Akynzeo 300-0.5mg Capsules

Akynzeo is a fixed combination of netupitant and palonosetron. Netupitant is a selective antagonist of the human substance P neurokinin-1 (NK1) receptor. Palonosetron is a selective serotonin-3 (5-HT3) receptor antagonist. Chemotherapy-induced nausea and vomiting (CINV) is mediated through two main pathways: acute CINV is primarily mediated by serotonin release from enterochromaffin cells in the gut, activating 5-HT3 receptors; delayed CINV is primarily mediated by substance P release in the central nervous system, activating NK1 receptors. By blocking both pathways, Akynzeo provides broad-spectrum antiemetic coverage for both acute and delayed CINV.

Urgent Side Effects: Seek Medical Help Right Away

Although rare, some people may experience severe and potentially life-threatening side effects while taking this medication. If you notice any of the following symptoms, contact your doctor immediately or seek emergency medical attention:

Signs of an allergic reaction, such as:
+ Rash
+ Hives
+ Itching
+ Red, swollen, blistered, or peeling skin with or without fever
+ Wheezing
+ Tightness in the chest or throat
+ Trouble breathing, swallowing, or talking
+ Unusual hoarseness
+ Swelling of the mouth, face, lips, tongue, or throat
Serotonin syndrome, a severe and potentially deadly condition, which may be more likely to occur if you are taking certain other medications. Warning signs include:
+ Agitation
+ Change in balance
+ Confusion
+ Hallucinations
+ Fever
+ Fast or abnormal heartbeat
+ Flushing
+ Muscle twitching or stiffness
+ Seizures
+ Shivering or shaking
+ Excessive sweating
+ Severe diarrhea
+ Upset stomach
+ Vomiting
+ Severe headache

Other Possible Side Effects

Like all medications, this drug can cause side effects. While many people may not experience any side effects or only minor ones, it is essential to discuss any concerns with your doctor. If you experience any of the following side effects or any other symptoms that bother you or do not go away, contact your doctor:

Constipation
Headache
Redness
Feeling tired or weak
* Upset stomach

This list is not exhaustive, and you may experience other side effects not mentioned here. If you have questions or concerns about side effects, consult your doctor. You can also report side effects to the FDA at 1-800-332-1088 or online at https://www.fda.gov/medwatch.

Before Taking This Medication: Important Information to Share with Your Doctor

It is essential to inform your doctor about the following:

Any allergies you have, including allergies to this medication, its components, or other substances. Be sure to describe the allergic reaction you experienced, including any symptoms that occurred.
Existing health conditions, such as kidney disease or liver disease, that may affect your ability to take this medication safely.

Additionally, tell your doctor about all the medications you are currently taking, including:

Prescription and over-the-counter (OTC) medications
Natural products
* Vitamins

Some medications, such as rifampin, St. John's Wort, and certain seizure medications, should not be taken with this drug. However, this is not an exhaustive list, and there may be other medications that interact with this drug.

To ensure your safety, it is crucial to discuss all your medications and health conditions with your doctor and pharmacist. They will help you determine whether it is safe to take this medication with your existing medications and health conditions. Never start, stop, or change the dose of any medication without first consulting your doctor.

It is essential to inform all your healthcare providers, including doctors, nurses, pharmacists, and dentists, that you are taking this medication. If you are pregnant, planning to become pregnant, or are breast-feeding, be sure to discuss this with your doctor. This conversation will help you understand the benefits and risks of taking this drug during pregnancy or breast-feeding, allowing you to make an informed decision about your care and the well-being of your baby.

• Dexamethasone (Netupitant is a moderate CYP3A4 inhibitor; reduce dexamethasone dose by approximately 50% on Day 1 when co-administered with Akynzeo).
• Strong CYP3A4 Inducers (e.g., Rifampin, Carbamazepine, Phenytoin, St. John's Wort): May significantly decrease netupitant plasma concentrations, reducing efficacy. Avoid co-administration if possible.

• CYP3A4 Substrates (e.g., Midazolam, Erythromycin, Oral Contraceptives, Warfarin, Cyclosporine, Tacrolimus, Everolimus, Sirolimus, Fentanyl, Alfentanil, Quinidine, Ergot alkaloids): Netupitant may increase plasma concentrations of co-administered CYP3A4 substrates. Monitor for increased adverse effects or adjust dose of the substrate as needed.
• Chemotherapeutic Agents (e.g., Docetaxel, Etoposide, Irinotecan, Paclitaxel, Vinblastine, Vincristine, Ifosfamide): Netupitant may increase exposure to these agents. Monitor for increased toxicity.

• Nausea
• Vomiting
• Headache
• Constipation
• Fatigue
• Dyspepsia
• Hiccups
• Dizziness
• Weakness

Limited data on Akynzeo use in pregnant women are insufficient to inform a drug-associated risk of adverse developmental outcomes. Use only if the potential benefit justifies the potential risk to the fetus.

It is not known whether netupitant or palonosetron are excreted in human milk. Due to the potential for serious adverse reactions in breastfed infants, advise women not to breastfeed during treatment with Akynzeo and for at least 1 month after the last dose.

Safety and effectiveness in pediatric patients have not been established.

No dose adjustment is necessary for elderly patients. Clinical studies did not show differences in efficacy or safety between elderly and younger patients, but greater sensitivity of some older individuals cannot be ruled out.

• Akynzeo is a single-dose, fixed-combination antiemetic that covers both acute and delayed CINV, simplifying antiemetic regimens.
• It is indicated for highly and moderately emetogenic chemotherapy.
• Due to netupitant's long half-life and CYP3A4 inhibition, a 50% reduction in dexamethasone dose is recommended on Day 1 when co-administered.
• Patients should be monitored for constipation, a common side effect of 5-HT3 antagonists.
• Consider potential drug interactions with other CYP3A4 substrates, especially those with narrow therapeutic indices.

• NK1 receptor antagonists (e.g., Aprepitant, Fosaprepitant, Rolapitant) administered with a 5-HT3 receptor antagonist (e.g., Ondansetron, Granisetron, Dolasetron) and Dexamethasone.
• Other 5-HT3 receptor antagonists alone or in combination with Dexamethasone (for MEC or less emetogenic regimens).

If your symptoms or health issues persist or worsen, it's essential to contact your doctor for further guidance. To ensure your safety, never share your medication with others or take someone else's medication. Some medications may come with an additional patient information leaflet, so be sure to check with your pharmacist for more information. If you have any questions or concerns about your medication, don't hesitate to reach out to your doctor, nurse, pharmacist, or other healthcare provider. In the event of a suspected overdose, immediately call your local poison control center or seek medical attention. When seeking help, be prepared to provide details about the medication taken, the amount, and the time it happened.