fosaprepitant

General

Pronunciation:
fos-a-prep-i-tant

Trade Name(s)

• Emend
• Focinvez

Ther. Class.

antiemetics

Pharm. Class.

neurokinin antagonists

Indications

• Prevention of acute and delayed nausea and vomiting associated with initial and repeat courses of highly emetogenic chemotherapy.
• Prevention of delayed nausea and vomiting associated with initial and repeat courses of moderately emetogenic chemotherapy.

Action

Acts as a selective antagonist at substance P/neurokinin 1 (NK₁ ) receptors in the brain.

Therapeutic Effect(s):

Decreased nausea and vomiting associated with chemotherapy.

Pharmacokinetics

Absorption: Following IV administration, fosaprepitant is rapidly converted to aprepitant, the active component. IV administration results in complete bioavailability.

Distribution: Crosses the blood brain barrier; remainder of distribution unknown.

Protein Binding: 95–99%.

Metabolism and Excretion: Mostly metabolized by the liver by the CYP3A4 isoenzyme; not renally excreted.

Half-life: Aprepitant: 9–13 hr.

TIME/ACTION PROFILE (antiemetic effect)

Contraindication/Precautions

Contraindicated in:

• Hypersensitivity;
• Concurrent use with pimozide;
• Lactation: Lactation.

Use Cautiously in:

• OB:  Use during pregnancy only if potential maternal benefit justifies potential fetal risk;
• Pedi:  Children <6 mo (safety and effectiveness not established).

Adverse Reactions/Side Effects

Derm: STEVENS-JOHNSON SYNDROME (SJS)

GI: diarrhea

Neuro: dizziness, fatigue, headache, weakness

Misc: hiccups, HYPERSENSITIVITY REACTIONS (including anaphylaxis), infusion reactions

* CAPITALS indicate life-threatening.
Underline indicate most frequent.

Interactions

Drug-Drug

• May significantly ↑ levels of  pimozide, which can ↑ risk of torsades de pointes; concurrent use contraindicated.
• May ↑ levels and risk of toxicity of  CYP3A4 substrates, including  docetaxel,  paclitaxel,  etoposide,  irinotecan,  ifosfamide,  imatinib,  vinorelbine,  vinblastine,  vincristine,  midazolam,  triazolam, and  alprazolam ; concurrent use should be undertaken with caution.
•  Moderate or strong CYP3A4 inhibitors, including  ketoconazole,  itraconazole,  nefazodone,  clarithromycin,  ritonavir,  nelfinavir, and  diltiazem, may ↑ levels and risk of toxicity.
•  Strong CYP3A4 inducers, including  rifampin,  carbamazepine, and  phenytoin, may ↓ levels and effectiveness.
• ↑ levels and risk of toxicity of  dexamethasone  (regimen reflects a 50% dose ↓); a similar effect occurs with  methylprednisolone  (↓ IV dose by 25%, ↓ PO dose by 50% when used concurrently).
• May ↓ the effects of  warfarin  (carefully monitor INR for 2 wk),  oral contraceptives  (use alternate method), and  phenytoin.

Route/Dosage

Prevention of Acute and Delayed Nausea and Vomiting Associated with Highly Emetogenic Chemotherapy

IV (Adults): Emend or Focinvez: 150 mg given 30 min prior to chemotherapy on Day 1 only.

IV (Children 12–17 yr and ≥6 kg): Single-day chemotherapy regimen (Emend or Focinvez): 150 mg given 30 min prior to chemotherapy on Day 1 only;  Multiday chemotherapy regimen (Emend): 115 mg given 30 min prior to chemotherapy on Day 1, then 80 mg once daily (as IV fosaprepitant or aprepitant oral capsules) for 2 days (Days 2 and 3);  Multiday chemotherapy regimen (Focinvez): 115 mg given 30 min prior to chemotherapy on Day 1, then 80 mg once daily (as aprepitant oral capsules) for 2 days (Days 2 and 3).

IV (Children 2–<12 yr and ≥6 kg): Single-day chemotherapy regimen (Emend or Focinvez): 4 mg/kg (max dose = 150 mg) given 30 min prior to chemotherapy on Day 1 only;  Multiday chemotherapy regimen (Emend): 3 mg/kg (max dose = 115 mg) given 30 min prior to chemotherapy on Day 1, then 2 mg/kg (max dose = 80 mg) (as IV fosaprepitant or aprepitant oral suspension) once daily for 2 days (Days 2 and 3);  Multiday chemotherapy regimen (Focinvez): 3 mg/kg (max dose = 115 mg) given 30 min prior to chemotherapy on Day 1, then 2 mg/kg (max dose = 80 mg) (as aprepitant oral suspension) once daily for 2 days (Days 2 and 3).

IV (Children 6 mo-<2 yr and ≥6 kg): Single-day chemotherapy regimen (Emend or Focinvez): 5 mg/kg (max dose = 150 mg) given 30 min prior to chemotherapy on Day 1 only;  Multiday chemotherapy regimen (Emend): 3 mg/kg (max dose = 115 mg) given 30 min prior to chemotherapy on Day 1, then 2 mg/kg (max dose = 80 mg) (as IV fosaprepitant or aprepitant oral suspension) once daily for 2 days (Days 2 and 3);  Multiday chemotherapy regimen (Focinvez): 3 mg/kg (max dose = 115 mg) given 30 min prior to chemotherapy on Day 1, then 2 mg/kg (max dose = 80 mg) (as aprepitant oral suspension) once daily for 2 days (Days 2 and 3).

