DrugindexOnline^{2nd edition}

Pronouncation: (ap-REH-pih-tant)
Class: Antiemetic, Antivertigo agent

Trade Names:
Emend
- Capsules 80 mg
- Capsules 125 mg

Mechanism of Action

Pharmacology

Selective high-affinity antagonist of human substance P/neurokinin 1 receptors.

Pharmacokinetics

Absorption

The bioavailability is approximately 60% to 65%. Following doses of 125 mg on day 1 and 80 mg on days 2 and 3, the mean C _max occurs at approximately 4 h and reaches about 1.5 mcg/mL.

Distribution

Plasma protein binding is greater than 95%. The mean Vd _ss is approximately 70 L. Aprepitant crosses the blood-brain barrier.

Metabolism

Data indicate aprepitant is extensively metabolized by CYP3A4 and, to a lesser degree, by CYP1A2 and CYP2C19.

Elimination

Following IV administration of a single 100 mg dose, 57% was excreted in the urine and 45% in the feces.

Special Populations

Renal Function Impairment

No dosage adjustment is necessary for patients with renal function impairment or end-stage renal disease undergoing hemodialysis.

Hepatic Function Impairment

No dosage adjustment is necessary in patients with mild or moderate hepatic function impairment.

Elderly

No dosage adjustment is necessary in elderly patients.

Race

No dosage adjustment is necessary based on race.

Indications and Usage

In combination with other antiemetic agents for the prevention of acute and delayed nausea and vomiting associated with initial and repeat courses of highly emetogenic cancer chemotherapy, including high-dose cisplatin; prevention of nausea and vomiting associated with initial and repeat courses of moderately emetogenic cancer chemotherapy.

Contraindications

Coadministration of astemazole, cisapride, pimozide, or terfenadine; hypersensitivity to any component of the product.

Dosage and Administration

Adults

PO 125 mg 1 h prior to chemotherapy treatment on day 1 and 80 mg/day in the morning on days 2 and 3. Administer in combination with a corticosteroid and 5-HT ₃ antagonist.

Storage/Stability

Store capsules at 68° to 77°F. Do not remove desiccant from bottle.

Drug Interactions

Contraceptives, oral

Because the efficacy of oral contraceptives may be reduced, patients may need an alternative or additional nonhormonal contraceptive.

CYP2C9 substrates (eg, phenytoin, tolbutamide, warfarin)

Plasma concentrations of these agents may be reduced. In patients receiving warfarin, monitor the INR in the 2-wk period (especially at 7 to 10 days) after starting aprepitant therapy.

CYP3A4 inducers (eg, carbamazepine, phenytoin, rifampin)

Plasma concentrations of aprepitant may be reduced, decreasing the therapeutic effect.

CYP3A4 inhibitors (eg, clarithromycin, diltiazem, itraconazole, ketoconazole, nefazodone, nelfinavir, ritonavir, troleandomycin)

Plasma concentrations of aprepitant may be elevated, increasing the risk of side effects.

CYP3A4 substrates (eg, alprazolam, cisapride, dexamethasone, docetaxel, etoposide, ifosfamide, imatinib, irinotecan, methylprednisolone, midazolam, paclitaxel, pimozide, vinblastine, vincristine, vinorelbine)

Plasma concentrations of these agents may be increased. Astemizole, cisapride, pimozide, and terfenadine are contraindicated with coadministration of aprepitant. Reduce the dexamethasone dose approximately 50%; reduce the IV and oral dose of methylprednisolone 25% and 50%, respectively, when administering aprepitant.

Paroxetine

Plasma levels of aprepitant and paroxetine may be decreased.

Laboratory Test Interactions

None well documented.

Adverse Reactions

CNS

Asthenia/fatigue (18%); headache (9%); dizziness (7%); insomnia (3%).

Dermatologic

Alopecia (24%); hot flush (3%); angioedema, Stevens-Johnson syndrome, urticaria.

EENT

Tinnitus (4%); pharyngolaryngeal pain (3%).

GI

Nausea (13%); anorexia, constipation, diarrhea (10%); dyspepsia, vomiting (8%); heartburn, stomatitis (5%); epigastric discomfort, gastritis (4%).

Hematologic-Lymphatic

Neutropenia (9%).

Lab Tests

Increased proteinuria (7%), ALT (6%), BUN (5%), serum creatinine (4%), and AST (3%).

Metabolic-Nutritional

Dehydration (6%).

Respiratory

Hiccups (11%).

Miscellaneous

Abdominal pain (5%); fever, mucous membrane disorder (3%).

Precautions

Monitor Monitor patient for antiemetic efficacy. Notify health care provider if nausea or vomiting are not prevented.

Pregnancy

Category B .

Lactation

Undetermined.

Children

Safety and efficacy not established.

Chronic therapy

Long-term continuous use for prevention of nausea or vomiting is not recommended.

Overdosage

Symptoms

Drowsiness, headache.

Patient Information

• Advise patient, family, or caregiver to read the patient information leaflet before starting therapy and with each refill.
• Advise patient, family, or caregiver that medication is designed to prevent nausea and vomiting caused by chemotherapy. It is not to be used to treat nausea or vomiting once it has started.
• Review dosing schedule with patient, including concomitant use of other antiemetics. Caution patient that first dose of aprepitant must be taken 1 h before chemotherapy administration to provide greatest protection against nausea and vomiting.
• Advise patient that medication regimen will greatly reduce likelihood of nausea or vomiting but that these reactions are still possible.
• Instruct patient to inform health care provider if medication regimen does not prevent nausea or vomiting.
• Advise patient to report any of the following symptoms to health care provider: intolerable headache; persistent or intolerable constipation, diarrhea, or nausea; persistent weakness or general body discomfort.
• Advise patient receiving warfarin therapy that clotting status will need to be monitored closely for 2 wk following use of aprepitant.
• Advise women taking oral contraceptives to use alternative or backup contraceptive methods while using aprepitant.
• Advise patient, family, or caregiver that follow-up visits and lab tests will be required to monitor therapy and to keep appointments.