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Pronunciation
(ap RE pi tant)
Generic Available (U.S.)
No
Index Terms
U.S. Brand Names
Canadian Brand Names
Pharmacologic Category
Pharmacologic Category Synonyms
Use: Labeled Indications
Prevention of acute and delayed nausea and vomiting associated with moderately- and highly-emetogenic chemotherapy (in combination with other antiemetics); prevention of postoperative nausea and vomiting (PONV)
Pregnancy Risk Factor
B
Pregnancy Considerations
Teratogenic effects were not observed in animal studies. There are no adequate and well-controlled studies in pregnant women; use only if clearly needed. Efficacy of hormonal contraceptive may be reduced; alternative or additional 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.
Lactation
Excretion in breast milk unknown/not recommended
Contraindications
Hypersensitivity to aprepitant or any component of the formulation; concurrent use with cisapride or pimozide
Warnings/Precautions
Disease-related concerns:
• Hepatic impairment: Use with caution in patients with severe hepatic impairment; has not been studied in patients with severe hepatic impairment (Child-Pugh class C).
• Nausea/vomiting: Appropriate use: Not studied for treatment of existing nausea and vomiting. Chronic continuous administration is not recommended.
Concurrent drug therapy issues:
• High potential for interactions: Use with caution in patients taking strong CYP3A4 inhibitors, moderate or strong CYP3A4 inducers and major CYP3A4 substrates; consider alternative agents that avoid or lessen the potential for CYP-mediated interactions. The effect on orally administered CYP3A4 substrates is greater than those administered intravenously. A single 40 mg aprepitant oral dose is not likely to alter plasma concentrations of CYP3A4 substrates.
Adverse Reactions
Note: Adverse reactions reported as part of a combination chemotherapy regimen or with general anesthesia.
>10%:
Central nervous system: Fatigue (≤18%)
Gastrointestinal: Nausea (6% to 13%), constipation (9% to 10%)
Neuromuscular & skeletal: Weakness (≤18%)
Miscellaneous: Hiccups (11%)
1% to 10%:
Cardiovascular: Hypotension (≤6%), bradycardia (≤4%)
Central nervous system: Dizziness (≤7%)
Endocrine & metabolic: Dehydration (≤6%)
Gastrointestinal: Diarrhea (≤10%), dyspepsia (≤6%), abdominal pain (≤5%), epigastric discomfort (4%), gastritis (4%), stomatitis (3%)
Hepatic: ALT increased (≤6%), AST increased (3%)
Renal: Proteinuria (7%), BUN increased (5%)
>0.5%: Acid reflux, acne, albumin decreased, alkaline phosphatase increased, anemia, anxiety, appetite decreased, arthralgia, back pain, bilirubin increased, candidiasis, confusion, conjunctivitis, cough, deglutition disorder, depression, diabetes mellitus, diaphoresis, DVT, dysphagia, dyspnea, dysuria, edema, eructation, erythrocyturia, febrile neutropenia, flatulence, flushing, glucosuria, herpes simplex, hyperglycemia, hypertension, hypoesthesia, hypokalemia, hyponatremia, hypothermia, hypovolemia, hypoxia, leukocytes increased, leukocyturia, malaise, MI, muscular weakness, musculoskeletal pain, myalgia, nasal secretion, obstipation, pain, palpitation, pelvic pain, peripheral neuropathy, pharyngitis, pharyngolaryngeal pain, pneumonitis, pruritus, pulmonary embolism, rash, renal insufficiency, respiratory infection, respiratory insufficiency, rigors, salivation increased, sensory neuropathy, septic shock, syncope, tachycardia, taste disturbance, thrombocytopenia, tremor, urinary tract infection, urticaria, vocal disturbance, weight loss, xerostomia
<0.5%, postmarketing, and/or case reports: Anaphylactic reaction, angioedema, disorientation, duodenal ulcer (perforating), dysarthria, enterocolitis, hypersensitivity reaction, miosis, neutropenic sepsis, pneumonia, sensory disturbance, Stevens-Johnson syndrome, visual acuity decreased, wheezing
Metabolism/Transport Effects
Substrate of CYP1A2 (minor), 2C19 (minor), 3A4 (major); Inhibits CYP2C9 (weak), 2C19 (weak), 3A4 (moderate); Induces CYP2C9 (weak), 3A4 (weak)
Drug Interactions
Antifungal Agents (Azole Derivatives, Systemic): May decrease the metabolism of Aprepitant. Risk C: Monitor therapy
Benzodiazepines (metabolized by oxidation): Aprepitant may increase the serum concentration of Benzodiazepines (metabolized by oxidation). Risk C: Monitor therapy
Budesonide (Systemic, Oral Inhalation): CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Budesonide (Systemic, Oral Inhalation). Management: Consider reducing the oral budesonide dose when used together with a CYP3A4 inhibitor. This interaction is likely less severe with orally inhaled budesonide. Monitor patients closely for signs/symptoms of corticosteroid excess. Risk D: Consider therapy modification
