extraordinary [18:9); caution advised in these patients. 1 4 12 Fosaprepitant metabolized by extrahepatic tissue; hepatic insufficiency not expected to alter conversion of fosaprepitant to aprepitant. 12 Common Adverse Effects Aprepitant capsules: Asthenia and/or fatigue, dizziness, hypoesthesia, nausea, anorexia, diarrhea, constipation, heartburn, abdominal pain, epigastric discomfort, dyspepsia, gastritis, stomatitis, pharyngolaryngeal pain, hiccups, perforating duodenal ulcer, enterocolitis, neutropenia, dehydration, hot flush, pruritus, hypotension, hypertension, sinus tachycardia, neutropenic sepsis, pneumonia, alopecia, bradycardia. 1 2 Fosaprepitant injection: Infusion site reactions (e.g., pain, induration), headache. 12 13 16 Since fosaprepitant dimeglumine for injection is converted into aprepitant, adverse effects associated with aprepitant also may be expected to occur with the injection. 12 Interactions for Aprepitant/Fosaprepitant Dimeglumine Drug interactions following fosaprepitant administration likely to occur with agents that interact with aprepitant. 12 Aprepitant is extensively metabolized, principally by CYP3A4 and to a lesser extent by CYP1A2 and CYP2C19. 1 12 16 The drug is a weak-to-moderate, dose-dependent inhibitor and an inducer of CYP3A4; 1 4 12 also an inducer of CYP2C9. 1 4 12 Drugs Metabolized by Hepatic Microsomal Enzymes CYP3A4 substrates: Possible altered metabolism of CYP3A4 substrates. 1 4 Aprepitant may inhibit or induce CYP3A4. 1 4 Inhibition of CYP3A4 is dose-dependent and moderate with the 125-mg/80-mg aprepitant regimen and weak with the single-dose, 40-mg regimen. 1 Possible increased plasma concentrations of concomitantly administered drugs, especially possible with higher aprepitant dosages (i.e., in a regimen consisting of 125 mg on day 1 followed by 80 mg on days 2 and 3) or with repeat administration at any aprepitant dose. 1 4 6 16 Aprepitant (at a dosage level of 125 mg on day 1 followed by 80 mg on days 2 and 3) may increase plasma concentrations of a CYP3A4 substrate to lesser extent when the substrate is given IV rather than orally. 1 6 18 Use with caution; dosage adjustment of the CYP3A4 substrate may be necessary. 1 4 12 CYP2C9 substrates: Possible increased metabolism and decreased plasma concentrations of the CYP2C9 substrate. 1 4 6 12 Drugs Affecting Hepatic Microsomal Enzymes CYP3A4 inhibitors: Possible decreased aprepitant metabolism, resulting in increased plasma aprepitant concentrations. 1 4 12 Use with caution. 1 4 12 16 CYP3A4 inducers: Possible increased aprepitant metabolism. 1 4 Potential for decreased aprepitant efficacy with strong CYP3A4 inducers. 1 4 12 Specific Drugs Drug Interaction Comments Antiemetics, 5-HT 3 receptor antagonists (e.g., dolasetron, granisetron, ondansetron) No clinically important effects on 5-HT 3 receptor antagonist pharmacokinetics 1 12 16 Antifungals, azoles (e.g., itraconazole, ketoconazole) Possible increased plasma aprepitant concentrations 1 4 Use with caution 1 4 Antineoplastic agents (e.g., etoposide, ifosfamide, imatinib, irinotecan, paclitaxel, vinblastine, vincristine) Possible increased plasma concentrations of antineoplastic agents metabolized by CYP3A4 1 4 Use caution; careful monitoring required 1 4 Astemizole (no longer commercially available in US) Increased plasma astemizole concentrations; 1 4 potential for serious or life-threatening reaction 1 2 4 Concomitant use contraindicated 1 4 Benzodiazepines (e.g., alprazolam, midazolam, triazolam) Possible increased plasma concentrations of benzodiazepines metabolized by CYP3A4 1 4 Consider potential effect of increased plasma benzodiazepine concentrations 1 4 12 16 IV midazolam: Dosage adjustment may be necessary when concurrently administered with oral aprepitant regimen of 125 mg on day 1 followed by 80 mg on days 2 and 3 1 Interaction not clinically important when midazolam administered with single dose of fosaprepitant 100 mg or single 40-mg dose of aprepitant 1 6 12 Carbamazepine Possible decreased plasma concentrations and decreased efficacy of aprepitant 1 4 Cisapride (commercially available in US only under limited-access protocol) Increased plasma cisapride concentrations; 1 4 potential for serious or life-threatening reaction 1 2 4 Concomitant use contraindicated 1 4 Contraceptives, oral Possible decreased plasma steroid concentrations and reduced contraceptive efficacy 1 4 Use alternative or additional contraceptive methods during fosaprepitant or aprepitant treatment and for 1 month after last dose 1 4 6 12 16 Corticosteroids (e.g., dexamethasone, methylprednisolone) Possible increased plasma concentrations of corticosteroids metabolized by CYP3A4, particularly with oral aprepitant regimen of 125 mg on day 1 followed by 80 mg on days 2 and 3 1 4 12 Decrease dosage of oral and IV corticosteroids if necessary. 