Version May 2024
Note: Dosing is for fosaprepitant (Emend IV); refer to the Aprepitant monograph for IV aprepitant (Cinvanti) dosing.
Chemotherapy-induced nausea and vomiting, prevention:
Highly emetogenic chemotherapy: IV: 150 mg on day 1 only (infusion should be completed ~30 minutes prior to chemotherapy). Administer in combination with a 5-HT3 antagonist on day 1, dexamethasone on days 1 to 4, and olanzapine on days 1 to 4 (Ref).
Moderately emetogenic chemotherapy: IV: 150 mg on day 1 only (infusion should be completed ~30 minutes prior to chemotherapy). Administer in combination with a 5-HT3 antagonist and dexamethasone on day 1.
Dosage adjustment for concomitant therapy: Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.
There are no dosage adjustments provided in the manufacturer's labeling; however, due to modest decreases in protein binding of aprepitant, the AUC of pharmacologically active unbound drug is not significantly affected in patients with kidney disease.
Hemodialysis: Hemodialysis conducted 4 or 48 hours after dosing had no significant impact on aprepitant pharmacokinetics (a negligible amount of an aprepitant dose is recovered in the dialysate).
Mild or moderate impairment (Child-Pugh class A or B): No dosage adjustment necessary.
Severe impairment (Child-Pugh class C): There is no dosage adjustment provided in the manufacturer's labeling (has not been studied); additional monitoring for adverse reactions may be needed.
Hypersensitivity reactions: Discontinue fosaprepitant infusion and manage appropriately. Do not reinitiate.
Refer to adult dosing.
(For additional information see "Fosaprepitant: Pediatric drug information")
Chemotherapy-induced nausea and vomiting, prevention; highly and moderately emetogenic chemotherapy :
Infants ≥6 months weighing ≥6 kg and Children <2 years:
Single-dose NK1 receptor antagonist regimen: Note: Use only with single-day chemotherapy regimens. IV: 5 mg/kg once; maximum dose: 150 mg/dose; administer ~90 minutes prior to chemotherapy on day 1 only; use in combination with a 5-HT3 antagonist with or without corticosteroid.
Three-day NK1 receptor antagonist regimen: Note: May be used with single-day or multiday chemotherapy regimens. Use in combination with a 5-HT3 antagonist with or without corticosteroid.
Day 1: Administer ~90 minutes prior to chemotherapy: IV: 3 mg/kg once; maximum dose: 115 mg/dose.
Day 2 and 3: Administer ~90 minutes prior to chemotherapy: IV: 2 mg/kg once daily for 2 doses; maximum dose: 80 mg/dose; alternatively, may follow with oral aprepitant on days 2 and 3.
Children 2 to <12 years:
Single-dose NK1 receptor antagonist regimen: Note: Use only with single-day chemotherapy regimens. IV: 4 mg/kg once; maximum dose: 150 mg/dose; administer ~90 minutes prior to chemotherapy on day 1 only; use in combination with a 5-HT3 antagonist with or without corticosteroid.
Three-day NK1 receptor antagonist regimen: Note: May be used with single-day or multiday chemotherapy regimens. Use in combination with a 5-HT3 antagonist with or without corticosteroid.
Day 1: Administer ~90 minutes prior to chemotherapy: IV: 3 mg/kg once; maximum dose: 115 mg/dose on day 1 only.
Day 2 and 3: Administer ~90 minutes prior to chemotherapy: IV: 2 mg/kg once daily for 2 doses; maximum dose: 80 mg/dose; alternatively, may follow with oral aprepitant on days 2 and 3.
Children ≥12 years and Adolescents ≤17 years:
Single-dose NK1 receptor antagonist regimen: Note: Use only with single-day chemotherapy regimens. IV: 150 mg once, administered ~60 minutes prior to chemotherapy on day 1 only; use in combination with a 5-HT3 antagonist with or without corticosteroid.
Three-day NK1 receptor antagonist regimen: Note: May be used with single-day or multiday chemotherapy regimens. Use in combination with a 5-HT3 antagonist with or without corticosteroid.
Day 1: Administer ~60 minutes prior to chemotherapy: IV: 115 mg once.
