Aprepitant Kit
Other active recalls for Aprepitant (different manufacturers) — 1 · tap to view
Past resolved recalls for this product (1)
🆔 Identity & classification
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🏷️ RxNorm drug class
This medicine belongs to the Substance P/Neurokinin-1 Receptor Antagonist class.
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🏭 Manufacturer & labeler
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🩺 Clinical
Aprepitant is used with other medications in adults and children 6 months of age and older to prevent nausea and vomiting that may occur after receiving cancer chemotherapy treatment. It is also used with other medications in adults and children 6 months of age and older to prevent delayed nausea and vomiting that may occur several days after receiving certain chemotherapy medications. Aprepitant is not used to treat nausea and vomiting that you already have. Aprepitant is in a class of medications called antiemetics. It works by blocking the action of neurokinin, a natural substance in the br...
Read the full MedlinePlus article ↗- Aprepitant is designed to prevent nausea and vomiting before they start — not to treat them once they've kicked in. It's given as part of a combination of anti-nausea medicines, us...
- What exactly is this medicine supposed to do for me?
- Not without a backup plan. Aprepitant can reduce how well hormonal birth control works — that includes the pill, the patch, implants, and some IUDs. This effect can last for a full...
- Can I take my birth control as usual while I'm on this?
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Supplement & herbal interactions
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💊 What it looks like
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🧪 Inactive Ingredients / Excipients
Inactive ingredients, also called excipients, are components of the drug product other than the active ingredient. They may include fillers, dyes, coatings, preservatives, flavors, or other formulation ingredients.
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💲 Pricing
A drug doesn't have one price. Each row is a different public payment system, and none is what you'd pay at the counter — that depends on your insurance. The ⓘ on each row explains what it measures.
| Price system | Per ea | Per package |
|---|---|---|
| Retail pharmacies payNADAC · weekly | $87.266 | — |
| Medicaid paysCMS SDUD · 12 mo | $604.67 | — |
| Medicare drug plans payPart D · Q2 2026 | $191.47 | — |
| Medicare Part B allowsASP · J8501 | $3.069 / J8501 unit | — |
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🧾 Billing & reimbursement
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🔁 Therapeutic equivalents
| Product | Labeler | Pack | NADAC/unit | TE | Status | Price vs. this |
|---|---|---|---|---|---|---|
| Aprepitant 13668-0594-87 | Torrent | 1 capsule | $87.266 | AB | Availability likely | — |
| Aprepitant 68462-0112-33 | Glenmark | 1 kit | $87.266 | AB | Availability likely | — |
| Aprepitant 68001-0669-15 | BluePoint | 1 capsule | $87.266 | AB | Availability likely | — |
| Aprepitantthis 00781-4063-36 | Sandoz | 1 capsule | $87.266 | AB | Availability likely | — |
| Emend 00006-3862-03 | Merck | 1 capsule | — | AB | FDA listed | — |
| Aprepitant 51407-0704-03 | Golden | 1 capsule | — | AB | FDA listed | — |
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⏳ Availability & generic status
This product is an FDA-approved generic. Other versions of the same drug are listed under Therapeutic equivalents, least expensive first.
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🗺️ Medicaid utilization & spend
📊 Medicare Part D spend CMS · PART D · 2026 (Q1)
🔬 Reported adverse events (FAERS)
Top reported reactions
Age at onset
Reporter sex
Serious outcomes
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📦 Packaging — all sizes for this product
| Package NDC | Description | Marketing start | Status |
|---|---|---|---|
| 00781-4063-36 You're viewing this | 1 KIT in 1 DOSE PACK (0781-4063-36) * 2 CAPSULE in 1 BLISTER PACK * 1 CAPSULE in 1 BLISTER PACK | 2016-12-27 | Active |
🧭 About this NDC listing & data coverage
Kit / multi-component package
This NDC identifies a kit — a package containing more than one component. Structured data (pricing, ingredients, equivalents) is often reported per component rather than for the kit NDC itself, which can make this page look thinner than the components' own pages.
