Dosage Forms
Excipient information presented when available (limited, particularly for generics); consult specific product labeling. [DSC] = Discontinued product
Capsule, Oral:
Emend: 40 mg, 80 mg, 125 mg [DSC]
Emend Tri-Pack: 80 mg & 125 mg
Generic: 40 mg, 80 mg, 125 mg, 80 mg & 125 mg
Emulsion, Intravenous:
Cinvanti: 130 mg/18 mL (18 mL) [contains alcohol, usp, egg phospholipids (egg lecithin), soybean oil]
Suspension Reconstituted, Oral:
Emend: 125 mg (1 ea)
Pharmacology
Mechanism of Action
Aprepitant prevents acute and delayed vomiting by inhibiting the substance P/neurokinin 1 (NK1) receptor; augments the antiemetic activity of 5-HT3 receptor antagonists and corticosteroids to inhibit acute and delayed phases of chemotherapy-induced emesis.
Pharmacokinetics/Pharmacodynamics
Distribution
Vd: IV, Oral: ~70 L; crosses the blood-brain barrier
Metabolism
Extensively hepatic via CYP3A4 (major); CYP1A2 and CYP2C19 (minor); forms 7 metabolites (weakly active)
Excretion
Primarily via metabolism
Time to Peak
Plasma: Pediatric: Capsule: ~4 hours; Suspension ~6 hours; Adults: 40 mg: ~3 hours; 125 mg followed by 80 mg for 2 days: ~4 hours
Half-Life Elimination
Terminal: IV, Oral: ~9 to 13 hours
Protein Binding
IV: >99%; Oral: >95%
Use in Specific Populations
Special Populations: Renal Function Impairment
Following a single oral aprepitant 240 mg dose in patients with severe renal impairment (CrCl <30 mL/minute) and end stage renal disease requiring hemodialysis, the AUC of total aprepitant (unbound and protein bound) decreased by 21% and Cmax decreased by 32% compared with healthy subjects. In patients with ESRD undergoing hemodialysis, the AUC of total aprepitant decreased by 42% and Cmax decreased by 32%. Hemodialysis conducted 4 or 48 hours after aprepitant dosing had no significant impact on aprepitant pharmacokinetics.
Use: Labeled Indications
IV (Cinvanti):
Prevention of chemotherapy-induced nausea and vomiting:
Prevention of acute and delayed nausea and vomiting associated with initial and repeat courses of highly emetogenic chemotherapy, including high-dose cisplatin, as single-dose aprepitant regimen (in combination with other antiemetics) in adults.
Prevention of delayed nausea and vomiting associated with initial and repeat courses of moderately emetogenic chemotherapy as a single-dose aprepitant regimen (in combination with other antiemetics) in adults.
Prevention of nausea and vomiting associated with initial and repeat courses of moderately emetogenic chemotherapy as a 3-day aprepitant regimen (in combination with other antiemetics) in adults.
Oral (Emend oral):
Prevention of chemotherapy-induced nausea and vomiting:
Prevention of acute and delayed nausea and vomiting associated with highly emetogenic chemotherapy (initial and repeat courses; in combination with other antiemetics) in patients ≥12 years (capsules) and in patients ≥6 months (oral suspension).
Prevention of nausea and vomiting associated with moderately emetogenic chemotherapy (initial and repeat courses; in combination with other antiemetics) in patients ≥12 years (capsules) and in patients ≥6 months (oral suspension).
Note: Generic aprepitant capsules are only approved for use in adults.
Postoperative nausea and vomiting (generic capsules): Prevention of postoperative nausea and vomiting (PONV) in adults. Note: The PONV indication was removed from the Emend capsule US prescribing information (in September 2019); however, it remains in the labeling for generic aprepitant capsules.
Limitations of use: Aprepitant has not been studied for the management of existing nausea and vomiting. Chronic, continuous administration is not recommended (has not been studied and chronic use may alter aprepitant's drug interaction profile).
Contraindications
Hypersensitivity to aprepitant or any component of the formulation; concurrent use with pimozide
Canadian labeling: Additional contraindications (not in the US labeling): Concurrent use with astemizole, cisapride, or terfenadine.
Dosage and Administration
Dosing: Adult
Note: Dosing is for aprepitant (Emend oral and Cinvanti IV); refer to the fosaprepitant monograph for Emend IV dosing.
Prevention of chemotherapy-induced nausea and vomiting:
Manufacturer's labeling:
Prevention of acute and delayed nausea/vomiting associated with highly-emetogenic chemotherapy:
IV (single-dose aprepitant regimen): 130 mg ~30 minutes prior to chemotherapy on day 1 (in combination with a 5-HT3 antagonist antiemetic on day 1 only and oral dexamethasone on days 1 to 4).