Day 2 and 3: Administer ~60 minutes prior to chemotherapy: IV: 80 mg once daily for 2 doses; alternatively, may follow with oral aprepitant on days 2 and 3.
Adolescents ≥18 years: Single-dose NK1 receptor antagonist regimen: IV: 150 mg once, administer ~50 to 60 minutes prior to chemotherapy on day 1 only; in combination with a 5-HT3 antagonist and corticosteroid.
Cyclic vomiting syndrome, supportive therapy: Fosaprepitant has not been studied for cyclic vomiting syndrome. However, it may be considered as an IV option for supportive therapy, using doses similar to those shown to be efficacious for prevention of chemotherapy-induced nausea and vomiting, based on clinical experience and indirect evidence from using oral aprepitant for acute treatment of cyclic vomiting syndrome in pediatric patients ≥4 years of age (Ref).
Dosage adjustment for concomitant therapy: Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.
There are no dosage adjustments provided in the manufacturer's labeling; however, adjustment is unlikely necessary as aprepitant is not renally excreted and does not require adjustment in renal impairment.
Hemodialysis: There are no dosage adjustments provided in the manufacturer's labeling; however, adjustment is unlikely necessary as aprepitant is not removed by hemodialysis.
Infants ≥6 months, Children, and Adolescents:
Mild or moderate impairment (Child-Pugh class A or B): No dosage adjustment necessary.
Severe impairment (Child-Pugh class C): There are no dosage adjustments provided in the manufacturer's labeling (has not been studied); additional monitoring may be needed.
The following adverse drug reactions and incidences are derived from product labeling unless otherwise specified. Adverse reactions reported with fosaprepitant (as part of a combination chemotherapy regimen) occurring at a higher frequency than standard antiemetic therapy. Also see aprepitant monograph for additional adverse reactions.
>10%:
Central nervous system: Fatigue (15%)
Gastrointestinal: Diarrhea (13%)
1% to 10%:
Central nervous system: Peripheral neuropathy (3%)
Gastrointestinal: Dyspepsia (2%)
Genitourinary: Urinary tract infection (2%)
Hematologic & oncologic: Neutropenia (8%), anemia (3%), leukopenia (2%)
Local: Infusion-site reaction (2% to 3%; includes induration at injection site, infusion-site pain, local pruritus, localized erythema)
Neuromuscular & skeletal: Weakness (4%), limb pain (2%)
<1%, postmarketing, and/or case reports: Anaphylactic shock, anaphylaxis, dyspnea, erythema, flushing, hypersensitivity reaction, hypotension, pruritus, skin rash, Stevens-Johnson syndrome, syncope, toxic epidermal necrolysis, urticaria
Hypersensitivity to fosaprepitant or any component of the formulation; concurrent use with pimozide.
Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.
Canadian labeling: Additional contraindications (not in the US labeling): Concurrent use with astemizole, terfenadine, or cisapride
Concerns related to adverse effects:
• Hypersensitivity: Hypersensitivity reactions, including dyspnea, erythema, flushing, hypotension, syncope, and anaphylaxis/anaphylactic shock have been reported during infusions.
• Infusion-site reactions: Infusion-site reactions, including erythema, pain, edema, thrombophlebitis, pruritus, and injection-site induration have occurred; the majority of severe infusion-related reactions (including thrombophlebitis, vasculitis, and necrosis) have been reported with administration of concomitant vesicant (anthracycline-based) chemotherapy, particularly when associated with extravasation. Most reactions occurred with the first three exposures to single fosaprepitant injections; some reactions persisted ≥2 weeks.
Dosage form specific issues:
• Polysorbate 80: Some dosage forms may contain polysorbate 80 (also known as Tweens). Hypersensitivity reactions, usually a delayed reaction, have been reported following exposure to pharmaceutical products containing polysorbate 80 in certain individuals (Isaksson 2002; Lucente 2000; Shelley 1995). Thrombocytopenia, ascites, pulmonary deterioration, and renal and hepatic failure have been reported in premature neonates after receiving parenteral products containing polysorbate 80 (Alade 1986; CDC 1984). See manufacturer's labeling.
