1 INDICATIONS AND USAGE 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).

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

Fosaprepitant for Injection is a substance P/neurokinin-1 (NK 1 ) receptor antagonist, indicated in adults and pediatric patients 6 months of age and older, in combination with other antiemetic agents, for the prevention of ( 1 ): 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 ( 1 ) Fosaprepitant for Injection has not been studied for treatment of established nausea and vomiting.

6 ADVERSE REACTIONS The following clinically significant adverse reactions are described elsewhere in the labeling: Hypersensitivity Reactions [see Warnings and Precautions (5.2) ] Infusion Site Reactions [see Warnings and Precautions (5.3) ] Most common adverse reactions in adults (≥2%) are: fatigue, diarrhea, neutropenia, asthenia, anemia, peripheral neuropathy, leukopenia, dyspepsia, urinary tract infection, pain in extremity.

( 6.1 ) Adverse reactions in pediatrics are similar to adults.

To report SUSPECTED ADVERSE REACTIONS, contact Qilu Pharma, INC.

at 484-838-0633/484-875-3013 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.

6.1 Clinical Trials Experience Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in clinical practice.

The overall safety of fosaprepitant for injection was evaluated in approximately 1800 adult and pediatric patients.

Adverse Reactions in Adults for the Prevention of Nausea and Vomiting Associated with MEC In an active-controlled clinical trial in patients receiving MEC, safety was evaluated in 504 patients receiving a single dose of fosaprepitant for injection in combination with ondansetron and dexamethasone (fosaprepitant for injection regimen) compared to 497 patients receiving ondansetron and dexamethasone alone (standard therapy).

The most common adverse reactions are listed in Table 6.

Table 6 Most Common Adverse Reactions in Patients Receiving MEC Reported in ≥2% of patients treated with the fosaprepitant for injection regimen and at a greater incidence than standard therapy.

Fosaprepitant for Injection, ondansetron, and dexamethasone fosaprepitant for injection regimen (N=504) Ondansetron and dexamethasone Standard therapy (N=497) fatigue 15% 13% diarrhea 13% 11% neutropenia 8% 7% asthenia 4% 3% anemia 3% 2% peripheral neuropathy 3% 2% leukopenia 2% 1% dyspepsia 2% 1% urinary tract infection 2% 1% pain in extremity 2% 1% Infusion-site reactions were reported in 2.2% of patients treated with the fosaprepitant for injection regimen compared to 0.6% of patients treated with standard therapy.

The infusion-site reactions included: infusion-site pain (1.2%, 0.4%), injection-site irritation (0.2%, 0.0%), vessel puncture-site pain (0.2%, 0.0%), and infusion-site thrombophlebitis (0.6%, 0.0%), reported in the fosaprepitant for injection regimen compared to standard therapy, respectively.

Adverse Reactions in Adults for the Prevention of Nausea and Vomiting Associated with HEC In an active-controlled clinical study in patients receiving HEC, safety was evaluated for 1143 patients receiving a single dose of fosaprepitant for injection compared to 1169 patients receiving the 3-day regimen of oral aprepitant [see Clinical Studies (14.1) ] .

The safety profile was generally similar to that seen in the MEC study with fosaprepitant and prior HEC studies with aprepitant.

However, infusion-site reactions occurred at a higher incidence in patients in the fosaprepitant group (3.0%) compared to those in the aprepitant group (0.5%).

The following additional infusion-site reactions occurred in the HEC study and were not reported in the MEC study described above: infusion-site erythema (0.5%, 0.1%), infusion-site pruritus (0.3%, 0.0%), and infusion-site induration (0.2%, 0.1%), reported in the fosaprepitant group compared to the aprepitant group, respectively.

Adverse Reactions in Pediatric Patients 6 Months to 17 Years of Age for the Prevention of Nausea and Vomiting Associated with HEC or MEC Single-Dose Fosaprepitant for Injection Regimen The safety of a single dose of fosaprepitant for injection in pediatric patients (6 months to 17 years) was evaluated in two active-controlled and a single-arm clinical study in patients who received either HEC or MEC.

Patients also received ondansetron with or without dexamethasone.

The adverse reaction profile was similar to adults.

The safety analysis included 69 pediatric patients who received the recommended dose.

An additional 70 patients received a single, higher-than-recommended dose.

The most common adverse reactions that occurred in >15% of patients who received the recommended dose were anemia, neutropenia, thrombocytopenia, and febrile neutropenia.

3-Day Fosaprepitant/Aprepitant Regimen In pediatric patients 12 to 17 years, the safety of the 3-day IV/oral/oral fosaprepitant/aprepitant regimen was evaluated in a single-arm clinical study including 12 patients who received a regimen of either HEC or MEC.

In pediatric patients 6 months to 12 years of age, the safety of the 3-day IV/oral/oral fosaprepitant/aprepitant regimen was not directly evaluated.

The safety of a single dose of fosaprepitant/aprepitant for injection (3 mg/kg) administered on day 1 of the 3-day IV/oral/oral regimen was evaluated in one active-controlled and one single-arm study including 48 pediatric patients 6 months to 12 years of age who received a regimen of either HEC or MEC.

The safety of the 3-day (IV/IV/IV) regimen of fosaprepitant for injection in pediatric patients (6 months to 17 years) was evaluated in a single-arm clinical study in 100 patients who received either HEC or MEC.

In these clinical studies, pediatric patients also received ondansetron with or without dexamethasone.

The adverse reaction profile in pediatric patients was similar to the profile in adult patients receiving a single dose of fosaprepitant for injection.

Because fosaprepitant is converted to aprepitant, those adverse reactions associated with aprepitant might also be expected to occur with fosaprepitant for injection.

See the full prescribing information for aprepitant capsules for complete safety information regarding studies performed with oral aprepitant.

6.2 Postmarketing Experience The following adverse reactions have been identified during post-approval use of fosaprepitant.

Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure.

Skin and subcutaneous tissue disorders: pruritus, rash, urticaria, Stevens-Johnson syndrome/toxic epidermal necrolysis [see Warnings and Precautions (5.2) ] .

Immune system disorders: hypersensitivity reactions including anaphylaxis and anaphylactic shock [see Contraindications (4) , Warnings and Precautions (5.2) ] .

Nervous system disorders: ifosfamide-induced neurotoxicity reported after fosaprepitant for injection and ifosfamide coadministration.