1 4 12 Decrease dosage of oral dexamethasone and methylprednisolone by 50% and IV methylprednisolone by 25% in patients receiving oral aprepitant regimen of 125 mg on day 1 followed by 80 mg on days 2 and 3; 1 6 12 16 dosage adjustment not recommended in patients receiving the single-dose, 40-mg regimen 6 Digoxin Pharmacokinetic interaction unlikely 1 4 12 16 Diltiazem Possible increased plasma aprepitant and diltiazem concentrations; no clinically important changes in ECG, heart rate, or BP observed 1 4 16 Small, but clinically meaningful, decrease in DBP, and possibly SBP, reported with concomitant fosaprepitant therapy; no clinically important changes in heart rate or PR interval observed 12 Use with caution 1 4 12 Docetaxel No effects on docetaxel pharmacokinetics with oral aprepitant regimen of 125 mg on day 1 followed by 80 mg on days 2 and 3 1 6 HIV protease inhibitors (nelfinavir, ritonavir) Possible increased plasma aprepitant concentrations 1 4 Use with caution 1 4 Macrolide antibiotics (e.g., clarithromycin, troleandomycin) Possible increased plasma aprepitant concentrations 1 4 Use with caution 1 4 Nefazodone Possible increased plasma aprepitant concentrations 1 4 Use with caution 1 4 Paroxetine Possible decreased plasma aprepitant and paroxetine concentrations 1 4 Phenytoin Possible decreased plasma concentrations and decreased efficacy of aprepitant; possible decreased plasma phenytoin concentrations 1 4 Pimozide Increased plasma pimozide concentrations; 1 4 potential for serious or life-threatening reaction 1 2 4 Concomitant use contraindicated 1 4 Rifampin Possible decreased plasma concentrations and decreased efficacy of aprepitant 1 4 Terfenadine (no longer commercially available the US) Increased plasma terfenadine concentrations; 1 4 potential for serious or life-threatening reaction 1 2 4 Concomitant use contraindicated 1 4 Tolbutamide Possible decreased plasma tolbutamide concentrations 1 4 Vinorelbine No effects on vinorelbine pharmacokinetics with oral aprepitant regimen of 125 mg on day 1 followed by 80 mg on days 2 and 3 1 Warfarin Possible decreased plasma S -warfarin concentrations and decreased PT 1 4 Monitor PT closely for 2 weeks (particularly 7 10 days) after initiation of fosaprepitant followed by aprepitant, the 3-day oral aprepitant regimen or administration of the single-dose aprepitant regimen 1 4 6 12 16 Aprepitant/Fosaprepitant Dimeglumine Pharmacokinetics Absorption Bioavailability Absolute mean oral bioavailability at doses of 80 125 mg is approximately 60 65%. 1 16 Absolute oral bioavailability of 40-mg dose not established. 1 Peak plasma concentrations achieved approximately 3 4 hours after oral administration. 1 16 Fosaprepitant undergoes hepatic and extrahepatic metabolism to aprepitant (the active moiety). 12 Plasma concentrations of fosaprepitant were below limits of quantification within 30 minutes following infusion completion. 12 Mean aprepitant plasma concentration 24 hours postdose similar between oral aprepitant (125-mg) dose and IV fosaprepitant (115-mg) dose. 12 Food Standard breakfast does not appreciably alter bioavailability. 1 16 Special Populations In patients with mild to moderate hepatic impairment, no clinically meaningful changes in systemic exposure relative to healthy individuals. 1 Not studied in patients with severe hepatic impairment (Child-Pugh score >9). 1 In patients with severe renal impairment or end-stage renal disease requiring hemodialysis, total (protein bound and unbound) aprepitant AUCs and peak plasma concentrations are decreased, but AUC of active unbound drug is unaffected. 1 In geriatric patients, no clinically meaningful changes in systemic exposure relative to younger adults. 1 Distribution Extent Crosses the placenta in animals; crosses the blood-brain barrier in humans. 1 Plasma Protein Binding >95%. 