Cinvanti

aprepitant · Injection, Emulsion · Intravenous

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

Uses

1 INDICATIONS AND USAGE CINVANTI, 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 as a single-dose regimen. delayed nausea and vomiting associated with initial and repeat courses of moderately emetogenic cancer chemotherapy (MEC) as a single-dose regimen. nausea and vomiting associated with initial and repeat courses of MEC as a 3-day regimen. CINVANTI is a substance P/neurokinin-1 (NK 1 ) receptor antagonist, indicated in adults, in combination with other antiemetic agents, 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 as a single-dose regimen. ( 1 ) delayed nausea and vomiting associated with initial and repeat courses of moderately emetogenic cancer chemotherapy (MEC) as a single-dose regimen. ( 1 ) nausea and vomiting associated with initial and repeat courses of MEC as a 3-day regimen. ( 1 ) Limitations of Use : CINVANTI has not been studied for treatment of established nausea and vomiting. ( 1 ) Limitations of Use CINVANTI has not been studied for the treatment of established nausea and vomiting.

Dosage and administration

Recommended Dosage ( 2.1 ): Administer CINVANTI intravenously as an injection over 2 minutes or an infusion over 30 minutes; complete the injection or infusion approximately 30 minutes prior to chemotherapy. HEC and MEC (Single-Dose Regimen) : The recommended dosage in adults is 130 mg on Day 1. MEC (3-Day Regimen) : The recommended dosage in adults is 100 mg on Day 1. Aprepitant capsules (80 mg) are given orally on Days 2 and 3. CINVANTI is part of a regimen that includes a corticosteroid and a 5-HT 3 antagonist. Preparation : See the full prescribing information for instructions. ( 2.2 ) 2.1 Prevention of Nausea and Vomiting Associated with HEC and MEC The recommended dosages in adults of CINVANTI, dexamethasone, and a 5-HT 3 antagonist for the prevention of nausea and vomiting associated with administration of HEC or MEC are shown in Table 1, Table 2 and Table 3 respectively. Administer CINVANTI intravenously either by injection over a two (2) minute period or by infusion over a thirty (30) minute period on Day 1, completing the injection or infusion approximately 30 minutes prior to chemotherapy. Table 1. Recommended Dosage of CINVANTI for the Prevention of Nausea and Vomiting Associated with HEC (Single-Dose Regimen) Agent Day 1 Day 2 Day 3 Day 4 CINVANTI 130 mg intravenously 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 aprepitant [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 recommended dosage None None None Table 2. Recommended Dosage of CINVANTI for the Prevention of Nausea and Vomiting Associated with MEC (Single-Dose Regimen) Agent Day 1 CINVANTI 130 mg intravenously 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 aprepitant [see Clinical Pharmacology (12.3) ] . 12 mg orally 5-HT 3 antagonist See selected 5-HT 3 antagonist prescribing information for recommended dosage Table 3. Recommended Dosage of CINVANTI for the Prevention of Nausea and Vomiting Associated with MEC (3-Day Regimen with Oral Aprepitant on Days 2 and 3) Agent Day 1 Day 2 Day 3 CINVANTI 100 mg intravenously None None Oral Aprepitant None 80 mg orally 80 mg orally 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 aprepitant [see Clinical Pharmacology (12.3) ] . 12 mg orally None None 5-HT 3 antagonist See selected 5-HT 3 antagonist prescribing information for recommended dosage None None 2.2 Preparation of CINVANTI for Administration Intravenous Injection over a period of 2 minutes For intravenous injection over a period of 2 minutes, administer 130 mg of CINVANTI as part of a HEC or MEC regimen or 100 mg as part of a MEC regimen as a single dose on Day 1. Aseptically withdraw 18 mL for the 130 mg dose or 14 mL for the 100 mg dose from the vial. Do not dilute. The infusion line should be flushed with normal saline before and after administration of CINVANTI. Intravenous Infusion over a period of 30 minutes Table 4 includes preparation instructions for CINVANTI for HEC or MEC as a 130 mg single-dose regimen, and for MEC as a 100 mg single-dose followed by 2 days of oral aprepitant as a 3-day regimen. Differences in preparation for each dose are displayed as bolded text. Table 4. Preparation Instructions for CINVANTI Intravenous Infusion Note: The differences in preparation for each recommended dosage of CINVANTI are displayed in bolded text (see Table 1 for HEC Regimen and Table 2 for MEC Regimen). Step 1 Aseptically withdraw 18 mL for the 130 mg dose or 14 mL for the 100 mg dose from the vial and transfer it into an infusion bag Use only Non-DEHP tubing, non-PVC infusion bags filled with 100 mL of 0.9% Sodium Chloride Injection, USP or 5% Dextrose for Injection, USP. Step 2 Gently invert the bag 4 to 5 times. Avoid shaking. Step 3 Before administration, inspect the bag for particulate matter and discoloration. Discard the bag if particulate and/or discoloration are observed. Caution : Do not mix CINVANTI with solutions for which physical and chemical compatibility have not been established. In-Use Storage Conditions for CINVANTI in Acceptable Intravenous Diluents Diluted CINVANTI solution is stable at ambient room temperature for up to 6 hours in 0.9% Sodium Chloride Injection, USP or 12 hours in 5% Dextrose Injection, USP or up to 72 hours if stored under refrigeration in 0.9% Sodium Chloride Injection, USP or in 5% Dextrose Injection, USP. 2.3 Compatibilities CINVANTI is compatible with 0.9% Sodium Chloride Injection, USP or 5% Dextrose Injection, USP. 2.4 Incompatibilities CINVANTI is incompatible with any solutions containing divalent cations (e.g. calcium, magnesium), including Lactated Ringer's Solution and Hartmann's Solution.

