Fosaprepitant

Product Type: HUMAN PRESCRIPTION DRUG

Route: INTRAVENOUS

Dosage Form:

NDC: 16714-248

Application: ANDA214616

Effective: 20230725

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.

2 DOSAGE AND ADMINISTRATION Recommended Adult Dosage ( 2.1 ) • Fosaprepitant for injection 150 mg on Day 1 as an intravenous infusion over 20 to 30 minutes. ( 2.1 ) • Complete the infusion approximately 30 minutes prior to chemotherapy. Recommended Dosage for Pediatric Patients (6 months to 17 years) Weighing at Least 6 kg ( 2.2 ) • 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 regimen of fosaprepitant for injection on Day 1 and fosaprepitant 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. Concomitant Antiemetics • See Full Prescribing Information for additional information. ( 2.1 , 2.2 ) 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-HT 3 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 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 none none none Dexamethasone* 12 mg orally 8 mg orally 8 mg orally twice daily 8 mg orally twice daily 5-HT 3 antagonist See selected 5-HT 3 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 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 Dexamethasone* 12 mg orally 5-HT 3 antagonist See selected 5-HT 3 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 Prevention of Nausea and Vomiting Associated with HEC and MEC in Pediatric Patients Therecommended pediatric dose regimens of fosaprepitant for injection, to be administered with a 5-HT 3 antagonist, with or without a corticosteroid,forthe prevention of nausea and vomiting associated with administration of single or multi-day chemotherapy regimens of HEC or MEC, are shown inTables 3 and 4. Single-day chemotherapy regimens include regimens in which HEC or MEC is administered for a single day only. Multi-daychemotherapy regimens include chemotherapy regimens in which HEC or MEC is administered for 2 or more days. Fosaprepitantfor Injection Dosage Regimens for Use with Single-Day Chemotherapy Regimens Forpediatric patients weighing at least 6 kg receiving single-day HEC or MEC, fosaprepitant for injection may be administered as: • a single dose regimen of fosaprepitant for injection infused through a central venous catheter on Day 1, as shown in Table 3; or • as a 3-day fosaprepitant regimen consisting of fosaprepitant for injection as an intravenous infusion through a central venous catheter on Day 1 and fosaprepitant capsules or fosaprepitant for oral suspension on Days 2 and 3, as shown in Table 4. Administerfosaprepitant for injection on Day 1 over 30 minutes (12 years to 17 years) or 60 minutes (6 months to less than 12 years), completingthe infusion approximately 30 minutes prior to chemotherapy. Table 3 Fosaprepitant for Injection Single Dose Regimen for the Prevention of Nausea and Vomiting Associated with Single-Day Regimens of HEC or MEC in Pediatric Patients 6 Months* to 17 Years Drug Age Regimen fosaprepitant for injection 12 Years to 17 Years 150 mg intravenously over 30 minutes 2 Years to less than 12 Years 4 mg/kg (maximum dose 150 mg) intravenously over 60 minutes 6 Months to less than 2 Years 5 mg/kg (maximum dose 150 mg) intravenously over 60 minutes Dexamethasone † 6 Months to 17 Years If a corticosteroid, such as dexamethasone, is co-administered, administer 50% of the recommended corticosteroid dose on Days 1 and 2. 5-HT 3 antagonist 6 Months to 17 Years See selected 5-HT 3 antagonist prescribing information for the recommended dosage * Dosing in pediatric patients less than 6 kg is not recommended † Administer dexamethasone 30 minutes prior to chemotherapy treatment on Day 1 Fosaprepitant for Injection Dosage Regimen for Use with Multi-Day Chemotherapy Regimens For pediatric patients weighing at least 6 kg receiving multi-day regimens of HEC or MEC, administer fosaprepitant for injection on Days 1, 2, and 3. Administer fosaprepitant for injection as an intravenous infusion through a central venous catheter on Day 1 and fosaprepitant capsules or fosaprepitant for oral suspension on Days 2 and 3, as shown in Table 4. Administer fosaprepitant for injection over 30 minutes (12 years to 17 years) or 60 minutes (6 months to less than 12 years), completing the infusionapproximately 30 minutes prior to chemotherapy. Table 4 3-Day Fosaprepitant for Injection Dosage Regimen for Prevention of Nausea and Vomiting Associated with Single or Multi-dayRegimensof HEC or MEC in Pediatric Patients 6 Months* to 17 Years Age of Pediatric Population Day 1 Day 2 Day 3 fosaprepitant for injection * 12 Years to 17 years 115 mg intravenously over 30 minutes 80 mg orally (fosaprepitant capsules)† 80 mg orally (fosaprepitant capsules)† 6 months to less than 12 years 3 mg/kg intravenously over 60 minutes (maximum dose 115 mg) 2 mg/kg orally (fosaprepitant for oral suspension) ‡ (maximum dose 80 mg) 2 mg/kg orally (fosaprepitant for oral suspension) ‡ (maximum dose 80 mg) Dexamethasone § 6 months to 17 Years If a corticosteroid, such as dexamethasone, is co-administered, administer 50% of the recommended corticosteroid dose on Days 1 through 4. 