Fosaprepitant (Emend) is an NK-1 (neurokinin-1) receptor inhibitor that is used in the treatment of acute and delayed onset of chemotherapy-induced vomiting in combination with other antiemetic medications.

Fosaprepitant Uses:

• Prevention of chemotherapy-induced nausea and vomiting:

  • Used in the prevention of acute and delayed nausea and vomiting associated with highly emetogenic chemotherapy, including high-dose cisplatin (initial and repeat courses; in combination with other antiemetics) in patients ≥6 months of age
  • Used in the prevention of delayed nausea and vomiting associated with moderately emetogenic chemotherapy (initial and repeat courses; in combination with other antiemetics) in patients 6 or more than 6 months of age.
  • Limitations of use:
    • Fosaprepitant has not been studied for the management of existing vomiting and nausea.

Adult dose:

Fosaprepitant (Emend) Dose in Adults

Fosaprepitant (Emend) Dose in the Prevention of chemotherapy-induced nausea/vomiting:

• Highly emetogenic chemotherapy:
  • IV: 150 mg on first day only (infusion should be completed about 30 minutes before initiating chemotherapy);
  • Administer in combination with a 5-HT3 antagonist on the first day only and with dexamethasone on days 1 to 4 (reduce dexamethasone dose by 50 percent on days 1 and 2)
• Moderately emetogenic chemotherapy:
  • IV: 150 mg on first day only (infusion should be completed about 30 minutes before initiating chemotherapy);
  • Administer in combination with a 5-HT3 antagonist and dexamethasone on first day (reduce dexamethasone dose by 50 percent )

Fosaprepitant (Emend) Dose in Childrens

Fosaprepitant (Emend) Dose in the prevention of Chemotherapy-induced nausea/vomiting;

(For highly and moderately emetogenic chemotherapy)

• Infants ≥6 months weighing ≥6 kg and Children <2 years:

  • Single-dose NK-1 receptor antagonist regimen:
    • Note: Use only with single-day chemotherapy regimens.
    • IV: 5 mg per kg one time;
    • The maximum dose: 150 mg per dose;
    • Administer about 90 minutes before initiating chemotherapy on day 1 only;
    • Use in combination with a 5-HT-3 antagonist with or without corticosteroid.
  • Three-day NK-1 receptor antagonist regimen:
    • Note: May be used with single-day or multiday chemotherapy regimens.
    • IV: 3 mg/kg once;
    • The maximum dose: 115 mg/dose;
    • Administer about 90 minutes before initiating chemotherapy on day 1 only followed by oral aprepitant on days 2 and 3;
    • Use in combination with a 5-HT3 antagonist with or without corticosteroid.

• Children 2 to <12 years:

  • Single-dose NK-1 receptor antagonist regimen:
    • Note: Use only with single-day chemotherapy regimens.
    • IV: 4 mg/kg once;
    • The maximum dose: 150 mg/dose;
    • Administer about 90 minutes before chemotherapy on day 1 only;
    • Use in combination with a 5-HT3 antagonist with or without corticosteroid.
  • Three-day NK-1 receptor antagonist regimen:
    • Note: May be used with single-day or multiday chemotherapy regimens.
    • IV: 3 mg/kg once;
    • The maximum dose: 115 mg/dose;
    • Administer about 90 minutes before initiating chemotherapy on day 1 only followed by oral aprepitant on days 2 and 3;
    • Use in combination with a 5-HT3 antagonist with or without corticosteroid.

• Children ≥12 years and Adolescents ≤17 years:

  • Single-dose NK-1 receptor antagonist regimen:
    • Note: Use only with single-day chemotherapy regimens.
    • IV: 150 mg once, administered about 60 minutes before initiating chemotherapy on day 1 only;
    • Use in combination with a 5-HT3 antagonist with or without corticosteroid.
  • Three-day NK-1 receptor antagonist regimen:
    • Note: May be used with single-day or multiday chemotherapy regimens.
    • IV: 115 mg once, administered about 60 minutes prior to chemotherapy on day 1 only followed by oral aprepitant on days 2 and 3;
    • Use in combination with a 5-HT antagonist with or without corticosteroid.

• Adolescents ≥18 years:

  • Single-dose NK-1 receptor antagonist regimen:
    • IV: 150 mg once, administer about 50 to 60 minutes before initiating chemotherapy on day 1 only; in combination with a 5HT3 antagonist and corticosteroid.

Fosaprepitant Pregnancy Category: B

• Animal reproduction studies of aprepitant did not show any adverse events.
• The effectiveness of hormonal contraceptives might be lower;
• Alternative or additional methods of contraception should be used both during treatment with fosaprepitant or aprepitant and for at least 1 month following the last fosaprepitant/aprepitant dose.