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| NDC identity (package / product / labeler codes) | ✓ Available |
| Labeler | ✓ Available |
| Product & package description | ✓ Available |
| Marketing category & status | ✓ Available |
| Active ingredient / dosage form / route | ✓ Available |
| FDA label (SPL via DailyMed) | ✓ Available |
| Package photos | ✓ Available |
| Inactive ingredients (structured) | — Not published for this NDC The labeler did not submit a structured excipient list, or no SPL is available. |
| NADAC pharmacy acquisition price (CMS) | ✓ Available |
| Orange Book / therapeutic-equivalence data | ✓ Available |
| HCPCS J-code billing crosswalk | ✓ Available |
| Medicaid utilization (CMS SDUD) | ✓ Available |
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📄 Full prescribing information FDA SPL
🎯 Indications and Usage ▾
1 INDICATIONS AND USAGE Aprepitant is a substance P/neurokinin 1 (NK 1 ) receptor antagonist. Aprepitant capsules is indicated • in combination with other antiemetic agents, in patients 12 years of age and older for prevention of: • acute and delayed nausea and vomiting associated with initial and repeat courses of highly emetogenic cancer chemotherapy (HEC) including high-dose cisplatin ( 1.1 ) • nausea and vomiting associated with initial and repeat courses of moderately emetogenic cancer chemotherapy (MEC) ( 1.1 ) • for prevention of postoperative nausea and vomiting (PONV) in adults ( 1.2 ) Limitations of Use ( 1.3 ) • Aprepitant capsules have not been studied for treatment of established nausea and vomiting. • Chronic continuous administration of aprepitant capsules are not recommended.
1.1Prevention of Chemotherapy Induced Nausea and Vomiting (CINV) Aprepitant capsules, in combination with other antiemetic agents, are indicated in patients 12 years 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. • nausea and vomiting associated with initial and repeat courses of moderately emetogenic cancer chemotherapy (MEC).
1.2Prevention of Postoperative Nausea and Vomiting (PONV) Aprepitant capsules are indicated in adults for the prevention of postoperative nausea and vomiting.
1.3Limitations of Use • Aprepitant capsules have not been studied for the treatment of established nausea and vomiting. • Chronic continuous administration of aprepitant capsules is not recommended because it has not been studied, and because the drug interaction profile may change during chronic continuous use.
⏱️ Dosage and Administration ▾
2 DOSAGE AND ADMINISTRATION Recommended Dosage for Prevention of Chemotherapy Induced Nausea and Vomiting (CINV) ( 2.1 ) • Aprepitant capsules in adults and pediatric patients 12 years of age and older: is 125 mg on Day 1 and 80 mg on Days 2 and 3. • Administer aprepitant capsules 1 hour prior to chemotherapy on Days 1, 2, and 3. If no chemotherapy is given on Days 2 and 3, administer aprepitant capsules in morning. • See Full Prescribing Information for recommended dosages of concomitant dexamethasone and 5-HT3 antagonist for HEC and MEC.
Recommended Dosage for PONV ( 2.2 ) • Adults: 40 mg aprepitant capsules within 3 hours prior to induction of anesthesia. Preparation and Administration ( 2.3 ) • Aprepitant capsules can be administered with or without food. • Swallow aprepitant capsules whole. • For details on preparation see Full Prescribing Information.
2.1Prevention of Chemotherapy Induced Nausea and Vomiting (CINV) Adults and Pediatric Patients 12 Years of Age and Older The recommended oral dosage of aprepitant capsules, dexamethasone, and a 5-HT 3 antagonist in adults and pediatric patients 12 years of age and older who can swallow oral capsules, for the prevention of nausea and vomiting associated with administration of HEC or MEC is shown in Table 1 or Table 2 , respectively. Table 1: Recommended Dosing for the Prevention of Nausea and Vomiting Associated with HEC Population Day1 Day 2 Day 3 Day 4 Aprepitant capsules Administer aprepitant capsules 1 hour prior to chemotherapy treatment on Days 1, 2, and 3.