Dosage forms and strengths

Injectable emulsion: 130 mg/18 mL (7.2 mg/mL) aprepitant as an opaque, off-white to amber emulsion, in single-dose vial Injectable emulsion: 130 mg/18 mL (7.2 mg/mL) aprepitant in single-dose vial ( 3 )

Contraindications

4 CONTRAINDICATIONS CINVANTI is contraindicated in patients: who are hypersensitive to any component of the product [see Description (11) ] . Hypersensitivity reactions including anaphylaxis have been reported [see Warnings and Precautions (5.2) , Adverse Reactions (6.2) ] . taking pimozide. Inhibition of CYP3A4 by aprepitant could result in elevated plasma concentrations of pimozide, 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 : Aprepitant is a substrate, weak-to-moderate (dose-dependent) inhibitor and an inducer of CYP3A4; see Full Prescribing Information for recommendations regarding contraindications, risk of adverse reactions, and dosage adjustment of CINVANTI and concomitant drugs. ( 4 , 5.1 , 7.1 , 7.2 ) Hypersensitivity Reactions (including anaphylaxis ): May occur during or soon after administration. If symptoms occur, discontinue CINVANTI and do not reinitiate it. ( 4 , 5.2 ) 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 CINVANTI. ( 5.3 , 7.1 ) Hormonal Contraceptives : Efficacy of contraceptives may be reduced during and for 28 days following administration of aprepitant. Use effective alternative or back-up methods of non-hormonal contraception. ( 5.4 , 7.1 , 8.3 ) 5.1 Clinically Significant CYP3A4 Drug Interactions Aprepitant is a substrate, weak-to-moderate (dose-dependent) inhibitor, and an inducer of CYP3A4. Use of CINVANTI with other drugs that are CYP3A4 substrates may result in increased plasma concentration of the concomitant drug. Use of pimozide with CINVANTI 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 CINVANTI 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 CINVANTI. Use of CINVANTI with strong CYP3A4 inducers (e.g., rifampin) may result in a reduction in aprepitant plasma concentrations and decreased efficacy of CINVANTI. See Table 8 and Table 9 for a listing of potentially significant drug interactions [see Drug Interactions (7.1 , 7.2) ]. 5.2 Hypersensitivity Reactions Serious hypersensitivity reactions, including anaphylaxis during or soon after administration of CINVANTI have occurred. Symptoms including dyspnea, eye swelling, flushing, pruritus and wheezing have been reported [see Adverse Reactions (6.2) ] . Monitor patients during and after administration. If hypersensitivity reactions occur, discontinue CINVANTI and administer appropriate medical therapy. Do not reinitiate CINVANTI in patients who experience these symptoms with previous use. 5.3 Decrease in INR with Concomitant Warfarin Coadministration of CINVANTI 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 CINVANTI with each chemotherapy cycle [see Drug Interactions (7.1) ] . 5.4 Risk of Reduced Efficacy of Hormonal Contraceptives Upon coadministration with CINVANTI, the efficacy of hormonal contraceptives may be reduced during administration of and for 28 days following the last dose of CINVANTI [see Clinical Pharmacology (12.3) ] . Advise patients to use effective alternative or back-up methods of non-hormonal contraception during treatment with CINVANTI and for 1 month following administration of CINVANTI or oral aprepitant, whichever is administered last [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) ] Most common adverse reactions are: Single-dose fosaprepitant with MEC (≥2%): fatigue, diarrhea, neutropenia, asthenia, anemia, peripheral neuropathy, leukopenia, dyspepsia, urinary tract infection, pain in extremity. ( 6.1 ) 3-day oral aprepitant with MEC (≥1% and greater than standard therapy): fatigue and eructation. ( 6.1 ) Single-dose fosaprepitant with HEC: generally similar to 3-day oral aprepitant. In addition, infusion site reactions (3%) occurred. ( 6.1 ) Single-dose CINVANTI (≥2%): headache and fatigue. ( 6.1 ) To report SUSPECTED ADVERSE REACTIONS, contact Heron Therapeutics, Inc. at 1-844-437-6611 and www.CINVANTI.com 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 CINVANTI was evaluated as a single-dose in healthy subjects and established from