Fosaprepitant

Fosaprepitant is a prescription medication indicated 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 (HEC) chemotherapy including high dose cisplatin
• delayed nausea and vomiting associated with initial and repeat courses of moderately emetogenic cancer (MEC) chemotherapy

Fosaprepitant is available under the following different brand names: Emend IV, Focinvez

Common side effects of Fosaprepitant include:

• tiredness
• hiccups
• nausea
• vomiting
• heartburn
• stomach pain
• diarrhea
• constipation
• loss of appetite
• increased thirst
• hot and dry skin
• weakness
• dizziness
• headache
• ringing in the ears
• fever
• chills
• body aches
• flu symptoms
• sleep problems (insomnia)
• pain or a hard lump on the injection site

Serious side effects of Fosaprepitant include:

• hives
• rash
• itching
• skin sores or peeling
• warmth or tingly feeling
• fast or weak heartbeats
• severe dizziness
• trouble breathing or swallowing
• swelling of the face, lips, tongue, or throat
• pain, redness, swelling, burning, blistering, or skin changes where the chemotherapy medicine was injected
• a lightheaded feeling
• pain or burning while passing urine
• low blood cell counts —fever, chills, tiredness, mouth sores, skin sores, easy bruising, unusual bleeding, pale skin, cold hands, and feet, feeling lightheaded or short of breath

Rare side effects of Fosaprepitant include:

• none

Seek medical care or call 911 at once if you have the following serious side effects:

• Severe headache, confusion, slurred speech, arm or leg weakness, trouble walking, coordination loss, unsteady, very stiff muscles, high fever, profuse sweating, or tremors;
• Serious eye symptoms such as sudden vision loss, blurred vision, tunnel vision, eye pain or swelling, or seeing halos around lights;
• Serious heart symptoms include fast, irregular, or pounding heartbeats; fluttering in the chest; shortness of breath; sudden dizziness, lightheadedness, or passing out.

This is not a complete list of side effects and other serious side effects or health problems that may occur because of the use of this drug. Call your doctor for medical advice about serious side effects or adverse reactions. You may report side effects or health problems to FDA at 1-800-FDA-1088.

Adult and pediatric dosage

Injection, powder for reconstitution

• 150 mg/vial (Emend IV)

Injection, solution

• 150 mg/50 mL (Focinvez)

Chemotherapy-induced nausea and vomiting

Adult dosage

• HEC
  • Day 1: 150 mg IV infused over 20 to 30 minutes approximately 30 minutes before chemotherapy plus dexamethasone 12 mg orally and a 5-HT3 antagonist
  • Day 2: Dexamethasone 8 mg orally in the morning
  • Days 3 and 4: Dexamethasone 8 mg orally two times a day (morning and evening)
  • NOTE: A 50% dosage reduction of dexamethasone on days 1 and 2 is recommended to account for drug interaction with aprepitant
• MEC
  • Day 1: 150 mg IV infused over 20 to 30 minutes approximately 30 minutes before chemotherapy plus dexamethasone 12 mg orally and a 5-HT3 antagonist

Pediatric dosage

IV (single-day chemotherapy regimens)

• Children younger than 6 months or who weigh less than 6 kg: Safety and efficacy not established
• Children aged between 6 months and less than 2 years: 5 mg/kg IV over 60 minutes approximately 30 minutes before chemotherapy; not to exceed 150 mg/dose
• Children aged between 2 years and less than 12 years: 4 mg/kg IV over 60 minutes approximately 30 minutes before chemotherapy; not to exceed 150 mg/dose
• Children aged between 12 and 17 years: 150 mg IV over 30 minutes approximately 30 minutes before chemotherapy
• In combination with dexamethasone and 5-HT3 antagonist (e.g., ondansetron)
• Recommended dosing for 6 months to 17 years for the prevention of nausea and vomiting associated with single-day regimens of HEC or MEC
• Dexamethasone: If a corticosteroid (e.g., dexamethasone) is coadministered, administer 50% of recommended corticosteroid dose on Days 1 and 2; administer 30 minutes before chemotherapy treatment on Day 1
• 5-HT3 antagonist: See selected 5-HT3 antagonist prescribing information for recommended dosage
• IV (multiday chemotherapy regimens)
• NOTE: May administer IV infusion on days 1, 2, and 3 or days 2 and 3 may use capsules or oral suspension instead
• Children aged 6 months or who weigh less than 6 kg: Safety and efficacy not established
• Children aged 6 months to less than 12 years
  • Day 1: 3 mg/kg IV over 60 minutes approximately 30 minutes before chemotherapy; not to exceed 115 mg/dose
  • Days 2 and 3 (IV): 2 mg/kg IV over 60 minutes approximately 30 minutes before chemotherapy; not to exceed 80 mg/dose, or
  • Days 2 and 3 (oral suspension): 2 mg/kg orally approximately 30 minutes before chemotherapy; not to exceed 80 mg/dose
• Children aged 12 to 17 years
  • Day 1: 115 mg IV over 30 minutes approximately 30 minutes before chemotherapy
  • Days 2 and 3 (IV): 80 mg IV over 30 minutes approximately 30 minutes before chemotherapy; not to exceed 80 mg/dose, or
  • Days 2 and 3 (capsules): 80 mg orally approximately 30 minutes before chemotherapy
  • Dexamethasone: If a corticosteroid (e.g., dexamethasone) is coadministered, administer 50% of recommended corticosteroid dose on Days 1 and 2; administer 30 minutes before chemotherapy treatment on day 1
  • 5-HT3 antagonist: See selected 5-HT3 antagonist prescribing information for recommended dosage

Dosage Considerations – Should be Given as Follows:

• See “Dosages”

If your medical doctor is using this medicine to treat your pain, your doctor or pharmacist may already be aware of any possible drug interactions and may be monitoring you for them. Do not start, stop, or change the dosage of any medicine before checking with your doctor, healthcare provider, or pharmacist first.