Focinvez: FDA approved August 2023; anticipated availability currently unknown. Information pertaining to this product within the monograph is pending revision. Focinvez is a 150 mg/50 mL ready to use single-dose vial and is indicated in adults and pediatric patients 6 months of age and older, in combination with other antiemetic agents, for the prevention of acute and delayed nausea and vomiting associated with initial and repeat courses of highly emetogenic cancer chemotherapy including high-dose cisplatin or delayed nausea and vomiting associated with initial and repeat courses of moderately emetogenic cancer chemotherapy. Consult prescribing information for additional information.
Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Solution Reconstituted, Intravenous:
Generic: 150 mg (1 ea)
Solution Reconstituted, Intravenous [preservative free]:
Emend: 150 mg (1 ea) [contains edetate (edta) disodium, lactose, polysorbate 80]
Generic: 150 mg (1 ea)
Yes
Solution (reconstituted) (Emend Intravenous)
150 mg (per each): $401.56
Solution (reconstituted) (Fosaprepitant Dimeglumine Intravenous)
150 mg (per each): $30.00 - $401.56
Disclaimer: A representative AWP (Average Wholesale Price) price or price range is provided as reference price only. A range is provided when more than one manufacturer's AWP price is available and uses the low and high price reported by the manufacturers to determine the range. The pricing data should be used for benchmarking purposes only, and as such should not be used alone to set or adjudicate any prices for reimbursement or purchasing functions or considered to be an exact price for a single product and/or manufacturer. Medi-Span expressly disclaims all warranties of any kind or nature, whether express or implied, and assumes no liability with respect to accuracy of price or price range data published in its solutions. In no event shall Medi-Span be liable for special, indirect, incidental, or consequential damages arising from use of price or price range data. Pricing data is updated monthly.
Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Solution Reconstituted, Intravenous:
Emend: 150 mg (1 ea) [contains disodium edta, lactose, polysorbate 80]
IV: Infuse over 20 to 30 minutes; infusion should be completed ~30 minutes prior to chemotherapy.
Avoid infusing fosaprepitant into small veins or through a butterfly catheter. If a severe infusion-site reaction occurs, stop infusion and manage appropriately.
Note: Administration information is for fosaprepitant (Emend IV); refer to the aprepitant monograph for IV aprepitant (Cinvanti) administration.
Parenteral:
IV: Administer by IV infusion.
Infants ≥6 months and Children <12 years: Infuse over 60 minutes; administer ~90 minutes prior to chemotherapy to ensure completion 30 minutes prior to the start of chemotherapy.
Children ≥12 years and Adolescents <17 years: Infuse over 30 minutes; administer ~60 minutes prior to chemotherapy to ensure completion 30 minutes prior to the start of chemotherapy.
Adolescents ≥18 years: Infuse over 20 to 30 minutes; administer ~50 to 60 minutes prior to chemotherapy to ensure completion 30 minutes prior to the start of chemotherapy.
Prevention of chemotherapy-induced nausea and vomiting:
Prevention of acute and delayed nausea and vomiting associated with initial and repeat courses of highly emetogenic chemotherapy, including high-dose cisplatin in patients ≥6 months of age (in combination with other antiemetic agents).
Prevention of delayed nausea and vomiting associated with initial and repeat courses of moderately emetogenic chemotherapy in patients ≥6 months of age (in combination with other antiemetic agents).
Limitations of use: Fosaprepitant has not been studied for the management of existing nausea and vomiting.
Fosaprepitant may be confused with aprepitant, fosamprenavir, fosnetupitant/palonosetron, fospropofol, fostamatinib, rolapitant
Fosaprepitant (Emend IV) may be confused with aprepitant IV (Cinvanti)
Emend for Injection (fosaprepitant) may be confused with Emend oral (aprepitant) which is an oral capsule formulation
Substrate of CYP1A2 (minor), CYP2C19 (minor), CYP3A4 (major); Note: Assignment of Major/Minor substrate status based on clinically relevant drug interaction potential; Inhibits CYP3A4 (weak); Induces CYP2C9 (weak)
Note: Interacting drugs may not be individually listed below if they are part of a group interaction (eg, individual drugs within “CYP3A4 Inducers [Strong]” are NOT listed). For a complete list of drug interactions by individual drug name and detailed management recommendations, use the Lexicomp drug interactions program by clicking on the “Launch drug interactions program” link above.