Oral:
Capsules: 125 mg 1 hour prior to chemotherapy on day 1, followed by 80 mg once daily on days 2 and 3 (in combination with a 5-HT3 antagonist antiemetic on day 1 and dexamethasone on days 1 to 4)
Suspension: Adults unable to swallow capsules: 3 mg/kg (maximum: 125 mg/dose) 1 hour prior to chemotherapy on day 1, followed by 2 mg/kg (maximum: 80 mg/dose) once daily on days 2 and 3 (in combination with a 5-HT3 antagonist antiemetic on day 1 and dexamethasone on days 1 to 4)
Prevention of delayed nausea/vomiting associated with moderately-emetogenic chemotherapy:
IV (single-dose aprepitant regimen): 130 mg ~30 minutes prior to chemotherapy on day 1 (in combination with a 5-HT3 antagonist antiemetic on day 1 only and dexamethasone on day 1 only).
Prevention of nausea/vomiting associated with moderately-emetogenic chemotherapy:
IV (3-day aprepitant regimen): 100 mg ~30 minutes prior to chemotherapy on day 1 (in combination with oral aprepitant 80 mg on days 2 and 3, a 5-HT3 antagonist antiemetic on day 1 only and dexamethasone on day 1 only).
Oral:
Capsules: 125 mg 1 hour prior to chemotherapy on day 1, followed by 80 mg once daily on days 2 and 3 (in combination with a 5-HT3 antagonist antiemetic and dexamethasone on day 1)
Suspension: Adults unable to swallow capsules: 3 mg/kg (maximum: 125 mg/dose) 1 hour prior to chemotherapy on day 1, followed by 2 mg/kg (maximum: 80 mg/dose) once daily on days 2 and 3 (in combination with a 5-HT3 antagonist antiemetic and dexamethasone on day 1)
Guideline recommendations:
Prevention of nausea/vomiting associated with highly-emetogenic chemotherapy (including anthracycline and cyclophosphamide [AC] regimens): Oral:
American Society of Clinical Oncology (ASCO [Hesketh 2017]): 125 mg prior to chemotherapy on day 1, followed by 80 mg once daily on days 2 and 3 (in combination with a 5-HT3 antagonist antiemetic on day 1 and dexamethasone on days 1 to 4 or days 1 to 3).
Multinational Association of Supportive Care in Cancer and European Society of Medical Oncology (MASCC/ESMO [Roila 2016]): 125 mg prior to chemotherapy on day 1, followed by 80 mg once daily on days 2 and 3 (in combination with dexamethasone and a 5-HT3 antagonist antiemetic on day 1, followed by dexamethasone for 3 to 4 more days).
Prevention of postoperative nausea and vomiting: Oral: Capsules (generic): 40 mg within 3 hours prior to anesthesia induction. Note: The postoperative nausea and vomiting indication was removed from the Emend capsule US prescribing information; however, it remains in the labeling for generic capsule products.
Dosing: Geriatric
Refer to adult dosing.
Dosing: Pediatric
Note: Concentration of oral suspension may vary (commercially available or extemporaneous compounded); use caution.
Chemotherapy-induced nausea and vomiting (CINV), prevention; highly and moderately emetogenic chemotherapy: Note: Use in combination with 5-HT3 antagonist antiemetic with or without dexamethasone depending upon patient age, chemotherapy emetogenic potential, and drug-interaction profile (refer to specific protocols or guidelines) (POGO [Patel 2017]).
Infants ≥6 months and Children <12 years weighing 6 to <30 kg: Oral: Oral suspension: 3 mg/kg 1 hour prior to chemotherapy on day 1, then 2 mg/kg/dose once daily on days 2 and 3. Note: For commercially available product (25 mg/mL), may round dose to nearest 2.5 mg (0.1 mL) for doses ≤25 mg or to the nearest 5 mg (0.2 mL) for doses >25 mg.
Children <12 years weighing ≥30 kg, Children ≥12 years, and Adolescents: Oral: Capsules, Oral suspension: 125 mg 1 hour prior to chemotherapy on day 1, followed by 80 mg once daily on days 2 and 3
Reconstitution
IV injection:
130 mg dose: Aseptically withdraw 18 mL from the aprepitant injection vial; no further dilution required.
100 mg dose: Aseptically withdraw 14 mL from the aprepitant injection vial; no further dilution required.
IV infusion: Prepare the infusion in NS or D5W only; aprepitant IV is incompatible in solutions containing divalent cations (eg, lactated Ringer's solution). Use only non-PVC bags and non-DEHP tubing.
130 mg dose: Aseptically withdraw 18 mL from the aprepitant injection vial and transfer into a 100 mL NS or D5W non-PVC infusion bag; gently invert 4 to 5 times (avoid shaking).
100 mg dose: Aseptically withdraw 14 mL from the aprepitant injection vial and transfer into a 100 mL NS or D5W non-PVC infusion bag; gently invert 4 to 5 times (avoid shaking).