• Fosaprepitant has severe interactions with the following drugs:
  • chloramphenicol
  • darunavir
  • flibanserin
  • lomitapide
  • lonafarnib
  • pimozide
  • ribociclib
  • tipranavir
• Fosaprepitant has serious interactions with at least 72 other drugs
• Fosaprepitant has moderate interactions with at least 187 other drugs
• Fosaprepitant has minor interactions with at least 54 other drugs

This information does not contain all possible interactions or adverse effects. Visit the RxList Drug Interaction Checker for any drug interactions. Therefore, before using this product, tell your doctor or pharmacist about all the products you use. Keep a list of all your medications with you and share this information with your doctor and pharmacist. Check with your healthcare professional or doctor for additional medical advice, health questions, or concerns.

Contraindications

• Hypersensitivity
• Concomitant pimozide

Effects of drug abuse

• None

Short-Term Effects

• See “What Are Side Effects Associated with Using Fosaprepitant?”

Long-Term Effects

• See “What Are Side Effects Associated with Using Fosaprepitant?”

Cautions

• Hypersensitivity reactions
  • Serious hypersensitivity reactions, including anaphylaxis and anaphylactic shock, during or soon after administration reported
  • Symptoms may include dyspnea, eye swelling, flushing, pruritus and wheezing
  • Monitor during and after IV administration
  • If hypersensitivity reactions occur, discontinue the drug, and administer appropriate medical therapy; do not reinitiate treatment in patients who experience these symptoms with previous use
• Infusion site reactions
  • Infusion site reactions (ISRs) reported after IV infusion
  • Majority of severe ISRs, including thrombophlebitis and vasculitis, were reported with concomitant vesicant (anthracycline-based) chemotherapy administration, particularly when associated with extravasation
  • Necrosis was also reported with concomitant vesicant chemotherapy
  • If a severe ISR develops during infusion, discontinue and administer appropriate medical treatment
• Drug interaction overview
• Fosaprepitant, a prodrug of aprepitant, is a weak CYP3A4 inhibitor
• Aprepitant is a CYP3A4 substrate, inhibitor (weak to moderate [dose dependent]), and inducer
• Aprepitant is also an inducer of CYP2C9
• Pimozide
• Contraindicated
  • Coadministration of pimozide (major CYP3A4 substrate) with aprepitant significantly increased plasma concentrations of pimozide, which may prolong QT interval
  • CYP3A4 substrates
    • Concomitant use of aprepitant and CYP3A4 substrates may result in increased plasma concentration of the CYP3A4 drugs
    • Moderate-to-strong CYP3A4 inhibitors
• Avoid
  • Coadministration of aprepitant or fosaprepitant may increase plasma concentrations and effects of aprepitant
  • Strong CYP3A4 inducers
• Avoid
  • Coadministration of aprepitant with strong CYP3A4 inducers (eg, rifampin, carbamazepine, phenytoin) may result in a substantial reduction in aprepitant plasma concentrations and decreased efficacy
  • Corticosteroids
• Modify dose
  • Aprepitant or fosaprepitant increases dexamethasone and methylprednisolone exposure
  • Reduce oral dexamethasone dose by approximately 50%
  • Reduce IV methylprednisolone dose by approximately 25% and oral methylprednisolone dose by approximately 50%
• Benzodiazepines
  • Monitor for benzodiazepine adverse effects
  • Coadministration of aprepitant or fosaprepitant with benzodiazepines metabolized by CYP3A4 (eg, midazolam, alprazolam, triazolam) may increase benzodiazepine levels and/or effects
• Warfarin
  • Monitor INR; adjust warfarin dose if needed
  • In patients on chronic warfarin therapy, monitor INR in the 2 weeks, particularly at 7 to 10 days, following aprepitant or fosaprepitant administration with each chemotherapy cycle
  • Coadministration with warfarin may decrease warfarin exposure owing to induction of CYP2C9, resulting in decreases in INR
• Oral contraceptives
  • Use effective alternant or backup methods (eg, condoms, spermicides) during treatment with aprepitant or fosaprepitant and for 1 month following administration
  • Coadministration with oral contraceptives may decrease estrogen and progestin exposure during administration and for 28 days after the last aprepitant dose

Pregnancy and Lactation

• Data are insufficient on use in pregnant women to inform about the drug-associated risk
• Contraception
  • Aprepitant or fosaprepitant may reduce the efficacy of hormonal contraceptives owing to induction of CYP3A4
  • Advise women of reproductive potential using hormonal contraceptives to use an effective alternative or backup non-hormonal contraceptive (eg, condoms, spermicides) during treatment and for 1 month after the last dose
• Lactation
  • Unknown if excreted in milk
  • Determine whether to discontinue nursing or to discontinue the drug, considering the importance of the drug to the mother