ALPRAZolam: CYP3A4 Inhibitors (Weak) may increase the serum concentration of ALPRAZolam. Risk C: Monitor therapy
Clofazimine: May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors). Risk C: Monitor therapy
CycloSPORINE (Systemic): CYP3A4 Inhibitors (Weak) may increase the serum concentration of CycloSPORINE (Systemic). Risk C: Monitor therapy
CYP3A4 Inducers (Moderate): May decrease the serum concentration of Fosaprepitant. Specifically, CYP3A4 Inducers (Moderate) may decrease serum concentrations of the active metabolite aprepitant. Risk C: Monitor therapy
CYP3A4 Inducers (Strong): May decrease the serum concentration of Fosaprepitant. Specifically, CYP3A4 Inducers (Strong) may decrease serum concentrations of the active metabolite aprepitant. Risk X: Avoid combination
CYP3A4 Inhibitors (Moderate): May increase the serum concentration of Fosaprepitant. Risk X: Avoid combination
CYP3A4 Inhibitors (Strong): May increase the serum concentration of Fosaprepitant. Risk X: Avoid combination
DexAMETHasone (Systemic): Fosaprepitant may increase the serum concentration of DexAMETHasone (Systemic). Management: Reduce the dexamethasone dose 50% when coadministered with aprepitant. Aprepitant prescribing information incorporates this recommendation into the dose provided for dexamethasone; further reduction is not necessary. Risk D: Consider therapy modification
Dofetilide: CYP3A4 Inhibitors (Weak) may increase the serum concentration of Dofetilide. Risk C: Monitor therapy
Fexinidazole: May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors). Risk X: Avoid combination
Finerenone: CYP3A4 Inhibitors (Weak) may increase the serum concentration of Finerenone. Risk C: Monitor therapy
Flibanserin: CYP3A4 Inhibitors (Weak) may increase the serum concentration of Flibanserin. Risk C: Monitor therapy
Fusidic Acid (Systemic): May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors). Risk X: Avoid combination
Hormonal Contraceptives: Fosaprepitant may decrease the serum concentration of Hormonal Contraceptives. Management: Advise patients to use an alternative method of contraception or a back-up method during coadministration with fosaprepitant, and to continue back-up contraception for 28 days after discontinuing fosaprepitant to ensure contraceptive reliability. Risk D: Consider therapy modification
Ifosfamide: Fosaprepitant may enhance the adverse/toxic effect of Ifosfamide. Specifically, the risk for ifosfamide induced encephalopathy may be increased. Fosaprepitant may increase serum concentrations of the active metabolite(s) of Ifosfamide. Specifically, concentrations of the active and toxic metabolites of ifosfamide may increase. Risk C: Monitor therapy
Ixabepilone: CYP3A4 Inhibitors (Weak) may increase the serum concentration of Ixabepilone. Risk C: Monitor therapy
Lemborexant: CYP3A4 Inhibitors (Weak) may increase the serum concentration of Lemborexant. Management: The maximum recommended dosage of lemborexant is 5 mg, no more than once per night, when coadministered with weak CYP3A4 inhibitors. Risk D: Consider therapy modification
Lomitapide: CYP3A4 Inhibitors (Weak) may increase the serum concentration of Lomitapide. Management: Patients on lomitapide 5 mg/day may continue that dose. Patients taking lomitapide 10 mg/day or more should decrease the lomitapide dose by half. The lomitapide dose may then be titrated up to a max adult dose of 30 mg/day. Risk D: Consider therapy modification
MethylPREDNISolone: Fosaprepitant may increase the serum concentration of MethylPREDNISolone. Management: Decrease the oral methylprednisolone dose by 50%, and decrease the intravenous methylprednisolone dose by 25%, when combined with fosaprepitant. Risk D: Consider therapy modification
Midazolam: CYP3A4 Inhibitors (Weak) may increase the serum concentration of Midazolam. Risk C: Monitor therapy