If no chemotherapy is given on Days 2 and 3, administer aprepitant capsules in the morning. Adults and Pediatric Patients 12 years and Older 125 mg orally 80 mg orally 80 mg orally none Dexamethasone Adults 12 mg orally 8 mg orally 8 mg orally 8 mg orally Pediatric Patients 12 years and Older If a corticosteroid, such as dexamethasone, is coadministered, administer 50% of the recommended corticosteroid dose on Days 1 through 4 [see Clinical Studies ( 14.3 )] . Administer dexamethasone 30 minutes prior to chemotherapy treatment on Day 1 and in the morning on Days 2 through 4.
A 50% dosage reduction of dexamethasone is recommended to account for a drug interaction with aprepitant capsules [see Clinical Pharmacology ( 12.3 )] . 5-HT 3 antagonist Adults and Pediatric Patients 12 years and Older See selected 5-HT 3 antagonist prescribing information for the recommended dosage none none none Table 2: Recommended Dosing for the Prevention of Nausea and Vomiting Associated with MEC Population Day1 Day 2 Day 3 Aprepitant capsules Administer aprepitant capsules 1 hour prior to chemotherapy treatment on Days 1, 2 and 3.
If no chemotherapy is given on Days 2 and 3, administer aprepitant capsules in the morning. Adults and Pediatric Patients 12 years and Older 125 mg orally 80 mg orally 80 mg orally Dexamethasone Adults 12 mg orally none none Pediatric Patients 12 years and Older If a corticosteroid, such as dexamethasone, is coadministered, administer 50% of the recommended corticosteroid dose on Days 1 through 4 [see Clinical Studies ( 14.3 )] . 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 capsules [see Clinical Pharmacology ( 12.3 )] . 5-HT 3 antagonist Adults and Pediatric Patients 12 years and Older See the selected 5-HT 3 antagonist prescribing information for recommended dosage none none
2.2Prevention of Postoperative Nausea and Vomiting (PONV) The recommended oral dosage of aprepitant capsules in adults is 40 mg within 3 hours prior to induction of anesthesia.
2.3Administration Instructions Aprepitant capsules can be administered with or without food. Aprepitant capsules • Swallow capsules whole.
💊 Dosage Forms and Strengths ▾
3 DOSAGE FORMS AND STRENGTHS Aprepitant Capsules, USP : • 40 mg: hard gelatin capsules with opaque white cap and opaque white body containing white to off white colored pellets. The cap is imprinted with ‘SZ’ and the body is imprinted with ‘525’ in black ink. • 80 mg: hard gelatin capsules with opaque white cap and clear transparent body containing white to off white colored pellets. The cap is imprinted with ‘SZ’ and the body is imprinted with ‘528’ in black ink. • 125 mg: hard gelatin capsules with opaque light blue cap and opaque white body containing white to off white colored pellets.
The cap is imprinted with ‘SZ’ and the body is imprinted with ‘529’ in black ink. Aprepitant Capsules, USP: 40 mg; 80 mg; 125 mg ( 3 )
⛔ Contraindications ▾
4 CONTRAINDICATIONS Aprepitant is contraindicated in patients: • who are hypersensitive to any component of the product. Hypersensitivity reactions including anaphylactic reactions have been reported [see Adverse Reactions ( 6.2 )] . • taking pimozide. Inhibition of CYP3A4 by aprepitant 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 ) • Concurrent use with pimozide. ( 4 )
⚠️ Warnings and Cautions ▾
5 WARNINGS AND PRECAUTIONS • CYP3A4 Interactions: Aprepitant is a substrate, weak-to-moderate inhibitor and inducer of CYP3A4; See Full Prescribing Information for recommendations regarding contraindications, risk of adverse reactions, and dosage adjustments of aprepitant and concomitant drugs. ( 4 , 5.1 , 7.1 , 7.2 ) • 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 aprepitant. ( 5.2 , 7.1 ) • Hormonal Contraceptives: Efficacy of contraceptives may be reduced during administration of and for 28 days following the last dose of aprepitant.
