Usage
Fosaprepitant is prescribed for the prevention of acute and delayed nausea and vomiting associated with highly emetogenic chemotherapy (HEC), including high-dose cisplatin, and delayed nausea and vomiting associated with moderately emetogenic chemotherapy (MEC). It is classified as an antiemetic specifically, a neurokinin-1 (NK1) receptor antagonist. It works by blocking the action of substance P, a neurotransmitter involved in the vomiting reflex, at the NK1 receptors in the brain and gastrointestinal tract.
Alternate Names
The active metabolite of fosaprepitant is aprepitant. Brand names for fosaprepitant include Emend for Injection and Focinvez.
How It Works
Pharmacodynamics: Fosaprepitant is rapidly metabolized to aprepitant, which exerts its antiemetic effect by antagonizing substance P at the NK1 receptors. This prevents substance P from binding to these receptors and triggering the vomiting reflex.
Pharmacokinetics: Fosaprepitant is administered intravenously and is rapidly converted to aprepitant in the body. It is then metabolized primarily by CYP3A4, with minor contributions from CYP2C9 and CYP2C19. Aprepitant is also an inducer of CYP2C9 and CYP3A4 as well as a substrate and a moderate inhibitor. Fosaprepitant is eliminated mainly through hepatic metabolism, with a small portion excreted in the urine.
Mode of Action: Aprepitant competitively binds to the NK1 receptor.
Elimination pathways: Primarily hepatic metabolism via CYP3A4, with a small amount excreted renally.
Dosage
Standard Dosage
Adults:
150 mg IV infused over 20-30 minutes approximately 30 minutes before chemotherapy on Day 1. This is given in conjunction with a corticosteroid (e.g., dexamethasone) and a 5-HT3 antagonist (e.g., ondansetron).
Children (6 months and older):
- 6 months to < 2 years: 5 mg/kg IV (max 150 mg) over 60 minutes about 30 minutes before chemotherapy.
- 2 years to < 12 years: 4 mg/kg IV (max 150 mg) over 60 minutes about 30 minutes before chemotherapy.
- 12 years to 17 years: 150 mg IV over 30 minutes about 30 minutes before chemotherapy.
For multi-day chemotherapy regimens, fosaprepitant is typically used on Day 1, followed by oral aprepitant on Days 2 and 3.
Special Cases:
- Elderly Patients: No dose adjustment is necessary.
- Patients with Renal Impairment: No dose adjustment is necessary.
- Patients with Hepatic Dysfunction: Use with caution in moderate to severe hepatic impairment. Dose adjustment may be needed.
- Patients with Comorbid Conditions: Consider drug interactions and adjust accordingly.
Clinical Use Cases
Fosaprepitant is specifically indicated for the prevention of chemotherapy-induced nausea and vomiting (CINV) associated with highly and moderately emetogenic chemotherapy regimens. It is not indicated for other clinical use cases like intubation, surgical procedures, mechanical ventilation, ICU use, or emergency situations.
Dosage Adjustments
Dose adjustments may be necessary for patients with hepatic impairment or those taking concomitant medications that interact with CYP3A4.
Side Effects
Common Side Effects:
Fatigue, hiccups, nausea, vomiting, constipation, diarrhea, loss of appetite, headache, dizziness, asthenia.
Rare but Serious Side Effects:
Hypersensitivity reactions (including anaphylaxis), infusion site reactions.
Long-Term Effects:
Data on the long-term effects of fosaprepitant are limited as it’s given as a single dose prior to chemotherapy.
Adverse Drug Reactions (ADR):
Anaphylaxis, Stevens-Johnson Syndrome/toxic epidermal necrolysis.
Contraindications
Hypersensitivity to fosaprepitant, aprepitant, or polysorbate 80. Concomitant use with pimozide, cisapride, astemizole, and terfenadine.
Drug Interactions
Fosaprepitant (and its active metabolite aprepitant) can interact with numerous drugs, particularly those metabolized by or affecting CYP3A4, CYP2C9, CYP2C19, and P-glycoprotein. These include warfarin, hormonal contraceptives, some chemotherapeutic agents, certain antibiotics (e.g., clarithromycin), antifungals (e.g., ketoconazole), and anticonvulsants (e.g., phenytoin). Always review a patient’s medication list for potential interactions before prescribing fosaprepitant.
Pregnancy and Breastfeeding
Pregnancy Category B. Insufficient data in pregnant women. Use only if clearly necessary. Breastfeeding is not recommended.
Drug Profile Summary
- Mechanism of Action: NK1 receptor antagonist, blocking substance P.
- Side Effects: Fatigue, hiccups, nausea, constipation, hypersensitivity reactions.
- Contraindications: Hypersensitivity, concomitant use with pimozide, cisapride, astemizole, and terfenadine.
- Drug Interactions: CYP3A4, CYP2C9, CYP2C19 substrates, inducers and inhibitors.
- Pregnancy & Breastfeeding: Use with caution in pregnancy; breastfeeding not recommended.
- Dosage: Adults: 150 mg IV on Day 1; Pediatric: weight/age-based dosing.
- Monitoring Parameters: Monitor for hypersensitivity reactions and infusion site reactions. In patients on warfarin therapy, closely monitor INR for two weeks following fosaprepitant administration.
Popular Combinations
Commonly used in combination with a corticosteroid (e.g., dexamethasone) and a 5-HT3 antagonist (e.g., ondansetron) for the prevention of CINV.
Precautions
Screen for allergies and hepatic impairment. Use caution in pregnancy and avoid during breastfeeding. Consider drug interactions. Monitor for hypersensitivity reactions. Advise patients about potential dizziness and fatigue. Advise patients about potential reduction in the effectiveness of hormonal contraceptives and recommend backup methods.
FAQs (Frequently Asked Questions)
Q1: What is the recommended dosage for Fosaprepitant?
A: Adults: 150 mg IV on Day 1. Pediatric: weight-based dosing; see detailed section above.
Q2: How is Fosaprepitant administered?
A: As an intravenous infusion over 20-30 minutes for adults and 30-60 minutes in pediatrics, approximately 30 minutes before chemotherapy.
Q3: What is the mechanism of action of Fosaprepitant?
A: It’s an NK1 receptor antagonist, preventing substance P from binding and triggering the vomiting reflex.
Q4: What are the most common side effects?
A: Fatigue, hiccups, nausea, constipation, diarrhea, headache, dizziness.
Q5: Are there any serious side effects I should be aware of?
A: Yes, hypersensitivity reactions (including anaphylaxis and anaphylactic shock), and infusion site reactions.
Q6: What are the contraindications for using Fosaprepitant?
A: Hypersensitivity to components, concurrent use with pimozide, cisapride, astemizole, and terfenadine.
Q7: Can Fosaprepitant be used in pregnant or breastfeeding women?
A: Pregnancy Category B - Use only if clearly needed. Breastfeeding is not recommended.
Q8: Does Fosaprepitant interact with other medications?
A: Yes, it can interact with numerous drugs, particularly those metabolized by or affecting CYP3A4. Consult a drug interaction checker before prescribing.
Q9: What should I monitor in patients receiving Fosaprepitant?
A: Monitor for hypersensitivity and infusion site reactions. In patients on warfarin therapy, closely monitor INR.
Q10: What other drugs are typically given with Fosaprepitant for chemotherapy-induced nausea and vomiting?
A: Corticosteroids (e.g., dexamethasone) and 5-HT3 antagonists (e.g., ondansetron).
