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5-HT3 + NK1 antagonist combo Pregnancy: Contraindicated during pregnancy. Women of childbearing potential should not be pregnant or become pregnant while on treatment; a pregnancy test should be performed on all pre-menopausal women prior to treatment and effective contraception used during therapy and for up to one month after treatment. Should not be used during breast-feeding — discontinue breast-feeding during treatment and for 1 month after the last dose.

Palonosetron with netupitant

Brand names: Akynzeo

This is a fixed-dose oral combination of the 5-HT3 receptor antagonist palonosetron with the NK1 receptor antagonist netupitant, used to prevent acute and delayed chemotherapy-induced nausea and vomiting.

Auto-extracted from the source labelling — not yet independently clinician-verified. These values were distilled from the UK SPC (or the US label where noted) but have not had a clinician sign-off. Confirm against the current SmPC before prescribing.

Adult dose

Dose: One 300 mg/0.5 mg capsule (netupitant 300 mg with palonosetron 0.5 mg)
Route: Oral — swallow the hard capsule whole; can be taken with or without food
Frequency: Single capsule approximately one hour prior to the start of each chemotherapy cycle
The recommended oral dexamethasone dose should be reduced by approximately 50% when co-administered with netupitant/palonosetron capsules. Elderly: no dosage adjustment necessary, but caution in patients over 75 years due to the long half-life of the active substances and limited experience in this population. Hepatic impairment: no adjustment for mild or moderate impairment (Child-Pugh 5-8); use with caution in severe impairment (Child-Pugh score 9 or more) as exposure to netupitant may be increased. Paediatric population: safety and efficacy in the paediatric population have not been established and no data are available.

Dose adjustments

Renal

Dosage adjustment is not considered necessary in mild to severe renal impairment. Pharmacokinetics have not been studied in end-stage renal disease requiring haemodialysis and no efficacy or safety data are available — use in these patients should be avoided.

Dose auto-extracted from UK Summary of Product Characteristics (SPC) via the eMC; US FDA prescribing information (openFDA / DailyMed) — cross-check; US labelling may differ from UK — not yet clinician-verified. Always confirm against the product SmPC and your local formulary before prescribing.

Contraindications

  • Hypersensitivity to the active substances or to any of the excipients
  • Pregnancy

Side effects

  • Headache (3.6%)
  • Constipation (3.0%)
  • Fatigue (1.2%)
  • Asthenia
  • Decreased appetite
  • Neutropenia

Interactions

  • Oral dexamethasone — reduce the dexamethasone dose by approximately 50% when co-administered (SPC 4.2)
  • Medicinal products that increase the QT interval or cause electrolyte abnormalities, and anti-arrhythmic medicinal products — exercise caution; correct hypokalaemia and hypomagnesaemia before administration (SPC 4.4)
  • Orally administered active substances metabolised primarily through CYP3A4 with a narrow therapeutic range — use with caution (SPC 4.4)
  • Chemotherapeutic agents that are CYP3A4 substrates (e.g. docetaxel, irinotecan) — netupitant is a moderate CYP3A4 inhibitor and can increase their exposure; monitor for increased toxicity. Netupitant may also affect the efficacy of chemotherapeutic agents that require CYP3A4 activation (SPC 4.4)
  • Other serotonergic medicinal products including SSRIs and SNRIs — reports of serotonin syndrome with 5-HT3 antagonists; observe for serotonin syndrome-like symptoms (SPC 4.4)
  • Note: SPC section 4.5 was not captured in this source bundle — interactions above are drawn from sections 4.2 and 4.4

Clinical monograph

How it works

Palonosetron blocks serotonin 5-HT3 receptors that mediate the acute emetic response, while netupitant blocks substance P at central neurokinin-1 receptors involved in delayed emesis, giving complementary antiemetic cover.

Prescribing in practice

  • Netupitant is a CYP3A4 inhibitor, so doses of CYP3A4-substrate co-medications such as dexamethasone and certain chemotherapy agents must be adjusted and interacting drugs reviewed.
  • Both components can prolong the QT interval, so use with caution alongside other QT-prolonging drugs and in patients with electrolyte disturbance.
  • It is given as a single oral dose before the chemotherapy cycle rather than as ongoing daily therapy and is usually combined with a corticosteroid.

Monitoring

Monitor the adequacy of emetic control across the cycle and consider ECG and electrolytes where additional QT-prolonging risk factors are present.

Counselling the patient

  • Take the single dose about an hour before chemotherapy starts.
  • Constipation, headache and tiredness are common; report severe constipation.
  • Tell the team about all other medicines, as this drug can change how some are handled.

Evidence & guidelines

The combination's efficacy in preventing chemotherapy-induced nausea and vomiting is supported by registration trials and reflected in antiemetic guidelines.

Reference: NICE TA313; ESMO; Drug verified in RxNorm (NLM); confirm dosing against the manufacturer SPC (eMC). Verify against your local formulary and current prescribing references before prescribing. The structured dose values shown have been reviewed by a clinician. Monograph status: clinician-reviewed (2026-07-04).

Related

Curated clinical cross-links plus same-class fallbacks.

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