Oral suspension: Aprepitant for oral suspension is packaged as a kit, with a 1 mL and a 5 mL oral dosing dispenser, one cap, one mixing cup, and the aprepitant pouch. Fill mixing cup with room temperature drinking water, using the 5 mL dosing dispenser, measure 4.6 mL of water from the mixing cup and discard unused water from cup. Make sure no air is in the dispenser. Add the 4.6 mL water back to the empty cup. Shake content of aprepitant pouch to bottom of pouch and pour entire contents of pouch into mixing cup, add lid and snap shut. Mix suspension by gently swirling 20 times, then gently invert cup 5 times (to avoid foaming, do not shake vigorously). This results in a 25 mg/mL cloudy pink to light pink suspension. If clumps are present, repeat mixing by gently swirling 20 times and gently inverting 5 times. If foam is present, wait for foam to disappear. Measure calculated dose into oral dosing dispenser (use the 1 mL dispenser if dose is ≤1 mL and the 5 mL dispenser if dose is >1 mL). If dose is <1 mL, round to nearest 0.1 mL; if dose is >1 mL, round to the nearest 0.2 mL. Make sure all air is removed from dispenser and dispenser contains the prescribed dose. Place cap on dispenser until it clicks. Discard mixing cup and any suspension remaining in cup. Refer to manufacturer's instructions for further preparation details.
Extemporaneously Prepared
Note: An aprepitant suspension (25 mg/mL) for oral administration is commercially available.
20 mg/mL Oral Suspension
A 20 mg/mL oral aprepitant suspension may be prepared with capsules and a 1:1 combination of Ora-Sweet and Ora-Plus (or Ora-Blend). Empty the contents of four 125 mg capsules into a mortar and reduce to a fine powder (process will take 10 to 15 minutes). Add small portions of vehicle and mix to a uniform paste. Add sufficient vehicle to form a liquid; transfer to a graduated cylinder, rinse mortar with vehicle, and add quantity of vehicle sufficient to make 25 mL. Label "shake well" and "refrigerate". Stable for 90 days refrigerated.
Dupuis LL, Lingertat-Walsh K, and Walker SE, "Stability of an Extemporaneous Oral Liquid Aprepitant Formulation," Support Care Cancer, 2009, 17(6):701-6.19043742
Administration
IV: Administration information is for aprepitant IV (Cinvanti); refer to fosaprepitant IV (Emend IV) monograph for fosaprepitant administration information.
IV injection: Inject over 2 minutes approximately one-half hour (30 minutes) prior to chemotherapy. Flush infusion line with NS before and after administration.
IV infusion: Infuse over 30 minutes approximately one-half hour (30 minutes) prior to chemotherapy. Use only non-DEHP tubing for administration of the IV infusion (not necessary if administering as an IV push).
Oral:
Prevention of chemotherapy-induced nausea/vomiting: Administer with or without food. First dose should be given 1 hour prior to chemotherapy; subsequent doses should be given 1 hour prior to chemotherapy or in the morning (if no chemotherapy is administered on days 2 and 3). Swallow capsules whole.
Oral suspension: Dose should be prepared by a health care provider and dispensed to patient or caregiver in an oral dispenser. Administer by placing the dispenser in the patient's mouth along the inner cheek and slowly dispensing the medicine.
Prevention of postoperative nausea/vomiting (oral): Administer within 3 hours prior to induction; follow health care provider instructions about food/drink restrictions prior to surgery. Swallow capsules whole.
Storage
Injection: Store intact vials at 2°C to 8°C (36°F to 46°F) or at room temperature for up to 60 days; do not freeze. When stored at ambient room temperature, solutions diluted for infusion in NS are stable for 6 hours and solutions diluted for infusion in D5W are stable for 12 hours. When refrigerated, solutions diluted for infusion in NS or D5W are stable for 72 hours.
Capsules: Store at room temperature of 20°C to 25°C (68°F to 77°F).
Oral suspension: Store unopened pouch at 20°C to 25°C (68°F to 77°F); excursions permitted between 15°C to 30°C (59°F to 86°F). Store in the original container. Do not open pouch until ready to use. Once prepared, if suspension is not used immediately, store refrigerated (between [2°C to 8°C/36°F to 46°F]) for up to 72 hours. When ready to use, the mixture may be kept at room temperature (between [20°C to 25°C/68°F to 77°F]) for up to 3 hours.