NiMODipine: CYP3A4 Inhibitors (Weak) may increase the serum concentration of NiMODipine. Risk C: Monitor therapy
Pimozide: Fosaprepitant may increase the serum concentration of Pimozide. The active metabolite aprepitant is likely responsible for this effect. Risk X: Avoid combination
Simvastatin: CYP3A4 Inhibitors (Weak) may increase serum concentrations of the active metabolite(s) of Simvastatin. CYP3A4 Inhibitors (Weak) may increase the serum concentration of Simvastatin. Risk C: Monitor therapy
Sirolimus (Conventional): CYP3A4 Inhibitors (Weak) may increase the serum concentration of Sirolimus (Conventional). Risk C: Monitor therapy
Sirolimus (Protein Bound): CYP3A4 Inhibitors (Weak) may increase the serum concentration of Sirolimus (Protein Bound). Management: Reduce the dose of protein bound sirolimus to 56 mg/m2 when used concomitantly with a weak CYP3A4 inhibitor. Risk D: Consider therapy modification
Tacrolimus (Systemic): CYP3A4 Inhibitors (Weak) may increase the serum concentration of Tacrolimus (Systemic). Risk C: Monitor therapy
Triazolam: CYP3A4 Inhibitors (Weak) may increase the serum concentration of Triazolam. Risk C: Monitor therapy
Ubrogepant: CYP3A4 Inhibitors (Weak) may increase the serum concentration of Ubrogepant. Management: In patients taking weak CYP3A4 inhibitors, the initial and second dose (given at least 2 hours later if needed) of ubrogepant should be limited to 50 mg. Risk D: Consider therapy modification
Vitamin K Antagonists (eg, warfarin): Fosaprepitant may decrease the serum concentration of Vitamin K Antagonists. Risk C: Monitor therapy
Aprepitant serum concentration may be increased when taken with grapefruit juice. Management: Avoid concurrent use.
Efficacy of hormonal contraceptive may be reduced; alternative or additional methods of contraception should be used during treatment with fosaprepitant and for at least 1 month following the last fosaprepitant dose.
Adverse events were not observed in animal reproduction studies.
It is not known if fosaprepitant is present in breast milk.
According to the manufacturer, the decision to breastfeed during therapy should consider the risk of infant exposure, the benefits of breastfeeding to the infant, and the benefits of treatment to the mother.
Monitor INR in patients on chronic warfarin therapy in the 2-week period (particularly at 7 to 10 days) following fosaprepitant administration. Monitor patients with severe hepatic impairment for adverse reactions. Monitor for signs/symptoms of hypersensitivity and infusion site reactions.
Fosaprepitant is a prodrug of aprepitant, a substance P/neurokinin 1 (NK1) receptor antagonist. Fosaprepitant is rapidly converted to aprepitant, which prevents acute and delayed vomiting by inhibiting the substance P/neurokinin 1 (NK1) receptor; also augments the antiemetic activity of the 5-HT3 receptor antagonist and corticosteroid activity and inhibits chemotherapy-induced emesis.
Distribution: Aprepitant: Vd: ~70 L; crosses the blood-brain barrier
Protein binding: Aprepitant: >95%
Metabolism:
Fosaprepitant: Hepatic and extrahepatic; rapidly (within 30 minutes after the end of infusion) converted to aprepitant (nearly complete conversion)
Aprepitant: Hepatic via CYP3A4 (major); CYP1A2 and CYP2C19 (minor); forms 7 weakly-active metabolites
Half-life elimination: Aprepitant: ~9 to 13 hours
Time to peak, plasma: Fosaprepitant is converted to aprepitant within 30 minutes after the end of infusion
Excretion: Urine (57%); feces (45%)
Altered kidney function: Following a single oral aprepitant 240 mg dose in patients with CrCl <30 mL/minute/1.73 m2, the AUC of total aprepitant (unbound and protein bound) decreased by 21% and Cmax decreased by 32% compared with healthy subjects. In patients with ESRD undergoing hemodialysis, the AUC of total aprepitant decreased by 42% and Cmax decreased by 32%.
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