Fosaprepitant

Fosaprepitant dimeglumine · Injection, Powder, Lyophilized, For Solution · Intravenous

Prescription (Rx) Substance P/Neurokinin-1 Receptor Antagonist 2 recalls

Uses

Fosaprepitant for Injection, in combination with other antiemetic agents, is indicated in adults 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, 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

Dosage ( 2.1 ) The recommended dosage in adults is 150 mg on Day 1 as an intravenous infusion over 20 to 30 minutes completing the infusion approximately 30 minutes prior to chemotherapy. See Full Prescribing Information for dosages of concomitant antiemetic(s) of Fosaprepitant for Injection. Preparation ( 2.2 ) Reconstitute with 5 mL of 0.9% sodium chloride. Add to infusion bag containing 145 mL 0.9% sodium chloride for a final concentration of 1 mg/mL. 2.1 Recommended Dosage 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 Dosage 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 Dosage 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 Preparation Instructions 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 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 physical and chemical compatibility have not been established. Fosaprepitant for Injection is incompatible with any solutions containing divalent cations (e.g., calcium, magnesium), 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)].

Dosage forms and strengths

Fosaprepitant for Injection: 150 mg fosaprepitant, white to off-white lyophilized powder in single-dose glass vial for reconstitution Fosaprepitant for Injection: 150 mg fosaprepitant, lyophilized powder in single-dose vial for reconstitution. ( 3 )

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 )

Warnings and precautions

5 WARNINGS AND PRECAUTIONS CYP3A4 Interactions: Fosaprepitant is a weak inhibitor of CYP3A4, and aprepitant, the active moiety, is a substrate, inhibitor, and inducer of CYP3A4; see Full Prescribing Information for recommendations regarding contraindications, risk of adverse reactions, and dosage adjustment of Fosaprepitant for Injection and concomitant drugs. ( 4 , 5.1 , 7.1 , 7.2 ) Hypersensitivity Reactions (including anaphylaxis and anaphylactic shock): May occur during or soon after infusion. If symptoms occur, discontinue the drug. Do not reinitiate Fosaprepitant for Injection if symptoms occur with previous use. ( 4 , 5.2 ) Infusion Site Reactions (including thrombophlebitis, necrosis, and vasculitis): Majority of reactions reported in patients receiving vesicant chemotherapy. Avoid infusion into small veins. Discontinue infusion and administer treatment if a severe reaction develops. ( 5.3 ) Warfarin (a CYP2C9 substrate): Risk of decreased INR of prothrombin time; monitor INR in 2-week period, particularly at 7 to 10 days, following initiation of Fosaprepitant for Injection. ( 5.4 , 7.1 ) Hormonal Contraceptives: Efficacy of contraceptives may be reduced during and for 28 days following administration of Fosaprepitant for Injection. Use effective alternative or back-up methods of contraception. ( 5.5 , 7.1 , 8.3 ) 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 for Injection with other drugs that are CYP3A4 substrates, may result in increased plasma concentration of the concomitant drug. Use of pimozide with Fosaprepitant for Injection is contraindicated due to the risk of significantly increased plasma concentrations of pimozide, potentially resulting in prolongation of the QT interval, a known adverse reaction of pimozide [see Contraindications ( 4 )] . Use of Fosaprepitant for Injection with strong or moderate CYP3A4 inhibitors (e.g., ketoconazole, diltiazem) may increase plasma concentrations of aprepitant and result in an increased risk of adverse reactions related to Fosaprepitant for Injection. Use of Fosaprepitant for Injection with strong CYP3A4 inducers (e.g., rifampin) may result in a reduction in aprepitant plasma concentrations and decreased efficacy of Fosaprepitant for Injection. See Table 7 and Table 8 for a listing of potentially significant drug interactions [see Drug Interactions ( 7.1 , 7.2 )] . 5.2 Hypersensitivity Reactions Serious hypersensitivity reactions, including anaphylaxis and anaphylactic shock, during or soon after infusion of fosaprepitant have occurred. Symptoms including flushing, erythema, dyspnea, hypotension and syncope have been reported [see Adverse Reactions ( 6.2 )] . Monitor patients during and after infusion. If hypersensitivity reactions occur, discontinue the infusion and administer appropriate medical therapy. Do not reinitiate Fosaprepitant for Injection in patients who experience these symptoms with previous use [see Contraindications ( 4 )] . 5.3 Infusion Site Reactions Infusion site reactions (ISRs) have been reported with the use of Fosaprepitant for Injection [see Adverse Reactions ( 6.1 )] . The majority of severe ISRs, including thrombophlebitis and vasculitis, were reported with concomitant vesicant (anthracycline-based) chemotherapy administration, particularly when associated with extravasation. Necrosis was also reported in some patients with concomitant vesicant chemotherapy. Most ISRs occurred with the first, second or third exposure to single doses of Fosaprepitant for Injection and in some cases, reactions persisted for two weeks or longer. Treatment of severe ISRs consisted of medical, and in some cases surgical, intervention. Avoid infusion of Fosaprepitant for Injection into small veins or through a butterfly catheter. If a severe ISR develops during infusion, discontinue the infusion and administer appropriate medical treatment. 5.4 Decrease in INR with Concomitant Warfarin Coadministration of Fosaprepitant for Injection with warfarin, a CYP2C9 substrate, may result in a clinically significant decrease in the International Normalized Ratio (INR) of prothrombin time [see Clinical Pharmacology ( 12.3 )] . Monitor the INR in patients on chronic warfarin therapy in the 2-week period, particularly at 7 to 10 days, following initiation of Fosaprepitant for Injection with each chemotherapy cycle [see Drug Interactions ( 7.1 )] . 5.5 Risk of Reduced Efficacy of Hormonal Contraceptives Upon coadministration with Fosaprepitant for Injection, the efficacy of hormonal contraceptives may be reduced during administration of and for 28 days following the last dose of Fosaprepitant for Injection [see Clinical Pharmacology ( 12.3 )] . Advise patients to use effective alternative or back-up methods of contraception during treatment with Fosaprepitant for Injection and for 1 month following administration of Fosaprepitant for Injection [see Drug Interactions ( 7.1 ), Use in Specific Populations ( 8.3 )] .