Aprepitant Images
Drug Interactions
Abemaciclib: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Abemaciclib. Monitor therapy
Acalabrutinib: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Acalabrutinib. Management: Reduce acalabrutinib dose to 100 mg once daily with concurrent use of a moderate CYP3A4 inhibitor. Monitor patient closely for both acalabrutinib response and evidence of adverse effects with any concurrent use. Consider therapy modification
AmLODIPine: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of AmLODIPine. Monitor therapy
Apixaban: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Apixaban. Monitor therapy
ARIPiprazole: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of ARIPiprazole. Management: Monitor for increased aripiprazole pharmacologic effects. Aripiprazole dose adjustments may or may not be required based on concomitant therapy and/or indication. Consult full interaction monograph for specific recommendations. Monitor therapy
Astemizole: Aprepitant may increase the serum concentration of Astemizole. Avoid combination
Asunaprevir: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Asunaprevir. Avoid combination
Avanafil: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Avanafil. Management: The maximum avanafil adult dose is 50 mg per 24-hour period when used together with a moderate CYP3A4 inhibitor. Patients receiving such a combination should also be monitored more closely for evidence of adverse effects. Consider therapy modification
Avapritinib: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Avapritinib. Management: Avoid use of moderate CYP3A4 inhibitors with avapritinib. If this combination cannot be avoided, reduce the avapritinib dose from 300 mg once daily to 100 mg once daily. Consider therapy modification
Axitinib: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Axitinib. Monitor therapy
Benzhydrocodone: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Benzhydrocodone. Specifically, the concentration of hydrocodone may be increased. Monitor therapy
Blonanserin: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Blonanserin. Monitor therapy
Bosentan: May decrease the serum concentration of CYP3A4 Substrates (High risk with Inducers). Monitor therapy
Bosentan: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Bosentan. Management: Concomitant use of both a CYP2C9 inhibitor and a CYP3A inhibitor or a single agent that inhibits both enzymes with bosentan is likely to cause a large increase in serum concentrations of bosentan and is not recommended. See monograph for details. Monitor therapy
Bosutinib: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Bosutinib. Avoid combination
Brexpiprazole: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Brexpiprazole. Management: The brexpiprazole dose should be reduced to 25% of usual if used together with both a moderate CYP3A4 inhibitor and a strong or moderate CYP2D6 inhibitor, or if a moderate CYP3A4 inhibitor is used in a CYP2D6 poor metabolizer. Monitor therapy
Brigatinib: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Brigatinib. Management: Avoid concurrent use of brigatinib with moderate CYP3A4 inhibitors when possible. If such a combination cannot be avoided, reduce the dose of brigatinib by approximately 40% (ie, from 180 mg to 120 mg, from 120 mg to 90 mg, or from 90 mg to 60 mg). Consider therapy modification
Bromocriptine: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Bromocriptine. Management: The bromocriptine dose should not exceed 1.6 mg daily with use of a moderate CYP3A4 inhibitor. The Cycloset brand specifically recommends this dose limitation, but other bromocriptine products do not make such specific recommendations. Consider therapy modification
Budesonide (Systemic): CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Budesonide (Systemic). Avoid combination
Budesonide (Topical): CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Budesonide (Topical). Management: Per US prescribing information, avoid this combination. Canadian product labeling does not recommend strict avoidance. If combined, monitor for excessive glucocorticoid effects as budesonide exposure may be increased. Consider therapy modification
Cannabidiol: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Cannabidiol. Monitor therapy
Cannabis: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Cannabis. More specifically, tetrahydrocannabinol and cannabidiol serum concentrations may be increased. Monitor therapy
Cilostazol: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Cilostazol. Management: Consider reducing the cilostazol dose to 50 mg twice daily in adult patients who are also receiving moderate inhibitors of CYP3A4. Consider therapy modification
Cisapride: Aprepitant may increase the serum concentration of Cisapride. Avoid combination
Clofazimine: May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors). Monitor therapy
Cobimetinib: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Cobimetinib. Management: Avoid the concomitant use of cobimetinib and moderate CYP3A4 inhibitors. If concurrent short term (14 days or less) use cannot be avoided, reduce the cobimetinib dose to 20 mg daily. Avoid combination
Codeine: CYP3A4 Inhibitors (Moderate) may increase serum concentrations of the active metabolite(s) of Codeine. Monitor therapy
Colchicine: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Colchicine. Management: Reduce colchicine dose as directed when using with a moderate CYP3A4 inhibitor, and increase monitoring for colchicine-related toxicity. See full monograph for details. Use extra caution in patients with impaired renal and/or hepatic function. Consider therapy modification
Conivaptan: May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors). Avoid combination
Corticosteroids (Systemic): Aprepitant may increase the serum concentration of Corticosteroids (Systemic). Management: No dose adjustment is needed for single 40 mg aprepitant doses. For other regimens, reduce oral dexamethasone or methylprednisolone doses by 50%, and IV methylprednisolone doses by 25%. Antiemetic regimens containing dexamethasone reflect this adjustment. Consider therapy modification
