effective pain relief. Future research should examine the effect of sleep disturbance of any etiology on pain control.

Prophylactic use of antiemetics for prevention of opioid-induced nausea and vomiting: a survey about Italian physicians' practice.

Antiemetics are being used both for the treatment and prophylaxis of opioid-induced nausea and vomiting (OINV) in clinical practice, despite the lack of evidence for the prophylactic benefit. Studies among Japanese physicians demonstrated over 80% prescribe antiemetics, with neuroleptic antipsychotics as the most commonly prescribed drugs. Our objective was to elucidate the current scenario of the prophylactic use of antiemetics for OINV among Italian physicians. We conducted a web-based cross-sectional national survey. All the invited participants received an e-mail with an 11-item electronic questionnaire accessible through a direct link. Anonymity was guaranteed. According to the exploratory intent of the survey, we did not predefine any formal statistical hypothesis. Associations between variables were tested by the Pearson chi-square or the Fisher exact test. From January to March 2017, 112 completed the electronic questionnaire (112/256, overall response rate, 43.7%). Nearly half of the participants were oncologists (54; 48.2%). Sixty-one (54.4%) physicians worked in palliative care units. About 45% of the interviewed prescribed prophylactic antiemetics at the beginning of opioid prescription. The most commonly chosen drugs for this purpose were prokinetics such as metoclopramide and domperidone (84%), followed by 5-HT3 antagonists (8%), neuroleptic antipsychotics (6%), and corticosteroids (2%). Ninety-one physicians (81%) declared to prescribe antiemetics at the occurrence of OINV, mainly prokinetics (N = 70; 77%). Italian physicians do not commonly prescribe prophylactic antiemetics for OINV. Unlike previously reported data, dopamine antagonists resulted the most commonly prescribed drugs. Prospective clinical trials are necessary to evaluate the real efficacy of this practice.

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.

To evaluate the prevention of opioid-induced nausea and vomiting (OINV) and the relief of moderate to severe acute pain by CL-108, a novel drug combining a low-dose antiemetic (rapid-release promethazine 12.5 mg) with hydrocodone 7.5 mg/acetaminophen 325 mg (HC/APAP) was used. This was a multicenter, randomized, double-blind, placebo- and active-controlled multidose study. After surgical extraction of two or more impacted third molar teeth (including at least one mandibular impaction), 466 patients with moderate to severe pain (measured on a categorical pain intensity scale [PI-CAT]) were randomized to CL-108, HC/APAP, or placebo. Over the next 24 hours, patients used the PI-CAT to assess pain at regular intervals whereas nausea, vomiting, and other opioid-related side effects were also assessed prospectively. Study medications were taken every four to six hours as needed; supplemental rescue analgesic and antiemetic medications were permitted. Co-primary end points were the incidence of OINV and the time-weighted sum of pain intensity differences over 24 hours (SPID24). Relative to HC/APAP treatment alone, CL-108 treatment reduced OINV by 64% (P < 0.001). Treatment with CL-108 significantly reduced pain intensity compared with placebo (SPID24 = 16.2 vs 3.5, P < 0.001). There were no unexpected or serious adverse events. CL-108 is a safe and effective combination analgesic/antiemetic for the prevention of OINV during treatment of moderate to severe acute pain.

Continuous administration of ramosetron with patient-controlled analgesia after laparoscopic distal gastrectomy does not delay postoperative bowel function recovery: A prospective, randomized, double-blinded study.

Background:Currently, 5-hydroxytryptamine type 3 (5-HT3) receptor antagonists are indicated to slow gastrointestinal motility in the diarrhea-predominant subtype of irritable bowel syndrome. They are commonly used to prevent or treat postoperative nausea and vomiting (PONV) and opioid-induced nausea and vomiting (OINV). We conducted a prospective, randomized, double-blinded study to investigate whether the continuous administration of ramosetron, a selective 5-HT3 receptor antagonist, for preventing PONV and/or OINV after laparoscopic distal gastrectomy (LDG) might influence bowel function recovery.Methods:Patients scheduled to undergo LDG were randomly assigned to 1 of 3 treatment regimens: no prophylactic ramosetron (Group C); ramosetron 0.6 mg added to 2-day intravenous patient-controlled analgesia (IV-PCA) (Group R0.6); and ramosetron 1.2 mg added to 2-day IV-PCA (Group R1.2). Postoperative recovery profiles of bowel function, incidence of postoperative nausea/vomiting and pain, and perioperative data that affected bowel function recovery were evaluated.Results:Seventy-three patients completed the study protocol. Parameters associated with postoperative recovery of bowel function, such as time to first flatus, time to first bowel movement, time to first defecation, and time to commencement of soft diet, were not significantly different between the 3 groups. The incidence of nausea 2 to 24 hours after surgery was significantly lower in Group R0.6 (20.0%) and Group R1.2 (12.5%) than in Group C (45.8%) (P < .022). The ratio of complete response 2 to 24 hours after surgery was significantly higher in Group R0.6 (80.0%) and Group R1.2 (87.5%) than in Group C (54.2%) (P < .022). The incidence of retching 24 to 48 hours after surgery was significantly lower in Group R0.6 (0.0%) and Group R1.2 (4.2%) than in Group C (16.7%) (P < .043).Conclusion:Continuous administration of ramosetron with patient-controlled analgesia to prevent PONV and OINV after LDG did not delay postoperative bowel function recovery.