Side effects

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 (≥2%) are: fatigue, diarrhea, neutropenia, asthenia, anemia, peripheral neuropathy, leukopenia, dyspepsia, urinary tract infection, pain in extremity. ( 6.1 ) To report SUSPECTED ADVERSE REACTIONS, contact Teva 1-888-838-2872 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 safety of Fosaprepitant for Injection has been established from adequate and well-controlled studies of another intravenous fosaprepitant product in chemotherapy induced nausea and vomiting [see Clinical Studies ( 14 )] . Adverse reactions reported in these studies are described below. Adverse Reactions 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 adult patients receiving a single intravenous dose of fosaprepitant 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* Intravenous fosaprepitant, 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 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 adult patients receiving a single intravenous dose of fosaprepitant 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. 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 another intravenous formulation 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.

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 ), Clinical Pharmacology ( 12.3 )] . Intervention Effective alternative or back-up methods of contraception (such as condoms or spermicides) should be used during treatment with Fosaprepitant for Injection and for 1 month following administration of Fosaprepitant for Injection. Examples birth control pills, skin patches, implants, and certain IUDs CYP2C9 Substrates Warfarin Clinical Impact Decreased warfarin exposure and decreased prothrombin time (INR) [see Warnings and Precautions (5.4), Clinical Pharmacology ( 12.3 )] . Intervention In patients on chronic warfarin therapy, monitor the prothrombin time (INR) in the 2-week period, particularly at 7 to 10 days, following administration of Fosaprepitant for Injection with each chemotherapy cycle. Other 5-HT 3 Antagonists Clinical Impact No change in the exposure of the 5-HT 3 antagonist [see Clinical Pharmacology ( 12.3 )] . Intervention No dosage adjustment needed Examples ondansetron, granisetron, dolasetron 7.2 Effect of Other Drugs on the Pharmacokinetics of Fosaprepitant/Aprepitant Aprepitant is a CYP3A4 substrate [see Clinical Pharmacology ( 12.3 )] . Coadministration of Fosaprepitant for Injection with drugs that are inhibitors or inducers of CYP3A4 may result in increased or decreased plasma concentrations of aprepitant, respectively, as shown in Table 8. Table 8 Effects of Other Drugs on Pharmacokinetics of Fosaprepitant/Aprepitant Moderate to Strong CYP3A4 Inhibitors Clinical Impact Significantly increased exposure of aprepitant may increase the risk of adverse reactions associated with Fosaprepitant for Injection [see Adverse Reactions ( 6.1 ), Clinical Pharmacology ( 12.3 )] . Intervention Avoid concomitant use of Fosaprepitant for Injection Examples Moderate inhibitor: diltiazem Strong inhibitors: ketoconazole, itraconazole, nefazodone, troleandomycin, clarithromycin, ritonavir, nelfinavir Strong CYP3A4 Inducers Clinical Impact Substantially decreased exposure of aprepitant in patients chronically taking a strong CYP3A4 inducer may decrease the efficacy of Fosaprepitant for Injection [see Clinical Pharmacology ( 12.3 )] . Intervention Avoid concomitant use of Fosaprepitant for Injection Examples rifampin, carbamazepine, phenytoin

