(ap RE pi tant)
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).
Postoperative nausea and vomiting: Prevention of postoperative nausea and vomiting (PONV) in adults.
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).
Hypersensitivity to aprepitant or any component of the formulation; concurrent use with pimozide
Canadian labeling: Additional contraindications (not in US labeling): Concurrent use with astemizole, cisapride, or terfenadine.
Prevention of chemotherapy-induced nausea/vomiting:
Manufacturers labeling:
Prevention of acute and delayed nausea/vomiting associated with highly-emetogenic chemotherapy:
Capsules: Oral: 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: Oral: 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 nausea/vomiting associated with moderately-emetogenic chemotherapy:
Capsules: Oral: 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: Oral: 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; Basch, 2011): 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 (MASCC) and European Society of Medical Oncology (ESMO) (Roila, 2010): 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 day 1 only [AC regimen])
Prevention of postoperative nausea/vomiting (PONV): Oral: 40 mg within 3 hours prior to anesthesia induction
Refer to adult dosing.
Manufacturers labeling:
Prevention of acute and delayed nausea/vomiting associated with highly-emetogenic chemotherapy:
Capsules: Children ≥12 years, and Adolescents: Oral: 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 [reduce dexamethasone dose to 50% of recommended dose])
Suspension: Infants ≥6 months (and ≥6 kg), Children <12 years (and ≥6 kg) and patients (any age and ≥6 kg) unable to swallow capsules: Oral: 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 [reduce dexamethasone dose to 50% of recommended dose])
Prevention of nausea/vomiting associated with moderately-emetogenic chemotherapy:
Capsules: Children ≥12 years, and Adolescents: Oral: 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 [reduce dexamethasone dose to 50% of recommended dose])
Suspension: Infants ≥6 months (and ≥6 kg), Children <12 years (and ≥6 kg) and patients (any age and ≥6 kg) unable to swallow capsules: Oral: 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 [reduce dexamethasone dose to 50% of recommended dose])
Pediatric guideline recommendations:Prevention of nausea/vomiting associated with highly-emetogenic chemotherapy: Pediatric Oncology Group of Ontario (POGO): Children ≥12 years and Adolescents: Oral: 125 mg prior to chemotherapy on day 1, followed by 80 mg once daily on days 2 and 3 (Dupuis 2013). The antiemetic regimen also includes a 5-HT3 antagonist and dexamethasone.
No dosage adjustment necessary.
ESRD undergoing dialysis: No dosage adjustment necessary. Aprepitant is not removed by hemodialysis.
Mild-to-moderate impairment (Child-Pugh class A or B): No dosage adjustment necessary.
Severe impairment (Child-Pugh class C): Use with caution; no data available; may require additional monitoring for adverse reactions.
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. 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 manufacturers instructions for further preparation details.
Capsules: Swallow whole.
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).
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: Administer within 3 hours prior to induction; follow health care provider instructions about food/drink restrictions prior to surgery.
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.
Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Capsule, Oral:
Emend: 40 mg, 80 mg, 125 mg, 80 mg & 125 mg
Suspension Reconstituted, Oral:
Emend: 125 mg (1 ea)
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 10-15 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.[PMID: 19043742]A suspension for oral administration is commercially available.