Prevention of Delayed Nausea and Vomiting Associated with Moderately Emetogenic Chemotherapy

IV (Adults): Emend or Focinvez: 150 mg given 30 min prior to chemotherapy on Day 1 only.

IV (Children 12–17 yr and ≥6 kg): Single-day chemotherapy regimen (Emend or Focinvez): 150 mg given 30 min prior to chemotherapy on Day 1 only;  Multiday chemotherapy regimen (Emend): 115 mg given 30 min prior to chemotherapy on Day 1, then 80 mg (as IV fosaprepitant or aprepitant oral capsules) once daily for 2 days (Days 2 and 3);  Multiday chemotherapy regimen (Focinvez): 115 mg given 30 min prior to chemotherapy on Day 1, then 80 mg (as aprepitant oral capsules) once daily for 2 days (Days 2 and 3).

IV (Children 2–<12 yr and ≥6 kg): Single-day chemotherapy regimen (Emend or Focinvez): 4 mg/kg (max dose = 150 mg) given 30 min prior to chemotherapy on Day 1 only;  Multiday chemotherapy regimen (Emend): 3 mg/kg (max dose = 115 mg) given 30 min prior to chemotherapy on Day 1, then 2 mg/kg (max dose = 80 mg) (as IV fosaprepitant or aprepitant oral suspension) once daily for 2 days (Days 2 and 3);  Multiday chemotherapy regimen (Focinvez): 3 mg/kg (max dose = 115 mg) given 30 min prior to chemotherapy on Day 1, then 2 mg/kg (max dose = 80 mg) (as aprepitant oral suspension) once daily for 2 days (Days 2 and 3).

IV (Children 6 mo-<2 yr and ≥6 kg): Single-day chemotherapy regimen (Emend or Focinvez): 5 mg/kg (max dose = 150 mg) given 30 min prior to chemotherapy on Day 1 only;  Multiday chemotherapy regimen (Emend): 3 mg/kg (max dose = 115 mg) given 30 min prior to chemotherapy on Day 1, then 2 mg/kg (max dose = 80 mg) (as IV fosaprepitant or aprepitant oral suspension) once daily for 2 days (Days 2 and 3);  Multiday chemotherapy regimen (Focinvez): 3 mg/kg (max dose = 115 mg) given 30 min prior to chemotherapy on Day 1, then 2 mg/kg (max dose = 80 mg) (as aprepitant oral suspension) once daily for 2 days (Days 2 and 3).

Availability (generic available)

Lyophilized powder for injection (Emend): 150 mg/vial

Solution for injection (Focinvez): 3 mg/mL

Assessment

• Assess nausea, vomiting, appetite, bowel sounds, and abdominal pain prior to and following administration.
• Monitor hydration, nutritional status, and intake and output. Patients with severe nausea and vomiting may require IV fluids in addition to antiemetics.
• Assess for rash periodically during therapy. May cause SJS. Discontinue therapy if severe rash or if rash accompanied by fever, general malaise, fatigue, muscle or joint aches, blisters, skin peeling, sores, oral lesions, conjunctivitis, hepatitis, and/or eosinophilia occurs.
• Monitor for signs and symptoms of infusion site reaction (erythema, edema, pain, thrombophlebitis). Treat symptomatically.
• Monitor for signs and symptoms of hypersensitivity reactions (flushing, erythema, dyspnea, hypotension, syncope) periodically during therapy. If symptoms occur, discontinue therapy and treat symptoms; do not reinitiate therapy if symptoms occur with first use.

Lab Test Considerations:

May cause mild, transient ↑ in alkaline phosphatase, AST, ALT, and BUN.

• May cause proteinuria, erythrocyturia, leukocyturia, hyperglycemia, hyponatremia, and ↑ leukocytes.
• May cause ↓ hemoglobin and WBC.

Implementation

• For chemotherapy, fosaprepitant is given as part of a regimen that includes a corticosteroid and a 5-HT₃  antagonist.

Patient/Family Teaching

• Instruct patient to take fosaprepitant as directed. Direct patient to read the  Patient Package Insert  before starting therapy and each time Rx renewed in case of changes.
• Instruct patient to notify health care professional if nausea and vomiting occur prior to administration.
• Advise patient to notify health care professional immediately if symptoms of hypersensitivity reaction (hives, rash, itching, redness of the face/skin, difficulty in breathing or swallowing) occur.
• Instruct patient to notify health care professional of all Rx or OTC medications, vitamins, or herbal products being taken and consult health care professional before taking any new medications.
• Advise patient and family to use general measures to decrease nausea (begin with sips of liquids and small, nongreasy meals; provide oral hygiene; remove noxious stimuli from environment).
• Rep:  Caution patient that fosaprepitant may decrease effectiveness of oral contraceptives. Advise patient to use alternate nonhormonal methods of contraception during and for 1 mo following treatment. Advise patient to notify health care professional if pregnancy is planned or suspected or if breastfeeding.

Evaluation/Desired Outcomes

• Decreased nausea and vomiting associated with chemotherapy.
• Prevention of postoperative nausea and vomiting.