What are the usage recommendations for Akynzeo (netupitant and palonosetron) in preventing chemotherapy-induced nausea and vomiting?

Akynzeo Usage Recommendations for Chemotherapy-Induced Nausea and Vomiting

Akynzeo (netupitant/palonosetron) should be administered as a single dose 1 hour before chemotherapy in combination with dexamethasone to prevent both acute and delayed chemotherapy-induced nausea and vomiting. 1

Formulations and Mechanism of Action

Akynzeo is available in multiple formulations:

• Oral capsules (300 mg netupitant/0.5 mg palonosetron)
• Injectable formulation (Ready-to-Use)
• Injectable formulation (To-be-Diluted)

Akynzeo combines two antiemetic agents:

• Palonosetron: A 5-HT3 receptor antagonist that prevents nausea and vomiting during the acute phase
• Netupitant (or fosnetupitant in IV formulations): An NK1 receptor antagonist that prevents nausea and vomiting during both acute and delayed phases

Dosing Recommendations by Chemotherapy Type

For Highly Emetogenic Chemotherapy (HEC), including Cisplatin-Based Regimens:

• Oral Akynzeo: 1 capsule 1 hour before chemotherapy
• Dexamethasone: 12 mg PO 30 minutes before chemotherapy on day 1, followed by 8 mg once daily on days 2-4
• IV Akynzeo: 1 vial infused over 30 minutes starting 30 minutes before chemotherapy 1

For Anthracycline-Cyclophosphamide Based Chemotherapy and Other Moderately Emetogenic Chemotherapy (MEC):

• Oral Akynzeo: 1 capsule 1 hour before chemotherapy
• Dexamethasone: 12 mg PO 30 minutes before chemotherapy on day 1 only
• No additional antiemetics required on days 2-4 1

Administration Guidelines

Oral Akynzeo:

• Can be taken with or without food
• Should be administered as a whole capsule 1
• For patients with difficulty swallowing, evidence suggests the capsule can be opened and contents administered separately while maintaining efficacy 2

IV Akynzeo (Ready-to-Use):

1. Inspect solution for particulate matter before administration
2. Insert vented IV set through septum (use immediately once punctured)
3. Invert and hang vial using attached strap
4. Administer over 30 minutes
5. Flush line with saline or dextrose after infusion 1

IV Akynzeo (To-be-Diluted):

1. Dilute with 30 mL of 5% Dextrose or 0.9% Sodium Chloride
2. Administer over 30 minutes
3. Flush line after infusion 1

Clinical Efficacy

Akynzeo has demonstrated superior efficacy compared to palonosetron alone:

• Higher complete response rates (no emesis, no rescue medication) in acute, delayed, and overall phases 3, 4
• Efficacy maintained over multiple chemotherapy cycles 4
• Non-inferior to aprepitant plus granisetron regimens 3

Special Considerations

• Limitations: IV formulations have not been studied for prevention of nausea and vomiting associated with anthracycline plus cyclophosphamide chemotherapy 1
• Compatibility: IV Akynzeo is compatible with IV dexamethasone sodium phosphate (can be infused simultaneously) 1
• Storage: Use immediately once the stopper is punctured for IV formulations 1

Common Pitfalls to Avoid

1. Inadequate coverage: Failing to provide dexamethasone on days 2-4 for highly emetogenic chemotherapy
2. Improper timing: Administering Akynzeo too close to chemotherapy (should be given 1 hour before for oral formulation)
3. Overlooking other causes of nausea: Always consider other potential causes such as radiotherapy, infection, electrolyte disturbances, constipation, gastrointestinal obstruction, brain metastases, or medication side effects 5
4. Inappropriate formulation selection: Using IV formulations for anthracycline-cyclophosphamide regimens where they haven't been studied

Akynzeo's fixed-dose combination offers a convenient option that aligns with guideline recommendations for CINV prevention, potentially improving adherence to antiemetic protocols 6.