Akynzeo

Name: Akynzeo

What Is Akynzeo?

Netupitant and palonosetron is a combination medicine used in adults to prevent nausea and vomiting caused by medicine to treat cancer (chemotherapy).

Netupitant and palonosetron helps prevent nausea and vomiting that occurs both during your chemotherapy treatment, or that occurs later on (delayed nausea and vomiting).

Netupitant and palonosetron is not for preventing nausea or vomiting caused by factors other than chemotherapy.

Netupitant and palonosetron may also be used for purposes not listed in this medication guide.

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.

You should not use this medicine if you are allergic to netupitant or palonosetron.

To make sure netupitant and palonosetron is safe for you, tell your doctor if you have:

  • liver disease;
  • kidney disease; or
  • if you have ever had an allergic reaction to a medicine for nausea or vomiting, such as dolasetron (Anzemet) or ondansetron (Zofran).

FDA pregnancy category C. It is not known whether netupitant and palonosetron will harm an unborn baby. Tell your doctor if you are pregnant or plan to become pregnant while using this medicine.

It is not known whether netupitant and palonosetron passes into breast milk or if it could harm a nursing baby. You should not breast-feed while using this medicine.

Netupitant and palonosetron is not approved for use by anyone younger than 18 years old.

What side effects can this medication cause?

Netupitant and palonosetron may cause side effects. Tell your doctor if any of these symptoms are severe or do not go away:

  • headache
  • stomach pain
  • heartburn
  • constipation
  • weakness
  • redness of the skin

Some side effects can be serious. If you experience any of the following symptoms, call your doctor immediately or seek emergency medical treatment:

  • hives
  • rash
  • itching
  • difficulty breathing or swallowing
  • shortness of breath
  • dizziness, lightheadedness, and fainting
  • fast, slow or irregular heartbeat
  • agitation
  • hallucinations (seeing things or hearing voices that do not exist)
  • fever
  • flushing
  • excessive sweating
  • confusion
  • nausea, vomiting, and diarrhea
  • loss of coordination
  • stiff or twitching muscles
  • seizures
  • coma (loss of consciousness)

Netupitant and palonosetron may cause other side effects. Call your doctor if you have any unusual problems while taking this medication.

If you experience a serious side effect, you or your doctor may send a report to the Food and Drug Administration's (FDA) MedWatch Adverse Event Reporting program online (http://www.fda.gov/Safety/MedWatch) or by phone (1-800-332-1088).

Brand names

  • Akynzeo®

Overdose

No specific information is available on the treatment of overdosage with AKYNZEO. In the event of overdose, AKYNZEO should be discontinued and general supportive treatment and monitoring should be provided. Because of the antiemetic activity of AKYNZEO, drug-induced emesis may not be effective. Dialysis studies have not been performed; due to the large volume of distribution, dialysis is unlikely to be an effective treatment for AKYNZEO overdose.

A total of 33 adult cancer patients were administered oral palonosetron at a dose of 90 μg/kg (equivalent to 6 mg fixed dose), as part of a dose ranging study. This is approximately 12 times the recommended oral dose of 0.5 mg palonosetron. This dose group had a similar incidence of adverse events compared to the other dose groups and no dose response effects were observed. The highest dose of netupitant administered to 1169 cancer patients was 300 mg. The highest dose of netupitant administered to 49 healthy subjects was 600 mg. A similar incidence of adverse events was observed when compared to lower doses of netupitant in the respective populations of cancer patients and healthy subjects.

Akynzeo Overview

Akynzeo is a prescription medication used to prevent nausea and vomiting in patients receiving cancer chemotherapy.

Akynzeo is available in capsule form and is taken 1 hour before the start of chemotherapy. It can be taken with or without food.

This medication comes in a single capsule that contains two medications: netupitant and palonosetron. Palonosetron is a serotonin receptor antagonist. This drug prevents nausea and vomiting during the first 24 hours after the start of cancer chemotherapy. Netupitant is a substance P/neurokinin 1 receptor antagonist. This drug prevents nausea and vomiting during both the acute phase(first 24 hours) and delayed phase (from 25 to 120 hours) after the start of cancer chemotherapy.

Common side effects of Akynzeo include headache, weakness, fatigue, indigestion and constipation.

Akynzeo can also cause dizziness. Do not drive or operate heavy machinery until you know how Akynzeo affects you.

Uses of Akynzeo

Akynzeo is a prescription medication used to prevent nausea and vomiting in patients receiving cancer chemotherapy.

This medication may be prescribed for other uses. Ask your doctor or pharmacist for more information.

What should I discuss with my healthcare provider before taking netupitant and palonosetron?

You should not use this medicine if you are allergic to netupitant or palonosetron.

To make sure netupitant and palonosetron is safe for you, tell your doctor if you have:

  • liver disease;

  • kidney disease; or

  • if you have ever had an allergic reaction to a medicine for nausea or vomiting, such as dolasetron (Anzemet) or ondansetron (Zofran).

FDA pregnancy category C. It is not known whether netupitant and palonosetron will harm an unborn baby. Tell your doctor if you are pregnant or plan to become pregnant while using this medicine.

