Aprepitant
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From MedlinePlus, U.S. National Library of Medicine
Substance P/Neurokinin-1 Receptor Antagonist
Dosing in kidney impairment
Patients with Renal Impairment The pharmacokinetics of aprepitant in patients with severe renal impairment and those with end stage renal disease (ESRD) requiring hemodialysis were similar to those of healthy subjects with normal renal function. No dosage adjustment is necessary for patients with any degree of renal impairment or for patients with ESRD undergoing hemodialysis.
Dosing in liver impairment
Patients with Hepatic Impairment The pharmacokinetics of aprepitant in patients with mild and moderate hepatic impairment were similar to those of healthy subjects with normal hepatic function. No dosage adjustment is necessary for patients with mild to moderate hepatic impairment (Child-Pugh score 5 to 9). There are no clinical or pharmacokinetic data in patients with severe hepatic impairment (Child-Pugh score greater than 9).
Therefore, additional monitoring for adverse reactions in these patients may be warranted when EMEND is administered [see Clinical Pharmacology ] .
Preparation and administration
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Preparation Instructions for EMEND for Oral Suspension -- for Healthcare Providers EMEND for oral suspension should be prepared by a healthcare provider. Once prepared, it may be administered either by a healthcare provider, patient, or caregiver. Before preparing EMEND: Do not open the pouch of EMEND until ready to prepare the medicine.
Store the pouch at room temperature [between 68°F-77°F (20°C-25°C)]. [See table below.] Figure Figure Figure Figure Figure Figure Figure Figure Figure Figure
Administration Instructions EMEND capsules and EMEND for oral suspension can be administered with or without food. EMEND capsules Swallow capsules whole. EMEND for oral suspension The dose will be prepared by the healthcare provider and dispensed to the patient or caregiver in an oral dispenser. Keep the dispenser in the refrigerator until administered to the patient.
The dose can be stored at room temperature for up to 3 hours before use. When ready to use, take the cap off the dispenser, place the dispenser in the patient's mouth along the inner cheek on either the right or left side. Slowly dispense the medicine. The dose must be used within 72 hours of preparation. Discard any doses remaining after 72 hours.
| Population | Day 1 | Day 2 | Day 3 | Day 4 | |
|---|---|---|---|---|---|
| EMEND for oral suspensionAfter preparation, the final concentration of EMEND for oral suspension is 25 mg/mL [see Dosage and Administration (2.3)]. Administer EMEND for oral suspension 1 hour prior to chemotherapy treatment on Days 1, 2, and 3. If no chemotherapy is given on Days 2 and 3, administer EMEND for oral suspension in the morning. | Pediatric Patients 6 Months to Less than12 Years or Pediatric and Adult Patients Unable to Swallow Capsules | 3 mg/kg orally Maximum dose 125 mg | 2 mg/kg orally Maximum dose 80 mg | 2 mg/kg orally Maximum dose 80 mg | none |
| Dexamethasone | Adults Unable to Swallow Capsules | See Table 1 or 2 | See Table 1 or 2 | See Table 1 or 2 | See Table 1 or 2 |
| Pediatric Patients 6 Months to Less than12 Years or Pediatric Patients Unable to Swallow Capsules | If a corticosteroid, such as dexamethasone, is co-administered, administer 50% of the recommended corticosteroid dose on Days 1 through 4 [see Clinical Studies (14.3)].Administer dexamethasone 30 minutes prior to chemotherapy treatment on Day 1. A 50% dosage reduction of dexamethasone is recommended to account for a drug interaction with EMEND [see Clinical Pharmacology (12.3)]. | ||||
| 5-HT3 antagonist | Pediatric Patients 6 Months to Less than12 Years or Pediatric and Adult Patients Unable to Swallow Capsules | See selected 5-HT3 antagonist prescribing information for the recommended dosage | none | none | none |
| EMEND for oral suspension is packaged as a kit with one 1 mL oral dosing dispenser, one 5 mL oral dosing dispenser, one cap and one mixing cup. | |
| Make sure no air is in the dispenser - if air is present, remove. Make sure the dispenser contains the prescribed dose. | |
Drug interactions
Check aprepitant against a medication listLabel text (9 paragraphs)
See Full Prescribing Information for a list of clinically significant drug interactions. ( 4 , 5.1 , 5.2 , 5.3 , 7.1 , 7.2 )
7.1 Effect of Aprepitant on the Pharmacokinetics of Other Drugs Aprepitant is a substrate, a weak-to-moderate (dose-dependent) inhibitor, and an inducer of CYP3A4. Aprepitant is also an inducer of CYP2C9 [see Clinical Pharmacology (12.3) ] . Aprepitant acts as a moderate inhibitor of CYP3A4 when administered as a 3-day regimen (125-mg/80-mg/80-mg) and can increase plasma concentrations of concomitant drugs that are substrates for CYP3A4. Some substrates of CYP3A4 are contraindicated with EMEND [see Contraindications (4) ] . Dosage adjustment of some CYP3A4 and CYP2C9 substrates may be warranted, as shown in Table 8.
Table 8: Effects of Aprepitant on the Pharmacokinetics of Other Drugs CYP3A4 Substrates Pimozide Clinical Impact Increased pimozide exposure. Intervention EMEND is contraindicated [see Contraindications (4) ] . Benzodiazepines Clinical Impact Increased exposure to midazolam or other benzodiazepines metabolized via CYP3A4 (alprazolam, triazolam) may increase the risk of adverse reactions [see Clinical Pharmacology (12.3) ]. Intervention Monitor for benzodiazepine-related adverse reactions.