(276) - Does opioid-induced nausea and vomiting (OINV) interfere with pain control?

Nausea and vomiting are distressing symptoms. Among other emetogenic medications, opioids are well-known pharmacologic causes of nausea and vomiting (i.e., OINV). Common sense suggests that OINV would interfere with pain control. Does it? What effect does OINV have on pain relief when patients are treated with a standard opioid-containing medication such as hydrocodone 7.5 mg/acetaminophen 325 mg (HC/APAP)? We had the opportunity to address this question in a randomized, double-blind, placebo-controlled trial by comparing pain reduction in patients treated with HC/APAP who developed OINV to pain reduction in patients treated with HC/APAP who did not. After unilateral first metatarsal bunionectomy with osteotomy and internal fixation without collateral procedures, adult patients were randomized under double-blind conditions to HC/APAP or placebo when they reported moderate-to-severe pain on a 0–10 numerical pain intensity rating scale. At specified intervals over the initial 48-hour post-op treatment observation period they rated the intensity of pain and nausea and documented episodes of vomiting and uses of antiemetics while taking study medication every 4–6 hours. Summed pain intensity differences were calculated over 48 hours (SPID48), in particular, to determine pain reduction in HC/APAP-treated patients with and without OINV. There were no significant clinical or demographic differences at baseline among 300 patients who were randomized to HC/APAP or placebo. OINV occurred in 45% of HC/APAP-treated patients. Mean SPID48 scores significantly differentiated HC/APAP treatment from placebo for all patients, for patients with OINV, and for patients without OINV. Mean SPID48 scores were approximately 40% lower for HC/APAP-treated patients who had OINV than for HC/APAP-treated patients who did not have OINV (P < .001). This study demonstrates that a commonly used opioid medication is significantly less effective as an analgesic for patients with OINV than patients without OINV. We conclude that OINV interferes with pain relief. Sponsored by Charleston Laboratories, Inc.

The pathophysiology, incidence, impact, and treatment of opioid-induced nausea and vomiting.

Opioid medications are integral in managing acute moderate-to-severe pain. Opioid analgesics bind to μ (mu), κ (kappa), or δ (delta) opioid receptors in the brain, spinal cord, and digestive tract. However, opioids cause adverse effects that may interfere with their therapeutic use. Some adverse effects wane over time, but patients using opioids for acute pain struggle with opioid-induced nausea and vomiting (OINV) the entire time they take the opioid. This article discusses the underlying mechanisms, clinical implications, and treatment strategies of OINV. Systematic search and review of Medline, PubMed, and Google Scholar for articles relating to OINV. In addition, package inserts provided pharmacologic data and dose recommendations as needed. Research suggests approximately 40% of patients may experience nausea and 15%-25% of patients may experience vomiting after opioid administration. Nausea often precedes vomiting, although they can occur separately. Many patients receiving opioids rate the nausea and vomiting as worse than their pain. Nausea and vomiting can lead to complications including electrolyte imbalances, malnutrition, and volume depletion, and can also negatively affect quality of life and postoperative recovery. There are several medications that can be used to treat OINV including serotonin receptor antagonists, dopamine receptor antagonists, and neurokinin-1 receptor antagonists. Healthcare providers should be proactive about discussing OINV with patients, as this may improve patient outcomes and pain relief.

Efficacy of Prophylactic Treatment for Oxycodone-Induced Nausea and Vomiting Among Patients with Cancer Pain (POINT): A Randomized, Placebo-Controlled, Double-Blind Trial.