adequate and well-controlled studies of intravenous fosaprepitant and/or oral aprepitant [see Clinical Studies (14) ] . Adverse reactions observed in these adequate and well-controlled studies are described below. Safety of CINVANTI A total of 200 healthy subjects received a single 130 mg dose of CINVANTI as a 30-minute infusion. Adverse reactions reported in at least 2% of subjects were headache (3%) and fatigue (2%). The safety profile of CINVANTI in 50 healthy subjects who received a single 2-minute injection was similar to that seen with a 30-minute infusion. Single-Dose Intravenous Fosaprepitant -- HEC In an active-controlled clinical study in patients receiving HEC, safety was evaluated for 1143 patients receiving a single intravenous dose of fosaprepitant, a prodrug of aprepitant, compared to 1169 patients receiving a 3-day regimen of oral aprepitant [see Clinical Studies (14.1) ] . When administered intravenously, fosaprepitant is converted to aprepitant within 30 minutes. The safety profile was generally similar to that seen in prior HEC studies with a 3-day regimen of oral aprepitant. However, infusion-site reactions occurred at a higher incidence in patients in the intravenous fosaprepitant group (3%) compared to those in the oral aprepitant group (0.5%). The reported infusion-site reactions included: infusion-site erythema, infusion-site pruritus, infusion-site pain, infusion-site induration and infusion-site thrombophlebitis. Adverse reactions associated with oral aprepitant may also be expected to occur with CINVANTI. See the full prescribing information for oral aprepitant for complete safety information. Single-Dose Intravenous Fosaprepitant -- MEC In an active-controlled clinical trial in patients receiving MEC, safety was evaluated in 504 patients receiving a single dose of intravenous fosaprepitant in combination with ondansetron and dexamethasone (intravenous fosaprepitant regimen) compared to 497 patients receiving ondansetron and dexamethasone alone (standard therapy). The most common adverse reactions are listed in Table 5. Table 5. Most Common Adverse Reactions in Patients Receiving MEC Reported in ≥2% of patients treated with the intravenous fosaprepitant regimen and at a greater incidence than standard therapy. Intravenous fosaprepitant, ondansetron, and dexamethasone Intravenous fosaprepitant 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 intravenous 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 8 infusion-site thrombophlebitis (0.6%, 0.0%), reported in the intravenous fosaprepitant regimen compared to standard therapy, respectively. 3-Day Oral Aprepitant -- MEC In 2 active-controlled clinical trials in patients receiving MEC, 868 patients were treated with a 3-day oral aprepitant regimen during Cycle 1 of chemotherapy and 686 of these patients continued into extensions for up to 4 cycles of chemotherapy. In both studies, oral aprepitant was given in combination with ondansetron and dexamethasone (oral aprepitant regimen) and was compared to ondansetron and dexamethasone alone (standard therapy) [see Clinical Studies (14.2) ] . In the combined analysis of Cycle 1 data for these 2 studies, adverse reactions were reported in approximately 14% of patients treated with the aprepitant regimen compared with approximately 15% of patients treated with standard therapy. Treatment was discontinued due to adverse reactions in 0.7% of patients treated with the aprepitant regimen compared with 0.2% of patients treated with standard therapy. The most common adverse reactions reported in patients treated with the oral aprepitant regimen with an incidence of at least 1% and greater than standard therapy are listed in Table 6. Table 6. Adverse Reactions (≥ 1%) in Patients Receiving MEC with a Greater Incidence in the Oral 3-Day Aprepitant Regimen Relative to Standard Therapy Oral Aprepitant Regimen (N = 868) Standard Therapy (N = 846) Fatigue 1.4 0.9 Eructation 1.0 0.1 A listing of adverse reactions reported in less than 1% in patients treated with the oral aprepitant regimen that occurred at an incidence greater than in patients treated with standard therapy are presented in the Less Common Adverse Reactions subsection below.

