Classifications: antiemetic; substance p/neurokinin 1 (nk1) receptor antagonist; Therapeutic: antiemetic
Pregnancy Category: B
80 mg, 125 mg capsules
Aprepitant is a selective substance P/neurokinin 1 (NK1) receptor antagonist. Substance P and the NK-1 receptors are present in areas in the brain that control the emetic reflex.
Aprepitant crosses the bloodbrain barrier and occupies brain NK1 receptors. Peripheral blockade by NK1 receptor antagonists at receptors located in the GI is an additional hypothesized mechanism of action.
Aprepitant augments the antiemetic activity of the 5-HT3-receptor antagonist, ondansetron, and inhibits both the acute and delayed phases of emesis induced by chemotherapy agents.
Prevention of acute and delayed nausea and vomiting associated with emetogenic chemotherapy.
Hypersensitivity to aprepitant; concurrent use of pimozide; children <18 y; lactation.
Chemotherapeutic agents metabolized through CYP3A4; severe hepatic impairment; severe renal impairment without dialysis;
pregnancy (category B).
Route & Dosage
|Chemotherapy-Induced Nausea & Vomiting
Adult: PO 125 mg 1 h prior to chemotherapy, then 80 mg qam for the next 2 d in conjunction with other antiemetics
- Ensure that capsule is swallowed whole with a full glass of water. Do not crush or sprinkle the contents of the capsule.
- Give 1 h before start of chemotherapy.
- Store at 20°25° C (68°77° F). Keep the desiccant in the original bottle.
Adverse Effects (≥1%)Body as a Whole: Fatigue,
asthenia, malaise, dehydration, fever. CNS:
, headache, peripheral neuropathy, sensory neuropathy, anxiety, confusion, depression
. GI: Constipation, diarrhea, anorexia, nausea, hiccups,
abdominal pain, gastritis
, gastroesophageal reflux, abnormal or impaired taste (dysgeusia), dyspepsia, dysphagia, flatulence,
hypersalivation, increased taste disturbance, increased AST and ALT. Hematologic:
Neutropenia, anemia. Musculoskeletal:
Pain, myalgia. Respiratory:
Cough, dyspnea, upper or lower respiratory infection, pneumonitis, respiratory insufficiency. Special Senses:
Increased risk of cardiovascular toxicity with dofetilide, pimozide;
may decrease warfarin
concentrations and INR; may decrease levels and effectiveness of oral contraceptives
; carbamazepine, griseofulvin, modafinil, rifabutin, rifapentine, phenobarbital, primidone
may decrease antiemetic efficacy; may increase levels of dexamethasone.
Because aprepitant is a substrate of CYP3A4, many additional drug interactions are theoretically possible. Food: Grapefruit juice
may decrease effectiveness of aprepitant. Herbal: St. John's wort
may decrease effectiveness of aprepitant.
6065% of oral dose reaches systemic circulation. Peak:
4 h. Duration:
95% protein bound; readily crosses the bloodbrain barrier. Metabolism:
In liver by CYP3A4. Elimination:
Not renally excreted. Half-Life:
Assessment & Drug Effects
- Monitor cardiac status especially with preexisting CV disease or concurrent use of any CYP3A4 substrate drug (e.g., ketoconazole,
itraconazole, nefazodone, troleandomycin, clarithromycin).
- Lab tests: Monitor PT/INR 710 d after 3-d regimen with concurrent warfarin use; monitor phenytoin level with concurrent
use; monitor serum electrolytes, UA, and CBC.
Patient & Family Education
- Report immediately to physician any of the following: skin rash; difficulty breathing or shortness of breath; rapid, slow,
or irregular heartbeat; changes in BP; dizziness or confusion; unexplained sharp or severe pain in leg or stomach; rectal
bleeding. Inform physician of all other drugs or herbal products you are using. Do not take new drugs (prescription, OTC,
herbal) without first consulting physician.
- Use barrier contraception in addition to oral contraceptives while taking drug.