CYP3A4 Inducers (Moderate): May decrease the serum concentration of CYP3A4 Substrates (High risk with Inducers). Monitor therapy
CYP3A4 Inducers (Strong): May decrease the serum concentration of Aprepitant. Avoid combination
CYP3A4 Inhibitors (Moderate): May increase the serum concentration of Aprepitant. Avoid combination
CYP3A4 Inhibitors (Strong): May increase the serum concentration of Aprepitant. Avoid combination
CYP3A4 Substrates (High risk with Inhibitors): Aprepitant may increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors). Monitor therapy
Dabrafenib: May decrease the serum concentration of CYP3A4 Substrates (High risk with Inducers). Management: Seek alternatives to the CYP3A4 substrate when possible. If concomitant therapy cannot be avoided, monitor clinical effects of the substrate closely (particularly therapeutic effects). Consider therapy modification
Dapoxetine: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Dapoxetine. Management: The dose of dapoxetine should be limited to 30 mg per day when used together with a moderate inhibitor of CYP3A4. Consider therapy modification
Deferasirox: May decrease the serum concentration of CYP3A4 Substrates (High risk with Inducers). Monitor therapy
Deflazacort: CYP3A4 Inhibitors (Moderate) may increase serum concentrations of the active metabolite(s) of Deflazacort. Management: Administer one third of the recommended deflazacort dose when used together with a strong or moderate CYP3A4 inhibitor. Consider therapy modification
Disopyramide: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Disopyramide. Monitor therapy
Dofetilide: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Dofetilide. Monitor therapy
Domperidone: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Domperidone. Management: Drugs listed as exceptions to this monograph are discussed in further detail in separate drug interaction monographs. Avoid combination
DOXOrubicin (Conventional): CYP3A4 Inhibitors (Moderate) may increase the serum concentration of DOXOrubicin (Conventional). Management: Seek alternatives to moderate CYP3A4 inhibitors in patients treated with doxorubicin whenever possible. One U.S. manufacturer (Pfizer Inc.) recommends that these combinations be avoided. Consider therapy modification
Dronabinol: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Dronabinol. Monitor therapy
Eletriptan: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Eletriptan. Management: The use of eletriptan within 72 hours of a moderate CYP3A4 inhibitor should be avoided. Consider therapy modification
Elexacaftor, Tezacaftor, and Ivacaftor: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Elexacaftor, Tezacaftor, and Ivacaftor. Management: When combined with moderate CYP3A4 inhibitors, two elexacaftor/tezacaftor/ivacaftor (100 mg/50 mg/75 mg) tablets should be given in the morning, every other day. Ivacaftor (150 mg) should be given in the morning, every other day on alternate days. Consider therapy modification
Eliglustat: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Eliglustat. Management: Use should be avoided under some circumstances. See full drug interaction monograph for details. Consider therapy modification
Encorafenib: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Encorafenib. Management: Avoid concomitant use of encorafenib and moderate CYP3A4 inhibitors whenever possible. If concomitant administration is unavoidable, decrease the encorafenib dose prior to initiation of the CYP3A4 inhibitor. See full monograph for details. Consider therapy modification
Entrectinib: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Entrectinib. Management: Avoid moderate CYP3A4 inhibitors during treatment with entrectinib. Reduce dose to 200 mg/day if combination cannot be avoided in adults and those 12 yrs of age or older with a BSA of at least 1.5 square meters. No alternative dosing provided for others. Consider therapy modification
Eplerenone: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Eplerenone. Management: When used concomitantly with moderate inhibitors of CYP3A4, eplerenone dosing recommendations vary by indication and international labeling. See full drug interaction monograph for details. Consider therapy modification
Erdafitinib: May decrease the serum concentration of CYP3A4 Substrates (High risk with Inducers). Monitor therapy
Erdafitinib: May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors). Monitor therapy
Estrogen Derivatives: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Estrogen Derivatives. Monitor therapy
Estrogen Derivatives (Contraceptive): Aprepitant may decrease the serum concentration of Estrogen Derivatives (Contraceptive). Management: Use of a non-hormone-based contraceptive is recommended. Consider therapy modification
Everolimus: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Everolimus. Management: Everolimus dose reductions are required for most indications. See full monograph or prescribing information for specific dose adjustment and monitoring recommendations. Consider therapy modification
FentaNYL: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of FentaNYL. Management: Monitor patients closely for several days following initiation of this combination, and adjust fentanyl dose as necessary. Consider therapy modification
Flibanserin: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Flibanserin. Avoid combination
Fosaprepitant: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Fosaprepitant. Avoid combination
Fusidic Acid (Systemic): May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors). Avoid combination
GuanFACINE: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of GuanFACINE. Management: Reduce the guanfacine dose by 50% when initiating this combination. Consider therapy modification
Halofantrine: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Halofantrine. Management: Extreme caution, with possibly increased monitoring of ECGs, should be used if halofantrine is combined with moderate CYP3A4 inhibitors. Drugs listed as exceptions to this monograph are discussed in separate drug interaction monographs. Monitor therapy
