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Fosaprepitant Dimeglumine

FDA Drug Information • Also known as: Emend, Focinvez, Fosaprepitant, Fosaprepitant Dimeglumine

Brand Names
Emend, Focinvez, Fosaprepitant, Fosaprepitant Dimeglumine
Dosage Form
POWDER
Product Type
BULK INGREDIENT

Description

11 DESCRIPTION Fosaprepitant for Injection is a sterile, lyophilized formulation containing fosaprepitant dimeglumine, a prodrug of aprepitant, a substance P/neurokinin-1 (NK 1 ) receptor antagonist, an antiemetic agent, chemically described as 1-Deoxy-1-(methylamino)-D-glucitol[3-[[(2 R ,3 S )-2-[(1 R )-1-[3,5-bis(trifluoromethyl)phenyl]ethoxy]-3-(4-fluorophenyl)-4-morpholinyl]methyl]-2,5-dihydro-5-oxo-1 H -1,2,4-triazol-1-yl]phosphonate (2:1) (salt). Its empirical formula is C 23 H 22 F 7 N 4 O 6 P ∙ 2(C 7 H 17 NO 5 ) and its structural formula is: Fosaprepitant dimeglumine is a white to off-white amorphous powder with a molecular weight of 1004.83. It is freely soluble in water. Each vial of fosaprepitant for injection for administration as an intravenous infusion contains 150 mg of fosaprepitant (equivalent to 245.3 mg of fosaprepitant dimeglumine) and the following inactive ingredients: edetate disodium (5.4 mg), polysorbate 80 (75 mg), lactose anhydrous (375 mg), sodium hydroxide and/or hydrochloric acid (for pH adjustment). Chemical Structure

What Is Fosaprepitant Dimeglumine Used For?

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.

Dosage and Administration

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/aprepitant regimen of fosaprepitant for injection on Days 1, 2, and 3. Aprepitant capsules or aprepitant for oral suspension may be used as an alternative 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 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) ] . 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 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 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) ] . 12 mg orally 5-HT 3 antagonist See selected 5-HT 3 antagonist prescribing information for the recommended dosage 2.2 Prevention of Nausea and Vomiting Associated with HEC and MEC in Pediatric Patients The recommended pediatric...

Side Effects (Adverse Reactions)

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...

Drug Interactions

7 DRUG INTERACTIONS See Full Prescribing Information for a list of clinically significant drug interactions. ( 4 , 5.1 , 5.4 , 5.5 , 7.1 , 7.2 ) 7.1 Effect of Fosaprepitant/Aprepitant on the Pharmacokinetics of Other Drugs When administered intravenously, fosaprepitant, a prodrug of aprepitant, is converted to aprepitant within 30 minutes. Therefore, drug interactions following administration of fosaprepitant for injection are likely to occur with drugs that interact with oral aprepitant. Fosaprepitant, given as a single 150-mg dose, is a weak inhibitor of CYP3A4, and the weak inhibition of CYP3A4 continues for 2 days after single dose administration. Single dose fosaprepitant does not induce CYP3A4. Aprepitant is a substrate, an inhibitor, and an inducer of CYP3A4. Aprepitant is also an inducer of CYP2C9 [see Clinical Pharmacology (12.3) ] . Some substrates of CYP3A4 are contraindicated with fosaprepitant for injection [see Contraindications (4) ] . Dosage adjustment of some CYP3A4 and CYP2C9 substrates may be warranted, as shown in Table 7. Table 7 Effects of Fosaprepitant/Aprepitant on the Pharmacokinetics of Other Drugs CYP3A4 Substrates Pimozide Clinical Impact Increased pimozide exposure Intervention Fosaprepitant for Injection is contraindicated [see Contraindications (4) ]. Benzodiazepines Clinical Impact Increased exposure to midazolam or other benzodiazepines metabolized via CYP3A4 (alprazolam, triazolam) may increase the risk of adverse reactions [see Clinical Pharmacology (12.3) ]. Intervention Monitor for benzodiazepine-related adverse reactions. Dexamethasone Clinical Impact Increased dexamethasone exposure [see Clinical Pharmacology (12.3) ]. Intervention Reduce the dose of oral dexamethasone by approximately 50% [see Dosage and Administration (2.1) ]. Methylprednisolone Clinical Impact Increased methylprednisolone exposure [see Clinical Pharmacology (12.3) ]. Intervention Reduce the dose of oral methylprednisolone by approximately 50% on Days 1 and 2 for patients receiving HEC and on Day 1 for patients receiving MEC. Reduce the dose of intravenous methylprednisolone by 25% on Days 1 and 2 for patients receiving HEC and on Day 1 for patients receiving MEC. Chemotherapeutic agents that are metabolized by CYP3A4 Clinical Impact Increased exposure of the chemotherapeutic agent may increase the risk of adverse reactions [see Clinical Pharmacology (12.3) ]. Intervention Vinblastine, vincristine, or ifosfamide or other chemotherapeutic agents Monitor for chemotherapeutic-related adverse reactions. Etoposide, vinorelbine, paclitaxel, and docetaxel No dosage adjustment needed. Hormonal Contraceptives Clinical Impact Decreased hormonal exposure during administration of and for 28 days after administration of the last dose of fosaprepitant for injection [see Warnings and Precautions (5.5) , Use in Specific Populations (8.3) , and Clinical Pharmacology (12.3) ]. Intervention Effective alternative or back-up methods of contraception (such as...