Although opioid-induced nausea and vomiting (OINV) often result in analgesic undertreatment in patients with cancer, no randomized controlled trials have evaluated the efficacy of prophylactic antiemetics for preventing OINV. We conducted this randomized, placebo-controlled, double-blind trial to evaluate the efficacy and safety of prophylactic treatment with prochlorperazine for preventing OINV. Cancer patients who started to receive oral oxycodone were randomly assigned in a 1:1 ratio to receive either prochlorperazine 5 mg or placebo prophylactically, given three times daily for 5 days. The primary endpoint was the proportion of patients who had a complete response (CR) during the 120 hours of oxycodone treatment. CR was defined as no emetic episode and no use of rescue medication for nausea and vomiting during 5 days. Key secondary endpoints were the proportion of patients with emetic episodes, proportion of patients with moderate or severe nausea, quality of life, and proportion of treatment withdrawal. From November 2013 through February 2016, a total of 120 patients were assigned to receive prochlorperazine (n = 60) or placebo (n = 60). There was no significant difference in CR rates (69.5% vs. 63.3%; p = .47) or any secondary endpoint between the groups. Patients who received prochlorperazine were more likely to experience severe somnolence (p = .048). Routine use of prochlorperazine as a prophylactic antiemetic at the initiation of treatment with opioids is not recommended. Further research is needed to evaluate whether other antiemetics would be effective in preventing OINV in specific patient populations. Prophylactic prochlorperazine seems to be ineffective in preventing opioid-induced nausea and vomiting (OINV) and may cause adverse events such as somnolence. Routine use of prophylactic prochlorperazine at the initiation of treatment with opioids is not recommended. Further research is needed to evaluate whether other antiemetics would be effective in preventing OINV in specific patient populations.

Preventing opioid-induced nausea and vomiting: Rest your head and close your eyes?

Although opioid-induced nausea and vomiting (OINV) is common and debilitating, its mechanism is still unclear. Recently, we suggested that opioids affect semicircular canal function and that this leads to a mismatch between canal input and other sensory information during head motion, which triggers OINV. Here, we assess if visual input is relevant for this mismatch. In a randomized-controlled crossover study 14 healthy men (26.9±3.4 years, mean±SD) were tested twice, once blindfolded and once with eyes open, with at least one-day washout. The opioid remifentanil was administered intravenously (0.15 μg/kg/min) for 60 minutes. After a thirty-minutes resting period, subjects’ head and trunk were passively moved. Nausea was rated before remifentanil start (T0), before the movement intervention (T30) and after 60 minutes (T60) of administration. At rest (T0, T30), median nausea ratings were zero whether subjects were blindfolded or not. Movement triggered nausea independently of visual input (nausea rating 1.5/3.0 (median/interquartile range) in the blindfolded, 2.5/6 in the eyes-open condition, χ2(1) = 1.3, p = 0.25). As movement exacerbates OINV independently of visual input, a clash between visual and semicircular canal information is not the relevant trigger for OINV. To prevent OINV, emphasis should be put on head-rest, eye-closure is less important.

(431) Efficacy of CL-108 compared to hydrocodone 7.5 mg/acetaminophen 325 mg in preventing vomiting and the use of anti-emetics, Opioid-Induced Nausea and Vomiting (OINV)

CL-108 (containing hydrocodone 7.5 mg, acetaminophen 325 mg [HC/APAP] with fast-release promethazine 12.5 mg) was formulated to provide analgesia and prevent opioid-induced nausea and vomiting (OINV). CL-108 has been shown to be an effective analgesic compared to placebo and to significantly reduce the incidence of moderate/severe nausea and vomiting and the use of anti-emetics compared to HC/APAP.1 Another definition of OINV includes only two criteria: any vomiting or use of anti-emetics. Because this objective definition is also used to determine the efficacy of a drug in preventing OINV, we used this 2-component endpoint to analyze the results of this study. After surgical extraction of at least 2 impacted molar teeth, 466 patients with moderate-to-severe pain were randomized to self-administer CL-108 (n=211), HC/APAP (n=205), or placebo (n=50) every 4–6 hours as needed for pain. On an hourly basis (while awake) over the first 24 post-op hours patients documented the intensity of pain and nausea and, importantly, the frequency of vomiting and use(s) of an antiemetic. There was 52% less risk of vomiting for patients who used CL-108 compared to HC/APAP-treated patients, who used more doses of anti-emetics than CL-108-treated patients (all p<0.001). HC/APAP-treated patients also used anti-emetics earlier (and more repeated doses) than CL-108-treated patients (p<0.001). Applying the stringent 2-component definition of OINV to these 24-hour results: patients who used CL-108 experienced significantly less OINV than patients who used HC/APAP, representing 64% relative reduction in the risk of developing OINV (p<0.001). We conclude that CL-108 has a substantive effect on the risk of developing of OINV, less than a standard treatment for moderate-to-severe pain that contains the same dosages of hydrocodone and acetaminophen. (1. Schachtel B, et al. J Pain. 2014.) Sponsored by Charleston Laboratories and Daiichi Sankyo.