Depending on the clinical situation (e.g., elderly patients) and degree of monitoring available, reduce the dose of intravenous midazolam Dexamethasone Clinical Impact Increased dexamethasone exposure [see Clinical Pharmacology (12.3) ]. Intervention Reduce the dose of oral dexamethasone by approximately 50% [see Dosage and Administration (2.1) ]. Methylprednisolone Clinical Impact Increased methylprednisolone exposure [see Clinical Pharmacology (12.3) ].
Intervention Reduce the dose of intravenous methylprednisolone by approximately 25% Reduce the dose of oral methylprednisolone by approximately 50% Chemotherapeutic agents that are metabolized by CYP3A4 Clinical Impact Increased exposure of the chemotherapeutic agent may increase the risk of adverse reactions [see Clinical Pharmacology (12.3) ] . Intervention Vinblastine, vincristine, or ifosfamide or other chemotherapeutic agents Monitor for chemotherapeutic-related adverse reactions. Etoposide, vinorelbine, paclitaxel, and docetaxel No dosage adjustment needed.
Hormonal Contraceptives Clinical Impact Decreased hormonal exposure during administration of and for 28 days after administration of the last dose of EMEND [see Warnings and Precautions (5.3) , Use in Specific Populations (8.3) , Clinical Pharmacology (12.3) ] . Intervention Effective alternative or back-up methods of contraception (such as condoms and spermicides) should be used during treatment with EMEND and for 1 month following the last dose of EMEND.
Examples birth control pills, skin patches, implants, and certain IUDs CYP2C9 Substrates Warfarin Clinical Impact Decreased warfarin exposure and decreased prothrombin time (INR) [see Warnings and Precautions (5.2) , Clinical Pharmacology (12.3) ] . Intervention In patients on chronic warfarin therapy, monitor the prothrombin time (INR) in the 2-week period, particularly at 7 to 10 days, following initiation of the 3-day EMEND regimen with each chemotherapy cycle. Other 5-HT 3 Antagonists Clinical Impact No change in the exposure of the 5-HT 3 antagonist [see Clinical Pharmacology (12.3) ] . Intervention No dosage adjustment needed Examples ondansetron, granisetron, dolasetron
7.2 Effect of Other Drugs on the Pharmacokinetics of Aprepitant Aprepitant is a CYP3A4 substrate [see Clinical Pharmacology (12.3) ] . Co-administration of EMEND with drugs that are inhibitors or inducers of CYP3A4 may result in increased or decreased plasma concentrations of aprepitant, respectively, as shown in Table 9. Table 9: Effects of Other Drugs on Pharmacokinetics of Aprepitant Moderate to Strong CYP3A4 Inhibitors Clinical Impact Significantly increased exposure of aprepitant may increase the risk of adverse reactions associated with EMEND [see Adverse Reactions (6.1) and Clinical Pharmacology (12.3) ] . Intervention Avoid concomitant use of EMEND.
Examples Moderate inhibitor: diltiazem Strong inhibitors: ketoconazole, itraconazole, nefazodone, troleandomycin, clarithromycin, ritonavir, nelfinavir Strong CYP3A4 Inducers Clinical Impact Substantially decreased exposure of aprepitant in patients chronically taking a strong CYP3A4 inducer may decrease the efficacy of EMEND [see Clinical Pharmacology (12.3) ] . Intervention Avoid concomitant use of EMEND. Examples rifampin, carbamazepine, phenytoin
Contraindications
4 CONTRAINDICATIONS EMEND is contraindicated in patients: who are hypersensitive to any component of the product. Hypersensitivity reactions including anaphylactic reactions have been reported [see Adverse Reactions (6.2) ] . taking pimozide. Inhibition of CYP3A4 by aprepitant could result in elevated plasma concentrations of this drug which is a CYP3A4 substrate, potentially causing serious or life-threatening reactions, such as QT prolongation, a known adverse reaction of pimozide [see Warnings and Precautions (5.1) ] . Known hypersensitivity to any component of this drug. ( 4 ) Concurrent use with pimozide. ( 4 )
Pregnancy and lactation
Pregnancy
8.1 Pregnancy Risk Summary There are insufficient data on use of EMEND in pregnant women to inform a drug associated risk. In animal reproduction studies, no adverse developmental effects were observed in rats or rabbits exposed during the period of organogenesis to systemic drug levels (AUC) approximately 1.5 times the adult human exposure at the 125-mg/80-mg/80-mg EMEND regimen [see Data ] . The estimated background risk of major birth defects and miscarriage for the indicated populations is unknown. In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2 to 4% and 15 to 20%, respectively.
Data Animal Data In embryofetal development studies in rats and rabbits, aprepitant was administered during the period of organogenesis at oral doses up to 1000 mg/kg twice daily in rats and up to the maximum tolerated dose of 25 mg/kg/day in rabbits. No embryofetal lethality or malformations were observed at any dose level in either species. The exposures (AUC) in pregnant rats at 1000 mg/kg twice daily and in pregnant rabbits at 125 mg/kg/day were approximately 1.5 times the adult exposure at the 125-mg/80-mg/80-mg EMEND regimen. Aprepitant crosses the placenta in rats and rabbits.
For breastfeeding, also see LactMed (National Library of Medicine), which summarizes milk levels and infant effects.
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