Use effective alternative or back-up methods of contraception. ( 5.3 , 7.1 , 8.3 )
5.1Clinically Significant CYP3A4 Drug Interactions Aprepitant is a substrate, a weak-to-moderate (dose-dependent) inhibitor, and an inducer of CYP3A4. • Use of aprepitant with other drugs that are CYP3A4 substrates, may result in increased plasma concentration of the concomitant drug. • Use of pimozide with aprepitant 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 aprepitant 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 aprepitant. • Use of aprepitant with strong CYP3A4 inducers (e.g., rifampin) may result in a reduction in aprepitant plasma concentrations and decreased efficacy of aprepitant.
See Table 10 and Table 11 for a listing of potentially significant drug interactions [see Drug Interactions ( 7.1 , 7.2 )] .
5.2Decrease in INR with Concomitant Warfarin Coadministration of aprepitant with warfarin, a CYP2C9 substrate, may result in a clinically significant decrease in 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 the 3-day regimen of aprepitant with each chemotherapy cycle, or following administration of a single 40 mg dose of aprepitant for the prevention of postoperative nausea and vomiting [see Drug Interactions ( 7.1 )].
5.3Risk of Reduced Efficacy of Hormonal Contraceptives Upon coadministration with aprepitant, the efficacy of hormonal contraceptives may be reduced during administration of and for 28 days following the last dose of aprepitant [see Clinical Pharmacology ( 12.3 )] . Advise patients to use effective alternative or back-up methods of contraception during treatment with aprepitant and for 1 month following the last dose of aprepitant [see Drug Interactions ( 7.1 ), Use in Specific Populations ( 8.3 )].
🤒 Adverse Reactions ▾
6 ADVERSE REACTIONS Most common adverse reactions (≥3%) are ( 6.1 ): Prevention of Chemotherapy Induced Nausea and Vomiting (CINV) • Adults: fatigue, diarrhea, asthenia, dyspepsia, abdominal pain, hiccups, white blood cell count decreased, dehydration, and alanine aminotransferase increased • Pediatrics: neutropenia, headache, diarrhea, decreased appetite, cough, fatigue, hemoglobin decreased, dizziness and hiccups PONV • Adults: constipation and hypotension To report SUSPECTED ADVERSE REACTIONS, contact Sandoz Inc., at 1-800-525-8747 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.
6.1Clinical 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 aprepitant was evaluated in approximately 6,800 individuals. Adverse Reactions in Adults in the Prevention of Nausea and Vomiting Associated with HEC and MEC In 2 active-controlled, double-blind clinical trials in patients receiving highly emetogenic chemotherapy (HEC) (Studies 1 and 2), aprepitant in combination with ondansetron and dexamethasone (aprepitant regimen) was compared to ondansetron and dexamethasone alone (standard therapy) [see Clinical Studies ( 14.1 )] .
In 2 active-controlled clinical trials in patients receiving moderately emetogenic chemotherapy (MEC) (Studies 3 and 4), aprepitant in combination with ondansetron and dexamethasone (aprepitant regimen) was compared to ondansetron and dexamethasone alone (standard therapy) [see Clinical Studies ( 14.2 )] . The most common adverse reaction reported in patients who received MEC in pooled Studies 3 and 4 was dyspepsia (6% versus 4%). Across these 4 studies there were 1412 patients treated with the aprepitant regimen during Cycle 1 of chemotherapy and 1099 of these patients continued into the Multiple-Cycle extension for up to 6 cycles of chemotherapy.
The most common adverse reactions reported in patients who received HEC and MEC in pooled Studies 1, 2, 3 and 4 are listed in Table 5. Table 5: Most Common Adverse Reactions in Patients Receiving HEC and MEC from a Pooled Analysis of HEC and MEC Studies Reported in ≥3% of patients treated with the aprepitant regimen and at a greater incidence than standard therapy. Aprepitant, ondansetron and dexamethasone Aprepitant regimen (N=1412) Ondansetron and dexamethasone Standard therapy (N=1396) fatigue 13% 12% diarrhea 9% 8% asthenia 7% 6% dyspepsia 7% 5% abdominal pain 6% 5% hiccups 5% 3% white blood cell count decreased 4% 3% dehydration 3% 2% alanine aminotransferase increased 3% 2% In a pooled analysis of the HEC and MEC studies, less common adverse reactions reported in patients treated with the aprepitant regimen are listed in Table 6 .
