Fosaprepitant (Page 7 of 8)

14.2 Prevention of Nausea and Vomiting Associated with MEC in Adults

In a randomized, parallel, double-blind, active comparator-controlled study, fosaprepitant 150 mg as a single intravenous infusion (N=502) in combination with ondansetron and dexamethasone (intravenous fosaprepitant regimen) was compared with ondansetron and dexamethasone alone (standard therapy) (N=498) (see Table 13) in patients receiving a MEC regimen. Patient demographics were similar between the two treatment groups. Of the total 1,000 patients included in the efficacy analysis, 41% were men, 84% White, 4% Asian, 1% American Indian/Alaska Native, 2% Black, 10% Multi-Racial, and 19% Hispanic/Latino ethnicity. Patient ages ranged from 23 to 88 years of age, with a mean age of 60 years. The most commonly administered MEC chemotherapeutic agents were carboplatin (51%), oxaliplatin (24%), and cyclophosphamide (12%).

Table 13 Treatment Regimens in Adult MEC Trial*

	Day 1	Day 2	Day 3
Intravenous Fosaprepitant Regimen
Fosaprepitant	150 mg intravenously over 20 to 30 minutes approximately 30 minutes prior to chemotherapy	none	none
Oral Dexamethasone†	12 mg	none	none
Oral Ondansetron‡	8 mg for 2 doses	none	none
Standard Therapy
Oral Dexamethasone	20 mg	none	none
Oral Ondansetron‡	8 mg for 2 doses	8 mg twice daily	8 mg twice daily
* Fosaprepitant placebo and dexamethasone placebo (on Day 1) were used to maintain blinding.
† Dexamethasone was administered 30 minutes prior to chemotherapy treatment on Day 1. The 12 mg dose reflects a dosage adjustment to account for a drug interaction with the fosaprepitant regimen [see Clinical Pharmacology (12.3)].
‡ The first ondansetron dose was administered 30 to 60 minutes prior to chemotherapy treatment on Day 1 and the second dose was administered 8 hours after first ondansetron dose.

The primary endpoint was complete response (defined as no vomiting and no rescue therapy) in the delayed phase (25 to 120 hours) of chemotherapy-induced nausea and vomiting. The results by treatment group are shown in Table 14.

Table 14 Percent of Adult Patients Receiving MEC Responding by Treatment Group

ENDPOINTS	Intravenous Fosaprepitant Regimen	Standard Therapy Regimen	P-Value	Treatment Difference (95% CI)
	(N=502)*	(N=498)*
	%	%
PRIMARY ENDPOINT
Complete Response†
Delayed phase‡	78.9	68.5	<0.001	10.4 (5.1, 15.9)
* N: Number of patients included in the intention to treat population.
† Complete Response = no vomiting and no use of rescue therapy.
‡ Delayed phase = 25 to 120 hours post-initiation of chemotherapy.

16 HOW SUPPLIED/STORAGE AND HANDLING

One single-dose glass vial containing 150 mg fosaprepitant as a sterile, white to off-white lyophilized powder for reconstitution. Supplied as follows:

NDC 0591-4385-79 1 vial per carton.

Storage

Store at 2° to 8°C (36° to 46°F).

For storage of reconstituted drug solution see Dosage and Administration 2.2.

17 PATIENT COUNSELING INFORMATION

Advise the patient to read the FDA-approved patient labeling (Patient Information).

Hypersensitivity

Advise patients that hypersensitivity reactions, including anaphylaxis and anaphylactic shock, have been reported in patients taking fosaprepitant. Advise patients to seek immediate medical attention if they experience signs or symptoms of a hypersensitivity reaction, such as hives, rash and itching, skin peeling or sores, flushing, difficulty in breathing or swallowing, or dizziness, rapid or weak heartbeat or feeling faint [see Warnings and Precautions (5.2)].

Infusion Site Reactions

Advise patients to seek medical attention if they experience new or worsening signs or symptoms of an infusion site reaction, such as erythema, edema, pain, necrosis, vasculitis, or thrombophlebitis at or near the infusion site [see Warnings and Precautions (5.3)].

Drug Interactions

Advise patients to discuss all medications they are taking, including other prescription, non-prescription medication or herbal products [see Contraindications (4), Warnings and Precautions (5.1)].

Warfarin: Instruct patients on chronic warfarin therapy to follow instructions from their healthcare provider regarding blood draws to monitor their INR during the 2-week period, particularly at 7 to 10 days, following initiation of Fosaprepitant for Injection with each chemotherapy cycle [see Warnings and Precautions (5.4)].

Hormonal Contraceptives: Advise patients that administration of Fosaprepitant for Injection may reduce the efficacy of hormonal contraceptives. Instruct patients to use effective alternative or back-up methods of contraception (such as condoms or spermicides) during treatment with Fosaprepitant for Injection and for 1 month following administration of Fosaprepitant for Injection [see Warnings and Precautions (5.5), Use in Specific Populations (8.3)].

Manufactured in Romania By:
Sindan Pharma SRL
11 Ion Mihalache Blvd.
Bucharest 1, Romania 011171

Or

Manufactured in Italy By:
Actavis Italy Spa A Socio Unico
Nerviano, Italy, 20014

Manufactured For:
Teva Pharmaceuticals USA, Inc. North Wales, PA 19454