It is not known whether netupitant and palonosetron passes into breast milk or if it could harm a nursing baby. You should not breast-feed while using this medicine.

Netupitant and palonosetron is not approved for use by anyone younger than 18 years old.

Netupitant and palonosetron side effects

Get emergency medical help if you have any of these signs of an allergic reaction: hives; chest pain, difficulty breathing; swelling of your face, lips, tongue, or throat.

Call your doctor at once if you have:

  • high levels of serotonin in the body--agitation, hallucinations, fever, fast heart rate, overactive reflexes, nausea, vomiting, diarrhea, loss of coordination, fainting.

Common side effects may include:

  • upset stomach, constipation;

  • headache;

  • skin redness; or

  • weakness, tired feeling.

This is not a complete list of side effects and others may occur. Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.

Commonly used brand name(s)

In the U.S.

  • Akynzeo

Available Dosage Forms:

  • Capsule

Therapeutic Class: Antiemetic

Pharmacologic Class: Neurokinin-1 Receptor Antagonist

Indications and Usage for Akynzeo

Akynzeo is indicated for the prevention of acute and delayed nausea and vomiting associated with initial and repeat courses of cancer chemotherapy, including, but not limited to, highly emetogenic chemotherapy. Akynzeo is an oral fixed combination of palonosetron and netupitant: palonosetron prevents nausea and vomiting during the acute phase and netupitant prevents nausea and vomiting during both the acute and delayed phase after cancer chemotherapy.

How Supplied/Storage and Handling

Akynzeo (300 mg netupitant/0.5 mg palonosetron) capsules: hard gelatin capsules with white body and caramel cap with “HE1” printed on the body. They are supplied as follows:

NDC # 69639-101-01: pack of one capsule in one blister

NDC # 69639-101-04: pack of four capsules (two capsules per blister strip).

Storage

Store at 20 °C to 25 °C (68 °F to 77 °F); excursions permitted from 15 °C to 30 °C (59 °F to 86 °F) [see USP Controlled Room Temperature].

Pregnancy & Lactation

Pregnancy Category: C

Lactation: Unknown if distributed in human breast milk

Pregnancy Categories

A:Generally acceptable. Controlled studies in pregnant women show no evidence of fetal risk.

B:May be acceptable. Either animal studies show no risk but human studies not available or animal studies showed minor risks and human studies done and showed no risk.

C:Use with caution if benefits outweigh risks. Animal studies show risk and human studies not available or neither animal nor human studies done.

D:Use in LIFE-THREATENING emergencies when no safer drug available. Positive evidence of human fetal risk.

X:Do not use in pregnancy. Risks involved outweigh potential benefits. Safer alternatives exist.

NA:Information not available.

Geriatric

Appropriate studies performed to date have not demonstrated geriatric-specific problems that would limit the usefulness of netupitant and palonosetron combination in the elderly. However, elderly patients are more likely to have kidney, liver, or heart problems, which may require caution in patients receiving netupitant and palonosetron combination.

Drug Interactions

Although certain medicines should not be used together at all, in other cases two different medicines may be used together even if an interaction might occur. In these cases, your doctor may want to change the dose, or other precautions may be necessary. When you are taking this medicine, it is especially important that your healthcare professional know if you are taking any of the medicines listed below. The following interactions have been selected on the basis of their potential significance and are not necessarily all-inclusive.

Using this medicine with any of the following medicines is not recommended. Your doctor may decide not to treat you with this medication or change some of the other medicines you take.

  • Apomorphine

Using this medicine with any of the following medicines is usually not recommended, but may be required in some cases. If both medicines are prescribed together, your doctor may change the dose or how often you use one or both of the medicines.

  • Almotriptan
  • Amineptine
  • Amitriptyline
  • Amitriptylinoxide
  • Amoxapine
  • Brompheniramine
  • Buprenorphine
  • Buspirone
  • Carbamazepine
  • Chlorpheniramine
  • Cilostazol
  • Citalopram
  • Clomipramine
  • Cocaine
  • Cyclobenzaprine
  • Desipramine
  • Desvenlafaxine
  • Dextromethorphan
  • Dibenzepin
  • Domperidone
  • Doxepin
  • Duloxetine
  • Efavirenz
  • Eletriptan
  • Enzalutamide
  • Escitalopram
  • Fentanyl
  • Fluoxetine
  • Fluvoxamine
  • Fosphenytoin
  • Frovatriptan
  • Furazolidone
  • Hydroxytryptophan
  • Imipramine
  • Iproniazid
  • Isocarboxazid
  • Levomilnacipran
  • Linezolid
  • Lithium
  • Lofepramine
  • Lorcaserin
  • Melitracen
  • Meperidine
  • Methadone
  • Methylene Blue
  • Milnacipran
  • Mirtazapine
  • Mitotane
  • Moclobemide
  • Naloxegol
  • Naratriptan
  • Nefazodone
  • Nialamide
  • Nortriptyline
  • Olaparib
  • Opipramol
  • Oxcarbazepine
  • Oxycodone
  • Paroxetine
  • Pentazocine
  • Phenelzine
  • Phenytoin
  • Piperaquine
  • Primidone
  • Procarbazine
  • Protriptyline
  • Rasagiline
  • Rifabutin
  • Rifampin
  • Rifapentine
  • Rizatriptan
  • Selegiline
  • Sertraline
  • Sibutramine
  • Simeprevir
  • St John's Wort
  • Sumatriptan
  • Tapentadol
  • Tianeptine
  • Tramadol
  • Tranylcypromine
  • Trazodone
  • Trimipramine
  • Tryptophan
  • Venlafaxine
  • Vilazodone
  • Vortioxetine
  • Zolmitriptan

Using this medicine with any of the following medicines may cause an increased risk of certain side effects, but using both drugs may be the best treatment for you. If both medicines are prescribed together, your doctor may change the dose or how often you use one or both of the medicines.