Table 6: Less Common Adverse Reactions in Aprepitant-Treated Patients from a Pooled Analysis of HEC and MEC Studies Reported in >0.5% of patients treated with the aprepitant regimen, at a greater incidence than standard therapy and not previously described in Table 5 . Infection and Infestations oral candidiasis, pharyngitis Blood and the Lymphatic System Disorders anemia, febrile neutropenia, neutropenia, thrombocytopenia Metabolism and Nutrition Disorders decreased appetite, hypokalemia Psychiatric Disorders anxiety Nervous System Disorders dizziness, dysgeusia, peripheral neuropathy Cardiac Disorders palpitations Vascular Disorders flushing, hot flush Respiratory, Thoracic and Mediastinal Disorders cough, dyspnea, oropharyngeal pain Gastrointestinal Disorders dry mouth, eructation, flatulence, gastritis, gastroesophageal reflux disease, nausea, vomiting Skin and Subcutaneous Tissue Disorders alopecia, hyperhidrosis, rash Musculoskeletal and Connective Tissue Disorders musculoskeletal pain General Disorders and Administration Site Condition edema peripheral, malaise Investigations a…
🔄 Drug Interactions ▾
7 DRUG INTERACTIONS See Full Prescribing Information for a list of clinically significant drug interactions. ( 4 , 5.1 , 5.2 , 5.3 , 7.1 , 7.2 )
7.1Effect of Aprepitant on the Pharmacokinetics of Other Drugs Aprepitant is a substrate, a weak-to-moderate (dose-dependent) inhibitor, and an inducer of CYP3A4. Aprepitant is also an inducer of CYP2C9 [see Clinical Pharmacology ( 12.3 )] . Aprepitant acts as a moderate inhibitor of CYP3A4 when administered as a 3-day regimen (125 mg/80 mg/80 mg) and can increase plasma concentrations of concomitant drugs that are substrates for CYP3A4.
Aprepitant acts as a weak inhibitor when administered as a single 40 mg dose and has not been shown to alter the plasma concentrations of concomitant drugs that are primarily metabolized through CYP3A4. Some substrates of CYP3A4 are contraindicated with aprepitant [see Contraindications ( 4 )]. Dosage adjustment of some CYP3A4 and CYP2C9 substrates may be warranted, as shown in Table 10 .
Table 10: Effects of Aprepitant on the Pharmacokinetics of Other Drugs CYP3A4 Substrates Pimozide Clinical Impact Increased pimozide exposure. Intervention Aprepitant 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 3-day aprepitant regimen • Monitor for benzodiazepine-related adverse reactions. • Depending on the clinical situation (e.g., elderly patients) and degree of monitoring available, reduce the dose of intravenous midazolam Single 40 mg dose of aprepitant • No dosage adjustment of the benzodiazepine needed Dexamethasone Clinical Impact Increased dexamethasone exposure [see Clinical Pharmacology ( 12.3 )]. Intervention 3-day aprepitant regimen • Reduce the dose of oral dexamethasone by approximately 50% [see Dosage and Administration ( 2.1 )].
Single 40 mg dose of aprepitant • No dosage adjustment of oral dexamethasone needed Methylprednisolone Clinical Impact Increased methylprednisolone exposure [see Clinical Pharmacology ( 12.3 )]. Intervention 3-day aprepitant regimen • Reduce the dose of intravenous methylprednisolone by approximately 25% • Reduce the dose of oral methylprednisolone by approximately 50% Single 40 mg dose of aprepitant • No dosage adjustment of methylprednisolone needed 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 ( 5.3 ), Use in Specific Populations (8.3), Clinical Pharmacology ( 12.3 )].
Intervention Effective alternative or back-up methods of contraception (such as condoms and spermicides) should be used during treatment with aprepitant and for 1 month following the last dose of aprepitant. 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 ( 5.2 ), 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 initiation of the 3-day aprepitant regimen with each chemotherapy cycle, or following administration of a single 40 mg dose of aprepitant.
