Fosaprepitant

FOSAPREPITANT- fosaprepitant dimeglumine injection, powder, lyophilized, for solution
Dr. Reddy’s Laboratories Inc.,

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1 INDICATIONS AND USAGE

Fosaprepitant for injection, in combination with other antiemetic agents, is indicated in adults for the prevention of:

• acute and delayed nauseaand vomiting associated with initial and repeat coursesof 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.Pediatric use information is approved for Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc.’s Emend (fosaprepitant) for injection. However, due to Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc.’s marketing exclusivity rights, this drug product is not labeled with that pediatric information.

2 DOSAGE AND ADMINISTRATION

2.1 Prevention of Nausea and Vomiting Associated with HEC and MEC in Adult Patients

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 injectionas an intravenous infusion on Day 1 over 20 to 30 minutes, completing the infusion approximately 30 minutes priorto chemotherapy.

Table 1 Recommended Adult Dosing 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 approximately 30 minutes prior to chemotherapy	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 ClinicalPharmacology (12.3)].

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

	Day 1
Fosaprepitant for injection	150 mg intravenously over 20 to 30 minutes approximately 30 minutes prior to chemotherapy
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 dimeglumine [see Clinical Pharmacology (12.3)].

Pediatric use information is approved for Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc.’s Emend (fosaprepitant) for injection. However, due to Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc.’s marketing exclusivity rights, this drug product is not labeled with that pediatric information.

2.3 Preparation of Fosaprepitant for Injection

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		AdultsThe entire volume of the prepared infusion bag (150 mL) should be administered.
Step 6		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 physicaland chemical compatibility have not been established. Fosaprepitant for injection is incompatible with any solutions containing divalent cations (e.g., Ca²⁺ , Mg²⁺), 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)].

Pediatric use information is approved for Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc.’s Emend (fosaprepitant) for injection. However, due to Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc.’s marketing exclusivity rights, this drug product is not labeled with that pediatric information.

3 DOSAGE FORMS AND STRENGTHS

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

4 CONTRAINDICATIONS

Fosaprepitant is contraindicated in patients:

• who are hypersensitive to any component of the product Hypersensitivity reactions includinganaphylactic 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)].

5 WARNINGS AND PRECAUTIONS

5.1 Clinically Significant CYP3A4 Drug Interactions

Fosaprepitant, a prodrug of aprepitant, is a weak inhibitor of CYP3A4, and aprepitant is a substrate, inhibitor, and inducer of CYP3A4.

• Use of fosaprepitant with other drugs that are CYP3A4 substrates, may result in increased plasma concentration of the concomitant drug.
  o Use of pimozidewith fosaprepitant is contraindicated due to the risk of significantly increased plasma concentrations of pimozide, potentially resulting in prolongation of the QT interval, a known adverse reactionof pimozide [seeContraindications (4)].
• Use of Fosaprepitant with strong or moderate CYP3A4 inhibitors (e.g., ketoconazole, diltiazem) may increase plasma concentrations of aprepitant and result in an increased risk of adversereactions related to fosaprepitant.
• Use of fosaprepitant with strong CYP3A4 inducers(e.g., rifampin) may result in a reductionin aprepitant plasma concentrations and decreased efficacy of fosaprepitant.See Table 7 and Table 8 for a listing of potentially significant drug interactions [see Drug Interactions (7.1, 7.2)].