- Updates in the Management of Postoperative Nausea and Vomiting. [Review]
- AAAdv Anesth 2018; 36(1):81-97
- Complementary Pharmacokinetic Profiles of Netupitant and Palonosetron Support the Rationale for Their Oral Fixed Combination for the Prevention of Chemotherapy-Induced Nausea and Vomiting. [Journal Article]
- JCJ Clin Pharmacol 2018 Nov 09
- NEPA is the first fixed-combination antiemetic composed of the neurokinin-1 receptor antagonist netupitant (netupitant; 300 mg) and the 5-hydroxytryptamine-3 receptor antagonist palonosetron (palonos...
NEPA is the first fixed-combination antiemetic composed of the neurokinin-1 receptor antagonist netupitant (netupitant; 300 mg) and the 5-hydroxytryptamine-3 receptor antagonist palonosetron (palonosetron; 0.50 mg). This study evaluated the pharmacokinetic profiles of netupitant and palonosetron. The pharmacokinetic profiles of both drugs were summarized using data from phase 1-3 clinical trials. netupitant and palonosetron have high absolute bioavailability (63%-87% and 97%, respectively). Their overall systemic exposures and maximum plasma concentrations are similar under fed and fasting conditions. netupitant binds to plasma proteins in a high degree (>99%), whereas palonosetron binds to a low extent (62%). Both drugs have large volumes of distribution (cancer patients: 1656-2257 L and 483-679 L, respectively). netupitant is metabolized by cytochrome P450 3A4 to 3 major pharmacologically active metabolites (M1, M2, and M3). palonosetron is metabolized by cytochrome P450 2D6 to 2 major substantially inactive metabolites (M4 and M9). Both drugs have similar intermediate-to-low systemic clearances and long half-lives (cancer patients: netupitant, 19.5-20.8 L/h and 56.0-93.8 hours; palonosetron: 7.0-11.3 L/h and 43.8-65.7 hours, respectively). netupitant and its metabolites are eliminated via the hepatic/biliary route (87% of the administered dose), whereas palonosetron and its metabolites are mainly eliminated via the kidneys (85%-93%). Altogether, these data explain the lack of pharmacokinetic interactions between netupitant and palonosetron at absorption, binding, metabolic, or excretory level, thus highlighting their compatibility as the oral fixed combination NEPA, with administration convenience that may reduce dosing mistakes and increase treatment compliance.
- CADTH Canadian Drug Expert Committee Recommendation: Netupitant/Palonosetron (Akynzeo — Purdue Pharma): Indication: Chemotherapy-induced nausea and vomiting [BOOK]
- BOOKCanadian Agency for Drugs and Technologies in Health: Ottawa (ON)
- Patient-Related Risk Factors for Nausea and Vomiting with Standard Antiemetics in Patients with Breast Cancer Receiving Anthracycline-Based Chemotherapy: A Retrospective Observational Study. [Journal Article]
- CTClin Ther 2018 Nov 01
- CONCLUSIONS: The present findings suggest that, among patients with breast cancer receiving anthracycline and treated with aprepitant, palonosetron, and dexamethasone, patients younger than 55 years and having a body mass index <27.5 kg/m2 are high-risk populations for chemotherapy-induced nausea and vomiting, whereas those with a history of habitual alcohol consumption is a low-risk one.
- Olanzapine plus aprepitant, palonosetron, and dexamethasone for nausea and vomiting in patients with breast cancer receiving anthracycline: A retrospective study. [Journal Article]
- SRSci Rep 2018 Nov 02; 8(1):16232
- This study aimed to compare the antiemetic efficacy and safety of a four-drug combination with those of a standard three-drug combination in Japanese patients with breast cancer treated with anthracy...
This study aimed to compare the antiemetic efficacy and safety of a four-drug combination with those of a standard three-drug combination in Japanese patients with breast cancer treated with anthracycline. We retrospectively analyzed data from Japanese patients with breast cancer, who had received their first cycle of anthracycline and were treated with aprepitant, palonosetron, and dexamethasone with or without olanzapine. This retrospective observational study was performed at Ehime University Hospital using the electronic medical records. Multivariable and propensity score-adjusted analyses were performed to compare the onset of complete response (CR) failure between the groups. One-hundred and thirty patients were included in this study and the four- and three-drug group had 22 and 108 patients, respectively. Similar to multivariable logistic regression analysis, propensity-adjusted logistic regression analysis revealed that the four-drug group was markedly associated with a decreased odds of CR failure in the overall, acute, and delayed phases (odds ratio [OR]: 0.27, 95% confidence interval [CI]: 0.10-0.73; OR: 0.28, 95% CI: 0.10-0.76; and OR: 0.15, 95% CI: 0.04-0.57, respectively). Additionally, treatment-related adverse events were well tolerated in both the groups. These findings suggest that the antiemetic efficacy of the four-drug combination is superior to that of the standard three-drug combination.