HYDROcodone: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of HYDROcodone. Monitor therapy
Ibrutinib: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Ibrutinib. Management: When treating B-cell malignancies, decrease ibrutinib to 280 mg daily when combined with moderate CYP3A4 inhibitors. When treating graft versus host disease, monitor patients closely and reduce the ibrutinib dose as needed based on adverse reactions. Consider therapy modification
Idelalisib: May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors). Avoid combination
Ifosfamide: Aprepitant may increase the serum concentration of Ifosfamide. Specifically, concentrations of the toxic metabolites of ifosfamide may increase. Monitor therapy
Ivabradine: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Ivabradine. Avoid combination
Ivacaftor: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Ivacaftor. Management: Ivacaftor dose reductions may be required; consult full monograph content for age- and weight-specific dosage recommendations. Consider therapy modification
Ivosidenib: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Ivosidenib. Management: Avoid use of moderate CYP3A4 inhibitors with ivosidenib whenever possible. If combined, monitor for increased ivosidenib toxicities. Drugs listed as exceptions are discussed in further detail in separate drug interaction monographs. Consider therapy modification
Larotrectinib: May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors). Monitor therapy
Lemborexant: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Lemborexant. Avoid combination
Levamlodipine: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Levamlodipine. Monitor therapy
Lomitapide: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Lomitapide. Avoid combination
Lorlatinib: May decrease the serum concentration of CYP3A4 Substrates (High risk with Inducers). Management: Avoid concurrent use of lorlatinib with any CYP3A4 substrates for which a minimal decrease in serum concentrations of the CYP3A4 substrate could lead to therapeutic failure and serious clinical consequences. Consider therapy modification
Lumateperone: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Lumateperone. Avoid combination
Lurasidone: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Lurasidone. Management: Lurasidone US labeling recommends reducing lurasidone dose by half with a moderate CYP3A4 inhibitor. Some non-US labeling recommends initiating lurasidone at 20 mg/day and limiting dose to 40 mg/day; avoid concurrent use of grapefruit products. Consider therapy modification
Manidipine: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Manidipine. Monitor therapy
Meperidine: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Meperidine. Monitor therapy
Mirodenafil: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Mirodenafil. Monitor therapy
Naldemedine: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Naldemedine. Monitor therapy
Nalfurafine: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Nalfurafine. Monitor therapy
Naloxegol: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Naloxegol. Avoid combination
Neratinib: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Neratinib. Avoid combination
NiMODipine: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of NiMODipine. Monitor therapy
Olaparib: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Olaparib. Management: Avoid use of moderate CYP3A4 inhibitors in patients being treated with olaparib, if possible. If such concurrent use cannot be avoided, the dose of olaparib should be reduced to 150 mg twice daily. Consider therapy modification
OxyCODONE: CYP3A4 Inhibitors (Moderate) may enhance the adverse/toxic effect of OxyCODONE. CYP3A4 Inhibitors (Moderate) may increase the serum concentration of OxyCODONE. Serum concentrations of the active metabolite Oxymorphone may also be increased. Monitor therapy
Palbociclib: May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors). Monitor therapy
PARoxetine: May decrease the serum concentration of Aprepitant. Aprepitant may decrease the serum concentration of PARoxetine. Monitor therapy
Pexidartinib: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Pexidartinib. Monitor therapy
Pimecrolimus: CYP3A4 Inhibitors (Moderate) may decrease the metabolism of Pimecrolimus. Monitor therapy
Pimozide: Aprepitant may increase the serum concentration of Pimozide. Avoid combination
Progestins (Contraceptive): Aprepitant may decrease the serum concentration of Progestins (Contraceptive). Management: Alternative or additional methods of contraception should be used both during treatment with aprepitant or fosaprepitant and for at least one month following the last aprepitant/fosaprepitant dose. Consider therapy modification
Propafenone: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Propafenone. Management: Drugs listed as exceptions to this monograph are discussed in further detail in separate drug interaction monographs. Monitor therapy
Ranolazine: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Ranolazine. Management: Limit the ranolazine adult dose to a maximum of 500 mg twice daily in patients concurrently receiving moderate CYP3A4 inhibitors (e.g., diltiazem, verapamil, erythromycin, etc.). Consider therapy modification
Rupatadine: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Rupatadine. Monitor therapy
Ruxolitinib: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Ruxolitinib. Monitor therapy
Salmeterol: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Salmeterol. Monitor therapy
Sarilumab: May decrease the serum concentration of CYP3A4 Substrates (High risk with Inducers). Monitor therapy
SAXagliptin: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of SAXagliptin. Monitor therapy
Sildenafil: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Sildenafil. Monitor therapy
Silodosin: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Silodosin. Monitor therapy
Siltuximab: May decrease the serum concentration of CYP3A4 Substrates (High risk with Inducers). Monitor therapy
Simeprevir: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Simeprevir. Avoid combination
