APREPITANT

AbsorptionFollowing oral administration of a single 40-mg dose of aprepitant in the fasted state, mean area under the plasma concentration-time curve (AUC 0 - ∞ ) was 7.8 mcg

• hr/mL and mean peak plasma concentration (C max ) was 0.7 mcg/mL, occurring at approximately 3 hours postdose (T max ). The absolute bioavailability at the 40-mg dose has not been determined. Following oral administration of a single 125-mg dose of aprepitant on Day 1 and 80 mg once daily on Days 2 and 3, the AUC 0-24hr wa...

14.1 Prevention of Nausea and Vomiting Associated with HEC in Adults Oral administration of aprepitant in combination with ondansetron and dexamethasone (aprepitant regimen) has been shown to prevent acute and delayed nausea and vomiting associated with HEC including high-dose cisplatin, and nausea and vomiting associated with MEC. In Studies 1 and 2, both multicenter, randomized, parallel, double-blind, controlled clinical studies in adults, aprepitant in combination with ondansetron and dexamethasone was compared with standard therapy (ondansetron and dexamethasone alone) in patients receivi...

Most common adverse reactions (≥3%) are ( 6.1 ): Prevention of Chemotherapy Induced Nausea and Vomiting (CINV)

• Adults: fatigue, diarrhea, asthenia, dyspepsia, abdominal pain, hiccups, white blood cell count decreased, dehydration, and alanine aminotransferase increased.
• Pediatrics: neutropenia, headache, diarrhea, decreased appetite, cough, fatigue, hemoglobin decreased, dizziness, and hiccups. PONV
• Adults: constipation and hypotension. To report SUSPECTED ADVERSE REACTIONS, contact Torren...

Aprepitant 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-threate...

• CYP3A4 Interactions : Aprepitant is a substrate, weak-to-moderate inhibitor and inducer of CYP3A4; See Full Prescribing Information for recommendations regarding contraindications, risk of adverse reactions, and dosage adjustments of aprepitant and concomitant drugs. ( 4 , 5.1 , 7.1 , 7.2 )
• Warfarin (a CYP2C9 substrate) : Risk of decreased INR of prothrombin time; monitor INR in 2-week period, particularly at 7 to 10 days, following initiation of aprepitant. ( 5.2 , 7.1 )
• Hormonal Contrace...

7 DRUG INTERACTIONS 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 a...