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Annals of Palliative Medicine Mar 2024Many of the drugs used for the treatment and alleviation of symptoms in cancer patients are known to inhibit or induce cytochrome P450 (CYP). Therefore, it is important...
BACKGROUND
Many of the drugs used for the treatment and alleviation of symptoms in cancer patients are known to inhibit or induce cytochrome P450 (CYP). Therefore, it is important to pay attention to the drug interactions of opioid analgesics that are metabolized by CYPs, because for example when using oxycodone metabolized by CYP3A4, it is possible that the effect will be attenuated or enhanced by the concomitant use of drugs that induce or inhibit CYP3A4. Aprepitant, an antiemetic drug used in many patients receiving anticancer drugs, is known as a moderate competitive inhibitor of CYP3A4. We experienced a case of respiratory depression caused by opioids, which was suspected to be caused by a drug interaction with antiemetics especially aprepitant.
CASE DESCRIPTION
The patient was a 72-year-old man. He had been treated with continuous oxycodone infusion for perianal pain associated with the rectal invasion of prostate cancer. No comorbidities other than renal dysfunction were observed. Oxycodone treatment was started at 48 mg/day, and was increased to 108 mg/day, and then the pain decreased. Once the pain was controlled, chemotherapy was planned. Antiemetics (dexamethasone, palonosetron, and aprepitant) were administered before anticancer drug administration. Approximately 3 hours after antiemetics administration and before the administration of the anticancer drugs, a ward nurse noticed that oversedation and respiratory depression had occurred. When the patient was called, he immediately woke up and was able to talk normally, so the anticancer drugs were administered as scheduled. About 2 hours after the nurse noticed oversedation, the attending physician reduced the dose of oxycodone infusion to 48 mg/day. After that, his drowsiness persisted, but his respiratory condition improved. Despite reducing the dose of oxycodone to less than half, the pain remained stable at numeric rating scale (NRS) 0-1, without the use of a rescue dose. The patient was discharged from the hospital 36 days after the administration of anticancer drugs, without any problems.
CONCLUSIONS
The cause of respiratory depression in this case was thought to be a combination of factors, including drug interactions between oxycodone and antiemetics, and oxycodone accumulation due to renal dysfunction.
Topics: Male; Humans; Aged; Antiemetics; Aprepitant; Analgesics, Opioid; Oxycodone; Cytochrome P-450 CYP3A; Morpholines; Antineoplastic Agents; Drug Interactions; Prostatic Neoplasms; Pain; Respiratory Insufficiency; Kidney Diseases
PubMed: 38584476
DOI: 10.21037/apm-23-581 -
Frontiers in Oncology 2024Nausea and vomiting are common side effects of Trastuzumab Deruxtecan (T-DXd), but guidelines for optimal management were not initially available. This retrospective...
BACKGROUND
Nausea and vomiting are common side effects of Trastuzumab Deruxtecan (T-DXd), but guidelines for optimal management were not initially available. This retrospective single-center study aimed at evaluating the efficacy of two antiemetic regimens in patients receiving T-DXd.
METHODS
Data from metastatic breast cancer patients receiving T-DXd were collected. Two groups were defined: patients treated with 5-HT3 receptor antagonists (RA) ± dexamethasone (5-HT3-group) and patients treated with a fixed oral combination of netupitant (NK1RA) and palonosetron ± dexamethasone (NK1 group). Physicians preferentially offered the NK1 regimen to patients at higher risk of nausea and vomiting based on internal recommendations. Only nausea and vomiting during cycles 1 and 2 were considered. Comparisons of nausea and vomiting by the antiemetic prophylaxis group were assessed using chi-square.