Use in specific populations

8.1 Pregnancy Risk Summary There are no available data on use of fosaprepitant in pregnant women to inform a drug-associated risk of adverse developmental outcomes. In animal reproduction studies, no adverse developmental effects were observed in rats or rabbits exposed during the period of organogenesis to systemic exposures (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. All pregnancies have a background risk of birth defect, loss, or other adverse outcomes. 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 1,000 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 1,000 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. 8.2 Lactation Risk Summary There are no data on the presence of aprepitant in human milk, the effects on the breastfed infant, or the effects on milk production. Aprepitant is present in rat milk. The developmental and health benefits of breastfeeding should be considered along with the mother’s clinical need for Fosaprepitant for Injection and any potential adverse effects on the breastfed infant from Fosaprepitant for Injection or from the underlying maternal condition. 8.3 Females and Males of Reproductive Potential Contraception Upon administration of Fosaprepitant for Injection, the efficacy of hormonal contraceptives may be reduced. Advise females of reproductive potential using hormonal contraceptives to use an effective alternative or back-up non-hormonal contraceptive (such as condoms or spermicides) during treatment with Fosaprepitant for Injection and for 1 month following the last dose [see Drug Interactions ( 7.1 ), Clinical Pharmacology ( 12.3 )] . 8.4 Pediatric Use This Fosaprepitant for Injection product is not approved for use in pediatric patients. This Fosaprepitant for Injection product contains 18.8 mg of edetate disodium (EDTA) per vial [see Description ( 11 )] . Edetate disodium is a chelator of metal ions, including calcium. Other fosaprepitant for injection products may contain less edetate disodium. 8.5 Geriatric Use Of the 1649 adult cancer patients treated with intravenous fosaprepitant in HEC and MEC clinical studies, 27% were aged 65 and over, while 5% were aged 75 and over. Other reported clinical experience has not identified differences in responses between elderly and younger patients. In general, use caution when dosing elderly patients as they have a greater frequency of decreased hepatic, renal or cardiac function and concomitant disease or other drug therapy [see Clinical Pharmacology ( 12.3 )] . 8.6 Patients with Hepatic Impairment The pharmacokinetics of aprepitant in patients with mild and moderate hepatic impairment were similar to those of healthy subjects with normal hepatic function. No dosage adjustment is necessary for patients with mild to moderate hepatic impairment (Child-Pugh score 5 to 9). There are no clinical or pharmacokinetic data in patients with severe hepatic impairment (Child-Pugh score greater than 9). Therefore, additional monitoring for adverse reactions in these patients may be warranted when Fosaprepitant for Injection is administered [see Clinical Pharmacology ( 12.3 )] .

Pregnancy

Pediatric use

8.4 Pediatric Use This Fosaprepitant for Injection product is not approved for use in pediatric patients. This Fosaprepitant for Injection product contains 18.8 mg of edetate disodium (EDTA) per vial [see Description ( 11 )] . Edetate disodium is a chelator of metal ions, including calcium. Other fosaprepitant for injection products may contain less edetate disodium.

Geriatric use

8.5 Geriatric Use Of the 1649 adult cancer patients treated with intravenous fosaprepitant in HEC and MEC clinical studies, 27% were aged 65 and over, while 5% were aged 75 and over. Other reported clinical experience has not identified differences in responses between elderly and younger patients. In general, use caution when dosing elderly patients as they have a greater frequency of decreased hepatic, renal or cardiac function and concomitant disease or other drug therapy [see Clinical Pharmacology ( 12.3 )] .

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.

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 (18.8 mg), meglumine (75 mg), povidone k12 (600 mg), and water for injection. Hydrochloric acid and/or meglumine may have been added for pH adjustment. formula image

Mechanism of action

12.1 Mechanism of Action Fosaprepitant is a prodrug of aprepitant and accordingly, its antiemetic effects are attributable to aprepitant. Aprepitant is a selective high-affinity antagonist of human substance P/neurokinin 1 (NK 1 ) receptors. Aprepitant has little or no affinity for serotonin (5-HT 3 ), dopamine, and corticosteroid receptors, the targets of existing therapies for chemotherapy-induced nausea and vomiting (CINV). Aprepitant has been shown in animal models to inhibit emesis induced by cytotoxic chemotherapeutic agents, such as cisplatin, via central actions. Animal and human Positron Emission Tomography (PET) studies with aprepitant have shown that it crosses the blood brain barrier and occupies brain NK 1 receptors. Animal and human studies have shown that aprepitant augments the antiemetic activity of the 5-HT 3 -receptor antagonist ondansetron and the corticosteroid dexamethasone and inhibits both the acute and delayed phases of cisplatin-induced emesis.

How supplied

Fosaprepitant for Injection is available as follows: 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 .