Cisapride: Aprepitant may increase the serum concentration of Cisapride. Risk X: 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. Risk D: Consider therapy modification
Conivaptan: May increase the serum concentration of CYP3A4 Substrates. Management: Upon completion/discontinuation of conivaptan, allow at least 7 days before initiating therapy with drugs that are CYP3A4 substrates. Risk D: Consider therapy modification
Contraceptives (Estrogens): Aprepitant may decrease the serum concentration of Contraceptives (Estrogens). Management: Use of a non-hormone-based contraceptive is recommended. Risk D: 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. Risk D: Consider therapy modification
Corticosteroids (Systemic): Aprepitant may increase the serum concentration of Corticosteroids (Systemic). Risk D: Consider therapy modification
CYP2C9 Substrates (High risk): CYP2C9 Inducers (Highly Effective) may increase the metabolism of CYP2C9 Substrates (High risk). Risk C: Monitor therapy
CYP3A4 Inducers (Strong): May increase the metabolism of CYP3A4 Substrates. Risk C: Monitor therapy
CYP3A4 Inhibitors (Moderate): May decrease the metabolism of CYP3A4 Substrates. Risk C: Monitor therapy
CYP3A4 Inhibitors (Strong): May decrease the metabolism of CYP3A4 Substrates. Risk D: Consider therapy modification
CYP3A4 Substrates: CYP3A4 Inhibitors (Moderate) may decrease the metabolism of CYP3A4 Substrates. Risk C: Monitor therapy
Dasatinib: May increase the serum concentration of CYP3A4 Substrates. Risk C: Monitor therapy
Deferasirox: May decrease the serum concentration of CYP3A4 Substrates. Risk C: Monitor therapy
Diltiazem: Aprepitant may increase the serum concentration of Diltiazem. Diltiazem may increase the serum concentration of Aprepitant. Risk C: Monitor therapy
Eplerenone: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Eplerenone. Management: A lower starting dose of eplerenone (25 mg once daily for adults) is recommended in patients with hypertension who are also taking drugs that are moderate inhibitors of CYP3A4. Risk D: 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. Risk D: Consider therapy modification
FentaNYL: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of FentaNYL. Management: Monitor patients extra closely for several days following initiation of the combination, and fentanyl dosage reductions should be made as appropriate. Risk D: Consider therapy modification
Halofantrine: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Halofantrine. Risk D: Consider therapy modification
Herbs (CYP3A4 Inducers): May increase the metabolism of CYP3A4 Substrates. Risk C: Monitor therapy
Lurasidone: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Lurasidone. Risk D: Consider therapy modification
PARoxetine: Aprepitant may decrease the serum concentration of PARoxetine. PARoxetine may decrease the serum concentration of Aprepitant. Risk C: Monitor therapy
Pimecrolimus: CYP3A4 Inhibitors (Moderate) may decrease the metabolism of Pimecrolimus. Risk C: Monitor therapy
Pimozide: Aprepitant may increase the serum concentration of Pimozide. Risk X: Avoid combination
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.). Risk D: Consider therapy modification
Rifamycin Derivatives: May increase the metabolism of Aprepitant. Risk C: Monitor therapy
Salmeterol: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Salmeterol. Risk C: Monitor therapy
Saxagliptin: CYP3A4 Inducers may decrease the serum concentration of Saxagliptin. Risk C: Monitor therapy
Saxagliptin: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Saxagliptin. Risk C: Monitor therapy
Tocilizumab: May decrease the serum concentration of CYP3A4 Substrates. Risk C: Monitor therapy
TOLBUTamide: Aprepitant may decrease the serum concentration of TOLBUTamide. Risk C: Monitor therapy
Tolvaptan: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Tolvaptan. Risk X: Avoid combination
Vilazodone: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Vilazodone. Risk C: Monitor therapy
Warfarin: Aprepitant may decrease the serum concentration of Warfarin. Risk C: Monitor therapy
Ethanol/Nutrition/Herb Interactions
Food: Aprepitant serum concentration may be increased when taken with grapefruit juice; avoid concurrent use.
Herb/Nutraceutical: Avoid St John's wort (may decrease aprepitant levels).
Storage
Store at room temperature of 20°C to 25°C (68°F to 77°F).
Mechanism of Action
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.