RESULTS
A total of 53 patients were included in the analysis. At cycle 1, 72% and 28% of patients received the 5-HT3 and NK1 prophylaxis, respectively. Overall, 58% reported nausea, with no differences between groups (58% vs. 60%; = 0.832), but with a trend for lower grade in the NK1 group (33.3% G1; 26.7% G2) compared to the 5-HT3 group (23.7% G1; 31.6% G2; 2.6% G3). Vomiting was reported by 21% and 0% of patients in the 5-HT3 and the NK1 group, respectively ( = 0.054). Among the 15 patients in the 5-HT3 group with nausea at cycle 1 who escalated to NK1 at cycle 2, nausea decreased from 100% to 53% ( = 0.022) and vomiting decreased from 47% to 13% ( = 0.046).
CONCLUSIONS
The NK1 regimen improved vomiting control at cycle 1 and, when introduced at cycle 2, significantly improved both nausea and vomiting. The biased NK1 selection for higher-risk patients may have dampened the differences between groups at cycle 1. These findings support enhanced control of T-DXd-related nausea and vomiting with NK1RA.
PubMed: 38529378
DOI: 10.3389/fonc.2024.1374547 -
Journal of Cardiothoracic and Vascular... May 2024This study assessed the efficacy of palonosetron, alone or with dexamethasone, in reducing postoperative nausea and/or vomiting (PONV) and its impact on hospitalization...
Intraoperative Prophylaxis with Palonosetron for Postoperative Nausea and/or Vomiting in Adults Undergoing Cardiothoracic Surgery Under General Anesthesia: A Single-Center Retrospective Study.
OBJECTIVE
This study assessed the efficacy of palonosetron, alone or with dexamethasone, in reducing postoperative nausea and/or vomiting (PONV) and its impact on hospitalization duration in patients who undergo adult cardiothoracic surgery (CTS) under general anesthesia.
DESIGN
This retrospective analysis involved 540 adult patients who underwent CTS from a single-center cohort, spanning surgeries between September 2021 and March 2023. Sensitivity, logistic, and Cox regression analyses evaluated antiemetic effects, PONV risk factors, and outcomes.
SETTING
At the Virginia Mason Medical Center (VMMC), Seattle, WA.
PARTICIPANTS
Adults undergoing cardiothoracic surgery at VMMC during the specified period.
INTERVENTIONS
Patients were categorized into the following 4 groups based on antiemetic treatment: dexamethasone, palonosetron, dexamethasone with palonosetron, and no antiemetic.
MEASUREMENTS AND MAIN RESULTS
Primary outcomes encompassed PONV incidence within 96 hours postoperatively. Secondary outcomes included intensive care unit stay duration and postoperative opioid use. Palonosetron recipients showed a significantly lower PONV rate of 42% (v controls at 63%). The dexamethasone and palonosetron combined group also demonstrated a lower rate of 40%. Sensitivity analysis revealed a notably lower 0- to 12-hour PONV rate for palonosetron recipients (9% v control at 28%). Logistic regression found decreased PONV risk (palonosetron odds ratio [OR]: 0.24; dexamethasone and palonosetron OR: 0.26). Cox regression identified varying PONV hazard ratios related to female sex, PONV history, and lower body mass index.
CONCLUSIONS
This single-center retrospective study underscored palonosetron's efficacy, alone or combined with dexamethasone, in managing PONV among adult patients who undergo CTS. These findings contribute to evolving antiemetic strategies in cardiothoracic surgery, potentially impacting patient outcomes and satisfaction positively.
Topics: Adult; Humans; Female; Palonosetron; Postoperative Nausea and Vomiting; Antiemetics; Retrospective Studies; Anesthesia, General; Dexamethasone
PubMed: 38472029
DOI: 10.1053/j.jvca.2024.01.036 -
Pediatric Hematology and Oncology Mar 2024Due to an evidence gap, the emetogenicity of intravenous (IV) pegaspargase was unable to be included in the clinical practice guideline classifying chemotherapy...
