Dosing and uses of Emend, fosaprepitant (aprepitant)
Adult dosage forms and strengths
capsule (aprepitant)
- 40mg
- 80mg
- 125mg
powder for injection (fosaprepitant)
- 150mg
oral suspension
- 125mg/pouch (once pouch is mixed with 4.6 mL drinking water, resulting suspension yields 25mg/mL)
Chemotherapy-Induced Nausea & Vomiting
Indicated for prevention of acute and delayed nausea and vomiting associated with initial and repeat courses of highly emetogenic cancer chemotherapy (HEC) including high-dose cisplatin; also indicated for nausea and vomiting associated with initial and repeat courses of moderately emetogenic cancer chemotherapy (MEC)
Use in combination with other antiemetics
IV
- HEC
- Day 1: 150 mg IV infused over 20-30 minutes ~30 minutes before chemotherapy plus dexamethasone 12 mg PO and a 5-HT3 antagonist
- Day 2: Dexamethasone 8 mg PO in AM
- Days 3 and 4: Dexamethasone 8 mg PO BID (morning and evening)
- Note: A 50% dosage reduction of dexamethasone on Days 1 and 2 is recommended to account for a drug interaction with aprepitant
- MEC
- Day 1: 150 mg IV infused over 20-30 minutes ~30 minutes before chemotherapy plus dexamethasone 12 mg PO and a 5-HT3 antagonist
OraL
- Day 1: 125 mg PO 1 hr prior to chemotherapy plus dexamethasone 12 mg PO (30 minutes before chemotherapy) and a 5-HT3 antagonist
- Days 2-3: 80 mg PO 1 hr prior to chemotherapy plus dexamethasone 8 mg PO qAM
- Day 4: Dexamethasone 8 mg PO in AM
Postoperative Nausea & Vomiting
Indicated for prevention of PONV
40 mg PO within 3 hr prior to anesthesia induction
Pediatric dosage forms and strengths
capsule (aprepitant)
- 80mg
- 125mg
oral suspension
- 125mg/pouch (once pouch is mixed with 4.6 mL drinking water, resulting suspension yields 25mg/mL)
Chemotherapy-Induced Nausea & Vomiting
Indicated for the prevention of acute and delayed nausea and vomiting associated with initial and repeat courses of highly emetogenic cancer chemotherapy (HEC) including high-dose cisplatin, and for moderately emetogenic cancer chemotherapy (MEC)
Capsule: Aged <12 years and weight <30 kg: Safety and efficacy not established
Oral suspension: Aged <6 months: Safety and efficacy not established
Capsule for aged ≥12 years or <12 years and weight ≥30 kg
- Day 1: 125 mg PO 1 hr prior to chemotherapy plus dexamethasone 12 mg PO (30 minutes before chemotherapy) and a 5-HT3 antagonist
- Days 2 and 3: 80 mg PO 1 hr prior to chemotherapy plus dexamethasone 8 mg PO qAM
- Day 4: Dexamethasone 8 mg PO in AM
Oral suspension for aged ≥6 months to <12 years
- Day 1: 3 mg/kg PO 1 hr prior to chemotherapy Days 2 and 3: 2 mg/kg PO 1 hr prior to chemotherapy
- Administer with concomitant dexamethasone and 5-HT3 antagonist (eg, ondansetron)
Dosing Considerations
Children must be able to swallow capsule whole
Has not been studied for treatment of established nausea and vomiting
Chronic continuous administration is not recommended because it has not been studied, and because the drug interaction profile may change during chronic continuous use
Emend, fosaprepitant (aprepitant) adverse (side) effects
CINV: generally similar to standard treatments
PONV: generally similar to ondansetron
>10% (only seen in CINV)
Headache
Asthenia/fatigue
Anorexia
Constipation
Diarrhea
Nausea
Alopecia
Hiccups
1-10% (selected)
Dizziness
Insomnia
Bradycardia
Hypotension
Pharyngolargeal pain
Mucosal inflammation
Stomatitis
Dyspepsia
Anemia
Neutropenia
Hot flash
Pruritus
Dehydration
Fever
Postmarketing Reports
Rash, urticaria, rarely Stevens-Johnson syndrome/toxic epidermal necrolysis; ifosfamide-induced neurotoxicity reported after aprepitant and ifosfamide coadministration
Warnings
Contraindications
Hypersensitivity
Concomitant pimozide, terfenadine (discontinued), astemizole (discontinued), cisapride
Cautions
Not indicated for treatment
Severe hepatic impairment (Child-Pugh score >9)
Decreased corticosteroid dose by 25% (IV) or 50% (PO) on days aprepitant is administered
May reduce efficacy of oral contraceptives - alternatives recommended during and for 1 month after last aprepitant dose
CYP3A4 inhibitor and CYP2C9 inducer
IV: Isolated reports of immediate hypersensitivity reactions including flushing, erythema, and dyspnea during infusion of fosaprepitant; discontinuation infusion and do reinitiate
Injection is incompatible with divalent cation-containing solutions
Severe and disabling arthralgia reported in patients taking DPP-4 inhibitors; consider as a possible cause for severe joint pain and discontinue drug if appropriate
Pregnancy and lactation
Pregnancy category: B
Lactation: It is not known whether this drug is excreted in milk. A decision should be made whether to discontinue nursing or to discontinue the drug, taking into account the importance of the drug to the mother.