Contraindications

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 )

Pregnancy and Breastfeeding

8.1 Pregnancy Risk Summary There are insufficient data on use of fosaprepitant for injection in pregnant women to inform a drug associated risk. In animal reproduction studies, no adverse developmental effects were observed in rats or rabbits exposed during the period of organogenesis to systemic drug levels (AUC) approximately equivalent to the exposure at the recommended human dose (RHD) of 150 mg [see Data ] . The estimated background risk of major birth defects and miscarriage for the indicated populations is unknown. In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2 to 4% and 15 to 20%, respectively. Data Animal Data In embryofetal development studies in rats and rabbits, aprepitant was administered during the period of organogenesis at oral doses up to 1000 mg/kg twice daily (rats) and up to the maximum tolerated dose of 25 mg/kg/day (rabbits). No embryofetal lethality or malformations were observed at any dose level in either species. The exposures (AUC) in pregnant rats at 1000 mg/kg twice daily and in pregnant rabbits at 25 mg/kg/day were approximately equivalent to the exposure at the RHD of 150 mg. Aprepitant crosses the placenta in rats and rabbits.

Overdosage

10 OVERDOSAGE There is no specific information on the treatment of overdosage with fosaprepitant or aprepitant. In the event of overdose, fosaprepitant for injection should be discontinued and general supportive treatment and monitoring should be provided. Because of the antiemetic activity of fosaprepitant for injection, drug-induced emesis may not be effective in cases of fosaprepitant for injection overdosage. Aprepitant is not removed by hemodialysis.

How Supplied

16 HOW SUPPLIED/STORAGE AND HANDLING Single-dose glass vial containing 150 mg of fosaprepitant as a white to off-white lyophilized powder for reconstitution. Supplied as follows: NDC 67184-0540-1 1 vial per carton. Storage Fosaprepitant for Injection vials must be refrigerated, store at 2°C to 8°C (36°F to 46°F). The reconstituted final drug solution is stable for 24 hours at ambient room temperature [at or below 25°C (77°F)]. Discard unused portion.

About This Information

This drug information is sourced from FDA-approved labeling via the openFDA database. It is intended for educational and reference purposes only. This is not medical advice. Always consult your healthcare provider before making decisions about medication. Drug information may be updated by the FDA; check with your pharmacist for the most current information.

What are side effects?

Side effects are unwanted reactions that can occur when taking a medication. They range from mild (headache, nausea) to severe (allergic reactions, organ damage). Not everyone experiences side effects, and severity varies. Report any concerning side effects to your doctor.

What are drug interactions?

Drug interactions occur when a medication is affected by another drug, food, or supplement. Interactions can make medications less effective or cause dangerous side effects. Always tell your doctor about all medications and supplements you take.