[Durgical](https://durgical.com/en/) › [DurgiPedia](https://durgical.com/en/durgipedia/) › [Pharmacology](https://durgical.com/en/pharmacology/) › [NK1 receptor antagonists](https://durgical.com/en/pharmacology/classes/nk1-receptor-antagonists/) › Netupitant and palonosetron # Netupitant and palonosetron ## NK1 receptor antagonists? NK1 receptor antagonists A fixed combination of an NK1 blocker and a 5-HT3 blocker, given before chemotherapy to prevent early and delayed nausea and vomiting. Updated Nov 1, 2026 ## Quick facts **Group** [NK1 receptor antagonists](https://durgical.com/en/pharmacology/classes/nk1-receptor-antagonists/) **Target** Neurokinin-1 (substance P) receptor, plus the 5-HT3 receptor (palonosetron) **Used for** Prevention of acute **Key effects** Headache · Constipation · Weakness **Monitor** Nausea and vomiting · Bowel habit **ATC** A04AA55 No doses: the clinician sets them by the current guideline. On this page - The basics Mechanism of action - Indications - Adverse effects - Pharmacokinetics - Memory aid - Safety Contraindications - Key interactions - What is monitored - Administration and safety - Pregnancy and breastfeeding - Nursing care - Study Test yourself - Connections Connections ## Mechanism of action ◎**Neurokinin-1 (substance P) receptor, plus the 5-HT3 receptor (palonosetron)**Netupitant and palonosetron ⓘ The figure shows netupitant bound to the human neurokinin-1 receptor. **Target in 3D:** Neurokinin-1 (substance P) receptor, plus the 5-HT3 receptor (palonosetron). PDB structure 6HLP (RCSB PDB, public domain). [View the structure at RCSB PDB](https://www.rcsb.org/structure/6HLP) · Drag to rotate · pinch to zoom Netupitant blocks neurokinin-1 receptors in the brainstem, so substance P cannot drive vomiting; this mainly protects against delayed nausea in the days after chemotherapy. Palonosetron blocks 5-HT3 receptors on vagal afferents and in the chemoreceptor trigger zone, which protects against acute nausea. Both drugs last a long time, so a single dose before chemotherapy covers several days. It is usually combined with dexamethasone. - Chemotherapy releases serotonin and substance P - Palonosetron blocks 5-HT3: acute phase protected - Netupitant blocks NK1: delayed phase protected ## Indications - Prevention of acute and delayed nausea and vomiting with moderately or highly emetogenic cancer chemotherapy ## Adverse effects ### Common - Headache - Constipation - Weakness, tiredness - Heartburn, abdominal pain - Skin redness ### Serious (rare, important) - Serotonin syndrome with other serotonergic drugs: agitation, fever, sweating, stiffness, twitching - Allergic reactions: rash, trouble breathing or swallowing - Fast, slow or irregular heartbeat; fainting ## Contraindications - Hypersensitivity to netupitant, palonosetron or any component ## Key interactions **SSRIs, SNRIs and other serotonergic drugs** Risk of serotonin syndrome **Strong CYP3A4 inducers (rifampicin)** Lower netupitant levels and less protection **Strong CYP3A4 inhibitors** Higher netupitant levels ## What is monitored - Nausea and vomiting in the days after chemotherapy - Bowel habit (constipation) - Signs of serotonin syndrome when combined with serotonergic drugs ## Administration and safety - A single oral dose before chemotherapy, usually with dexamethasone. - Because both parts act for days, it is not repeated on the following days of the same cycle unless ordered. - The patient's other medicines are checked for serotonergic drugs and CYP3A4 interactions. ## Pregnancy and breastfeeding Human data are limited; use in pregnancy needs a clear benefit and is discussed with the oncology team. ## Nursing care - Give it on time before chemotherapy as ordered. - Ask about antidepressants and other serotonergic drugs. - Track nausea, vomiting, food and fluid intake for several days. - Teach to report agitation, fever, stiffness or a racing or irregular heartbeat. ## Pharmacokinetics **Metabolism** Netupitant mainly by CYP3A4; palonosetron partly in the liver **Half-life** Both components have long half-lives, netupitant longer than palonosetron ## Memory aid «One capsule, two locks»: NK1 lock for later days, 5-HT3 lock for day one. ## Test yourself Think of the answer, then tap the question to see it. ## Which phase of chemotherapy nausea does netupitant mainly prevent? The delayed phase, by blocking NK1 receptors. ## Which phase does palonosetron mainly cover? The acute phase, by blocking 5-HT3 receptors. ## Why is one dose enough for several days? Both drugs have long half-lives. ## Which drug interaction risk is checked with antidepressants? Serotonin syndrome. [Add to my cards (4)](https://durgical.app/estudiar/?add=/en/pharmacology/netupitant-and-palonosetron/) [More Pharmacology questions →](https://durgical.com/en/practice/?f=pharmacology) ## Connections ## Related drugs 5 - [Palonosetron](https://durgical.com/en/pharmacology/palonosetron/) - [Aprepitant](https://durgical.com/en/pharmacology/aprepitant/) - [Fosaprepitant](https://durgical.com/en/pharmacology/fosaprepitant/) - [Ondansetron](https://durgical.com/en/pharmacology/ondansetron/) - [Dexamethasone](https://durgical.com/en/pharmacology/dexamethasone/) [← Back to the class: NK1 receptor antagonists](https://durgical.com/en/pharmacology/classes/nk1-receptor-antagonists/) Educational content on how drugs work; not a prescribing guide and no substitute for a health professional's advice. No doses are given. Sources: [Netupitant and Palonosetron: MedlinePlus Drug Information](https://medlineplus.gov/druginfo/meds/a614053.html) (MedlinePlus (U.S. National Library of Medicine), 2026); [ATCDDD - ATC/DDD Index](https://atcddd.fhi.no/atc_ddd_index/?code=A04AA55) (WHO Collaborating Centre for Drug Statistics Methodology, 2026); [RCSB PDB - 6HLP: Crystal structure of the Neurokinin 1 receptor in complex with the small molecule antagonist Netupitant](https://www.rcsb.org/structure/6HLP) (RCSB Protein Data Bank, 2026). ## **Spotted a mistake?** We are always improving for the community. Tell us what is wrong and our team will review it. Report a mistake Representative model, for educational purposes only. --- Source: https://durgical.com/en/pharmacology/netupitant-and-palonosetron/ License: CC BY 4.0 (https://creativecommons.org/licenses/by/4.0/). Cite as: DurgiPedia (durgical.com), https://durgical.com/en/pharmacology/netupitant-and-palonosetron/