Due to an evidence gap, the emetogenicity of intravenous (IV) pegaspargase was unable to be included in the clinical practice guideline classifying chemotherapy emetogenicity in pediatric patients. This single-center, retrospective chart review describes the proportion of pediatric patients who did not vomit during the acute phase (complete response; CR) after receiving IV pegaspargase and provides an emetogenicity classification using a preexisting framework. Of 44 patients who received IV pegaspargase between 2011 and 2020, 13 received a serotonin receptor antagonist plus dexamethasone or palonosetron alone and all experienced a CR. We, therefore, recommend classifying IV pegaspargase as moderately emetogenic.
PubMed: 38454568
DOI: 10.1080/08880018.2024.2311886 -
Supportive Care in Cancer : Official... Mar 2024We investigated the intensity and duration of nausea as well as its impact on health-related quality of life among cisplatin-treated patients who participated in a study...
Characteristics of nausea and its impact on health-related quality of life in cisplatin-treated patients receiving dexamethasone-sparing prophylaxis: an analysis of the LUNG-NEPA study.
PURPOSE
We investigated the intensity and duration of nausea as well as its impact on health-related quality of life among cisplatin-treated patients who participated in a study of dexamethasone (DEX)-sparing regimens based on NEPA (netupitant/palonosetron).
METHODS
This retrospective analysis included chemo-naive patients from a trial evaluating non-inferiority of DEX on day 1 (DEX1 arm) combined with NEPA, compared with the same regimen with DEX administered on days 1-4 (DEX4; reference arm) following cisplatin (≥ 70 mg/m) administration. Nausea intensity was self-rated using a four-point Likert scale. Extended nausea duration was considered ≥ 3 days within the 5 days post-chemotherapy. Patients completed the Functional Living Index-Emesis (FLIE) questionnaire on day 6.
RESULTS
In the DEX1 arm, more patients (20/76) experienced acute nausea, influencing the outcome of delayed nausea (38/76). During days 1 to 5, 51.3% (39/76) and 39.5% (30/76) of patients experienced nausea in the DEX1 and DEX4 arms, respectively (P = 0.192). Of these, 43.6% and 60% reported moderate-to-severe nausea, respectively, in the DEX1 and DEX4 arms (P = 0.200), while 74.4% and 56.7% of patients experienced extended nausea duration (P = 0.122). Similar between-arm rates of nauseated patients reported an impact on daily life (79.5% vs. 70%; P = 0.408). In analyses stratified for antiemetic regimen, moderate-to-severe nausea or extended nausea duration was associated with an impact on daily life (P ≤ 0.001).
CONCLUSION
Despite the higher incidence, there was no suggestion of any strong adverse effect of NEPA plus single-dose DEX on the characteristics of nausea as well as its impact on daily life in patients with cisplatin-induced nausea. Further prospective controlled study is warranted.
TRIAL REGISTRATION
ClinicalTrials.gov identifier: NCT04201769. Registration date: 17/12/2019.
Topics: Humans; Quality of Life; Cisplatin; Retrospective Studies; Nausea; Dexamethasone; Lung
PubMed: 38433125
DOI: 10.1007/s00520-024-08406-5 -
Journal of Oncology Pharmacy Practice :... Feb 2024Clinical practice guidelines (CPGs) recommending palonosetron for the prevention and management of chemotherapy-induced nausea and vomiting (CINV) were adapted for use...
INTRODUCTION
Clinical practice guidelines (CPGs) recommending palonosetron for the prevention and management of chemotherapy-induced nausea and vomiting (CINV) were adapted for use at our institution. Palonosetron was restricted for use in patients experiencing breakthrough CINV and receiving highly emetogenic chemotherapy (HEC) or undergoing stem cell transplant conditioning and in patients with refractory CINV receiving HEC. Given the significant cost of palonosetron, we aimed to determine the proportion of chemotherapy blocks where palonosetron use was discordant with the institutional policy or source CPG.
