Overview
11 DESCRIPTION Aprepitant capsules, USP contain the active ingredient, aprepitant, USP. Aprepitant, USP is a substance P/neurokinin 1 (NK 1 ) receptor antagonist, an antiemetic agent, chemically described as 5-[[(2 R ,3 S )-2-[(1 R )-1-[3,5bis(trifluoromethyl)phenyl]ethoxy]-3-(4-fluorophenyl)-4-morpholinyl]methyl]-1,2-dihydro-3 H -1,2,4-triazol-3one.
Mechanism of Action
12 CLINICAL PHARMACOLOGY 12.1 MECHANISM OF ACTION Aprepitant is a selective high-affinity antagonist of human substance P/neurokinin 1 (NK 1 ) receptors. Aprepitant has little or no affinity for serotonin (5-HT 3 ), dopamine, and corticosteroid receptors, the targets of existing therapies for chemotherapy-induced nausea and vomiting (CINV) and postoperative nausea and vomiting (PONV). Aprepitant has been shown in animal models to inhibit emesis induced by cytotoxic chemotherapeutic agents, such as cisplatin, via central actions. Animal and human Positron Emission Tomography (PET) studies with aprepitant have shown that it crosses the blood brain barrier and occupies brain NK 1 receptors.
Indications
- 1 INDICATIONS AND USAGE Aprepitant is a substance P/neurokinin 1 (NK1) receptor antagonist. Aprepitant capsules are indicated • in combination with other antiemetic agents, in patients 12 years of age and older for prevention of: o acute and delayed nausea and vomiting associated with initial and repeat courses of highly emetogenic cancer chemotherapy (HEC) including high-dose cisplatin ( 1.1 ) o nausea and vomiting associated with initial and repeat courses of moderately emetogenic cancer chemotherapy (MEC) ( 1.1 ) • for prevention of postoperative nausea and vomiting (PONV) in adults ( 1.
Common Doses
- 125 mg
- 80 mg
- 40 mg
- 12 mg
Dosage
2 DOSAGE AND ADMINISTRATION Recommended Dosage for Prevention of Chemotherapy Induced Nausea and Vomiting (CINV) ( 2.1 ) •Aprepitant capsules in adults and pediatric patients 12 years of age and older: is 125 mg on Day 1 and 80 mg on Days 2 and 3. • Administer aprepitant 1 hour prior to chemotherapy on Days 1, 2, and 3. If no chemotherapy is given on Days 2 and 3, administer aprepitant in morning. See Full Prescribing Information for recommended dosages of concomitant dexamethasone and 5-HT 3 antagonist for HEC and MEC. Recommended Dosage for PONV ( 2.
Contraindications
- 4 CONTRAINDICATIONS 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-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.
Side Effects
- 6 ADVERSE REACTIONS 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 Torrent Pharma Inc. at 1-800-912-9561 or FDA at 1-800-FDA-1088 or www.fda.
Interactions
- 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 acts as a moderate inhibitor of CYP3A4 when administered as a 3-day regimen (125mg/80-mg/80-mg) and can increase plasma concentrations of concomitant drugs that are substrates for CYP3A4.