aprepitant

aprepitant,

an antiemetic agent.

indications This drug is used to prevent nausea and vomiting associated with cancer chemotherapy (including high-dose cisplatin). It is used in combination with other antiemetics.

contraindications Known hypersensitivity to this drug prohibits its use.

adverse effects Adverse effects of this drug include insomnia, anxiety, depression, confusion, peripheral neuropathy, bradycardia, deep vein thrombosis, hypertension, abdominal pain, anorexia, gastritis, vomiting, heartburn, serum creatine, proteinuria, dysuria, anemia, asthenia, fatigue, dehydration, fever, hiccups, tinnitus, and increased aspartate aminotransferase, alanine aminotransferase, and blood urea nitrogen. Life-threatening side effects include thrombocytopenia and neutropenia. Common side effects include headache, dizziness, diarrhea, constipation, and nausea.

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aprepitant

Emend

Pharmacologic class: Substance P and neurokinin-1 antagonist

Therapeutic class: Adjunctive antiemetic

Pregnancy risk category B

Action

Augments antiemetic activity of ondansetron (a 5-hydroxytryptamine₃-receptor antagonist) and dexamethasone. Also inhibits cisplatin-induced emesis.

Availability

Capsules: 40 mg, 80 mg, 125 mg

⊘Indications and dosages

➣ To prevent acute and delayed nausea and vomiting caused by highly emetogenic cancer chemotherapy

Adults: 125 mg P.O. 1 hour before chemotherapy on day 1; then 80 mg P.O. once daily in morning on days 2 and 3. Give with 12 mg dexamethasone P.O. and 32 mg ondansetron I.V. on day 1, and with 8 mg dexamethasone P.O. on days 2 to 4.

➣ Prevention of postoperative nausea and vomiting

Adults: 40 mg P.O. once within 3 hours before induction anesthesia

Contraindications

• Hypersensitivity to drug
• Concurrent pimozide, terfenadine, astemizole, or cisapride therapy
• Breastfeeding

Precautions

Use cautiously in:
• patients receiving concurrent warfarin or CYP3A4 inhibitors
• pregnant patients.

Administration

• Give 1 hour before chemotherapy on day 1, together with other antiemetics as prescribed.
• Give on mornings of days 2 and 3.

Route	Onset	Peak	Duration
P.O.	Unknown	Unknown	Unknown

Adverse reactions

CNS: dizziness, neuropathy, headache, insomnia, asthenia, fatigue

EENT: tinnitus

GI: nausea, vomiting, constipation, diarrhea, epigastric discomfort, gastritis, heartburn, abdominal pain, anorexia

Hematologic: neutropenia

Other: fever, dehydration, hiccups

Interactions

Drug-drug. CYP3A4 inducers (carbamazepine, phenytoin, rifampin): decreased aprepitant blood level

CYP3A4 inhibitors (azole antifungals, clarithromycin, nefazodone, ritonavir): increased aprepitant blood level

Dexamethasone, methylprednisolone: increased steroid exposure

Docetaxel, etoposide, ifosfamide, imatinib, irinotecan, paclitaxel, vinblastine, vincristine, vinorelbine: increased blood levels of these drugs

Hormonal contraceptives: decreased contraceptive efficacy

Paroxetine: decreased efficacy of either drug

Pimozide: increased blood level and toxic effects of aprepitant

Tolbutamide, warfarin: CYP2C9 induction, decreased efficacy of these drugs

Patient monitoring

• Monitor neurologic status. Institute measures to prevent injury as needed.
• Assess nutritional and hydration status.
• Monitor CBC.

Patient teaching

• Tell patient that drug may cause CNS effects. Explain that he'll be monitored to ensure his safety.
• Advise patient to minimize GI upset by eating small, frequent servings of food and drinking plenty of fluids.
• Caution patient to avoid driving and other hazardous activities until he knows how drug affects concentration, hearing, strength, balance, and alertness.
• As appropriate, review all other significant and life-threatening adverse reactions and interactions, especially those related to the drugs mentioned above.