Overview
11 DESCRIPTION AKYNZEO (300 mg netupitant/0.5 mg palonosetron) capsules are an oral combination product of netupitant, a substance P/neurokinin 1 (NK-1) receptor antagonist, and palonosetron hydrochloride, a serotonin-3 (5-HT 3 ) receptor antagonist. Both netupitant and palonosetron hydrochloride are anti-nausea and anti-emetic agents.
Mechanism of Action
12 CLINICAL PHARMACOLOGY 12.1 Mechanism of Action Netupitant is a selective antagonist of human substance P/neurokinin 1 (NK-1) receptors. Palonosetron is a 5-HT 3 receptor antagonist with a strong binding affinity for this receptor and little or no affinity for other receptors. Cancer chemotherapy may be associated with a high incidence of nausea and vomiting, particularly when certain agents, such as cisplatin, are used. 5-HT 3 receptors are located on the nerve terminals of the vagus in the periphery and centrally in the chemoreceptor trigger zone of the area postrema. Chemotherapeutic agents produce nausea and vomiting by stimulating the release of serotonin from the enterochromaffin cells of the small intestine.
Indications
- 1 INDICATIONS AND USAGE AKYNZEO capsules is indicated in combination with dexamethasone in adults 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 capsules is a 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.
Common Doses
- 8 mg
- 12 mg
- 30 mL
- 20 mL
Dosage
2 DOSAGE AND ADMINISTRATION Recommended Dosage AKYNZEO capsules: The recommended dosage is one AKYNZEO capsule administered 1 hour prior to the start of chemotherapy, with or without food. ( 2.1 ) Preparation and Administration AKYNZEO injection is supplied either as a Ready-to-Use (with hanger) vial or a To-be-Diluted vial. (2.2) AKYNZEO for injection requires dilution prior to administration. ( 2.3 ) See full prescribing information for information on preparation, administration, and incompatibilities for each product. (2.2, 2.3, 2.4 ) 2.
Contraindications
- 4 CONTRAINDICATIONS None. None ( 4 )
Side Effects
- 6 ADVERSE REACTIONS The following clinically significant adverse reactions are found elsewhere in the labeling: Hypersensitivity Reactions [see Warnings and Precautions ( 5.1 )] Serotonin Syndrome [see Warnings and Precautions ( 5.2 )] Most common adverse reactions (≥3%) for AKYNZEO capsules are headache, asthenia, dyspepsia, fatigue, constipation and erythema ( 6.1 ) The safety profile of AKYNZEO for injection was generally similar to that seen with AKYNZEO capsules. ( 6.1 ) To report SUSPECTED ADVERSE REACTIONS, contact HELSINN at 1-844-357-4668 or FDA at 1-800-FDA-1088 or www.fda.
Interactions
- 7 DRUG INTERACTIONS CYP3A4 Substrates: inhibition of CYP3A4 by netupitant can result in increased plasma concentrations of the concomitant drug for 6 days after single dosage administration of AKYNZEO; avoid concomitant CYP3A4 substrates for one week, if feasible. If not avoidable, consider dose reduction of the CYP3A4 substrate ( 7.1 ) CYP3A4 Inducers (e.g., rifampin): decreased plasma concentrations of netupitant; avoid use ( 7.2 ) 7.1 Effects of AKYNZEO on Other Drugs Interaction with CYP3A4 Substrates Netupitant is a moderate inhibitor of CYP3A4.