5-HT 3 antagonist 6 months to 17 Years See selected 5-HT 3 antagonist prescribing information for the recommended dosage. *Dosing in pediatric patients less than 6 kg is not recommended. † For patients 12 years to 17 years unable to swallow oral capsules, fosaprepitant for oral suspension can be used instead on Days 2 and 3 ‡ For patients less than 12 years of age who weigh at least 40 kg and who are able to swallow oral capsules, Fosaprepitant capsules can be used instead on Days 2 and 3 § Administer dexamethasone 30 minutes prior to chemotherapy treatment on Day 1. treatment on Day 1. Additional pediatric use information is approved for Merck Sharp & Dohme LLC's EMEND (fosaprepitant) for injection. However, due to Merck Sharp & Dohme LLC's marketing exclusivity rights, this drug product is not labeled with that 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 Determine the volume to be administered from this prepared infusion bag, based on the recommended dose [see Dosage and Administration ( 2.1 , 2.2 )] . Adults The entire volume of the prepared infusion bag (150 mL) should be administered. Pediatrics In patients 12 years and older, the volume to be administered is calculated as follows: • Volume to administer (mL) equals the recommended dose (mg) In patients 6 months to less than 12 years, the volume to be administered is calculated as follows: • Volume to administer (mL) = recommended dose (mg/kg) x weight (kg) o Note: Do not exceed the maximum dose [see Dosage and Administration ( 2.2 )] In pediatric patients, the entire volume in the infusion bag may not be required. Step 6 If necessary, for volumes less than 150 mL, the calculated volume can be transferred to an appropriate size bag or syringe prior to administration by infusion. Step 7 Before administration, inspect the bag for particulate matter and discoloration. Discard the bag if particulate and/or discoloration are observed. The recommended dose of fosaprepitant for injection is based on the patient’s age and weight. 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., Ca 2+ , Mg 2+ ), 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)]. Discard unused portion.

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 )]. • Known hypersensitivity to any component of this drug. ( 4 , 5.2 ) • Concurrent use with pimozide. ( 4 )

Not available.

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 NorthStar Rx LLC at 1-800-206-7821 or FDA at 1-800-FDA-1088 or ww.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 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* Fosaprepitant for injection, ondansetron, and dexamethasone † (N=504) Ondansetron and dexamethasone ‡ (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% * Reported in ≥2% of patients treated with the fosaprepitant regimen and at a greater incidence than standard therapy. † Fosaprepitant regimen ‡ Standard therapy Infusion-site reactions were reported in 2.2% of patients treated with the fosaprepitant 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 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 EMEND (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 Regimen In pediatric patients 12 to 17 years, the safety of the 3-day IV/oral/oral fosaprepitant 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 regimen was not directly evaluated. The safety of a single dose of fosaprepitant 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. 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 fosaprepitant capsules for complete safety information regarding studies performed with oral aprepitant. oral aprepitant. Additional pediatric use information is approved for Merck Sharp & Dohme LLC's EMEND (fosaprepitant) for injection. However, due to Merck Sharp & Dohme LLC's marketing exclusivity rights, this drug product is not labeled with that information. 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 and ifosfamide coadministration.