Name: Akynzeo


  • Eisai, Inc

Akynzeo Interactions

Tell your doctor about all the medicines you take, including prescription and non-prescription medicines, vitamins, and herbal supplements. Especially tell your doctor if you take:

  • benzodiazepines including alprazolam (Xanax), midazolam, and triazolam (Halcion)
  • certain chemotherapy medications such as cyclophosphamide (Cytoxan), docetaxel (Docefrez, Taxotere), etoposide, ifosfamide (Ifex), imatinib (Gleevec), irinotecan (Camptosar), paclitaxel (Taxol), vinblastine, vincristine, and vinorelbine (Navelbine)
  • dexamethasone
  • erythromycin (E.E.S., Ery-tab, others)
  • fentanyl (Abstral, Actiq, Duragesic, Fentora, Lazanda, Onsolis, Subsys)
  • ketoconazole (Nizoral)
  • lithium (Lithobid)
  • medications to treat migraines such as almotriptan (Axert), eletriptan (Relpax), frovatriptan (Frova), naratriptan (Amerge), rizatriptan (Maxalt), sumatriptan (Imitrex), and zolmitriptan (Zomig)
  • methylene blue
  • mirtazapine (Remeron)
  • monoamine oxidase (MAO) inhibitors including isocarboxazid (Marplan), linezolid (Zyvox), phenelzine (Nardil), selegiline (Eldepryl, Emsam, Zelapar), and tranylcypromine (Parnate)
  • phenobarbital
  • rifampin (Rifadin, Rimactane, in Rifater, in Rifamate)
  • selective serotonin reuptake inhibitors (SSRIs) such as citalopram (Celexa), escitalopram (Lexapro), fluoxetine (Prozac, Sarafem, in Symbyax), fluvoxamine (Luvox), paroxetine (Brisdelle, Paxil, Pexeva), and sertraline (Zoloft)
  • tramadol (Conzip, Ultram, in Ultracet)

This is not a complete list of Akynzeo drug interactions. Ask your doctor or pharmacist for more information.

Akynzeo and Pregnancy

Tell your doctor if you are pregnant or plan to become pregnant.

The FDA categorizes medications based on safety for use during pregnancy. Five categories - A, B, C, D, and X - are used to classify the possible risks to an unborn baby when a medication is taken during pregnancy.

Akynzeo falls into category C. In animal studies, pregnant animals were given this medication and had some babies born with problems. No well-controlled studies have been done in humans. Therefore, this medication may be used if the potential benefits to the mother outweigh the potential risks to the unborn child.

Akynzeo Dosage

Take this medication exactly as prescribed by your doctor. Follow the directions on your prescription label carefully.

The dose your doctor recommends may be based on the following:

  • the condition being treated

The recommended dose of Akynzeo is one capsule (300 mg netupitant/0.5mg palonosetron) approximately 1 hour before chemotherapy. It is usually administered with dexamethasone.

What happens if I overdose?

Seek emergency medical attention or call the Poison Help line at 1-800-222-1222.

Proper Use of Akynzeo

Take this medicine only as directed by your doctor. Do not take more of it, do not take it more often, and do not take it for a longer time than your doctor ordered.

This medicine should come with a patient information leaflet. Read and follow the instructions carefully. Ask your doctor if you have any questions.

Take this medicine with or without food.


The dose of this medicine will be different for different patients. Follow your doctor's orders or the directions on the label. The following information includes only the average doses of this medicine. If your dose is different, do not change it unless your doctor tells you to do so.

The amount of medicine that you take depends on the strength of the medicine. Also, the number of doses you take each day, the time allowed between doses, and the length of time you take the medicine depend on the medical problem for which you are using the medicine.

  • For oral dosage form (capsules):
    • For prevention of nausea and vomiting caused by chemotherapy:
      • Adults—One capsule given within 1 hour before starting cancer treatment.
      • Children—Use and dose must be determined by your doctor.

Missed Dose

If you miss a dose of this medicine, take it as soon as possible. However, if it is almost time for your next dose, skip the missed dose and go back to your regular dosing schedule. Do not double doses.


Store the medicine in a closed container at room temperature, away from heat, moisture, and direct light. Keep from freezing.

Keep out of the reach of children.

Do not keep outdated medicine or medicine no longer needed.

Ask your healthcare professional how you should dispose of any medicine you do not use.

What do I need to tell my doctor BEFORE I take Akynzeo?

  • If you have an allergy to Akynzeo (netupitant and palonosetron) or any part of this medicine.
  • If you are allergic to any drugs like this one, any other drugs, foods, or other substances. Tell your doctor about the allergy and what signs you had, like rash; hives; itching; shortness of breath; wheezing; cough; swelling of face, lips, tongue, or throat; or any other signs.
  • If you have any of these health problems: Kidney disease or liver disease.
  • If you are taking rifampin.

This medicine may interact with other drugs or health problems.

Tell your doctor and pharmacist about all of your drugs (prescription or OTC, natural products, vitamins) and health problems. You must check to make sure that it is safe for you to take Akynzeo with all of your drugs and health problems. Do not start, stop, or change the dose of any drug without checking with your doctor.

