Fosaprepitant

FOSAPREPITANT- fosaprepitant dimeglumine injection, powder, lyophilized, for solution
Actavis Pharma, Inc.

1 INDICATIONS AND USAGE

Fosaprepitant for Injection, in combination with other antiemetic agents, is indicated in adults 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).

Limitations of Use

• Fosaprepitant for Injection has not been studied for the treatment of established nausea and vomiting.

2 DOSAGE AND ADMINISTRATION

2.1 Recommended Dosage

The recommended dosage of Fosaprepitant for Injection, dexamethasone, and a 5-HT₃ antagonist for the prevention of nausea and vomiting associated with administration of HEC or MEC in adults is shown in Table 1 or Table 2, respectively. Administer Fosaprepitant for Injection as an intravenous infusion on Day 1 over 20 to 30 minutes, completing the infusion approximately 30 minutes prior to chemotherapy.

Table 1 Recommended Dosage for the Prevention of Nausea and Vomiting Associated with HEC

	Day 1	Day 2	Day 3	Day 4
Fosaprepitant for Injection	150 mg intravenously over 20 to 30 minutes	none	none	none
Dexamethasone*	12 mg orally	8 mg orally	8 mg orally twice daily	8 mg orally twice daily
5-HT3 antagonist	See selected 5-HT3 antagonist prescribing information for the recommended dosage	none	none	none
* Administer dexamethasone 30 minutes prior to chemotherapy treatment on Day 1 and in the morning on Days 2 through 4. Also administer dexamethasone in the evenings on Days 3 and 4. A 50% dosage reduction of dexamethasone on Days 1 and 2 is recommended to account for a drug interaction with Fosaprepitant for Injection [see Clinical Pharmacology (12.3)].

Table 2 Recommended Dosage for the Prevention of Nausea and Vomiting Associated with MEC

	Day 1
Fosaprepitant for Injection	150 mg intravenously over 20 to 30 minutes
Dexamethasone*	12 mg orally
5-HT3 antagonist	See selected 5-HT3 antagonist prescribing information for the recommended dosage
* Administer dexamethasone 30 minutes prior to chemotherapy treatment on Day 1. A 50% dosage reduction of dexamethasone is recommended to account for a drug interaction with Fosaprepitant for Injection [see Clinical Pharmacology (12.3)].

2.2 Preparation Instructions

Table 5 Preparation Instructions for Fosaprepitant for Injection (150 mg)

Step 1	Aseptically inject 5 mL 0.9% Sodium Chloride Injection, USP into the vial. Assure that 0.9% Sodium Chloride Injection, USP is added to the vial along the vial wall in order to prevent foaming. Swirl the vial gently. Avoid shaking and jetting 0.9% Sodium Chloride Injection, USP into the vial.
Step 2	Aseptically prepare an infusion bag filled with 145 mL of 0.9% Sodium Chloride Injection, USP.
Step 3	Aseptically withdraw the entire volume from the vial and transfer it into the infusion bag containing 145 mL of 0.9% Sodium Chloride Injection, USP to yield a total volume of 150 mL and a final concentration of 1 mg/mL.
Step 4	Gently invert the bag 2 to 3 times.
Step 5	Before administration, inspect the bag for particulate matter and discoloration. Discard the bag if particulate and/or discoloration are observed.

Caution: Do not mix or reconstitute Fosaprepitant for Injection with solutions for which physical and chemical compatibility have not been established. Fosaprepitant for Injection is incompatible with any solutions containing divalent cations (e.g., calcium, magnesium), including Lactated Ringer’s Solution and Hartmann’s Solution.

Storage

The reconstituted final drug solution is stable for 24 hours at ambient room temperature [at or below 25°C (77°F)].

3 DOSAGE FORMS AND STRENGTHS

Fosaprepitant for Injection: 150 mg fosaprepitant, white to off-white lyophilized powder in single-dose glass vial for reconstitution

4 CONTRAINDICATIONS

Fosaprepitant for Injection is contraindicated in patients:

• who are hypersensitive to any component of the product. Hypersensitivity reactions including anaphylactic reactions, flushing, erythema, and dyspnea have been reported [see Warnings and Precautions (5.2), Adverse Reactions (6.2)].
• taking pimozide. Inhibition of CYP3A4 by aprepitant, the active moiety, could result in elevated plasma concentrations of this drug, which is a CYP3A4 substrate, potentially causing serious or life-threatening reactions, such as QT prolongation, a known adverse reaction of pimozide [see Warnings and Precautions (5.1)].