THERAPEUTICS

Brands

• Akynzeo

Generic?

• No

Class

• Antiemetic

Commonly Prescribed for

(FDA approved in bold)

• Prevention of chemotherapy-induced nausea and vomiting (CINV)

• Nausea and vomiting (gastroenteritis, postoperative)

• Pruritus

How the Drug Works

• Netupitant: selectively inhibits substance P (vomit inducer) at neurokinin 1 (NK1) receptors with long-lasting brain receptor (brainstem, area postrema) saturation after single dose

• Palonosetron: second-generation 5-HT3 antagonist with higher binding affinity and longer plasma half-life. It may trigger 5-HT3 receptor internalization and prolong receptor inhibition

How Long Until It Works

• Typically less than an hour

If It Works

• Use at lowest effective dose

If It Doesn't Work

• Increase dose, or discontinue and change to another agent

Best Augmenting Combos for Partial Response or Treatment-Resistance

• May add D2 antagonist, antihistamine, benzodiazepine, or corticosteroid

Tests

• None required

ADVERSE EFFECTS (AEs)

How the Drug Causes AEs

• Not known

Notable AEs

• Headache, asthenia, dyspepsia, fatigue, constipation, and erythema

Life-Threatening or Dangerous AEs

• Serotonin syndrome

• Hypersensitivity reactions such as angioedema and Stevens-Johnson syndrome have been reported

Weight Gain

• Unusua

Sedation

• Unusual

What to Do About AEs

• Reduce dose or discontinuation

Best Augmenting Agents to Reduce AEs

• Symptomatic management

DOSING AND USE

Usual Dosage Range

• 1 capsule

Dosage Forms

• Capsule: 300mg netupitant and 0.5mg palonosetron

How to Dose

• One capsule 1 hour and dexamethasone 12mg 30 minutes prior to chemotherapy on day 1. Dexamethasone 8mg orally once daily on days 2 to 4 if under highly emetogenic chemotherapy (cisplatin)

Dosing Tips

• Can be taken with or without food. Only for short-term use

Overdose

• May develop drowsiness or headache

Long-Term Use

• Not been studied

Habit Forming

• No

How to Stop

• No need to taper

Pharmacokinetics

• Netupitant: Tmax: 5 hours. Half-life: 80 hours. > 99.5% protein bound. Metabolized by CYP3A4 and inhibits CYP3A4