Sirolimus: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Sirolimus. Management: Monitor for increased serum concentrations of sirolimus if combined with a moderate CYP3A4 inhibitor. Lower initial sirolimus doses or sirolimus dose reductions will likely be required. Consider therapy modification
Sonidegib: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Sonidegib. Management: Avoid concomitant use of sonidegib and moderate CYP3A4 inhibitors when possible. When concomitant use cannot be avoided, limit CYP3A4 inhibitor use to less than 14 days and monitor for sonidegib toxicity (particularly musculoskeletal adverse reactions). Consider therapy modification
Stiripentol: May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors). Management: Use of stiripentol with CYP3A4 substrates that are considered to have a narrow therapeutic index should be avoided due to the increased risk for adverse effects and toxicity. Any CYP3A4 substrate used with stiripentol requires closer monitoring. Consider therapy modification
Suvorexant: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Suvorexant. Management: The recommended dose of suvorexant is 5 mg daily in patients receiving a moderate CYP3A4 inhibitor. The dose can be increased to 10 mg daily (maximum dose) if necessary for efficacy. Consider therapy modification
Tamsulosin: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Tamsulosin. Monitor therapy
Tazemetostat: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Tazemetostat. Management: Avoid coadministration of tazemetostat and moderate CYP3A4 inhibitors. If coadministration cannot be avoided, dose reductions are required. See full monograph for dosing recommendations. Consider therapy modification
Terfenadine: Aprepitant may increase the serum concentration of Terfenadine. Avoid combination
Tetrahydrocannabinol: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Tetrahydrocannabinol. Monitor therapy
Tezacaftor and Ivacaftor: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Tezacaftor and Ivacaftor. Management: When combined with moderate CYP3A4 inhibitors, tezacaftor/ivacaftor should be given in the morning, every other day. Ivacaftor alone should be given in the morning, every other day on alternate days. Consider therapy modification
Ticagrelor: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Ticagrelor. Monitor therapy
Tocilizumab: May decrease the serum concentration of CYP3A4 Substrates (High risk with Inducers). Monitor therapy
Tofacitinib: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Tofacitinib. Monitor therapy
TOLBUTamide: Aprepitant may decrease the serum concentration of TOLBUTamide. Monitor therapy
Tolvaptan: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Tolvaptan. Management: Jynarque dose requires adjustment when used with a moderate CYP3A4 inhibitor. See labeling or full interaction monograph for specific recommendations. Use of Samsca with moderate CYP3A4 ihibitors should generally be avoided. Consider therapy modification
Trabectedin: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Trabectedin. Monitor therapy
Triazolam: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Triazolam. Management: Consider triazolam dose reduction in patients receiving concomitant moderate CYP3A4 inhibitors. Consider therapy modification
Ubrogepant: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Ubrogepant. Management: Use an initial ubrogepant dose of 50 mg and avoid a second dose for 24 hours when used with moderate CYP3A4 inhibitors. Consider therapy modification
Udenafil: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Udenafil. Monitor therapy
Ulipristal: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Ulipristal. Management: This is specific for when ulipristal is being used for signs/symptoms of uterine fibroids (Canadian indication). When ulipristal is used as an emergency contraceptive, patients receiving this combination should be monitored for ulipristal toxicity. Avoid combination
Venetoclax: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Venetoclax. Management: Reduce the venetoclax dose by at least 50% in patients requiring these combinations. Consider therapy modification
Vilazodone: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Vilazodone. Monitor therapy
Vindesine: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Vindesine. Monitor therapy
Warfarin: Aprepitant may decrease the serum concentration of Warfarin. Monitor therapy
Zanubrutinib: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Zanubrutinib. Management: Decrease the zanubrutinib dose to 80 mg twice daily during coadministration with a moderate CYP3A4 inhibitor. Further dose adjustments may be required for zanubrutinib toxicities, refer to prescribing information for details. Consider therapy modification
Zopiclone: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Zopiclone. Management: The starting adult dose of zopiclone should not exceed 3.75 mg if combined with a moderate CYP3A4 inhibitor. Monitor patients for signs and symptoms of zopiclone toxicity if these agents are combined. Consider therapy modification
Zuclopenthixol: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Zuclopenthixol. Monitor therapy
Adverse Reactions
Adverse reactions may be reported in combination with other antiemetic agents. As reported for highly emetogenic cancer chemotherapy or moderately emetogenic cancer chemotherapy, unless otherwise noted as reported for postoperative nausea and vomiting (PONV).
>10%:
Central nervous system: Fatigue (adults: 1% to 13%; children & adolescents: 5%)
Hematologic & oncologic: Neutropenia (children & adolescents: 13%; adults: <3%)
1% to 10%:
Cardiovascular: Hypotension (PONV: 6%), bradycardia (PONV: <3%), flushing (<3%), palpitations (<3%), peripheral edema (<3%), syncope (PONV: <3%)
Central nervous system: Headache (children & adolescents: 9%), dizziness (<3% to 5%), anxiety (<3%), hypoesthesia (PONV: <3%), hypothermia (PONV: <3%), malaise (<3%), peripheral neuropathy (<3%), abnormal behavior (children & adolescents: 2%), agitation (children & adolescents: 2%)
Dermatologic: Pruritus (3%), alopecia (<3%), hyperhidrosis (<3%), skin rash (<3%), urticaria (<3%)