Other 5-HT3 Antagonists Clinical Impact No change in the exposure of the 5-HT3 antagonist [see Clinical Pharmacology ( 12.3 )]…
👥 Use in Specific Populations ▾
8 USE IN SPECIFIC POPULATIONS
8.1Pregnancy Risk Summary There are insufficient data on use of aprepitant 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 1.5 times the adult human exposure at the 125 mg/80 mg/80 mg aprepitant regimen (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 in rats and up to the maximum tolerated dose of 25 mg/kg/day in 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 1.5 times the adult exposure at the 125 mg/80 mg/80 mg aprepitant regimen. Aprepitant crosses the placenta in rats and rabbits.
8.2Lactation Risk Summary Lactation studies have not been conducted to assess 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 aprepitant and any potential adverse effects on the breastfed infant from aprepitant or from the underlying maternal condition.
8.3Females and Males of Reproductive Potential Contraception Upon administration of aprepitant, 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 and spermicides) during treatment with aprepitant and for 1 month following the last dose [see Drug Interactions ( 7.1 ), Clinical Pharmacology ( 12.3 )] .
8.4Pediatric Use Prevention of Nausea and Vomiting Associated with HEC or MEC The safety and effectiveness of aprepitant capsules in pediatric patients 12 years of age and older for the prevention of acute and delayed nausea and vomiting associated with initial and repeat courses of HEC, including high-dose cisplatin, and MEC. Use of aprepitant in these age groups is supported by evidence from 302 pediatric patients in a randomized, double-blind, active comparator controlled clinical study (n=207 patients aged 6 months to less than 12 years, n=95 patients aged 12 through 17 years).
Aprepitant was studied in combination with ondansetron with or without dexamethasone (at the discretion of the physician) [see Clinical Studies ( 14.3 )] . Adverse reactions were similar to those reported in adult patients [see Adverse Reactions ( 6.1 )] . The safety and effectiveness of aprepitant for the prevention of nausea and vomiting associated with HEC or MEC have not been established in patients less than 6 months.
Prevention of Postoperative Nausea and Vomiting (PONV) The safety and effectiveness of aprepitant has not been established for the prevention of postoperative nausea and vomiting in pediatric patients. Juvenile Animal Study A study was conducted in young rats to evaluate the effects of aprepitant on growth and on neurobehavioral and sexual development. Rats were treated at oral doses up to the maximum feasible dose of 1000 mg/kg twice daily (providing exposure in male rats lower than the exposure at the recommended pediatric human dose and exposure in female rats equivalent to the pediatric human exposure) from the early postnatal period (Postnatal Day 10) through Postnatal Day 58.
Slight changes in the onset of…
🤰 Pregnancy ▾
8.1Pregnancy Risk Summary There are insufficient data on use of aprepitant 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 1.5 times the adult human exposure at the 125 mg/80 mg/80 mg aprepitant regimen (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 in rats and up to the maximum tolerated dose of 25 mg/kg/day in 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 1.5 times the adult exposure at the 125 mg/80 mg/80 mg aprepitant regimen. Aprepitant crosses the placenta in rats and rabbits.
🧒 Pediatric Use ▾
8.4Pediatric Use Prevention of Nausea and Vomiting Associated with HEC or MEC The safety and effectiveness of aprepitant capsules in pediatric patients 12 years of age and older for the prevention of acute and delayed nausea and vomiting associated with initial and repeat courses of HEC, including high-dose cisplatin, and MEC. Use of aprepitant in these age groups is supported by evidence from 302 pediatric patients in a randomized, double-blind, active comparator controlled clinical study (n=207 patients aged 6 months to less than 12 years, n=95 patients aged 12 through 17 years).
Aprepitant was studied in combination with ondansetron with or without dexamethasone (at the discretion of the physician) [see Clinical Studies ( 14.3 )] . Adverse reactions were similar to those reported in adult patients [see Adverse Reactions ( 6.1 )] . The safety and effectiveness of aprepitant for the prevention of nausea and vomiting associated with HEC or MEC have not been established in patients less than 6 months.
