Fosaprepitant

Fosaprepitant for injection, in combination with other antiemetic agents, is indicated in adults and pediatric patients 6 months of age and older 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.

• delayed nausea and vomiting associated with initial and repeat courses of moderately emetogenic cancer chemotherapy (MEC).

• Fosaprepitant for injection 150 mg on Day 1 as an intravenous infusion over 20 to 30 minutes.

• Complete the infusion approximately 30 minutes prior to chemotherapy.

• See Full Prescribing Information for pediatric dosage regimens by age.

• For single dose chemotherapy regimens:
  single dose of fosaprepitant for injection on Day 1.

• For single or multi-day chemotherapy regimens:
  3-day  fosaprepitant for injection regimen of fosaprepitant for injection on Day 1 and aprepitant capsules or  fosaprepitant for oral suspension on Days 2 and 3.

• Administer fosaprepitant for injection through a central venous catheter as an intravenous infusion over 30 minutes (12 years to 17 years) or 60 minutes (6 months to less than 12 years).

• Complete the infusion approximately 30 minutes prior to chemotherapy.

• See Full Prescribing Information for additional information.

Fosaprepitant for injection: 150 mg fosaprepitant, white to off white cake or powder in single-dose glass vial for reconstitution.

There are insufficient data on use of fosaprepitant in pregnant women to inform a drug associated risk. In  animal reproduction studies, no adverse developmental   effects were observed in rats or rabbits exposed during the period of organogenesis to systemic drug levels (AUC) approximately equivalent to the exposure at the recommended human dose (RHD) of 150 mg

The estimated  background risk of major birth defects and miscarriage for the indicated populations is unknown. In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2 to 4% and 15 to 20%, respectively.

In  embryofetal  development  studies  in rats  and rabbits, aprepitant was  administered during  the period of organogenesis at oral doses up to 1000 mg/kg twice daily (rats) and up to the maximum tolerated dose of 25 mg/kg/day (rabbits). No embryofetal lethality or malformations were observed at any dose level in either species. The exposures (AUC) in pregnant rats at 1000 mg/kg twice daily and in  pregnant rabbits at 25 mg/kg/day were   approximately equivalent to the exposure at the RHD of 150 mg. Aprepitant crosses the placenta in rats and rabbits. 

• CYP3A4 Interactions:
  Fosaprepitant is a weak inhibitor of CYP3A4, and aprepitant, the active moiety, is a substrate, inhibitor, and inducer of CYP3A4; see Full Prescribing Information for recommendations regarding contraindications, risk of adverse reactions, and dosage adjustment of fosaprepitant and concomitant drugs.
• Hypersensitivity Reactions (including anaphylaxis and anaphylactic shock)
  : May occur during or soon after infusion. If symptoms occur, discontinue the drug. Do not reinitiate fosaprepitant if symptoms occur with previous use.
• Infusion Site Reactions (including thrombophlebitis, necrosis, and vasculitis):
  Majority of reactions reported in patients receiving vesicant chemotherapy. Avoid infusion into small veins. Discontinue infusion and administer treatment if a severe reaction develops. (5.3)
• Warfarin (a CYP2C9 substrate):
  Risk of decreased INR of prothrombin time; monitor INR in 2–week period, particularly at 7 to 10 days, following initiation of fosaprepitant.  
• Hormonal Contraceptives:
  Efficacy of contraceptives may be reduced during and for 28 days following administration of fosaprepitant. Use effective alternative or back-up methods of contraception.