Fosaprepitant use during breastfeeding:

• It is unknown if fosaprepitant can be found in breast milk.
• According to the manufacturer breastfeeding during therapy should be considered in order to minimize the risk to the infant as well as the benefits to the mother.

Fosaprepitant (Emend) Dose in Kidney disease:

The manufacturer's labeling doesn't provide any dosage adjustments; however, due to modest decreases in protein binding of aprepitant, the AUC of the pharmacologically active unbound drug is not significantly affected in patients with renal disease.

• Hemodialysis:
  • Aprepitant is not removed by hemodialysis.

Fosaprepitant (Emend) Dose in Liver disease:

• Mild or moderate impairment (Child-Pugh class A or B):

  • No dosage adjustment is required.

• Severe impairment (Child-Pugh class C):

  • The manufacturer's labeling doesn't provide any dosage adjustments (has not been studied);
  • Additional monitoring may be needed in these patients.

Common Side Effects of Fosaprepitant (Emend):

• Central nervous system:

  • Fatigue

• Gastrointestinal:

  • Diarrhea

Less Common Side Effects of Fosaprepitant (Emend):

• Central nervous system:

  • Peripheral neuropathy

• Gastrointestinal:

  • Dyspepsia

• Genitourinary:

  • Urinary tract infection

• Hematologic & oncologic:

  • Neutropenia
  • Anemia
  • Leukopenia

• Local:

  • Infusion-site reaction includes
    • Induration at injection site
    • Local pruritus
    • Localized erythema
    • Infusion-site pain

• Neuromuscular & skeletal:

  • Weakness
  • Limb pain

Contraindications to Fosaprepitant (Emend):

• Hypersensitivity to fosaprepitant and any component of the formulation
• concurrent use with pimozide

Canadian labeling:

• Concurrent use with terfenadine, astemizole, or cisapride.

Warnings and precautions

• Hypersensitivity

  • Hypersensitivity reactions may occur during the infusion manifesting as erythema, flushing, dyspnea, hypotension, syncope, and anaphylaxis/anaphylactic shock.
  • Stop the infusion if you experience symptoms of an allergic reaction. Do not re-initiate.

• Reactions at the infusion site:

  • Infusion site reactions can manifest as edema or thrombophlebitis and erythema.
  • The majority of severe infusion-related reactions (including vasculitis, thrombophlebitis, and necrosis) have been reported with administration of concomitant vesicant (anthracycline-based) chemotherapy, particularly when associated with extravasation.
  • The majority of reactions were experienced within three to four exposures to one fosaprepitant injection. Some reactions lasted for up 2 weeks.
  • If you experience severe reactions at the infusion site, stop the infusion and provide appropriate treatment.
  • Avoid putting fosaprepitant in small veins.

• Hepatic impairment

  • Patients with hepatic impairment should use caution.
  • It has not been tested in patients with severe liver impairment (Child-Pugh Class C).

• Nausea/vomiting:

  • Not used in the treatment of nausea and vomiting.

Fosaprepitant: Drug Interaction

Monitoring parameters:

Consider INR in patients on chronic warfarin therapy in the 2-week period (particularly at 7 to 10 days) following fosaprepitant administration; Monitor the patient for sign and symptoms of hypersensitivity and infusion site reactions.

How to administer Fosaprepitant (Emend)?

• It is administered as an intravenous infusion.
• The infusion should be completed ~30 minutes prior to chemotherapy.
• Infuse over 20 to 30 minutes.

Mechanism of action of Fosaprepitant (Emend):

• Fosaprepitant (a prodrug for aprepitant) is an inhibitor of the substance P/neurokinin-1 (NK1) receptor. 
• Fosaprepitant is quickly converted by the body to aprepitant.
• This prevents acute or delayed vomiting by blocking the substance P/neurokinin1 (NK1) receptor.
• It also increases the antiemetic activities of the 5HT3 receptor antagonist, corticosteroid activity, and inhibits chemotherapy-induced nausea.

Distribution:

• The blood-brain barrier is broken by the Aprepitant

Protein binding:

• Aprepitant: >95%

Metabolism:

• Fosaprepitant: Hepatic and extrahepatic; It is rapidly metabolized within 30 minutes after the end of infusion and converted to aprepitant (nearly complete conversion)
• Aprepitant is mainly metabolized in the liver 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%)

International Brand Names of Fosaprepitant:

• Apritant IV
• Emend IV
• Ivemend
• Pranitand
• Emend
• Prevenausia
• Proemend

Fosaprepitant Brand Names in Pakistan:

There is no brand available in Pakistan