DESCRIPTION
Mechanism of Action
• Selective high-affinity antagonist of substance P/neurokinin 1 (NK1)
receptors.
• Inhibits the acute and delayed phases of chemotherapy-induced
emesis.
• Little to no affinity for 5-HT3, dopamine, or corticosteroid receptors.
Absorption
Well absorbed by the gastrointestinal (GI) tract, and oral bioavailability is
on the order of 60%–65%. Peak plasma levels reached in 4 hours. Ingestion
of food does not alter the extent of absorption.
Distribution
Crosses the blood-brain barrier and enters the central nervous system
(CNS). Greater than 95% of drug is bound to plasma proteins.
Metabolism
Undergoes extensive metabolism in the liver, principally by the CYP3A4
liver microsomal system. The main route of elimination of parent drug is via
liver metabolism. The parent drug and its metabolites are not renally
excreted. The elimination half-life ranges from 9–13 hours.
Indications
1. Prevention of acute and delayed nausea and vomiting associated with
highly emetogenic cancer chemotherapy, including high-dose cisplatin.
2. Prevention of nausea and vomiting associated with moderately
emetogenic cancer chemotherapy.
3. Prevention of postoperative nausea and vomiting (PONV).
Dosage Range
1. Oral: Recommended dose is 125 mg PO given 1 hour before chemotherapy
and 80 mg PO on days 2 and 3 after chemotherapy.
2. Intravenous: Recommended dose is 115 mg IV 30 minutes before
chemotherapy on day 1 only.
3. PONV: 40 mg PO within 3 hours prior to induction of anesthesia.
Special Considerations
1. Use with caution in patients on chronic warfarin anticoagulation.
Coagulation parameters, PT/INR, should be closely monitored in the
2-week period, especially at days 7 and 10, following aprepitant therapy.
2. Patients should be advised to report to their physician the use of any
nonprescription or herbal medications, as significant drug interactions
can occur with aprepitant and other drugs.
3. Well tolerated in patients with mild-to-moderate liver dysfunction.
Caution should be exercised in patients with severe hepatic insufficiency
(Child-Pugh score .9).
4. No dose adjustment is required for patients with renal insufficiency
and/or in those undergoing hemodialysis.
5. Pregnancy category B. Breastfeeding should be avoided.
Toxicity 1
Fatigue is most common side effect. CNS effects include headache and
insomnia.
Toxicity 2
GI side effects include constipation and/or diarrhea.
Toxicity 3
Hiccups observed in 10% of patients.
Toxicity 4
Anorexia.
SPECIFICATION
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