ArticleSupportive care in cancer : official journal of the Multinational Association of Supportive Care in Cancer2013
Effect of netupitant, a highly selective NK₁ receptor antagonist, on the pharmacokinetics of palonosetron and impact of the fixed dose combination of netupitant and palonosetron when coadministered with ketoconazole, rifampicin, and oral contraceptives.
Article in Supportive care in cancer : official journal of the Multinational Association of Supportive Care in Cancer, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers, 1 of them a synthesis that pooled it.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
15 citing papers in PubMed, 1 synthesis or guideline pooled it, 31 citations in OpenAlex.
- 2016 Updated MASCC/ESMO Consensus Recommendations: Prevention of Nausea and Vomiting Following High Emetic Risk Chemotherapy.Supportive care in cancer : official journal of the Multinational Association of Supportive Care in Cancer · 2017Pooled it
- Challenges in the Development of Intravenous Neurokinin-1 Receptor Antagonists: Results of a Safety and Pharmacokinetics Dose-Finding, Phase 1 Study of Intravenous Fosnetupitant.Clinical pharmacology in drug development · 2022Trial
- Effects of rolapitant administered orally on the pharmacokinetics of dextromethorphan (CYP2D6), tolbutamide (CYP2C9), omeprazole (CYP2C19), efavirenz (CYP2B6), and repaglinide (CYP2C8) in healthy subjects.Supportive care in cancer : official journal of the Multinational Association of Supportive Care in Cancer · 2019Trial
- Effect of netupitant, a highly selective NK₁ receptor antagonist, on the pharmacokinetics of midazolam, erythromycin, and dexamethasone.Supportive care in cancer : official journal of the Multinational Association of Supportive Care in Cancer · 2013Trial
- Nausea and vomiting in an evolving anticancer treatment landscape: long-delayed and emetogenic antibody-drug conjugates.Future oncology (London, England) · 2025Review
- A scoping review of interventions to prevent and treat adverse events during treatment of rifampin-susceptible tuberculosis.PloS one · 2025Article
- Review
- A phase 1 pharmacokinetic study of oral NEPA, the fixed combination of netupitant and palonosetron, in Chinese healthy volunteers.Cancer chemotherapy and pharmacology · 2021Article
- 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 of clinical pharmacology · 2019Article
- Role of CYP3A in Oral Contraceptives Clearance.Clinical and translational science · 2018Review
- Drug-drug interaction profile of components of a fixed combination of netupitant and palonosetron: Review of clinical data.Journal of oncology pharmacy practice : official publication of the International Society of Oncology Pharmacy Practitioners · 2016Review
- Management of acute and delayed chemotherapy-induced nausea and vomiting: role of netupitant-palonosetron combination.Therapeutics and clinical risk management · 2016Review
- Netupitant/Palonosetron: A Review in the Prevention of Chemotherapy-Induced Nausea and Vomiting.Drugs · 2015Review
- Netupitant/Palonosetron.Hospital pharmacy · 2015Article
- A Review of NEPA, a Novel Fixed Antiemetic Combination with the Potential for Enhancing Guideline Adherence and Improving Control of Chemotherapy-Induced Nausea and Vomiting.BioMed research international · 2015Review
Corrections and comments
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Authors and funding
6 authors at 4 institutions in 4 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
objectivesNeurokinin-1 receptor antagonists (NK1 RAs) are commonly coadministered with a 5-HT3 RA such as palonosetron to prevent nausea and vomiting induced by chemotherapy. Netupitant, a new highly selective NK1 RA, is both a substrate for and a moderate inhibitor of CYP3A4. Three studies were designed to evaluate the potential drug-drug interaction of netupitant with palonosetron and of the fixed dose combination of netupitant and palonosetron, NEPA, with an inhibitor (ketoconazole), an inducer (rifampicin) and a substrate (oral contraceptives) of CYP3A4.
methodsStudy 1 was a three-way crossover in 18 healthy subjects receiving netupitant alone, palonosetron alone, and the combination of both antiemetics. Studies 2 and 3 were two-way crossover trials where healthy subjects received NEPA (the fixed dose combination of netupitant and palonosetron). In study 2, 36 subjects received NEPA alone (day 1) and in combination with ketoconazole or rifampicin. In study 3, 24 healthy women received ethinylestradiol/levonorgestrel alone or in combination with NEPA (day 1).
resultsThere were no significant pharmacokinetic interactions between netupitant and palonosetron. Ketoconazole increased netupitant area under curve (AUC) by 140 % and C max by 25 %. Rifampicin decreased netupitant AUC by 83 % and C max by 62 %. NEPA did not significantly affect exposure to ethinylestradiol, while systemic exposure to levonorgestrel increased by 40 %, but this was not considered clinically relevant.
conclusionsThere were no clinically relevant interactions between netupitant and palonosetron, or between NEPA and oral contraceptives. The coadministration of NEPA with inhibitors or inducers of CYP3A4 may require dose adjustments. Treatments were well tolerated.
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