What are some things I need to know or do while I take Akynzeo?

  • Tell all of your health care providers that you take this medicine. This includes your doctors, nurses, pharmacists, and dentists.
  • Tell your doctor if you are pregnant or plan on getting pregnant. You will need to talk about the benefits and risks of using Akynzeo while you are pregnant.
  • Tell your doctor if you are breast-feeding. You will need to talk about any risks to your baby.

If OVERDOSE is suspected

If you think there has been an overdose, call your poison control center or get medical care right away. Be ready to tell or show what was taken, how much, and when it happened.

How do I store and/or throw out Akynzeo?

  • Store at room temperature.
  • Store in a dry place. Do not store in a bathroom.
  • Keep all drugs in a safe place. Keep all drugs out of the reach of children and pets.
  • Check with your pharmacist about how to throw out unused drugs.


Mechanism of Action

Netupitant: Tachykinin NK1 receptor (substance P) antagonist

Palonosetron: 5-hydroxytryptamine 3 (5-HT3) receptor antagonist; binds to 5-HT3 receptors both in peripheral and central nervous system, with primary effects in GI tract


Peak plasma time

  • netupitant: 5 hr
  • palonosetron: 5 hr

Peak plasma concentration

  • netupitant: 434 ng/mL
  • palonosetron: 1.53 ng/mL


  • netupitant: 14,401 ng•hr/mL
  • palonosetron: 56.7 ng•hr/mL


Protein bound

  • netupitant: >99.5%
  • palonosetron: 62%


  • netupitant: 1982 L
  • palonosetron: 8.3 L/kg



  • Metabolized mainly by CYP3A4, and to a lesser degree by CYP2C9 and CYP2D6
  • Extensively metabolized to form three major metabolites: desmethyl derivative, M1; N-oxide derivative, M2; and OH-methyl derivative, M3
  • Metabolites M1, M2, and M3 were shown to bind to the substance P/neurokinin 1 (NK1) receptor


  • Metabolized mainly by CYP2D6, and to a lesser extent by CYP3A4 and CYP1A2
  • 50% metabolized to form 2 primary metabolites: N-oxide-palonosetron and 6-S hydroxy-palonosetron



  • netupitant: 96 hr; 80 hr (patients with cancer)
  • palonosetron: 44 hr; 48 hr (patients with cancer)

Total body clearance

  • netupitant: 20.3 L/hr
  • palonosetron: 160 mL/hr/kg

Renal clearance

  • palonosetron: 66.5 mL/hr/kg


  • netupitant: 70% feces; 4% urine
  • palonosetron: 5-8% feces; 85-93% urine


Information about this netupitant-and-palonosetron-oral-route
Pregnancy Category Explanation
All Trimesters C Animal studies have shown an adverse effect and there are no adequate studies in pregnant women OR no animal studies have been conducted and there are no adequate studies in pregnant women.

Important information

Follow all directions on your medicine label and package. Tell each of your healthcare providers about all your medical conditions, allergies, and all medicines you use.

How should I take Akynzeo?

Take Akynzeo exactly as prescribed by your doctor. Follow all directions on your prescription label. Do not use this medicine in larger or smaller amounts or for longer than recommended.

Akynzeo is usually taken 1 hour before the start of chemotherapy. Follow your doctor's instructions.

You may take Akynzeo with or without food.

This medicine is given ahead of time and will not treat nausea or vomiting you already have.

Store at room temperature away from moisture and heat.

Akynzeo dosing information

Usual Adult Dose of Akynzeo for Nausea/Vomiting - Chemotherapy Induced:

Highly Emetogenic Chemotherapy, Including Cisplatin Based Chemotherapy:
-Day 1: One capsule (300 mg netupitant/0.5 mg palonosetron) orally approximately 1 hour prior to the start of chemotherapy along with 12 mg dexamethasone orally 30 minutes prior to chemotherapy
-Days 2 to 4: One capsule (300 mg netupitant/0.5 mg palonosetron) orally approximately 1 hour prior to the start of chemotherapy along with 8 mg dexamethasone orally once a day

Anthracyclines, Cyclophosphamide Based Chemotherapy, and Chemotherapy Not Considered Highly Emetogenic:
-Day 1: One capsule (300 mg netupitant/0.5 mg palonosetron) orally approximately 1 hour prior to the start of chemotherapy along with 12 mg dexamethasone orally 30 minutes prior to chemotherapy
-Days 2 to 4: One capsule (300 mg netupitant/0.5 mg palonosetron) orally approximately 1 hour prior to the start of chemotherapy; dexamethasone administration not necessary

-Can be taken with or without food

Use: Prevention of acute and delayed nausea and vomiting associated with initial and repeat courses of cancer chemotherapy

Netupitant / palonosetron Breastfeeding Warnings

A decision should be made to discontinue breastfeeding or discontinue the drug, taking into account the importance of the drug to the mother. Excreted into human milk: Unknown Excreted into animal milk: Data not available Comments: The effects in the nursing infant are unknown.