Drug interactions

See full prescribing information for a list of clinically significant drug interactions. ( 4 , 5.1 , 5.3 , 5.4 , 7.1 , 7.2 ) 7.1 Effect of Aprepitant on the Pharmacokinetics of Other Drugs Aprepitant is a substrate, weak-to-moderate (dose-dependent) 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 CINVANTI [see Contraindications (4) ] . Dosage adjustment of some CYP3A4 and CYP2C9 substrates may be warranted, as shown in Table 8. Table 8. Effects of Aprepitant on the Pharmacokinetics of Other Drugs CYP3A4 Substrates Pimozide Clinical Impact Increased pimozide exposure. Intervention CINVANTI 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 aprepitant [see Warnings and Precautions (5.4) , Use in Specific Populations (8.3) , and Clinical Pharmacology (12.3) ] . Intervention Effective alternative or back-up methods of contraception (such as condoms or spermicides) should be used during treatment with CINVANTI and for 1 month following administration of CINVANTI or oral aprepitant, whichever is administered last. 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 (5.3) , 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 CINVANTI with each chemotherapy cycle. Other Antiemetic Agents 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 Aprepitant Aprepitant is a CYP3A4 substrate [see Clinical Pharmacology (12.3) ] . Co-administration of CINVANTI with drugs that are inhibitors or inducers of CYP3A4 may result in increased or decreased plasma concentrations of aprepitant, respectively, as shown in Table 9. Table 9. Effects of Other Drugs on Pharmacokinetics of Aprepitant Moderate to Strong CYP3A4 Inhibitors Clinical Impact Significantly increased exposure of aprepitant may increase the risk of adverse reactions associated with CINVANTI [see Adverse Reactions (6.1) and Clinical Pharmacology (12.3) ]. Intervention Avoid concomitant use of CINVANTI. 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 CINVANTI [see Clinical Pharmacology (12.3) ]. Intervention Avoid concomitant use of CINVANTI. Examples rifampin, carbamazepine, phenytoin

Use in specific populations

Pregnancy : May cause fetal harm. ( 8.1 ) 8.1 Pregnancy Risk Summary There are no available data on CINVANTI use in pregnant women to inform a drug-associated risk of adverse developmental outcomes. Avoid use of CINVANTI in pregnant women due to the alcohol content (see Clinical Considerations ). In animal reproduction studies, no adverse developmental effects were observed in rats or rabbits exposed during the period of organogenesis to systemic drug concentrations (area under the plasma-concentration time curve [AUC]) of aprepitant approximately equivalent to the exposure at the recommended human dose (RHD) of CINVANTI 130 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. Clinical Considerations Fetal/Neonatal adverse reactions CINVANTI contains alcohol. Published studies have demonstrated that alcohol is associated with fetal harm including central nervous system abnormalities, behavioral disorders, and impaired intellectual development. There is no safe level of alcohol exposure in pregnancy; therefore, avoid use of CINVANTI in pregnant women. 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 125 mg/kg/day were approximately equivalent to the exposure at the RHD of CINVANTI 130 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 CINVANTI and any potential adverse effects on the breastfed infant from CINVANTI or from the underlying maternal condition. 8.3 Females and Males of Reproductive Potential Contraception Upon administration of CINVANTI, 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 CINVANTI and for 1 month following the last dose of CINVANTI or oral aprepitant, whichever is administered last [see Warnings and Precautions (5.4) , Drug Interactions (7.1) , Clinical Pharmacology (12.3) ] . 8.4 Pediatric Use The safety and effectiveness of CINVANTI have not been established in pediatric patients. 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 with fosaprepitant and/or oral aprepitant 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 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 CINVANTI is administered [see Clinical Pharmacology (12.3) ] .

Pregnancy

8.1 Pregnancy Risk Summary There are no available data on CINVANTI use in pregnant women to inform a drug-associated risk of adverse developmental outcomes. Avoid use of CINVANTI in pregnant women due to the alcohol content (see Clinical Considerations ). In animal reproduction studies, no adverse developmental effects were observed in rats or rabbits exposed during the period of organogenesis to systemic drug concentrations (area under the plasma-concentration time curve [AUC]) of aprepitant approximately equivalent to the exposure at the recommended human dose (RHD) of CINVANTI 130 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. Clinical Considerations Fetal/Neonatal adverse reactions CINVANTI contains alcohol. Published studies have demonstrated that alcohol is associated with fetal harm including central nervous system abnormalities, behavioral disorders, and impaired intellectual development. There is no safe level of alcohol exposure in pregnancy; therefore, avoid use of CINVANTI in pregnant women. 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 125 mg/kg/day were approximately equivalent to the exposure at the RHD of CINVANTI 130 mg. Aprepitant crosses the placenta in rats and rabbits.