Prevention of Postoperative Nausea and Vomiting (PONV) The safety and effectiveness of aprepitant has not been established for the prevention of postoperative nausea and vomiting in pediatric patients. Juvenile Animal Study A study was conducted in young rats to evaluate the effects of aprepitant on growth and on neurobehavioral and sexual development. Rats were treated at oral doses up to the maximum feasible dose of 1000 mg/kg twice daily (providing exposure in male rats lower than the exposure at the recommended pediatric human dose and exposure in female rats equivalent to the pediatric human exposure) from the early postnatal period (Postnatal Day 10) through Postnatal Day 58.
Slight changes in the onset of sexual maturation were observed in female and male rats; however, there were no effects on mating, fertility, embryonic-fetal survival, or histomorphology of the reproductive organs. There were no effects in neurobehavioral tests of sensory function, motor function, and learning and memory.
🧓 Geriatric Use ▾
8.5Geriatric Use Of the 544 adult cancer patients treated with aprepitant in CINV clinical studies, 31% were aged 65 and over, while 5% were aged 75 and over. Of the 1120 adult cancer patients treated with aprepitant in PONV clinical studies, 7% were aged 65 and over, while 2% were aged 75 and over. Other reported clinical experience with 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 ▾
10 OVERDOSAGE No specific information is available on the treatment of overdosage. Drowsiness and headache were reported in one patient who ingested 1440 mg of aprepitant (approximately 11 times the maximum recommended single dose). In the event of overdose, aprepitant should be discontinued and general supportive treatment and monitoring should be provided.
Because of the antiemetic activity of aprepitant, drug-induced emesis may not be effective in cases of aprepitant overdosage. Aprepitant is not removed by hemodialysis.
🧬 Clinical Pharmacology ▾
12 CLINICAL PHARMACOLOGY
12.1Mechanism 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, the targets of existing therapies for chemotherapy-induced nausea and vomiting (CINV) and postoperative nausea and vomiting (PONV). 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.
12.2Pharmacodynamics NK 1 Receptor Occupancy In two single-blind, multiple-dose, randomized, and placebo-controlled studies, healthy young men received oral aprepitant doses of 10 mg (N=2), 30 mg (N=3), 100 mg (N=3) or 300 mg (N=5) once daily (0.08, 0.24, 0.8, and 2.4 times the maximum recommended single dose, respectively) for 14 days with 2 or 3 subjects on placebo. Both plasma aprepitant concentration and NK 1 receptor occupancy in the corpus striatum by positron emission tomography were evaluated, at predose and 24 hours after the last dose.
At aprepitant plasma concentrations of approximately 10 ng/mL and 100 ng/mL, the NK 1 receptor occupancies were approximately 50% and 90%, respectively. The oral aprepitant regimen for CINV produced mean trough plasma aprepitant concentrations greater than 500 ng/mL in adults, which would be expected to, based on the fitted curve with the Hill equation, result in greater than 95% brain NK 1 receptor occupancy. However, the receptor occupancy for either CINV or PONV dosing regimen has not been determined.
In addition, the relationship between NK 1 receptor occupancy and the clinical efficacy of aprepitant has not been established. Cardiac Electrophysiology In a randomized, double-blind, positive-controlled, thorough QTc study, a single 200 mg dose of fosaprepitant had no effect on the QTc interval. Maximum aprepitant concentrations after a single 200 mg dose of fosaprepitant were 4- and 9-fold higher than that achieved with oral aprepitant 125 mg and 40 mg, respectively.
QT prolongation with the recommended oral aprepitant dosing regimens for CINV and PONV is not expected.
12.3Pharmacokinetics Absorption Following oral administration of a single 40 mg dose of aprepitant in the fasted state, mean area under the plasma concentration-time curve (AUC 0-∞ ) was 7.8 mcg•hr/mL and mean peak plasma concentration (C max ) was 0.7 mcg/mL, occurring at approximately 3 hours postdose (T max ). The absolute bioavailability at the 40 mg dose has not been determined. Following oral administration of a single 125 mg dose of aprepitant on Day 1 and 80 mg once daily on Days 2 and 3, the AUC 0-24hr was approximately 19.6 mcg•hr/mL and 21.2 mcg•hr/mL on Day 1 and Day 3, respectively.