Cautions for Akynzeo


None known.1


Sensitivity Reactions

Hypersensitivity reactions, including anaphylaxis, reported in palonosetron-treated patients with or without known hypersensitivity to other 5-HT3 receptor antagonists.1 29 30 (See Advice to Patients.)

Serotonin Syndrome

Serotonin syndrome (in some cases fatal) reported in patients receiving 5-HT3 receptor antagonists.1 Most cases were associated with concomitant use of other serotonergic drugs (e.g., SSRIs, SNRIs, MAO inhibitors, mirtazapine, fentanyl, lithium, tramadol, IV methylene blue).1 Serotonin syndrome occurring with overdosage of another 5-HT3 receptor antagonist alone (ondansetron) also reported.1 31 The majority of reports of serotonin syndrome related to 5-HT3 receptor antagonist use occurred in a post-anesthesia care unit or infusion center.1

Manifestations of serotonin syndrome may include mental status changes (e.g., agitation, hallucinations, delirium, coma), autonomic instability (e.g., tachycardia, labile BP, dizziness, diaphoresis, flushing, hyperthermia), neuromuscular symptoms (e.g., tremor, rigidity, myoclonus, hyperreflexia, incoordination), and seizures with or without GI symptoms (e.g., nausea, vomiting, diarrhea).1

Monitor patients for emergence of serotonin syndrome, particularly during concomitant use of other serotonergic drugs.1 If symptoms of serotonin syndrome occur, discontinue fixed-combination netupitant and palonosetron and initiate supportive treatment.1 (See Specific Drugs under Interactions.)

Specific Populations


Category C.1


Not known whether netupitant or palonosetron distributed into human milk.1 Discontinue nursing or the fixed combination.1

Pediatric Use

Safety and efficacy not established in patients <18 years of age.1

Geriatric Use

No substantial differences in safety relative to younger adult cancer patients in clinical studies.1 (See Geriatric Patients under Dosage and Administration and see Special Populations, under Pharmacokinetics.)

Hepatic Impairment

No dosage adjustment necessary in patients with mild to moderate hepatic impairment (Child-Pugh score 5–9).1 (See Special Populations, under Pharmacokinetics.)

Limited data in patients with severe hepatic impairment (Child-Pugh score >9); avoid use in such patients.1

Renal Impairment

No dosage adjustment necessary in patients with mild or moderate renal impairment.1

Avoid use in patients with severe renal impairment or end-stage renal disease.1 (See Special Populations, under Pharmacokinetics.)

Common Adverse Effects

Headache,1 3 26 asthenia,1 dyspepsia,1 2 fatigue,1 constipation,1 26 erythema.1


  • Palonosetron, a second-generation 5-HT3 receptor antagonist, is pharmacologically related to first-generation 5-HT3 receptor antagonists (e.g., dolasetron, granisetron, ondansetron),5 11 13 14 15 35 but has a higher potency and higher binding affinity for 5-HT3 receptors, a longer elimination half-life, and a different molecular interaction with 5-HT3 receptors than these other 5-HT3 receptor antagonists and little or no affinity for other receptors.1 2 3 5 11 27 28 35 36

  • Netupitant is a selective antagonist at substance P/NK1 receptors.1 2 3 27 28 35 36

  • Netupitant crosses the blood-brain barrier and occupies NK1 receptors in the brain.1

  • Antiemetic activity of palonosetron for acute nausea and vomiting appears to be mediated via inhibition of serotonin activity both centrally (in area postrema and chemoreceptor trigger zone) and peripherally (in GI tract).1 5 6 7 8 9 10 12 13 15 16 17

  • Delayed emesis mainly associated with activation of tachykinin family NK1 receptors, which are widely distributed in the central and peripheral nervous systems, by substance P.1 Netupitant inhibits substance P-mediated responses in in vitro and in vivo studies.1 In addition, the combination of palonosetron and netupitant may inhibit the action of substance P synergistically.2 3 27 35 36





Hypersensitivity reactions (eg, anaphylaxis) reported in patients treated with palonosetron, with or without known hypersensitivity to other 5-HT3 receptor antagonists

Serotonin syndrome has been reported with 5-HT3 receptor antagonists (eg, palonosetron); most reports have been associated with concomitant use of serotonergic drugs (eg, selective serotonin reuptake inhibitors (SSRIs), serotonin and norepinephrine reuptake inhibitors (SNRIs), monoamine oxidase inhibitors, mirtazapine, fentanyl, lithium, tramadol, and IV methylene blue); discontinue netupitant/palonosetron if symptoms occur

Drug interactions overview

  • Netupitant is a CYP3A4 substrate and a moderate inhibitor of CYP3A4
  • Palonosetron is mainly metabolized by CYP2D6 and to a lesser extent by CYP3A4 and CYP1A2
  • Strong CYP3A4 inducers (eg, rifampin) can decrease netupitant/palonosetron efficacy by substantially reducing plasma concentrations of the netupitant component; avoid use
  • Concomitant use with a strong CYP3A4 inhibitor (eg, ketoconazole) can increase the systemic exposure to the netupitant component; no dosage adjustment is necessary for single dose administration

Patient Handout

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