Pediatric use

8.4 Pediatric Use The safety and effectiveness of CINVANTI have not been established in pediatric patients.

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 with fosaprepitant and/or oral aprepitant 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 aprepitant. In the event of overdose, CINVANTI should be discontinued and general supportive treatment and monitoring should be provided. Because of the antiemetic activity of CINVANTI, drug-induced emesis may not be effective in cases of CINVANTI overdosage. Aprepitant is not removed by hemodialysis.

Description

11 DESCRIPTION CINVANTI injectable emulsion contains the active ingredient, aprepitant. Aprepitant is a substance P/neurokinin 1 (NK 1 ) receptor antagonist, an antiemetic agent, chemically described as 5-[[(2 R ,3 S )-2-[(1 R )-1-[3,5-bis(trifluoromethyl)phenyl]ethoxy]-3-(4-fluorophenyl)-4-morpholinyl]methyl]-1,2-dihydro-3 H -1,2,4-triazol-3-one. Its empirical formula is C 23 H 21 F 7 N 4 O 3 , and its structural formula is: Aprepitant is a white to off-white crystalline solid, with a molecular weight of 534.43. It is practically insoluble in water. Aprepitant is sparingly soluble in ethanol and isopropyl acetate and slightly soluble in acetonitrile. CINVANTI (aprepitant) injectable emulsion is a sterile, opaque, off-white to amber liquid in a single-dose vial for intravenous use. Each vial contains 130 mg aprepitant in 18 mL of emulsion. The emulsion also contains the following inactive ingredients: egg lecithin (2602 mg), dehydrated alcohol (513 mg), sodium oleate (87 mg), soybean oil (1734 mg), sucrose (973 mg), and water for injection (12142 mg). Chemical Structure

Mechanism of action

12.1 Mechanism of Action 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. 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 show 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

16 HOW SUPPLIED/STORAGE AND HANDLING CINVANTI injectable emulsion is supplied as an opaque, off-white to amber emulsion in a single-dose glass vial containing 130 mg/18 mL (7.2 mg/mL) aprepitant: NDC 47426-201-01 1 single-dose vial per carton Storage CINVANTI injectable emulsion vials must be refrigerated, store at 2°C-8°C (36°F-46°F). CINVANTI injectable emulsion vials can remain at room temperature up to 60 days. Do not freeze.

Storage

Storage CINVANTI injectable emulsion vials must be refrigerated, store at 2°C-8°C (36°F-46°F). CINVANTI injectable emulsion vials can remain at room temperature up to 60 days. Do not freeze.

Patient information

Advise the patient to read the FDA-approved patient labeling (Patient Information). Hypersensitivity Advise patients that hypersensitivity reactions, including anaphylaxis, have been reported [see Warnings and Precautions (5.2) ] . Advise patients to stop taking CINVANTI and seek immediate medical attention if they experience signs or symptoms of a hypersensitivity reaction, such as hives, rash and itching, skin peeling or sores, or difficulty in breathing or swallowing, or dizziness, rapid or weak heartbeat or feeling faint. 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 CINVANTI with each chemotherapy cycle [see Warnings and Precautions (5.3) ] . Hormonal Contraceptives : Advise patients that administration of CINVANTI may reduce the efficacy of hormonal contraceptives. Instruct patients to use effective alternative or back-up methods of non-hormonal contraception (such as condoms or spermicides) during treatment with CINVANTI and for 1 month following administration of CINVANTI or oral aprepitant, whichever is administered last [see Warnings and Precautions (5.4) , Use in Specific Populations (8.3) ] . Pregnancy Advise pregnant women of the potential risk to a fetus and to avoid use of CINVANTI during pregnancy [see Use in Specific Populations (8.1) ].

Label text from the FDA structured product label by Heron Therapeutics, Inc. (revised Apr 1, 2026). Long sections are shortened; the complete label is on DailyMed.

Active ingredients

Aprepitant in 1 product

Cinvanti NDC products (1)

NDC	Strength & form	Labeler	Type
47426-201	Aprepitant 130 mg/18mL Injection, Emulsion	Heron Therapeutics, Inc.	NDA

Frequently asked questions

What is Cinvanti used for?

What are the side effects of Cinvanti?

Who makes Cinvanti?

Cinvanti is listed by 1 labeler in the FDA NDC directory, including Heron Therapeutics, Inc..