Pharmacodynamics/Kinetics
Distribution: Vd: ~70 L; crosses the blood brain barrier
Protein binding: >95%
Metabolism: Extensively hepatic via CYP3A4 (major); CYP1A2 and CYP2C19 (minor); forms 7 metabolites (weakly active)
Bioavailability: ~60% to 65%
Half-life elimination: Terminal: ~9-13 hours
Time to peak, plasma: ~3-4 hours
Dosage
Oral: Adults:
Prevention of chemotherapy-induced nausea/vomiting: 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 corticosteroid and 5-HT3 antagonist antiemetic)
Prevention of PONV: 40 mg within 3 hours prior to induction
Dosage adjustment in renal impairment: No dose adjustment necessary in patients with renal disease or end-stage renal disease maintained on hemodialysis.
Dosage adjustment in hepatic impairment:
Mild-to-moderate impairment (Child-Pugh classes A and B): No adjustment necessary
Severe impairment (Child-Pugh class C): Use caution; no data available
Administration: Oral
Chemotherapy induced nausea/vomiting: Administer with or without food. First dose should be given 1 hour prior to antineoplastic therapy; subsequent doses should be given in the morning.
PONV: Administer within 3 hours prior to induction; follow healthcare providers instructions about food/drink restrictions prior to surgery.
Dietary Considerations
May be taken with or without food.
Patient Education
This medication is intended to prevent or treat nausea/vomiting; it may be prescribed in combination with other medications; follow directions and timing exactly. May by taken with or without food; do not take with grapefruit juice. Report unusual fatigue, weakness, dizziness, disorientation, abdominal discomfort, chest pain, or respiratory distress to prescriber.
Geriatric Considerations
In two studies by the manufacturer, with a total of 544 patients, 31% were >65 years of age, while 5% were >75 years. No differences in safety and efficacy were noted between elderly subjects and younger adults. No dosing adjustment is necessary.
Additional Information
Oncology Comment: Aprepitant is recommended in the American Society of Clinical Oncology (ASCO) oncology antiemetic guidelines for use in combination with a serotonin receptor antagonist and dexamethasone for chemotherapy with high emetic risk and for chemotherapy regimens of moderate emetic risk which contain an anthracycline and cyclophosphamide (Kris, 2006). The National Comprehensive Cancer Network® (NCCN) Clinical Practice Guidelines in Oncology for Antiemesis (version 1.2011) recommend the same use of aprepitant as is in the ASCO recommendation. In addition to the moderately emetogenic chemotherapy listed above, the NCCN guidelines suggest that aprepitant may also be used for select moderately emetogenic regimens containing carboplatin, cisplatin, doxorubicin, epirubicin, ifosfamide, irinotecan and methotrexate. Either fosaprepitant 115 mg or aprepitant (125 mg orally) are administered on day 1; for day 2 and 3, patients should receive aprepitant 80 mg orally.
Dental Health: Effects on Dental Treatment
Key adverse event(s) related to dental treatment: Hiccups, stomatitis, and mucous membrane disorder.
Dental Health: Vasoconstrictor/Local Anesthetic Precautions
No information available to require special precautions
Mental Health: Effects on Mental Status
Fatigue and weakness are common; may cause dizziness
Mental Health: Effects on Psychiatric Treatment
Contraindicated with pimozide. Nausea is common; may be additive when used with SSRIs; monitor. Nefazodone may inhibit aprepitant's metabolism, while carbamazepine may increase its metabolism. Plasma levels of alprazolam, midazolam, and triazolam may be increased when combined with aprepitant. Plasma levels of paroxetine may be decreased with combined use; monitor.
Nursing: Physical Assessment/Monitoring
Use with caution in presence of severe hepatic impairment. Monitor for fatigue, weakness, gastrointestinal disturbance, and dehydration.
Dosage Forms
Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Capsule, oral:
Emend®: 40 mg, 80 mg, 125 mg
Combination package, oral [each package contains]:
Emend®: Capsule: 80 mg (2s) and Capsule: 125 mg (1s)
Pricing: U.S. (www.drugstore.com)
Capsules (Emend)
40 mg (5): $288.98
80 mg (2): $217.03
80 mg (6): $632.97
80 & 125 mg (3): $374.76
125 mg (6): $944.00
Extemporaneously Prepared
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.
References
Kris MG, Hesketh PJ, Somerfield MR, et al, “American Society of Clinical Oncology Guideline for Antiemetics in Oncology: Update 2006,” J Clin Oncol, 2006, 24(18):2932-47.
Multinational Association of Supportive Care in Cancer (MASCC), “Antiemetic Guidelines,” Updated April 2010. Available at http://data.memberclicks.com/site/mascc/MASCC_Guidelines_English_2010.pdf
National Comprehensive Cancer Network® (NCCN), “Clinical Practice Guidelines in Oncology™: Antiemesis,” Version 1.2011. Available at http://www.nccn.org/professionals/physician_gls/PDF/antiemesis.pdf
International Brand Names
Lexi-Comp.com
Last full review/revision May 2011
Content last modified May 2011
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