(436) Opioid-induced nausea and vomiting (OINV) in post-operative patients: a comparison of CL-108 to hydrocodone 7.5 mg/acetaminophen 325 mg

OINV is a common pharmacologic side effect of opioids which patients often describe as more annoying than pain. CL-108, consisting of hydrocodone 7.5mg/ acetaminophen 325mg (HC/APAP) with rapid-release promethazine 12.5mg, is an analgesic being developed for the relief of moderate-to-severe pain and the prevention of OINV. An oral surgery study1 demonstrated the efficacy of CL-108 over 24 hours for pain compared to placebo and for OINV compared to HC/APAP (both p<0.001). To study CL-108 over 48 hours, a randomized, double-blind, phase III trial evaluated pain intensity reduction by CL-108 compared to placebo and the incidence of OINV compared to HC/APAP in patients following orthopedic surgery. To improve assay sensitivity, the study population was enriched by identifying patients with a history suggestive of being likely to develop nausea. After undergoing primary unilateral first metatarsal bunionectomy, 552 patients rated pain intensity on a categorical scale. If they had moderate or severe pain confirmed on a 0-10 numerical pain intensity rating scale (PI-NRS) patients were randomized to CL-108, HC/APAP, or placebo under double-blind conditions. They used the PI-NRS at regular intervals over 48 hours while documenting the presence, severity, and frequency of nausea, retching, and vomiting. Patients remedicated every 4-6 hours and took antiemetic and supplementary (rescue) analgesic medications as needed. The co-primary endpoints were SPID48 (for analgesia) and a composite OINV prevention endpoint (no vomiting or use of antiemetic over 48 hours). Patients who used CL-108 had significant pain relief compared to placebo and 74% reduction in the risk of developing OINV relative to patients who used HC/APAP (both p<0.001), with NNT of 4. There were no unexpected or serious side effects. We conclude that CL-108 is a safe and effective analgesic for moderate-to-severe pain and the prevention of OINV. (1. Schachtel, B J Pain. 2014.) Sponsored by Charleston Laboratories and Daiichi Sankyo.

WITHDRAWN: (438) Efficacy of CL-108 compared to hydrocodone 7.5 mg/acetaminophen 325 mg in preventing vomiting and the use of anti-emetics, Opioid-Induced Nausea and Vomiting (OINV).

The Publisher regrets that this abstract is an accidental duplication of abstract (431), also published in the 2016 American Pain Society Scientific Meeting abstracts supplement: J Pain 17:S82, 2016, http://dx.doi.org/10.1016/j.jpain.2016.01.408. The duplicate abstract (438) has therefore been withdrawn. The full Elsevier Policy on Article Withdrawal can be found at http://www.elsevier.com/locate/withdrawalpolicy.

WITHDRAWN: (440) Opioid-Induced Nausea and Vomiting (OINV) in Post-Operative Patients: A Comparison of CL-108 to Hydrocodone 7.5 mg/Acetaminophen 325 mg.

The Publisher regrets that this abstract is an accidental duplication of abstract (436), also published in the 2016 American Pain Society Scientific Meeting abstracts supplement: J Pain 17:S83, 2016, http://dx.doi.org/10.1016/j.jpain.2016.01.413. The duplicate abstract (440) has therefore been withdrawn. The full Elsevier Policy on Article Withdrawal can be found at http://www.elsevier.com/locate/withdrawalpolicy.

Prophylactic Use of Antiemetics for Prevention of Opioid-Induced Nausea and Vomiting: A Questionnaire Survey among Japanese Physicians.

Antiemetics are being used both for the treatment and prophylaxis of opioid-induced nausea and vomiting (OINV) in clinical practice, despite the lack of evidence for the prophylactic benefit. Data regarding the actual status of prophylactic antiemetic use for OINV remain to be elucidated. The objective of this study was to evaluate the practice among Japanese physicians of the prophylactic use of antiemetics when starting opioids prescription for the prevention of opioid-induced nausea and vomiting. This questionnaire survey was targeted among physicians experienced in cancer pain treatment at two institutions of Japan (Nagoya University Hospital and Ichinomiya City Municipal Hospital). The questionnaire assessed the physicians' practice and beliefs regarding the prophylactic antiemetics prescription when they start opioids in patients with cancer pain. Questionnaires were filled in and received from 112 physicians from two institutions. Eighty-two percent of physicians prescribed prophylactic antiemetics at the beginning of opioid prescription, and the most commonly prescribed drug for this purpose was prochlorperazine (88%). Despite the lack of evidence, Japanese physicians commonly prescribe prophylactic antiemetics, most commonly prochlorperazine, for OINV. Prospective clinical trials are necessary to evaluate the efficacy of this practice.