Pregnancy categories
A: Generally acceptable. Controlled studies in pregnant women show no evidence of fetal risk.
B: May be acceptable. Either animal studies show no risk but human studies not available or animal studies showed minor risks and human studies done and showed no risk.
C: Use with caution if benefits outweigh risks. Animal studies show risk and human studies not available or neither animal nor human studies done.
D: Use in LIFE-THREATENING emergencies when no safer drug available. Positive evidence of human fetal risk.
X: Do not use in pregnancy. Risks involved outweigh potential benefits. Safer alternatives exist.
NA: Information not available.
Pharmacology of Emend, fosaprepitant (aprepitant)
Mechanism of action
Substance P/neurokinin 1 (NK1) receptor antagonist
Absorption
Bioavailability: 60-65% (PO)
Peak plasma time
- 125 mg PO once: 4 hr
- 80 mg PO twice: 4 hr
- 40 mg PO once: 3 hr
Peak plasma concentration
- 125 mg PO once: 1.6 mcg/mL
- 80 mg PO twice: 1.4 mcg/mL
- 40 mg PO once: 0.7 mcg/mL
- 150 mg IV once: 4.15 mcg/mL
AUC
- 125 mg PO once: 19.6 mcg·hr/mL
- 80 mg PO twice: 21.2 mcg·hr/mL
- 150 mg IV once: 37.38 mcg·hr/mL
Distribution
Protein bound: >95%
Vd: 70 L
Metabolism
Hepatic CYP3A4 (major); CYP1A2, CYP2C19 (minor)
Fosaprepitant (IV form) rapidly converted to aprepitant in vivo
Enzymes inhibited: CYP3A4
Enzymes induced: CYP2C9
Elimination
Half-life: 9-13 hr
Total body clearance: 62-90 mL/min
Excretion (IV admin): 57% urine; 45% feces
Dialyzable: No
Administration
IV Incompatibilities
Divalent cation-containing solutions (Ca++, Mg++, Zn++ etc), eg, Lr
IV Preparation
Aseptically inject 5 mL 0.9% NaCl into vial along the vial wall in order to prevent foaming; avoid jetting the 0.9% NaCl into the viaL
Gently swirl to dissolve; do not shake
Aseptically withdraw entire volume from vial and transfer it into a prepared infusion bag of 145 mL 90.9% NaCl to yield a total volume of 150 mL and a final concentration of 1 mg/mL
Gently invert bag 2-3 times to mix
Stable for 24 hr at ambient room temperature (ie, ≤25°C [77°F])
IV Administration
Infuse IV over 20-30 min
Do not mix with other drugs
Oral Administration
Take with or without food
Capsule: Swallow capsule whole
Oral suspension
- Dose is prepared by a pharmacist and dispensed to the patient or caregiver in an oral dispenser/oral syringe; once pouch is mixed with 4.6 mL drinking water, the resulting concentration is 25 mg/mL
- Keep the dispenser in the refrigerator until administered to the patient
- The dose can be stored at room temperature for up to 3 hr before use
- When ready to use, take the cap off the dispenser, place the dispenser in the patient’s mouth along the inner cheek on either the right or left side
- Slowly administer the medicine along the inner cheek
- Use dose within 72 hr of preparation
- Discard any doses remaining after 72 hr
Storage
Oral suspension
- Unopened pouch
- 20-25°C (68-77°F); excursions permitted between 15-30°C (between 59-86°F)
- Store in the original container
- Do not open pouch until ready to prepare for use
- Prepared dose
- If the dose is not administered immediately after measuring, store filled oral dosing dispenser(s) in the refrigerator (between 36-46°F [2-8°C]) for up to 72 hr prior to use
- When dispensing dose(s) to the patient or caregiver, instruct them to refrigerate the oral dosing dispenser(s) until they are ready to administer the dose
- When ready to use, the mixture can be kept at room temperature (68-77°F [20°C-25°C]) for up to 3 hr