  • Dexamethasone

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.

Akynzeo side effects

Get emergency medical help if you have any of these signs of an allergic reaction to Akynzeo: hives; chest pain, difficulty breathing; swelling of your face, lips, tongue, or throat.

Call your doctor at once if you have:

  • high levels of serotonin in the body - agitation, hallucinations, fever, fast heart rate, overactive reflexes, nausea, vomiting, diarrhea, loss of coordination, fainting.

Common Akynzeo side effects may include:

  • upset stomach, constipation;

  • headache;

  • skin redness; or

  • weakness, tired feeling.

This is not a complete list of side effects and others may occur. Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.

For the Consumer

Applies to netupitant / palonosetron: oral capsule

Along with its needed effects, netupitant / palonosetron may cause some unwanted effects. Although not all of these side effects may occur, if they do occur they may need medical attention.

Check with your doctor immediately if any of the following side effects occur while taking netupitant / palonosetron:

Incidence not known
  • Agitation
  • confusion
  • dizziness
  • fever
  • hearing or seeing things that are not there
  • muscle twitching
  • overactive reflexes
  • poor coordination
  • shivering
  • sweating
  • trembling or shaking

Some side effects of netupitant / palonosetron may occur that usually do not need medical attention. These side effects may go away during treatment as your body adjusts to the medicine. Also, your health care professional may be able to tell you about ways to prevent or reduce some of these side effects. Check with your health care professional if any of the following side effects continue or are bothersome or if you have any questions about them:

More common
  • Headache
  • fatigue
  • unusual tiredness or weakness
Less common
  • constipation
  • flushing or redness of the skin
  • heartburn
  • indigestion
  • stomach discomfort, upset, or pain

Akynzeo Pharmacokinetics

Absorption

Absorption

Palonosetron: Well absorbed following oral administration, with absolute bioavailability reaching 97%.1

Plasma Concentrations

Netupitant: Measurable plasma concentrations achieved within 0.25–3 hours.1

Peak plasma concentrations of netupitant and palonosetron attained in approximately 5 hours.1

Special Populations

Netupitant: In patients with mild or moderate hepatic impairment, mean exposure was 67 and 86% higher, respectively, than in healthy individuals; mean peak concentration was approximately 40 and 41% higher, respectively, than in healthy individuals.1

Palonosetron: In patients with mild or moderate hepatic impairment, mean exposure was 33 and 62% higher, respectively, than in healthy individuals; mean peak concentration was approximately 14% higher and unchanged, respectively, compared with healthy individuals.1

Mild and moderate renal impairment: Pharmacokinetics of netupitant not affected.1

Severe renal impairment: Pharmacokinetics of netupitant not studied; pharmacokinetics of palonosetron not substantially affected.1 Pharmacokinetics of netupitant and palonosetron not studied in patients with end-stage renal disease requiring hemodialysis.1

In a population pharmacokinetic analysis, age (range: 29–75 years of age) did not affect pharmacokinetics of netupitant or palonosetron in cancer patients receiving the fixed combination.1 In healthy individuals >65 years of age, mean systemic exposure and peak concentration were 25 and 36% higher for netupitant, respectively, and 37 and 10% higher for palonosetron, respectively, compared with those in healthy younger adults (22–45 years of age).1

Distribution

Plasma Protein Binding

Netupitant: >99.5% and >97% for netupitant and its principal metabolites (M1, M2, and M3), respectively.1

Palonosetron: Approximately 62%.1

Elimination

Metabolism

Netupitant: Extensively metabolized primarily by CYP3A4 and, to a lesser extent, by CYP2C9 and CYP2D6.1

Palonosetron: In vitro studies suggest CYP2D6 and, to a lesser extent, CYP3A4 and CYP1A2 involved in metabolism.1

Elimination Route

Netupitant: Approximately 50% of a single dose recovered in urine and feces within 120 hours following oral administration.1 A total of approximately 4 and 71% of a radioactive dose recovered in urine and feces collected over 336 hours, respectively; <1% recovered in urine as unchanged drug.1

Palonosetron: 85–93% of palonosetron dose excreted in urine and 5–8% excreted in feces; approximately 40% of the dose recovered in urine as unchanged drug.1

Half-life

Netupitant: 80 hours in cancer patients.1

Palonosetron: 48 hours in cancer patients.1

Stability

Storage

Oral

Capsules

20–25°C (may be exposed to 15–30°C).1

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