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Aprepitant

Medically reviewed on March 25, 2018

Pronunciation

(ap RE pi tant)

Index Terms

  • L 754030
  • MK 869

Dosage Forms

Excipient information presented when available (limited, particularly for generics); consult specific product labeling.

Capsule, Oral:

Emend: 40 mg, 80 mg, 125 mg

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)

Brand Names: U.S.

  • Cinvanti
  • Emend
  • Emend Tri-Pack

Pharmacologic Category

  • Antiemetic
  • Substance P/Neurokinin 1 Receptor Antagonist

Pharmacology

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.

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%

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 highly emetogenic chemotherapy, including high-dose cisplatin (initial and repeat courses; in combination with other antiemetics) in adults.

Prevention of nausea and vomiting associated with moderately emetogenic chemotherapy (initial and repeat courses; 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).

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).

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.

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: 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 nausea/vomiting associated with moderately-emetogenic chemotherapy:

IV: 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 (PONV): Oral: 40 mg within 3 hours prior to anesthesia induction

Dosing: Geriatric

Refer to adult dosing.

Dosing: Pediatric

Manufacturer's labeling:

Prevention of acute and delayed nausea and 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 and 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 Oncology Group of Ontario (POGO) guidelines: Recommended antiemetic regimen combinations in pediatric patients ≥6 months receiving chemotherapy agents that do not potentially interact with aprepitant (Dupuis 2013; Patel 2017):

High emetogenic risk: Aprepitant (oral), plus ondansetron or granisetron or palonosetron, plus dexamethasone.

High emetogenic risk and cannot receive corticosteroids (due to contraindications): Aprepitant (oral) plus palonosetron.

Moderate emetogenic risk and cannot receive corticosteroids (due to contraindications): Aprepitant (oral) plus ondansetron or granisetron or palonosetron.

Infants ≥6 months, Children, and Adolescents: Oral: 3 mg/kg (maximum dose: 125 mg) on day 1 prior to chemotherapy, followed by 2 mg/kg (maximum dose: 80 mg) once daily on days 2 and 3.

Dosing: Renal Impairment

No dosage adjustment necessary.

ESRD undergoing dialysis: No dosage adjustment necessary. Aprepitant is not removed by hemodialysis (<0.2% of a dose is recovered in the dialysate).

Dosing: Hepatic Impairment

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.

Reconstitution

Prepare the injection 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.

Injection (130 mg): Prepare a non-PVC infusion bag with 130 mL of NS or D5W; aseptically withdraw 18 mL from the aprepitant injection vial and transfer into the infusion bag to yield a total volume of 148 mL; gently invert 4 to 5 times (avoid shaking).

Injection (100 mg): Prepare a non-PVC infusion bag with 100 mL of NS or D5W; aseptically withdraw 14 mL from the aprepitant injection vial and transfer into the infusion bag to yield a total volume of 114 mL; 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

A suspension for oral administration is commercially available.

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):701-6.19043742

Administration

IV: Infuse over 30 minutes approximately one-half hour (30 minutes) prior to chemotherapy. Use only non-DEHP tubing for administration. Administration information is for aprepitant IV (Cinvanti); refer to fosaprepitant IV (Emend IV) monograph for fosaprepitant administration.

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 (oral): Administer within 3 hours prior to induction; follow health care provider instructions about food/drink restrictions prior to surgery.

Storage

Injection: Store intact vials at 2°C to 8°C (36°F to 46°F); do not freeze. Vials may remain at room temperature for up to 60 days. 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.

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.

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

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

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

Ceritinib: May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors). Management: Use of ceritinib with a narrow therapeutic index CYP3A substrate (eg, alfentanil, cyclosporine, dihydroergotamine, ergotamine, fentanyl, pimozide, quinidine, sirolimus, tacrolimus) should be avoided when possible. 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

Codeine: CYP3A4 Inhibitors (Moderate) may decrease 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

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

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: May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors). Monitor therapy

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 cardiac status (eg, ECG), should be used with concurrent use of halofantrine with any moderate CYP3A4 inhibitor(s). 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: When treating B-cell malignancies, decrease ibrutinib to 140 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 are required; consult full monograph content for specific age- and weight-based recommendations. No dose adjustment is needed when using ivacaftor/lumacaftor with a moderate CYP3A4 inhibitor. Consider therapy modification

Lomitapide: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Lomitapide. 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

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

Pimecrolimus: CYP3A4 Inhibitors (Moderate) may decrease the metabolism of Pimecrolimus. Monitor therapy

Pimozide: Aprepitant may increase the serum concentration of Pimozide. Avoid combination

Pitolisant: May decrease the serum concentration of CYP3A4 Substrates (High risk with Inducers). Management: Combined use of pitolisant with a CYP3A4 substrate that has a narrow therapeutic index should be avoided. Other CYP3A4 substrates should be monitored more closely when used with pitolisant. Consider therapy modification

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. 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

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: 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 John's Wort: May decrease the serum concentration of CYP3A4 Substrates (High risk with Inducers). 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 (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. Consider therapy modification

Tamsulosin: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Tamsulosin. Monitor therapy

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: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Tezacaftor. Management: When combined with moderate CYP3A4 inhibitors, tezacaftor/ivacaftor (100 mg/150 mg) should be given in the morning, every other day. Ivacaftor (150 mg) alone should be given in the evening, every other day, on alternate days from tezacaftor/ivacaftor. 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

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

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

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 ALT (3%), increased serum alkaline phosphatase (<3%), increased serum AST (<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: 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%)

<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 with fosaprepitant or oral aprepitant. Symptoms have included flushing, erythema, dyspnea, hypotension, and syncope. Monitor for hypersensitivity reaction during and following infusion; if a reaction occurs, discontinue infusion and manage appropriately. Do not re-initiate aprepitant IV if hypersensitivity symptoms occur during the initial infusion.

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 prothrombin time (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, use is not recommended in pediatric patients weighing <6 kg. Not approved for prevention of postoperative nausea and vomiting in children.

Dosage form specific issues:

• Aprepitant IV: The IV aprepitant formulation is an emulsion which 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 Considerations

Adverse events were not observed in animal reproduction studies. 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 fosaprepitant or aprepitant and for at least 1 month following the last fosaprepitant/aprepitant dose.

Patient Education

• 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, increased thirst, 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.

Further information

Always consult your healthcare provider to ensure the information displayed on this page applies to your personal circumstances.

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