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
Blonanserin: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Blonanserin. Monitor therapy
Bosentan: May decrease the serum concentration of CYP3A4 Substrates. 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
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
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
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
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. Use extra caution in patients with impaired renal and/or hepatic function. Consider therapy modification
Conivaptan: May increase the serum concentration of CYP3A4 Substrates. Avoid combination
Contraceptives (Estrogens): Aprepitant may decrease the serum concentration of Contraceptives (Estrogens). Management: Use of a non-hormone-based contraceptive is recommended. Consider therapy modification
Contraceptives (Progestins): Aprepitant may decrease the serum concentration of Contraceptives (Progestins). 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
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
CYP2C9 Substrates: CYP2C9 Inducers (Strong) may increase the metabolism of CYP2C9 Substrates. Management: Consider an alternative for one of the interacting drugs. Some combinations may be specifically contraindicated. Consult appropriate manufacturer labeling. Consider therapy modification
CYP3A4 Inducers (Moderate): May decrease the serum concentration of CYP3A4 Substrates. 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: Aprepitant may increase the serum concentration of CYP3A4 Substrates. Monitor therapy
Dabrafenib: May decrease the serum concentration of CYP3A4 Substrates. 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/day when used together with a moderate inhibitor of CYP3A4. Consider therapy modification
Dasatinib: May increase the serum concentration of CYP3A4 Substrates. Monitor therapy
Deferasirox: May decrease the serum concentration of CYP3A4 Substrates. Monitor therapy
Diclofenac (Systemic): CYP2C9 Inducers (Strong) may decrease the serum concentration of Diclofenac (Systemic). 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. 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
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
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
Everolimus: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Everolimus. Management: Everolimus dose reductions are required for patients being treated for subependymal giant cell astrocytoma or renal cell carcinoma. See 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: May increase the serum concentration of CYP3A4 Substrates. Monitor therapy
Fusidic Acid (Systemic): May increase the serum concentration of CYP3A4 Substrates. 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. Consider therapy modification
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: If a moderate CYP3A inhibitor must be used, consider reducing the dose of ibrutinib to 140mg daily and monitor closely for signs of toxicity. Avoid combination
Idelalisib: May increase the serum concentration of CYP3A4 Substrates. 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 are required; consult prescribing information for specific age- and weight-based recommendations. Consider therapy modification
Lomitapide: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Lomitapide. Avoid combination
Luliconazole: May increase the serum concentration of CYP3A4 Substrates. Monitor therapy
Lurasidone: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Lurasidone. Management: U.S. labeling: start at 20 mg/day and limit to max of 80 mg/day with moderate CYP3A4 inhibitor. Canadian labeling: limit to max of 40 mg/day with moderate CYP3A4 inhibitor; avoid concomitant use of grapefruit products. Consider therapy modification
Mirodenafil: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Mirodenafil. Monitor therapy
Naloxegol: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Naloxegol. 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 such concurrent use cannot be avoided, the dose of olaparib should be reduced to 200 mg twice daily. Avoid combination
Osimertinib: May increase the serum concentration of CYP3A4 Substrates. Osimertinib may decrease the serum concentration of CYP3A4 Substrates. Monitor therapy
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. Monitor therapy
PARoxetine: May decrease the serum concentration of Aprepitant. Aprepitant may decrease the serum concentration of PARoxetine. 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
Propafenone: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Propafenone. 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
Salmeterol: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Salmeterol. 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
Siltuximab: May decrease the serum concentration of CYP3A4 Substrates. Monitor therapy
Simeprevir: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Simeprevir. Avoid combination
Sirolimus: Aprepitant may increase the serum concentration of Sirolimus. Monitor therapy
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
St Johns Wort: May decrease the serum concentration of CYP3A4 Substrates. Management: Consider an alternative for one of the interacting drugs. Some combinations may be specifically contraindicated. Consult appropriate manufacturer labeling. Consider therapy modification
Stiripentol: May increase the serum concentration of CYP3A4 Substrates. 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. 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
Ticagrelor: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Ticagrelor. Monitor therapy
Tocilizumab: May decrease the serum concentration of CYP3A4 Substrates. Monitor therapy
TOLBUTamide: Aprepitant may decrease the serum concentration of TOLBUTamide. Monitor therapy
Tolvaptan: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Tolvaptan. Avoid combination
Trabectedin: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Trabectedin. Avoid combination
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
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
In patients receiving concurrent warfarin, monitor INR/PT for 2 weeks (particularly at 7 to 10 days) following aprepitant administration; signs/symptoms of hypersensitivity reaction.
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: 13%; children & adolescents: 5%)
Hematologic & oncologic: Neutropenia (children & adolescents: 13%; adults: <3%)
0.5% 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: 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 ALT (3%), increased serum alkaline phosphatase (<3%), increased serum AST (<3%), increased serum bilirubin (PONV: <3%)
Infection: Candidiasis (<3%), postoperative infection (PONV: <3%)
Neuromuscular & skeletal: Weakness ( ≤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%)
<0.5% (Limited to important or life-threatening): Anaphylaxis, angioedema, hypersensitivity reaction, pruritus, Stevens-Johnson syndrome, toxic epidermal necrolysis
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.