METHODS
A retrospective review of the health records of patients who received palonosetron between 1 July 2019 and 30 June 2020 was undertaken. Details of palonosetron use, antiemetic regimen and the date and time of each vomit during the acute and delayed phases were collected for each chemotherapy block where palonosetron was given. Discordance with the institutional policy and the source CPG was determined by assessing the indication for palonosetron and the dose. In the subset of chemotherapy blocks where information regarding vomiting episodes was available, the extent of acute phase chemotherapy-induced vomiting (CIV) control was reported.
RESULTS
Four hundred thirty-eight chemotherapy blocks, representing 122 patients (mean age 9 years), receiving 595 palonosetron doses were included. Palonosetron use was discordant with institutional policy during most (72%; 314/438) of the chemotherapy blocks analyzed. However, palonosetron use was concordant with the source CPG during most chemotherapy blocks (74%; 326/438). Complete CIV control during the acute phase was observed in 66% (195/295) of chemotherapy blocks where palonosetron was given, irrespective of concomitant antiemetics administered.
CONCLUSION
The majority of palonosetron use at our institution was discordant with institutional policy, but concordant with the source CPG. Our institutional policy has since been updated to be more aligned with the source CPG.
PubMed: 38425048
DOI: 10.1177/10781552241233489 -
Journal of Clinical Medicine Feb 2024Prior speculation suggests that selective 5-hydroxytryptamine-3 receptors and neurokinin-1 receptor antagonists may increase arrhythmia risk and induce...
Effect of Selective 5-Hydroxytryptamine-3 Receptor and Neurokinin-1 Receptor Antagonists on Hemodynamic Changes and Arrhythmogenic Potential in Patients Receiving Chemotherapy: A Retrospective, Observational Study.
Prior speculation suggests that selective 5-hydroxytryptamine-3 receptors and neurokinin-1 receptor antagonists may increase arrhythmia risk and induce electrocardiographic changes. This study examined the effect of anti-emetic medications on arrhythmogenic potential and hemodynamic alterations. We considered patients aged 18 or above receiving chemotherapy between June 2013 and December 2013. Patients were grouped by anti-emetic medication: intravenous granisetron (Group G), oral aprepitant plus IV granisetron (Group AG), IV palonosetron (Group P), and oral aprepitant plus IV palonosetron (Group AP). We recorded blood pressure and electrocardiography initially and at the thirtieth minute post-medication, focusing on P dispersion, QTc dispersion, and systolic/diastolic blood pressure alterations. The study included 80 patients (20 per group). Baseline systolic/diastolic blood pressure and P dispersion showed no significant variance. However, the baseline QTc dispersion was significantly lower in Groups P and AP than G and AG. The thirtieth-minute systolic/diastolic blood pressures were significantly lower than the baseline for Groups AG and AP, and the heart rates decreased in all groups. Group P showed significantly fewer blood pressure changes. We found no arrhythmogenic potential linked to granisetron, palonosetron, and aprepitant. Hypotension was more frequent at 30 min post-medication in granisetron or aprepitant recipients. Considering no hypotension occurred when using palonosetron alone, this treatment was deemed safer.
PubMed: 38337537
DOI: 10.3390/jcm13030843 -
JCO Global Oncology Jan 2024The effectiveness of a dexamethasone (DEX)-free regimen for chemotherapy-induced nausea and vomiting (CINV) prophylaxis in patients receiving highly emetogenic... (Randomized Controlled Trial)
Randomized Controlled Trial
PURPOSE
The effectiveness of a dexamethasone (DEX)-free regimen for chemotherapy-induced nausea and vomiting (CINV) prophylaxis in patients receiving highly emetogenic chemotherapy (HEC) is not known.
METHODS
This was a double-blind, phase III trial designed to show the noninferiority of a DEX-free regimen (olanzapine, palonosetron, and fosaprepitant [OPF]) compared with the DEX-containing regimen (olanzapine, palonosetron, and DEX [OPD]). Chemotherapy-naïve patients age 18-80 years receiving single-day HEC were randomly assigned 1:1 to receive either the OPD regimen or the OPF regimen. The primary objective was to compare complete response (CR) rates for vomiting during the overall period (start of chemotherapy to 120 hours). Secondary objectives included CR for vomiting during the acute period (0-24 hours) and delayed period (24-120 hours), CR for nausea, and comparison of toxicities and patient-reported outcomes.
