Netupitant + Palonosetron

Indications

Netupitant + Palonosetron is used for: Chemotherapy-Induced Nausea & Vomiting

Adult Dose

Chemotherapy-Induced Nausea & Vomiting Capsules: Indicated for in combination with dexamethasone in adults prevention of acute and delayed nausea and vomiting (N/V) associated with cancer chemotherapy, including, but not limited to, highly emetogenic chemotherapy Injection: Indicated in combination with dexamethasone in adults for prevention of acute and delayed N/V associated with initial and repeat courses of highly emetogenic chemotherapy Highly emetogenic chemotherapy Includes cisplatin-based chemotherapy 1 capsule (300 mg/0.5 mg) PO ~1 hr before starting chemotherapy OR 1 reconstituted vial (235mg/0.25mg) IV over 30 min starting 30 min before chemotherapy PLUS Dexamethasone 12 mg PO 30 minutes prior to chemotherapy on day 1 and 8 mg PO qDay on days 2-4 Chemotherapy not considered highly emetogenic Includes anthracyclines and cyclophosphamide-based chemotherapy 1 capsule (300 mg/0.5 mg) PO ~1 hr before starting chemotherapy PLUS Dexamethasone 12 mg PO 30 minutes prior to chemotherapy on day 1 Administration of dexamethasone on days 2-4 is not necessary Hepatic impairment Mild or moderate (Child-Pugh 5-8): No dosage adjustment required Severe (Child-Pugh >9): Avoid use

Child Dose

<18 years: Safety and efficacy not established

Renal Dose

Renal impairment Mild or moderate (CrCl 30-60 mL/min): No dosage adjustment required Severe (CrCl <30 mL/min) or end-stage renal disease (ESRD): Avoid use

Administration

IV Preparation Injection contains no antimicrobial preservatives Inject 20 mL D5W or 0.9% NaCl along the vial wall and not jetted in order to prevent foaming; swirl vial gently Prepare an infusion vial or bag filled with 30 mL of D5W or 0.9% NaCl Withdraw entire contents of the reconstituted vial and transfer it into the infusion vial or bag to yield a total volume of 50 mL Gently invert vial or bag until complete dissolution Before administration, inspect final diluted solution for particulate matter and discoloration; discard vial or bag if particulates and/or discoloration are observed IV Administration Infuse over 30 minutes At the end of the infusion, flush infusion line with the same carrier solution to ensure complete drug administration Oral Administration Capsules: Take with or without food

Contra Indications

Precautions

Hypersensitivity reactions (eg, anaphylaxis) reported in patients treated with palonosetron, with or without known hypersensitivity to other 5-HT3 receptor antagonists Serotonin syndrome has been reported with 5-HT3 receptor antagonists (eg, palonosetron); most reports have been associated with concomitant use of serotonergic drugs (eg, selective serotonin reuptake inhibitors (SSRIs), serotonin and norepinephrine reuptake inhibitors (SNRIs), monoamine oxidase inhibitors, mirtazapine, fentanyl, lithium, tramadol, and IV methylene blue); discontinue netupitant/palonosetron if symptoms occur

Pregnancy-Lactation

Interactions

Netupitant is a CYP3A4 substrate and a moderate inhibitor of CYP3A4 Palonosetron is mainly metabolized by CYP2D6 and to a lesser extent by CYP3A4 and CYP1A2 Strong CYP3A4 inducers (eg, rifampin) can decrease netupitant/palonosetron efficacy by substantially reducing plasma concentrations of the netupitant component; avoid use Concomitant use with a strong CYP3A4 inhibitor (eg, ketoconazole) can increase the systemic exposure to the netupitant component; no dosage adjustment is necessary for single dose administration

Adverse Effects

Side effects of Netupitant + Palonosetron : 1-10% Headache (9%) Asthenia (8%) Fatigue (4-7%) Dyspepsia (4%) Constipation (3%) Erythema (3%) <1% Increased AST/ALT >3 x ULN and total bilirubin >ULN (0.3%) Increased AST/ALT >3 x ULN and total bilirubin >2 x ULN (0.1%) Increased AST/ALT >10 x ULN and total bilirubin >ULN (0%)

Mechanism of Action

Netupitant: Tachykinin NK1 receptor (substance P) antagonist Palonosetron: 5-hydroxytryptamine 3 (5-HT3) receptor antagonist; binds to 5-HT3 receptors both in peripheral and central nervous system, with primary effects in GI tract