Patient 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 Manufactured For: Teva Pharmaceuticals Parsippany, NJ 07054

Label text from the FDA structured product label by Actavis Pharma, Inc. (revised Jun 30, 2022). Long sections are shortened; the complete label is on DailyMed.

Active ingredients

Fosaprepitant Dimeglumine in 19 products

Fosaprepitant NDC products (19)

NDC	Strength & form	Labeler	Type
83634-776	Fosaprepitant Dimeglumine 150 mg/5mL Injection, Powder, Lyophilized, For Solution	Avenacy, LLC	ANDA
0338-0008	Fosaprepitant Dimeglumine 150 mg/5mL Injection, Powder, Lyophilized, For Solution	Baxter Healthcare Corporation	ANDA
71839-104	Fosaprepitant Dimeglumine 150 mg/5mL Injection, Powder, Lyophilized, For Solution	BE Pharmaceuticals Inc.	ANDA
68001-421	Fosaprepitant Dimeglumine 150 mg/5mL Injection, Powder, Lyophilized, For Solution	BluePoint Laboratories	ANDA
68001-675	Fosaprepitant Dimeglumine 150 mg/5mL Injection, Powder, Lyophilized, For Solution	BluePoint Laboratories	ANDA
68001-523	Fosaprepitant Dimeglumine 150 mg/5mL Injection, Powder, Lyophilized, For Solution	BluePoint Laboratories	ANDA
72162-2636	Fosaprepitant Dimeglumine 150 mg/5mL Injection, Powder, Lyophilized, For Solution	Bryant Ranch Prepack	ANDA
31722-165	Fosaprepitant Dimeglumine 150 mg/5mL Injection, Powder, Lyophilized, For Solution	Camber Pharmaceuticals, Inc.	ANDA
71731-5111	Fosaprepitant Dimeglumine 150 mg/5mL Injection, Powder, Lyophilized, For Solution	Chia Tai Tianqing Pharmaceutical Group Co., Ltd.	ANDA
43598-948	Fosaprepitant Dimeglumine 150 mg/5mL Injection, Powder, Lyophilized, For Solution	Dr. Reddy's Laboratories Inc.,	ANDA
43598-859	Fosaprepitant Dimeglumine 150 mg/5mL Injection, Powder, Lyophilized, For Solution	Dr. Reddy's Laboratories Inc.,	ANDA
43598-671	Fosaprepitant Dimeglumine 150 mg/1 Injection, Powder, Lyophilized, For Solution	Dr. Reddy's Laboratories Inc.,	ANDA
63323-972	Fosaprepitant Dimeglumine 150 mg/5mL Injection, Powder, Lyophilized, For Solution	Fresenius Kabi USA, LLC	ANDA
67457-889	Fosaprepitant Dimeglumine 150 mg/5mL Injection, Powder, Lyophilized, For Solution	Mylan Institutional LLC	ANDA
72603-450	Fosaprepitant Dimeglumine 150 mg/5mL Injection, Powder, Lyophilized, For Solution	Northstar Rx LLC	ANDA
16714-248	Fosaprepitant Dimeglumine 150 mg/5mL Injection, Powder, Lyophilized, For Solution	NorthStar RxLLC	ANDA
72205-054	Fosaprepitant Dimeglumine 150 mg/5mL Injection, Powder, Lyophilized, For Solution	Novadoz Pharmaceuticals LLC	ANDA
72205-083	Fosaprepitant Dimeglumine 150 mg/5mL Injection, Powder, Lyophilized, For Solution	Novadoz Pharmaceuticals LLC	ANDA
0591-4385	Fosaprepitant Dimeglumine 150 mg/1 Injection, Powder, Lyophilized, For Solution	Actavis Pharma, Inc.	NDA

Fosaprepitant recalls

D-0262-2024 Jan 31, 2024 · Class II · Terminated
Lack of Sterility Assurance: Aseptic process simulation failure.
D-1391-2020 Jul 22, 2020 · Class III · Terminated
Labeling Error: Label Error on Declared Strength: Carton label and product insert incorrectly states the quantity of the excipient edetate disodium (EDTA) as 5.4 mg / vial, rather than the actual amount of 18.8 mg /…

Frequently asked questions

What is Fosaprepitant used for?

What are the side effects of Fosaprepitant?

Who makes Fosaprepitant?

Fosaprepitant is listed by 14 labelers in the FDA NDC directory, including Avenacy, LLC, Baxter Healthcare Corporation, BE Pharmaceuticals Inc., BluePoint Laboratories.

Has Fosaprepitant been recalled?

The FDA enforcement database lists 2 recalls for Fosaprepitant, most recently D-0262-2024 (class ii): Lack of Sterility Assurance: Aseptic process simulation failure.