Endocrine & metabolic: Dehydration (≤3%), decreased serum albumin (PONV: <3%), decreased serum potassium (PONV: <3%), decreased serum sodium (<3%), hot flash (<3), hypokalemia (<3%), hypovolemia (PONV: <3%), increased serum glucose (PONV: <3%), weight loss (<3%)
Gastrointestinal: Constipation (PONV: ≤9%), diarrhea (6% to 9%), dyspepsia (≤7%), abdominal pain (≤6%), hiccups (4% to 5%), decreased appetite (<3% to 5%), dysgeusia (<3%), eructation (<3%), flatulence (<3%), gastritis (<3%), gastroesophageal reflux disease (<3%), nausea (<3%), vomiting (<3%), xerostomia (<3%)
Genitourinary: Proteinuria (<3%)
Hematologic & oncologic: Decreased hemoglobin (children & adolescents: 5%), decreased white blood cell count (≤4%), anemia (<3%), febrile neutropenia (<3%), hematoma (PONV: <3%), thrombocytopenia (<3%)
Hepatic: Increased serum alanine aminotransferase (3%), increased serum alkaline phosphatase (<3%), increased serum aspartate aminotransferase (<3%), increased serum bilirubin (PONV: <3%)
Infection: Candidiasis (<3%), postoperative infection (PONV: <3%)
Local: Induration at injection site (3%), inflammation at injection site (3%), infusion site reaction (3%)
Neuromuscular & skeletal: Asthenia (≤7%), musculoskeletal pain (<3%)
Renal: Increased blood urea nitrogen (<3%)
Respiratory: Cough (<3% to 5%), dyspnea (<3%), hypoxia (PONV: <3%), oropharyngeal pain (<3%), pharyngitis (<3%), respiratory depression (PONV: <3%)
Miscellaneous: Wound dehiscence (PONV: <3%)
<1%, postmarketing, and/or case reports: Abdominal distention, abnormal dreams, abnormal gait, acne vulgaris, anaphylaxis, angioedema, anxiety, cardiac disease, chest discomfort, chills, cognitive dysfunction, conjunctivitis, decreased neutrophils, disorientation, drowsiness, dysfunction, dysuria, edema, epigastric distress, euphoria, hematuria, hyperglycemia, hypersensitivity reaction, hyponatremia, increased thirst, lethargy, muscle cramps, myalgia, neutropenic enterocolitis, oily skin, perforated duodenal ulcer, pollakiuria, polyuria, polydipsia, post nasal drip, skin lesion, skin photosensitivity, sneezing, staphylococcal infection, Stevens-Johnson syndrome, stomatitis, throat irritation, tinnitus, toxic epidermal necrolysis, weight gain
Warnings/Precautions
Concerns related to adverse effects:
- Hypersensitivity: Hypersensitivity reactions, including anaphylactic reactions, have been reported. Symptoms have included dyspnea, erythema, eye swelling, flushing, hypotension, pruritus, syncope, and wheezing. Monitor for hypersensitivity reaction during and following infusion; if a reaction occurs, discontinue infusion and manage appropriately. Do not re-initiate.
Disease-related concerns:
- Hepatic impairment: Use with caution in patients with severe hepatic impairment (Child-Pugh class C); has not been studied.
Concurrent drug therapy issues:
- Drug-drug interactions: Potentially significant interactions may exist, requiring dose or frequency adjustment, additional monitoring, and/or selection of alternative therapy. Consult drug interactions database for more detailed information. A clinically significant decrease in INR or PT may occur with concurrent warfarin therapy; monitor INR/PT for 2 weeks (particularly at 7 to 10 days) following aprepitant administration in each chemotherapy cycle.
Special populations:
- Pediatrics: For prevention of chemotherapy-induced nausea and vomiting, oral suspension use is not recommended in pediatric patients weighing <6 kg. Generic aprepitant capsules are not approved for use in pediatric patients.
Dosage form specific issues:
- Aprepitant IV: The IV aprepitant formulation is an emulsion that also contains the excipients alcohol, egg lecithin, soybean oil, and sucrose.
Monitoring Parameters
In patients receiving concurrent warfarin, monitor INR/PT for 2 weeks (particularly at 7 to 10 days) following aprepitant administration; monitor for signs/symptoms of hypersensitivity reaction.
Pregnancy
Pregnancy Considerations
The injection formulation contains ethanol; use should be avoided in females who are pregnant.
Efficacy of hormonal contraceptive may be reduced during and for 28 days following the last aprepitant dose; alternative or additional effective methods of contraception should be used both during treatment with aprepitant and for at least 1 month following the last aprepitant dose.
Patient Education
What is this drug used for?
- It is used to prevent upset stomach and throwing up.
Frequently reported side effects of this drug
- Loss of strength and energy
- Diarrhea
- Lack of appetite
- Abdominal pain
- Hiccups
- Constipation
- Headache
- Heartburn
Other side effects of this drug: Talk with your doctor right away if you have any of these signs of:
- Infection
- Severe dizziness
- Passing out
- Dry mouth
- Dry eyes
- Increased thirst
- Stevens-Johnson syndrome/toxic epidermal necrolysis like red, swollen, blistered, or peeling skin (with or without fever); red or irritated eyes; or sores in mouth, throat, nose, or eyes.
- Signs of a significant reaction like wheezing; chest tightness; fever; itching; bad cough; blue skin color; seizures; or swelling of face, lips, tongue, or throat.
Note: This is not a comprehensive list of all side effects. Talk to your doctor if you have questions.
Consumer Information Use and Disclaimer: This information should not be used to decide whether or not to take this medicine or any other medicine. Only the healthcare provider has the knowledge and training to decide which medicines are right for a specific patient. This information does not endorse any medicine as safe, effective, or approved for treating any patient or health condition. This is only a brief summary of general information about this medicine. It does NOT include all information about the possible uses, directions, warnings, precautions, interactions, adverse effects, or risks that may apply to this medicine. This information is not specific medical advice and does not replace information you receive from the healthcare provider. You must talk with the healthcare provider for complete information about the risks and benefits of using this medicine.