- Errata. [Published Erratum]
- IJInt J Pharm Compd 2018 Nov-Dec; 22(6):527
- Ketamine 50-mg/mL Injection, IJPC Jul/Aug 2013 pg 331. "Evaluation of the Stability of Ketoprofen in Pluronic Lecithin Organogel and the Determination of an Appropriate Beyond-use Date" IJPC Jul/Aug ...
Ketamine 50-mg/mL Injection, IJPC Jul/Aug 2013 pg 331. "Evaluation of the Stability of Ketoprofen in Pluronic Lecithin Organogel and the Determination of an Appropriate Beyond-use Date" IJPC Jul/Aug 2014 pg 348-350. "Rolapitant Injectable Emulsion with Palonosetron Hydrochloride Admixture" IJPC May/Jun 2018 pg 237.
- Effectiveness of Antiemetic Regimens for Highly Emetogenic Chemotherapy-Induced Nausea and Vomiting: A Systematic Review and Network Meta-Analysis. [Review]
- OOncologist 2018 Oct 17
- CONCLUSIONS: Our meta-analysis supports the conclusion that olanzapine-containing regimens are the most effective for CINV of highly emetogenic chemotherapy. We confirmed that NK1RA + PAL + Dex is the most effective of conventional regimens. Substituting olanzapine for an Nk-1 receptor antagonist may offer a less costly and more effective alternative for patients.Nausea and vomiting during chemotherapy often pose difficulties for patients and doctors, making it hard to continue the proper therapy and to maintain the quality of life. This article gives insights into the optimal choice of medicine to treat nausea during chemotherapy. The findings reported here provide readers with a robust efficacy ranking of antinausea medicine, which can be used as a reference for the best possible treatment. Furthermore, the 70% less costly drug, olanzapine, is suggested to be equally effective to aprepitant in reducing nausea and vomiting. The possibility of offering a cost-effective treatment to a wider range of the population is discussed.
- Evolving role of neurokinin 1-receptor antagonists for chemotherapy-induced nausea and vomiting. [Review]
- OTOnco Targets Ther 2018; 11:6459-6478
- To examine pharmacologic and clinical characteristics of neurokinin 1 (NK1)-receptor antagonists (RAs) for preventing chemotherapy-induced nausea and vomiting (CINV) following highly or moderately em...
To examine pharmacologic and clinical characteristics of neurokinin 1 (NK1)-receptor antagonists (RAs) for preventing chemotherapy-induced nausea and vomiting (CINV) following highly or moderately emetogenic chemotherapy, a literature search was performed for clinical studies in patients at risk of CINV with any approved NK1 RAs in the title or abstract: aprepitant (capsules or oral suspension), HTX019 (intravenous [IV] aprepitant), fosaprepitant (IV aprepitant prodrug), rolapitant (tablets or IV), and fixed-dose tablets combining netupitant or fosnetupi-tant (IV netupitant prodrug) with the 5-hydroxytryptamine type 3 (5HT3) RA palonosetron (oral or IV). All NK1 RAs are effective, but exhibit important differences in efficacy against acute and delayed CINV. The magnitude of benefit of NK1-RA-containing three-drug vs two-drug regimens is greater for delayed vs acute CINV. Oral rolapitant has the longest half-life of available NK1 RAs, but as a consequence should not be administered more frequently than every 2 weeks. In general, NK1 RAs are well tolerated; however, IV rolapitant was recently removed from US distribution, due to hypersensitivity and anaphylaxis, and IV fosaprepitant is associated with infusion-site reactions and hypersensitivity presumed related to its polysorbate 80 excipient. Also, available NK1 RAs have potential drug-drug interactions. Adding an NK1 RA to 5HT3 RA and dexamethasone significantly improves CINV control vs the two-drug regimen. Newer NK1 RAs offer more formulation options, higher acute-phase plasma levels, or improved tolerability, and increase clinicians' opportunities to maximize benefits of this important class of antiemetics.
- Corrigendum: Anti-emetic Action of the Brain-Penetrating New Ghrelin Agonist, HM01, Alone and in Combination With the 5-HT3 Antagonist, Palonosetron and With the NK1 Antagonist, Netupitant, Against Cisplatin- and Motion-Induced Emesis in Suncus murinus (House Musk Shrew). [Published Erratum]
- FPFront Pharmacol 2018; 9:1102
- [This corrects the article DOI: 10.3389/fphar.2018.00869.].
[This corrects the article DOI: 10.3389/fphar.2018.00869.].
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- Real-world efficacy: intravenous palonosetron three-drug regimen for chemotherapy-induced nausea and vomiting with highly emetogenic chemotherapy. [Journal Article]
- JCJ Comp Eff Res 2018 Oct 11
- CONCLUSIONS: Even within a recommended three-drug antiemetic regimen, palonosetron may provide suboptimal chemotherapy-induced nausea and vomiting control with HEC in real-world settings.