Drug Guide
Netupitant; Palonosetron Hydrochloride
Classification
Therapeutic: Antiemetic
Pharmacological: NK1 receptor antagonist (Netupitant) and 5-HT3 receptor antagonist (Palonosetron)
FDA Approved Indications
- Prevention of chemotherapy-induced nausea and vomiting (CINV) in patients receiving multiple-day chemotherapy or high-dose cisplatin-containing chemotherapy
Mechanism of Action
Netupitant blocks neurokinin-1 (NK1) receptors in the central nervous system, reducing nausea and vomiting signals. Palonosetron blocks 5-HT3 receptors, preventing the serotonin-mediated activation of vagal nerve terminals which triggers vomiting.
Dosage and Administration
Adult: Typically, one tablet (300 mg Netupitant and 0.5 mg Palonosetron) taken orally 1 hour prior to chemotherapy; may be repeated as per regimen.
Pediatric: Safety and efficacy not established; generally not recommended for pediatric use.
Geriatric: No specific dosage adjustment required, but elderly patients should be monitored as with other medications.
Renal Impairment: No specific adjustment indicated, but caution advised.
Hepatic Impairment: Hepatic impairment may increase exposure; monitor patient response.
Pharmacokinetics
Absorption: Well absorbed orally, with peak plasma concentrations within 4 hours for Palonosetron and variable for Netupitant.
Distribution: High protein binding (~99%) for both drugs.
Metabolism: Palonosetron is metabolized primarily via the liver; Netupitant is extensively metabolized by CYP3A4.
Excretion: Palonosetron is mainly excreted in the urine; Netupitant metabolites are excreted mainly in feces.
Half Life: Palonosetron approximately 40 hours; Netupitant approximately 96 hours.
Contraindications
- Hypersensitivity to any component of Akynzeo.
Precautions
- Use with caution in patients with known hypersensitivity to 5-HT3 antagonists; monitor for infusion reactions.
Adverse Reactions - Common
- Fatigue (Common)
- Headache (Common)
- Constipation (Common)
Adverse Reactions - Serious
- Anaphylaxis (Rare)
- Oral mucositis (Rare)
- Cardiac arrhythmias (QT prolongation) (Potential risk, monitor QT interval in susceptible patients.)
Drug-Drug Interactions
- CYP3A4 inhibitors or inducers may alter Netupitant levels.
- Concomitant use with apomorphine is contraindicated due to hypotension and loss of consciousness.
Drug-Food Interactions
- No significant food interactions identified.
Drug-Herb Interactions
- Limited data; caution advised with herbal products affecting CYP3A4 activity.
Nursing Implications
Assessment: Monitor for allergic reactions, QT prolongation (ECG if indicated), and efficacy in preventing nausea and vomiting.
Diagnoses:
- Risk for nausea and vomiting
- Potential allergic reaction
Implementation: Administer 1 hour before chemotherapy with water, whole; do not crush or chew.
Evaluation: Assess effectiveness by patient report of nausea/vomiting episodes, monitor for adverse reactions.
Patient/Family Teaching
- Take the medication exactly as prescribed, 1 hour before chemotherapy.
- Report any signs of allergic reactions, including rash, swelling, or difficulty breathing.
- Be aware of possible side effects like headache or constipation.
Special Considerations
Black Box Warnings:
- None currently for this drug combination.
Genetic Factors: Limited data; pharmacogenetic testing not routinely required.
Lab Test Interference: No significant interference reported.
Overdose Management
Signs/Symptoms: Nausea, vomiting, and CNS effects possible.
Treatment: Supportive care; symptomatic treatment; no specific antidote.
Storage and Handling
Storage: Store at 25°C (77°F); protect from moisture and excessive heat.
Stability: Stable up to the expiration date when stored properly.