1 Elimination Metabolism Fosaprepitant rapidly metabolized to aprepitant in liver by CYP3A4 and to lesser extent by CYP1A2 and 2C19; also metabolized in extrahepatic tissues. 12 16 Aprepitant extensively metabolized to weakly active metabolites, principally by CYP3A4 and to a lesser extent by CYP1A2 and CYP2C19. 1 Elimination Route Eliminated principally by metabolism; not renally excreted. 1 Following a single IV dose of radiolabeled fosaprepitant in healthy individuals, 57 and 45% of radioactivity recovered in urine and feces, respectively. 16 Half-life Terminal half-life is approximately 9 13 hours. 1 16 Special Populations Not removed by hemodialysis. 1 4 Stability Storage Oral Capsules 20 25 C. 1 Desiccant should remain in original bottle. 1 Parenteral Injection 2 8 C. 12 Following reconstitution and dilution to final concentration of 1 mg/mL in 0.9% sodium chloride injection, store at room temperature ( 25 C); use within 24 hours. 12 Compatibility For information on systemic interactions resulting from concomitant use, see Interactions. Parenteral Do not mix or reconstitute with solutions containing divalent cations (e.g., lactated Ringer s solution, Hartmann s solution). 12 Solution Compatibility Incompatible Ringer s injection, Lactated 12 Hartmann s solution 12 Actions Fosaprepitant is a prodrug; pharmacologically active once metabolized to aprepitant. 12 16 Aprepitant occupies NK 1 receptors in the brain. 1 3 4 Acts in the CNS to inhibit cancer chemotherapy-induced nausea and vomiting (including both acute and delayed emesis induced by cisplatin) and postoperative nausea and vomiting. 1 3 4 Augments the antiemetic activity of ondansetron and dexamethasone. 1 3 4 Advice to Patients Importance of reading the fosaprepitant and aprepitant patient information provided by the manufacturer before beginning therapy and rereading each time the prescription is renewed. 1 2 12 Importance of using fosaprepitant and aprepitant only as directed by the clinician. 1 2 12 Importance of taking first oral aprepitant (125-mg) dose 1 hour before initiation of antineoplastic chemotherapy. 1 2 Advise patients that aprepitant may be taken with or without food. 2 12 17 Importance of taking aprepitant (40-mg) dose within 3 hours prior to induction of anesthesia for prevention of postoperative nausea and vomiting. 1 Importance of discontinuing aprepitant and promptly contacting a clinician if symptoms of an allergic reaction occur. 2 12 17 Importance of women informing clinicians if they are or plan to become pregnant or plan to breast-feed. 1 2 Importance of women using alternative or additional contraceptive methods during fosaprepitant or aprepitant use (and for 1 month after last dose) if oral contraceptives are being taken. 1 2 12 Importance of informing clinician of existing or contemplated concomitant therapy, including prescription and OTC drugs and herbal products. 1 2 12 Importance of closely monitoring prothrombin time in patients receiving chronic warfarin therapy during the 2 weeks (particularly 7 10 days) after initiation of fosaprepitant followed by aprepitant, or the 3-day oral aprepitant regimen for each antineoplastic chemotherapy cycle, or administration of aprepitant for prevention of postoperative emesis. 1 2 12 Importance of informing patients of other important precautionary information. 1 2 (See Cautions.) Preparations Excipients in commercially available drug preparations may have clinically important effects in some individuals; consult specific product labeling for details. Please refer to the ASHP Drug Shortages Resource Center for information on shortages of one or more of these preparations. Aprepitant Routes Dosage Forms Strengths Brand Names Manufacturer Oral Capsules 40 mg Emend Merck 80 mg Emend Merck 125 mg Emend Merck Fosaprepitant Dimeglumine Routes Dosage Forms Strengths Brand Names Manufacturer Parenteral For IV infusion only 115 mg (of fosaprepitant) Emend Merck AHFS DI Essentials. Copyright 2017, Selected Revisions December 5, 2016. American Society of Health-System Pharmacists, Inc., 4500 East-West Highway, Suite 900, Bethesda, Maryland 20814. References 1. Merck. Emend (aprepitant) capsules prescribing information. Whitehouse Station, NJ; 2008 Feb. 2. Merck. Emend (aprepitant) capsules patient information. Whitehouse Station, NJ; 2008 Apr. 3. Sorbera LA, Castaner J, Bayes M at al. Aprepitant and L-758298. Drugs Fut . 