Following oral administration of aprepitant 125 mg on day 1 and 80 mg once daily on days 2 and 3 to patients with mild hepatic impairment (Child-Pugh score 5 to 6), the AUC of aprepitant was 11% lower on day 1 and 36% lower on day 3 compared with healthy subjects; in patients with moderate hepatic impairment (Child-Pugh score 7 to 9), the AUC of aprepitant was 10% higher on day 1 and 18% higher on day 3. These differences are not considered clinically meaningful.
Following oral administration of aprepitant 125 mg on day 1 and 80 mg once daily on days 2 through 5, the AUC of aprepitant was 21% higher on day 1 and 36% higher on day 5; the Cmax was 10% higher on day 1 and 24% higher on day 5. These differences are not considered clinically meaningful.
Following a single oral aprepitant dose ranging from 40 to 375 mg, the AUC was 14% higher and the Cmax was 22% higher in women (compared to males); the half-life of aprepitant is 25% lower in females; the Tmax occurs at approximately the same time. These differences are not considered clinically meaningful.
Following a single oral aprepitant dose ranging from 40 to 375 mg, the AUC of aprepitant was ~42% higher and the Cmax was ~29% higher in Hispanic patients compared to Caucasians (there was no difference in AUC and Cmax between Black patients and Caucasians). The AUC of aprepitant was ~62% higher and the Cmax was ~41% higher in Asian patients compared to Caucasians. These differences are not considered clinically meaningful.
Obesity: In patients with BMI ranging from 18 to 36 kg/m2, for every 5 kg/m2 increase in BMI, the AUC and Cmax of aprepitant decreased by 11%. These differences are not considered clinically meaningful.
Concerns related to adverse effects:
- Hypersensitivity: Hypersensitivity reactions, including anaphylactic reactions have been reported.
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. Due to a risk of significantly increased pimozide plasma concentrations and potential for QT prolongation, concurrent use with pimozide is contraindicated. Other CYP3A4-mediated drug interactions may occur. In patients receiving concurrent warfarin, a clinically significant decrease in INR or prothrombin time (PT) may occur; monitor INR/PT for 2 weeks (particularly at 7 to 10 days) following aprepitant administration.
Special populations:
- Pediatrics: For prevention of chemotherapy-induced nausea and vomiting, use is not recommended in pediatric patients weighing <6 kg. Not approved for prevention of postoperative nausea and vomiting in children.
Adverse events were not observed in animal reproduction studies. 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 fosaprepitant or aprepitant and for at least 1 month following the last fosaprepitant/aprepitant dose.
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.
Vd: ~70 L; crosses the blood-brain barrier
Extensively hepatic via CYP3A4 (major); CYP1A2 and CYP2C19 (minor); forms 7 metabolites (weakly active)
Primarily via metabolism
Plasma: Pediatric: Capsule: ~4 hours; Suspension ~6 hours; Adults: 40 mg: ~3 hours; 125 mg followed by 80 mg for 2 days: ~4 hours
Terminal: ~9 to 13 hours
>95%
- Discuss specific use of drug and side effects with patient as it relates to treatment. (HCAHPS: During this hospital stay, were you given any medicine that you had not taken before? Before giving you any new medicine, how often did hospital staff tell you what the medicine was for? How often did hospital staff describe possible side effects in a way you could understand?)
- Patient may experience loss of strength and energy, diarrhea, lack of appetite, abdominal pain, hiccups, constipation, headache, or heartburn. Have patient report immediately to prescriber signs of infection, severe dizziness, passing out, dry mouth, dry eyes, thirsty, or signs of Stevens-Johnson syndrome/toxic epidermal necrolysis (red, swollen, blistered, or peeling skin [with or without fever]; red or irritated eyes; or sores in mouth, throat, nose, or eyes) (HCAHPS).
- Educate patient about signs of a significant reaction (eg, 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. Patient should consult prescriber for additional questions.
Intended Use and Disclaimer: Should not be printed and given to patients. This information is intended to serve as a concise initial reference for healthcare professionals to use when discussing medications with a patient. You must ultimately rely on your own discretion, experience and judgment in diagnosing, treating and advising patients.