RESULTS
Three hundred forty-six patients received the study interventions, 174 in the OPD arm and 172 in the OPF arm. The DEX-free OPF arm had significantly higher CR rates for vomiting compared with the DEX-containing OPD arm in acute (94.7% 85.6%; < .004), delayed (81.9% 50.5%; < .001), and overall (79.6% 48.8%; < .001) periods. For nausea, CR rates in the OPF arm were higher in delayed (53.4% 39.6%; = .009) and overall (50.5% 39.1%; = .031) periods but not in the acute period (77.9% 81.6%; = .39). Fatigue ( = .009) and drowsiness ( = .002) were more in the OPF arm in the acute period and insomnia ( < .001) in the OPD arm in the overall period.
CONCLUSION
This study shows that a DEX-free OPF regimen is efficacious and should be considered a standard option for acute and delayed CINV prophylaxis for HEC.
Topics: Humans; Adolescent; Young Adult; Adult; Middle Aged; Aged; Aged, 80 and over; Antiemetics; Palonosetron; Olanzapine; Vomiting; Nausea
PubMed: 38237092
DOI: 10.1200/GO.23.00301 -
Annals of Medicine 2023Butorphanol has been used to reduce the incidence and severity of neuraxial morphine-induced pruritus. Palonosetron is a commonly used antiemetic for the prevention of... (Randomized Controlled Trial)
Randomized Controlled Trial
Comparison of the ED50 of prophylactic butorphanol in preventing morphine-induced pruritus with or without palonosetron: a prospective, double-blinded, randomized dose-response trial using an up-down sequential allocation method.
BACKGROUND
Butorphanol has been used to reduce the incidence and severity of neuraxial morphine-induced pruritus. Palonosetron is a commonly used antiemetic for the prevention of postoperative nausea and vomiting. The aim of our study was to compare the effective dose in 50% of subjects (ED50) of intravenous butorphanol infusion with or without a single intravenous bolus of palonosetron for preventing pruritus induced by epidural administration of morphine.
METHODS
A total of 120 parturients were randomly assigned to receive an intravenous bolus injection of palonosetron plus continuous infusion of butorphanol (Group P + B) or an intravenous bolus of saline plus continuous infusion of butorphanol (Group B) after epidural administration of morphine. The antipruritic effect was graded as satisfactory (numerical rating scale (NRS) of pruritus ≤3) or unsatisfactory (NRS >3) within 48 h after morphine treatment. The first patient in each group received butorphanol infusion at a rate of 4 µg/kg/h. The infusion dose for each subsequent patient in the corresponding group was increased by 0.2 µg/kg/h after an unsatisfactory response or decreased by 0.2 µg/kg/h after a satisfactory response. The ED50 was calculated for each group and compared using up-down sequential analysis.
RESULTS
The ED50 (mean [95% confidence interval (CI)]) of the dose of intravenous butorphanol infusion for preventing moderate to severe pruritus was lower in Group P + B (3.29 µg/kg/min [3.25-3.34 µg/kg/min]) than in Group B (3.57 µg/kg/min [3.47-3.67 µg/kg/min]) ( < 0.05).
CONCLUSIONS
Under the conditions of the present study, a prophylactic use of 0.25 mg palonosetron reduced the ED50 of prophylactic infusion of butorphanol by approximately 8% to achieve a satisfactory antipruritic effect after epidural morphine for post-caesarean analgesia.
Topics: Pregnancy; Female; Humans; Butorphanol; Morphine; Palonosetron; Antipruritics; Prospective Studies; Pruritus; Double-Blind Method
PubMed: 38233748
DOI: 10.1080/07853890.2024.2304671