2002; 27:211-22. 4. Merck. Emend (aprepitant) product information form for the American Hospital Formulary Service. 2003. 5. Merck. Dear pharmacist letter regarding Emend (aprepitant). 2003 Apr. 6. Merck, Whitehouse Station, NJ: Personal communication. 7. Kris MG, Hesketh PJ, Somerfield MR et al. American Society of Clinical Oncology guideline for antiemetics in oncology: update 2006. J Clin Oncol . 2006; 24:2932-2947. [PubMed 16717289] 8. Hesketh PJ, Grunberg SM, Gralla RJ et al. The oral neurokinin-1 antagonist aprepitant for the prevention of chemotherapy-induced nausea and vomiting: a multinational, randomized, double-blind, placebo-controlled trial in patients receiving high-dose cisplatin the Aprepitant Protocol 052 Study Group. J Clin Oncol . 2003; 21:4112-9. [PubMed 14559886] 9. Poli-Bigelli S, Rodrigues-Pereira J, Carides AD et al. Addition of the neurokinin 1 receptor antagonist aprepitant to standard antiemetic therapy improves control of chemotherapy-induced nausea and vomiting: results from a randomized, double-blind, placebo-controlled trial in Latin America. Cancer . 2003; 97:3090-8. [PubMed 12784346] 11. Warr DG, Hesketh PJ, Gralla RJ. et al. Efficacy and tolerability of aprepitant for the prevention of chemotherapy-induced nausea and vomiting in patients with breast cancer after moderately emetogenic chemotherapy. J Clin Oncol . 2005; 23:2822-30. [PubMed 15837996] 12. Merck. Emend (fosaprepitant dimeglumine) for injection prescribing information. Whitehouse Station, NJ; 2008 Feb. 13. Lasseter KC, Gambale J, Jin B et al. Tolerability of fosaprepitant and bioequivalency to aprepitant in healthy subjects. J Clin Pharmacol . 2007; 47:834-40. [PubMed 17525168] 14. Diemunsch P, Gan TJ, Philip BK et al. Single-dose aprepitant vs ondansetron for the prevention of postoperative nausea and vomiting: a randomized, double-blind Phase III trial in patients undergoing open abdominal surgery. Br J Anesth . 2007; 99:202-11. 15. Gan TJ, Apfel CC, Kovac A et al. A randomized, double-blind comparison of the NK 1 antagonist, aprepitant, versus ondansetron for the prevention of postoperative nausea and vomiting. Anesth Anal . 2007; 104:1082-9. 16. Navari RM. Fosaprepitant (MK-0517): a neurokinin-1 receptor antagonist for the prevention of chemotherapy-induced nausea and vomiting. Expert Opin. Investig. Drugs . 2007; 16:1977-85. 17. Merck. Emend (fosaprepitant dimeglumine) for injection patient information. Whitehouse Station, NJ; 2009 Feb. 18. Merck. Whitehouse Station, NJ: Personal communication. 19. Basch E, Prestrud AA, Hesketh PJ et al. Antiemetics: American Society of Clinical Oncology clinical practice guideline update. J Clin Oncol . 2011; 29:4189-98. [PubMed 21947834] 20. Hesketh PJ, Bohlke K, Lyman GH et al. Antiemetics: American Society of Clinical Oncology focused guideline update. J Clin Oncol . 2016; 34:381-6. [PubMed 26527784] Next Interactions Print this page Add to My Med List More about aprepitant Side Effects During Pregnancy Dosage Information Drug Images Drug Interactions Support Group Pricing & Coupons En Español 12 Reviews Add your own review/rating Drug class: NK1 receptor antagonists Consumer resources Aprepitant ... +3 more Professional resources Aprepitant (FDA) Aprepitant (Wolters Kluwer) Other brands: Emend Related treatment guides Nausea/Vomiting, Postoperative Nausea/Vomiting, Chemotherapy Induced]} FEATURED: CAR-T Cell Therapy Overview Mechanism of Action KTE-C19 Studies KTE-C19 Cancer Targets Adverse Events Manufacturing Drug Status Rx Availability Prescription only B Pregnancy Category No proven risk in humans N/A CSA Schedule Not a controlled drug Approval History Drug history at FDA Manufacturers Sandoz Inc. Glenmark Pharmaceuticals Inc., USA Drug Class NK1 receptor antagonists Related Drugs Nausea / Vomiting, Chemotherapy Induced lorazepam , ondansetron , Zofran , Ativan , dexamethasone , metoclopramide , Reglan , Decadron , Marinol , dronabinol , More... Nausea / Vomiting, Postoperative ondansetron , Zofran , metoclopramide , Reglan , Zofran ODT , Emend , Aloxi , granisetron , palonosetron , droperidol , Kytril , aprepitant , More... Aprepitant Rating 12 User Reviews 9.9 /10 12 User Reviews 9.9 Rate it! Aprepitant Images Aprepitant systemic 40 mg (G 583) View all images} } probably the greatest
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