The C max of 1.6 mcg/mL and 1.4 mcg/mL were reached in approximately 4 hours (T max ) on Day 1 and Day 3, respectively. At the dose range of 80 to 125 mg, the mean absolute oral bioavailability of aprepitant is approximately 60 to 65%. Oral administration of the capsule with a standard high-fat breakfast had no clinically meaningful effect on the bioavailability of aprepitant.
The pharmacokinetics of aprepitant were non-linear across the clinical dose range. In healthy young adults, the increase in AUC 0-∞ was 26% greater than dose proportional between 80 mg and 125 mg single doses administered in the fed state. Distribution Aprepitant is greater than 95% bound to plasma proteins.
The mean apparent volume of distribution at steady state (Vd ss ) was approximately 70 L in humans. Aprepitant crosses the blood…
🧬 Mechanism of Action ▾
12.1Mechanism 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, the targets of existing therapies for chemotherapy-induced nausea and vomiting (CINV) and postoperative nausea and vomiting (PONV). 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 / Storage and Handling ▾
16 HOW SUPPLIED/STORAGE AND HANDLING Aprepitant capsules, USP 40 mg, are hard gelatin capsules with opaque white cap and opaque white body containing white to off white colored pellets. The cap is imprinted with ‘SZ’ and the body is imprinted with ‘525’ in black ink. NDC 0781-2321-06, unit-dose package of 1 NDC 0781-2321-51, unit-dose package of 5 Aprepitant capsules, USP 80 mg, are hard gelatin capsules with opaque white cap and clear transparent body containing white to off white colored pellets.
The cap is imprinted with ‘SZ’ and the body is imprinted with ‘528’ in black ink. NDC 0781-2322-68, unit-dose package of 6 NDC 0781-2322-46, unit of use bi-fold package of 2 Aprepitant capsules, USP 125 mg, are hard gelatin capsules with opaque light blue cap and opaque white body containing white to off white colored pellets. The cap is imprinted with ‘SZ’ and the body is imprinted with ‘529’ in black ink.
NDC 0781-2323-68, unit-dose package of 6 NDC 0781-4063-36, unit of use tri-fold pack containing one 125 mg capsule and two 80 mg capsules. Storage Store at 20° to 25°C (68° to 77°F) [see USP Controlled Room Temperature].
📋 Description ▾
11 DESCRIPTION Aprepitant capsules, USP contain 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. Each aprepitant capsule, USP for oral administration contains either 40 mg, 80 mg or 125 mg of aprepitant and the following inactive ingredients: hydroxypropyl cellulose, microcrystalline cellulose, sodium lauryl sulfate and sucrose.
The aprepitant capsule shell for 40 mg and 80 mg consists of gelatin and titanium dioxide. The aprepitant capsule shell for 125 mg consists of FD&C Blue #1, gelatin and titanium dioxide. The capsule is printed with edible black pharmaceutical ink.
The printing ink contains black iron oxide, propylene glycol and shellac. This product meets USP dissolution test 2. structural_formula
💬 Information for Patients ▾
17 PATIENT COUNSELING INFORMATION Advise the patient to read the FDA-approved patient labeling (Patient Information). Hypersensitivity Reactions Advise patients that hypersensitivity reactions, including anaphylaxis, have been reported in patients taking aprepitant. Advise patients to stop taking aprepitant 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.
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 the 3-day regimen of aprepitant with each chemotherapy cycle, or following administration of a single 40 mg dose of aprepitant for the prevention of postoperative nausea and vomiting [see Warnings and Precautions ( 5.2 )] .
Hormonal Contraceptives: Advise patients that administration of aprepitant may reduce the efficacy of hormonal contraceptives. Instruct patients to use effective alternative or back-up methods of contraception (such as condoms and spermicides) during treatment with aprepitant and for 1 month following the last dose of aprepitant [see Warnings and Precautions ( 5.3 ), Use in Specific Populations ( 8.3 )] . Finished Drug Product Manufactured by Novartis d.o.o.
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